"APPLICATION_ID","ACTIVITY","ADMINISTERING_IC","APPLICATION_TYPE","ARRA_FUNDED","AWARD_NOTICE_DATE","BUDGET_START","BUDGET_END","CFDA_CODE","CORE_PROJECT_NUM","ED_INST_TYPE","FOA_NUMBER","FULL_PROJECT_NUM","FUNDING_ICs","FUNDING_MECHANISM","FY","IC_NAME","NIH_SPENDING_CATS","ORG_CITY","ORG_COUNTRY","ORG_DEPT","ORG_DISTRICT","ORG_DUNS","ORG_FIPS","ORG_IPF_CODE","ORG_NAME","ORG_STATE","ORG_ZIPCODE","PHR","PI_IDS","PI_NAMEs","PROGRAM_OFFICER_NAME","PROJECT_START","PROJECT_END","PROJECT_TERMS","PROJECT_TITLE","SERIAL_NUMBER","STUDY_SECTION","STUDY_SECTION_NAME","SUBPROJECT_ID","SUFFIX","SUPPORT_YEAR","DIRECT_COST_AMT","INDIRECT_COST_AMT","TOTAL_COST","TOTAL_COST_SUB_PROJECT"
"9784447","IK2","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","IK2BX004642","","RFA-BX-18-008","1IK2BX004642-01","","OTHERS","2020","Veterans Affairs","","SEATTLE","UNITED STATES","","09","020232971","US","481094","VA PUGET SOUND HEALTHCARE SYSTEM","WA","981081532","Heart failure causes significant morbidity and mortality. It is the most common discharge diagnosis for Veterans hospitalized in a VA healthcare system, and the annual mortality of Veterans with heart failure is 15%. Mutations in myosin heavy chain 7 (MYH7) are common causes of genetic cardiomyopathies that lead to heart failure. As genetic testing is increasingly performed, new MYH7 variants are continuously discovered; however, this is complicated by findings of variants of unknown significance and by lack of disease-modifying treatments. This proposal seeks to identify MYH7 variants that induce heart failure and then better understand the disease process in human heart cells. This precision medicine approach, in turn, may potentially lead to novel disease-modifying therapies for patients with heart failure due to MYH7 mutations.","15689308; ","YANG, KAI-CHUN DANIEL;","","10/01/2019","09/30/2024","Accounting; Address; Affect; American; Award; base; Biological Assay; Cardiac Myocytes; Cardiac Myosins; cardiac tissue engineering; cardiogenesis; Cardiomyopathies; Caring; Cells; cellular engineering; Clinical; clinically relevant; Co-Immunoprecipitations; Data; Diagnosis; Dilated Cardiomyopathy; Disease; Disease model; Dominant-Negative Mutation; EFRAC; Emotional; experimental study; familial dilated cardiomyopathy; Functional disorder; Future; gain of function; General Population; Genetic; Genetic Databases; Genetic screening method; Genomics; Goals; Guidelines; Healthcare; Healthcare Systems; heart cell; Heart failure; high throughput screening; Human; human disease; Hypertrophic Cardiomyopathy; Impairment; improved; Induced Mutation; induced pluripotent stem cell; inherited cardiomyopathy; innovation; Intervention; Knock-out; Lead; loss of function; Mammalian Cell; Medical; Methods; Modeling; Morbidity - disease rate; mortality; Muscle; Mutagenesis; mutant; Mutation; Myosin ATPase; Myosin Heavy Chains; myosin-binding protein C; new therapeutic target; novel; overexpression; Pathogenesis; Pathogenicity; Patients; Play; precision medicine; preservation; Process; protein degradation; Protein Isoforms; protein protein interaction; Proteins; Research; Ring Finger Domain; Risk; Rodent; Role; Techniques; Testing; Therapeutic Intervention; Thick Filament; Training; Two-Hybrid System Techniques; ubiquitin-protein ligase; Up-Regulation; Variant; variant of unknown significance; Veterans; Work; yeast two hybrid system; Yeasts; ","Dissecting the mechanism of how dominant negative MYH7 mutations lead to genetic cardiomyopathies","004642","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9814664","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000545","","RFA-BX-16-001","5I01BX000545-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","The leading cancer in men in the U.S. is prostate cancer. It is also a leading cancer in our aging Veteran population. To date, there are no curative treatments for advanced stages of prostate cancer, including recurrent and metastatic disease. Although hormone therapy and chemotherapy can palliate prostate cancer, they are generally not curative. This proposal will analyze systematically how to improve the treatment of prostate cancer by targeting additional pathways activated in this disease in specific combinations with or without hormone therapy. Both cell culture and mouse models will be used. These studies will provide novel information on how to develop more effective treatment regimens for prostate cancer. Thus, the proposal is highly relevant to the healthcare mission of the Department of Veterans Affairs as well as the healthcare of the general population.","8339091; ","HUSSAIN, ARIF ;","","10/01/2009","09/30/2020","active method; Address; Adenocarcinoma; Aging; Anabolism; androgen deprivation therapy; androgen independent prostate cancer; Androgen Receptor; androgen sensitive; androgenic; Androgens; antitumor effect; Apoptosis; base; Cancer Patient; castration resistant prostate cancer; Cell Culture Techniques; Cell Cycle; Cell Proliferation; Cells; chemotherapy; Clinic; Clinical; clinical development; clinically relevant; Combined Modality Therapy; curative treatments; Data; Development; Disease; disorder control; docetaxel; Drug Interactions; effective therapy; Feedback; Future; General Population; Generations; Genomic approach; Goals; Growth; Healthcare; high risk; Hormonal; hormone therapy; Human; improved; In Vitro; in vivo; inhibitor/antagonist; insight; knock-down; Lesion; male; Malignant neoplasm of prostate; Malignant Neoplasms; Mediating; Mediator of activation protein; men; metabolome; Metastatic Prostate Cancer; Mission; Modeling; Molecular; mouse model; novel; Outcome; palliate; Pathway interactions; Patients; Pharmaceutical Preparations; Population; pre-clinical; preclinical study; Production; prostate cancer cell; prostate cancer cell line; prostate cancer model; prostate cancer risk; Prostate Cancer therapy; Radiation; Receptor Signaling; recruit; Recurrence; Resistance; SCID Mice; Signal Pathway; Signal Transduction; small hairpin RNA; Small Interfering RNA; Source; Steroids; Systemic Therapy; taxane; Testis; Therapeutic Effect; Time; Translating; Translations; Treatment Protocols; Treatment-related toxicity; tumor; tumor xenograft; Veterans; Work; Xenograft Model; Xenograft procedure; ","Multi-Faceted Targeting of Treatment-Sensitive and Treatment-Resistant Prostate Cancer","000545","ONCA","Oncology A ","","","08","","","",""
"9814676","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001396","","RFA-BX-15-001","5I01BX001396-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOMA LINDA","UNITED STATES","","31","612729368","US","481116","VA LOMA LINDA HEALTHCARE SYSTEM","CA","923571000","PUBLIC HEALTH RELEVANCE    Project Narrative There is an urgent need for development of novel anabolic drugs for the treatment of osteoarthritis, a debilitating degenerative joint disease of enormous economic burden in the U.S. and worldwide. Based on exciting preliminary data that prolyl hydroxylase domain protein (PHD)2 and PHD3 regulate proliferation and differentiation of articular cartilage progenitors, studies proposed in this application will examine the role and mechanism of action of these two enzymes in articular cartilage development, maintenance and pathogenesis. Because Phd2 and Phd3 sequences are conserved between mice and humans, future confirmation of a role for these proteins in humans could provide a basis for the future development of PHD- based novel drugs to promote articular cartilage development for treatment of osteoarthritis, the most common joint disorder in aging veterans and in the general population.","1879197; ","MOHAN, SUBBURAMAN ;","","04/01/2012","09/30/2020","Affect; Age; aggrecan; Aging; arthropathies; articular cartilage; Ascorbic Acid; Ascorbic Acid Deficiency; base; Biology; bone; bone cell; bone mass; Bone remodeling; Bone Spur; cartilage cell; cartilage degradation; cartilage development; Cell Nucleus; cell type; Chondrocytes; Conserved Sequence; Cytosine; Data; Degenerative polyarthritis; Development; differential expression; Disabled Persons; Disease; DNA; DNA Methylation; Economic Burden; Elderly; Enzymes; Epigenetic Process; Event; Failure; Financial Hardship; Fracture; Funding; Future; Gene Expression Regulation; General Population; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genome; Genomics; Goals; HIF1A gene; Histology; Human; Hydroxylation; Hypoxia Inducible Factor; Impairment; Individual; Injury; joint mobilization; Joints; Knock-out; Knockout Mice; Lead; Maintenance; Medial meniscus structure; Mediating; Medical; member; microCT; Mixed Function Oxygenases; Modification; Molecular; mouse model; Mus; Musculoskeletal Diseases; novel; novel therapeutics; obesity genetics; osteoblast differentiation; Osteoblasts; Osteogenesis; Osteopenia; Pathogenesis; Pathway interactions; Pharmacotherapy; Phenotype; Play; Population; Positioning Attribute; predictive modeling; Prevalence; Process; Procollagen-Proline Dioxygenase; progenitor; promoter; Protein Family; Proteins; Public Health; public health relevance; regenerative therapy; Regulation; response; Role; Signal Transduction; Signaling Molecule; skeletal; socioeconomics; subchondral bone; substantia spongiosa; targeted treatment; Tertiary Protein Structure; Testing; therapy development; Transcription Initiation Site; Trauma; Veterans; ","Prolyl Hydroxylases, Epigenetics and Osteoarthritis","001396","ENDB","Endocrinology B ","","","08","","","",""
"9814699","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003377","","RFA-BX-15-003","5I01BX003377-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","PUBLIC HEALTH RELEVANCE:        Traumatic brain injury (TBI) is a devastating condition as currently no therapy is available to alleviate post-TBI neurological deficits. The proposed study will explore interleukin 4 (IL-4) as a promising recovery-enhancing treatment for TBI. We will investigate whether and how delayed delivery of IL-4 into the injured brain enhances white matter integrity and improves long-term neurological outcomes after experimental TBI. Positive results from this proposal may help identify a potential neurorestorative therapy for the prevention of long-term disability after TBI.","2084976; ","CHEN, JUN ;","","10/01/2016","09/30/2020","Action Potentials; Aftercare; Anti-inflammatory; Astrocytes; Axon; axon regeneration; axonal degeneration; base; Behavior; Biological Process; Brain; Brain Injuries; Cause of Death; Cell Differentiation process; Cell Maturation; Coculture Techniques; Cognitive; Cognitive deficits; controlled cortical impact; Corpus Callosum; cytokine; Data; Demyelinations; Dichloromethylene Diphosphonate; disability; Disease; Exhibits; Failure; Fiber; Generations; gray matter; Human; Immunotherapy; improved; In Vitro; in vivo; Inflammation; Inflammatory; inflammatory marker; Injections; injured; Interleukin-15; interleukin-19; Interleukin-4; Intranasal Administration; Knockout Mice; Liposomes; macrophage; Mediating; Microglia; Military Personnel; Modeling; Myelin; Myelin Sheath; myelination; nanomolar; nanoparticle; neglect; Nervous System Physiology; Neuroglia; Neurologic Deficit; Neurological outcome; neurological recovery; Neurons; neurorestoration; novel; novel therapeutics; oligodendrocyte precursor; Oligodendroglia; Outcome; Peroxisome Proliferator-Activated Receptors; Phenotype; post stroke; PPAR alpha; precursor cell; Prevention therapy; Production; Proliferating; promoter; public health relevance; Quality of life; receptor; Recovery; Regulation; Rehabilitation therapy; remyelination; repaired; Reproducibility; Role; Signal Transduction; success; System; Testing; tissue repair; transcription factor; Traumatic Brain Injury; Traumatic Brain Injury recovery; United States; Veterans; white matter; white matter injury; ","Interleukin-4 as a Novel therapy for Traumatic Brain Injury","003377","NURC","Neurobiology C ","","","04","","","",""
"9815322","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002316","","RFA-BX-17-001","5I01BX002316-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LONG BEACH","UNITED STATES","","47","625399951","US","481011","VETERANS HEALTH ADMINISTRATION","CA","908225201","Project Narrative From the Women?s Health Initiative clinical trial in 25,000 post-menopausal women results show that in women starting hormones within 10 years of the menopause, estrogen replacement menopause clearly reduces the occurrence of heart attacks. Others and we showed that estrogen reduces heart enlargement in rodents that results from poorly controlled high blood pressure in humans. We propose that estrogen prevents high blood pressure and blocks heart enlargement that compromises the function of the heart leading to heart failure. Estrogen acting through one of the estrogen receptors may prevent this in women disposed to developing heart enlargement. By giving a very selective drug that stimulates the estrogen receptor in the heart, but does not stimulate breast or uterine cancer, post-menopausal women and perhaps men (including veterans) may benefit.","1869124; ","LEVIN, ELLIS R;","","04/01/2014","09/30/2022","Acetylesterase; Acute; advanced disease; Agonist; Angiotensin II; Animal Model; Animals; Antihypertensive Agents; APLN gene; Atherosclerosis; Binding; Blood Pressure; Breast; Cardiac; Cardiac development; Cardiac Myocytes; Cardiomegaly; Cardiovascular Diseases; Cardiovascular system; Cell membrane; Cell model; Cell Nucleus; Cells; Clinical Trials; Complex; coronary fibrosis; Cre-LoxP; Data; Development; Disease; Disease Progression; Dose; EP300 gene; Epigenetic Process; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Estrogen Replacements; estrogenic; Estrogens; Event; Female; Fibrosis; functional disability; G-Protein-Coupled Receptors; Gene Proteins; Genes; Growth Factor; HDAC5 gene; Heart; Heart Block; Heart Diseases; Heart failure; heart function; Heart Hypertrophy; Heart Ventricle; Histologic; Histone Deacetylase; Hormone replacement therapy; Hormones; Human; human disease; human female; human model; Hypertension; Hypertrophy; In Vitro; in vivo; in vivo Model; Incidence; Infusion procedures; Knockout Mice; Left; Ligands; male; malignant breast neoplasm; Mammals; Membrane; men; Menopause; Messenger RNA; Modeling; mouse model; Mus; Muscle Cells; Myocardial Infarction; myocardin; Neonatal; Nuclear; Nuclear Proteins; Peptides; Pharmaceutical Preparations; Placebos; Postmenopause; prevent; Prevention; Process; Property; Prospective Studies; protein expression; Protein Isoforms; Proteins; Rattus; receptor; recruit; Reperfusion Injury; response; Rodent; Role; Signal Transduction; System; Testing; transcription factor; Uterine Cancer; Uterus; Ventricular; Veterans; Woman; Women's Health; ","Estrogen receptor and the cardiovascular system","002316","ENDA","Endocriniology A ","","","06","","","",""
"9815328","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003224","","RFA-BX-16-001","5I01BX003224-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Active military service members are exposed to lots of sun, often have poor access to sun protection, and frequently have sunburns during deployment. Thus, they have high rates of skin cancer as Veterans subsequently in life, typically years following active duty. Recent studies have suggested that skin cancer will continue to be a significant health burden for Veterans and VA in the foreseeable future. Vitamin D deficiency is also highly prevalent in the Veterans. This project seeks to understand how the vitamin D signaling pathway may prevent skin cancers. It will provide a rational basis for guiding future health policy in both VA and DOD on appropriate dietary guidelines and sun protective behavior in Veterans. This project's findings may also suggest strategies to pharmacologically prevent the most common skin cancers and for non-surgically treating them once they occur that may be eventually tested in clinical trials.","1927487; ","OH, DENNIS H;","","10/01/2016","03/31/2021","Address; Affect; Anabolism; Animal Model; Animals; base; Biological; Biological Assay; Biological Models; bone health; Calcium; carcinogenesis; Cellular biology; Chemicals; Cholecalciferol; Clinical Trials; Complement; Coupled; Cutaneous; CYP27B1 gene; Cytochrome P450; Data; delta opioid receptor; Dermatologist; dietary guidelines; Disease; DNA Damage; DNA lesion; DNA Repair; DNA Repair Gene; Dose; Enzyme Inhibition; experimental study; Exposure to; Future; Gene Expression; gene repair; General Population; Genes; Genomics; Health; Health Benefit; Health Policy; Human; In Vitro; Individual; inhibitor/antagonist; insight; Institute of Medicine (U.S.); keratinocyte; Ketoconazole; Knockout Mice; Laboratories; Lesion; Life; Ligands; Measures; Mediating; Metabolism; Military Personnel; Minerals; mouse model; Mus; Mutation Analysis; Mutation Spectra; non-genomic; Nucleotide Excision Repair; nutrition; Pathway interactions; Pharmacology; Phenotype; photolysis; photoprotection; Photosynthesis; Physiological; Play; prevent; Production; protective behavior; Proteins; Public Health; Radiation Induced DNA Damage; Recommendation; repaired; Reporting; Research; Research Proposals; Resistance; response; Risk; Role; service member; Signal Pathway; Signal Transduction; Skin; Skin Cancer; skin cancer prevention; small hairpin RNA; Sun Exposure; sun protection; Sunburn; Sunlight; Supplementation; Testing; The Sun; TP53 gene; tumor; ultraviolet; ultraviolet irradiation; Ultraviolet Rays; Uncertainty; UV carcinogenesis; UV induced; Veterans; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Vitamin D3 Receptor; Work; ","Role of Vitamin D in cutaneous DNA repair","003224","IMMA","Immunology A ","","","04","","","",""
"9815329","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003892","","RFA-BX-17-001","5I01BX003892-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Spinal Cord Injury (SCI) is damage to the spinal cord that results in permanent loss of function such as mobility or feeling below injury. There are approximately 270,000 Americans living with SCI, and approximately 20,000 of those injured are Veterans (data from Paralyzed Veterans of America). The number of such injuries is increasing as a result of the Afghanistan war. Thus, care and treatment of spinal cord injured veterans is important to the VA patient care mission. Corticospinal tract (CST) is a very important descending motor system that controls voluntary movement in humans, and appears to be the most refractory motor system from which to elicit regeneration. The proposed study is to characterize a clinical relevant chronic moderate bilateral lower cervical contusion model at cellular and molecular levels and to develop new therapies. The success of this project will benefit those veterans and civilians who suffer SCI.","6904303; ","LU, PENGZHE ;","","10/01/2018","09/30/2022","Acute; Adult; Affect; Afghanistan; American; Americas; Animal Model; Animals; Apoptosis; Atrophic; Axon; axon growth; axon regeneration; Back; base; Bilateral; Bioinformatics; Candidate Disease Gene; Caring; Cervical; Cervical spinal cord structure; Chronic; Cicatrix; clinically relevant; Contusions; Corticospinal Tracts; Data; Data Set; Development; Disease; Down-Regulation; Exhibits; Expeditions; experience; Extracellular Matrix; Feeling; Fishes; Functional disorder; Future; Generations; Genes; Genetic Transcription; Grant; Growth; guided inquiry; Hand functions; Histologic; Human; In Vitro; in vivo evaluation; injured; Injury; Knowledge; Lesion; Lesion by Stage; loss of function; Messenger RNA; Methods; Microglia; Mission; Modeling; Molecular; molecular pathology; molecular targeted therapies; Motor; motor control; Movement; Natural regeneration; nerve stem cell; neurite growth; Neurites; Neuroglia; neuronal cell body; Neurons; novel therapeutics; Outcome; Paralysed; Pathway interactions; Patient Care; postnatal; Process; Quadriplegia; Quality of life; Rattus; Recovery; Refractory; Research; RiboTag; Signal Transduction; Spinal Cord; Spinal Cord Contusions; Spinal cord injury; Spinal cord injury patients; Spinal Ganglia; Stem cell transplant; success; System; Techniques; Testing; therapeutic development; therapy development; Time; Tissues; tool; transcriptome; transcriptome sequencing; vector; Veterans; War; Work; ","Characterization of Chronic Contusive Spinal Cord Injury and Promotion of Corticospinal Tract Regeneration","003892","NURC","Neurobiology C ","","","02","","","",""
"9815334","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004080","","RFA-BX-17-001","5I01BX004080-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","Dry eye disease (DED) is a common condition that can cause discomfort, poor quality of vision and worsened quality of life. DED is more common among patients using multiple medications, including glaucoma medications, and in patients with depression, anxiety and post-traumatic stress disorder. DED is more common among older people and women. As Veterans age and there are increasing numbers of female Veterans, DED has become increasingly important for VA to address. Moreover, Veterans with DED have risk factors for worse outcomes and can have more severe symptoms than the general population. Many types of DED are associated with ocular surface inflammation and over-activity of the immune system, including components of the innate immune system. This project will demonstrate the utility of histatin peptides as a treatment for DED, and their ability to decrease damaging elements of the innate immune system. The results of this project will enhance healthcare for Veterans by creating a novel class of treatments for DED.","7018046; ","AAKALU, VINAY ;","","10/01/2018","09/30/2022","Adaptive Immune System; Address; Advanced Development; Affect; Age; Aging; Anti-Bacterial Agents; Anti-inflammatory; antimicrobial; Anxiety; aqueous; Area; B-Lymphocytes; Benzalkonium Chloride; clinically relevant; Communities; Complex; corneal epithelial wound healing; corneal epithelium; cytokine; Data; Desiccation; Development; Disease; Disease model; effective therapy; Elements; Enhancers; Epithelial; Epithelium; Equilibrium; evaporation; Eye diseases; eye dryness; Family; Female; Film; Functional disorder; Gene Expression; General Population; Genes; Glaucoma; Health; Healthcare; histatin 1; Histidine; histidine-rich proteins; Human; IL8 gene; Immune; Immune response; Immune signaling; Immune system; improved; In Vitro; in vitro Model; in vivo; in vivo Model; Incidence; Inflammation; Inflammatory; Innate Immune System; innovation; Interleukin-1; Interleukin-6; Investigational Therapies; lacrimal; Lead; Light; Lipopolysaccharides; MAPK14 gene; Matrix Metalloproteinases; Mediating; Mediator of activation protein; Mental Depression; Methods; Mitogens; Modeling; mouse model; Mucositis; Myelogenous; Natural Immunity; novel; novel therapeutics; Nuclear; ocular pain; ocular surface; Oral; oral biology; Outcome; palliative; Pathway Analysis; Pathway interactions; Patients; Peptides; Pharmaceutical Preparations; Physiological; Population; Post-Traumatic Stress Disorders; Production; Property; Protein Kinase; Proteins; Quality of life; Research; Risk; Risk Factors; Saliva; Salivary; Signal Pathway; Signal Transduction; Stimulus; Symptoms; System; targeted treatment; Testing; Therapeutic Agents; therapeutic target; TNF gene; Toll-like receptors; Topical application; Toxic effect; Transcription Factor AP-1; translational model; Veterans; Vision; Visual; Woman; Wound Healing; ","Novel Treatments for Modulation of Innate Immunity in Veteran Related Eye Diseases","004080","NURF","Neurobiology F ","","","02","","","",""
"9815340","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004231","","RFA-BX-18-001","5I01BX004231-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SEATTLE","UNITED STATES","","09","020232971","US","481094","VA PUGET SOUND HEALTHCARE SYSTEM","WA","981081532","Cardiovascular disease and type 2 diabetes are present at a high level in the veterans? population. Dietary fat can contribute directly and indirectly to the development of these diseases, and high dietary sucrose can additionally contribute to a ?high cardiovascular risk? metabolic profile. We have shown that moderate high fat diet increases sugar-seeking behavior, in rats. The proposed studies will examine the effects of specific dietary fatty acids (palmitic and oleic acids) on sucrose-seeking behavior, and the brain genetic and signaling mechanisms that underlie this behavior. New understanding of the cell-signaling capability of dietary fats, and influence on neural and molecular substrates for sucrose-seeking behavior, will move the field towards the goal of establishing lifestyle and pharmacotherapeutic interventions for veterans. .","1888157; ","LATTEMANN, DIANNE FIGLEWICZ;","","10/01/2018","09/30/2022","Acute; Address; Age; Astrocytes; Attitude; Behavior; Behavioral; Biological; Brain; calmodulin-dependent protein kinase II; cardiometabolism; Cardiovascular Diseases; cardiovascular risk factor; Cardiovascular system; cell type; Cells; ChIP-seq; Chronic; Clinical; Corpus striatum structure; Cyclic AMP-Dependent Protein Kinases; Data; demethylation; design; Development; diabetes risk; Diet; Diet Habits; Dietary Fats; Dietary Fatty Acid; Dietary Sucrose; Disease; Drug abuse; drug of abuse; drug reward; Eating; Energy Intake; Epigenetic Process; Fatty acid glycerol esters; Female; Food; Fructose; Gene Expression; Gene Expression Regulation; Gene Proteins; Genes; Genetic; Genetic Transcription; Goals; Harvest; High Fat Diet; histone modification; Histones; Hyperphagia; Hypothalamic structure; immunocytochemistry; insight; Intake; Intervention; Life Style; Light; Link; Lysine; Measures; Metabolic; Metabolic Diseases; metabolic profile; Methodology; Methylation; Middle Hypothalamus; Modification; Molecular; Motivation; Neuroglia; Neurons; Non-Insulin-Dependent Diabetes Mellitus; novel; Nutritional; Obesity; Oleic Acids; Palate; Palmitates; Palmitic Acids; Pathology; Pathway interactions; Pattern; Pharmacology; Phenotype; Phosphorylation; Population; preference; Proteins; psychologic; Public Health; Publishing; Rattus; Recommendation; relating to nervous system; Reporting; Rewards; Risk; Role; Self Administration; Signal Transduction; Site; Stearates; Stimulus; Sucrose; sugar; Synapses; Testing; Therapeutic; Veterans; Weight Gain; ","Dietary fatty acids, cell signals, and sucrose intake","004231","ZRD1","Special Emphasis Panel ","","","02","","","",""
"9815357","IK2","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","IK2BX004105","","RFA-BX-17-008","5IK2BX004105-02","","OTHERS","2020","Veterans Affairs","","PALO ALTO","UNITED STATES","","18","046017455","US","481014","VETERANS ADMIN PALO ALTO HEALTH CARE SYS","CA","943041207","A disturbing number of Veterans suffer from cognitive dysfunction due to dementia that has a high likelihood of progressing into Alzheimer's disease. Neurodegeneration is a complex process, involving synaptic dysfunction and memory loss. We aim to examine the signaling molecule Brain-Derived Neurotrophic Factor (BDNF), considered particularly important for neural health and synaptic plasticity in the context of Alzheimer's disease, by assessing its role in magnetic brain stimulation. Transcranial magnetic brain stimulation has been shown to increase BDNF and thus potentially improve cognitive performance in dementia. Information gained from this proposal will enhance our knowledge of both cognitive decline and treatment options. Given that Veterans with cognitive impairment create a huge burden on themselves and others, it is critical to focus research on this eff ort.","14496368; ","MCNERNEY, MARGARET WINDY;","","10/01/2018","09/30/2023","3xTg-AD mouse; Acute; Age; Alzheimer's Disease; Animal Model; Animals; base; Biochemical; Biochemistry; Biological Markers; biomarker evaluation; Blood specimen; Brain; Brain Diseases; Brain Pathology; Brain region; Brain-Derived Neurotrophic Factor; Caregivers; Caring; Cells; Cerebrospinal Fluid; Chronic; clinical translation; Cognition; Cognitive; cognitive function; cognitive performance; cognitive rehabilitation; cohort; Complex; Dementia; Disease; effective therapy; Electromagnetics; experimental study; Failure; Functional disorder; Funding Opportunities; Future; Health; Human; human model; Impaired cognition; Impairment; improved; Individual; innovation; insight; Intervention; Knowledge; Link; locus ceruleus structure; Magnetism; Measurement; Measures; Mediating; Medical; Memory; Memory Loss; Mentors; mild cognitive impairment; Molecular; mouse model; Mus; Nerve Degeneration; neurochemistry; Neurodegenerative Disorders; Neuronal Plasticity; neurotrophic factor; Neurotrophic Tyrosine Kinase Receptor Type 2; novel therapeutic intervention; Pathology; Patients; Performance; Peripheral; Phosphotransferases; Plasma; Population; pre-clinical; prevent; Process; Production; Proteins; receptor; Rehabilitation therapy; relating to nervous system; repetitive transcranial magnetic stimulation; Research; Resources; Role; Senile Plaques; Signal Pathway; Signal Transduction; Signaling Molecule; Structure; Synapses; Synaptic plasticity; System; tau Proteins; technology development; Test Result; Testing; Therapeutic; Transgenic Mice; Translating; Treatment outcome; treatment strategy; Tropomyosin; Urine; Veterans; Vietnam; Work; ","BDNF-mediated effects of rTMS on cognitive dysfunction in Veterans","004105","NURD","Neurobiology D ","","","02","","","",""
"9815401","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001146","","RFA-BX-15-001","5I01BX001146-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","PUBLIC HEALTH RELEVANCE:        Of veterans returning from Iraq and Afghanistan seeking health care at V.A. facilities 2001-2007, 35% received a mental health diagnosis (Cohen BE, J Gen Intern Med 25:18, 2010). Mood disorders are among the most common of these diagnoses, and leading causes of death and disability. Furthermore, the V.A. spends billions of dollars per year on healthcare for veterans with these disorders. The biological basis of mood disorders is poorly understood, however, and novel approaches are needed. Dysfunction of circadian (ca. 24 hr) biological rhythms has been suspected for many years to play a role in mood disorders. With recent developments in circadian biology, it is now possible to test the function of the circadian clock a the molecular level in cells cultured from human patient skin samples, or in brain cells from mouse models of mood disorders, where the clocks can also be manipulated. The studies proposed here, by delineating the role of circadian clocks in depression, could lead to improved treatments for this common disorder afflicting our nation's veterans.","1864336; ","WELSH, DAVID K;","","01/01/2012","09/30/2020","Afghanistan; ARNTL gene; Behavior; Behavioral; Biological; Biological Clocks; Biological Rhythm; Biology; Bioluminescence; Body Temperature; Brain; brain cell; Brain region; Cause of Death; Cell Nucleus; Cell physiology; Cells; cellular imaging; circadian; Circadian Dysregulation; circadian pacemaker; Circadian Rhythms; Clinical; Clinical Research; Clock protein; common treatment; CREB1 gene; cryptochrome; Cultured Cells; Data; Defect; depressed patient; depression model; Development; Diagnosis; Diagnostic; disability; Disease; Dominant-Negative Mutation; Exhibits; Failure; Fibroblasts; Firefly Luciferases; Functional disorder; Gene Expression; Genes; Genetic; Genetic Polymorphism; Goals; Healthcare; Human; Hypothalamic structure; Image; improved; Injections; Internships; Iraq; knock-down; Knock-in; Lead; Learned Helplessness; Lentivirus Vector; Major Depressive Disorder; Measures; Melatonin; Mental Depression; Mental Health; Molecular; Monitor; Mood Disorders; mood regulation; Moods; Motor Activity; mouse model; Mus; mutant; Neurons; novel strategies; Nucleus Accumbens; Patients; Periodicity; Phase; Phenotype; Play; public health relevance; Reporter; Reporter Genes; Repression; Research Design; Research Methodology; Resistance; response; Rewards; RNA; Rodent; Rodent Model; Role; Sampling; Signal Pathway; Signal Transduction; Skin; Sleep Disorders; Slice; small hairpin RNA; Source; suprachiasmatic nucleus; Testing; Therapeutic; tool; Veterans; Viral Vector; ","Cellular Circadian Clocks in Mood Disorders","001146","NURR","Neurobiology R ","","","08","","","",""
"9815402","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000333","","RFA-BX-16-002","5I01BX000333-10","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","Over 50% of combat wounds sustained by OIF/OEF/OND Veterans are musculoskeletal extremity injuries and a significant long-term complication of such orthopedic injury is delayed or non-union. Physical injuries are not the only lasting effects of combat for these Veterans as over 60% receive antidepressants for a wide range of depressive and depressive-associated disorders including post-traumatic stress disorder (PTSD). Studies suggest that the major prescribed class of antidepressant, selective serotonin reuptake inhibitors (SSRIs), is related to poor bone health. Thus, both non-union and fractures occurring while on SSRIs reflect complicated fractures that would clinically benefit from new methods to enhance healing. Our data show that the hematopoietic stem cell (HSC) is a novel source of osteogenic stem/progenitor cells that may serve as a cell- based therapy in these cases. Targeting HSC-derived osteogenic progenitors is innovative, easily translated to clinic, and will have far-reaching benefit for military personnel and Veterans at high risk of complicated fracture.","7775909; ","LARUE, AMANDA C.;","","04/01/2009","09/30/2021","Affect; AMD3100; Animals; Antidepressive Agents; Atrophic; base; Blast Injuries; Blood; bone; bone cell; bone healing; bone health; bone morphogenetic protein 2; bone morphogenetic protein 9; Bone Regeneration; Bone remodeling; Calvaria; Cell Compartmentation; Cell Therapy; Cell Transplantation; Cell Transplants; Cells; Chondrocytes; Clinic; Clinical; clinical application; Clone Cells; combat; Complex; Complication; Data; Defect; depressive symptoms; Development; Devices; Disease; experience; experimental study; FDA approved; Femoral Fractures; Fracture; Fracture Healing; Goals; healing; Healthcare; hematopoietic differentiation; Hematopoietic Stem Cell Mobilization; Hematopoietic stem cells; high risk; Impaired wound healing; Impairment; Implant; In Vitro; in vitro testing; in vivo; injured; Injury; injury and repair; innovation; Intervention; Limb structure; Major Depressive Disorder; Mesenchymal Stem Cells; Methods; migration; Military Personnel; Mission; Modality; Modeling; mouse model; Mus; Musculoskeletal; musculoskeletal injury; negative affect; novel; novel therapeutics; Operative Surgical Procedures; Orthopedics; Osteoblasts; Osteocytes; Osteogenesis; osteogenic; osteoprogenitor cell; Paroxetine; paxil; peripheral blood; Pharmacological Treatment; Population; Post-Traumatic Stress Disorders; Pre-Clinical Model; Prevalence; progenitor; Publishing; recruit; repaired; Role; Selective Serotonin Reuptake Inhibitor; Sertraline; Somatomedins; Source; stem; stem cell differentiation; Stem cells; Survivors; Testing; Therapeutic; Time; Transgenic Mice; Translating; transplant model; Trauma; Veterans; Work; Wound Healing; ","Potential of Hematopoietic Stem Cell-Based Therapies for Complicated Fractures","000333","SURG","Surgery ","","","10","","","",""
"9815406","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001753","","RFA-BX-16-001","5I01BX001753-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOS ANGELES","UNITED STATES","","33","066689118","US","481012","VA GREATER LOS ANGELS HEALTHCARE SYSTEM","CA","900731003","In 2000 our lab and Mignot?s lab discovered that a loss of hypocretin neurons is present in all human narcoleptics. We found gliosis, an indication of inflammation, in the hypocretin cell region in narcoleptics. In 2013 our lab and Scammell?s lab discovered that there is a massive increase in the number of histamine neurons in all human narcoleptics. We hypothesize that the histamine cell increase is either the cause, or result of, an inflammatory process that destroys the hypocretin cells in narcolepsy. Inflammation is a central component of Alzheimer?s and Parkinson?s disease. Histamine is known to produce inflammation in the periphery and opens the blood-brain barrier. A better understanding of the destruction of hypocretin and other neurons in narcolepsy will advance our understanding of all 3 disorders.","1859335; ","SIEGEL, JEROME M;","","10/01/2012","09/30/2020","Acetylcholine; Affect; Aging; Alzheimer's Disease; Amphetamines; Amygdaloid structure; Animal Genetics; Animal Model; Animals; Antibodies; Antidepressive Agents; Antigens; Antihistamines; Appearance; Arousal; Autoimmune Diseases; Axon; Blood - brain barrier anatomy; Brain; Brain Injuries; Brain region; Brain Stem; Canis familiaris; Cataplexy; Cell Count; cell injury; cell killing; Cell Size; Cells; Collection; Data; Denervation; Disease; Dopamine; Drug usage; experience; Failure; gamma hydroxybutyrate; General Population; Genetic; Genetic Models; Genotype; Glial Fibrillary Acidic Protein; Gliosis; Golgi Apparatus; Grant; Haplotypes; Histamine; Histidine Decarboxylase; HLA Antigens; Household; Human; Human Genetics; hypocretin; Hypothalamic structure; Immune system; Immune Targeting; immunoreactivity; In Vitro; Incidence; Infection; Inflammation; Inflammatory; Insect Bites; insight; Investigation; Knockout Mice; Label; Laboratories; Lead; Link; locus ceruleus structure; Mediating; Mediation; Methods; Modeling; Monozygotic twins; Morphology; Mus; mutant; Mutation; Narcolepsy; Nature; Neurodegenerative Disorders; neuron loss; Neurons; Neurotransmitters; Norepinephrine; orexin B receptor; Paper; Parkinson Disease; Pathology; Patients; Pattern; Peptides; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; prevent; Process; Publishing; Regulation; Reporting; Research Personnel; response; Role; Secondary to; Serotonin; Silver; Sleep; Stains; Substantia nigra structure; Symptoms; System; T-Lymphocyte; Testing; Time; Tissues; Toxic effect; venlafaxine; Ventral Tegmental Area; Work; ","What Causes Human Narcolepsy?","001753","NURR","Neurobiology R ","","","08","","","",""
"9815440","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003725","","RFA-BX-16-001","5I01BX003725-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NEW ORLEANS","UNITED STATES","","","828108790","US","481038","SOUTHEAST LOUISIANA VETERANS HEALTH CARE","LA","701611011","Project Narrative The research proposed in this grant will have a significant impact because when successfully completed it will fill key gaps in our understanding of the basic mechanism of insulin deficiency and type 2 diabetes in a large segment of the aging and androgen-deficient male population of the Veterans Healthcare system. This information will provide the foundation for development of approaches to modulate the androgen receptor (AR) to prevent diabetes without prostate or cardiovascular side effects. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page","7923490; ","MAUVAIS-JARVIS, FRANCK ;","","10/01/2017","09/30/2021","Address; Aging; Androgen Receptor; androgen sensitive; Androgens; base; Beta Cell; Cardiovascular system; Cell physiology; Cells; Clinical; clinically relevant; Cyclic AMP; Cyclic AMP Receptors; Cyclic AMP-Dependent Protein Kinases; Data; design; Development; Diabetes Mellitus; Diabetes prevention; diabetes risk; Drug Targeting; Epidemic; Estrogen Receptors; estrogenic; Exhibits; Failure; Female; Foundations; Functional disorder; Generations; Genetic; GLP-I receptor; glucagon-like peptide 1; Glucose; Goals; Grant; Gynecology; Healthcare Systems; High Fat Diet; Human; human male; Hyperglycemia; innovation; Insulin deficiency; Insulin Resistance; insulin secretion; Investigation; islet; Islet Cell; Knowledge; Laboratories; Life Expectancy; Ligands; male; Mediating; men; Metabolic; Metabolic dysfunction; Methods; Molecular; mouse model; Mus; Non-Insulin-Dependent Diabetes Mellitus; novel; novel strategies; novel therapeutics; Nuclear; Peptides; Pharmacology; Physiological; Pilot Projects; Population; prevent; Prostate; Prostate Cancer therapy; Publishing; Research; Risk; Risk Factors; Rodent; Role; Selective Estrogen Receptor Modulators; side effect; Signal Transduction; Structure of beta Cell of islet; Testosterone; Therapeutic; therapeutic target; Time; Tissues; tool; transcription factor; Veterans; Woman; Work; ","The role of the androgen receptor in insulin secretion","003725","ENDA","Endocriniology A ","","","03","","","",""
"9869755","Y01","HL","","N","","","","","Y01HL150030","","","AHL15003001-1-0-1","NHLBI:353239\","INTERAGENCY AGREEMENTS","2019","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","","","","","","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","; ",",  ;","","","","Blood donor; Communicable Diseases; Databases; Evaluation; Funding; Geography; Hepatitis B Virus; Hepatitis C virus; HIV; Infection; infection risk; interest; Intervention; Monitor; National Heart, Lung, and Blood Institute; Research Activity; Risk Factors; Risk Marker; System; Testing; Time trend; Transfusion; trend; Vascular blood supply; ","Temporal Trends in Transfusion ?Transmissible Infections Risks and Monitoring of Donor Risk Factors in the US Blood Supply Project (TTIMS)","","","","","","","","","353239",""
"9870011","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004858","","RFA-BX-19-022","1IK6BX004858-01","","OTHERS","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","Age-related macular degeneration (AMD) is an age-related disease with genetic and environmental risk factors that is significantly affected by smoking. AMD has two outcomes, wet AMD or dry AMD; and while there are treatments for the former, none are available for the latter. Developing novel treatment strategies, is therefore essential to reduce the incidence and progression of AMD and improve quality of life for veterans with AMD. The goal of our research is to study mechanisms underlying AMD in cell- and animal- based experiments and develop novel diagnostic and treatment strategies to reduce the damage produced by the disease or help repair the tissues affected. Our long-term goal is to translate our treatment strategies from animal models to our veterans, which makes this research highly relevant to the VA mission.","6573140; ","ROHRER, BAERBEL ;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award for Dr. Barbel Rohrer","004858","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9872724","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004852","","RFA-BX-19-022","1IK6BX004852-01","","OTHERS","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","The number of veterans afflicted with MS is estimated at about 30,000; and some studies have suggested that the incidence of MS is higher in certain veteran populations than in civilian populations. Knowledge of specific genetic factors that are a risk for MS, as well as finding new treatments could help reduce minimize MS rate and symptom severity in patients. With increasing age, more and more veterans will develop AD, possibly at higher rates due to environmental factors or dietary factors, which will create new challenges for the VA healthcare systems. Our studies on the relationships between alcohol consumption and AD, or exposure to warfarins or superwarfarins and development of treatments to minimize their detrimental effects, could therefore help prevent the overall increase in AD rates.","1904215; ","FEINSTEIN, DOUGLAS L.;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award Application","004852","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9763694","I01","VA","2","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX002872","","RFA-BX-18-001","2I01BX002872-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CLEVELAND","UNITED STATES","","14","093016124","US","481118","LOUIS STOKES CLEVELAND VA MEDICAL CENTER","OH","441413204","The introduction of antibiotics >80 years ago was a revolutionary occurrence that saved the lives of millions of people. Yet, in 2014, a high-profile review estimated that the number of deaths due to untreatable infections could reach 10 million by 2050; thus, foreshadowing the evaporation of effective antibiotic therapies. ?- Lactamase-mediated resistance by Gram-negative pathogens is an existing threat to Veterans and the general population. Of these Gram-negatives, Burkholderia cepacia complex (Bcc) is emerging as important group of antibiotic-resistant pathogens and our understanding of these unique pathogens remains underdeveloped. Patients with lung diseases (i.e., chronic obstructive pulmonary disorder (COPD), asthma, and cystic fibrosis) are highly susceptible to acquire Bcc infections such as pneumonia and bacteremia. Moreover, in the last 17 years, Bcc was found throughout the US VA healthcare system and resulted in a 35% mortality rate for affected Veterans. The goal of this project is to discover novel therapies to treat highly drug-resistant Bcc infections.","10348881; ","PAPP-WALLACE, KRISZTINA MARGARET;","","10/01/2015","09/30/2023","Address; Affect; Affinity; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Asthma; Award; Bacteremia; base; beta-Lactam Resistance; beta-Lactamase; beta-Lactams; Binding; Biochemical; Biological; Biological Assay; Burkholderia cepacia complex; Burkholderia Infections; carbapenemase; Ceftazidime; Cells; Cellular Morphology; Cephalosporinase; Cessation of life; Chromosomes; Chronic; Chronic Obstructive Airway Disease; Clinical; Complex; Crystallization; Crystallography; Cystic Fibrosis; Development; Disease Outbreaks; Drug resistance; drug resistant pathogen; Electrophoretic Mobility Shift Assay; evaporation; Exposure to; Fluorescence; Gene Expression; Gene Proteins; General Population; Genes; Genetic Transcription; genome analysis; Goals; Healthcare Systems; Imipenem; Immunoblotting; in vivo; in vivo evaluation; Individual; Infection; inhibitor/antagonist; Isoelectric Focusing; Kinetics; Knock-out; knockout gene; Lactamase; Lactams; Lead; Libraries; Ligands; Link; Lung diseases; Measures; Mediating; Medical; member; Membrane; Microscopy; Modeling; molecular mass; molecular modeling; mortality; Multi-Drug Resistance; multi-drug resistant pathogen; Mutation; New Agents; novel; novel strategies; novel therapeutics; Organism; Outcome; pathogen; Patients; Penicillin-Binding Proteins; Phase-Contrast Microscopy; Phenotype; Piperacillin; Pneumonia; PPBP gene; Predisposition; Preparation; Prevalence; Production; Protein Inhibition; Proteins; Regulation; Resistance; resistance mechanism; Retrospective Studies; Risk; small molecule; small molecule inhibitor; Spectrometry, Mass, Electrospray Ionization; Structure; Testing; Therapeutic; VDAC1 gene; Veterans; whole genome; ","Targeting Burkholderial ?-lactamases: Structure, function, and regulation","002872","ZRD1","Special Emphasis Panel ","","","05","","","",""
"9814683","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003188","","RFA-BX-16-001","5I01BX003188-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","One in two women, and one in five men, over age 50 will experience an osteoporotic fracture during their lifetime. Osteoporosis-related fragility fractures cause high morbidity and excess mortality in our aging Veteran population, and add tremendously to VA Healthcare costs. One area of unmet need is to develop new `anabolic' therapies for severe osteoporosis. The goal of this project is to test whether the unique pharmacodynamic properties of a `biased' agonist of the type 1 parathyroid hormone receptor (PTH1R) enables it to circumvent the limitations of current therapeutics. Each of three specific aims compares conventional and biased PTH1R agonists in a different pre-clinical rodent model of metabolic bone disease to test whether biased agonism affords specific advantages in terms of reduced side effects and retained effectiveness in settings where a conventional PTH1R agonist is ineffective or contraindicated. Completion of this project may ultimately lead to the development of novel therapeutics that will benefit Veterans of both genders.","1867550; ","LUTTRELL, LOUIS M;","","10/01/2016","09/30/2020","Address; Adverse effects; Affect; Age; Aging; Agonist; American; Anabolic Agents; analog; Area; arrestin3; Arrestins; attributable mortality; bone; Bone Formation Stimulation; bone fragility; bone loss; bone mass; Bone Resorption; bone turnover; Calcium; Cattle; Chronic Kidney Failure; Clinical; comparative efficacy; congenic; Continuous Infusion; Cyclic AMP; Development; Disease model; Dose; Drug Kinetics; Effectiveness; Excess Mortality; experience; experimental study; Exposure to; FDA approved; Female; Forteo; Fracture; fracture risk; fragility fracture; functional genomics; G-Protein-Coupled Receptors; Gender; Goals; Gonadal Steroid Hormones; GTP-Binding Proteins; Health Care Costs; Healthcare; Heterotrimeric GTP-Binding Proteins; hormone analog; Hypercalcemia; Hyperparathyroidism; In Vitro; in vivo; Injections; insight; Kidney Failure; Knockout Mice; Lead; Ligands; male; Mediating; men; Metabolic Bone Diseases; Mission; Modeling; Morbidity - disease rate; mouse model; Mus; Nephrectomy; novel; novel strategies; novel therapeutics; osteoblast differentiation; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; osteoporosis with pathological fracture; Parathyroid Hormone Receptor; Pathway interactions; Pharmacodynamics; Pharmacology; Population; pre-clinical; Preclinical Testing; Property; PTH gene; receptor; Receptor Activation; receptor coupling; Receptor Signaling; Regimen; renal calcium; Renal Osteodystrophy; response; Rodent Model; Role; Secondary Hyperparathyroidism; side effect; Signal Pathway; Signal Transduction; skeletal; substantia spongiosa; targeted treatment; Testing; Therapeutic; validation studies; Veterans; Withdrawal; Woman; Work; ","Functionally-selective parathyroid hormone analogs as therapeutics in metabolic bone disease","003188","ENDB","Endocrinology B ","","","04","","","",""
"9814696","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003692","","RFA-BX-16-001","5I01BX003692-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","Urothelial carcinoma (bladder cancer) is the fourth most common cancer in the VHA accounting for 7% of all cancers. More than half of bladder cancer is associated with smoking and potential deployment-related carcinogens. The majority of bladder cancer (up to 80%) is non-muscle invasive and bladder cancer remains the most costly cancer to treat due to a high frequency of both recurrence (up to 70% at five years) and progression (25% at five in high-risk patients). The long-term goal of our research is to investigate the molecular and epigenetic pathways driving invasion of bladder cancer. Our central hypothesis is that the protein Enhancer of Zeste-2 (EZH2) drives invasion of bladder cancer by causing global changes in histone methylation that shifts cellular identity to an invasive and stem cell-like phenotype via an epithelial to mesenchymal transition. In this proposal, we investigate the role of EZH2 in invasion, determine the transcriptional and histone targets, and identify novel EZH2-based therapies for treatment of Veterans.","6069708; ","MEEKS, JOSHUA JAMES;","","10/01/2016","09/30/2020","Accounting; actionable mutation; Address; Affect; Aggressive course; Automobile Driving; base; Bioinformatics; Bladder; Bladder Neoplasm; cancer cell; Cancer cell line; Cancer Etiology; cancer initiation; cancer invasiveness; Cancer Model; Carcinogens; Carcinoma; Cause of Death; Cell Proliferation; Cells; Cessation of life; Chromatin; chromatin immunoprecipitation; chromatin remodeling; clinical investigation; Complex; cost; Data; Databases; Development; Diagnosis; DNA Sequence Alteration; Enhancers; Epigenetic Process; epithelial to mesenchymal transition; Exposure to; Frequencies; Gene Expression; Gene Expression Regulation; gene repression; Genes; Genetic; Genetic Transcription; Genomic medicine; Global Change; Goals; high risk; histone methylation; histone methyltransferase; Histones; Human; in vivo Model; inhibitor/antagonist; innovation; Interdisciplinary Study; Investigation; knock-down; Link; Lysine; Malignant neoplasm of urinary bladder; Malignant Neoplasms; Mediating; men; Metastatic Neoplasm to Lymph Nodes; Methylation; Modeling; Molecular; mouse model; Mus; Muscle; Mutation; non-muscle invasive bladder cancer; novel; novel therapeutic intervention; novel therapeutics; Occupational Exposure; overexpression; Pathway interactions; Patients; personalized medicine; Pharmacology; Phenotype; Polycomb; pre-clinical; precision genetics; Process; Proliferating; Property; protein expression; Proteins; Recurrence; Regulator Genes; Repression; Research; Resistance; Risk; Role; Smoking; Specimen; Stem cells; stem-like cell; targeted agent; targeted treatment; Therapeutic; therapeutic development; therapeutic target; therapy resistant; Tissue Microarray; Transcription Initiation Site; Transferase; Transitional Cell Carcinoma; tumor; tumor initiation; tumor progression; Urothelial Cell; Veterans; ","The Role of EZH2 in Non-Muscle Invasive Bladder Cancer","003692","ONCA","Oncology A ","","","04","","","",""
"9815325","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002746","","RFA-BX-17-001","5I01BX002746-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","Since current clinical imaging (MRI/PET) can only detect tumors larger than 10 million tumor cells, it is exceedingly difficult to distinguish whether cancer therapies shrink tumor size by killing tumors or causing tumor cell scattering. These two scenarios have vastly different implications for the metastatic spread of cancer that eventually causes patient death. There are now more than 2.2 million women Veterans in the United States, and the health concerns of this growing female Veteran population are a VA priority. The National Cancer Institute estimates that 1 out of 8 women will develop breast cancer in their lifetime, yielding a current population of 275,000 female Veterans who will confront breast cancer and require effective treatment. This project will develop strategies to improve breast cancer treatment for the growing female Veteran population.","6948120; ","MARTIN, STUART S;","","10/01/2018","09/30/2022","Actins; Affect; Animals; Antineoplastic Agents; Area; automated image analysis; base; Behavior; Biomedical Engineering; Blood Circulation; Blood Vessels; Breast Cancer Cell; Breast Cancer cell line; Breast cancer metastasis; Breast Cancer Patient; Breast Cancer therapy; Breast Cancer Treatment; Cancer Center; cancer imaging; cancer recurrence; cancer risk; cancer therapy; cell growth; Cells; Cessation of life; Characteristics; chemotherapy; Clinical; clinical imaging; Clinical Treatment; clinically relevant; confocal imaging; Confocal Microscopy; Core Biopsy; Detection; Distant; drug testing; effective therapy; Ensure; Epithelial; Epothilones; ERBB2 gene; FDA approved; Female; Growth; Health; Hour; Image; improved; Incidence; Individual; individual patient; individual response; individualized medicine; Laboratories; Legal patent; Magnetic Resonance Imaging; malignant breast neoplasm; Malignant Neoplasms; Mammospheres; Maryland; Measurement; Measures; Metastatic to; Methods; Microfluidic Microchips; Microfluidics; Microtubule Stabilization; Microtubules; Modeling; Modification; Molecular; molecular marker; molecular phenotype; Molecular Profiling; mouse model; multidisciplinary; Mus; National Cancer Institute; Neoplasm Circulating Cells; Neoplasm Metastasis; neoplastic cell; new technology; novel; off-patent; Operative Surgical Procedures; optical imaging; Patient Noncompliance; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; phenotypic biomarker; Plasma; Population; Positron-Emission Tomography; pressure; prevent; Publishing; Recurrence; Research Priority; Residual state; response; response biomarker; Risk; risk minimization; Sampling; Stem cells; Surface; Tail; taxane; Technology; Testing; Time Study; tissue culture; Tissues; Translating; Translations; Transplantation; treatment strategy; Tubulin; tumor; tumor growth; United States; Universities; Veins; Veterans; Woman; Women's Health; wound; Wound Healing; Xenograft Model; Xenograft procedure; ","Rapid analysis of patient tumor cell drug responses to reduce metastatic risk","002746","CAMM","Cellular and Molecular Medicine ","","","02","","","",""
"9815330","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003893","","RFA-BX-17-001","5I01BX003893-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NEW ORLEANS","UNITED STATES","","","828108790","US","481038","SOUTHEAST LOUISIANA VETERANS HEALTH CARE","LA","701611011","Experience of a life-threatening psychological trauma significantly increases the likelihood of developing post-traumatic stress disorder (PTSD), an anxiety disorder. Exposure of rodents to natural predator odors causes emotional stress, alters endocannabinoid (2-AG) levels and leads to anxiety- like behaviors. Our investigation of the cellular mechanisms underlying a psychological stress-induced reduction in 2-AG tone and possible pharmacological interventions to reverse such a change may suggest new therapeutic approaches by which an increase in 2-AG levels could be used to treat PTSD.","8666742; ","LIU, SIQIONG JUNE;","","10/01/2018","09/30/2022","2-arachidonylglycerol; 2-arachidonylglycerol signaling; Adrenergic Agents; Adrenergic Receptor; Affect; Animal Model; Anxiety; Anxiety Disorders; anxiety-like behavior; Applications Grants; Attenuated; Behavioral; biological adaptation to stress; Brain region; Cerebellum; Chronic stress; conditioned fear; Data; designer receptors exclusively activated by designer drugs; Development; Emotional Stress; endocannabinoid signaling; Endocannabinoids; Enzymes; Exhibits; experience; experimental study; Extinction (Psychology); FDA approved; fear memory; Foxes; Fright; gamma-Aminobutyric Acid; General Population; Genetic Transcription; Impairment; in vivo; Individual; Interneurons; Intervention; Investigation; Knowledge; Learning; Life; Life Experience; lipoprotein lipase; locus ceruleus structure; LoxP-flanked allele; Membrane; Memory; memory consolidation; Memory impairment; memory retention; Mental Depression; Mental Health; Metabolism; Modeling; Monoacylglycerol Lipases; Mood Disorders; Mus; neural circuit; neuronal excitability; Neurons; new therapeutic target; Norepinephrine; novel; novel strategies; novel therapeutic intervention; Odors; Pain; Pharmaceutical Preparations; Pharmacology; Phenotype; Post-Traumatic Stress Disorders; Potassium Channel; presynaptic; prevent; Production; Psychological Stress; psychological trauma; Purkinje Cells; Receptor Signaling; reduce symptoms; Regulation; Research; response; Rodent; Role; Signal Pathway; Stress; stressor; Structure of molecular layer of cerebellar cortex; Synaptic Transmission; synthetic enzyme; Testing; transmission process; traumatic event; treatment strategy; Urine; Veterans; ","Psychological stress reduces endocannabinoid tone: mechanisms and possible treatments","003893","MHBA","Mental Health and Behavioral Science A ","","","02","","","",""
"9815429","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003687","","RFA-BX-16-001","5I01BX003687-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","MINNEAPOLIS","UNITED STATES","","05","071774624","US","481047","MINNEAPOLIS VA  MEDICAL CENTER","MN","554172309","Non-exercise activity thermogenesis (NEAT) and the spontaneous physical activity that drives it are involved in individual variation in propensity to become obese with overfeeding. Some individuals remain lean in the face of overfeeding, and a high level of NEAT predisposes one to be thin. A discovery made by our lab is the finding that the natural brain chemical called orexin (which occurs in humans) initiates NEAT. Our goal is to understand the parts of the brain in which orexin works so that we can develop therapies for humans based on increasing NEAT. To obtain knowledge needed to do this, we will study mouse brain orexin circuits and possible treatment strategies. This will help determine how best to develop orexin-based treatments for obesity and other brain mechanisms that promote NEAT. We will use a new technology (DREADDS) that allows us to stimulate and monitor the activity of orexin neurons. We will also determine if serotonin affects NEAT. By refining possible drug targets, we will inform individualized treatment for obesity.","1944196; 1878927 (contact); ","BILLINGTON, CHARLES J.; KOTZ, CATHERINE M (contact);","","10/01/2017","09/30/2021","Acute; addiction; Affect; Animal Model; Animals; Antidepressive Agents; Area; base; Body Weight; Body Weight decreased; Brain; Brown Fat; Calories; Cells; Chemicals; Chronic; Clinical; Comorbidity; compare effectiveness; Data; designer receptors exclusively activated by designer drugs; Disease; dorsal raphe nucleus; Drug Targeting; Effectiveness; Energy Metabolism; Equipment; Exercise; Expenditure; Goals; Health; Human; hypocretin; Hypothalamic structure; Individual; individual variation; individualized medicine; Injury; Knowledge; Laboratories; Lateral; Length; Location; Measures; Mediating; Methods; Monitor; Mus; Nerve; Neurons; Neuropeptides; Neurotransmitters; new technology; novel therapeutics; Obesity; obesity treatment; orexin A; Outcome; Output; Pharmaceutical Preparations; Physical activity; Play; Population; precision medicine; prevent; Property; receptor; response; Role; Serotonin; Serotonin Agents; serotonin receptor; Site; Study models; targeted treatment; Testing; therapy development; therapy duration; Thermogenesis; Thinness; treatment strategy; Veterans; Weight; Weight Gain; weight gain prevention; Work; ","Orexin and serotonin interactions to promote physical activity and prevent obesity","003687","ENDA","Endocriniology A ","","","03","","","",""
"9815439","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003688","","RFA-BX-17-001","5I01BX003688-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","In cancer, chemokines drive the transit of tumor cells and pathologic cell traffic that includes migration of tolerance-promoting dendritic cells (DCs) from the tumor to draining lymph nodes (DLNs). In lung cancer, such tumor-infiltrating DCs (TIDCs) induce immune-suppression. Initial work shows that genetically targeting certain complex sugars (glycans) specifically on DCs may slow lymphatic TIDC traffic and induce maturation of TIDCs, which importantly correlates with carcinoma growth inhibition and an anti-tumor immune profile. While this strategy appears to effectively ?re-program? immunity against the tumor, our understanding of mechanisms and pre-clinical targeting approaches in lung cancer models remains limited. Herein, we employ novel genetic methods and inhibitors to interfere with such glycans in TIDCs, while examining for anti-tumor immunologic shifts in the tumor and DLNs. This study examines novel mechanisms and validates key genetic targets to induce anti-tumor immunity and tumor regression in lung cancer, with an eye to therapeutic translation. !","2168683; ","FUSTER, MARK M;","","10/01/2017","09/30/2021","Activities of Daily Living; Address; Affect; Anabolism; anti-cancer; Antigen Presentation; Antigens; Antisense Oligonucleotides; Area; base; Binding; Cancer Model; Cancer Patient; Carbohydrates; Carcinoma; CCL21 gene; CD8-Positive T-Lymphocytes; cell behavior; Cell Communication; Cell Maturation; cell motility; Cell physiology; Cell surface; Cells; chemokine; chemokine receptor; Chest; Clinical; Complex; CX3CL1 gene; CXCL12 gene; cytokine; Cytolysis; Dendrites; Dendritic cell activation; Dendritic cell tumor; Dendritic Cells; Development; Disease remission; Drug Design; effector T cell; Enzymes; Equilibrium; Eye; Genetic; Goals; Growth; Heparan Sulfate Biosynthesis; Heparitin Sulfate; Human; Immune; immune function; Immune Tolerance; Immunity; Immunologics; Immunophenotyping; Immunosuppression; Immunosuppressive Agents; Immunotherapy; improved; inhibitor/antagonist; Kinetics; KRAS2 gene; Lead; Lewis Lung Carcinoma; lung Carcinoma; Lung Neoplasms; lymph nodes; Lymphatic; Lymphatic Endothelium; Lymphatic vessel; lymphocyte proliferation; Malignant neoplasm of lung; Malignant Neoplasms; Mediating; Methods; migration; mimetics; Modeling; Molecular; Mus; mutant; Mutation; Neoplasm Metastasis; neoplastic cell; novel; novel strategies; novel therapeutics; Ovalbumin; Ovum; Pathologic; Pathway interactions; Patients; Phenotype; Polysaccharides; pre-clinical; Preparation; Primary Neoplasm; Production; programs; Property; Proteoglycan; proteoglycan core protein; receptor; Regulatory T-Lymphocyte; response; scaffold; Signal Transduction; small molecule inhibitor; sugar; sulfation; Surface; syndecan; T cell response; T-Lymphocyte; targeted agent; Testing; Therapeutic; trafficking; Transgenic Organisms; Translations; tumor; Tumor Antigens; tumor growth; Tumor Immunity; tumor microenvironment; tumor progression; Unspecified or Sulfate Ion Sulfates; Ursidae Family; Validation; Work; ","Dendritic Cell Proteoglycans and Reprogramming Cancer Immunity","003688","ONCB","Oncology B ","","","03","","","",""
"9815442","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003897","","RFA-BX-17-001","5I01BX003897-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","We hypothesize that hearing loss caused by two different classes of agents, platinum chemotherapy and aminoglycoside antibiotics, is due to free radical damage in the ear, and that inflammation will exacerbate these effects. We will perform preclinical studies to determine if chemoprotection with the thiols sodium thiosulfate and/or N-acetylcysteine decreases inflammation-enhanced ototoxicity. We will also evaluate high- resolution neuroimaging with ferumoxytol iron oxide nanoparticles as a biomarker for cochlear inflammation and ototoxicity.","1863992; ","NEUWELT, EDWARD A.;","","10/01/2017","09/30/2021","Acetylcysteine; Acute; Aminoglycoside Antibiotics; aminoglycoside-induced ototoxicity; Aminoglycosides; Animal Model; Animals; Auditory Brainstem Responses; base; Basic Science; Biological; Biological Markers; Bone Marrow; Brain; Brain Neoplasms; Carboplatin; CD14 Antigen; cell injury; Cell Survival; Cells; Chemoprotection; Chemoprotective Agent; chemotherapeutic agent; chemotherapy; Chemotherapy-Oncologic Procedure; Cisplatin; Clinic; Cochlea; Contrast Media; Detection; DNA Intercalation; Dose; Dose-Limiting; Ear; Endotoxemia; ferumoxytol; Free Radical Formation; Free Radicals; Funding; Gentamicins; Glutathione; Goals; Hair Cells; Hearing; hearing impairment; Hour; Image; imaging biomarker; Imaging Techniques; immune activation; Immunohistochemistry; improved; Infection; Infiltration; Inflammation; Inflammatory; Injections; Innate Immune Response; Innate Immune System; Intravenous; iron oxide nanoparticle; Kidney; Knock-out; Lesion; Lipopolysaccharides; macromolecule; macrophage; Magnetic Resonance Imaging; Measures; Mediating; Microglia; middle ear disorder; Molecular; Monitor; monocyte; nephrotoxicity; neuroimaging; neuroinflammation; neutrophil; Neutrophil Infiltration; novel; otoacoustic emission; ototoxicity; Outcome; pathogen; Pathway interactions; patient population; Patients; Pattern; Permeability; peroxidation; Pharmaceutical Preparations; Phase III Clinical Trials; Platinum; preclinical study; Process; Protein Synthesis Inhibition; Quality of life; Rattus; Reactive Nitrogen Species; Reactive Oxygen Species; Regimen; Reproducibility; Research; Resolution; Risk; side effect; Signal Transduction; sodium thiosulfate; Solid Neoplasm; Stimulus; Sulfhydryl Compounds; Testing; Therapeutic Agents; therapeutic biomarker; Therapeutic Uses; therapy outcome; Time; Tissues; tool; Toxic effect; Toxicity due to chemotherapy; Treatment Protocols; tumor; ","Chemoprotection and imaging for aminoglycoside and chemotherapy toxicities","003897","NURB","Neurobiology B ","","","03","","","",""
"9815443","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003913","","RFA-BX-17-001","5I01BX003913-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","Sphingolipids are complex lipid molecules that control a variety of cellular functions. Knowledge of the transport of these lipids in blood and their contribution to the development of neuropathy is limited. We will measure the amounts of these lipids in blood from Veterans with type 1 diabetes without neuropathy and determine if differences in the blood levels of specific sphingolipids can predict the future development of neuropathy. We also will investigate potential mechanisms whereby sphingolipids in lipoproteins may contribute to diabetic neuropathy by incubating human Schwann cells in culture with lipoproteins prepared from Veterans with neuropathy and determine the changes in cell metabolism which result. These are the first studies to analyze the sphingolipid composition in blood from Veterans with the neuropathy associated with diabetes and most importantly, to determine the potential for plasma sphingolipid concentrations to predict the development of neuropathy in Veterans with diabetes.","1887336; ","KLEIN, RICHARD LOUIS;","","10/01/2017","09/30/2021","Affect; Afferent Neurons; Age; Blood; cancer therapy; Cell membrane; Cell physiology; Cells; Cellular Metabolic Process; Ceramides; Clinical; Complex; Complication; Cross-Sectional Studies; Data; Data Analyses; Development; Diabetes Mellitus; Diabetic Neuropathies; diabetic patient; Disease; Exhibits; Future; Gender; Hereditary Sensory and Autonomic Neuropathies; High Density Lipoproteins; Human; In Vitro; in vivo; Incubated; Insulin-Dependent Diabetes Mellitus; Intervention; Investigation; Knowledge; lipid transport; Lipids; Lipoproteins; Low-Density Lipoproteins; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Medical; Membrane; Metabolism; Neurons; Neuropathy; neurotoxic; Non-Insulin-Dependent Diabetes Mellitus; Patients; Peripheral Nervous System Diseases; Pharmacology; Pilot Projects; Plasma; Plasma Cells; Race; recruit; Role; Sampling; Schwann Cells; Secondary to; Sphingolipids; Testing; Tissues; United States; Very low density lipoprotein; Veterans; ","The Role of Deoxysphingolipids in Peripheral Neuropathy","003913","NURB","Neurobiology B ","","","03","","","",""
"9815445","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004049","","RFA-BX-17-001","5I01BX004049-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BIRMINGHAM","UNITED STATES","","07","082140880","US","481003","BIRMINGHAM VA MEDICAL CENTER","AL","352331927","Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that is characterized by high autoantibody titers and elevated type I interferon (IFN) responses. Our use of powerful new techniques, including single cell gene expression analysis, has generated data indicating that intrinsically elevated IFN? production by early immature B cells imprints altered responses to IFN? signaling on the maturing B cells. This both promotes escape of autoreactive cells from normal deletion process and shifts development of suppressive regulatory B cells toward a proinflammatory phenotype. This paradigm shifting hypothesis will be tested using advanced in vivo and in vitro techniques to distinguish the roles of intrinsic B cell defects and environmental signals; test the proposed imprinting of the maturing B cells and its effects on tolerance induction and maintenance; and test if the intrinsic or imprinted B cell defects correspond to disease activity and therapeutic responsiveness in SLE patients at the BVAMC.","6209428; ","MOUNTZ, JOHN D;","","10/01/2017","09/30/2021","Antibodies; Antigens; Apoptotic; Autoantibodies; Autoantigens; autocrine; Autoimmune Diseases; Autoimmunity; Automobile Driving; autoreactive B cell; autoreactivity; B-Lymphocyte Subsets; B-Lymphocytes; base; Biological Response Modifier Therapy; Bone Marrow; Caring; Cell Compartmentation; Cell Maturation; Cell Separation; Cell Survival; Cells; Chimera organism; Chronic; Clinical; Cluster Analysis; cytokine; Data; Defect; design; Development; Disease; Elements; Environmental Risk Factor; Event; Exhibits; experimental study; Flow Cytometry; FOXP3 gene; Funding; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Generations; Genetic Predisposition to Disease; Genetic Transcription; Goals; Grant; IFNAR1 gene; Immunocompetent; immunogenic; Immunoglobulin Idiotypes; imprint; improved; In Vitro; in vivo; insight; inter-individual variation; Interferon Receptor; Interferon Type I; Interferon-alpha; Interferon-beta; Interferons; Interleukin-10; IRF3 gene; Lupus; Maintenance; Mature B-Lymphocyte; Mediating; migration; Modeling; Molecular; mouse model; Mouse Strains; Mus; novel; Nuclear; Nucleic Acids; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phenotype; Play; Population; precision medicine; Process; Production; receptor-mediated signaling; Receptors, Antigen, B-Cell; Reporter; Resolution; response; Role; Signal Transduction; single cell analysis; Specificity; Systemic Lupus Erythematosus; T-Lymphocyte; Techniques; Testing; Therapeutic; therapeutic target; TLR7 gene; tool; transcription factor; Transitional Cell; Up-Regulation; Work; ","Interferon Beta Initiated Development of Immunogenic T1 B cells in Lupus","004049","IMMA","Immunology A ","","","03","","","",""
"9868210","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004835","","RFA-BX-19-022","1IK6BX004835-01","","OTHERS","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Our on-going research employs state-of-the-art technologies along with novel preclinical animal models to explore molecular and cellular mechanisms underlying the pathogeneses of several devastating diseases that afflict large populations of our VA patients, including osteoporosis, bone fracture, mineral imbalance, traumatic and ischemic brain injuries, and Alzheimer's Diseases. All of those diseases greatly impact on the quality of life of our veterans and impose substantial social and financial burden on the VA healthcare system and the entire VA community as a whole. Successful completion of our highly translational research projects will not only advance our understanding of how those diseases develop, but also lead to timely therapies to prevent and/or treat the diseases. Indeed, one of the concepts that we developed to repurpose 2 FDA-approved drugs for a new combined therapy for osteoporosis will soon be tested clinically by our VA colleague to treat VA patients afflicted with osteoporosis. If validated, this new therapy could be soon available clinically.","6061231; ","CHANG, WENHAN ;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award","004835","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9870202","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004984","","RFA-BX-19-022","1IK6BX004984-01","","OTHERS","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","The long-term goal of my research is to understand the cellular and molecular mechanisms governing skeletal development, homeostasis and repair. One project examines fuel consumption by osteoblasts and osteocytes under normal conditions and in response to well-defined stimuli, which increase bone cell energy demands. Such information will help clarify how and why bone communicates with other energy consuming tissues, and may explain the close association between the existence of bone disease and diabetes in humans; which should have an immediate impact on the management, treatment and prevention of these related metabolic disturbances. In a second project, we are using novel approaches to characterize the timing of innervation, and the consequence of blocking nerve action on bone development and repair. These studies represent the first comprehensive approach to investigating the function of sensory nerves in bone.","6799588; ","CLEMENS, THOMAS L;","","10/01/2019","09/30/2026","","BLR&D Research Career Scientist Award Application","004984","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9988956","Y01","HL","","N","","","","","Y01HL170010","","","AHL17001001-1-0-1","NHLBI:1717000\","INTERAGENCY AGREEMENTS","2019","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","","","","","","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","; ",",  ;","","","","Address; Adult; Algorithms; American; authority; Back; Blood Pressure; Body Composition; Body fat; Body measure procedure; Body Weight decreased; Calendar; Calibration; Cardiovascular Diseases; cardiovascular disorder risk; cardiovascular fitness; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Child; Cholesterol; Chronic; Clinic; Clinical; Collection; Congresses; cost effective; Country; Data; Devices; disability; Documentation; Dual-Energy X-Ray Absorptiometry; Environment; Equation; Funding; Goals; Government; Health; Health Status; Health Surveys; Healthy People 2020; heart disease risk; High Density Lipoprotein Cholesterol; Hypertension; improved; Institutes; Laws; lean body mass; lifestyle factors; Low-Density Lipoproteins; Lung; Lung diseases; Measurement; Measures; Mercury; Monitor; National Health and Nutrition Examination Survey; National Heart, Lung, and Blood Institute; Nutritional status; obesity prevention; Patient Self-Report; Pattern; Performance; Phase; Physical activity; Physicians; Policies; Population; Prevalence; Prevention; programs; Protocols documentation; Questionnaires; Recording of previous events; Research; Risk; Risk Factors; Risk Reduction; Site; Sleep; Sleep Disorders; Sleep disturbances; sleep health; sleep pattern; sleep quality; Sphygmomanometers; Standardization; Surveys; System; Testing; Time; Training; Travel; trend; trend analysis; Triglycerides; United States Dept. of Health and Human Services; United States National Center for Health Statistics; United States National Institutes of Health; ","The National Health and Nutrition Examination Survey (NHANES) 2017-2018, Cardiovascular Disease Component","","","","","","","","","1717000",""
"10015189","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003033","","RFA-BX-14-004","5I01BX003033-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","PUBLIC HEALTH RELEVANCE:         It is increasingly becoming clear that exposure to different war zone chemicals increases the risk of having Parkinson's disease (PD). Here, based on our exciting preliminary results, we will examine therapeutic efficacy of cinnamon and its metabolite sodium benzoate (NaB), an FDA-approved drug and a widely-used food additive, in MPTP mouse models of PD. Furthermore, from the academic point of view, we will also investigate a novel mode of action of cinnamon and NaB at the molecular level. Together, a positive outcome of this grant proposal will highlight undiscovered properties of NaB and cinnamon, and enhance the possibility of treating patients with PD with easily available cinnamon powder or its metabolite NaB as primary or adjunct therapy.","6124977; ","PAHAN, KALIPADA ;","","10/01/2015","09/30/2020","Affect; agent orange; Agonist; alpha synuclein; Alpha-Synuclein transgenic mouse; Alzheimer's Disease; Animal Model; Applications Grants; Astrocytes; Attenuated; base; Benzoates; Bradykinesia; Brain; Cell Line; Chemicals; Chronic; Cinnamon - dietary; Clinical; Corpus striatum structure; CREB1 gene; Disease Progression; dopaminergic neuron; effective therapy; Event; Exhibits; Exposure to; fatty acid oxidation; FDA approved; feeding; Flavoring; Food Additives; Genes; Genetic Transcription; glial activation; glial cell-line derived neurotrophic factor; Gliosis; Growth; Human; Hyperammonemia; Impairment; improved; in vivo; Incidence; Inclusion Bodies; Injections; Intoxication; Investigation; Lewy Bodies; Mediating; Molecular; Motor Activity; mouse model; Mus; Nerve Degeneration; Neurodegenerative Disorders; neuroprotection; Neurotransmitters; neurotrophic factor; neurturin; nigrostriatum; novel; Oral; Oral Administration; Outcome; Parkinson Disease; Parkinsonian Disorders; Pathogenesis; Pathologic; Pathway interactions; Patients; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Plasma; Play; Poison; posture instability; Powder dose form; Process; Production; Property; public health relevance; Research; Risk; Role; Sodium; Spices; Symptoms; synuclein; Testing; Therapeutic; Toxic effect; Treatment Efficacy; Tremor; United States; Up-Regulation; Veterans; War; ","Cinnamon and its metabolite sodium benzoate in Parkinsonism","003033","NURE","Neurobiology E ","","","05","","","",""
"9189493","IK2","VA","1","N","10/21/2019","10/01/2016","09/30/2017","999","IK2HX001775","","RFA-HX-16-011","1IK2HX001775-01A2","","OTHERS","2020","Veterans Affairs","","PROVIDENCE","UNITED STATES","","02","182465745","US","10018779","PROVIDENCE VA  MEDICAL CENTER","RI","029084734","The proposed research is relevant to VHA's mission to ?honor America's Veterans by providing exceptional healthcare that improves their health and well-being.? Patient-directed cash benefit programs, like Veteran- Directed Home and Community Based Services and VBA's Aid and Attendance and Housebound benefits, employ personalized strategies that consider Veterans' unique conditions, needs, and circumstances. These cash benefits are expected to affect Veterans' use of, unmet need for, and satisfaction with supportive services. As a result, they may also affect their health and functioning. However, there remains no evidence on reasons for their variability in utilization or their effectiveness in meeting Veteran's long-term care (LTC) needs and controlling escalating spending on long-term services and supports (LTSS). Therefore, it is important that we understand the utilization and effectiveness of these programs, as well as Veterans' experiences with these programs, to both inform the delivery of LTSS within VA and improve Veterans' health and well-being.","10381499; ","THOMAS, KALI ST. MARIE;","","10/01/2016","09/30/2021","Accident and Emergency department; Admission activity; Affect; Age; aged; Americas; Award; base; Behavioral Model; Budgets; care delivery; care systems; career; Caring; Case Manager; Characteristics; Communities; community based service; comparative effectiveness; Consumption; cost; cost effective; Data; Data Collection; disability; Disabled Persons; Effectiveness; effectiveness research; Enrollment; Ensure; Evaluation Research; evidence base; experience; Financial compensation; Foundations; Future; Goals; Health; health administration; Health Care Costs; health care service utilization; Healthcare; Home environment; Home Health Aides; Hospitalization; Human Resources; implementation research; Improve Access; improved; innovation; insight; Intervention; Interview; K-Series Research Career Programs; Knowledge; Leadership; Long-Term Care; Medical; Medical center; meetings; Methodology; Methods; Mission; Monitor; Nursing Homes; Outcome; Participant; Patient Care; Patients; Pensions; Perception; person centered; Personal Satisfaction; personalized strategies; Policies; Population; Positioning Attribute; Primary Health Care; Process; Program Effectiveness; Program Evaluation; programs; Qualifying; Qualitative Research; Quality of life; Research; Research Methodology; Research Training; residence; Role; satisfaction; Scientist; Self Care; service delivery; service programs; Services; skills; Staging; Structure; Suggestion; System; Training; United States Department of Veterans Affairs; Variant; Veterans; Vulnerable Populations; Waiting Lists; ","Evaluating Cash Benefit Programs for Veterans' Long Term Care","001775","CDA0","HSR&D Career Development Award  ","","A2","01","","","",""
"9782560","IK2","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","IK2BX004648","","RFA-BX-18-008","1IK2BX004648-01","","OTHERS","2020","Veterans Affairs","","NASHVILLE","UNITED STATES","","05","156385783","US","481084","VETERANS HEALTH ADMINISTRATION","TN","372122637","Esophageal Squamous Cell Cancer (ESCC) accounts for approximately 90% of the incident 456,000 esophageal cancers worldwide. Data from the VA Central Cancer Registry (VACCR) between 1995-2005 revealed 3,493 new cases of ESCC (44% of all esophageal cancers). Patients often present with advanced disease, as 60-91% of patients presented with at least Stage II disease, and 26% present with metastatic disease. Current therapies include a combination of chemotherapy, radiation, and surgical intervention, which are not specific and in many cases not effective. Median survival time after diagnosis is 14.2-15.3 months. As such, new, more specific therapies are necessary. The advent of immune checkpoint inhibitors to reactivate antitumor immunosurvelliance and clearance represents a new treatment avenue for difficult to manage cancers. Our overarching hypothesis is that eosinophils could be cellular targets for immunotherapy in difficult to manage patients with ESCC.","14144344; ","CHOKSI, YASH ;","","10/01/2019","09/30/2024","3-Dimensional; Adoptive Cell Transfers; advanced disease; Aftercare; Alcohol consumption; antioxidant enzyme; Apoptosis; Area; Biology; Blood Vessels; Bone Marrow; Carcinoma; CCL11 gene; Cells; Cellular Structures; cellular targeting; Chemotactic Factors; clinically relevant; Coculture Techniques; Combination Drug Therapy; Culture Techniques; cytokine; cytotoxic; Data; Deglutition; Diagnosis; Disease; Dysplasia; Electrons; eosinophil; eosinophil peroxidase; Eosinophilia; Eotaxin; Epithelial; Epithelial Cells; Epithelium; Equilibrium; Esophageal; Esophageal carcinoma; Esophageal Intraepithelial Neoplasia; Esophageal Neoplasms; Esophageal Squamous Cell; Esophageal Squamous Cell Carcinoma; Esophagectomy; Esophagus; glutathione peroxidase; health related quality of life; High Prevalence; Homeostasis; Human; human disease; human model; Hydrogen Peroxide; IL8 gene; Immune; Immune checkpoint inhibitor; Immunotherapy; improved; Infiltration; Inflammatory Response; insight; Interleukin-10; Interleukin-2; Interleukin-5; Lead; Light; Lipids; Malignant Epithelial Cell; Malignant neoplasm of esophagus; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Mediating; Metastatic Neoplasm to Lymph Nodes; Methods; Modeling; Modification; mouse model; Mus; neoplasm registry; neoplastic cell; Operative Surgical Procedures; Organoids; Oxidants; oxidation; Oxidative Stress; Oxides; Pathway interactions; Patients; Peroxidases; Play; Population; Production; Radiation; Reactive Oxygen Species; recruit; Reduced Glutathione; Regulation; Role; Signal Transduction; smoking prevalence; Squamous cell carcinoma; Stage at Diagnosis; Testing; Therapeutic Intervention; Thiocyanates; Time; Tissues; TNF gene; tumor; Tumor Biology; Tumor Immunity; tumor initiation; tumor microenvironment; tumor progression; tumorigenesis; tumorigenic; Water; ","The role of eosinophils and oxidative stress in esophageal malignancy","004648","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9812839","IK6","VA","5","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX003777","","RFA-CX-16-022","5IK6BX003777-04","","OTHERS","2020","Veterans Affairs","","DURHAM","UNITED STATES","","01","043241082","US","481065","DURHAM VA MEDICAL CENTER","NC","277053875","My research focus is on Veterans who have been diagnosed with posttraumatic stress disorder (PTSD), a war- related illness. I was among the first to document hostility, violence and anger among individuals (both men and women) with PTSD. I was also among the first researchers to observe that individuals with PTSD self-report and are diagnosed with more physical health problems, including cardiovascular disorders. This work has led to several significant contributions in understanding the behavioral and psychophysiological mechanisms that may contribute to increased risk of poor health among persons with PTSD. I have investigated mechanisms that may explain the association between increased prevalence and higher nicotine dependence in smokers with PTSD. I have developed a novel mobile health intervention that has shown tremendous promise toward reducing smoking among those with PTSD and other psychiatric disorders. I will continue my research program on PTSD and co- morbid conditions through empirical investigation of trauma exposure, PTSD symptoms and genetic factors.","1878219; ","BECKHAM, JEAN C.;","","10/01/2016","09/30/2023","Acoustics; Afghanistan; African American; Aggressive behavior; Alcohols; Anger; Applications Grants; Area; Award; Behavior Therapy; Behavioral; behavioral health; Blood Pressure; Candidate Disease Gene; Cardiovascular Diseases; cardiovascular risk factor; career; Cigarette; Clinical; Clinical Trials; Collaborations; Collection; cooperative study; craving; Cues; Data; dehydroepiandrosterone; Development; development policy; Diagnosis; diaries; Distress; DNA; Education; Emotional; Evaluation; evidence base; experience; Funding; Gene Expression; Genetic; Genetic Diseases; genome wide association study; Grant; Health; Heart Rate; heart rate variability; Homelessness; Hostility; Impairment; improved; Individual; instrument; Intervention; Investigation; Iraq; Laboratories; Lead; Manuscripts; Marijuana; Medical; men; Mental disorders; Meta-Analysis; Methods; Methylation; mHealth; modifiable risk; Monitor; mortality; negative affect; Nicotine; Nicotine Dependence; novel; Patient Self-Report; Patients; Persons; Physical activity; physical conditioning; Population; Positioning Attribute; Post-Traumatic Stress Disorders; prepulse inhibition; Pressoreceptors; Prevalence; programs; Provider; psychiatric symptom; psychologic; Psychophysiology; Publishing; Randomized Clinical Trials; reduce symptoms; Registries; Relapse; Research; Research Personnel; response; Risk; Risk Behaviors; Risk Factors; RNA; Role; Sampling; Schizophrenia; Scientist; screening; service utilization; Services; Site; Sleep; Smoker; Smoking; smoking addiction; Smoking Behavior; smoking cessation; Smoking Cessation Intervention; smoking prevalence; smoking relapse; Stimulus; Stress; Substance abuse problem; suicidal behavior; Symptoms; therapy development; Time; Tobacco; Training Activity; Trauma; trauma exposure; treatment as usual; United States National Institutes of Health; Veterans; Vietnam; Violence; War; Woman; Work; ","CSR&D Research Career Scientist Award","003777","RCSR","Research Career Scientist ","","","04","","","",""
"9814685","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003279","","RFA-BX-16-001","5I01BX003279-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","The 2011 update of the United States National Drug Control Strategy identified active military personnel, veterans, and their families as populations requiring special support to deal with their drug abuse problems. Drug addiction interferes with the diagnosis and treatment of other psychiatric disorders, and VA patients who abuse drugs use VA resources at disproportionate levels. As there are no approved pharmacological treatments for psychostimulant abuse, analysis of endogenous and recombinant dopamine receptors expressed in neurons, in mammalian cell lines, and in the behaving rodent are powerful model systems with which to perform basic research that should contribute to the development of rational strategies for developing such therapies for treatment of substance abuse and other neuropsychiatric disorders related to dysfunction of the dopamine system.","6421456; ","NEVE, KIM ARTHUR;","","10/01/2016","09/30/2020","Address; Agonist; Alternative Splicing; Autoreceptors; Axon; base; Basic Science; Behavior; behavior measurement; behavioral sensitization; Biological Models; Calcium; Calcium-Binding Proteins; Cell Line; Cocaine; Corpus striatum structure; desensitization; Development; Diagnosis; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; dopamine system; dopaminergic neuron; Drug abuse; Drug Addiction; Drug Controls; drug seeking behavior; Drug usage; Electrophysiology (science); Exhibits; Family; Functional disorder; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; insight; Knock-out; Knockout Mice; Left; Mammalian Cell; Measures; Mediating; member; Membrane; Mental disorders; Midbrain structure; Military Personnel; Modeling; Motor Activity; Mus; mutant; nervous system disorder; neurochemistry; Neurons; neuropsychiatric disorder; Organism; Parkinson Disease; Pathway interactions; Patients; Pharmacological Treatment; Phenotype; Population; postsynaptic; preference; presynaptic; Property; Proteins; receptor; Recombinants; Regulation; Resources; reuptake; Rewards; RNA Splicing; Rodent; Schizophrenia; Signal Transduction; stimulant abuse; substance abuse treatment; Taste aversion; Testing; therapeutic target; United States; Update; Variant; Veterans; Virus; Wild Type Mouse; Work; ","Dopamine D2 Receptor Splice Variants and Autoreceptor Function","003279","NURA","Neurobiology A ","","","04","","","",""
"9814692","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002996","","RFA-BX-15-001","5I01BX002996-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOUISVILLE","UNITED STATES","","03","086765245","US","481037","LOUISVILLE VA MEDICAL MEDICAL CENTER","KY","402061433","PUBLIC HEALTH RELEVANCE:        Alcohol abuse exacts a major toll on health and health costs in Veterans. Even though there is an 'epidemic' of hepatitis C in the U.S. and the Veterans Administration, alcohol-related liver injury remains a higher cause of mortality. Studies from the Veterans Administration showed that patients with cirrhosis and superimposed alcoholic hepatitis had > 60% mortality over a four-year period of time, with most of those deaths occurring in the first few months. Thus, the prognosis for this stage of ALD is worse than many common types of cancer, such as breast, prostate and colon. Unfortunately, there is no FDA-approved therapy for any stage of ALD, and this makes the need for this proposed research even more compelling. The proposed studies will help to better understand the molecular mechanisms of alcohol-induced liver and intestinal injury, including alcohol-diet interactions, which may lead to identification of new therapeutic targets and potential dietary interventions for treating ALD, as well as help to explain why only some heavy drinkers develop clinically important ALD.","1902075; ","MCCLAIN, CRAIG J.;","","10/01/2016","09/30/2020","Ablation; Address; Affect; Alcohol abuse; Alcoholic beverage heavy drinker; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcohols; Animal Model; Animals; Arachidonate 15-Lipoxygenase; Attenuated; base; Blood; Breast; cancer type; Cations; Cell Death; Cessation of life; Chronic; Cirrhosis; Clinical; Colon; cytokine; Data; Development; Diet; Dietary Fats; Dietary Intervention; endoplasmic reticulum stress; Enzymes; Epidemic; Ethanol; Etiology; Experimental Animal Model; Fatty Liver; FDA approved; Genetic; Health Care Costs; Heavy Drinking; Hepatic; Hepatitis C; Hepatocyte; Hepatotoxicity; Human; human study; In Vitro; in vitro testing; in vivo; Inflammasome; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Injury; Interleukin-1 beta; Interleukin-18; Intestines; Knockout Mice; Kupffer Cells; Laboratories; Lead; Ligands; Link; Linoleic Acids; Liver; liver inflammation; liver injury; macrophage; Mediating; mitochondrial dysfunction; Molecular; monocyte; Morbidity - disease rate; mortality; new therapeutic target; nonalcoholic steatohepatitis; novel; octadecadienoic acid; outcome forecast; oxidation; Oxides; Pathogenesis; Patients; peripheral blood; Permeability; Pharmacology; Play; Population; Prostate; public health relevance; Publishing; receptor; Research; Role; Signal Transduction; Steatohepatitis; stressor; therapeutic target; Time; toxicant; Translating; United States Department of Veterans Affairs; Unsaturated Fats; Up-Regulation; Vanilloid; Veterans; Whole Blood; ","Dietary Fat and Alcoholic Liver Disease","002996","GAST","Gastroenterology ","","","04","","","",""
"9815332","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004062","","RFA-BX-17-001","5I01BX004062-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","Deleterious psychiatric outcomes following stress, including posttraumatic stress disorder, anhedonia (a reduced capacity to experience pleasure), and suicidality afflict many recently deployed combat Veterans. Recent evidence has shown that low doses of the anesthetic ketamine rapidly improve these afflictions within hours following a single administration. However, the use of ketamine as a treatment is limited outside of a hospital or clinic due to its abuse potential and dissociative effects, and there are concerns regarding the long- term use of ketamine. Our goal is to validate an improved intervention for the treatment of stress-related disorders in Veterans, given what we know of ketamine's relevant pharmacological actions. We have found that a metabolic byproduct of ketamine, hydroxynorketamine, is devoid of abuse potential and other side effects. We will test hydroxynorketamine in preclinical models of outcomes related to posttraumatic stress disorder and anhedonia to determine its potential efficacy for these indications.","8443660; ","GOULD, TODD D;","","10/01/2018","09/30/2022","Acoustics; Affect; Alzheimer's Disease; Anesthetics; Anhedonia; Antidepressive Agents; Clinic; Clinical; Clinical Treatment; clinically relevant; combat; conditioned fear; conditioning; Data; Development; Dose; drug development; Electroencephalogram; endophenotype; Excitatory Amino Acid Antagonists; experience; experimental study; Exposure to; Extinction (Psychology); Foundations; Fright; Glutamate Receptor; Glutamates; Goals; Home environment; Hospitals; Hour; Human; improved; Individual; inhibitor/antagonist; Intervention; Ketamine; Lead; Life; Measures; Medial; Mediating; Mental Depression; Mental disorders; Metabolic; Metabolism; Motivation; Mus; N-Methylaspartate; Nature; neurotransmission; novel; Outcome; Parkinson Disease; Patients; Peripheral; Pharmaceutical Preparations; Pharmacologic Actions; Pharmacology; pleasure; Population; Post-Traumatic Stress Disorders; pre-clinical; Pre-Clinical Model; Preclinical Testing; predictive test; preference; Prefrontal Cortex; prevent; Prevention; Property; Receptor Activation; Reporting; Research; Resistance; response; Role; Schizophrenia; Series; Severities; side effect; sleep abnormalities; Startle Reaction; Stress; stress related disorder; Sucrose; suicidal risk; Suicide; Symptoms; Testing; Therapeutic; Therapeutic Effect; Therapeutic Uses; Translational Research; Treatment Efficacy; Veterans; Work; ","Hydroxynorketamine for the Treatment of PTSD and Anhedonia","004062","MHBA","Mental Health and Behavioral Science A ","","","02","","","",""
"9815349","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001991","","RFA-BX-17-001","5I01BX001991-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOS ANGELES","UNITED STATES","","33","066689118","US","481012","VA GREATER LOS ANGELS HEALTHCARE SYSTEM","CA","900731003","The proposed study is designed to better understand molecular mechanisms underlying activation of the liver cell type called hepatic stellate cells (HSCs) which cause cirrhosis. Our research has discovered HSCs promote liver tumor development by actions of the enzyme called stearoyl Co-A desaturase (SCD). Proposed research will aim to elucidate how this tumor promotion takes place using the genetic mouse models, global screening for lipids in tumor microenvironment, global gene expression profiling, isolation of HSCs from the liver tumor models and characterizing lipids and lipid-encapsulated molecules released by tumor-associated HSCs. These efforts will help identify new therapeutic targets for cirrhosis and liver cancer which are common complications of chronic liver disease among veteran patients.","2105294; ","TSUKAMOTO, HIDEKAZU ;","","10/01/2013","09/30/2022","3' Untranslated Regions; Ablation; ADD-1 protein; Address; Attenuated; base; beta catenin; Binding; Binding Proteins; Biological; Cell Fate Control; cell type; Cells; Cholesterol; Cholesterol Homeostasis; chronic liver disease; Cirrhosis; desaturase; design; Development; Down-Regulation; eicosanoid metabolism; Eicosanoids; Encapsulated; Enhancers; Enzymes; Epigenetic Process; Fatty Liver; feeding; Gene Expression Profiling; Generations; Genes; Genetic; Genetic Transcription; Goals; Guanosine Triphosphate Phosphohydrolases; Hepatic; Hepatic Fibrogenesis; Hepatic Stellate Cell; hepatocellular carcinoma cell line; Hepatocyte; Heterochromatin; HuR protein; innovation; insight; Karyopherins; lipid metabolism; Lipids; liver development; Liver Fibrosis; Liver neoplasms; Malignant neoplasm of liver; Mediating; Messenger RNA; Metabolism; Methyl-CpG-Binding Protein 2; Modality; Modeling; Molecular; Monounsaturated Fatty Acids; morphogens; mouse model; mRNA Stability; Mus; neoplastic cell; new therapeutic target; Nitrosamines; novel; Nuclear Import; Nude Mice; Oleic Acids; palmitoleic acid; Pathway interactions; Patients; PPAR gamma; prevent; Protein Isoforms; Published Comment; recruit; Regulation; Research; Research Support; response; Role; Saturated Fatty Acids; screening; self-renewal; Series; Stearoyl-CoA Desaturase; stellate cell; stem-like cell; stemness; Testing; Therapeutic; Tissues; Transcriptional Regulation; transcriptome; transcriptomics; tumor; tumor growth; tumor initiation; Tumor Initiators; tumor microenvironment; Tumor Promotion; Tumor Suppression; tumorigenic; Veterans; wound; Xenograft Model; ","Molecular Mechanisms of Stellate Cell Activation in Liver Fibrosis","001991","GAST","Gastroenterology ","","","06","","","",""
"9815351","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003436","","RFA-BX-17-001","5I01BX003436-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","The inflammatory bowel diseases (IBD) affect approximately 50 thousand US veterans and the number of affected veterans is increasing. Although we have effective therapies, such anti-TNF agents, these are costly to produce and administer. Recent estimates for the cost of biologics at our VA range between 8 (adalimumab) and 50 (ustekinumab) thousand dollars per patient/year at the lowest prescribed doses. Thus, there is a need for new medications, particularly those with less side effects, lower costs and ease of administration by pill form. Here, we use unique mouse IBD models and human intestinal biopsies to investigate the mechanism of action of a new family of oral anti-inflammatories that has already shown great promise for the treatment of IBD. We expect that our studies might lead to the discovery and wide use of these new safe and effective oral drugs that are easier to take, have fewer side effects and are less costly to produce and administer.","3078732; ","RIVERA-NIEVES, JESUS ;","","10/01/2018","09/30/2022","adalimumab; adaptive immune response; Address; Affect; Agonist; Animals; Anti-Inflammatory Agents; Antibodies; Attenuated; base; Binding; Biological; Biopsy; Blood; Blood Vessels; cell motility; Cell physiology; Cells; Cellular biology; Chronic; Clinic; clinical efficacy; Clinical Research; Clinical Trials; clinically relevant; Colitis; cost; Cytometry; Data; Dendritic Cells; Disease; Disease model; Dose; Drug Design; effective therapy; Family; FDA approved; FOXP3 gene; G-Protein-Coupled Receptors; Goals; Health; Human; Human Characteristics; human disease; Hypersensitivity; Ileitis; Immune; Immune response; Immunology; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Inflammatory Infiltrate; innovation; Institutes; inter-institutional; Intestines; Lamina Propria; Lead; Literature; lymph nodes; Lymphocyte; Mediating; Mesentery; Microscopy; migration; Molecular; mouse model; Multiple Sclerosis; multiple sclerosis treatment; Mus; Nature; neglect; new therapeutic target; novel; novel imaging technique; novel strategies; novel therapeutics; One-Step dentin bonding system; Oral; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; pill; Play; pleiotropism; Pre-Clinical Model; preclinical study; Production; receptor; Regulation; Regulatory T-Lymphocyte; Research; Research Institute; response; Risk; risk minimization; Role; Sampling; side effect; Signal Transduction; Skin; Sphingolipids; sphingosine 1-phosphate; Sphingosine-1-Phosphate Receptor; stem; T cell differentiation; T cell response; T-Lymphocyte; Techniques; Therapeutic; Therapeutic Intervention; Time; TNF gene; trafficking; Translating; translational approach; Treatment Efficacy; Ulcerative Colitis; Veterans; ","Dendritic Cell Regulation by Sphingosine-1-phosphate in Inflammatory Bowel Disease","003436","GAST","Gastroenterology ","","","02","","","",""
"9815450","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003938","","RFA-BX-17-001","5I01BX003938-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","HINES","UNITED STATES","","07","067445429","US","481028","EDWARD HINES JR VA HOSPITAL","IL","601413030","Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness within the VHA and worldwide. Associated with elevated intraocular pressure (IOP), current treatment options for POAG are limited and often refractive. The molecular mechanism responsible for elevated IOP remain elusive, but most likely involves aberrant expression and signaling of transforming growth factor-?2 (TGF-?2). We propose that targeted disruption of TGF-?2 expression or signaling within the TM/JCT with mitochondrial-targeted antioxidant-encapsulating nanoparticles will increase outflow facility and lower IOP. We show that mitochondrial-targeted antioxidants significantly attenuate expression and release of TGF-?2 from cultured human TM cells. Here, we will establish mitochondrial-targeted antioxidant-encapsulating nanoparticles as a novel strategy by which to manage elevated IOP associated with POAG. Successful completion of the proposed study will facilitate translation of this developing technology for the management of Veterans with POAG.","1909014; ","STUBBS, EVAN B.;","","10/01/2017","09/30/2021","Affect; Age-Years; Anterior; Antioxidants; Aqueous Humor; Attenuated; Blindness; Cells; Clinical; cytokine; Deposition; Development; Dose; Encapsulated; Extracellular Matrix; Eye; Family suidae; Functional disorder; Gene Expression; Glaucoma; Goals; Histology; Human; immunocytochemistry; Immunohistochemistry; In Vitro; Individual; inhibitor/antagonist; Intervention; Investigation; laser capture microdissection; Mediating; Medication Management; Methodology; Mitochondria; Molecular; nanoparticle; Neurodegenerative Disorders; Neurons; novel strategies; optic nerve disorder; oxidative damage; Oxidative Stress; palliative; Patients; Physiologic Intraocular Pressure; Prevalence; Primary Open Angle Glaucoma; Production; Quality of life; Quantitative Reverse Transcriptase PCR; Reactive Oxygen Species; Reporting; Resistance; Role; Signal Pathway; Signal Transduction; socioeconomics; Source; Surgical Management; targeted treatment; Technology; Testing; Therapeutic; Time; Tissues; Trabecular meshwork structure; Transforming Growth Factor beta; Transforming Growth Factor Beta 2; Translations; Veterans; ","Mitochondrial-Targeted Antioxidant-Encapsulating Nanoparticles as a Promising Therapeutic Strategy in Regulating Outflow Resistance","003938","NURF","Neurobiology F ","","","03","","","",""
"9815454","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003249","","RFA-BX-16-004","5I01BX003249-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Approximately 80,000 veterans with Parkinson?s disease (PD) receive care from the Department of Veterans Affairs. Agent Orange and other environmental toxins have been associated with an increased incidence of this disease. Although many symptoms of Parkinson?s disease are treatable, progression of the underlying disease cannot be slowed by any currently available intervention. The present studies aim to improve our understanding of how this disease progresses over time, and to explore a potential treatment approach using animal models of the disease. The studies are based on idea that neuronal accumulation of ?-synuclein leads to consumption of the endogenous antioxidant glutathione, and that drugs which facilitate glutathione synthesis in neurons can improve neuronal survival.","1880148; ","SWANSON, RAYMOND A;","","10/01/2016","09/30/2020","Affect; agent orange; alpha synuclein; Animal Disease Models; Animal Model; Antioxidants; base; Binding; Biological Markers; Caring; Cell Culture System; Cell Culture Techniques; Cells; Cerebrospinal Fluid; Chemicals; Consumption; Data; Disease; disease phenotype; Disease Progression; DNA Sequence Alteration; Dopamine; Doxycycline; EAAT3; Exhibits; Gap Junctions; Genetic; Glutathione; Glutathione Disulfide; Human; Idiopathic Parkinson Disease; Impairment; improved; in vivo; Incidence; Injury; Intervention; Link; Measures; Mediating; metabolomics; Metals; Midbrain structure; Mitochondria; Modeling; Molecular Chaperones; Motor; mouse model; Mouse Strains; mouse synuclein alpha; multicatalytic endopeptidase complex; Mus; Nerve Degeneration; Neuroblastoma; neuronal survival; Neurons; overexpression; oxidation; Oxidation-Reduction; oxidative damage; Oxidative Stress; Parkinson Disease; Pathogenicity; Pathology; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; preclinical efficacy; Process; Production; protein folding; Proteins; Quality Control; Reactive Oxygen Species; repaired; response; Role; Signal Transduction; Stains; Study models; Sulfhydryl Compounds; Symptoms; synuclein; targeted biomarker; Testing; Time; Toxic Environmental Substances; Toxin; Transgenic Mice; Transition Elements; treatment effect; Veterans; ","Thiol repletion therapy for Parkinson's disease","003249","NURE","Neurobiology E ","","","04","","","",""
"9815456","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003856","","RFA-BX-17-001","5I01BX003856-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","In the present proposal, we will develop clinically-translatable tumor-specific near-infrared fluorescence labeling of primary and metastatic pancreatic and colorectal cancer using novel patient-derived orthotopic xenograft (PDOX) nude and humanized mouse models. We will validate humanized tumor specific anti-CEA and anti-CA 19-9 antibodies for their ability to label tumors. We will evaluate long wavelength dyes that have increased depth of penetration and ability to detect the smallest tumor deposits and provide the highest tumor to background ratios and specificity compared to dyes in the visible range. We will utilize near infrared fluorescence-guided surgery (FGS) combined with adjuvant photoimmunotherapy as a means to improve surgical outcomes for gastrointestinal cancers in PDOX humanized NSG mouse models. The completion of these aims will set the stage for clinical trials of fluorescent-antibody based FGS that can change the paradigm of surgical oncology and greatly improve outcomes of recalcitrant cancers.","2086061; ","BOUVET, MICHAEL ;","","10/01/2017","09/30/2021","absorption; Achievement; Adjuvant; Anti-CEA Antibody; Antibodies; antibody conjugate; Applications Grants; base; Cancer Etiology; cancer type; Cessation of life; Clinical; Clinical Trials; clinically translatable; Colon Carcinoma; Colorectal Cancer; cost; cytotoxic; Deposition; Detection; Development; Disease; Dose; Dyes; Excision; experimental study; Exposure to; Fluorescence; fluorescence imaging; fluorescence-guided surgery; Fluorescent Antibody Technique; fluorophore; Future; Gastrointestinal Neoplasms; Goals; Grant; Hematoxylin and Eosin Staining Method; Heterogeneity; Human; human model; humanized antibody; humanized monoclonal antibodies; humanized mouse; Image; Imagery; Immunohistochemistry; improved; improved outcome; in vivo; Individual; irradiation; Label; Laboratories; lead candidate; Light; Liver; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Malignant Neoplasms; Methods; Monoclonal Antibodies; mouse model; Mus; Neoplasm Metastasis; novel; Nude Mice; operation; Operative Surgical Procedures; Outcome; pancreatic cancer model; Patient-Focused Outcomes; Patients; Penetration; Photobleaching; photoimmunotherapy; Photosensitization; Phototoxicity; phthalocyanine; Population; portability; Primary Neoplasm; Principal Investigator; Property; Recurrence; Regimen; Research; Research Personnel; response; Signal Transduction; Specificity; Staging; Stains; success; Surgeon; surgery outcome; Surgical Oncology; Testing; Time; Tissues; tumor; Tumor Antigens; Tumor Burden; Tumor stage; Validation; Veterans; Xenograft Model; Xenograft procedure; ","Development of Near Infrared Fluorescence-Guided Surgical Navigation and Tumor Specific Photoimmunotherapy for Improved Outcomes for GI Cancers","003856","CAMM","Cellular and Molecular Medicine ","","","03","","","",""
"9815461","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003754","","RFA-BX-16-001","5I01BX003754-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BIRMINGHAM","UNITED STATES","","07","082140880","US","481003","BIRMINGHAM VA MEDICAL CENTER","AL","352331927","The experiments proposed here are aimed at improving our understanding of skeletal stem cells. These are cells capable of producing all three components of the skeleton, bone, cartilage and stroma. Understanding the biology of these skeletal stem cells is highly relevant for the healthcare of veterans. The need for new bone formation is important in a number of surgical procedures including spinal fusion, joint replacement and dental implants. These surgeries represent some of the most common procedures performed in the veteran population. A major concern in the success of these procedures is the formation of quality new bone to support the secure the implant. Understanding how to improve bone formation can decrease complications of all these procedures. Furthermore, it has the potential to allow for new bone formation in critical defects of returning warfighters who are suffering large numbers of extremity injuries in current conflicts.","7568859; ","YANG, GEORGE P;","","07/01/2017","09/30/2021","Affect; aging population; Apoptosis; Autologous; Biological; Biological Assay; Biology; Blood Vessels; bone; Bone callus; Bone Development; bone healing; bone morphogenic protein; bone quality; Bone Regeneration; Bone remodeling; Bone Transplantation; Cartilage; cartilage regeneration; Cell Differentiation process; Cell Proliferation; Cell Survival; cell type; Cells; Cellular biology; Chondrocytes; Chondrogenesis; Clinical; Clonal Expansion; Conflict (Psychology); cost; Data; daughter cell; Defect; Degenerative Disorder; Degenerative polyarthritis; Dental Implants; Development; Ensure; Exhibits; experimental study; Failure; Fibrous capsule of kidney; Fracture; Fracture Healing; Growth; healing; Healthcare; Hindlimb; Hip Fractures; Hydrogels; Implant; improved; improved outcome; In Vitro; in vitro Assay; in vivo; in vivo Model; Individual; Industry; Injury; insight; irradiation; Knock-out; Knockout Mice; Laboratories; Limb structure; Mesenchymal; Methods; Modeling; Morbidity - disease rate; mortality; Mus; Natural regeneration; novel; Operative Surgical Procedures; Orthopedic Procedures; Osteoblasts; Osteocytes; Osteogenesis; osteogenic; Pathway interactions; Patients; Phenotype; Physical condensation; Play; Population; Powder dose form; Predisposition; Procedures; Process; progenitor; Proteins; Publishing; Recombinants; regenerative; repaired; Replacement Arthroplasty; Research Personnel; Role; Secure; Series; Site; skeletal; Skeleton; Spinal Fusion; Stem cells; Stimulus; success; surgery outcome; targeted treatment; Techniques; Testing; therapeutic target; therapy development; therapy outcome; Time; tool; Transgenic Mice; Translating; Veterans; Wild Type Mouse; ","Identifying Approaches to Enhance Bone and Cartilage Regeneration","003754","SURG","Surgery ","","","04","","","",""
"9832139","IK2","VA","5","N","10/25/2019","10/01/2019","09/30/2020","999","IK2BX004346","","RFA-BX-18-008","5IK2BX004346-02","","OTHERS","2020","Veterans Affairs","","COLUMBIA","UNITED STATES","","04","082263013","US","481123","HARRY S. TRUMAN MEMORIAL VA HOSPITAL","MO","652015275","Project Narrative The goal of this VA CDA-2 proposal is to develop the candidate into a successful VA research scientist and determine how immunotherapy can be used in combination with standard chemotherapy (FOLFOX) in colon and rectal cancer. Colon and rectal cancer affects a large number of veterans. Despite excellent screening programs, a sizable number of these patients present with advanced disease. While treatment for patients has improved, there is still significant need for progress. An ideal area to target is combination immunotherapy with FOLFOX. Cytotoxic T cells are associated with improved survival and treatment response in colorectal cancer and are the primary mediator of anti-tumor immunity. In this proposal, we will test how FOLFOX chemotherapy alters cytotoxic T cells in the tumor and the abiliy to combine these therapies. The data garnered in this study will serve to establish the PI's research program and develop future clinical trials.","10256286; ","MITCHEM, JONATHAN B;","","10/01/2018","09/30/2023","advanced disease; Affect; Antigens; Antitumor Response; Area; arm; Cancer Control; cancer diagnosis; career; Cell Count; Cell Death; cell injury; Cell physiology; cell type; chemotherapy; Chemotherapy-Oncologic Procedure; Clinical Data; Clinical Trials; Clinical Trials Design; Colon Carcinoma; Colorectal Cancer; Combination Drug Therapy; Combination immunotherapy; Combined Modality Therapy; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; design; Development; early phase trial; Education; Ensure; exhaustion; Funding; Future; Generations; Goals; Human; Immune; immune checkpoint blockade; Immune response; Immune signaling; Immune system; Immune Targeting; immunogenicity; Immunologic Adjuvants; Immunotherapy; improved; Individual; Inflammatory; Interferon Type I; Interleukin-12; Malignant Neoplasms; Mediator of activation protein; Memory; Mentorship; Methods; Microsatellite Repeats; Modeling; mouse model; multidisciplinary; Mutation; novel therapeutics; Pathway interactions; Patients; pre-clinical; programs; Publishing; Radiation therapy; recruit; Rectal Cancer; Regimen; Research; Resistance; response; Scientist; screening program; Signal Transduction; skill acquisition; Stimulator of Interferon Genes; success; System; T-Lymphocyte; Testing; The Cancer Genome Atlas; Therapeutic; TLR3 gene; TNF gene; Treatment Efficacy; treatment response; tumor; tumor growth; Tumor Immunity; tumor microenvironment; Tumor-infiltrating immune cells; United States National Institutes of Health; Veterans; Work; ","Optimizing anti-tumor immunity for maximal therapeutic efficacy in Colorectal Cancer","004346","ZRD1","Special Emphasis Panel ","","","02","","","",""
"9842265","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002234","","RFA-BX-18-001","5I01BX002234-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Osteoarthritis (OA) is the most common form of arthritis, and an enormous and expensive public health problem. There are yet no medical therapies (disease modifying OA drugs (DMOADS)) to prevent or effectively slow the primary disease process. Age and obesity are the primary risk factors for OA development. Veterans are at high risk of developing OA, because over 12.4 millions veterans are age 65 or older, and nearly 80% of veterans are obese. Thus, the unmet medical need for new and effective therapeutics for OA is particularly urgent for the special needs of the health care of Veterans. Completion of these highly translational studies will potentially provide a novel approach to protect cartilage from degradation by targeted inhibition of ATP-citrate lyase, a metabolic enzyme that is overactive in OA, thereby suppressing OA development and progression.","7054253; ","BRYAN, RU ;","","10/01/2014","09/30/2022","5'-AMP-activated protein kinase; Acetyl Coenzyme A; Acetylation; Age; age related; aggrecan; aggrecanase; Aging; Anabolism; analog; Anti-inflammatory; Arthritis; articular cartilage; ATP Citrate (pro-S)-Lyase; Attenuated; Autophagocytosis; Back; Bioavailable; Bioenergetics; Biosensor; Caloric Restriction; Carbon; Cartilage; cartilage degradation; Catabolism; Cell Nucleus; Cells; Chondrocytes; Citrates; Citric Acid Cycle; Cyclic AMP-Dependent Protein Kinases; Cytosol; Degenerative polyarthritis; design; Development; Disease; Energy Metabolism; Enzymes; Epigenetic Process; Equilibrium; Extracellular Matrix; Failure; Fatty Acids; Functional disorder; Garcinia; Gene Expression; Genes; Genetic Transcription; Glucose; Healthcare; High Fat Diet; high risk; Histone Acetylation; Human; Hyaline Cartilage; in vivo; Inflammation; Inflammatory; inhibitor/antagonist; insight; Insulin Resistance; Insulin-Like Growth Factor I; Interleukin-1 beta; Knee Osteoarthritis; Knockout Mice; Lipids; Lysine; Mediating; Medical; Metabolic; Metabolism; mimetics; Mitochondria; MMP3 gene; Modeling; Modification; mRNA Expression; Mus; Nitric Oxide; novel; novel strategies; Nuclear Translocation; Obesity; Oral; Organ; Pharmaceutical Preparations; Pharmacology; Phenotype; Phosphorylation; prevent; Process; Production; promoter; Protein Acetylation; Protein Kinase; Proteins; Public Health; Quality Control; Recycling; Rest; Risk; Risk Factors; Role; Signal Transduction; Synovial joint; Testing; Therapeutic; Tissues; transcription factor; translational study; Treatment Efficacy; Veterans; ","ATP-Citrate Lyase As A Novel Metabolic Target for Osteoarthritis","002234","ZRD1","Special Emphasis Panel ","","","06","","","",""
"9871349","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004856","","RFA-BX-19-022","1IK6BX004856-01","","OTHERS","2020","Veterans Affairs","","COLUMBIA","UNITED STATES","","04","082263013","US","481123","HARRY S. TRUMAN MEMORIAL VA HOSPITAL","MO","652015275","Prostate cancer remains the second leading cause of male death and the most commonly diagnosed cancer in male veterans in the United States. The research program currently being performed by VA Research Career Scientist Dr. Timothy Hoffman is focused on developing a novel cancer cell targeted radioactive drug therapy called targeted alpha therapy (TAT) to deliver effective prostate tumor targeted radiation therapy. TAT has the potential to be used in patients at all stages of disease, independent of androgen status or chemotherapy resistance status; thereby, offering a new paradigm in treatment for those patients who have progressive disease that is not controlled by currently available treatment options. The types of drugs under development in the Hoffman laboratory belong to a class of drugs called theranostics because the same drug can be used for both therapeutic applications to treat disease and also used for diagnostic applications to identify the presence and extent of disease when the appropriate radioisotope (diagnostic or therapeutic) is employed.","7067322; ","HOFFMAN, TIMOTHY J.;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award Application","004856","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9871481","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004854","","RFA-BX-19-022","1IK6BX004854-01","","OTHERS","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Dr. Lau is a key and contributing member of the San Francisco VA Health Care System. He is a world authority in the genetics of the male-specific Y chromosome and an expert in molecular genetics and animal modeling of human diseases. He has developed a vigorous research program to investigate the contributions of the male- specific portion of the human genome (genetic materials) to gender disparities in various cancers and diseases. He correlates the laboratory results to the clinical features and outcomes and identifies biomarkers for precise diagnosis and prognosis in prostate and liver cancers, cardiovascular and neurodegenerative diseases. He establishes animal models for various cancer and human diseases, affecting many of our Veterans. His studies have shed critical insights on the disease mechanisms and provided therapeutic targets for development of effective treatment plans for human cancers and diseases. His research has provided significant translational potentials to improve the healthcare of our Veterans in the twenty-first century.","1859953; ","LAU, YUN-FAI CHRIS ;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award Application","004854","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9873550","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004851","","RFA-BX-19-022","1IK6BX004851-01","","OTHERS","2020","Veterans Affairs","","NORTH LITTLE ROCK","UNITED STATES","","02","082573742","US","10006869","CENTRAL ARKANSAS VETERANS HLTHCARE SYS","AR","721141709","This research is highly relevant to the healthcare of veterans, who comprise an aging population with elevated incidence of traumatic brain injury (TBI). Both age and TBI increase the risk of AD, PD, and other neurodegenerative diseases. By seeking basic principles that govern protein aggregation across many neuropathies, we hope to gain insights and develop novel interventions (e.g., drugs) that apply to diverse neurological pathologies including ?orphan diseases? that are too rare or underfunded to attract substantial research effort aimed at their prevention or cure.","11108219; ","SHMOOKLER REIS, ROBERT JOSEPH;","","10/01/2019","09/30/2026","","BLR&D Research Career Scientist Award","004851","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9977855","Y01","HL","","N","","","","","Y01HL130080","","","AHL13008001-1-0-1","NHLBI:156917\","INTERAGENCY AGREEMENTS","2019","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","","","","","","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","; ",",  ;","","","","Agreement; Blood Pressure; Budgets; Cholesterol; Consultations; cost; Data; Data Collection; Data Files; design; Healthy People 2020; Heart Diseases; Institutional Review Boards; instrument; Interviewer; Maintenance; Measures; Myocardial Infarction; National Health Interview Survey; Office Management; operation; Preparation; Publications; Questionnaire Designs; Sampling; Stroke; Testing; Training; Travel; Weight; ","Healthy People 2020 (HDS) Heart Disease and Stroke ","","","","","","","","","156917",""
"10020775","I01","VA","5","N","10/21/2019","04/01/2019","03/31/2020","999","I01RX000971","","RFA-RX-13-001","5I01RX000971-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","PUBLIC HEALTH RELEVANCE:         The prevalence of obesity and other chronic conditions such as cardiovascular disease and diabetes among veterans with SCI/D is widely documented. Physical inactivity and energy imbalance are common risk factors for these conditions. However, there are no objective assessment tool that can help veterans with SCI/D to track their free-living physical activities and energy expenditure. This proposal directly supports the mission of the VHA SCI/D Program by delivering such a tool to help veterans with SCI/D and professionals make better personal and clinical decisions on physical activity, energy balance, and healthier lifestyle. A healthy lifestyle in veterans with SCI/D could reduce the incidence and severity of secondary conditions, reduce direct healthcare cost, and lead to better overall health and higher quality of life.","2425558; 8080631 (contact); 9651193; ","COOPER, RORY A.; DING, DAN  (contact); SPUNGEN, ANN MICHELE;","","04/01/2015","03/31/2020","Accelerometer; Address; arm; Assessment tool; base; Biological Clocks; Cardiovascular Diseases; Chronic; Clinical; Data; Decision Making; Devices; Diabetes Mellitus; Disease; doubly-labeled water; energy balance; Energy Metabolism; Equation; Ergometry; exercise intervention; Health; Health Care Costs; healthy lifestyle; Incidence; Indirect Calorimetry; Intervention; Lead; Life Style; Light; Linear Regressions; Lower Extremity; Machine Learning; Manual wheelchair; Measurement; Measures; Medical center; Memory; Methods; Mission; Modeling; Monitor; Motor Vehicles; Movement; Obesity; Output; Patient Self-Report; Pattern; Performance; Physical activity; physical inactivity; Population; predictive modeling; Prevalence; programs; public health relevance; Quality of life; rehabilitation engineering; Research Personnel; Rest; Risk Factors; Sampling; sedentary lifestyle; Self Perception; Severities; Signal Transduction; Sleep; Spinal cord injury; strength training; Strenuous Exercise; Time; tool; total energy expenditure; Upper Extremity; Veterans; Visit; Weight maintenance regimen; Wheelchair propulsion; Wheelchairs; Work; ","Field-Based Assessment of Energy Expenditure in Spinal Cord Injury","000971","RRD2","Musculoskeletal Health & Function ","","","05","","","",""
"10041868","P30","CA","5","N","10/23/2019","12/01/2018","11/30/2019","","P30CA016520","","PAR-13-386","5P30CA016520-43","NCI:76195\","RESEARCH CENTERS","2019","NATIONAL CANCER INSTITUTE","","PHILADELPHIA","UNITED STATES","","03","042250712","US","6463801","UNIVERSITY OF PENNSYLVANIA","PA","191046205","","1857505; ","DEMICHELE, ANGELA ;","PTAK, KRZYSZTOF","01/15/1997","11/30/2020","","Breast Cancer Research Program","016520","NCI","Subcommittee I - Transistion to Independence ","7379","","43","47303","28892","","76195"
"9716790","IK6","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","IK6RX003075","","RFA-RX-18-017","1IK6RX003075-01","","OTHERS","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","Stroke, spinal cord injury, traumatic brian injury and other neurological conditions lead to long-term disability and significant and growing healthcare expenses in the veteran and general population. Effective neurorehabilitation interventions can minimize functional disability, improve quality of life and reduce costly long-term care expenditures. However, we often do not understand the exact nature of individual impairments and the mechanisms underlying how they will respond to different interventions. My ultimate research goal is to translate and individualize innovative rehabilitation interventions, and this will be achieved through better understanding fundamental concepts of locomotion and developing mechanism-based rehabilitation interventions and measurements. Additionally, I facilitate VA team science by obtaining rehabilitation research infrastructure grants and training the next generation of clinicians, engineers and basic scientists.","3137725; ","KAUTZ, STEVEN A.;","","10/01/2019","09/30/2026","Affect; Archives; Award; base; Biomechanics; Brain; career; career development; Characteristics; Chronic; Clinical; clinically relevant; Collaborations; Computer Simulation; Corticospinal Tracts; cost; Data Collection; density; disability; Doctor of Philosophy; Dose; Electroencephalography; Engineering; Expenditure; Foundations; functional disability; Funding; Gait; General Population; Goals; Grant; Healthcare; hemiparesis; human subject; imaging biomarker; Impairment; improved; Individual; Influentials; Infrastructure; Injury; innovation; Interdisciplinary Study; Intervention; Journals; Laboratories; Lead; leg paresis; Lesion; Locomotion; Locomotor training; Long-Term Care; Measurement; Measures; Mechanics; Mentors; Modeling; Motion; Motor Pathways; motor recovery; Multi-Institutional Clinical Trial; multidisciplinary; Muscle function; Musculoskeletal; Nature; Neptune; Neurologic; Neuromechanics; neurophysiology; neuroregulation; Neurorehabilitation; next generation; Paper; Paresis; Pathway interactions; Performance; Population; post stroke; Posture; programs; Publications; Publishing; Quality of life; Rehabilitation Research; Rehabilitation therapy; rehabilitative care; Research; Research Activity; Research Infrastructure; Research Personnel; Research Support; responders and non-responders; response; Science; Scientist; simulation; Speed; Spinal cord injury; Stroke; stroke patient; stroke rehabilitation; synergism; Training; Training and Infrastructure; Translating; Upper Extremity; vagus nerve stimulation; Veterans; Walking; Work; ","RR&D Research Career Scientist Award Application","003075","RRD7","Rehabilitation Engineering & Prosthetics/Orthotics  ","","","01","","","",""
"9780702","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004820","","RFA-CX-18-001","1I01BX004820-01A1","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","WEST HAVEN","UNITED STATES","","03","039624291","US","481020","VA CONNECTICUT HEALTHCARE SYSTEM","CT","065162770","Substance use (SU) disorders collectively represent the single most preventable cause of disease, disability, and death in the United States. Veterans are at higher risk than the general population for complications related to SU. Chronic pain is a risk factor for opioid drug use and is compounded by the other SU. Although SU and chronic pain both have a heritable component, isolating specific genes that affect risk across substances and that may also affect risk for chronic pain has been hampered by small sample sizes and ambiguous phenotypes. We will use the Million Veteran Program sample with SU phenotypes based on longitudinal quantity-frequency data from the VA electronic health record, and novel techniques in genome- wide association computational analysis to overcome the limitations of previous work and advance the field by enhancing the screening, diagnosis and treatment of multi-SU and SU disorders. Finally, incorporating pain phenotypes will help to elucidate the genetic variation that contributes to their frequent co-occurrence with SU.","8214491 (contact); 1869385; ","JUSTICE, AMY CAROLINE (contact); KRANZLER, HENRY RICHARD;","","10/01/2019","09/30/2023","Address; Admixture; Affect; African American; Aging; Alcohol consumption; Alcohol or Other Drugs use; Alcohol Phenotype; Alcohols; American; base; Behavior; Cessation of life; chronic pain; Clinical; Clinical assessments; Clinical Data; clinically relevant; Cohort Studies; Complex; Computer Analysis; Data; Data Reporting; Development; Diagnosis; disability; Disease; Dose; Electronic Health Record; Enrollment; Environmental Risk Factor; European; Frequencies; functional disability; Gene Frequency; General Population; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; genetic risk factor; Genetic study; genetic variant; Genetic Variation; genome wide association study; Genomics; Health; Healthcare; Heritability; high risk; indexing; Individual; individual variation; innovation; interest; International Classification of Disease Codes; Joints; Latino; Light; Link; Measurement; Measures; Mediation; Meta-Analysis; Modeling; morphine equivalent; never smoking; novel; Opioid; opioid use; Pain; pain score; Participant; Pathway interactions; Patient Self-Report; Patients; Pharmacy facility; Phenotype; pleiotropism; Population; Population Group; Preparation; prescription opioid; Principal Component Analysis; programs; Records; Risk; Risk Behaviors; Risk Factors; Role; routine care; Sample Size; Sampling; screening; Sensitivity and Specificity; Series; sex; Sex Differences; Single Nucleotide Polymorphism; Smoking Status; Substance Use Disorder; Surveys; Techniques; Time; Tobacco; Tobacco Phenotype; Tobacco use; trait; Twin Studies; United States; Validation; Variant; Veterans; wiki; Work; ","Genetic Vulnerability for Sustained Multi-Substance Use in MVP","004820","ZRD1","Special Emphasis Panel ","","A1","01","","","",""
"9780742","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004661","","RFA-BX-18-001","1I01BX004661-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","WEST HAVEN","UNITED STATES","","03","039624291","US","481020","VA CONNECTICUT HEALTHCARE SYSTEM","CT","065162770","Viral infections have more severe chronic consequences in individuals exposed to cigarette smoke (CS) than those who are not. We show that excessive accumulation of MAVS aggregates in mice exposed to CS and influenza virus (Flu) contributes to increased lung pathology. This grant will determine the mechanism of CS- induced dysregulation of mitochondrial antiviral signaling (MAVS) during Flu and the role of PINK1 kinase in correcting this dysregulation. We will characterize the pathways leading to excessive MAVS signaling and the mechanisms by which PINK1 limits MAVS aggregation. The downstream effects of PINK1-MAVS interactions and the effects on pathological pulmonary outcomes will be studied. We will explore the therapeutic potential of PINK1 augmentation using genetic and pharmacological approaches. Lastly, we will study the MAVS aggregation pathway in patients with smoking exposure and viral infections. A clear understanding of MAVS- PINK1 interactions can provide a new target to limit Flu-mediated pathology in CS-related lung diseases.","8893630; ","DELA CRUZ, CHARLES S;","","10/01/2019","09/30/2023","Acute; Address; Adverse effects; aggregation pathway; Antiviral Agents; base; Chronic; Chronic Obstructive Airway Disease; cigarette smoke; cigarette smoke-induced; Disease; Event; exposure to cigarette smoke; Fibroblasts; flu; Genetic; Grant; Growth Factor; Health; Homeostasis; improved; Individual; Inflammasome; Inflammation; Inflammatory; Influenza; influenzavirus; Injury; insight; Lung; macrophage; Mediating; Mitochondria; Mus; novel; null mutation; Outcome; Outer Mitochondrial Membrane; Pathogenesis; Pathologic; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmacology; Phosphotransferases; Play; prion-like; PTEN gene; PTEN-induced putative kinase; Pulmonary Fibrosis; Pulmonary Inflammation; Pulmonary Pathology; Regulation; Reporting; Respiratory physiology; response; response to injury; Role; Signal Transduction; Signaling Molecule; Smoke; Smoking; smoking-related lung disease; Smooth Muscle Actin Staining Method; Stains; Stress Fibers; Therapeutic; Tissues; transcriptomics; Viral Respiratory Tract Infection; Virus; Virus Diseases; Zidovudine; ","MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD","004661","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9781093","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004710","","RFA-BX-18-001","1I01BX004710-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","COLUMBIA","UNITED STATES","","04","082263013","US","481123","HARRY S. TRUMAN MEMORIAL VA HOSPITAL","MO","652015275","Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a worldwide public health problem. It is more common in the military and Veteran population compared to the general US population. NAFLD covers a disease spectrum ranging from fat deposition in the liver (steatosis) to non-alcoholic steatohepatitis (NASH) that may progress to end-stage liver disease and primary liver cancer and hence there is critical need for effective therapy. Because mitochondria play a central role in development of NAFLD, we are proposing studies to uncover the mechanisms underlying regulation of mitochondrial trifunctional protein, the major enzyme complex in the breakdown of fatty acids in the mitochondria, by SIRT3 and Thyroid hormones that lead to increased mitochondrial fatty acid oxidation and reversal of NAFLD. The proposed human and animal studies will provide critical insights into the pathogenic and therapeutic role of mitochondrial trifunctional protein and will provide new information to support the discovery of novel therapeutic targets for treatment of NAFLD.","1903131; ","IBDAH, JAMAL A;","","10/01/2019","09/30/2023","Acetylation; Address; Adenoviruses; Aging; Animals; Biochemical; Complex; Core Facility; Cultured Cells; Data; Defect; Deposition; Development; Disease; Dose; effective therapy; Fatty acid glycerol esters; fatty acid oxidation; Fatty Acids; Fatty Liver; Fibrosis; Future; Gene Expression; Gene Proteins; Health; Hepatocyte; Histologic; Histology; Hormones; Human; human data; human subject; human tissue; imaging study; improved; In Vitro; in vivo; Inflammation; inflammatory marker; insight; Knowledge; Lead; Link; Liver; Liver diseases; Liver Failure; Liver Mitochondria; long chain fatty acid; Lysine; Measurement; Measures; Military Personnel; Missouri; Mitochondria; mitochondrial dysfunction; Molecular; mouse model; Mouse Protein; Multienzyme Complexes; Mus; Neonatal; new therapeutic target; non-alcoholic fatty liver disease; non-genomic; Non-Insulin-Dependent Diabetes Mellitus; nonalcoholic steatohepatitis; novel; Obesity; overexpression; Pathogenicity; Pathologic; patient population; Patients; Play; Population; Prevalence; Primary carcinoma of the liver cells; Primary Malignant Neoplasm of Liver; protein complex; protein expression; Proteins; Proteomics; Public Health; receptor; Regulation; Reporting; response; Role; Sampling; Severity of illness; Sirtuins; Site; Steatohepatitis; Sudden Death; Testing; Therapeutic; Thyroid Gland; Thyroid Hormones; Time; treatment strategy; Triiodothyronine; Universities; Veterans; Work; ","Role of non-genomic regulation of mitochondrial trifunctional protein in NAFLD","004710","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9781856","IK2","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","IK2BX004219","","RFA-BX-18-008","1IK2BX004219-01A1","","OTHERS","2020","Veterans Affairs","","SALT LAKE CITY","UNITED STATES","","02","009094756","US","481089","VA SALT LAKE CITY HEALTHCARE SYSTEM","UT","841480001","Asthma is one of the major airway inflammatory diseases impacting millions worldwide. Sex disparities exist in asthma in the general population, but more so in the Veteran population. In particular, female Veterans have a higher incidence of acute and chronic airway exacerbations in comparison to male Veterans. The proposed research is relevant to the Veterans Affairs? mission because the number of female Veterans has continuously grown in the past 3 decades and with the growth of this population, distinct healthcare issues have arisen. The current proposal is aimed at identifying sex-specific immunologic approaches focused on innate immune lymphoid cells to limit the burden of asthma in the distinct, male and female Veteran populations.","12629731; ","WARREN, KRISTI J;","","10/01/2019","09/30/2024","Acute; Adult; Airway Disease; airway epithelium; airway hyperresponsiveness; Allergens; Allergic; allergic airway disease; Allergic inflammation; Asthma; asthmatic; asthmatic airway; Attention; B-Lymphocytes; base; biological sex; Blood; career; Caring; CC chemokine receptor 4; CCL11 gene; CCL17 gene; CCL22 gene; CCL3 gene; Cell Proliferation; Cell Survival; Cells; Cessation of life; chemokine; chemokine receptor; Chronic; Clinical; Communities; Complex; cytokine; Data; Dendritic Cells; design; Diagnosis; Disease; Doctor of Philosophy; Environment; eosinophil; Estrogens; Event; Extrinsic asthma; Feedback; Female; Functional disorder; Funding; Future; General Population; Goals; Gonadal Steroid Hormones; Health; Healthcare; Healthcare Systems; Hormones; Hospitals; Human; human data; Hypersensitivity; Immune; Immunobiology; Immunologics; in vivo; Incidence; individualized medicine; Inflammation; Inflammatory; Inflammatory Response; Innate Immune System; interest; Interleukin 2 Receptor Gamma; Interleukin-13; Interleukin-2; Interleukin-5; Interleukin-7; Iowa; Link; Lung; Lymphoid Cell; macrophage; male; Mediating; Mediator of activation protein; Medical; Medical center; Medical Research; men; Mentorship; migration; Mission; mouse allergy; Mus; Nebraska; novel; Ovarian; Ovarian hormone; Pathology; Pathway interactions; personalized therapeutic; Pilot Projects; Play; Population; Population Growth; post-doctoral training; Production; Progesterone; Proliferating; Prostaglandin D2; recruit; Reporting; Research; Research Personnel; Research Proposals; respiratory; Respiratory Signs and Symptoms; response; Role; Science; Scientist; Severity of illness; sex; Sex Differences; sex disparity; Signal Pathway; Signal Transduction; Source; Symptoms; Testosterone; Therapeutic Studies; Translating; Universities; Utah; Veterans; Woman; Work; ","Migration and signaling in ILC2 in asthma:  Male and female differences","004219","ZRD1","Special Emphasis Panel ","","A1","01","","","",""
"9814666","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001702","","RFA-BX-16-001","5I01BX001702-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","IOWA CITY","UNITED STATES","","02","028084333","US","481031","IOWA CITY VA MEDICAL CENTER","IA","522462208","The proposed project focuses on a protein called TRAF3 that prevents abnormal survival of B cells, the type of white blood cell that produces antibodies. Cancers of B cells are the most common type of blood cell cancer, and are currently approximately 5% of all cancers in the US. The incidence of B cell cancers has been steadily increasing over the past 40 years. Importantly, the specific types of B cell cancers most relevant to the proposed studies are considered `presumptive diseases' of Veterans who were exposed to ionizing radiation or herbicides like Agent Orange during their service, and mutations in TRAF3 are common in these cancers. The proposed work will determine how TRAF3 normally prevents excess B cell survival, how abnormal survival of B cells lacking normal amounts of TRAF3 occurs, and potential ways this can be blocked.","1902028; ","BISHOP, GAIL A.;","","10/01/2012","09/30/2020","Adaptor Signaling Protein; Address; age group; agent orange; Aging; Antibody-Producing Cells; Autoantibodies; Autoimmune Diseases; B lymphoid malignancy; B-Cell Activation; B-Cell Development; B-Cell Lymphomas; B-Cell Neoplasm; B-lymphocyte Cancer; B-Lymphocytes; Biological Models; Blood Cells; cancer cell; Cell membrane; Cell Survival; cell type; Cells; Cessation of life; clinically relevant; Disease; Disease remission; Drug Compounding; Drug resistance; Event; evidence base; Exposure to; Funding; Gender; Genes; Genetic; Goals; Hematologic Neoplasms; Herbicides; Human; improved; Incidence; Infiltration; inhibitor/antagonist; Ionizing radiation; Knowledge; Leukocytes; Libraries; lifetime risk; loss of function; Lymphoid; Malignant Neoplasms; Mediating; Membrane; men; mouse model; Multiple Myeloma; Mus; Mutation; Nuclear; Organ; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Play; Population; Predisposition; prevent; Prevention; Process; Production; Proliferating; Proteins; receptor; Recurrence; Regulation; Relapse; restraint; Risk; Role; Sampling; Services; Signal Transduction; small molecule; Survival Rate; Therapeutic; Time; Tissues; TLR5 gene; TNF receptor-associated factor 3; TNFRSF5 gene; tumor; Veterans; Work; ","TRAF3 as a key regulator of B cell survival pathways","001702","HEMA","Hematology ","","","08","","","",""
"9814673","IK2","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","IK2BX002712","","RFA-BX-14-008","5IK2BX002712-05","","OTHERS","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","PUBLIC HEALTH RELEVANCE:         Traumatic brain injury (TBI) is a major cause of disability in the Veteran population, often resulting in long-term cognitive and behavioral impairments that prevent return to the workforce and community. Disturbed sleep and excessive daytime sleepiness are among the most pervasive and enduring sequelae after TBI. Mild TBI is a clinical diagnosis, and currently no criteria exist to predict who will continue to experience debilitating neurological symptoms. There is a pressing need for more effective, mechanistic-based therapies for the treatment of TBI and associated post-concussive symptoms. Our research aims to 1) quantify electroencephalographic (EEG)-based markers of sleep and wakefulness in TBI that can aid in the prediction of functional recovery, 2) evaluate brain glutamate changes during wakefulness in TBI, and 3) evaluate the mechanisms by which a promising dietary therapy composed of branched chain amino acids restores glutamate and wakefulness in TBI.","6841556; ","LIM, MIRANDA M;","","10/01/2015","09/30/2020","Attention; base; Behavior; behavioral impairment; Brain; Brain Injuries; Brain region; Branched-Chain Amino Acids; Chronic; clinical Diagnosis; Cognitive; cognitive recovery; common symptom; Communities; community reintegration; Comorbidity; Data; Development; Diet; disability; Drowsiness; effective therapy; Electroencephalography; Electron Microscopy; Electrophysiology (science); Employment; Event; Excessive Daytime Sleepiness; experience; extracellular; Functional disorder; gamma-Aminobutyric Acid; Glutamates; Goals; hypocretin; Hypothalamic structure; Impaired cognition; Impairment; improved; in vivo; Individual; Link; Measures; Memory; Microdialysis; mild traumatic brain injury; mouse model; Mus; Nerve; neurobehavioral; Neurologic Symptoms; Neurons; neuropsychiatry; new therapeutic target; novel strategies; Outcome; persistent symptom; Pharmacology; Physiological; Play; Population; Post-Concussion Syndrome; prevent; public health relevance; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Sleep; Sleep disturbances; sleep pattern; sleep quality; Sleep Wake Cycle; Synapses; Techniques; temporal measurement; Testing; Therapeutic Intervention; therapeutic target; Traumatic Brain Injury; Traumatic Brain Injury recovery; treatment optimization; Veterans; Wakefulness; Work; ","Sleep-wake disturbances in traumatic brain injury","002712","NURR","Neurobiology R ","","","05","","","",""
"9814677","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001923","","RFA-BX-16-001","5I01BX001923-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PALO ALTO","UNITED STATES","","18","046017455","US","481014","VETERANS ADMIN PALO ALTO HEALTH CARE SYS","CA","943041207","Steroid hormones are mainly produced by the adrenal gland and gonads. They regulate a diverse array of physiological processes including the maintenance of carbohydrate, lipid and protein metabolism, salt and water balance, immunity, blood pressure, muscle and bone growth, reproduction and secondary sex characteristics. It is well-established that aging in Veterans, like the general population, leads to a decline in testosterone production and alterations in adrenal steroid production in both sexes. The goal of this project is to examine the role of cytosolic and mitochondrial superoxide dismutase-peroxiredoxin axes in age- related and oxidative stress-mediated decline in steroid synthesis in experimental rodent models. Successful completion of the proposed studies may identify the novel target(s) that can be exploited in the management of clinical conditions such as hypogonadism, sexual dysfunction, fragility, dyslipidemia and other steroid metabolic disorders seen in older Veterans and the general aging population.","1865125; ","AZHAR, SALMAN ;","","10/01/2012","09/30/2020","Ablation; Adrenal Glands; Age; age related; aged; Aging; aging population; Aldosterone; Androgens; antioxidant enzyme; Antioxidants; Attenuated; Biochemical; Blood Pressure; Bone Growth; bone mass; carbohydrate metabolism; cardiovascular risk factor; Carrier Proteins; Cell Line; Cells; Cellular biology; Cholesterol; Chronic; Clinical Management; Cross-Sectional Studies; Data; Defect; dehydroepiandrosterone; Down-Regulation; Dyslipidemias; Equilibrium; Estrogens; Fatty acid glycerol esters; frailty; General Population; Genetic; Goals; Gonadal structure; Human; Hydrocortisone; Hypogonadism; Immunity; Impairment; Incidence; Insulin Resistance; Intervention; Knockout Mice; Laboratories; leydig interstitial cell; Life; Link; lipid metabolism; Longitudinal Studies; Maintenance; MAP Kinase Gene; MAPK14 gene; Measurement; Mediating; men; Menopause; Mental Depression; Messenger RNA; Metabolic; Metabolic Diseases; Mitochondria; Mitogen-Activated Protein Kinase Inhibitor; Modeling; Molecular; Molecular Biology Techniques; mouse model; Mus; Muscle; Non-Insulin-Dependent Diabetes Mellitus; novel; Osteopenia; Osteoporosis; Ovarian; Ovary; Oxidants; oxidation; oxidative damage; Oxidative Stress; peroxiredoxin; peroxiredoxin I; Pharmacology; Physiological Processes; prevent; Production; Progesterone; protein metabolism; protein transport; Proteins; Proteomics; Quantitative Reverse Transcriptase PCR; Rattus; reconstitution; Reproduction; response; Rodent; Rodent Model; Role; sex; Sex Characteristics; Sex Functioning; Sexual Dysfunction; Side; SNAP receptor; SOD2 gene; Sodium Chloride; Steroid biosynthesis; steroid hormone; Steroids; superoxide dismutase 1; System; Techniques; Testing; Testosterone; transcriptome sequencing; Veterans; Water; Western Blotting; ","Role of Cholesterol in Age-related Decline in Steroidogenesis","001923","ENDA","Endocriniology A ","","","08","","","",""
"9814688","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003454","","RFA-BX-15-001","5I01BX003454-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","MADISON","UNITED STATES","","02","086683091","US","481071","WM S. MIDDLETON MEMORIAL VETERANS HOSP","WI","537052254","PUBLIC HEALTH RELEVANCE    The goal of our research is to understand the cause of benign prostate hyperplasia and lower urinary tract symptoms (BPH/LUTS) in aging men. BPH/LUTS is a prevalent condition among aging men in general but recent studies show an even higher incidence among Veterans and, in addition, a significant association with PTSD. Despite being a major health issue for Veterans, a recent Veterans Administration study reveals that most Veterans with BPH/LUTS are not being treated properly. In part, this is attributable to the complex nature of BPH/LUTS and failure of primary physicians to offer appropriate treatment. We expect our research to provide important new insight into the development of BPH/LUTS and its treatment. The result will be to provide tools for the primary physician to confidently select the best treatment for each patient.","1898719; ","BUSHMAN, WADE A.;","","10/01/2016","09/30/2020","Acute; Adult; afferent nerve; Aging; Behavior; Benign Prostatic Hypertrophy; Bladder; cholinergic; Chronic; Clinical; Clinical Trials; common symptom; Complex; Development; epigenetic regulation; Evaluation; experimental study; Failure; Fibrosis; Frequencies; Goals; Health; Human; human tissue; Incidence; Increased frequency of micturition; Individual; Inflammation; insight; interest; Intervention; irritation; lower urinary tract symptoms; Measures; Medical; men; Motor; mouse model; Nature; Nerve; Nocturia; Obstruction; Operative Surgical Procedures; Overactive Bladder; Patients; Pharmacology; Physicians; Plant Roots; Play; Post-Traumatic Stress Disorders; prevent; Prostate; prostate biopsy; Prostatic; Protocols documentation; public health relevance; Radical Prostatectomy; Research; Resistance; response; Role; Severities; Specimen; Stream; Symptoms; Testing; therapeutic target; Tissues; tool; United States Department of Veterans Affairs; Universities; Urethra; urinary; Urodynamics; Veterans; Wisconsin; ","Role of Inflammation and Fibrosis in Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms","003454","SURG","Surgery ","","","04","","","",""
"9815311","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX002061","","RFA-BX-17-001","5I01BX002061-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","Chronic hepatitis C virus (HCV) infection is associated with diseases or conditions that affect organs other than the liver, including the brain. The introduction of direct-acting antiviral (DAA) therapies has transformed the treatment of HCV, and the VA is now offering DAA therapy to all Veterans with HCV treated within VA health care systems. To accompany this effort, studies are needed to evaluate the impact of DAA therapy and obtaining a sustained viral response on brain function and the implications of having an alcohol use disorder, a co-occurring disorder that may hinder recovery. Results from this study are expected to determine the extent of improvement in brain function (e.g., nerve cell connectivity and thinking abilities) and reduction in inflammation that is achieved by successful completion of DAA therapy. This new information will: 1) address a gap in our knowledge concerning the effects of alcohol use on brain function following DAA therapy, 2) delineate the role of a network of immune factors in the brain healing process, and 3) enable targeted treatments.","2105498; ","LOFTIS, JENNIFER M;","","10/01/2013","09/30/2022","addiction; Address; Adult; Affect; Alcohol abuse; alcohol and other drug; Alcohol consumption; Alcohol dependence; alcohol effect; Alcohol or Other Drugs use; alcohol use disorder; Antiviral Agents; Antiviral Therapy; Attention; base; Behavior; Biological Markers; Blood specimen; Brain; brain dysfunction; Brain imaging; Brain Pathology; C-reactive protein; Caring; Chronic; Chronic Hepatitis C; chronic infection; Clinical; clinical practice; cognitive ability; cognitive function; Collection; Comorbidity; comparison group; Control Groups; cytokine; Data; Diffusion Magnetic Resonance Imaging; Disease; drug of abuse; Evaluation; executive function; Extrahepatic; Fatigue; Flow Cytometry; Fogs; follow-up; Functional Magnetic Resonance Imaging; functional outcomes; healing; Healthcare Systems; Hepatitis C; Hepatitis C Therapy; Hepatitis C virus; imaging modality; immune activation; immune function; Immune response; Immunoassay; Immunologic Factors; Immunologics; Impaired cognition; Impairment; improved; Inflammation; Inflammatory; Inflammatory Response; Interferons; Interleukin-1; Interleukin-10; Interleukin-8; Intervention; Investigation; Knowledge; Laboratories; Life; Linear Models; Liquid substance; Liver; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Medical; Memory; Mental Depression; Mental Health; Metabolic Clearance Rate; Methods; Moods; Nervous System Physiology; Nervous System Trauma; Neuraxis; neuroimaging; Neurons; neuropsychiatric symptom; neuropsychiatry; Neuropsychology; Oral; Organ; Outcome; Participant; Patients; Pharmaceutical Preparations; Phenotype; physical conditioning; Polymerase Chain Reaction; Prefrontal Cortex; Process; prospective; protein B; Publishing; Questionnaires; Recovery; Regimen; relating to nervous system; repository; Research; response; Rest; Risk; Role; S100 Calcium Binding Protein; sample collection; side effect; Signal Transduction; standard of care; Substance abuse problem; T-Lymphocyte; targeted treatment; Testing; therapy outcome; Thinking; Time; TimeLine; Toxic effect; Translating; treatment guidelines; Treatment outcome; treatment strategy; Urine; Veterans; Viral; Virus Diseases; white matter; Work; ","HCV and co-morbid alcohol use disorders: a translational investigation of antiviral therapy outcomes on CNS function","002061","NURA","Neurobiology A ","","","06","","","",""
"9815339","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004221","","RFA-BX-17-001","5I01BX004221-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","MADISON","UNITED STATES","","02","086683091","US","481071","WM S. MIDDLETON MEMORIAL VETERANS HOSP","WI","537052254","RELEVANCE STATEMENT:  The objective of this proposal is to define the role and functional significance of an important kinase known as the polo like kinase 4 (PLK4) in melanoma development and progression. This study is important because melanoma is one of the deadliest form of skin cancers. Further, several studies have found an increased risk of melanoma in Veterans. The US military currently is, and has been engaged, in missions all over the world, including recently, in the Middle EAST. Deployment to these regions is accompanied with a significant change in the climate, diet, stress and obvious exposures to war related chemicals, which impose increased risk for several diseases, including melanoma. Our study on the proposed identification of PLK4 as a novel pro- proliferative gene (and its downstream targets) in melanoma, may improve therapeutic options for the management of this neoplasm.","6564950; ","AHMAD, NIHAL ;","","10/01/2018","09/30/2022","Afghanistan; alpha Tubulin; Apoptosis; Archives; base; Biology; Biopsy; BRAF gene; cancer cell; cancer diagnosis; Cancer Patient; cancer therapy; Cell Culture Techniques; Cell Cycle; Cell Cycle Regulation; Cell Line; cell transformation; Centrioles; Centrosome; Cessation of life; Chemicals; chemotherapy; Cilia; Climate; Data; Defect; Dermatologic; Development; Diagnosis; Diagnostic; Diet; Disease; Disease Outcome; Exposure to; Expression Profiling; Female; Gene Chips; Genes; Genetic; Goals; Growth; Growth and Development function; Healthcare; high risk; Hospitals; Human; Human Resources; human tissue; improved; In Vitro; in vitro Model; in vivo; Incidence; indexing; inhibitor/antagonist; Iraq; knock-down; Laboratories; Lead; liquid crystal polymer; Literature; male; Malignant Neoplasms; malignant stomach neoplasm; melanocyte; melanoma; Melanoma Cell; Metastatic Melanoma; Middle East; Military Personnel; Mission; Modeling; Molecular; mouse model; Mutation; neoplasm registry; Neoplasms; Nevus; NOD/SCID mouse; novel; novel diagnostics; novel strategies; Nude Mice; Outcome Study; overexpression; Patients; pericentrin; Phosphotransferases; Play; PLK1 gene; Population; Process; prognostic; prospective; Protein-Serine-Threonine Kinases; Proteins; Proteomics; Recurrence; Research; Resistance development; response; Risk; RNA Interference; Role; S-Phase Fraction; Sampling; senescence; Skin; Skin Cancer; small molecule; small molecule inhibitor; Specimen; spectrograph; standard of care; Stress; suicidal; targeted treatment; Testing; Therapeutic; therapy resistant; Tissue Microarray; Tissues; TP53 gene; Transgenic Mice; Trimethoprim-Sulfamethoxazole; tumor; tumorigenic; ultraviolet; UV Radiation Exposure; Validation; Veterans; War; Work; Xenograft Model; Xenograft procedure; ","Role of polo like kinase 4 in melanomagenesis and melanoma progression","004221","ONCE","Oncology E ","","","02","","","",""
"9815345","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004264","","RFA-BX-17-001","5I01BX004264-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","The current Veteran population in the U.S. and Puerto Rico is approximately 22 million; of these, nearly 200,000 female Veterans will be diagnosed with breast cancer during their lifetimes. Of those people who succumb to basal-like breast cancer, nearly all die because of the spread of breast cancer outside the breast. The goal of this proposal is to reduce breast cancer mortality. The proposed studies will investigate how the enzyme endothelial lipase LIPG contributes to the progression of early-stage basal-like breast cancer to invasive breast cancer. We will determine how LIPG facilitates the spread of breast cancer. Preliminary data strongly demonstrated this study?s feasibility. The proposed studies have the potential to provide meaningful findings that can be translated to a clinical setting.","8779680; ","ZHOU, QUN ;","","10/01/2018","09/30/2022","Animals; Architecture; Automobile Driving; base; Basement membrane; Behavioral; Breast; Breast Cancer Cell; breast cancer diagnosis; breast cancer progression; cancer cell; cancer stem cell; Cell Differentiation process; Cell physiology; Cells; Chemoprevention; Clinical; clinically relevant; Color; combat; Data; design; Development; Diagnosis; Dietary Factors; Drug Delivery Systems; drug discovery; Drug Kinetics; Duct (organ) structure; Ductal; Enzymes; Epidermal Growth Factor Receptor; Epithelial Cells; Epithelium; ERBB2 gene; Estrogen Receptor alpha; Event; Extracellular Matrix; Feasibility Studies; Female; Foundations; Genetic; Glucosides; Goals; health administration; hormone therapy; Human; Impairment; Incidence; infiltrating duct carcinoma; inhibitor/antagonist; Intake; LIPG gene; Lobular; Luteolin; Maintenance; malignant breast neoplasm; Malignant Neoplasms; mammary epithelium; Mammary gland; Mammary Neoplasms; Mesenchymal; Metabolism; Metastatic breast cancer; Metastatic malignant neoplasm to brain; Metastatic Neoplasm to the Lung; Methodology; Methods; Molecular; Molecular Target; mortality; mouse model; Myoepithelial; Myoepithelial cell; Myoepithelioma; nanoparticle; Neoplasm Circulating Cells; Neoplasm Metastasis; neoplastic cell; new technology; Newly Diagnosed; novel; novel chemoprevention; Palmitic Acids; patient population; Patients; Phenotype; Plants; Population; prevent; progesterone receptor A; Progesterone Receptors; promoter; Public Health; Puerto Rico; receptor; Reporter; restoration; Risk Factors; Saturated Fatty Acids; screening; Signal Pathway; Signal Transduction; stem-like cell; Taraxacum; targeted treatment; Testing; Tissues; Toxic effect; Translating; triple-negative invasive breast carcinoma; tumor; Tumor Cell Invasion; tumor heterogeneity; Tumor Initiators; Tumor Suppressor Proteins; United States; Veterans; western diet; Woman; Work; ","Palmitic Acid and Basal-like Breast Cancer Progression","004264","ONCA","Oncology A ","","","02","","","",""
"9815352","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003651","","RFA-BX-17-001","5I01BX003651-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","Stroke is a devastating disease as currently no therapy is available to alleviate post-stroke neurological deficits. The proposed study will explore interleukin 33 (IL-33) as a promising immune therapy for ischemic stroke. We will investigate whether and how nasal delivery of IL-33 into the ischemic brain protects against ischemic brain injury and improves long-term neurological outcomes after experimental stroke. This information will be valuable for future development of new therapy for stroke and, possibly, other neurological disorders.","8415697; ","HU, XIAOMING ;","","10/01/2018","09/30/2022","3-Dimensional; Acute; Adult; Aftercare; aged; Attenuated; Automobile Driving; Brain; Brain Diseases; Brain Infarction; Brain Injuries; brain repair; cell injury; Cells; Cerebral Ischemia; Cessation of life; Clear Cell; Clinical; Coculture Techniques; cytokine; Data; deprivation; Development; Dichloromethylene Diphosphonate; disability; Disease; Dose; effective therapy; Exhibits; functional disability; Functional disorder; functional outcomes; Future; Glucose; gray matter; Immune; Immune response; immunoregulation; Immunotherapy; Impairment; improved; In Vitro; in vivo; Inflammation; Inflammation Mediators; Inflammatory; Infusion procedures; Injury; Interleukin Activation; Interleukin-1 Receptors; Interleukin-10; Interleukins; Intranasal Administration; Ischemia; Ischemic Brain Injury; Ischemic Stroke; Knockout Mice; Light; macrophage; Medical; Methods; Microglia; Middle Cerebral Artery Occlusion; Military Personnel; Mus; Myelin; nervous system disorder; Nervous System Physiology; Neuroglia; Neurologic; Neurologic Deficit; Neurological outcome; neurological recovery; neuron loss; Neurons; neutralizing antibody; Nose; novel; novel therapeutics; Nuclear; Oligodendroglia; Oxygen; Pathology; Phenotype; Play; post stroke; preservation; Production; protective effect; protective factors; Proteins; receptor; Recovery; Regulation; release factor; Reperfusion Therapy; Research; response; Role; Signal Pathway; Signal Transduction; Spinal cord injury; Stroke; stroke model; stroke therapy; success; Survivors; Testing; Therapeutic; Therapeutic Studies; Tissue Preservation; United States; Veterans; white matter; white matter injury; ","Interleukin-33 as an immune therapy for stroke","003651","NURC","Neurobiology C ","","","02","","","",""
"9815404","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001149","","RFA-BX-16-001","5I01BX001149-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","The burden of depression, both from a societal and economic standpoint, ranks second only to ischemic heart disease. By the year 2020, the World Health Organization projects that depression will be the leading cause of disability worldwide. Depression and suicide are particularly prevalent in military returning from deployment and the population of Veterans they become. As many as one third are resistant to antidepressants and they are at greatest risk for suicide. We will use cultured cells to screen new compounds with potential antidepressant activity and attempt to identify common molecular themes among antidepressants. We will also determine whether these molecular signatures are observed in blood cells from depressed and treated patients. Knowledge gained from this study should help to develop a rapid and inexpensive screen for antidepressant responsiveness, allowing changes in therapy long before the current 4-6 week lag time.","1860545; ","RASENICK, MARK M.;","","10/01/2011","09/30/2020","accomplished suicide; Adenylate Cyclase; Animal Model; antidepressant effect; Antidepressive Agents; Attention; Autopsy; base; Biological Markers; Biology; biosignature; Blood Cells; Blood Platelets; Blood Tests; Brain; Cell Fraction; Cells; Chemicals; Chimeric Proteins; Chronic; Clinical; Clinical Research; Coupling; Cultured Cells; Cyclic AMP; Data; Depressed mood; Depression and Suicide; Depressive disorder; design; disability; Economics; Event; fatty acylation; Fright; Funding; GTP-Binding Protein alpha Subunits, Gs; Heterotrimeric GTP-Binding Proteins; Human; In Vitro; Individual; insight; Ketamine; Knowledge; Laboratories; Lead; Link; Lipids; Measures; Membrane; Membrane Microdomains; Mental Depression; Methodology; Military Personnel; Molecular; Molecular Profiling; Movement; Myocardial Ischemia; Neuroglia; Neurons; novel; Pathway interactions; Patients; Peripheral; Pharmaceutical Preparations; Population; Production; Property; Proteins; Research; Resistance; response; scaffold; screening; Screening procedure; side effect; Signal Transduction; Site; social stigma; Speed; suicidal risk; Suicide; Synapses; System; Therapeutic; Time; Tissues; Translating; treatment duration; treatment response; Triton X100; uptake; Veterans; Work; World Health Organization; ","Lipid raft localization of Gsa as a biomarker for depression and therapeutic response","001149","CAMM","Cellular and Molecular Medicine ","","","08","","","",""
"9815405","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001228","","RFA-BX-16-001","5I01BX001228-07","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","Aurora","UNITED STATES","","06","003252830","US","481018","VA EASTERN COLORADO HEALTH CARE SYSTEM","CO","800457211","PROJECT NARRATIVE The risk of developing melanoma doubles if an individual is exposed to >5 sunburns at any age. Sun exposure is part of the daily life for U.S. troops, and the exposure during US military service has been linked to increased melanoma incidence. Furthermore, melanoma is more common than other cancers in young women, an increasingly significant population in the VA and in the active-duty military. Despite the progress in breakthrough therapeutics over the last several years, melanoma remains a challenge in clinical oncology. An immune response to melanoma cells is often generated and augmented by therapeutics, however tumor cells escape from the destruction. Thus, understanding mechanisms responsible for immune escape is critical for the successful treatment of melanoma and prevention of tumor relapse for VA patients. We found that human melanoma cells exhibit a feature of IL-1-mediated autoinflammation and that an immunosuppressive cytokine, IL-37, is elevated in melanoma blood samples. We will study the role of IL-37 in human melanoma.","6856394; ","FUJITA, MAYUMI ;","","07/01/2012","09/30/2021","adaptive immunity; Age; angiogenesis; anti-tumor immune response; autoinflammation; Biological; Blood; Blood Cells; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell-Mediated Cytolysis; Cells; Cessation of life; Clinical; Clinical Oncology; CTAG1 gene; CTLA4 gene; cytokine; Cytotoxic T-Lymphocytes; Data; Development; differential expression; Exhibits; Exposure to; extracellular; Family; Genes; Genetic Transcription; HLA-A2 Antigen; Homologous Gene; Human; Immune; Immune checkpoint inhibitor; Immune response; Immune system; immunogenicity; Immunologics; Immunosuppression; Immunosuppressive Agents; In Vitro; in vivo; in vivo imaging; Incidence; Individual; Inflammasome; Inflammation; Inflammatory; inflammatory milieu; inhibitor/antagonist; Innate Immune System; Interleukin Activation; Interleukin-1; Interleukin-1 beta; Interleukin-1 Receptors; Interleukins; Investigation; Life; Link; Lymphocyte; Malignant Neoplasms; Mediating; melanoma; Melanoma Cell; Metastatic Melanoma; Microarray Analysis; Military Personnel; Molecular; mouse model; Multiprotein Complexes; Natural Immunity; Neoplasm Metastasis; neoplastic cell; new therapeutic target; novel; Patients; peripheral blood; peripheral tolerance; Phenotype; Play; Population; Prevention; Process; Production; Receptor Signaling; Regulatory T-Lymphocyte; Relapse; Risk; Role; Sampling; Services; Signal Pathway; Skin Cancer; Source; Stimulus; success; Sun Exposure; Sunburn; T cell response; T-Lymphocyte; Testing; TGF Beta Signaling Pathway; Therapeutic; Therapeutic Agents; transcriptome; Transforming Growth Factor beta; Treatment Efficacy; tumor; Tumor Escape; tumor growth; Tumor Immunity; tumor progression; Whole Blood; young woman; ","Autoinflammation in Human Melanoma","001228","ONCE","Oncology E ","","","07","","","",""
"9815417","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001793","","RFA-BX-17-001","5I01BX001793-07","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","Current disease modifying therapies (DMT) for MS are only approved for relapsing subtypes of MS; no DMTs have been approved for progressive MS (PMS), resulting in reduced community participation, low quality of life, and high burdens on health care systems. Lipoic acid (LA) has shown great promise for PMS therapy in animal models, in vitro studies, and a small pilot clinical trial. The goal of this study is to begin the translation of this promise into clinical practice by establishing the mechanisms of action of LA and identifying biomarkers that can be used to assess its therapeutic effects in vivo. This will provide critical information in the design of a larger clinical trial in people with MS. To do so, we are proposing to study the effects of LA on a variety of cell types involved in the pathogenesis of MS and the role of the cyclic AMP and Nrf2 signaling cascades in regulating these processes. The results of these studies will provide guidance in issues relating to drug toxicities, contraindications, and potentially in the diagnosis or treatment of different forms or stages of MS.","9752595; ","SALINTHONE, SONEMANY ;","","01/01/2013","09/30/2021","Affect; Animal Model; Antioxidants; Biochemical; Biological Assay; Biological Markers; Biological Process; Blood - brain barrier anatomy; cell type; Cells; Central Nervous System Diseases; cerebral atrophy; Cessation of life; chemokine; Clinical; clinical practice; Clinical Trials; cohort; Community Participation; copolymer 1; cost; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; cyclooxygenase 1; cytokine; Data; design; Development; Diagnosis; Dinoprostone; disability; disabling disease; Disease; Disease Progression; Dose; Double-Blind Method; Drug toxicity; Endothelial Cells; Epoprostenol; Exhibits; Experimental Autoimmune Encephalomyelitis; falls; FDA approved; Fumarates; Goals; Gold; Grant; Healthcare Systems; Human; Immune; Immunosuppressive Agents; improved; In Vitro; in vivo; Inflammation Mediators; Inflammatory; Injections; Injury; insight; Interferon-beta; Intravenous infusion procedures; Knowledge; Lesion; Life; Lymphopenia; macrophage; magnetic resonance imaging biomarker; Mediating; Mediator of activation protein; Microglia; migration; Mitochondria; Modeling; monocyte; Multi-Institutional Clinical Trial; multi-site trial; Multiple Sclerosis; multiple sclerosis patient; natalizumab; Nervous System Physiology; Neuraxis; Neurons; NK Cell Activation; nuclear factor-erythroid 2; Nucleic Acids; Oligodendroglia; Oxidation-Reduction; Oxidative Stress; Pathogenesis; Pathway interactions; Patients; Permeability; Phagocytosis; Pharmaceutical Preparations; Pharmacologic Substance; pilot trial; Placebos; prevent; Process; Production; Property; protective effect; Quality of life; Reagent; Relapse; Relapsing-Remitting Multiple Sclerosis; Respiration; response; Role; Second Messenger Systems; Severity of illness; Side; side effect; Signal Transduction; small molecule; Spinal Cord; Suggestion; T-Cell Activation; T-Lymphocyte; Testing; Therapeutic; Therapeutic Effect; Thioctic Acid; Toxic effect; transcription factor; Translating; Translations; treatment strategy; trend; Vascular Endothelium; Walking; Work; ","Mechanisms of action: the effects of lipoic acid on macrophages,endothelial cells and CNS function in MS","001793","NURB","Neurobiology B ","","","07","","","",""
"9815432","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003232","","RFA-BX-15-001","5I01BX003232-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","Aurora","UNITED STATES","","06","003252830","US","481018","VA EASTERN COLORADO HEALTH CARE SYSTEM","CO","800457211","PUBLIC HEALTH RELEVANCE        Cancer often has an indolent state that exists for a long time before evolving into an aggressive tumor. This application will use a unique experimental model and comprehensive approaches to identify cellular processes and molecular markers to determine if a given indolent tumor will evade to aggressive malignancy. The proposed functional validation of markers will simultaneously test therapeutic strategies to hold indolence in check.","7838047; ","WANG, XIAO-JING ;","","10/01/2016","09/30/2020","Affect; angiogenesis; Apoptosis; B-Lymphocytes; base; Behavior; Biological Models; biomarker identification; biomarker validation; cancer cell; candidate marker; candidate validation; Cell Death; cell growth; cell motility; Cell physiology; Cells; Cessation of life; chemokine; Comparative Study; cytokine; Data; design; Dyes; Epithelial; Equilibrium; Experimental Models; Fibroblasts; Hibernation; Human; human model; Immune; In Vitro; in vivo; Individual; Indolent; Infiltration; Inflammatory; Keratin; knock-down; macrophage; Malignant Neoplasms; Mediating; Mesenchymal; Metastatic Neoplasm to the Lung; Molecular; molecular marker; Morbidity - disease rate; mouse model; Mouse Strains; Mus; mutant; Mutation; Neoplasm Metastasis; neoplastic cell; Oral cavity; outcome forecast; Patients; Plasma; Play; Population; predictive marker; Primary Neoplasm; Property; public health relevance; Risk; Role; self-renewal; Side; Signal Transduction; Site; Skin; Small Interfering RNA; Squamous Cell; Squamous cell carcinoma; Squamous Differentiation; Stem cells; Stress; System; T-Lymphocyte; Testing; Therapeutic; therapeutic evaluation; Time; Transforming Growth Factor beta; Transplantation; tumor; Tumor Bank; Tumor Cell Invasion; Tumor Expansion; Tumor Immunity; Tumor Initiators; Tumor-associated macrophages; Tumor-Derived; ","Mechanisms of Breaking Indolence in Squamous Cell Carcinoma","003232","ONCE","Oncology E ","","","04","","","",""
"9815441","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003877","","RFA-BX-16-001","5I01BX003877-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LEXINGTON","UNITED STATES","","06","018766373","US","481036","VA MEDICAL CENTER - LEXINGTON, KY","KY","405022235","Relevance of the Project to Veterans' Health: Worldwide, thrombotic events, e.g., strokes and heart attacks, account for 1 of 4 deaths, not caused by communicable diseases. Thrombotic events are major killers of aging veterans especially female veterans. Platelets are essential for clot formation, but targeting them to control thrombosis requires a greater understanding of how platelet work. In this proposal we look at two aspects of platelet cell biology, exocytosis and endocytosis, to determine how and why platelets both release clotting components and take them up them during clot formation. Our experiments will generate the critical mechanistic insights needed to effectively control platelet function and thus limit thrombosis in aging veterans.","1887348; ","WHITEHEART, SIDNEY WALDO;","","10/01/2017","09/30/2021","Acute; Address; Adhesions; Affect; Age; Aging; Amino Acid Sequence; Autophagocytosis; base; Biochemical; Biological Assay; Blood Platelets; Blood Vessels; Cardiovascular Diseases; Caring; Carotid Artery Injuries; Cause of Death; Cell physiology; Cellular biology; Cessation of life; clinically significant; Clot retraction; Coagulation Process; Communicable Diseases; Complex; Cytoplasmic Granules; Data; Disease; Endocytosis; Equilibrium; Event; Exocytosis; experimental study; familial hemophagocytic lymphohistiocytosis; Female; Fibrinogen; Gene Deletion; genome wide association study; glycosylation; Goals; granuphilin; Growth; Guanosine Triphosphate Phosphohydrolases; Health; health management; Hemorrhage; Hemostatic function; Hyperactive behavior; improved; In Vitro; in vitro Assay; in vivo; Infarction; insight; Integrins; Knock-out; Knockout Mice; Knowledge; male; Mediating; Membrane; Membrane Fusion; Mission; Modeling; Molecular; Molecular Chaperones; Molecular Probes; Morbidity - disease rate; mortality; Mouse Strains; Mus; Myocardial Infarction; Pathology; Patients; Physicians; platelet function; Population; Precision Medicine Initiative; Process; Protein Biochemistry; protein protein interaction; Proteins; Publishing; Reaction; recruit; response; restenosis; Risk; Risk Factors; risk variant; RNA Splicing; Role; S-nitro-N-acetylpenicillamine; Sampling; SNAP receptor; Stroke; synaptotagmin; syntaxin; syntaxin 11; syntaxin A; syntaxin-2; Tail; target SNARE proteins; targeted treatment; Therapeutic Intervention; therapeutic target; Thrombosis; Thrombus; trafficking; Transgenic Mice; Translations; treatment strategy; vesicular SNARE proteins; Veterans; Work; ","Targeting Platelet Endocytosis and Exocytosis to Control Thrombosis","003877","HEMA","Hematology ","","","03","","","",""
"9815447","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003005","","RFA-BX-15-002","5I01BX003005-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BRONX","UNITED STATES","","13","040077133","US","481060","JAMES J PETERS VA  MEDICAL CENTER","NY","104683904","PUBLIC HEALTH RELEVANCE:        At least 20% of Iraq and Afghanistan veterans are diagnosed with post-traumatic stress disorder (PTSD), and this number is even higher when combined with traumatic brain injury (TBI). Currently, there are no effective disease modification treatments for this devastating disorder. PTSD-like depression and anxiety are associated with maladaptation of synaptic plasticity in the brain's reward circuit, which controls depression and anxiety-like behaviors. In this study, we wil identify bioactive polyphenol compounds that target synaptic plasticity mechanisms as a potential alternative therapeutic approach for preventing and treating depression and anxiety disorders.","2479101; ","PASINETTI, GIULIO MARIA;","","10/01/2016","09/30/2020","Actins; Affect; Afghanistan; Animals; Anxiety; Anxiety Disorders; anxiety-like behavior; Applications Grants; Attenuated; attenuation; Award; base; behavior test; behavioral outcome; behavioral response; Bioavailable; Brain; C57BL/6 Mouse; Chronic stress; depression model; design; Development; Diagnosis; Dietary Polyphenol; Disease; Dose; Down-Regulation; efficacy study; Electrophysiology (science); Engineering; Epigenetic Process; Excitatory Synapse; experience; Exposure to; Freedom; Gene Expression; Genes; Genetic; Glutamate Transporter; Goals; Grant Review; Guanosine Triphosphate Phosphohydrolases; In Vitro; in vivo; Individual; Inhibitory Synapse; Iraq; Link; Measures; Mediating; Mental Depression; Modeling; Modification; Molecular Target; Monitor; Moods; mouse model; Mus; Neuronal Plasticity; Neurons; novel; Nucleus Accumbens; operation; Oral Administration; oral supplementation; Outcome; Outcome Study; Pathologic; Phenotype; Play; polyphenol; Population; Post-Traumatic Stress Disorders; postsynaptic; pre-clinical; Pre-Clinical Model; preclinical efficacy; Preclinical Testing; Preparation; preservation; presynaptic; prevent; Prodrugs; promoter; prophylactic; Proteins; psychologic; public health relevance; Research Project Grants; resilience; response; Rewards; Role; Safety; safety assessment; screening; Simplexvirus; Site; Slice; social defeat; Social Interaction; social stress; Stress; Surveys; Synapses; Synaptic plasticity; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Therapeutic Studies; Toxic effect; Transgenic Mice; Traumatic Brain Injury; treatment response; Vesicle; vesicular GABA transporter; Veterans; ","Novel Prophylactic and Therapeutic Interventions for Stress-Induced Depression","003005","NURA","Neurobiology A ","","","04","","","",""
"9815458","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003919","","RFA-BX-17-001","5I01BX003919-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","TUCSON","UNITED STATES","","03","084471531","US","481007","SOUTHERN ARIZONA VA HEALTH CARE SYSTEM","AZ","857230001","Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive and deadly fibrotic lung disease, with a median survival rate of less than 3 years. IPF disproportionately affects the aging veteran population. No drug treatment has been shown to definitively improve quality of life for IPF patients; clearly, improved therapies for IPF are needed. Although aging is a well-recognized risk factor for IPF, the contribution of aging to the cellular/molecular mechanism(s) leading to this disease remains poorly understood. These studies will provide novel insight into why the healing process `goes awry' in aging, resulting in susceptibility to disease. Further, we will evaluate the preclinical efficacy of a drug candidate (currently in phase II clinical trials for cancer indications) for IPF.","8407333; ","HECKER, LOUISE ;","","10/01/2017","09/30/2021","Acute; Affect; Age; age related; aged; Aging; Animal Model; Antineoplastic Agents; Apoptosis; Automobile Driving; cancer clinical trial; Cells; Chronic; Cicatrix; Clinical; clinical translation; cohort; cytokine; Data; Development; Disease; Down-Regulation; drug candidate; Enzymes; Exhibits; extracellular; Failure; Fibroblasts; Fibrosis; Functional disorder; Genetic; genetic approach; healing; Healthcare; Human; Hydrogen Peroxide; idiopathic pulmonary fibrosis; Impairment; improved; In Vitro; in vivo; in vivo Model; inhibitor/antagonist; Injury; Innate Immune Response; insight; Knock-out; Lung; Lung diseases; lung injury; Mediating; Modeling; Molecular; mouse model; Mus; Myofibroblast; NADPH Oxidase; neutralizing antibody; nicotinamide phosphoribosyltransferase; novel; novel therapeutics; Oxidants; Pathogenesis; Pathologic; Patients; Pharmacology; Pharmacotherapy; Phase II Clinical Trials; Phenotype; Play; Population; pre-clinical; preclinical efficacy; Predisposition; Process; promoter; Proteins; Pulmonary Fibrosis; Quality of life; receptor; Resistance; Resolution; response; Risk Factors; Role; senescence; Signal Transduction; Structure of parenchyma of lung; Survival Rate; Testing; Therapeutic Agents; therapeutic target; Tissues; TLR4 gene; Transforming Growth Factor beta; Treatment Efficacy; treatment strategy; Up-Regulation; Veterans; ","The role of Nampt in age-associated persistent lung fibrosis","003919","PULM","Respiration ","","","03","","","",""
"9815459","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003171","","RFA-BX-16-001","5I01BX003171-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOS ANGELES","UNITED STATES","","33","066689118","US","481012","VA GREATER LOS ANGELS HEALTHCARE SYSTEM","CA","900731003","Lung cancer is the leading cause of cancer death in the world and among our Veteran population. With the existing therapeutic interventions, the long term survival for lung cancer patients remain low and only 15% survive for 5 years following diagnosis. New therapeutic strategies are needed. Findings from this study has potential for the development of novel immune based therapy for lung cancer.","1858211; ","SHARMA, SHERVEN ;","","10/01/2016","09/30/2020","adaptive immune response; Address; anti-PD1 therapy; Antibodies; Antitumor Response; Autologous; Automobile Driving; base; Biological Models; Cancer Etiology; Cancer Model; Cancer Patient; CCL21 gene; CD8-Positive T-Lymphocytes; CD8B1 gene; Cessation of life; checkpoint therapy; chemokine; Clinical; Clinical Trials; Combined Modality Therapy; Combined Vaccines; CXCL10 gene; CXCL9 gene; Data; Dendritic Cells; Development; Diagnosis; Disease; Dose; effector T cell; Frequencies; Gene-Modified; Geographic Locations; Goals; Immune; immune checkpoint blockade; Immune checkpoint inhibitor; Immune response; Immunity; immunoregulation; Immunotherapy; improved; In Situ; in vivo; Individual; Infiltration; Injections; innovation; Interferon Type II; Lung; Lymphocyte; Malignant neoplasm of lung; Measures; Mediating; Molecular; Mus; Myelogenous; Non-Small-Cell Lung Carcinoma; novel; novel therapeutic intervention; Pathway interactions; Patients; PDCD1LG1 gene; Peptides; Physiologic pulse; Play; Population; pre-clinical; Pre-Clinical Model; preclinical study; Property; recruit; Regulatory T-Lymphocyte; Reporting; Research Design; response; Role; SLEB2 gene; subcutaneous; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; Therapeutic; Therapeutic Intervention; TNF gene; tumor; Tumor Antigens; Tumor Burden; tumor growth; Tumor-associated macrophages; Tumor-infiltrating immune cells; uptake; Vaccination; Vaccine Therapy; Vaccines; Veterans; ","Programming Durable Immune Responses in Lung Cancer","003171","ONCB","Oncology B ","","","04","","","",""
"9831579","I21","VA","5","N","10/21/2019","10/01/2019","09/30/2020","999","I21RX002902","","RFA-RX-18-012","5I21RX002902-02","","RESEARCH CENTERS","2020","Veterans Affairs","","BUFFALO","UNITED STATES","","26","020653809","US","481057","VA WESTERN NEW YORK HEALTHCARE SYSTEM","NY","142151129","Frailty is a clinical condition of poor physiological reserve that increases risks for adverse health outcomes including falls, hospitalization and mortality. Exercise is beneficial for the prevention and even reversal of frailty, yet participation among older individuals is limited. Short session high intensity interval training (HIIT) is emerging as a promising exercise strategy that achieves performance gains with lower time commitment. The goal of this pilot proposal is to establish the feasibility of HIIT exercise training protocols in 65-85 year old individuals, as well as to demonstrate the ability to detect functional and physiologic benefits. We anticipate our preliminary research findings will lay the foundation for future human clinical studies that will permit us to significantly improve the health of our veterans.","1954153; ","TROEN, BRUCE R.;","","10/01/2018","09/30/2020","Activities of Daily Living; Adherence; Aerobic; Affect; Age; Age-Years; aged; Aging; balance testing; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials; Cognitive; cohort; conditioning; cost; Data; disability; Drops; Elderly; Exercise; exercise intensity; exercise training; Exhibits; fall risk; falls; Foundations; frailty; functional gain; Future; Gait speed; Goals; grasp; Health; Healthcare; Healthcare Systems; Hospitalization; Hospitals; Human; human old age (65+); human very old age (85+); improved; Incidence; indexing; Individual; Interval training; Intervention; Lead; male; men; mental state; MicroRNAs; Modality; mortality; Mus; muscle form; muscle strength; next generation; older patient; Outcome; Participant; Patients; Performance; Physical Performance; Physiological; Physiological Adaptation; Pilot Projects; Population; predicting response; Predisposition; prevent; Prevention; Primary Health Care; prognostic tool; programs; Protocols documentation; Public Health; Publishing; quadriceps muscle; Quality of life; Recommendation; Recovery; recruit; Regimen; Reporting; Research; resistance exercise; retention rate; Risk; Risk Factors; RNA; RNA Sequences; Sampling; sarcopenia; satisfaction; screening; sedentary; Serum; Surveys; Technology; Testing; Time; Training; transcriptome sequencing; Universities; Veterans; Woman; ","Enhancing functional capacity in older adults with short session high intensity interval training","002902","RRDS","Rehabilitation Research and Development SPiRE Program ","","","02","","","",""
"9859193","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004419","","RFA-CX-17-004","5I01BX004419-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BIRMINGHAM","UNITED STATES","","07","082140880","US","481003","BIRMINGHAM VA MEDICAL CENTER","AL","352331927","Amyotrophic lateral sclerosis is a relentless disease of motor neurons that leads to progressive paralysis of the muscles and ultimately death. There is a significantly increased incidence of this disease in our veterans of foreign wars, and treatment options are limited and with only modest effect. Initiation of ALS and its progression is markedly influenced by neuroinflammation that is triggered by immune cells in the central nervous system. This proposal will address the molecular mechanisms of neuroinflammation in ALS by focusing on microglia which are key contributors to the immune response in ALS. This work will identify novel pathways that can be targeted for new therapies in this devastating disease.","1894867; ","KING, PETER H;","","10/01/2018","09/30/2022","Address; Adopted; Alzheimer's Disease; Amyotrophic Lateral Sclerosis; Animal Model; Anti-inflammatory; Area; Astrocytes; Attenuated; attenuation; Cells; Central Nervous System Diseases; Cessation of life; Chemicals; chemokine; Chemotaxis; Clinical; cytokine; Data; Degenerative Disorder; Disease; Disease Progression; effective therapy; Elements; Emotional; Exhibits; Extracellular Matrix; Family; Frustration; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; glial activation; Goals; Hand; HuR protein; Immune; Immune response; In Vitro; in vivo Model; Incidence; Inflammation Mediators; Inflammatory; Inflammatory Response; injured; innovation; Interleukin 6 Receptor; Interleukin-1; Interleukin-10; Interleukin-12; Interleukin-6; Investigation; Knock-out; Link; macrophage; Mediating; Mediator of activation protein; Microglia; migration; Mission; MME gene; Molecular; Motor; Motor Neuron Disease; mouse model; Multiple Sclerosis; Mus; Muscle; mutant; Neuraxis; Neurodegenerative Disorders; Neuroglia; neuroinflammation; Neurons; neuroprotection; new therapeutic target; NOS2A gene; novel; novel therapeutic intervention; novel therapeutics; Oligodendroglia; Onset of illness; Paralysed; Parkinson Disease; Pathway interactions; Patients; Peripheral; Phase II Clinical Trials; Phenotype; Phosphodiesterase Inhibitors; Physicians; Play; Population; Post-Transcriptional Regulation; Process; Production; programs; promoter; Property; Publications; recruit; Regulation; Regulator Genes; Research; response; RNA-Binding Proteins; RNA-Protein Interaction; Role; Signal Transduction; Signaling Molecule; small molecule inhibitor; Spinal cord injury; Stroke; superoxide dismutase 1; Testing; therapeutic target; Tissues; TNF gene; Toxic effect; Up-Regulation; Veterans; War; Work; ","Role of Microglial Hur in promoting neuroinflammation and ALS disease progression","004419","NURE","Neurobiology E ","","","02","","","",""
"9870479","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004857","","RFA-BX-19-022","1IK6BX004857-01","","OTHERS","2020","Veterans Affairs","","PORTLAND","UNITED STATES","","03","089461255","US","481073","PORTLAND VA MEDICAL CENTER","OR","972392964","U.S.  servicemen  and  women  encountered  malaria  during  the  Revolutionary  War  and  every  US  war since that time. Malaria and antimalarials are two of the most common biological and chemical  exposures  of  US  veterans.  Multidrug  resistant  parasites  have  spread  to  virtually  all  malarious  regions  of  the  world.  New  drug  strategies  for  prevention  and  treatment  of  malaria  are  urgently  needed. My lab is committed to the development of safe and effective drugs that can be used in  all  individuals,  regardless  of  their  station:  children,  adults,  men,  women,  pregnant,  unborn,  or  genetically deficient in the enzyme glucose 6-­phosphate dehydrogenase (G6PD). The resultant  advantages  of  avoiding  drug  toxicity,  febrile  illness  and  complex  medical  management  during  deployment are self-­evident, as are the benefits to both short and long-­term health of the soldier. ","1978072; ","RISCOE, MICHAEL KEVIN;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Renewal Award Application","004857","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9782075","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004821","","RFA-CX-18-001","1I01BX004821-01A1","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","DECATUR","UNITED STATES","","04","824835805","US","481023","VETERANS HEALTH ADMINISTRATION","GA","300334004","Most veterans will develop atherosclerotic cardiovascular disease (CVD) during their lifetime. Research to date has largely focused on the role of traditional risk factors and the occurrence of CVD outcomes. Genes and the environment work in concert to foster the development of traditional risk factors and subsequently increase the risk for clinical vascular disease. This project provides the opportunity to investigate the role of genes and environment as causative in the development of the risk factors and the association of genes with CVD itself. It also expands the scope to include new CVD risk factors including blood cell indices, inflammatory conditions, valvular heart disease, obstructive sleep apnea, and atrial fibrillation. The project we describe creates the framework for the VA to participate in the process for CVD research concerning MVP assessment, risk factors and CVD outcomes.","6806522; ","WILSON, PETER WYMAN;","","10/01/2019","09/30/2023","Address; adjudication; African American; Age; Alcohol consumption; Ambulatory Care; American; Arthritis; Atherosclerosis; Atrial Fibrillation; base; Bioinformatics; Blood Cells; blood glucose regulation; Blood Pressure; Body mass index; Cardiovascular Diseases; cardiovascular disorder risk; cardiovascular risk factor; Cessation of life; clinical Diagnosis; clinical risk; cohort; Cohort Studies; Complete Blood Count; Coronary Artery Bypass; Coronary heart disease; Data; Data Element; Data Sources; Databases; Development; Diabetes Mellitus; Diet; Disease Outcome; Electronic Health Record; Elements; Enrollment; Environment; Ethnic Origin; European; Event; Food; Fostering; Frequencies; Funding; Future; Genes; Genetic; genetic association; Genetic Risk; genetic risk factor; genetic variant; Genetic Variation; genome wide association study; Glycosylated hemoglobin A; Health; healthy aging; heart disease risk; Heart Valve Diseases; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hispanic Americans; Incidence; indexing; Inflammatory; Intake; Investigation; LDL Cholesterol Lipoproteins; Link; Lipids; Longitudinal prospective study; Low-Density Lipoproteins; Measurement; Measures; Medicare; Methods; Myocardial Infarction; Nutrient; Obstructive Sleep Apnea; Outcome; Outpatients; Participant; Patient Self-Report; percutaneous coronary intervention; Pharmacological Treatment; Phenotype; Physical activity; Population Group; post stroke; precision medicine; predictive modeling; Prevalence; Primary Health Care; Process; professional atmosphere; programs; prospective; Questionnaires; Race; rare variant; Recording of previous events; Recurrence; Research; Research Design; Risk; Risk Factors; Role; sex; Smoking; Stroke; structural heart disease; Subgroup; survival outcome; survivorship; Techniques; Testing; Time; trait; treatment effect; Triglycerides; valvular stenosis; Variant; Vascular Diseases; Veterans; virtual; Visit; White Blood Cell Count procedure; Work; ","Cardiovascular Disease Risk Factors, Cardiovascular Disease Risk Prediction, and Genetics in the Million Veteran Program","004821","ZRD1","Special Emphasis Panel ","","A1","01","","","",""
"9786077","I01","VA","5","N","10/21/2019","10/01/2019","09/30/2020","999","I01RX001813","","RFA-RX-16-003","5I01RX001813-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","Greater than one third of older Veterans are obese. Obesity is a major risk factor for mobility problems. It is estimated that 11 million older adults have a mobility disability and four million use walking assistive devices. Dietary programs that restrict caloric intake have been successful in achieving weight loss. However, some research has shown that weight loss can result in loss of muscle mass which may reduce physical function. This could be detrimental to older obese Veterans with mobility disability. There has been little research on the effectiveness of a combined exercise and weight loss program in older obese Veterans who use assistive devices. We believe that our novel multimodality balance intervention along with a structured weight loss program will be effective at reducing weight and improving walking speed, balance, strength and quality of life in obese, older Veterans with mobility disability.","1901034; ","KATZEL, LESLIE I.;","","10/01/2016","09/30/2020","Abdomen; adult obesity; Aerobic; Age; American; Area; Baltimore; base; Biological Markers; Biomechanics; Body Composition; Body fat; Body Weight decreased; Capsicum; Cessation of life; Clinical; clinical care; Collaborations; Communities; Comorbidity; deconditioning; Diet; Dietary Intervention; Dietitian; disability; Dual-Energy X-Ray Absorptiometry; education research; effective intervention; Effectiveness; Elderly; Energy Intake; Energy Metabolism; Enrollment; Equilibrium; Exercise; exercise intervention; exercise rehabilitation; experience; fall risk; Fatigue; Fatty acid glycerol esters; fitness; functional independence; functional status; Gait; Gait speed; Geriatrics; Goals; group intervention; Hip region structure; Hospitalization; Human; Impairment; improved; improved functioning; improved mobility; Individual; Injury; instrument; instrumental activity of daily living; Intervention; intervention program; Intramuscular; Isometric Exercise; Laboratories; Lateral; Lead; Lower Extremity; Maryland; Measurement; Measures; Mediation; Medical; Medical center; Methods; Movement; multidisciplinary; multimodality; Muscle; muscle form; Muscular Atrophy; novel; nutrition; Nutritional; Obesity; Outcome Measure; Patient Self-Report; Performance; Physical activity; Physical Function; Physiological; portability; Prevalence; programs; Quality of life; Randomized; Randomized Clinical Trials; Research; Resources; Risk Factors; Robotics; sarcopenia; sarcopenic obesity; Scanning; Self-Help Devices; Spiral Computed Tomography; Step Tests; Structure; Supervision; System; Testing; Thigh structure; Time; Translating; Universities; Upper Extremity; Veterans; Walking; walking speed; Weight; weight loss program; X-Ray Computed Tomography; ","Multimodal Exercise and Weight Loss in Older Veterans with Dysmobility","001813","RRD6","Blank ","","","04","","","",""
"9814669","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001123","","RFA-BX-15-001","5I01BX001123-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","PUBLIC HEALTH RELEVANCE        Renal cell carcinoma (RCC) is one of the most common malignancies among our Veterans. The major barrier or clinical challenge is that despite the recent advances in the understanding of the biological basis of RCC, the management of the disease, especially in the advanced metastatic phase, remains a significant challenge. The rationale is that the c-Myc/HIF pathway is important in kidney cancer progression and metastasis. To address this problem, we will investigate the role of a set of miRNAs that directly target the c-Myc/HIF pathway and thereby inhibit kidney cancer progression and metastasis. Accomplishment of this study will be a significant step forward in understanding miRNA-mediated regulation of the c-Myc/HIF pathway and designing novel miRNA-based therapeutic strategies for metastatic kidney cancer among our Veterans. We believe that the work proposed is highly relevant to Veterans health and the VA mission.","1857727; ","DAHIYA, RAJVIR ;","","10/01/2011","09/30/2020","3' Untranslated Regions; 5' Untranslated Regions; Address; angiogenesis; Apoptosis; base; Binding; Biological; Biological Assay; bone; c-myc Genes; cancer cell; Cancer cell line; Cancer Patient; Cell Cycle; cell growth; Cell physiology; Clinical; clinical biomarkers; clinically significant; Complex; CpG Islands; Data; design; Diagnosis; Disease Management; DNA Methylation; DNA Modification Methylases; DNA sequencing; DNMT3a; DNMT3B gene; Epigenetic Process; Epithelial; Event; experimental study; Expression Profiling; Genes; Goals; Health; Histologic; Histone Acetylation; histone modification; Histones; Hypermethylation; Implant; In Situ Hybridization; In Vitro; in vivo; in vivo Model; Lead; Literature; Liver; Luciferases; Lung; lymph nodes; Malignant Neoplasms; Mediating; Mesenchymal; Messenger RNA; Methylation; MicroRNAs; migration; Mission; Mitotic Cell Cycle; Molecular; Monitor; Mus; Neoplasm Metastasis; NOD/SCID mouse; novel; Oncogenic; Organ; Outcome; outcome forecast; overexpression; Pathway interactions; Phase; Play; predict clinical outcome; promoter; Promoter Regions; Proteins; public health relevance; Publishing; Regulation; Renal carcinoma; Renal Cell Carcinoma; Repression; Role; Series; sodium bisulfite; Techniques; Testing; Therapeutic; therapeutic miRNA; therapeutic target; Time; tumor; tumor progression; Tumor Suppressor Proteins; Veterans; Work; ","Regulation of c-Myc/HIF pathway in the management of kidney cancer","001123","ONCA","Oncology A ","","","08","","","",""
"9814678","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001176","","RFA-BX-16-001","5I01BX001176-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PHILADELPHIA","UNITED STATES","","03","071609291","US","481078","PHILADELPHIA VA MEDICAL CENTER","PA","191044551","Pulmonary fibrosis is a devastating interstitial lung disease (ILD) marked by unrelenting respiratory failure and death. It is increasingly recognized that lung epithelial cell dysfunction plays an important role in the pathogenesis of ILD. Over 50 different mutations in the Surfactant Protein C (SP-C) gene in humans are associated with lung fibrosis. Since SP-C is made and secreted by alveolar type 2 epithelial cells, SP-C mutations can be used as model substrates to probe the role of epithelial cell dysfunction in ILD pathogenesis. Using novel cell systems and mouse models expressing these mutations we will characterize molecular mechanisms regulating cellular quality control responses (e.g. the unfolded protein response, proteasomal degradation, autophagy) used by epithelial cells for maintenance of homeostasis in health and how their failure contributes to ILD development. Results funded by this project will permit rapid assessment of new therapeutic targets for ILD treatment.","1871720; ","BEERS, MICHAEL FRANCIS;","","07/01/2012","09/30/2020","Affect; Age; age related; Alveolar; alveolar lamellar body; Anabolism; Apoptosis; Architecture; Automobile Driving; Autophagocytosis; base; biological adaptation to stress; Biophysics; Cell Maintenance; Cell membrane; Cell Separation; Cells; Cellular biology; Cessation of life; Chronic; Cicatrix; Clinical; clinically relevant; Coupled; cytotoxicity; Data; design; Development; Diffuse; Disease; disease phenotype; Distal; DNA Sequence Alteration; Dose; Elderly; endoplasmic reticulum stress; Epithelial; Epithelial Cells; Exclusion; Exhibits; experience; Failure; Family; Fibroblasts; Functional disorder; Funding; Gases; Gene Dosage; Genes; Genetic; Genetic Models; Goals; Growth; Hand; Health; Homeostasis; Human; Hydrophobicity; idiopathic pulmonary fibrosis; Impairment; In Vitro; in vivo; Infection; Inflammatory; Injury; injury and repair; Interstitial Lung Diseases; Knock-in Mouse; Lung; lung development; Lung diseases; lung injury; Mediating; Methods; Modeling; Molecular; mouse model; Mus; mutant; Mutant Strains Mice; Mutation; new therapeutic target; Nitrates; novel; Pathogenesis; Pathway interactions; Patients; Pattern; Pharmacology; Phenotype; Phospholipids; Play; Predisposition; programs; Progress Reports; Protein Isoforms; Proteins; proteostasis; Publishing; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Protein C; Quality Control; Reagent; respiratory; Respiratory Failure; response; Role; Route; Seminal; Series; Stress; surfactant; System; Testing; Therapeutic; Time; tool; Toxic effect; trafficking; Translating; Translations; Variant; Work; Wound Healing; ","Surfactant Protein C Mutations and Interstitial Lung Disease","001176","PULM","Respiration ","","","08","","","",""
"9815355","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004037","","RFA-BX-17-003","5I01BX004037-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","TAMPA","UNITED STATES","","14","929194256","US","481155","JAMES A. HALEY VA MEDICAL CENTER","FL","336124745","Granulocyte-colony stimulating factor (G-CSF) is a large protein that has been shown to improve recovery from brain injury in a mouse model of traumatic brain injury (TBI). We have learned from earlier research that G-CSF acts both directly on brain and on blood cells to promote brain repair. The endocannabinoid (eCB) system also appears to mediate neuro-reparative actions following brain injury. G-CSF and the eCB system overlap in the repair process both at the level of brain and the periphery, especially involving a bone marrow-derived cell population (BMDC). The primary objective of this project is to study the mechanisms of G-CSF interaction with the eCB system in repair and regenerative processes in a mouse model of TBI. The ultimate goal is to develop a combination of G-CSF and cannabinoid agents to treat veterans who have suffered TBI.","10803229; ","SONG, SHIJIE ;","","10/01/2018","09/30/2022","2-arachidonylglycerol; Agonist; Amides; anandamide; Animals; Anti-inflammatory; Apoptosis; arm; Astrocytosis; Basic Science; Behavioral; Blood Cells; bone circulation; Bone Marrow; Bone Marrow Transplantation; Brain; Brain Injuries; Brain region; brain repair; Brain-Derived Neurotrophic Factor; Cannabinoids; CB2 receptor antagonist; Cell Differentiation process; Cells; chemokine; Clinic; CNR1 gene; CNR2 gene; Colony-Stimulating Factor Therapy; Contralateral; controlled cortical impact; Corpus striatum structure; CSF3 gene; cytokine; design; Disease; Endocannabinoids; endogenous cannabinoid system; Ethanolamines; Fatty Acids; Fostering; frontal lobe; glial cell-line derived neurotrophic factor; Goals; Granulocyte Colony-Stimulating Factor; Hippocampus (Brain); Human; improved; inhibitor/antagonist; Injury; Interleukin-3; Knockout Mice; Lesion; Leukocytes; Ligands; Mediating; Messenger RNA; Microglia; monocyte; mouse model; Mus; Neuraxis; Neurodegenerative Disorders; neurogenesis; neuroinflammation; Neurons; neurotrophic factor; Performance; Phenotype; Population; Process; programs; Proteins; Protocols documentation; Radial; receptor; receptor expression; Recovery; Recovery of Function; recruit; regenerative; relating to nervous system; repaired; Research; response; Role; Site; stem; Stem cells; Stroke; System; Testing; Therapeutic Agents; Time; Transgenic Organisms; Traumatic Brain Injury; Traumatic Brain Injury recovery; treatment guidelines; Veterans; water maze; ","Interaction of GCSF with the Endocannabinoid System in Promoting Brain Repair","004037","NURC","Neurobiology C ","","","02","","","",""
"9815361","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004312","","RFA-BX-17-003","5I01BX004312-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","More than 360,000 armed service members sustained a TBI during combat and training from 2000 to 2016. Although a number of fluid biomarkers have emerged for detecting acute phases of TBI, biomarkers that detect persistent pathology and symptoms have been understudied. The VA is faced with treating TBI years after the initial injury, hence biomarkers associated with persistent symptoms and comorbidities are urgently needed to aid diagnosis, prognosis and development of targeted treatment strategies. Exosomes are secreted vesicles that are released from most types of cells including neurons. Neuronal exosomes are a readily detectable in blood, and are promising tools for aiding diagnosis of neurodegenerative disorders. This project will determine if circulating proteins and RNA carried in neuronal exosomes have utility as biomarkers for TBI and the associated persistent symptoms of TBI. This study will support the development of diagnostic tools for deployment-related TBI. !","7265491 (contact); 7027087; ","RISBROUGH, VICTORIA B (contact); RISSMAN, ROBERT A;","","10/01/2018","09/30/2022","Acute; Address; Affect; Afghanistan; Alzheimer's Disease; Alzheimer?s disease biomarker; Amyloid beta-Protein; associated symptom; base; Behavioral; Biological Markers; biomarker validation; Blood; Blood specimen; Brain Injuries; Caliber; Calpain; cell type; Cells; Chronic; Cleaved cell; Clinical Trials; Cognitive; cognitive performance; cohort; combat; Comorbidity; Companions; cost; Data; Dementia; Detection; Development; Diagnosis; Diagnostic; Endosomes; Enrollment; Evaluation; Exhibits; exosome; experience; functional decline; functional disability; Future; Genes; Genetic; genome-wide; Human; Image; Impaired cognition; Individual; Inflammatory; Injury; Intervention; Length; Life; Light; Link; Liquid substance; Longitudinal prospective study; Marines; Measures; Membrane; Mental Health; Messenger RNA; MicroRNAs; mild cognitive impairment; mild traumatic brain injury; Molecular; N-terminal; Nerve Degeneration; Neurobiology; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; neurofilament; Neurofilament-L; neurogranin; Neurologic; Neuronal Dysfunction; Neuronal Injury; Neurons; neuropathology; Neuropsychology; novel; outcome forecast; Participant; Pathogenicity; Pathology; Pathway interactions; Patients; Performance; peripheral blood; persistent symptom; Phase; physical conditioning; Plasma; Population Attributable Risks; Post-Concussion Syndrome; potential biomarker; Process; prospective; protein biomarkers; protein expression; protein S precursor; Proteins; Publishing; Recording of previous events; Regulation; Reporting; resilience; Risk; Risk Factors; RNA; sample collection; Sampling; service member; Severities; Small RNA; Source; specific biomarkers; Specificity; Spectrin; Symptoms; Synapses; targeted treatment; tau Proteins; tau-1; Testing; therapeutic target; Tissues; tool; Training; transcriptome sequencing; Traumatic Brain Injury; treatment strategy; Unconscious State; Vesicle; vesicular release; Veterans; Work; ","Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI","004312","NURC","Neurobiology C ","","","02","","","",""
"9815410","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001733","","RFA-BX-17-001","5I01BX001733-07","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","INDIANAPOLIS","UNITED STATES","","07","608434697","US","481029","RLR VA MEDICAL CENTER","IN","462022803","Diabetes mellitus (DM) is a disorder of glucose homeostasis that affects over 29 million Americans and nearly one in four Veterans. DM is a leading cause of blindness, kidney failure, and cardiovascular disease, and the incidence of this disorder is expected to double by 2050, suggesting increased numbers of Veterans will seek care for DM and that increased expenditures will be needed to provide this care. Pancreatic ? cell dysfunction is a central component of the pathophysiology of both major forms of DM, yet current therapies do little to address this facet of the disease. The goal of this proposal is to define how altered calcium regulation in the pancreatic ? cell impacts insulin production and secretion. The translational impact of this work will be the identification of novel pathways that can be targeted clinically as a means of preserving ? cell function and survival in DM.","8206234; ","EVANS-MOLINA, CARMELLA EVANS;","","04/01/2013","09/30/2021","5'-AMP-activated protein kinase; Active Biological Transport; Address; Affect; American; Autoimmune Process; Award; Beta Cell; Binding Proteins; Blindness; blood glucose regulation; Ca(2+)-Transporting ATPase; Calcium; Calcium Signaling; Cardiovascular Diseases; care seeking; Caring; Cations; Cell membrane; Cell physiology; Cell Survival; cell type; Cellular Stress; Clinical; Complement; Complex; Data; Defect; Diabetes Mellitus; diabetic; diabetogenic; Diet; Disease; Dose; Endoplasmic Reticulum; endoplasmic reticulum stress; euglycemia; Evolution; Expenditure; experimental study; Extracellular Space; Failure; Functional disorder; Funding; gain of function; Genetic; Genetic Transcription; Glucose; Goals; Grant; Health; Healthcare Systems; High Fat Diet; Homeostasis; human model; Hyperglycemia; Image; Impairment; improved; In Vitro; in vitro Model; in vivo; Incidence; Individual; Inflammatory; Insulin; Insulin Resistance; insulin secretion; Insulin-Dependent Diabetes Mellitus; Intervention; Ions; Kidney Failure; knock-down; Knowledge; Lead; loss of function; Maintenance; Mediating; Metabolic; Modeling; Molecular; Multiprotein Complexes; Mus; Non-Insulin-Dependent Diabetes Mellitus; novel; Obesity; Organelles; Pathogenesis; Pathway interactions; Pattern; Peripheral; Pharmacology; Phenotype; phosphoproteomics; Phosphorylation; Play; preservation; Prevalence; Process; Production; programs; Protein Kinase; Pump; Regulation; Research; response; Rodent Model; Role; Secretory Cell; sensor; Signal Pathway; Signal Transduction; Source; STIM1 gene; Streptozocin; Stress; Structure of beta Cell of islet; Syndrome; Testing; translational impact; Veterans; Work; ","Regulation of Calcium Homeostasis in the Pancreatic Beta Cell","001733","ENDA","Endocriniology A ","","","07","","","",""
"9815412","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001478","","RFA-BX-16-001","5I01BX001478-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","INDIANAPOLIS","UNITED STATES","","07","608434697","US","481029","RLR VA MEDICAL CENTER","IN","462022803","Roughly 25% men over the age of 50 will suffer an osteoporotic fracture during their senior years, and the 1- year mortality rate following a hip fracture is nearly 2× as high for men as for women. One-fifth of those who were ambulatory before their hip fracture require long-term care afterward. Beyond their age, other lifestyle factors make veterans particularly susceptible to osteoporosis, including smoking, alcohol consumption, and an inactivity. Moreover, many Vietnam veterans were exposed to environmental factors during the war, such as the dioxin TCDD (found in Agent Orange), which put them at much greater risk for osteoporosis. Recently, the VA amended its adjudication regulation to establish a presumption of service connection for osteoporosis for former Prisoners of War (POWs) who were detained or interned for at least 30 days, and more recently, for those diagnosed with posttraumatic stress dis-order (PTSD), and whose osteoporosis is at least 10% disabling. There is a clear need to identify new treatment options for veterans that suffer from low bone mass disease.","6137583; ","ROBLING, ALEXANDER G;","","01/01/2012","09/30/2020","Address; adjudication; Affect; Age; Age-Years; agent orange; Alcohol consumption; American; Anabolism; Antibodies; Back; base; Bed rest; Biological; Biology; bone; Bone Diseases; bone health; bone loss; bone mass; bone metabolism; Clinical; clinical efficacy; cortical bone; Data; design; Deterioration; Diagnosis; Dioxins; Disease; disease-causing mutation; Dose; Drug Industry; Drug usage; Ensure; Environmental Risk Factor; Event; Exposure to; FDA approved; Financial compensation; Fracture; Future; Genetic; Genetic Transcription; Glucocorticoids; Goals; Health; Hip Fractures; Homeostasis; Homing; human disease; Hyperostosis; Immunosuppression; improved; in vivo; Individual; Inflammation; inhibitor/antagonist; Injections; insight; knockout gene; lifestyle factors; Long-Term Care; Measurement; Measures; mechanical load; Mechanics; mechanotransduction; Mediating; member; men; Minor; Modeling; mortality; mouse model; Mus; Mutation; neutralizing antibody; Osteogenesis; Osteoporosis; osteoporosis with pathological fracture; Osteoporotic; Outcome; Paralysed; Pathway interactions; Patients; Pharmacology; Phenotype; Play; Population; Post-Traumatic Stress Disorders; prednisolone; prevent; Prisoner; Process; programs; Property; Reagent; receptor; Regimen; Regulation; Reporting; Research; response; Risk; Role; Services; Signal Pathway; Signal Transduction; Site; skeletal; Skeleton; Smoking; Stimulus; substantia spongiosa; Surface; Tail Suspension; Tetrachlorodibenzodioxin; Therapeutic; therapeutic target; therapy design; Time; Up-Regulation; Van Buchem disease; Veterans; Vietnam; War; wasting; Wasting Syndrome; WNT Signaling Pathway; Woman; Work; ","Harnessing the anabolic potential of Wnt signaling to improve bone health","001478","ENDB","Endocrinology B ","","","08","","","",""
"9815415","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002288","","RFA-BX-16-001","5I01BX002288-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NASHVILLE","UNITED STATES","","05","156385783","US","481084","VETERANS HEALTH ADMINISTRATION","TN","372122637","Acute Respiratory Distress Syndrome (ARDS) is a common and life-threatening cause of acute respiratory failure affecting over 190,000 Americans and 14,000 Veterans per year, 30-50% of whom will die. Thus there is an urgent need for new therapeutic approaches. We have identified a novel and protective role for the coagulation protein Tissue Factor (TF) in ARDS that is in distinct contrast to much of the existing knowledge of TF in ARDS. Despite encouraging animal studies suggesting that blocking TF may protect the lung, human studies have not shown benefit from blocking TF using an intravenous therapy in patients with ARDS. Our studies in mouse and human lung injury models suggest that one reason for these negative clinical studies is that TF is protective in the lung. Our project will help to understand how TF protects lung cells from injury. Furthermore we have found that a therapy targeted at enhancing TF function, coagulation factor VII, is protective in ARDS and could change the way we treat patients with this deadly condition.","8791484; ","BASTARACHE, JULIE ANNE;","","10/01/2017","09/30/2021","Abnormal Cell; Actins; Acute Lung Injury; Acute respiratory failure; Adhesions; Adult Respiratory Distress Syndrome; Affect; Alveolar; Alveolar Macrophages; American; Animals; Anticoagulants; Attenuated; Binding; Biological Models; Blood capillaries; Blood Coagulation Factor VII; Cancer Biology; Cell Adhesion; cell injury; Cell Line; Cell Migration Pathway; cell motility; Cell surface; Cells; Clinical; clinical efficacy; Clinical Research; clinically relevant; Coagulants; Coagulation Process; Complex; Computer Simulation; Cultured Cells; Data; Development; Ensure; Epithelial; Epithelial Cells; Epithelium; Experimental Designs; experimental study; extracellular; Extracellular Domain; Fibrin; Foundations; Generations; Genetic; Goals; Human; human model; In Vitro; in vivo; Inflammatory; Injury; insight; Integral Membrane Protein; Integrin Binding; Integrins; Intravenous; Klebsiella pneumonia bacterium; Knock-out; Knowledge; Laboratories; Lead; Libraries; Life; Ligand Binding; Ligands; Link; Lipopolysaccharides; Lung; lung injury; Malignant neoplasm of lung; Measurement; Mediating; Methods; Modeling; Molecular; mortality; mouse model; Mus; mutant; novel; novel therapeutic intervention; novel therapeutics; overexpression; Pathogenesis; Pathologic; Pathway interactions; Patients; Permeability; Pharmacologic Substance; Pharmacology; Prevention approach; protective effect; protein structure; Proteins; Publishing; Recombinants; Research Personnel; Resources; response; Role; skills; Structural Protein; targeted treatment; Testing; Therapeutic; therapeutic evaluation; Thrombin; Thromboplastin; Transgenic Mice; Type II Epithelial Receptor Cell; Up-Regulation; Veterans; Work; ","Potential Protective Mechanisms of Tissue Factor in Acute Lung Injury","002288","PULM","Respiration ","","","03","","","",""
"9815418","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001799","","RFA-BX-16-001","5I01BX001799-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","INDIANAPOLIS","UNITED STATES","","07","608434697","US","481029","RLR VA MEDICAL CENTER","IN","462022803","This proposal studies the pathogenesis of T-cell leukemias and lymphomas and directly benefits Veterans' health by advancing the development of targeted therapy and biomarkers. We will study specific genetic mutations and how they interact to cause these aggressive hematologic malignancies. The studies provide a foundation for the development of novel therapeutic targets in these treatment-resistant cancers.","8482382; ","DAVE, UTPAL P;","","10/03/2012","10/01/2021","actionable mutation; Acute T Cell Leukemia; Adult T-Cell Leukemia/Lymphoma; Advanced Development; Affect; Age Distribution; Apoptosis; base; Biological Markers; Bone Marrow; Caring; chemotherapy; Chemotherapy-Oncologic Procedure; Clinical; Cytokine Activation; Cytokine Signaling; Cytotoxic agent; Data; Development; Disease; DNA Sequence Alteration; drug sensitivity; Elderly; experience; FDA approved; Female; Fibrinogen; FLT3 gene; Foundations; Functional disorder; gain of function; Gene Expression Profiling; Genes; Genetic Transcription; Health; Hematologic Neoplasms; Human; IL2RG gene; in vivo; inhibitor/antagonist; JAK1 gene; JAK3 gene; knock-down; Laboratories; leukemia; leukemia/lymphoma; leukemogenesis; Lymphocyte Function; Lymphoma; male; Malignant Neoplasms; mouse model; mutant; Mutate; Mutation; Myeloid Leukemia; Neoplasms; new therapeutic target; novel marker; novel therapeutic intervention; Oncogenes; Oncogenic; overexpression; Pathogenesis; Pathway interactions; Phenotype; Phosphorylation; Population; precision medicine; progenitor; protein complex; Proteins; Resistance; Rhombotin 2; RUNX1 gene; Sampling; self-renewal; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Stat5 protein; Stem cells; Stimulus; synergism; T-Cell and NK-Cell Neoplasm; T-Cell Development; T-Cell Leukemia; T-Cell Transformation; T-Lymphocyte; targeted biomarker; targeted treatment; Testing; therapeutic target; transcription factor; Transgenic Mice; Transplantation; tumor initiation; Tumor stage; Veterans; Work; young adult; ","Pathophysiology of Adult T-cell Leukemia/Lymphoma","001799","HEMA","Hematology ","","","08","","","",""
"9815431","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004033","","RFA-BX-17-001","5I01BX004033-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","RICHMOND","UNITED STATES","","03","146678115","US","481091","VA VETERANS ADMINISTRATION HOSPITAL","VA","232490001","Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and it disproportionately impacts our veteran population. Despite the progress made on understanding the pathogenesis of NAFLD/nonalcoholic steatohepatitis (NASH), the specific mechanisms responsible for NAFLD/NASH development and progression remain largely unknown. Importantly, there is no FDA-approved therapy for NAFLD/NASH. Natural products are becoming increasingly attractive approaches for the treatment of various liver diseases including NAFLD/NASH. However, the scientific basis for the use of natural products is largely lacking. This application will uncover the novel mechanisms underlying the therapeutic effect of berberine, a natural plant medicine, on NAFLD/NASH and provide critical scientific evidence for future clinical trials and development of new therapeutic strategies for NAFLD/NASH.","8055059; ","ZHOU, HUIPING ROSE;","","10/01/2017","09/30/2021","Affect; Alkaloids; Animal Model; Anti-inflammatory; Apoptosis; Asia; base; Berberine; Bile Acids; biological adaptation to stress; Cholesterol; Cholesterol Homeostasis; chronic liver disease; Clinic; clinical development; Clinical Trials; Communicable Diseases; Complementary and alternative medicine; cytokine; Development; Disease; Disease Progression; Dyslipidemias; endoplasmic reticulum stress; Epithelial Cells; Equilibrium; Fatty acid glycerol esters; FDA approved; Future; gut microbiota; Health; Hepatic; Hepatocyte; HuR protein; Hypoglycemia; Immune; Immune response; in vivo; Inflammation; Inflammatory; Inflammatory Response; Insulin Resistance; Interleukin-6; Intestinal permeability; Intestines; Isoquinolines; Knock-out; Lead; Link; lipid metabolism; Lipids; Lipopolysaccharides; Liver diseases; long chain fatty acid; macrophage; Mediating; Medicinal Herbs; Medicine; Metabolic; Metabolic Diseases; metabolic endotoxemia; Metabolic syndrome; Metabolism; MicroRNAs; Modeling; Molecular; Natural Products; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel therapeutic intervention; Nucleotides; Pathogenesis; Pharmaceutical Preparations; Pharmacology; Plants; Population; Property; protective effect; Proteins; Reporting; Research; response; RNA-Binding Proteins; Role; Saturated Fatty Acids; Signal Pathway; Testing; Therapeutic Agents; Therapeutic Effect; therapeutic evaluation; TNF gene; transcription factor CHOP; Treatment Efficacy; Untranslated RNA; Veterans; western diet; ","Mechanisms of Berberine for the Treatment of Non-Alcoholic Fatty Liver Disease","004033","GAST","Gastroenterology ","","","03","","","",""
"9815435","IK2","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","IK2BX003509","","RFA-BX-16-008","5IK2BX003509-03","","OTHERS","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","Prevalence of cardiovascular diseases in the United States is high, and is known to be even greater within its Veteran population. This may be due to a stronger presence of associated risk factors (such as smoking) and, among the Vietnam-Era Veterans, Agent Orange exposure (linked to development of vascular disease and diabetes). Currently available treatment for advanced arterial occlusive disease is procedure based and subject to high cost and high failure rates. Worse, many veterans are not suitable candidates for intervention, leaving them no effective options for revascularization. By completing the work that we propose, we will gain important insight into a critical mechanism for collateral growth which will pave the way for pharmacotherapy development. Such a therapy would have great impact on the functional status of veterans and nonveterans alike, potentially salvaging limbs and maintaining quality of life.","10828347; ","MCENANEY, RYAN M;","","10/01/2017","09/30/2022","Affect; agent orange; Aging; Agonist; Anatomy; angiogenesis; Angioplasty; Area; Arterial Occlusive Diseases; Arteries; arteriole; Automobile Driving; base; Beds; Biochemical; Biological; Blood capillaries; Blood flow; Blood Vessels; Bypass; Caliber; Cardiovascular Diseases; Cause of Death; Cell Adhesion Molecules; Cells; Clinical; cost; cytokine; Data; density; Development; Diabetes Mellitus; disability; Disease; Endothelial Cells; Endothelium; extracellular; Extracellular Space; Failure; falls; femoral artery; functional status; General Population; Generations; Goals; Growth; High Prevalence; in vivo; Inflammation; Inflammatory; innovation; insight; Intervention; Investigation; Ischemia; Knowledge; Laboratories; Ligation; Limb Salvage; Link; Liquid substance; Maintenance; Measures; mechanical force; Mechanics; Mediating; Medical; MicroRNAs; Modeling; Molecular; Nitric Oxide; novel; novel therapeutics; Nucleotides; Operative Surgical Procedures; P2Y2 receptor; Patients; Perfusion; Pharmacology; Pharmacotherapy; Population; Prevalence; prevent; Procedures; Process; Production; Publishing; Purinoceptor; Quality of life; receptor; receptor expression; Recovery; recruit; Research; response; Risk Factors; Role; Science; shear stress; Signal Transduction; Signaling Molecule; skills; Smoking; Stents; Stress; success; System; targeted treatment; Techniques; therapeutic angiogenesis; Thick; Tissues; Translational Research; United States; vascular bed; Vascular Diseases; vascular inflammation; Vascular remodeling; Veins; Veterans; Vietnam; Work; ","Purinergic signaling and arteriogenesis","003509","CARB","Cardiovascular Studies B ","","","03","","","",""
"9815448","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003742","","RFA-BX-16-001","5I01BX003742-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","EAST ORANGE","UNITED STATES","","10","087286308","US","10018809","VA NEW JERSEY HEALTH CARE SYSTEM","NJ","070181023","Project narrative The uncontrolled cell proliferation that represents the hallmark of neoplastic disease not only involves deregulated cell proliferation but also requires adjustments in the energy metabolism that fuels the cells growth particularly altered glutamine metabolisms. Our proposed studies will interrogate possible relationship between altered glutamatergic signaling and glutamine metabolisms in melanoma.","1871027; ","CHEN, SUZIE ;","","10/01/2017","09/30/2020","Affect; Agonist; Amino Acids; Apoptosis; Archives; Biochemical Pathway; Biological; Biopsy Specimen; Blood; cancer cell; Cancer Cell Growth; carboxylation; Cell Count; Cell Cycle Arrest; cell growth; Cell Line; Cell Proliferation; Cells; Clinical; combinatorial; Development; Disease; Ectopic Expression; Elements; Energy Metabolism; Ensure; Environment; Etiology; experimental study; General Population; Genetic; Genotype; Glutamate Receptor; glutamatergic signaling; Glutamates; Glutaminase; Glutamine; Homeostasis; Human; Hypoxia; IL8 gene; In Vitro; in vivo; Individual; insight; Lesion; Ligands; Link; Malignant - descriptor; Malignant Neoplasms; MAP Kinase Gene; Mediating; Medical center; melanocyte; melanoma; Melanoma Cell; Metabolic; Metabolism; metabotropic glutamate receptor type 1; metaplastic cell transformation; Mitochondria; mitochondrial metabolism; Modeling; mouse model; Mus; neoplastic; neoplastic cell; Neurons; Normal Cell; Normal tissue morphology; novel therapeutics; NRAS gene; Nutrient; outcome prediction; overexpression; oxidation; Pathway interactions; Patients; Pharmacology; PI3K/AKT; pre-clinical; Pre-Clinical Model; Proliferating; receptor; Regimen; Role; Sampling; Signal Transduction; Specimen; System; Testing; transcription factor; Transgenic Mice; Transgenic Organisms; Translations; tumor; tumor growth; tumorigenesis; uncontrolled cell growth; Up-Regulation; Vascular blood supply; Vascular Endothelial Growth Factors; VHL protein; Xenograft procedure; ","GRM1-induced HIF-1? and reprogramming of glutamine metabolisms in melanoma","003742","ONCE","Oncology E ","","","03","","","",""
"9815453","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003195","","RFA-BX-15-001","5I01BX003195-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN ANTONIO","UNITED STATES","","21","078493228","US","481157","SOUTH TEXAS VETERANS HEALTH CARE SYSTEM","TX","782294404","PUBLIC HEALTH RELEVANCE:        Depression will soon become the leading cause of disability world-wide, yet we understand remarkably little about the mechanism(s) that contribute to the development of depressive disorders. Brain-derived neurotrophic factor (BDNF) has been strongly implicated as a molecular mediator of both vulnerability and effective antidepressant responses. We have identified a potentially novel role for BDNF as a negative regulator of microglial activity and the neuroinflammatory response.","9757813; ","O'CONNOR, JASON C;","","10/01/2016","09/30/2020","Address; Affinity; Anhedonia; Animal Model; Animals; Anterior; Antidepressive Agents; Anxiety; Attention; Autopsy; base; BDNF gene; Behavior; Behavioral; behavioral response; Biological Models; Brain; brain tissue; Brain-Derived Neurotrophic Factor; Chronic stress; cingulate cortex; Clinic; Clinical; Cognitive; Complex; cytokine; Data; Depressed mood; Depressive disorder; depressive symptoms; design; Development; Diagnosis; disability; Etiology; Exhibits; experimental study; flexibility; Frequencies; gene environment interaction; Gene Frequency; Genetic Polymorphism; high risk; Hippocampus (Brain); Human; human model; human subject; Human Volunteers; humanized mouse; Immune; Impairment; improved; Impulsivity; In Vitro; in vivo; Individual; Inflammation; Knockout Mice; Knowledge; Kynurenine; Laboratories; Link; Major Depressive Disorder; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Metabolism; Methodology; Microglia; mild cognitive impairment; Military Personnel; Molecular; mouse model; mRNA Expression; Mus; neural circuit; neurobiological mechanism; neuroinflammation; neurotoxic; Neurotrophic Tyrosine Kinase Receptor Type 2; novel; novel diagnostics; novel therapeutic intervention; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Peripheral; Personal Satisfaction; Phenotype; Play; Population; pre-clinical; Pre-Clinical Model; Prefrontal Cortex; Proteins; public health relevance; Recombinants; Refractory; relating to nervous system; response; Risk Factors; Rodent; Rodent Model; Role; Signal Transduction; Single Nucleotide Polymorphism; Stress; Suicide; suicide rate; Symptoms; System; Testing; Therapeutic; Tissue Sample; Translating; Tryptophan Metabolism Pathway; Veterans; ","Role of Brain-derived Neurotrophic Factor in Regulating Neuroinflammantion and Mental Health","003195","MHBA","Mental Health and Behavioral Science A ","","","04","","","",""
"9815463","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003924","","RFA-BX-16-001","5I01BX003924-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","Project Narrative The development of sepsis from infection is a leading cause of death worldwide. The development of multiple organ dysfunction secondary to sepsis/infection accounts for most of these deaths; however, our understanding of the processes that lead to organ dysfunction/failure and the subsequent development of therapeutics that effectively reverse or prevent the processes have been limited. In the proposed study, we will investigate how mitochondria as the source of energy and mitochondrial signaling are central to the control of inflammation and the development of adaptive responses to prevent organ injury in sepsis. The study focuses on the role of mitochondria as a `cellular rheostat' that then elicits responses to allow cells and tissues to adapt to the septic insult by preventing bioenergetic failure, cell death, and organ dysfunction.","8661782; ","ZUCKERBRAUN, BRIAN SCOTT;","","10/01/2017","09/30/2021","Address; Affect; Aging; Antibiotics; Area; Autophagocytosis; base; Behavior; Bioenergetics; Biogenesis; Biology; Caloric Restriction; Categories; Cause of Death; Cell Death; cell injury; Cells; Cellular biology; Cessation of life; clinically relevant; Complex; Critical Care; Data; Development; Disease; Electron Transport; Energy-Generating Resources; Ensure; Environmental Risk Factor; Epigenetic Process; Event; Evolution; Excision; Failure; Family; Functional disorder; Future; Genetic; Health; Human; improved outcome; individualized medicine; Infection; Inflammation; Inflammatory Response; injured; Injury; innovation; insight; Investigation; Laboratories; Lead; Life Style; lifestyle factors; Longevity; Maintenance; Measures; Mediating; metabolomics; Mitochondria; Modern Medicine; Molecular; Multiple Organ Failure; novel; Organ; organ growth; Organism; Outcome; pathogen; Patient risk; Patients; Pattern; personalized approach; personalized medicine; Physical Exercise; Physiology; Population; prevent; Process; Publishing; reconstitution; Recovery; Regimen; Regulation; Research; Respiration; response; Rewards; Risk; Role; Secondary to; Sepsis; septic; septic patients; Signal Transduction; Stimulus; Stress; Supportive care; Survivors; Syndrome; targeted treatment; Testing; Therapeutic; therapeutic development; Tissues; United States; Veterans; Work; ","The Mitochondria As Regulators Of Inflammation In Sepsis","003924","SURG","Surgery ","","","03","","","",""
"9842266","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004594","","RFA-CX-18-001","5I01BX004594-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Alcoholic liver disease affects several million people in the United States and is the most important cause of liver cirrhosis among Veterans. Results from this innovative study will benefit Veterans health by increasing our understanding of the role that specific gut bacteria play in the progression of alcoholic liver disease. We will also identify innovative intervention strategies to prevent or ameliorate these diseases in Veterans. Our novel findings can easily be translated into Veteran patients suffering from alcohol abuse and liver disease.","8779474; ","SCHNABL, BERND G.;","","10/01/2018","09/30/2022","Affect; Alcohol abuse; Alcohol dependence; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcoholism; Alcohols; anakinra; antimicrobial; Bacteriophages; base; Binding; Biological Models; Bone Marrow; Cells; Cessation of life; Chronic; chronic alcohol ingestion; cytokine; Data; defined contribution; Development; Disease; dysbiosis; Endotoxins; Enterococcus faecalis; Ethanol; Etiology; Experimental Models; Feces; feeding; Functional disorder; Gnotobiotic; gut bacteria; gut colonization; gut microbiota; gut-liver axis; Health; Hepatic; Hepatocyte; Hepatotoxicity; humanized mouse; Inflammation; Inflammatory; innovation; insight; Interleukin-1 beta; Interleukin-1 Receptors; Intervention; Intestinal Mucosa; Intestinal permeability; Intestines; islet; Kupffer Cells; Laboratories; Lead; Leaky Gut; Lipopolysaccharides; Liver; Liver Cirrhosis; Liver diseases; liver inflammation; liver injury; Lytic; Mediating; Medical; microbial; microbiome; microbiome research; microbiota; Modeling; Molecular; Morbidity - disease rate; mortality; mouse model; Mucous Membrane; Mus; Myelogenous; Natural regeneration; Nature; novel; novel strategies; pathogen; Pathogenesis; Patients; Play; Pre-Clinical Model; prevent; problem drinker; Proteins; Publications; receptor; Research; response; Role; Sampling; Surface; Testing; TLR2 gene; Transgenic Organisms; Translating; United States; Veterans; Virulence Factors; ","The role of Enterococcus faecalis in alcoholic liver disease","004594","ZRD1","Special Emphasis Panel ","","","02","","","",""
"9852294","I01","VA","5","N","10/23/2019","10/01/2019","03/31/2021","999","I01BX003833","","RFA-BX-18-001","5I01BX003833-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","MILWAUKEE","UNITED STATES","","04","078952454","US","481162","CLEMENT J. ZABLOCKI VA MEDICAL CENTER","WI","532950001","Breathing high concentrations of oxygen causes leakage of fluid into the lung airspaces and diminishes the lung?s capacity to oxygenate the blood. Our new data supports critical involvement of the engines of energy production (mitochondria) in the cells lining the blood vessels of the lungs in this injury response. Using novel tools that facilitate quantification of the structure and function of the mitochondria in the vessel lining cells, we will examine the role of these energy production sites in the leakage response of lungs exposed to a high oxygen environment, such as occurs in patients requiring mechanical ventilation. Factors which increase the risk of acute lung injury are alcohol abuse, obesity and chronic lung disease requiring oxygen, all conditions which are more common in veterans than the population in general. Therefore, these studies are of particular importance to veterans.","1879361; ","JACOBS, ELIZABETH R;","","04/01/2019","03/31/2023","Acute Lung Injury; Alcohol abuse; animal tissue; Animals; base; Blood; Blood Vessels; Breathing; Cells; Cessation of life; Chimeric Proteins; Chronic lung disease; clinically relevant; Critical Illness; Cultured Cells; Data; DNA; DNA Damage; Edema; Electrical Resistance; Endothelial Cells; Endothelium; Environment; Exhibits; Experimental Designs; Exposure to; Extravasation; Filtration; Functional disorder; Fusion Protein Expression; Gases; genetic manipulation; human tissue; Hydrogen; Hyperoxia; Image; imaging biomarker; in vivo; in vivo imaging; Inhalation; Injury; Investigation; Label; Lead; Link; Liquid substance; Lung; Lung Capacity; Lung diseases; lung injury; Measures; Mechanical ventilation; Mediating; Microvascular Permeability; Mitochondria; Mitochondrial DNA; mitochondrial dysfunction; mitochondrial membrane; Molecular; monolayer; Morbidity - disease rate; mortality; Mus; novel; Nuclear; Obesity; overexpression; Oxidative Stress; Oxygen; Patients; Permeability; Population; Prevention approach; Preventive Intervention; Production; protein expression; Proteins; Pulmonary Edema; Reactive Oxygen Species; Recombinants; repair enzyme; repaired; response; response to injury; Risk; Rodent; Role; Secondary to; Signal Transduction; single photon emission computed tomography; Site; Small Interfering RNA; Stress; Structure; Subfamily lentivirinae; targeted nucleases; Testing; therapeutic target; Time; Tissues; tool; Vascular Endothelium; Veterans; Work; ","Role of mitochondrial dysfunction in hyperoxia-induced pulmonary vascular endothelial injury","003833","ZRD1","Special Emphasis Panel ","","","02","","","",""
"9778059","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004626","","RFA-BX-18-001","1I01BX004626-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","TAMPA","UNITED STATES","","14","929194256","US","481155","JAMES A. HALEY VA MEDICAL CENTER","FL","336124745","While the incidence of physical wounds has dropped in Veterans of Operation Iraqi Freedom, Operation Enduring Freedom and Operation New Dawn, many soldiers are returning from deployment suffering from psychological wounds that manifest as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), with sleep disturbances as the most common comorbidity. We have found that a gene called FKBP5 may contribute significantly to susceptibility to these disorders. In this grant, we will investigate how this gene contributes to these disorders that arise due to deployment-associated stress and determine whether strategies aimed at depleting FKBP5 could be beneficial for the treatment of stress-induced psychological disorders.","12474011; ","BLAIR, LAURA JENELLE;","","10/01/2019","09/30/2023","Aging; Animal Model; Antisense Oligonucleotides; Antisense Technology; base; Behavior; Behavior assessment; Behavioral; biological adaptation to stress; Biological Assay; Biology; Brain; Cell Line; Cells; chaperone machinery; circadian; Circadian desynchrony; Circadian Dysregulation; Circadian Rhythm Sleep Disorders; Circadian Rhythms; common symptom; Comorbidity; Complex; conditioned fear; Conflict (Psychology); demethylation; design; Disease; DNA; Drops; Drug Targeting; Effectiveness; Ensure; Exposure to; Extinction (Psychology); Feedback; FK506 binding protein 5; Freedom; Functional disorder; Gap Junctions; Genes; genetic variant; Glucocorticoids; Goals; Grant; Half-Life; Heat shock proteins; Hormones; Hydrocortisone; hypothalamic-pituitary-adrenal axis; improved; In Vitro; in vivo; Incidence; inhibitor/antagonist; knock-down; Knowledge; Label; Lead; Libraries; Link; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mental disorders; Military Personnel; Molecular Chaperones; Mood Disorders; mouse model; multicatalytic endopeptidase complex; Mus; Neurons; novel; novel strategies; Oligonucleotides; operation; overexpression; Periodicity; Phenotype; photo switch; Population; Post-Traumatic Stress Disorders; Predisposition; preference; prepulse inhibition; Prosencephalon; protein degradation; Proteins; psychiatric symptom; psychologic; Psychopathology; Regulation; Reporting; resilience; Resistance; response; Response Elements; Risk; Role; Route; Serum; Shock; Single Nucleotide Polymorphism; Sleep disturbances; sleep regulation; small hairpin RNA; Soldier; steroid hormone; Stress; stress resilience; stressor; Sucrose; Symptoms; System; Tacrolimus Binding Proteins; Tail Suspension; targeted treatment; Testing; therapy development; Time; tool; Transgenic Mice; Translations; Triage; Veterans; Wild Type Mouse; Work; ","Controlling FKBP51 for the treatment of PTSD","004626","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9780367","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004666","","RFA-BX-18-001","1I01BX004666-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","OKLAHOMA CITY","UNITED STATES","","05","020719316","US","481072","OKLAHOMA CITY VA MEDICAL CENTER","OK","731045007","Osteoarthritis is one of the most common causes of joint pain and physical disability. Veterans are more likely to develop osteoarthritis compared to the general population because of their high rates of trauma and injury. There are no treatments available to prevent osteoarthritis, and long-term medication use to reduce osteoarthritis pain adds additional health risks for Veterans. The proposed research is relevant to Veterans' health because it will develop fundamental knowledge about how osteoarthritis joint inflammation can be reduced. This knowledge is expected to lead to new approaches for treating osteoarthritis progression and pain.","7015479; ","GRIFFIN, TIMOTHY M;","","10/01/2019","09/30/2023","Acute; Address; Adipose tissue; Affect; Agonist; Analgesics; Animal Model; Animals; Anti-inflammatory; Arthralgia; base; Biological; Biological Response Modifier Therapy; cellular engineering; Chronic; Consumption; Coupling; Cumulative Trauma Disorders; cytokine; Data; Degenerative polyarthritis; Development; disability; Disease; Drug Design; Drug Targeting; Environment; Exercise; exercise intervention; Exercise Therapy; Fatty acid glycerol esters; fatty acid metabolism; fatty acid oxidation; Fatty Acids; Fibrosis; Flow Cytometry; functional outcomes; gait examination; General Population; Genetic; genetic approach; Glucose; Glycolysis; Goals; Hand; Health; Histopathology; Image; Impairment; improved; improved outcome; in vivo; in vivo evaluation; Inflammation; Inflammation Mediators; Inflammatory; Injury; innovation; instrument; Intervention; joint inflammation; Joints; Knee; Knee joint; Knee Osteoarthritis; Knowledge; Lead; lipid biosynthesis; lipid metabolism; Lipids; Lipolysis; macrophage; Macrophage Activation; Measures; mechanical allodynia; Medial meniscus structure; Mediating; Metabolic; Metabolism; Methods; Modeling; Molecular; Molecular Target; mouse model; Mus; nanoparticle; Nociception; Non-Steroidal Anti-Inflammatory Agents; novel strategies; novel therapeutics; Operative Surgical Procedures; Opioid; Oral; osteoarthritis pain; Outcome; Pain; Pain management; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Phenotype; Physical therapy; Physical therapy exercises; Physically Handicapped; PPAR alpha; PPAR gamma; Pre-Clinical Model; prevent; Production; Regenerative Medicine; Research; Resolution; response; Risk; rosiglitazone; Running; side effect; Stem cells; Synovial Fluid; Synovial joint; Synovial Membrane; Testing; Therapeutic Effect; Therapeutic Uses; Time; Tissue Engineering; tissue repair; Tissues; Transducers; Trauma; treadmill; treatment strategy; uptake; Veterans; ","Targeting Molecular Transducers of Exercise for Osteoarthritis Therapies","004666","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9780820","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004660","","RFA-BX-18-001","1I01BX004660-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","OMAHA","UNITED STATES","","02","844360367","US","481160","OMAHA VA  MEDICAL CENTER","NE","681051850","Rheumatoid arthritis (RA) is a systemic autoimmune disease estimated to affect up to 2% of all VA healthcare users, highly relevant since male veterans with RA experience more than twice the mortality as age- matched men from the general population. We have recently shown that malondialdehyde-acetaldehyde adducts (MAA), formed during inflammation and resulting oxidative stress, are expressed in RA joint tissues and immune responses to MAA are robustly associated with autoantibodies that are nearly exclusive to RA. Proposed research efforts will focus on identifying the immunologic mechanisms linking MAA adduct formation with the development and progression of RA and will identify novel biomarkers that could be used for diagnosis and predicting future disease. Importantly, results from this work will lead to an improved understanding factors leading to RA development and will provide insight into new approaches in treatment and prevention.","7332065; ","MIKULS, TED RICHARD;","","10/01/2019","09/30/2023","Acetaldehyde; adaptive immune response; adduct; Adjuvant; Affect; Age; Aging; Antibodies; Antigens; Arginine deiminase; Arthritis; Attenuated; Autoantibodies; Autoimmune Responses; Autoimmunity; base; Binding; Biological; Bypass; Calcium; Carrier Proteins; Cell Line; cell type; Cells; Characteristics; chelation; Chinese Hamster Ovary Cell; citrullinated protein; Citrulline; cytotoxic; Data; design; Development; Diagnosis; Dihydropyridines; disability; Disease; Disease Progression; Epitopes; Event; experience; experimental study; Fibrosis; Frequencies; Future; General Population; Healthcare; Human; Immune; Immune response; Immunization; immunogenic; Immunologic Adjuvants; Immunologics; improved; In Vitro; in vivo; Individual; Inflammation; Inflammatory; Inflammatory Response; inhibitor/antagonist; innovation; insight; joint destruction; Joints; Laboratories; Lead; Link; Lipid Peroxidation; male; Malondialdehyde; Mediating; men; MHC Class II Genes; Modification; Morbidity - disease rate; mortality; mortality risk; mRNA Expression; Mus; neoantigens; novel marker; novel strategies; Outcome; outcome forecast; Oxidative Stress; Pathogenesis; Pathogenicity; Patients; Peptides; Play; Population; Post-Translational Protein Processing; Prevention; Process; Proteins; receptor; receptor binding; Reporting; Research; response; Rheumatoid Arthritis; rheumatologist; Role; Sampling; scavenger receptor; Seminal; seropositive; Signal Transduction; societal costs; Structure; Synovial Cell; Synovial Membrane; systemic autoimmune disease; T cell response; Time; Tissues; uptake; Veterans; Woman; Work; ","Pathogenic Role of Malondialdehyde-Acetaldehyde Adducts in Rheumatoid Arthritis","004660","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9781539","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004768","","RFA-BX-18-001","1I01BX004768-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","Aurora","UNITED STATES","","06","003252830","US","481018","VA EASTERN COLORADO HEALTH CARE SYSTEM","CO","800457211","Myelodysplastic syndrome (MDS) is a myeloid malignancy in which cytopenias result from ineffective hematopoiesis and morphologic evidence of myeloid dysplasia exists. MDS is primarily a disease of aging populations, with the vast majority of cases occurring after age 60. MDS-induced dysplasias and eventual progression to acute myeloid leukemia are usually fatal. Unfortunately, therapies for MDS are largely ineffective, with only limited options for most patients. Environmental exposure to numerous toxic chemicals has been associated with several types of blood cancer, indicating that military veterans may be at increased risk for MDS and similar disorders. Thus, improved treatment for this deadly disease represents a large unmet need for veterans. The proposed studies are designed as a foundation for the development of new therapeutic strategies for MDS and related forms of blood cancer.","3051020; ","JORDAN, CRAIG T.;","","10/01/2019","09/30/2023","Acute Myelocytic Leukemia; Aftercare; Age; Aging; Automobile Driving; Azacitidine; base; Biologic Characteristic; Biological; Biology; cancer stem cell; Cell Count; Cells; Cessation of life; Clinical; Clinical Trials; Clinical Trials Design; cytopenia; Data; design; Development; Diagnostic; Disease; Dysmyelopoietic Syndromes; Dysplasia; Energy Metabolism; Environmental Exposure; Exposure to; Foundations; Future; Generations; Goals; Grant; Heart Diseases; Hematopoietic Neoplasms; Hematopoietic stem cells; Hematopoietic System; high risk; IL3RA gene; improved; in vivo; Ineffective Hematopoiesis; insight; Laboratory Research; Laboratory Study; Marrow; Mediating; Medical; Metabolic; Metabolic Pathway; Metabolism; Military Personnel; Molecular; Morbidity - disease rate; Morphology; Myelogenous; Myeloproliferative disease; novel strategies; novel therapeutic intervention; novel therapeutics; Oxidative Phosphorylation; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phase Transition; Phenotype; Poison; Population; Pre-Clinical Model; preclinical study; Preclinical Testing; prognostic tool; Property; Protein Biosynthesis; protein expression; Reactive Oxygen Species; Regimen; Research; Resolution; response; Risk; Sampling; single cell technology; single-cell RNA sequencing; stem; stem cell population; stem cell therapy; Stem cells; Study models; Surface Antigens; targeted treatment; Testing; Therapeutic Agents; Therapeutic Intervention; therapeutic target; therapy development; therapy resistant; Time; treatment strategy; Up-Regulation; Veterans; ","Therapeutic Targeting of MDS Stem Cells","004768","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9784448","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004748","","RFA-BX-18-001","1I01BX004748-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","KANSAS CITY","UNITED STATES","","05","844272125","US","481049","KANSAS CITY VA MEDICAL CENTER","MO","641282226","Among military veterans, substance abuse is a strong predictor of both subsequent healthcare utilization and mortality. For veterans who abuse heroin or other opioids, mental health conditions are highly prevalent. These include disorders of mood and anxiety. Although opioid abuse is an important health problem for both veterans and the general population, only limited medications are currently available for treating patients who are addicted to opioids. Melatonin is a hormone and neurotransmitter which plays a role in establishing daily and seasonal rhythms and may also contribute to perception of pain and drug addiction. This project will use an animal model of opioid addiction to determine how melatonin influences the brain mechanisms underlying perception of pain and addiction.","1883821; ","GRASING, KENNETH W.;","","10/01/2019","09/30/2023","addiction; Agonist; Animal Model; Animals; antidepressant effect; Antidepressive Agents; Antioxidants; Anxiety; Attenuated; awake; Behavior; Bolus Infusion; Brain; brain tissue; circadian; Clinical; Cocaine; craving; Cues; Darkness; Dependence; Disease; Dose; Drug Addiction; Drug Kinetics; Economics; Evaluation; Extinction (Psychology); Food; General Population; Health; health administration; health care service utilization; Heroin Abuse; Home environment; Hormones; Hour; Human; improved; Inflammation; Inflammation Mediators; Injections; innovation; Intake; Interruption; Light; Measures; Medical; Melatonin; Melatonin Receptors; Mental Depression; Mental Health; Methods; Military Personnel; Modeling; Mood Disorders; Morphine; morphine administration; mortality; motivated behavior; Naloxone; Neurotransmitters; novel; open label; Opiate Addiction; opiate tolerance; Opioid; opioid abuse; opioid use; opioid use disorder; opioid withdrawal; Oral; Outcome; Overdose; Oxidative Stress; Pain management; pain perception; pain relief; Patients; Periodicity; Pharmaceutical Preparations; Pharmacotherapy; Pineal gland; Plasma; Play; preference; Prevalence; prevent; Property; Rattus; receptor; reinforced behavior; Relapse; Reporting; Rewards; Role; Safety; Self Administration; Serotonin; Serotonin Receptor 5-HT2C; Severities; Sleep; Sleep disturbances; Sleep Wake Cycle; social; Structure; Substance abuse problem; Swimming; Translating; Veterans; Wistar Rats; Withdrawal; ","Translating Melatonin- and Serotonin-2C Interactions into Improved Treatments for Pain and Opioid-Use Disorders","004748","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9814667","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001179","","RFA-BX-15-001","5I01BX001179-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","MIAMI","UNITED STATES","","24","079275714","US","481022","MIAMI VA HEALTH CARE SYSTEM","FL","331251624","PUBLIC HEALTH RELEVANCE:    Project Narrative Gastric carcinoma is the third most common cause of cancer related-death worldwide. According to the World Health Organization, National Cancer Institute, and epidemiological data, individuals with chronic H. pylori infection carry a 3 - to-6 fold higher ris of developing gastric cancer. Recent studies of U.S soldiers deployed to the Middle East and Far East have shown that the incidence of H. pylori infection was 7.3 percent per year compared to 2.5 percent of U.S. military recruits living at home, which represents a major increase in risk. We will investigate the role of TFF1 protein in protecting against H. pylori-induced inflammation and oncogenic signaling that lead to the development of gastric cancer. Our results will have a strong impact on understanding the biology and could have a potential role in the preventive, early diagnosis, and possibly therapeutic interventions in gastric cancer.","7001109; ","EL-RIFAI, WAEL ;","","04/01/2012","09/30/2020","Address; angiogenesis; Anti-inflammatory; base; beta catenin; Biological; Biological Process; Biology; Cancer Etiology; cancer statistics; carcinogenesis; carcinogenicity; Carcinogens; Cessation of life; ChIP-seq; Chronic; chronic infection; Clinical Research; Clinical Trials; clinically significant; Data; Development; Diagnostic; Early Diagnosis; epidemiologic data; epidemiology study; Epidermal Growth Factor Receptor; Epithelial Cells; Epithelium; Etiology; Event; Far East; Future; Gastric Adenocarcinoma; Gastric Intraepithelial Neoplasia; Gastric mucosa; Gatekeeping; Genes; Genetic Transcription; global health; Goals; Helicobacter Infections; Helicobacter pylori; high risk; Histologic; Home environment; Human; IL6 gene; Immune Evasion; improved; In Vitro; in vivo Model; Incidence; Individual; Infection; Inflammation; Inflammatory; inhibitor/antagonist; Intestinal Metaplasia; Knockout Mice; Knowledge; Lead; Malignant Neoplasms; malignant stomach neoplasm; Mediating; metaplastic cell transformation; Middle East; Military Personnel; Molecular; Molecular Target; mouse model; National Cancer Institute; novel; Oncogenic; Patients; Peptides; Population; Pre-Clinical Model; Preventive; prognostic; protective factors; Proteins; public health relevance; Publications; Pyloric antrum; recruit; Regimen; Reporting; response; Risk; Risk Factors; Role; Shapes; Signal Transduction; Soldier; SRC gene; STAT3 gene; Stomach; Stomach Carcinoma; TFF1 gene; Therapeutic; therapeutic evaluation; Therapeutic Intervention; therapeutic target; Time; TP53 gene; transcriptome sequencing; Tumor Suppressor Proteins; tumorigenesis; World Health Organization; ","Molecular Pathobiology of Gastric Carcinogenesis","001179","GAST","Gastroenterology ","","","08","","","",""
"9814668","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001669","","RFA-BX-16-001","5I01BX001669-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PALO ALTO","UNITED STATES","","18","046017455","US","481014","VETERANS ADMIN PALO ALTO HEALTH CARE SYS","CA","943041207","Rheumatoid arthritis is the most frequent inflammatory disease in the VA rheumatology practice. The introduction of cytokine inhibitors has reduced the inflammatory burden and improved the management of the disease. However, they do not induce lasting remissions while their chronic administration compromises the immune competence of the patient. Insights into pathogenetic mechanisms upstream of the effector pathways will be necessary to prevent or cure disease. T lymphocytes are key players in the rheumatoid inflammation. We will examine their epigenome that controls gene expression and determine how these epigenetic signatures influence gene transcription upon activation and how they intersect with disease risk genes that have been identified for RA. In addition to providing pathogenetic insights, such epigenetic signatures can also function as biomarkers.","1885543; ","GORONZY, JORG J;","","04/01/2012","09/30/2020","Abnormal Cell; Age; Aging; antigen-specific T cells; Antigens; Apoptosis; Arthritis; Autoantibodies; Autoantigens; Autoimmune Diseases; Binding; Biochemical Pathway; Biological Assay; Biological Markers; CD4 Positive T Lymphocytes; cell age; Cell physiology; Cells; Chromatin; chromatin modification; Chronic; Clinical; clinical practice; Computer Analysis; cytokine; Data; Defect; Disease; Disease Management; Disease remission; disorder risk; DNA Repair; DNA Sequence; effector T cell; EMSA; Enhancers; Environment; Epigenetic Process; epigenome; Failure; Functional disorder; Gene Expression; Genetic Transcription; genome-wide; Glucose; HLA-DRB1; Immune Tolerance; Immunocompetence; Immunologics; immunosenescence; improved; Inflammation; Inflammatory; inhibitor/antagonist; insight; Maps; Memory; Methotrexate; Modeling; neoantigens; novel strategies; Oxidative Stress; Pathway interactions; patient population; Patients; Pentosephosphate Pathway; Peptides; peripheral blood; Population; Predisposition; prevent; promoter; Psoriatic Arthritis; Reporter Genes; Research Personnel; Rest; Rheumatoid Arthritis; Rheumatology; risk variant; senescence; Serum; Signal Transduction; Site; Speed; Synovitis; T cell differentiation; T memory cell; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Tissues; TNF gene; transcription factor; transcriptome; Transposase; treatment response; Viral; ","Chromatin Accessibility and Transcription Factor Networks in Rheumatoid Arthritis","001669","IMMA","Immunology A ","","","08","","","",""
"9814679","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002947","","RFA-BX-15-003","5I01BX002947-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","TAMPA","UNITED STATES","","14","929194256","US","481155","JAMES A. HALEY VA MEDICAL CENTER","FL","336124745","PUBLIC HEALTH RELEVANCE:        Traumatic brain injury caused by blast exposure causes the accumulation of a protein called tau in the brain.  The accumulation of tau is thought to be neurotoxic leading to the memory problems and brain dysfunction that accompanies TBI, but this is not known. In this proposal, we will determine if small molecules can protect tau from a pathogenic cascade caused by the molecular chaperone Hsc70. This could lead to new treatments for Veterans suffering from TBI.","1892376; ","KANG, DAVID E;","","10/01/2016","09/30/2020","Autophagocytosis; axon injury; base; Binding; Biological Assay; Brain; brain dysfunction; brain tissue; Cells; Cleaved cell; Cognitive deficits; Complement; Decision Making; Disease; drug candidate; Drug Kinetics; Family; Foundations; Hand; improved; in vivo; inhibitor/antagonist; innovation; Lead; Libraries; MAPT gene; Mediating; Memory; Microtubules; Molecular Chaperones; Nerve Degeneration; Neurons; neurotoxic; Outcome; Pathogenicity; Permeability; Post-Translational Protein Processing; potency testing; preservation; Process; Property; Proteins; public health relevance; Recycling; scaffold; screening; Seeds; side effect; small hairpin RNA; small molecule; Structure; System; tau aggregation; tau mutation; tau Proteins; Tauopathies; Therapeutic; tool; Toxic effect; trafficking; Traumatic Brain Injury; Triage; vector; Vertebral column; Veterans; ","Targeting Tau for TBI","002947","NURD","Neurobiology D ","","","04","","","",""
"9814686","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003259","","RFA-BX-15-001","5I01BX003259-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","WEST HAVEN","UNITED STATES","","03","039624291","US","481020","VA CONNECTICUT HEALTHCARE SYSTEM","CT","065162770","PUBLIC HEALTH RELEVANCE:        8. Obesity and the metabolic syndrome are all significantly increased in the veteran population and are a major health problem. An important manifestation of this is non-alcoholic steatohepatitis (NASH), which is now the most common liver disease in the veteran population and can progress to cirrhosis and liver cancer. NASH results in a very high degree of morbidity due to fatigue, jaundice, ankle swelling and itching. In addition NASH also results in increased mortality due to cirrhosis, hepatocellular cancer as well as liver failure.  Currently there are no effective treatments for NASH. During this Merit Review Award we have identified many of the cellular pathways responsible for the sterile liver inflammation that causes NASH. We now propose to identify how these pathways are activated, and to test inhibitors of these pathways to allow for the development of specific therapy for NASH.","6490737; ","MEHAL, WAJAHAT ZAFAR;","","10/01/2016","09/30/2020","Acute; Ankle; Award; Biochemical; cell free DNA; Cell Line; Cells; Cessation of life; Characteristics; Cirrhosis; Clinical; Clinical Trials; cytokine; Data; Development; DNA; DNA receptor; effective therapy; Etiology; Fatigue; Fatty Liver; Grant; Health; Healthcare; Hepatocyte; Human; Icterus; immune activation; Inflammasome; Inflammation; Inflammatory; Inflammatory Response; inhibitor/antagonist; Interleukin-1 beta; Investigation; Kupffer Cells; Ligands; Liver; Liver diseases; Liver Failure; liver inflammation; liver injury; macrophage; Malignant neoplasm of liver; Malignant Neoplasms; Metabolic syndrome; Mitochondria; Mitochondrial DNA; Modeling; Molecular; monocyte; Morbidity - disease rate; mortality; mouse model; Mus; nonalcoholic steatohepatitis; Obesity; oxidation; Oxides; Pancreas; Pathway interactions; Patients; Phase; Phase II Clinical Trials; Plasma; Plasma Cells; Population; Primary carcinoma of the liver cells; Production; Pruritus; public health relevance; Publications; Reporter; Role; Safety; Source; Sterility; Swelling; Testing; Tissues; TLR9 gene; Up-Regulation; Veterans; Work; ","Cell-free DNA is a driver of non-alcoholic steatohepatitis via TLR9 activation","003259","GAST","Gastroenterology ","","","04","","","",""
"9815309","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000113","","RFA-CX-17-001","5I01BX000113-09","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","Veteran surgical patients commonly suffer critical illness, and a high percentage of these patients in the intensive care units incur stress-related injuries to their very vulnerable intestinal lining. These injuries can result in malnutrition, overwhelming bacterial infection, and death. Despite the medical advances of the past few decades, therapies for these stress injuries are, for the most part, conservative, as there is no current pharmacologic therapy available. This proposal explores the use of a new molecule that could potentially prevent injury and loss of the intestinal epithelial cells, and lead to improved outcomes of critically ill Veteran patients.","3101286; ","TURNER, DOUGLAS J;","","04/01/2009","09/30/2022","absorption; Address; Adherens Junction; Affect; Apoptosis; Apoptotic; Bacteria; Bacterial Infections; base; Biological Process; Cell Proliferation; Cell Surface Receptors; Cell Survival; Cells; Cessation of life; cost; Critical Illness; Cultured Cells; Data; Decontamination; Digestion; Disease; E-Cadherin; Endothelial Cells; Endothelium; Epithelial; Epithelial Cells; Event; Exclusion; Exposure to; extracellular; Food; Functional disorder; gastrointestinal; gastrointestinal epithelium; gastrointestinal function; Gastrointestinal Injury; Goals; Gut Mucosa; Human; improved; improved outcome; In Vitro; in vivo; injured; Injury; Intensive Care Units; intestinal epithelium; Intestinal Mucosa; Intestines; Ischemia; IV Fluid; Lead; Ligands; Maintenance; Malnutrition; Measures; Mechanics; Medical; Methods; MicroRNAs; Molecular; Mucous Membrane; Mus; novel; novel strategies; Nutrient; Operative Surgical Procedures; Outcome; overexpression; Pathologic; Pathway interactions; Patients; Permeability; Pharmacology; Physiological; Population; preservation; prevent; protein E; Proteins; Publishing; receptor; Recovery; Regulation; repaired; Reperfusion Therapy; Research; response; Rest; Role; Sepsis; Sphingolipids; sphingosine 1-phosphate; SPHK1 enzyme; Stimulus; Stress; Surgical Injuries; Testing; Therapeutic Effect; Therapeutic Uses; Tight Junctions; Tissues; Tube; Veterans; wasting; Work; ","Barrier Dysfunction in Severe Surgical Diseases","000113","SURG","Surgery ","","","09","","","",""
"9815317","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000798","","RFA-BX-18-001","5I01BX000798-10","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","Sleep disturbance is a frequent and common complaint among our Veterans and within the general population. Veterans suffering from post-traumatic stress disorder (PTSD) and depression have severe sleep disorders. In PTSD, there is a marked hyperarousal that makes it difficult for patients to fall asleep. The cause of the insomnia in PTSD is not known because we do not have a clear understanding of the brain circuits that induce sleep. I am using new genetically engineered tools such as optogenetics, pharmacogenetics, deep-brain imaging and CLARITY to identify the brain circuits responsible for specific behaviors, such as sleep. My laboratory is actively engaged in mapping neural circuits, and training a new generation of scientists in the use of cutting-edge neuroscience tools and methods.","6772857; ","SHIROMANI, PRIYATTAM J.;","","10/01/2010","09/30/2022","Action Potentials; Alzheimer's Disease; American; Animals; Area; Arousal; Automobile Driving; awake; Axon; base; Behavior; Brain; Brain imaging; Calcium; calcium indicator; Conscious; Data; Data Analyses; Electrophysiology (science); Elements; Endoscopes; falls; Female; Funding; gamma-Aminobutyric Acid; General Population; Generations; Genetic Engineering; Glutamates; hypnotic; hypocretin; Hypothalamic structure; Image; imaging modality; Individual; Laboratories; Lateral; Life; Link; male; Maps; melanin-concentrating hormone; Memory; Mental Depression; Methods; Microscope; Modeling; Moods; Mus; network models; neural circuit; Neurobiology; Neurons; Neuropeptides; Neurosciences; Neurotransmitters; non rapid eye movement; optogenetics; Patients; Pharmacogenetics; Phenotype; Photons; Pontine structure; Population; Post-Traumatic Stress Disorders; Preoptic Areas; Publishing; Rattus; Regulation; REM Sleep; Research; Research Personnel; Scientist; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Sleeplessness; Solid; Stress; Testing; tool; Tracer; Training; Veterans; ","Sleep Neurobiology and Circuitry","000798","ZRD1","Special Emphasis Panel ","","","10","","","",""
"9815318","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001262","","RFA-BX-18-001","5I01BX001262-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CHARLESTON","UNITED STATES","","01","039807318","US","481111","RALPH H JOHNSON VA MEDICAL CENTER","SC","294015703","While methylprednisolone as a therapy in spinal cord injury (SCI) has been found to have limited benefits and many side effects, use of estrogen has been shown to be neuroprotective in experimental SCI with improvement of function in an animal model. The goal of this project is to employ focal delivery of nanoparticle estrogen in SCI and assess the therapeutic efficacy. Our data indicate such focal delivery of nanoparticle estrogen may have significant clinical benefits in the recovery of function in human SCI.","1878512; ","BANIK, NAREN L;","","10/01/2012","09/30/2022","Acute; angiogenesis; Animal Model; Anti-inflammatory; Apoptosis; Astrocytes; Attenuated; Axon; Biological Availability; Calcium Signaling; Cell Differentiation process; Cell Maturation; Cells; Chronic; Cicatrix; Clinical; Clinical Trials; Data; Dose; Drug Delivery Systems; Epithelial; established cell line; estrogenic; Estrogens; Exposure to; Extracellular Matrix; Fibroblasts; Formulation; functional improvement; Gait; General Population; glial cell-line derived neurotrophic factor; Glial Fibrillary Acidic Protein; Gliosis; Goals; Grant; Growth Factor; Hormonal; Hormones; Human; Immune; immunoregulation; improved; In Vitro; Inflammation; Inflammatory; Injections; Injury; Intervention; Lesion; medication safety; Methylprednisolone; Microglia; Modeling; Myelin; myelination; nano; nanoparticle; nanoparticle delivery; Natural regeneration; Neuroglia; Neurons; neuroprotection; Neuroprotective Agents; novel; novel marker; novel strategies; oligodendrocyte precursor; Oligodendroglia; Phase; Pilot Projects; Plasma; precursor cell; preservation; primary endpoint; Production; protective effect; Rattus; Recovery of Function; regenerative; Route; Safety; Sepharose; side effect; Signal Transduction; Spinal Cord; Spinal cord injury; T cell response; Techniques; Testing; Th1 Cells; Therapeutic; Therapeutic Agents; tissue regeneration; Tissues; Translations; Treatment Efficacy; Vascular Endothelial Growth Factors; Veterans; Vimentin; ","Hormonal Intervention Protects Axon-myelin to Promote Functional Recovery in SCI","001262","ZRD1","Special Emphasis Panel ","","","06","","","",""
"9815319","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001981","","RFA-BX-17-001","5I01BX001981-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","COLUMBIA","UNITED STATES","","04","082263013","US","481123","HARRY S. TRUMAN MEMORIAL VA HOSPITAL","MO","652015275","Cardiovascular disease (CVD) is a major cause of increased morbidity and mortality in male and female veterans, especially those with diabetes. One early marker for CVD is the process called ?stiffness? of cardiovascular tissue. However, the mechanisms by which environmental factors such as a western diet (high in fat and refined carbohydrates) may promote this stiffness and associated CVD, in obesity and type 2 diabetes are poorly understood and will be studied in proposed research. Understanding the biochemical pathways should contribute to the identification of access points leading to cardiovascular stiffness should lead to specific interventional strategies including new drugs and dietary interventions to prevent CVD in overweight women and men.","12588857; ","LASTRA, GUIDO ;","","04/01/2013","09/30/2022","1-Phosphatidylinositol 3-Kinase; A/J Mouse; Aldosterone; American; American Heart Association; Angiotensin II; Atomic Force Microscopy; Attenuated; Awareness; base; Bioavailable; Biochemical Pathway; Biological Availability; Blood Vessels; Carbohydrates; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; cardiovascular disorder risk; Cardiovascular system; Cells; Collagen; Connective Tissue; Consumption; coronary fibrosis; crosslink; Data; Diabetes Mellitus; Diet; Dietary Intervention; Docking; Endothelial Cells; Endothelium; Environmental Risk Factor; enzyme activity; epithelial Na+ channel; extracellular; Extracellular Matrix; Fatty acid glycerol esters; feeding; Female; Fibrosis; FRAP1 gene; Funding; Genetic; Glycocalyx; Goals; Grant; Health; Heart; Image; Impairment; improved; In Vitro; in vivo; indexing; Individual; Infiltration; Inflammation; innovation; insight; Insulin; insulin receptor substrate 1 protein; Insulin Resistance; insulin signaling; Insulin Signaling Pathway; Intervention; Knock-out; knockout animal; Knockout Mice; Knowledge; Lead; lifetime risk; macrophage; Magnetic Resonance Imaging; male; Measures; Mediating; men; Metabolic; Mineralocorticoid Receptor; Mineralocorticoids; Modeling; Molecular; monocyte; Morbidity - disease rate; mortality; mouse model; Mus; Muscle; Nitric Oxide; Nitric Oxide Synthase; Non-Insulin-Dependent Diabetes Mellitus; novel; novel therapeutics; Obesity; Overnutrition; Overweight; patch clamp; Phosphorylation; Physiologic pulse; PI3 gene; polymerization; prevent; Process; Proto-Oncogene Proteins c-akt; Rattus; receptor; Receptor Signaling; recruit; Relaxation; Research; Ribosomal Protein S6 Kinase; Rodent; Rodent Model; Role; saturated fat; Serine; Sex Differences; Sgk protein; Signal Pathway; Signal Transduction; Site; Skeletal Muscle; Structure; Sucrose; Techniques; Therapeutic; Time; Tissues; transglutaminase 2; Translating; two photon microscopy; Type 2 diabetic; United States National Institutes of Health; Vascular Endothelial Cell; Veterans; western diet; Wild Type Mouse; Woman; Work; ","Cell Specific Mineralocorticoid Signaling, Insulin Resistance and Cardiovascular Stiffness","001981","ENDA","Endocriniology A ","","","06","","","",""
"9815335","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004092","","RFA-BX-17-001","5I01BX004092-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","ALBUQUERQUE","UNITED STATES","","01","073242369","US","481055","ALBUQUERQUE VA MEDICAL CENTER","NM","871085153","Lung cancer is the leading cause of cancer death among veterans; the lack of effective therapy provides the impetus to search for alternative, anti-neoplastic, chemopreventive agents and treatment strategies. Grape seed procyanidin extract (GSE) is used to promote cardiovascular health, and milk thistle silymarin extract (MTE) is used to promote hepatobiliary health; both natural agents have independently been reported to exert anti-neoplastic effects against lung cancer. Based on our encouraging in vitro findings showing unequivocal synergistic anti-cancer effects exerted by the combinations of GSE and MTE, the purpose of this continuing renewal Merit Review proposal is to evaluate the in vivo anti-neoplastic properties of combinations of leucoselect phytosome and siliphos, which are standardized GSE and MTE complexed with soy phospholipid to enhanced bioavailability, in mouse models of lung cancer, to determine their pharmacokinetics and pharmacodynamics against lung cancer, identify suitable surrogate endpoint biomarkers and set the stage for clinical trials in the near future.","1950401; ","MAO, JENNY T;","","10/01/2018","09/30/2022","A549; Aftercare; anti-cancer; Antineoplastic Agents; Antioxidants; Apoptosis; Apoptotic; base; Biological Availability; Biological Markers; Biological Models; BIRC5 gene; Blood; cancer biomarkers; cancer cell; Cancer cell line; cancer chemoprevention; Cancer Etiology; cardiovascular health; Cardiovascular system; CASP3 gene; Cell Line; Cessation of life; Chemical Structure; Chemopreventive Agent; Cleaved cell; Clinical; Clinical Trials; Coculture Techniques; Collection; Complex; Crude Extracts; Cultured Cells; Data; Dose; Drug Kinetics; effective therapy; Eicosanoids; Epigenetic Process; Epithelial Cells; Expression Profiling; FHIT gene; Food Supplements; Freezing; Future; Gene Chips; Gene Expression; grape seed; Growth; Health; Health Food; Hepatobiliary; Human; IGF2R gene; improved; In Vitro; in vivo; indexing; Induction of Apoptosis; inflammatory marker; Inhibition of Cell Proliferation; insight; Interleukin-10; Interleukin-12; Interleukin-6; Lead; Lung; lung cancer prevention; Lung Neoplasms; lung tumorigenesis; Malignant neoplasm of lung; Malignant Neoplasms; Maximum Tolerated Dose; Measures; Mediating; MicroRNAs; Milk Thistle; Milk thistle extract; Molecular; Monitor; mouse model; Mus; neoplastic cell; novel; Nude Mice; Oral; Oral Administration; Organ; Outcome; Pathway interactions; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacodynamics; pharmacokinetics and pharmacodynamics; Phase; Phospholipids; Physiological; Plasma; polyphenol; Pre-Clinical Model; predicting response; Premalignant Cell; Procyanidins; Property; PTEN gene; Reporting; Sampling; Signal Pathway; Silymarin; Site; soy; Standardization; Structure; Structure of parenchyma of lung; Surrogate Endpoint; Surrogate Markers; System; Testing; Time; TP53 gene; Translating; treatment duration; treatment group; treatment response; treatment strategy; tumor growth; Tumor Immunity; Tumor Volume; tumor xenograft; Veterans; Water; Xenograft Model; Xenograft procedure; ","Combinations of Grape Seed and Milk Thistle Extracts Against Lung","004092","ONCB","Oncology B ","","","02","","","",""
"9815336","IK2","VA","5","N","10/25/2019","10/01/2019","09/30/2020","999","IK2BX004097","","RFA-BX-17-008","5IK2BX004097-02","","OTHERS","2020","Veterans Affairs","","BUFFALO","UNITED STATES","","26","020653809","US","481057","VA WESTERN NEW YORK HEALTHCARE SYSTEM","NY","142151129","Ischemic heart disease continues to be the leading cause of mortality and morbidly in the United States, impacting the lives of millions of Veterans each year. This project seeks to identify novel therapeutic approaches and targets to simulate heart muscle regeneration, including those that would not require the administration of stem cell populations. This would enhance the treatment of Veterans with a wide spectrum of cardiac disease including heart failure and myocardial infarction.","12415311; ","LANG, JENNIFER K;","","10/01/2018","09/30/2024","Acute myocardial infarction; Address; Anti-inflammatory; Apoptotic; Caliber; Cardiac; Cardiac Myocytes; cardiac regeneration; cardiac repair; cardioprotection; Cell membrane; cell preparation; Cell Therapy; Cells; Clinical Research; Data; Environment; Enzymes; exosome; experimental study; extracellular; Fibroblasts; Fibrosis; functional decline; Genes; Genetic; Goals; Heart; Heart Diseases; Heart failure; heart function; Human; improved functioning; In Vitro; in vivo; Infarction; Inflammation; injured; Injury; intercellular communication; Ischemia; knock-down; Left Ventricular Function; macrophage; Mediating; Mediator of activation protein; Membrane; Membrane Lipids; Messenger RNA; MicroRNAs; mortality; mouse model; Multivesicular Body; muscle regeneration; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Natural regeneration; novel; novel therapeutic intervention; paracrine; Paracrine Communication; Patient Care; Patients; Pharmacology; Phenotype; Physiological; prevent; Proteins; Recovery; repaired; Reporting; response; restoration; Role; Sphingomyelinase; stem cell population; Stem cells; success; Testing; tool; United States; Up-Regulation; vector; Vesicle; Veterans; Work; ","The Functional Role of Exosomes in Stem Cell Mediated Cardiac Repair","004097","CARA","Cardiovascular Studies A ","","","02","","","",""
"9815434","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003413","","RFA-BX-16-001","5I01BX003413-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","TAMPA","UNITED STATES","","14","929194256","US","481155","JAMES A. HALEY VA MEDICAL CENTER","FL","336124745","Oncolytic virotherapy has reemerged as a potential alternative to chemo- and radio-therapies, however, its application to lung cancers has been limited. Importantly, targeting oncolytic viruses to tumors in general and especially in the lung remains a major hurdle and a critical need. A nearly harmless common cold virus, the respiratory syncytial virus (RSV), that infects and kills lung cancer cells, was recently found to replicate in human mesenchymal stem cells (MSCs), which are known to target to tumors. Based on these developments, this proposal plans to develop and test RSV-infected MSCs as an oncolytic virotherapy for lung cancers, which is the number one killer among cancers and the second most commonly diagnosed cancer among military veterans.","1864091; 8485161 (contact); ","MOHAPATRA, SHYAM S; MOHAPATRA, SUBHRA  (contact);","","10/01/2017","09/30/2021","3-Dimensional; anti-cancer; Antineoplastic Agents; Apoptosis; base; Biopsy; cancer cell; cancer diagnosis; cancer heterogeneity; Cancer Patient; cancer therapy; Cell Death; Cell Line; Cell Therapy; cell type; Cells; chemoradiation; Clinical; Clinical Trials; clinically relevant; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Common Cold Virus; CRISPR/Cas technology; cytochrome c; Data; Development; Dioxygenases; Diploidy; Disease; Engineering; Epithelial Cells; Human; Immunocompetent; In Vitro; in vivo; indoleamine; Infection; innovation; Interferon-beta; Lewis Lung Carcinoma; Lung; Lung Neoplasms; Malignant neoplasm of lung; Malignant Neoplasms; Mediating; Mesenchymal Stem Cells; Methods; Military Personnel; Mitochondria; Modeling; Motivation; mouse model; neoplastic; neoplastic cell; Non-Small-Cell Lung Carcinoma; Nonstructural Protein; novel; novel strategies; novel therapeutic intervention; Oncolytic; oncolytic virotherapy; Oncolytic viruses; Outcome; Positioning Attribute; programs; Property; Proteins; Reagent; Resistance development; Respiration; Respiratory syncytial virus; Respiratory Syncytial Virus Infections; stem cell therapy; Survival Rate; System; Testing; Therapeutic; Translating; Tropism; tumor; Tumor Immunity; tumorigenesis; Up-Regulation; Veterans; Viral; Viral Antigens; Viral Proteins; Voltage-Dependent Anion Channel; WI 38 cell; ","Tumor targeted engineered stem cells for treatment of lung cancer","003413","ONCB","Oncology B ","","","03","","","",""
"9823775","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002195","","RFA-BX-13-001","5I01BX002195-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NASHVILLE","UNITED STATES","","05","156385783","US","481084","VETERANS HEALTH ADMINISTRATION","TN","372122637","Project Narrative  Obesity has become a worldwide epidemic resulting in increased incidence of many different diseases. Recent evidence suggests that weight cycling is associated with elevated risk of diabetes and cardiovascular disease. As such, scientific discovery toward understanding the mechanisms by which weight cycling has adverse metabolic effects is of utmost importance.","1884906; ","HASTY, ALYSSA H;","","07/01/2014","09/30/2022","adaptive immune response; adaptive immunity; Adipocytes; Adipose tissue; Antibodies; Antigens; Biological Assay; Body Weight; Body Weight decreased; Cardiovascular Diseases; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Count; Cells; Clonal Expansion; Comorbidity; Data; Defect; Development; diabetes risk; Disease; effector T cell; Epidemic; Equilibrium; fasting glucose; Fat-Restricted Diet; Fatty acid glycerol esters; feeding; Flow Cytometry; General Population; Genes; glucose tolerance; Human; Immune; Immune response; Immune system; Immunologic Memory; Impairment; Incidence; Inflammation; Inflammatory; Insulin Resistance; insulin sensitivity; insulin signaling; Kinetics; Lead; Light; Liver; Lymphocyte Count; macrophage; Memory; Metabolic; Metabolic Diseases; Metabolic dysfunction; metabolic phenotype; mouse model; Mus; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Obesity; obesity development; Organ; Pathologic; Phase; Phenotype; Play; Population; Prevalence; prevent; Publishing; Regulatory T-Lymphocyte; response; Risk; Scientist; T cell response; T memory cell; T-Lymphocyte; Testing; Therapeutic; Time; Weight; Weight Gain; ","Immunologic memory to metabolic cycling","002195","ZRD1","Special Emphasis Panel ","","","06","","","",""
"9907654","IS1","VA","1","N","10/21/2019","09/01/2019","09/30/2020","999","IS1BX003984","","RFA-BX-19-017","1IS1BX003984-01A1","","OTHER RESEARCH-RELATED","2020","Veterans Affairs","","PROVIDENCE","UNITED STATES","","02","182465745","US","10018779","PROVIDENCE VA  MEDICAL CENTER","RI","029084734","This Shared Equipment Evaluation Program application seeks to obtain equipment that will benefit numerous researchers at the Providence VAMC to improve Veteran care. This equipment is used to assay individual genetic variation in samples from Veterans and others with Veteran-relevant medical conditions (e.g., addiction, diabetes, heart disease, depression, PTSD, etc.). By examining individual differences at the 'omic levels (i.e., assessing variation throughout the genome), the hope is to identify unique targets for intervention using a precision medicine approach. Inherent to this line of research is the consideration of the possibility that not all treatments work equally well in all individuals. By studying these individual differences at the molecular level, we hope to tailor treatments to Veterans based upon their unique genetic and epigenetic background.","7878534; ","RUDOLPH, JAMES L;","","09/01/2019","09/30/2020","addiction; Aging; Area; base; Behavioral; Biological; Biological Assay; Cardiovascular Diseases; Caring; Clinical; Clinical Data; Communities; Complement; Controlled Study; cost effective; Country; Data; Detection; Diabetes Mellitus; Disease; DNA Methylation; Epigenetic Process; epigenetic variation; Equipment; Genes; Genetic; Genetic Variation; Genome; Genomics; Health; health care delivery; health service use; Heart Diseases; improved; Individual; Individual Differences; individualized medicine; Infrastructure; innovation; instrument; instrumentation; Intervention; Investments; Laboratories; Manufacturer Name; Medical; Medical center; Medical Research; Mental Depression; Minor; Molecular; Phenotype; Positioning Attribute; Post-Traumatic Stress Disorders; precision medicine; Program Evaluation; Psyche structure; psychogenetics; Psychopathology; Publications; Reader; Reading; Recording of previous events; rehabilitation science; Rehabilitation therapy; relating to nervous system; Request for Applications; Research; research and development; Research Infrastructure; Research Personnel; Sampling; Services; Suicide; Technology; Therapeutic; Variant; Veterans; Work; ","ShEEP Request for Illumina iScan","003984","ZRD1","Special Emphasis Panel ","","A1","01","","","",""
"9981442","IK2","VA","5","N","10/23/2019","09/01/2017","08/31/2018","999","IK2HX001914","","RFA-HX-16-011","5IK2HX001914-02","","OTHERS","2020","Veterans Affairs","","Aurora","UNITED STATES","","06","003252830","US","481018","VA EASTERN COLORADO HEALTH CARE SYSTEM","CO","800457211","More than 500,000 Veterans are prescribed opioid pain medications long-term. There is inadequate evidence supporting long-term use and growing evidence of harm caused by opioid medications, including overdose death. Risk of overdose death is highest on high-dose opioid medications. Decreasing or discontinuing opioid medications may prevent overdose but may also negatively affect pain and quality of life. Our work will evaluate dose reduction or discontinuation of long-term opioid medications. We will interview Veterans taking opioid medications to describe perspectives on stopping these medications. We will work with Veterans and healthcare providers to develop and pilot a primary care-based program to support Veterans who wish to stop taking opioid medications. This work addresses an important and timely topic as opioid discontinuation is a goal of current VA initiatives on opioid safety. Our Veteran-centered, primary care-based approach is consistent with the VA?s National Pain Management Strategy and its Stepped Care Model of pain care.","11901132; ","FRANK, JOSEPH ;","","09/01/2016","08/31/2021","Address; Adult; Adverse event; Alcohol or Other Drugs use; American; Area; arm; Award; Back; base; behavior change; care providers; career; career development; Caring; Cessation of life; Characteristics; Chronic; chronic pain; Clinical; Clinical Pharmacists; Clinical Trials Design; collaborative care; Colorado; Communities; Computerized Medical Record; Consensus; Data; Data Collection; design; Development; Dose; Education; Effectiveness; Ensure; Environment; evidence base; experience; Feasibility Studies; Funding; Future; Goals; health administration; health care service utilization; Health Personnel; Healthcare Systems; high risk; Illicit Drugs; improved; Injury; interest; Intervention; Interview; Lead; Life; Manuals; Measurement; Measures; Medical; Medication Management; Mental disorders; Mentors; Mentorship; Modeling; motivational enhancement therapy; multidisciplinary; negative affect; Observational Study; Opioid; Opioid Analgesics; opioid overdose; opioid therapy; Overdose; overdose death; overdose risk; Pain; Pain Clinics; Pain management; pain model; Pain quality; Pain Research; Palliative Care; patient engagement; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pilot Projects; Pragmatic clinical trial; prescription opioid; Prevalence; prevent; Primary Care Physician; primary care setting; Primary Health Care; programs; Protocols documentation; Provider; Psychologist; Quality of life; recruit; Reporting; Research; Research Personnel; Resources; response; Risk; Role; Safety; Severities; side effect; Structure; Techniques; Telephone; Testing; therapy design; therapy development; Time; Training; United States; Universities; vehicular accident; Veterans; Work; ","Development and Testing of a Prescription Opioid Tapering Intervention","001914","CDA0","HSR&D Career Development Award  ","","","02","","","",""
"9781542","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004767","","RFA-BX-18-001","1I01BX004767-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Asthma is a highly prevalent disease, affecting up to 8% of the U.S. population, with $82 billion in economic costs due to lost productivity and healthcare utilization. Veterans are affected equally to the general population, and in some cases at higher rates due to inhalation exposures. Even though we have studied asthma for years and have defined many molecular pathways involved in pathogenesis, there are many asthmatics who do not respond to current therapies. The goal of the work proposed is to look at asthma from the perspective of pulmonary endothelial cells, which act as a barrier between circulating immune cells and the lung parenchyma. We hope to identify HIF-1? or HIF-2? within pulmonary endothelial cells as new therapeutic targets for the treatment of asthma endotypes that have not been responsive to conventional treatments. Along the way we will determine how HIF-1? or HIF-2? regulate pulmonary endothelial cell function, including activation and expression of adhesion factors leading to recruitment and transmigration of leukocytes into the lungs.","10385606; ","CROTTY ALEXANDER, LAURA ELISE;","","10/01/2019","09/30/2023","Adhesions; Adult asthma; Affect; Airway Disease; Allergic; Allergic inflammation; American; anti-IgE; Antiinflammatory Effect; Asthma; asthma exacerbation; asthma model; asthmatic; Back; Biological Products; Blood Circulation; Blood Vessels; body system; Cell Adhesion Molecules; cell motility; Cell physiology; Cell Proliferation; cell type; Cells; Chronic; Chronic Disease; conventional therapy; cost; Data; Development; Disease; disorder control; Double Effect; drug development; economic cost; Emergency department visit; Endothelial Cells; eosinophil; Gatekeeping; General Population; Goals; Health Care Costs; health care service utilization; Healthcare Systems; Heterogeneity; Hospitalization; Human; Hypoxia Inducible Factor; IL5 gene; Immune; immune function; Immunologics; Individual; Inflammation; Inflammatory; Inflammatory Response; Inhalation Exposure; Interleukin-17; Knock-out; knockout gene; Knockout Mice; Leukocytes; Lung; Lymphocyte; macrophage; Metabolism; Modeling; Molecular; mouse model; Movement; Mus; Myeloid Cells; neutrophil; new therapeutic target; novel therapeutics; Pathogenesis; Pathologic; Pathway interactions; Pharmaceutical Preparations; Phenotype; Physiological; Play; Population; prevent; Productivity; promoter; protein profiling; Proteins; pulmonary function; Pulmonary Inflammation; Quality of life; recruit; Regulation; response; Role; Schools; small molecule inhibitor; Steroid Resistance; Steroid-resistant asthma; Steroids; Structure of parenchyma of lung; Surface; T-Lymphocyte; targeted treatment; Testing; Therapeutic; Time; tool; Veterans; Work; ","Hypoxia inducible factors in pulmonary endothelial cells regulate allergic inflammatory airways disease","004767","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9871451","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004982","","RFA-BX-19-022","1IK6BX004982-01","","OTHERS","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","Our lab primarily focuses on central nervous system (CNS) cell signaling that leads to neuronal death in Parkinson's disease (PD) and Alzheimer's disease (AD) and demyelination in multiple sclerosis (MS). We will try to suppress neurotoxic signaling pathways and/or boost neuroprotective signaling pathways in different animal models of neurodegenerative diseases by nontoxic drugs in order to achieve neuroprotection and functional recovery. 1","6124977; ","PAHAN, KALIPADA ;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Application","004982","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9948538","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002680","","RFA-BX-15-001","5I01BX002680-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","PUBLIC HEALTH RELEVANCE    Rotator cuff tears are increasingly common in the aging population. Patients with a nonfunctional rotator cuff are difficult to elevate the arm to perform activities of daily living. ith the aging of our Veteran population, rotator cuff tears are becoming a more and more important health issue for the VA patients. The development of muscle fibrosis and fatty infiltration (FI) ar critical factors that determine the clinical outcome of patients with this injury. However, there i no effective treatment for this disease at this time due to our limited understanding of the mechanisms. Successful achievement of this project will define the cellular source and important molecular pathways responsible rotator cuff muscle fibrosis and FI. Results from this study may lead to new therapeutic approaches to treat this disease. Therefore, our proposal has particular significance for the VA population.","8871132; ","KIM, HUBERT T.;","","10/01/2015","09/30/2020","Achievement; Activities of Daily Living; Adipocytes; Age; Age-Years; Aging; aging population; Animal Model; arm; Atrophic; BMP7 gene; Bone Morphogenetic Proteins; Cell Differentiation process; Cell Lineage; Cell Proliferation; Cells; Chemicals; Clinical; common treatment; Denervation; Disease; effective therapy; Endothelium; Fibroblasts; fibrogenesis; Fibrosis; Gene Expression; General Population; Health; humerus; Impairment; improved; In Vitro; in vivo; Infiltration; inhibitor/antagonist; Injury; Lead; Link; lipid biosynthesis; Modeling; Molecular; Movement; Mus; Muscle; Muscle Development; Muscle function; Muscular Atrophy; Names; novel; novel therapeutic intervention; Operative Surgical Procedures; Orthopedics; Outcome; Pathologic; Pathology; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmacological Treatment; Pharmacology; Pilot Projects; Play; Population; Positioning Attribute; prevent; Prevention; progenitor; protein expression; public health relevance; Regulation; repaired; Reporter; Reporting; Role; Rotator Cuff; rotator cuff injury; rotator cuff tear; satellite cell; scapula; Shoulder; Signal Pathway; Signal Transduction; Signaling Protein; Skeletal Muscle; Source; stem cell differentiation; Stem cells; Surgeon; System; Tendon structure; Time; Transforming Growth Factor beta; Transgenic Organisms; Veterans; Work; ","TGFb and BMP signaling in muscle atrophy and degradation after massive RCT","002680","SURG","Surgery ","","","05","","","",""
"10002159","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002444","","RFA-BX-14-004","5I01BX002444-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","IOWA CITY","UNITED STATES","","02","028084333","US","481031","IOWA CITY VA MEDICAL CENTER","IA","522462208","PUBLIC HEALTH RELEVANCE:         Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly fatal form of neurodegenerative disease that strikes military veterans more frequently than the general population. There are currently no treatments capable of stopping or slowing disease progression, and the research proposed in this application seeks to discover and evaluate neuroprotective drug leads for the treatment of ALS in order to identify small molecules suitable for IND-enabling toxicology as a prelude to testing in humans.","6404609; ","PIEPER, ANDREW A;","","01/01/2015","09/30/2020","Address; Adenine; Affect; Amyotrophic Lateral Sclerosis; analog; Aniline; Animal Model; axonal degeneration; base; Biochemical; Biological Assay; Biological Availability; Blood; Brain; Carbazoles; Cells; Cessation of life; Characteristics; Chemicals; Chemistry; Collaborations; design; Development; dimer; Disease; Disease Progression; Dose; Doxorubicin; Drug Kinetics; Drug toxicity; efficacy testing; Enzyme Activators; Enzymes; Ethnic Origin; first-in-human; General Population; Genetic study; Goals; Hippocampus (Brain); Human; improved; In Vitro; in vitro Assay; in vitro testing; in vivo; Injury; insight; Laboratories; Lead; Mediating; Medical center; meetings; member; men; Military Personnel; Modeling; Molecular Target; Motor; Motor Neurons; Movement; Mus; mutant; Mutant Strains Mice; Nerve Degeneration; Neurodegenerative Disorders; neuron loss; neuronal survival; Neurons; neuroprotection; Neuroprotective Agents; Niacinamide; Nicotinamide adenine dinucleotide; Nicotinamide Mononucleotide; nicotinamide phosphoribosyltransferase; novel; novel therapeutics; Oral; Outcome Measure; Parkinson Disease; Pathogenicity; Patients; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; pre-clinical; Pre-Clinical Model; preclinical development; preservation; Prevalence; Process; professor; Property; protective efficacy; public health relevance; Race; Rattus; Research; research clinical testing; Resources; Rodent; Rodent Model; Safety; scaffold; Science; screening; Series; Severity of illness; Skeletal Muscle; small molecule; Solubility; Spinal Cord; superoxide dismutase 1; System; Testing; Texas; Toxic effect; Toxicology; Transgenic Animals; Transgenic Mice; Traumatic Brain Injury; Treatment Efficacy; Universities; Variant; Veterans; Woman; ","Neuroprotective Small Molecules as Novel Treatments for ALS","002444","NURE","Neurobiology E ","","","05","","","",""
"10023146","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002644","","RFA-BX-14-001","5I01BX002644-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PHILADELPHIA","UNITED STATES","","03","071609291","US","481078","PHILADELPHIA VA MEDICAL CENTER","PA","191044551","PUBLIC HEALTH RELEVANCE:         The success of the adaptive immune system depends upon the generation of effector cells and the maintenance of memory to the pathogens previously encountered. Immune responses rely on interactions between CD4+ T cells, a white blood cell that organizes the immune response, and B cells that produce the antibodies that prevent secondary infections. In the current proposal, we show that the timing and location of interactions between CD4+ T cells and B cells determines whether blocking antibodies and memory cells to prevent secondary infections are generated. We will utilize mouse models to explore the biologic mechanisms that determine how different responses are generated to either protein vaccinations or viral infections. Establishing a better paradigm for the activation of CD4+ T cells and antibody-producing B cells should guide the development of improved vaccines and improve the health of both soldiers and Veterans.","1888794; ","LAUFER, TERRI M.;","","10/01/2015","09/30/2020","Adaptive Immune System; Address; Adjuvant; Antibodies; Antibody-Producing Cells; Antigen-Presenting Cells; Antigens; Autoantibodies; B-Cell Development; B-Lymphocytes; Biological; Biological Markers; Biology; Blocking Antibodies; CD4 Positive T Lymphocytes; Cell Communication; cell fixing; Cell Lineage; Cell Maintenance; Cell physiology; Cells; cellular targeting; Chromatin; Clinical; Cytokine Gene; Data; Dendritic Cells; Development; differentiated B cell; Disease; Dissection; DNA Methylation; Effector Cell; effector T cell; Enzymes; Epigenetic Process; epigenetic regulation; Eragrostis; Event; Future; Generations; Genes; Genetic Transcription; genome-wide; Health; Helper-Inducer T-Lymphocyte; histone modification; Histones; HIV; Humoral Immunities; Immune response; Immunization; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Somatic Hypermutation; imprint; improved; Individual; Infection; Influenza; Influenza A virus; Influenza vaccination; influenza virus vaccine; insight; Investigation; Lead; Leukocytes; Location; Lupus; Lymphocytic choriomeningitis virus; Lymphoid; Mediating; Memory; Memory B-Lymphocyte; MHC Class II Genes; Modeling; Modification; Molecular; Molecular Target; mouse model; Mouse Strains; Mus; neutralizing antibody; Nucleosomes; Organ; Outcome; pathogen; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Post-Translational Protein Processing; preservation; prevent; Process; Proteins; public health relevance; Reaction; Repression; response; Rheumatoid Arthritis; secondary infection; Series; Site; Soldier; Source; Structure of germinal center of lymph node; success; T cell differentiation; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; transcription factor; Translating; Vaccinated; Vaccination; Vaccines; Veterans; Viral; Virus; Virus Diseases; ","Distinct MHCII APC Requirements for T Cell and B Cell Effector Functions","002644","IMMA","Immunology A ","","","05","","","",""
"9766444","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004639","","RFA-BX-18-001","1I01BX004639-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LEXINGTON","UNITED STATES","","06","018766373","US","481036","VA MEDICAL CENTER - LEXINGTON, KY","KY","405022235","Sepsis is a major health issues for public and for veterans. The mortality rate of sepsis is high, exceeding 30%, due to a lack of efficient therapy. A great barrier for sepsis therapy is that sepsis is a multi-factor disease, which may explain why extensive efforts (more than 100 clinical trials) to block a single component in inflammatory or coagulation pathways have had little impact on patient survival. Here, we propose a new approach for sepsis therapy - targeting multiple factors in sepsis with a new type of synthetic high density lipoprotein (sHDL, YDZL3). Our proposal is well-supported by clinical findings, the existing knowledge of HDL and our preliminary studies. Completion of this study will provide a body of mechanistic and preclinical data for a novel sHDL-based therapy for sepsis and position it for future Investigational New Drug (IND) studies and rapid clinical translation, which will improve the health of public and veterans.","8132330; ","LI, XIANG-AN ;","","10/01/2019","09/30/2023","Animals; Bacteria; base; Biological; Biology; Blood; cecal ligation puncture; cell injury; Cessation of life; Clinical; Clinical Data; clinical translation; Clinical Trials; Coagulation Process; Data; Disease; Dose; Drops; drug development; Drug Kinetics; effective therapy; Effector Cell; Endogenous Factors; Endothelial Cells; endothelial dysfunction; Endotoxins; experience; Frequencies; Future; Generations; Grant; Health; High Density Lipoprotein therapy; High Density Lipoproteins; Hospitals; Immune; Immune response; Immunity; improved; In Vitro; in vivo; Infection; Inflammatory; Inflammatory Response; Injury; innovation; Investigational Drugs; Knockout Mice; Knowledge; Lead; macrophage; Mediating; Modeling; mortality; Mus; neutrophil; novel; novel strategies; Operative Surgical Procedures; Organ; outcome forecast; overexpression; Pathogenesis; Pathway interactions; Patients; Play; Positioning Attribute; Postoperative Period; pre-clinical; Property; protective effect; Public Health; reconstitution; Regimen; Reporting; response; Risk; Risk Factors; Role; Sepsis; septic; septic patients; Signal Transduction; success; targeted treatment; Testing; Therapeutic; therapeutic target; tool; Toxic effect; treatment optimization; Treatment Protocols; Vascular Endothelial Cell; Veterans; ","HDL as a therapeutic target for sepsis","004639","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9775769","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004743","","RFA-BX-18-010","1I01BX004743-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BRONX","UNITED STATES","","13","040077133","US","481060","JAMES J PETERS VA  MEDICAL CENTER","NY","104683904","NARRATIVE Depression, anxiety, and other stress-related disorders are widespread psychological conditions with broad health implications. Approximately 30% of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans are affected by depression. We have identified two phytochemicals, dihydrocaffeic acid (DHCA) and malvidin-3-O-glucoside (Mal-gluc) that are effective in preventing and treating depression in both males and females in multiple experimental models of depressions. The current application is based on the recommendation from the FDA that in order to advance these compounds to Phase I human clinical trial, additional pharmacological and toxicological studies in rodents are needed. Outcomes from the studies proposed in this application will provide critical information for immediate translational application in veterans as well as civilians to treat mood and anxiety disorders, including depression, acute stress disorders and posttraumatic stress disorders either alone or as add-on treatment with currently available antidepressants.","9719729; ","WANG, JUN ;","","10/01/2019","09/30/2023","Acids; acute toxicity; acute traumatic stress disorder; Adverse event; Affect; Anhedonia; Animal Model; Animals; Antidepressive Agents; Anxiety; Anxiety Disorders; Area; Autopsy; base; Behavior; Biological Availability; Body Weight; Brain; Cardiovascular system; Chronic; Clinical; Clinical Chemistry; Clinical Research; Clinical Trials; cytokine; Data; Depressed mood; depression model; design; Development; Disease; Disease remission; DNA Methylation; Dose; Drug Kinetics; Epigenetic Process; Experimental Models; Female; Food; Freedom; Generations; Genes; Glucosides; Goals; Health; Hematology; Heterogeneity; Histology; Histone Acetylation; Hour; Human; improved; In Vitro; in vivo; Individual; Inflammation; Inflammatory; Interleukin-6; Intervention; Intravenous; intravenous injection; Introns; Investigational Drugs; Lead; male; Mediating; Memory impairment; Mental Depression; Mental Health; Metabolic; Monitor; monoamine; Mood Disorders; Morbidity - disease rate; mortality; Mus; new therapeutic target; noradrenergic; novel therapeutics; Nucleus Accumbens; operation; Oral; Oral Administration; Outcome; Outcome Study; overtreatment; Patients; Peripheral; Pharmaceutical Preparations; pharmacokinetic characteristic; Pharmacology; Pharmacology and Toxicology; Phase; Phenotype; Physical Examination; Phytochemical; Plasma; Post-Traumatic Stress Disorders; pre-clinical; Prevalence; prevent; Property; psychologic; rac1 GTP-Binding Protein; Rattus; Recommendation; Recovery; resilience; Resistance; Rodent; Safety; safety study; self-neglect; Social isolation; Sprague-Dawley Rats; Stress; stress disorder; stress related disorder; success; Synapses; Synaptic plasticity; System; Testing; Therapeutic; Time; Toxic effect; Toxicokinetics; Toxicology; Traumatic Brain Injury; Veterans; Water consumption; ","Development of dihydrocaffeic acid and malvidin- 3 - glucoside for the treatment of depression and anxiety disorders","004743","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9782671","I01","VA","1","N","10/21/2019","10/01/2019","09/30/2020","999","I01BX004694","","RFA-BX-18-001","1I01BX004694-01","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","KANSAS CITY","UNITED STATES","","05","844272125","US","481049","KANSAS CITY VA MEDICAL CENTER","MO","641282226","PROJECT NARRATIVE Alcoholic hepatitis is a severe acute liver disease with significant 30-day mortality but most heavy drinkers do not develop liver disease. This project will examine the hypothesis that adaptive changes in liver macrophages normally protect the liver from inflammation due to alcohol. It will determine the factors necessary to form protective macrophages and evaluate how these can be used for prevention and treatment of alcoholic liver disease.","1879160; ","WEINMAN, STEVEN A;","","10/01/2019","09/30/2023","Acute Alcoholic Hepatitis; acute liver disease; Affect; alcohol exposure; Alcoholic beverage heavy drinker; Alcoholic Hepatitis; Alcoholic Liver Cirrhosis; Alcoholic Liver Diseases; Alcoholic steatohepatitis; Alcohols; Animals; Anti-inflammatory; Apoptotic; Appearance; Autopsy; Awareness; Bacterial Translocation; base; binge drinking; Cell Count; Cell Death; Cells; Chronic; Cirrhosis; Complex; cytokine; Data; Development; Diet; Disease; Equilibrium; Ethanol; Etiology; Evolution; Excision; experimental study; Failure; feeding; Fibrosis; Gene Expression; Gene Expression Profile; genetic signature; Goals; Hepatic; Hepatocyte; Human; IL4 gene; In Vitro; in vivo; Individual; Inflammation; Inflammatory; Inflammatory Infiltrate; Inflammatory Response; Injury; Interleukin-13; Intestines; intrahepatic; Knowledge; Kupffer Cells; Lead; Liver; Liver diseases; liver inflammation; liver injury; liver transplantation; macrophage; Maintenance; Measures; Minority; monocyte; mortality; mouse model; Mus; Natural regeneration; Nature; novel therapeutic intervention; Patients; Pattern; peripheral blood; Phenotype; Play; Population; Prevention; Process; Production; Property; receptor; Recovery; repaired; Research; Research Personnel; response; Role; Severities; Signal Transduction; single-cell RNA sequencing; Source; Specimen; Techniques; Time; Tissues; Transcriptional Activation; Work; ","Role of macrophage evolution in hepatic adaptation to alcohol.","004694","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9814680","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002978","","RFA-BX-16-001","5I01BX002978-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Neurodegenerative diseases represent a major challenge in the health care for the civilian and Veterans populations. In particular, there are concerns that exposure to traumatic brain injury during combat may increase the propensity of neurodegeneration in Veterans. In a recent survey of combat brigades involved in Operation Iraqi Freedom, it was estimated that ~15% of respondents had sustained at least one episode of TBI. As these military personnel retire from their active duty, the consequences of TBI will become major problems for the Veterans health system. To further investigate the mechanisms of neurodegeneration, we propose to investigate how loss-of-function in frontotemporal dementia gene Progranulin causes neuroinflammation and neurodegeneration. Results from this proposal will not only provide mechanistic insights into the biology of PGRN in the pathogenesis of neurodegeneration, they will also serve as novel platforms to identify new biomarkers and therapeutic targets to prevent and treat neurodegeneration.","6710941; ","HUANG, ERIC J;","","10/01/2016","09/30/2020","Adult; Affect; age related; Aging; Attention; barrel cortex; Behavioral; Biological Markers; Biology; Brain; Cells; Characteristics; Coculture Techniques; cohort; combat; Complement; Complement 1q; Complement Activation; cytokine; cytotoxic; Disease; Exhibits; Exposure to; Flow Cytometry; Freedom; Frontotemporal Dementia; Future; Gene Expression; Gene Expression Profiling; Genes; genetic approach; Goals; Health system; Healthcare; human disease; Immune; Immune Response Genes; improved; Inflammatory; Injury; injury and repair; Innate Immune Response; insight; ITGAM gene; Knock-out; Knowledge; Lateral posterior nucleus of thalamus; Lead; Learning; loss of function; macrophage; Medial; Mediating; Microarray Analysis; Microglia; Military Personnel; Molecular; Molecular Profiling; mouse model; Mus; mutant; Mutate; Mutation; Natural Immunity; Nerve Degeneration; neural circuit; Neurodegenerative Disorders; neuroinflammation; neuron loss; neuronal cell body; Neurons; neuropathology; novel; operation; Pathogenesis; Pathway interactions; Patients; PGRN gene; Pharmacology; Phenotype; Population; prevent; Production; Protein Deficiency; protein expression; Proteins; Respondent; Role; Sensorimotor functions; Spinal Cord; Surveys; Synapses; Testing; Thalamic Nuclei; therapeutic target; Toxin; Traumatic Brain Injury; Up-Regulation; Veterans; Work; ","Mechanisms of Progranulin Deficiency in Neuroinflammation and Neurodegeneration","002978","NURD","Neurobiology D ","","","04","","","",""
"9814682","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003168","","RFA-BX-15-001","5I01BX003168-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","PUBLIC HEALTH RELEVANCE        Tauopathies are a group of neurological diseases in which accumulation of a brain protein called `Tau' damages brain cells. These diseases, which include Alzheimer's disease and head injury, are collectively a major cause of chronic disability in Veterans. There are currently no effective treatments for tauopathies; medications that prevent disease progression would have a significant and positive impact on Veterans' health. To address this challenge, we have developed a series of unique experimental models. The zebrafish shares numerous similarities in genetics and brain structure with humans. We have made zebrafish whose brains contain human Tau and proteins that glow different colors to indicate biochemical changes, allowing us to measure the abnormalities caused by Tau accumulation in the living brain cells of an intact animal for the first time. Coupled with a rapid testing platform for anti-Tau drugs, we will use these models to elucidate the biochemical events linking Tau accumulation to brain cell damage, and to discover novel treatments for tauopathy.","8125638; ","BURTON, EDWARD ALAN;","","10/01/2016","09/30/2020","Address; Alzheimer's Disease; Animals; Autopsy; base; Biochemical; Biochemistry; Bioenergetics; Biological Assay; Biological Models; Brain; brain cell; Brain Injuries; Cell Death; cell injury; Chronic; chronic traumatic encephalopathy; CNS degeneration; Color; Complex; Consensus; Coupled; Craniocerebral Trauma; Cultured Cells; Cytoplasmic Protein; Data; Dementia; Development; disability; Disease; Disease Progression; drug discovery; effective therapy; Event; Experimental Models; experimental study; Frontotemporal Dementia; Genetic; genome wide association study; Glutathione; Haplotypes; Health; Human; Image; imaging modality; Impairment; In Vitro; in vivo; insight; Intervention; Investigation; Lead; Link; Literature; MAPT gene; Measures; Mediator of activation protein; Methods; Mitochondria; mitochondrial dysfunction; Mitochondrial Proteins; Modeling; Molecular; Molecular Target; Motor; Mutation; Nerve Degeneration; nervous system disorder; neurobehavioral; Neurodegenerative Disorders; Neurologic; neuron loss; Neuronal Dysfunction; Neurons; neuropathology; neurotoxic; novel; novel strategies; Nuclear; oculomotor; Outer Mitochondrial Membrane; overexpression; oxidation; Oxidation-Reduction; oxidative damage; Oxidative Stress; Pathogenesis; Pathogenicity; Pathologic; Pharmaceutical Preparations; Phenocopy; Phenotype; Pigments; prevent; Production; Progressive Supranuclear Palsy; protein complex; protein function; Protein Import; protein oligomer; Proteins; public health relevance; Publishing; ratiometric; Reactive Oxygen Species; Reagent; reflectance confocal microscopy; Reporter; Reporting; Reproducibility; Research; Respiratory physiology; Risk; Series; small molecule; small molecule libraries; Specimen; Structure; Symptoms; targeted treatment; tau aggregation; tau mutation; tau Proteins; Tauopathies; Testing; Therapeutic; therapeutic development; therapeutic target; Time; Tissues; Transgenic Organisms; translocase; Treatment Efficacy; Variant; Veterans; Zebrafish; ","Pathogenesis and drug discovery for tauopathy","003168","NURD","Neurobiology D ","","","04","","","",""
"9814691","IK2","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","IK2BX003486","","RFA-BX-16-008","5IK2BX003486-04","","OTHERS","2020","Veterans Affairs","","TEMPLE","UNITED STATES","","31","029847394","US","10018464","OLIN TEAGUE VETERANS CENTER","TX","765047451","The proposed research program is highly relevant to the VA mission and its successful completion will likely benefit the healthcare of United States Veterans. The risk of liver disease due to drug and alcohol abuse, as well as viral hepatitis, is increasing in the United States Veteran population. This is evident by a substantial increase in the prevalence of cirrhosis in United States Veterans over the last 15 years. Liver diseases remain one of the most common reasons for hospitalization and mortality in United States Veterans. This high rate of mortality is due to a relative lack of treatment options once liver disease progresses to liver failure with liver transplantation being the only effective treatment. Therefore, targeting thrombospondin-1, which has been shown to effect processes that are linked to liver failure, could identify new therapies for patients who suffer from acute liver injury or chronic liver disease.","12190093; ","MCMILLIN, MATTHEW ;","","10/01/2016","09/30/2021","Acetaminophen; Acute; Acute Liver Failure; acute liver injury; Address; Alcohol abuse; Alcohol Hepatotoxicity; Apoptosis; Azoxymethane; bile duct; Biliary; Cell Communication; Cell Culture Techniques; Cell Cycle; Cell physiology; Cells; Cessation of life; Cholestasis; Chronic; chronic liver disease; Cirrhosis; Classification; Clinical Trials; Comorbidity; Development; Disease; Drug abuse; effective therapy; Endothelial Cells; experimental study; Extrahepatic; Fibrosis; Functional disorder; General Population; Glycoproteins; Goals; Healthcare; Healthcare Systems; Hepatic; Hepatic Encephalopathy; Hepatocyte; Hepatotoxicity; High Prevalence; Hospitalization; Human; Impairment; Inflammation; Injury; Investigation; Knowledge; Lead; Ligation; Link; Liver; Liver diseases; Liver Failure; Liver Fibrosis; liver function; liver injury; liver transplantation; Mission; Mitotic; Modeling; mortality; Mus; Natural regeneration; Necrosis; Neurologic; novel; novel therapeutics; Operative Surgical Procedures; Pathogenesis; Pathogenicity; Pathologic; Pathologic Processes; Pathology; Patients; Permeability; Physiological; Population; Prevalence; Process; programs; Proteins; Quality of life; Rattus; Research; Risk; Role; Severities; side effect; Signal Pathway; Signal Transduction; Signaling Protein; Therapeutic Intervention; therapeutic target; Thrombospondin 1; Transforming Growth Factor beta; Transforming Growth Factors; United States; Veterans; Viral hepatitis; ","Pathogenic role of thrombospondin-1 in acute and chronic liver failure","003486","GAST","Gastroenterology ","","","04","","","",""
"9814694","IK6","VA","5","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX003610","","RFA-BX-16-022","5IK6BX003610-04","","OTHERS","2020","Veterans Affairs","","OKLAHOMA CITY","UNITED STATES","","05","020719316","US","481072","OKLAHOMA CITY VA MEDICAL CENTER","OK","731045007","Many Veterans report that life stressors worsen or even initiate gastrointestinal symptomatology, including abdominal pain and abnormal bowel habits resembling those seen in patients with irritable bowel syndrome (IBS). My research is highly relevant to the patient-care mission of the VA, since the VA cares for a Veteran population that has been exposed to severe stress during deployment. When combined with a history of early life stress, deployment stress may lead to the development of chronic abdominal pain and may increase the susceptibility of a soldier, especially a female soldier, to the adverse effects of combat-related stress. Successful completion of the research within my laboratory will offer new insights into the mechanisms of brain-gut dysfunction that likely lead to chronic abdominal pain. Importantly our findings may identify novel targets for new therapies directed at the brain to improve the treatment or even reduce the risk for visceral pain in veterans.","8272948; ","GREENWOOD-VAN MEERVELD, BEVERLEY ;","","10/01/2016","09/30/2023","Abdominal Pain; Address; Adult; Adverse effects; Affect; American; Amygdaloid structure; Anxiety; anxiety-like behavior; Area; authority; Award; Basic Science; behavioral pharmacology; Biology; Brain; career; Caring; cell motility; Chronic; chronic abdominal pain; Clinical Sciences; combat; Communication; Contracts; Corticosterone; Corticotropin-Releasing Hormone; design; Development; Diagnosis; Digestive System Disorders; Disease; Disease Outbreaks; Down-Regulation; early life stress; editorial; Electrophysiology (science); Emotional; Exhibits; experience; experimental study; Exposure to; Extramural Activities; Female; Foundations; Functional disorder; Funding; Future; Gastroenterology; gastrointestinal; Gastrointestinal tract structure; Gene Expression; Gene Targeting; Genes; Glucocorticoid Receptor; Goals; graduate student; Grant; Gulf War; Habits; HCN1 channel; Health; Healthcare; Hypersensitivity; Ileus; improved; Industry; Industry Collaboration; industry partner; Inflammatory Bowel Diseases; innovation; insight; interest; International; Interstitial Cystitis; Intestines; Investigational Therapies; Irritable Bowel Syndrome; Joints; Journals; knock-down; Knowledge; Laboratories; Lead; Leadership; Life; Mediating; Methods; Military Personnel; Mission; Molecular; neural circuit; Neural Pathways; Neuraxis; Neuronal Plasticity; Neurons; Neuropharmacology; neuropsychopharmacology; Neurosciences; new therapeutic target; Nociception; novel; novel therapeutics; Oklahoma; Organ; Pain; pain sensitivity; Pathway interactions; Patient Care; Patients; Pharmacology; Population; Postdoctoral Fellow; Postoperative Period; pre-clinical; Predisposition; Presbyterian Church; Privatization; programs; Psychiatry; Publications; Reagent; receptor; receptor expression; Recording of previous events; Regulation; relating to nervous system; Reporting; Research; research and development; Research Project Grants; research study; resilience; response; Risk; Risk Factors; Rodent Model; Role; Scientific Advances and Accomplishments; Scientist; Services; Sex Differences; Sexual abuse; Soldier; Solid; Stress; stressor; symptomatology; Symptoms; System; targeted treatment; Techniques; undergraduate student; United States National Institutes of Health; Universities; Veterans; Visceral; Visceral pain; Woman; ","BLR&D Research Career Scientist Award Application","003610","RCSR","Research Career Scientist ","","","04","","","",""
"9815321","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002230","","RFA-BX-17-001","5I01BX002230-06","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","DURHAM","UNITED STATES","","01","043241082","US","481065","DURHAM VA MEDICAL CENTER","NC","277053875","Parkinson?s disease (PD) is a debilitating neurodegenerative disease that affects over 40,000 veterans each year. The cause of Parkinson?s disease is unknown, however, there is evidence that environmental toxins such as the pesticide, rotenone, and the herbicide, Agent Orange, may play a role. Military veterans exposed to Agent Orange have an increased incidence of PD and the Institute of Medicine concluded in its report ?Veterans and Agent Orange: Update 2008?, that 'exposure to Agent Orange and other herbicides used during the Vietnam War is associated with an increased chance of developing Parkinson's disease.' In addition, from 1953 to 1987, water sources at Camp Lejeune, NC were contaminated with industrial solvents that are correlated with PD and VA recognized PD as associated with exposure to Agent Orange or other herbicides during military service. To date, the mechanism by which environmental toxins cause PD remains unknown. The current proposal will determine how environmental toxins like Agent Orange affect cells in the gut to cause PD.","1877307; ","LIDDLE, RODGER A.;","","04/01/2014","09/30/2022","Address; adeno-associated viral vector; Affect; agent orange; alpha synuclein; alpha synuclein gene; Animals; Apical; Axon; Brain; Brain Stem; Cell Line; Cell model; Cells; Clinical; Constipation; Cytoplasmic Inclusion; Cytosol; Data; Development; Diagnosis; Diagnostic tests; Disease; dopaminergic neuron; dorsal motor nucleus; Enteral; Enteric Nervous System; Enteroendocrine Cell; experience; Exposure to; feeding; Food; Functional disorder; Future; gastrointestinal; gastrointestinal symptom; Gastrointestinal tract structure; Gastroparesis; Gene Expression; gut microbiota; Herbicides; Hormones; Human; In Vitro; Incidence; Industrialization; Ingestion; Institute of Medicine (U.S.); Intestines; Knowledge; Lead; Lewy Bodies; Location; Medical; Methods; Military Personnel; Modeling; Motor; motor deficit; mouse model; Movement Disorders; Mucous Membrane; Nerve; Nerve Growth Factor Receptors; Nervous system structure; neural circuit; Neurodegenerative Disorders; Neuroendocrine Cell; neurofilament; Neurons; Neurophysiology - biologic function; Neurotoxins; Organoids; overexpression; Parkinson Disease; pars compacta; Pathogenesis; Pathologic; Pathology; Patients; Pesticides; Play; Positioning Attribute; Prevention; prion-like; Process; Property; protein aggregate; Proteins; recruit; Reporting; Risk; Role; Rotenone; Route; Secretory Vesicles; Sensory; Services; Signal Transduction; Solvents; Source; Substantia nigra structure; Surface; Synapses; synuclein; targeted agent; Testing; theories; tool; Toxic Environmental Substances; transmission process; Travel; Update; Vagotomy; Vagus nerve structure; Veterans; Vietnam; War; Water; ","Gut Neuroendocrine Cell Signaling","002230","GAST","Gastroenterology ","","","06","","","",""
"9815347","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000105","","RFA-BX-17-001","5I01BX000105-10","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","DECATUR","UNITED STATES","","04","824835805","US","481023","VETERANS HEALTH ADMINISTRATION","GA","300334004","Fractures are a serious medical problem among aging Veterans and in the general population with almost 50% of older women and 30% of older men likely to suffer a fracture in their lifetimes. Fractures can be devastating and are associated with crippling disability requiring rehabilitation in up to 75% of individuals with loss of independence and significant decline in quality of life. A 2007 study of elderly veterans by Bass et al., reported that mortality within one year of hip fracture was 18% for women and 32% for men. Economic burden of fracture in the US is projected to reach $25 billion/annum by 2025. As the largest integrated health care system in the US, the VA is on the front lines of fracture treatment and rehabilitation and will have to continue to wrestle with these ever-expanding medical costs. The studies in this application deal with novel mechanisms to promote bone regeneration using pharmacological manipulation to exploit a recently identified quirk in the immune system, capable of promoting new bone formation. Our goal is to improve bone density to prevent fracture.","6078988; ","WEITZMANN, MERVYN NEALE;","","04/01/2009","09/30/2022","Age; aged; Aging; Anabolic Agents; Anabolism; anergy; Animal Model; Anti-inflammatory; Antibodies; Antigen-Presenting Cells; Antigens; base; Bass; Biological Assay; bisphosphonate; bone; Bone Density; bone loss; bone mass; Bone Regeneration; Bone remodeling; Bone Resorption; bone turnover; CD28 gene; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Clinical; Clonal Expansion; Collagen-Induced Arthritis; compliance behavior; cost; CREB1 gene; CRISPR/Cas technology; CTLA4-Ig; Cyclic AMP; Cyclic AMP Response Element; Cyclic AMP-Dependent Protein Kinases; cytokine; Development; disability; Disease; Dose; Dual-Energy X-Ray Absorptiometry; Economic Burden; Elderly; Elements; Enzyme-Linked Immunosorbent Assay; Event; FDA approved; Female; Flow Cytometry; Forteo; FOXP3 gene; Fracture; Future; Gap Junctions; General Population; Generations; Goals; Health Expenditures; Healthcare Systems; Hip Fractures; Human; Hysteria; IL2RA gene; Immune; Immune system; Immunophenotyping; Immunosuppressive Agents; improved; In Vitro; in vivo; indexing; Individual; Infection; Inflammation; Inflammatory; inflammatory milieu; Inflammatory Response; Injections; Integrated Health Care Systems; Knock-out; Knockout Mice; Lead; Leadership; Ligands; Luciferases; male; Mediating; Mediator of activation protein; Medical; Medical Care Costs; men; Metabolic; Methods; Molecular Analysis; Morbidity - disease rate; mortality; mouse model; Mus; Mutation Analysis; novel; Null Lymphocytes; older men; older women; Operative Surgical Procedures; Osteoblasts; Osteogenesis; Osteoporosis; Ovalbumin; parathyroid hormone (1-34); Pathway interactions; Patients; peer; Pentoxifylline; Pharmaceutical Preparations; Pharmacology; Physiological; Population Study; prevent; Prevention; Prevention therapy; Production; programs; promoter; prospective; PTH gene; Quality of life; reconstitution; Rehabilitation therapy; Reporter; Reporting; response; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid Arthritis; Role; Rolipram; Schedule; side effect; Signal Transduction; Signal Transduction Pathway; skeletal; Skeletal system; Skeleton; Societies; Stains; Stimulus; Structure; Surface; T cell anergy; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; Transgenic Mice; Transplantation; Vaccination; Validation; Veterans; Viral Antigens; WNT Signaling Pathway; WNT10B gene; Woman; Work; Wrestling; X-Ray Computed Tomography; ","Bone Formation and the Immuno-Skeletal Interface","000105","ENDB","Endocrinology B ","","","10","","","",""
"9815348","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX000508","","RFA-BX-17-001","5I01BX000508-10","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","IOWA CITY","UNITED STATES","","02","028084333","US","481031","IOWA CITY VA MEDICAL CENTER","IA","522462208","Although the prevalence of smoking has declined, chronic obstructive pulmonary disease (COPD) and its attendant pathological pulmonary abnormality, emphysema, are common and disproportionately contribute to hospitalizations and health care costs among veterans. Because most of the currently available therapies only address symptoms, identification of strategies that limit disease progression remains an important goal. This proposal will investigate mechanisms that regulate the movement and positioning of structural cells which form the lung air sacs. These cells are required to form the gas-exchange region of the developing lung and for regenerating damaged air sacs. These studies are also relevant to vascular diseases including stroke, diabetes, and chronic renal insufficiency, which are also common among veterans.","1918351; ","MCGOWAN, STEPHEN E;","","10/01/2009","09/30/2022","1-Phosphatidylinositol 3-Kinase; 3-Dimensional; Actins; Adaptor Signaling Protein; Address; Adult; Air Sacs; Alveolar; Alveolar Duct; American; Architecture; Arginine; Attenuated; BCAR1 gene; Bronchopulmonary Dysplasia; cell motility; Cell Polarity; Cells; Cellular Structures; Chronic Kidney Insufficiency; Chronic Obstructive Airway Disease; Clinical; Collagen; Collagen Fiber; Cytoskeleton; Defect; Development; Diabetes Mellitus; discoidin domain receptor 2; Disease; Disease Progression; Distal; Elastic Fiber; Elastin; Environment; extracellular; Extracellular Matrix; Extracellular Matrix Proteins; Fibrillar Collagen; Fibroblasts; Focal Adhesions; Gases; Generations; Goals; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Guanosine Triphosphate Phosphohydrolases; Health Care Costs; Hospitalization; Impairment; improved; Integrins; Knowledge; Learning; Link; Location; Lung; Lung diseases; mechanical force; Mechanics; Mediating; Membrane; Membrane Lipids; Membrane Microdomains; Metalloproteases; migration; MMP14 gene; mouse model; Movement; Mus; Myofibroblast; Natural regeneration; Neuropilin-1; Newborn Infant; Outcome; Pathogenesis; Pathologic; PDGFA gene; Phosphorylation; Physiology; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor alpha Receptor; polarized cell; Population; Positioning Attribute; Process; Production; Protein Kinase; Proteins; Pulmonary Emphysema; Pulmonary Fibrosis; rac1 GTP-Binding Protein; Receptor Protein-Tyrosine Kinases; recruit; Regulation; repaired; Signal Pathway; Signal Transduction; smoking prevalence; Stroke; Symptoms; trafficking; Vascular Diseases; Veterans; ","Guidance of pulmonary fibroblast migration during alveolar septal formation","000508","PULM","Respiration ","","","10","","","",""
"9815358","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004131","","RFA-BX-17-001","5I01BX004131-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","OKLAHOMA CITY","UNITED STATES","","05","020719316","US","481072","OKLAHOMA CITY VA MEDICAL CENTER","OK","731045007","Majority of the veterans diagnosed with hepatocellular carcinoma (HCC) present advanced, metastatic tumors (78%) with median survival of 4.5-9.2 months. The national prevalence and mortality due to cirrhosis and HCC in VA health care users have increased by approximately 3- fold during the last decade. Chemotherapy, surgical resection, radiation, and local ablation are not effective in a large group of veteran patients with these liver diseases. The proposed studies will allow us to investigate directly the molecular mechanisms that regulate key oncogenic programs in human hepatocytes and to evaluate the efficacy of targeting a tumor stem cell-related protein, DCLK1, which potentially promotes tumorigenesis in multiple organs. !","8710262; ","HOUCHEN, COURTNEY WAYNE;","","10/01/2017","09/30/2021","Ablation; Alcoholic Liver Cirrhosis; Antineoplastic Agents; BAY 54-9085; beta catenin; Biological Assay; Biology; c-myc Genes; Cancer Burden; Cancer Etiology; cancer initiation; Cause of Death; Cell Culture Techniques; Cell Cycle Progression; Cell Lineage; cell motility; Cells; Cessation of life; Characteristics; chemotherapy; Chronic Hepatitis; Chronic viral hepatitis; Cirrhosis; Colon; Data; Development; Diabetes Mellitus; Diagnosis; disease diagnosis; Drug usage; Epithelial; Epithelial Cells; Etiology; Excision; Exposure to; Fatty Liver; FDA approved; FUS-1 Protein; gamma secretase; genotoxicity; Goals; Growth; Health; Healthcare; Hepatic; Hepatitis C virus; Hepatocyte; hepatoma cell; Hepatotoxicity; hepatotoxin; Human; Immunodeficient Mouse; improved; Incidence; Inflammation; inhibitor/antagonist; Injury; Intestines; Investigation; knock-down; Liver; Liver diseases; liver injury; Liver neoplasms; liver transplantation; Luciferases; Malignant neoplasm of liver; Malignant neoplasm of pancreas; Malignant Neoplasms; Medical; Mesenchymal; Metabolic Diseases; Microtubule Bundle; migration; Molecular; Molecular Target; mortality; mouse model; Mus; Mutation; Neoplasm Metastasis; neoplastic; new therapeutic target; Nodule; non-alcoholic; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; notch protein; novel; novel therapeutics; Nude Mice; Obesity; Oncogenes; Oncogenic; Operative Surgical Procedures; Organ; outcome forecast; overexpression; Pancreas; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Phosphotransferases; Prevalence; prevent; Primary carcinoma of the liver cells; programs; Proteins; Protocols documentation; Public Health; Radiation; Relapse; Reporter; Resistance; Risk; Risk Factors; RNA Interference; Role; S100A9 gene; self-renewal; Series; Serum; Signal Pathway; Signal Transduction; Signal Transduction Pathway; small hairpin RNA; Small Interfering RNA; Solid Neoplasm; stem cell population; Survival Rate; Testing; Therapeutic Agents; TNF gene; Transforming Growth Factor beta; Transitional Cell Carcinoma; Transplantation; Treatment Efficacy; trend; tumor; tumor growth; tumor initiation; tumor progression; Tumor Stem Cells; Tumor Suppressor Genes; tumor xenograft; Tumor-Derived; tumorigenesis; tumorigenic; Up-Regulation; Veterans; Virus Diseases; Xenograft Model; ","DCLK1 is a Novel Molecular Target in Hepatocellular Carcinoma","004131","GAST","Gastroenterology ","","","03","","","",""
"9815365","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004252","","RFA-BX-17-001","5I01BX004252-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LEXINGTON","UNITED STATES","","06","018766373","US","481036","VA MEDICAL CENTER - LEXINGTON, KY","KY","405022235","Obesity, an imbalance of energy intake and energy expenditure, is a major risk factor for the development of insulin resistance and type 2 diabetes. Preliminary studies identified that CD47 is a novel regulator of obesity- associated brown fat cell dysfunction. In this application, while delineating mechanisms of CD47 to regulate brown adipocyte function, study will also focus on the development of novel therapeutic strategies in the treatment of obesity and its associated metabolic complications.","7837422; ","WANG, SHUXIA ;","","10/01/2018","09/30/2022","Adipocytes; Adipose tissue; Animal Model; Animals; Antisense Oligonucleotides; Attenuated; base; blood glucose regulation; Body fat; Body mass index; Body Weight; Brown Fat; Carnitine Palmitoyltransferase I; CD47 gene; Cell Line; Cell membrane; Cell physiology; Cells; clinically significant; combat; Comorbidity; Complex; Cyclic AMP; Cyclic GMP; Data; Development; Diet; Eating; Energy Intake; Energy Metabolism; Exhibits; Fatty acid glycerol esters; Fatty Liver; Functional disorder; Genes; genome-wide analysis; Genotype; High Fat Diet; Homeostasis; Human Genome; human subject; immune function; improved; In Vitro; in vivo; Insulin Resistance; Investigation; knock-down; Knockout Mice; lipid biosynthesis; lipid metabolism; Liver diseases; Mediating; Metabolic; Mitochondria; Modeling; Molecular; mouse model; Mus; Nerve; Non-Insulin-Dependent Diabetes Mellitus; novel; novel therapeutics; Obese Mice; Obesity; obesity development; Obesity Epidemic; obesity genetics; obesity treatment; oxidation; prevent; receptor; Resistance; Respiration; Risk Factors; Rodent; Rodent Model; Role; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism; System; Testing; Therapeutic; therapeutic target; Thermogenesis; Tissues; tool; Wild Type Mouse; Work; ","CD47 as a therapeutic target for obesity","004252","ENDA","Endocriniology A ","","","02","","","",""
"9815408","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001556","","RFA-BX-16-001","5I01BX001556-08","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","LOS ANGELES","UNITED STATES","","33","066689118","US","481012","VA GREATER LOS ANGELS HEALTHCARE SYSTEM","CA","900731003","Post-traumatic stress disorder (PTSD) and depression are highly prevalent in US combat Veterans. Insomnia and disturbed sleep are common features in these and other mood and anxiety disorders. Chronic hyperactivity in brain corticotropin releasing factor (CRF) systems has been linked to PTSD and depression. Building on findings from the previous funding period, experiments proposed here are designed to identify critical sleep regulatory circuits targeted by CRF and evaluate the hypothesis that elevated CRF signaling during chronic mild-moderate stress causes disruption of fundamental diencephalic and brainstem circuits that regulate sleep homeostasis. The goal is to identify critical nodes in these circuits that can be targeted for therapeutic interventions. Severity of insomnia and sleep disturbance have been linked to symptom severity and recurrence in PTSD and depression. Preservation of sleep homeostasis during chronic stress may be a strategy to promote stress resilience and improve outcomes in mood and anxiety disorders.","2429640; ","SZYMUSIAK, RONALD ;","","10/01/2011","09/30/2020","Acute; Address; Adenosine; Adverse effects; Amygdaloid structure; Anxiety Disorders; Architecture; Axon; Behavioral; Brain; Brain Stem; Cell Nucleus; Chronic; Chronic stress; circadian; Circadian desynchrony; Circadian Dysregulation; Clozapine; Cognitive; combat; common symptom; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; CRH gene; Data; density; design; Development; Disease; Drug Delivery Systems; Drug usage; Endocrine; experimental study; Female; FOS gene; Funding; Goals; Health; Homeostasis; Hyperactive behavior; Hypothalamic dysfunction; Hypothalamic structure; hypothalamic-pituitary-adrenal axis; immunoreactivity; Impairment; improved outcome; Infusion procedures; Injections; Knock-in Mouse; Laboratories; Light; light effects; Link; Maintenance; male; Mediating; Mental Depression; Mental disorders; Metabolism; Microdialysis; Microinjections; modifiable risk; Mood Disorders; Mus; Neurobiology; Neurons; Neuropeptides; Opsin; Outcome; Oxides; paraventricular nucleus; Phase; Physiologic pulse; Physiological; Population; Post-Traumatic Stress Disorders; preservation; prevent; Process; Psychological Stress; Rattus; receptor; Recovery; Recurrence; response; Rhodopsin; Risk Factors; Role; Severities; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; sleep onset; sleep pattern; sleep regulation; Sleeplessness; Stress; stress resilience; stressor; Structure of terminal stria nuclei of preoptic region; suprachiasmatic nucleus; Symptoms; System; targeted treatment; Therapeutic Intervention; Training; Veterans; Wakefulness; Work; ","Impact of Corticotropin Releasing Factor on Sleep Regulation","001556","NURR","Neurobiology R ","","","08","","","",""
"9815413","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001921","","RFA-BX-17-001","5I01BX001921-07","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BALTIMORE","UNITED STATES","","07","796532609","US","481039","BALTIMORE VA MEDICAL CENTER","MD","212011524","Venous thrombus embolism (VTE) which includes deep venous thrombosis (DVT) is a common and serious clinical problem with 350,000 to 600,000 cases per year in the United States and 200,000 deaths from pulmonary embolism. Military personnel are at increased risk of DVT due to significant periods of travel, prolonged evacuation times, dehydration, and tobacco use. Over half of the surgical patients at Veterans Affair Medical Centers develop VTE. The incidence in Veterans is likely to increase due to increasing age and obesity. Existing therapies for DVT rely on anticoagulants, which do not enhance resolution of the clots, but only prevent further clot development. Delayed or incomplete clot resolution frequently leads to post- thrombotic syndrome- a long-term complication associated with debilitating limb swelling, pain, and recurrent skin ulceration. The goal of this research is to better understand the molecular and cellular processes that regulate thrombus resolution, so that specific therapies to accelerate the resolution process can be developed.","7040487; ","ANTALIS, TONI M;","","07/01/2013","09/30/2021","Acute; Adjuvant; Affect; Age; Agonist; Air; American; Anti-inflammatory; Anticoagulants; Award; base; Biological Assay; Biomechanics; Blood coagulation; Cell Culture Techniques; Cell physiology; Cell Survival; Cells; Cessation of life; chemokine; Chronic; Clinical; Clinical Research; clinical translation; clinically relevant; Coagulation Process; Competence; Complication; cytokine; Cytolysis; Data; Deep Vein Thrombosis; Dehydration; Development; Disease; effective therapy; Embolism; Experimental Animal Model; Experimental Models; experimental study; Fibrin; Fibrin split products; Fibrinolysis; Flow Cytometry; Generations; Genetic; Goals; Health; Hospitalization; Human; Immune response; Immunohistochemistry; Immunosuppressive Agents; improved; in vivo; Incidence; Inflammation; Inflammatory; inhibitor/antagonist; Injury; insight; Knowledge; Lead; Leg; Leg Ulcer; Limb structure; macrophage; Malignant Neoplasms; Mediating; Medical center; Messenger RNA; Methods; Military Personnel; Molecular; Molecular Analysis; Morbidity - disease rate; mortality; mouse model; Mus; neutrophil; Neutrophilic Infiltrate; novel; Obesity; Obstruction; Operative Surgical Procedures; outcome forecast; Pain; Paralysed; Pathogenesis; Pathway interactions; Patients; Peptide Hydrolases; Peptides; Phenotype; Plasmin; Plasminogen; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Play; Population; Postphlebitic Syndrome; Pre-Clinical Model; premature; prevent; Process; programs; Property; Protein Analysis; Pulmonary Embolism; recruit; Recurrence; Regulation; repaired; Research; Resolution; Risk; Risk Factors; Role; Serine Proteinase Inhibitors; Serpins; Signal Pathway; Signal Transduction; Skin; Skin Ulcer; Source; Swelling; System; Testing; Therapeutic; thrombolysis; Thrombus; Time; TLR4 gene; Tobacco use; Trauma; Travel; United States; Urokinase; urokinase inhibitor; Veins; Venous; Venous Thrombosis; Veterans; ","Proteolytic Pathways in Venous Thrombus Resolution","001921","HEMA","Hematology ","","","07","","","",""
"9815416","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002324","","RFA-BX-16-001","5I01BX002324-07","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PALO ALTO","UNITED STATES","","18","046017455","US","481014","VETERANS ADMIN PALO ALTO HEALTH CARE SYS","CA","943041207","The major focus of our work is to use understand the cellular and molecular mechanisms that lead to fibrosis and adiposis of muscle (or muscle fibroadipogenic degeneration (MFD)) in the setting on injury, diseases, and aging. MFD reduces muscle strength and increase muscle stiffness. A population of mesenchymal stem cells, known as ?fibroadipogenic progenitors? (?FAPs?), exists within skeletal muscle. While FAPS may be important to support muscle regeneration, it has been suggested that these cells may be responsible for degenerative changes that occur when muscle regeneration is impaired. The goal of our studies is to understand what mechanisms control the fate and function of these FAPs and to determine the extent to which we can modulate the behavior of these cells in order to reduce the amount of fibrosis that develops in muscle, whether in injury, degenerative diseases, or aging. Our long-term goals are to develop therapies for enhancing muscle function in order to improve the health and quality of life of Veterans with muscle injuries and muscle dysfunction.","1878892; ","RANDO, THOMAS A.;","","10/01/2013","09/30/2021","Accounting; Activities of Daily Living; Adipocytes; Adopted; Age; age related; Age-Months; age-related muscle loss; aged; Aging; alpha Toxin; Automobile Driving; base; Bioinformatics; Biological Assay; Biology; Breeding; cell behavior; Cell Culture System; Cells; cohort; Coupled; Data; Degenerative Disorder; Diphtheria Toxin; Disease; Environment; experience; experimental study; Fibrosis; functional decline; Functional disorder; gain of function; Genes; Genetic; Goals; Health; Homeostasis; Impairment; improved; In Vitro; in vivo; Individual; Infiltration; injured; Injury; insight; Intramuscular; Investigation; Label; Lead; loss of function; Mediator of activation protein; Mesenchymal Stem Cells; Metabolic Diseases; MicroRNAs; Mission; Molecular; Mus; Muscle; muscle aging; Muscle Cells; muscle degeneration; Muscle Development; Muscle function; muscle regeneration; Muscle satellite cell; muscle stiffness; Natural regeneration; novel; offspring; Pathologic; Pathology; Pathway interactions; Phase; Platelet-Derived Growth Factor alpha Receptor; Population; Prevalence; prevent; Process; progenitor; Quality of life; recombinase-mediated cassette exchange; Recovery; reduced muscle strength; regenerative; Regulation; repaired; response to injury; Role; Skeletal Muscle; Skeletal muscle injury; stem cell biology; stem-like cell; study population; Tamoxifen; Testing; Therapeutic; therapy development; Tissues; tool; Transcript; transcriptome sequencing; Transplantation; Treatment Efficacy; Undifferentiated; Veterans; Work; ","Regulation of Muscle Fibrosis in Response to Injury and Aging","002324","CAMM","Cellular and Molecular Medicine ","","","07","","","",""
"9815427","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003453","","RFA-BX-17-002","5I01BX003453-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Trauma- and osteoporosis-induced fractures cause dramatic morbidity and mortality, which greatly impact the survival and quality of life of our veterans and impose steep emotional burdens on VA families and financial burden on the VA Health Systems. Current intermittent PTH therapy is suboptimal in healing bone factures and rehabilitating osteoporotic skeleton and produces adverse side effects. This new proposal aims to delineate molecular and cellular mechanisms underlying the osteoanabolic actions and the adverse effects of PTH, establish a new paradigm for the anabolic actions of intermittent PTH, and devise a more robust regimen to promote fracture healing and restore osteoporotic skeleton to reduce future risks of facture. Successful completion of this highly translational and clinically relevant project will generate an essential blueprint for designs of clinical trials using 2 already available pharmaceutics (PTH1-34 and calcimimetics) for treating bone fracture and osteoporosis concurrently in large populations of our VA patients.","6061231; ","CHANG, WENHAN ;","","10/01/2017","09/30/2021","Acute; Adult; Adverse effects; Aging; Agonist; Anabolism; angiogenesis; Applications Grants; base; bone; Bone callus; Bone Diseases; bone healing; bone mass; bone strength; Bone structure; Calcium-Sensing Receptors; Cartilage; Cell Death; Cells; Chondrocytes; Chondrogenesis; Clinical; Clinical Trials; Clinical Trials Design; clinically relevant; Contralateral; cortical bone; Data; Debridement; Development; Disease; Dose; Emotional; Environmental Hazards; Exposure to; extracellular; Family; FDA approved; Financial Hardship; Fracture; Fracture Healing; Future; healing; Health system; Hematoma; Histologic; Hormone secretion; hormone therapy; Hormones; Hypercalcemia; Hyperparathyroidism; improved; Individual; Inflammatory Response; Injections; Injury; Invaded; Mechanics; Mediating; Military Personnel; Minerals; Molecular; Morbidity - disease rate; mortality; Mus; novel; Osteoblasts; osteochondral tissue; Osteoclasts; Osteogenesis; osteogenic; Osteoporosis; Osteoporotic; osteoporotic bone; osteosarcoma; Parathyroid gland; Patients; Pharmaceutical Preparations; Pharmacy (field); Population; Pre-Clinical Model; prevent; Procedures; Production; progenitor; Psyche structure; PTH gene; Quality of life; Receptor Signaling; Recovery of Function; recruit; Regimen; Rehabilitation therapy; repaired; Reporting; response; Risk; Shapes; side effect; Signal Transduction; Site; skeletal; Skeleton; Speed; Stress; Structure; substantia spongiosa; synergism; Testing; Tibial Fractures; Time; transdifferentiation; Trauma; Traumatic injury; Treatment Efficacy; Veterans; ","A novel treatment for bone fracture repair","003453","ENDB","Endocrinology B ","","","03","","","",""
"9815433","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003262","","RFA-BX-16-001","5I01BX003262-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Individualized therapeutics for K-RAS mutant lung adenocarcinoma are nonexistent. Recently, we have identi?ed key roles for NOTCH UPREGULATION and SOX2 DOWNREGULATION in cells that are trans- formed by mutant K-RAS. K-RAS induced lung cancer is very relevant to the Veteran population because it is most correlated with smoking. Inhibitors of these pathways may be very bene?cial for Veterans. 1","9698679; ","ONAITIS, MARK ;","","10/01/2017","09/30/2021","Adenocarcinoma; Alleles; Biological Assay; Cancer Patient; Cell Communication; cell transformation; Cells; Characteristics; chemosensitizing agent; Clinical; Complex; Data; Development; Differentiation Therapy; Distal; efficacy testing; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Event; experimental study; EZH2 gene; Genes; Genetic; genetic approach; Genetic Recombination; Genetic Transcription; Glare; Goals; Heterogeneity; high throughput screening; Human; Human Cell Line; In Vitro; in vitro Assay; in vivo; individualized medicine; inhibitor/antagonist; Interruption; Knock-out; KRAS2 gene; Lead; Lesion; Light; LoxP-flanked allele; Lung; Lung Adenocarcinoma; Maintenance; Malignant neoplasm of lung; mimetics; mortality; Mus; mutant; Mutation; Non-Small-Cell Lung Carcinoma; notch protein; novel; novel strategies; novel therapeutic intervention; novel therapeutics; Oncogenes; Pathway interactions; Patients; Peripheral; Phenotype; Population; progenitor; Prognostic Factor; programs; Proliferating; Publishing; respiratory; response; Signal Pathway; Smoking; Stem cells; Structure of respiratory epithelium; Testing; Therapeutic; therapeutic target; TP53 gene; transcription factor; Transgenic Mice; treatment strategy; tumor; tumor initiation; Tumor Suppression; tumor xenograft; Type II Epithelial Receptor Cell; Up-Regulation; Validation; Veterans; ","Proximal Differentiation Therapy for K-Ras-Induced Lung Adenocarcinoma","003262","ONCB","Oncology B ","","","03","","","",""
"9815455","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003212","","RFA-BX-16-002","5I01BX003212-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN FRANCISCO","UNITED STATES","","12","078763885","US","481016","VETERANS AFFAIRS MED CTR SAN FRANCISCO","CA","941211545","Metabolic bone disease and skeletal fractures are major clinical problems in the veteran population. New therapies are needed to treat male and female veterans with osteoporosis and with non-osteoporotic fractures. The goal of these studies is to identify fundamental mechanisms for regulating the formation of bone forming and fat storing cells in the bone marrow. These studies will directly test the significance of these mechanisms for the development of osteoporosis, the progression of diet-induced obesity- associated metabolic disorders, and the repair of skeletal fractures. With the identification of these mechanisms, new avenues for the development of novel treatments for skeletal and metabolic disorders will follow.","1888176; ","NISSENSON, ROBERT ;","","10/01/2016","09/30/2020","Adipocytes; adipokines; adiponectin; Adipose tissue; Affect; Aging; Anorexia Nervosa; Anti-inflammatory; Attention; B-Lymphocytes; base; biological adaptation to stress; Biomechanics; bone; Bone Density; Bone Diseases; bone loss; Bone Marrow; Bone Marrow Cells; bone mass; Bone Regeneration; Cell Differentiation process; Cell physiology; Cells; Clinical; cost; delta protein; deprivation; Development; Diet; Environment; Equilibrium; ERG gene; Fatty acid glycerol esters; Female; Fracture; Fracture Healing; G Protein Gene; G-Protein Signaling Pathway; gain of function; Genetic Models; Goals; GTP-Binding Proteins; Health; High Fat Diet; Homeostasis; Human; improved; in vivo; insight; insulin sensitizing drugs; Light; lipid biosynthesis; male; Marrow; Mediating; Mesenchymal Differentiation; Mesenchymal Stem Cells; Metabolic; Metabolic Bone Diseases; Metabolic Diseases; Metabolic stress; Metabolism; Modeling; Molecular; Mus; novel; novel therapeutics; Obesity; osteoblast differentiation; Osteoblasts; Osteogenesis; osteogenic; Osteoporosis; osteoprogenitor cell; Oxidative Stress; Participant; Pertussis Toxin; Phenotype; Physiological; Play; Population; preference; Production; Reactive Oxygen Species; repaired; Role; Signal Transduction; Signaling Protein; skeletal; skeletal disorder; Stromal Cells; Structure; substantia spongiosa; Testing; therapy development; Veterans; WNT Signaling Pathway; ","Inhibitory G protein (Gi) signaling in bone disease and repair","003212","ENDB","Endocrinology B ","","","04","","","",""
"9815457","IK6","VA","5","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX003615","","RFA-BX-16-022","5IK6BX003615-04","","OTHERS","2020","Veterans Affairs","","ANN ARBOR","UNITED STATES","","12","096318480","US","481045","VETERANS HEALTH ADMINISTRATION","MI","481052303","Fungal and bacterial infections are a major source of morbidity and mortality in veterans with compromised immune systems as a result of AIDS, substance abuse, or stemming from treatment of malignancy, auto-immune disease, or organ transplantation. Persistent microbial lung infections in immunocompetent or mildly immunocompromised veterans results in chronic lung disease. Antibiotic therapies are often inadequate; thus enhanced knowledge of pulmonary host defense is essential for the development of new therapies or vaccine strategies to treat these patient populations. Strategies designed to diminish or enhance immunomodulatory pathways hold the greatest promise for enhancing therapies of persistent infections, malignancy, allergies, autoimmune disease, or organ transplants. Dr. Olszewski?s studies identify and test the role of immunological pathways during infections. His studies also dissect interactions of microbial factors with host defenses to identify mechanisms of their evasion and potential therapeutic targets within microbes. These studies are an essential step in design of new therapies strategies against infections.","1952716; ","OLSZEWSKI, MICHAL A;","","10/01/2016","09/30/2021","Acquired Immunodeficiency Syndrome; Animal Model; Antibiotic Therapy; Antifungal Agents; antimicrobial; Autoimmune Diseases; Award; Bacterial Infections; career; chronic infection; Chronic lung disease; Clinical Data; Communicable Diseases; Communities; Cryptococcus; Cryptococcus neoformans; design; Development; Disease; Drug resistance; Drug toxicity; Effectiveness; Exhibits; experience; Exposure to; Foundations; fungus; Goals; Host Defense; Host Defense Mechanism; Hypersensitivity; Immune Evasion; Immune response; Immune system; Immunocompetent; Immunocompromised Host; Immunologics; Immunologist; Immunology; immunomodulatory therapies; immunoregulation; Infection; Inflammatory; interest; Knowledge; Learning; Location; Lung; Lung infections; Malignant Neoplasms; Microbe; microbial; microorganism interaction; Military Personnel; Morbidity - disease rate; mortality; Mycoses; novel; novel therapeutics; novel vaccines; Organ Transplantation; Organism; pathogen; Pathway interactions; patient population; Physicians; pre-clinical; Research; Resistance development; Risk; Role; Scientist; Services; Signal Transduction; Source; stem; Substance abuse problem; Testing; Therapeutic; therapeutic target; Training; translational study; Veterans; Work; ","BLR&D Research Career Scientist Award Application","003615","RCSR","Research Career Scientist ","","","04","","","",""
"9815921","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003850","","RFA-BX-17-001","5I01BX003850-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CINCINNATI","UNITED STATES","","01","084758143; 827658092","US","481069","CINCINNATI VA MEDICAL CENTER RESEARCH","OH","452202213","Rheumatoid Arthritis (RA) is a devastating systemic disease, which without intensive medical attention and often very expensive therapeutics, often results in joint destruction and virtually complete physical incapacity. We have developed new results that suggest Epstein-Barr virus (EBV) may be a possible cause of RA and have shown that this virus can infect cells from the joints and alter the expression of RA genes. We identified a protein from the virus that potentially alters gene expression in ways that encourage the development of RA and propose to explore its actions in cells, which if our suspicions are established, will provide the basis to change how RA is diagnosed, treated, and, perhaps, even prevented.","2089538; ","KAUFMAN, KENNETH M;","","10/01/2018","09/30/2022","Alleles; Arthritis; Autoantibodies; Award; B-Lymphocytes; base; CD8-Positive T-Lymphocytes; Cell Line; Cells; ChIP-seq; Chronic; Complex; cyclic citrullinated peptide; Data; Degenerative polyarthritis; Dependence; design; Development; Diagnosis; differential expression; disorder control; DNA; DNA Binding; Elements; Environment; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Etiology; experience; experimental study; Fibroblast virus; Fibroblasts; Foundations; Frequencies; Future; Gene Expression; Gene Expression Profile; Gene Expression Regulation; gene product; Genes; Genetic; Genetic Risk; Human; Human Herpesvirus 4; Immune; Immune response; Individual; infected B cell; Infection; Inflammatory; Inflammatory Response; insight; Investigation; joint destruction; Joints; Learning; Lytic Virus; medical attention; microbiome; Modeling; Nature; novel therapeutic intervention; Nuclear Antigens; Pathogenesis; Pathology; Patients; Peptides; Population; prevent; Prevention strategy; Probability; Process; programs; Property; Publications; PubMed; Quantitative Trait Loci; Regulator Genes; Relative Risks; response; Rheumatoid Arthritis; Risk; risk variant; single-cell RNA sequencing; Site; small molecule libraries; Specificity; Synovial Membrane; Systemic disease; T cell response; Testing; Therapeutic; Tissues; transcription factor; transcriptome sequencing; Variant; Viral; Viral Antigens; viral DNA; Viral Proteins; virtual; Virus; Virus Diseases; Work; ","DNA Binding of Human and Viral Transcription Factors is Associated with Rheumatoid Arthritis Risk Loci","003850","IMMA","Immunology A ","","","02","","","",""
"9872088","Y01","HL","","N","","","","","Y01HL120020","","","AHL12002001-1-0-1","NHLBI:142000\","INTERAGENCY AGREEMENTS","2019","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","","","","","","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","; ",",  ;","","","","base; Biological Assay; Blood; Blood donor; Blood Tests; Cameroon; co-infection; Detection; Diagnostic tests; Genetic Variation; Genotype; HIV; Human Herpesvirus 8; Nanotechnology; new technology; Nucleic Acid Amplification Tests; Performance; Plasma; Prevalence; Recombinants; Safety; Serological; urban area; vaccine development; Variant; Viral; Virus; ","HIV Genetic Diversity and Blood Safety - Cameroon","","","","","","","","","142000",""
"9978667","I01","VA","5","N","10/22/2019","10/01/2019","09/30/2020","999","I01BX001356","","RFA-BX-14-001","5I01BX001356-09","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BOSTON","UNITED STATES","","07","034432265","US","481041","VA BOSTON HEALTH CARE SYSTEM","MA","021304817","PUBLIC HEALTH RELEVANCE:         The broad objective of this research program is to understand the cellular mechanisms underlying alterations in sleep spindles in schizophrenia (Sz), a disease which is highly prevalent in the VA and which consumes ~40 % of the VA mental healthcare budget. Recent studies in Sz patients have provided consistent evidence for abnormalities in the number and intrinsic frequency of sleep spindles, a waxing and waning electroencephalographic (EEG) pattern, together with associated cognitive problems. However the cellular mechanisms underlying spindles are poorly understood, thereby hindering development of pharmacologic treatments. Our research will test a model of Sz abnormalities related to the downregulation of the activity of a particular type of thalamic reticular neuron found to be abnormal elsewhere in Sz, the GABA parvalbumin- containing neuron. We will also investigate a PV neuron GABA receptor likely responsible for the pharmacologic improvement of spindle and cognitive deficits in Sz to aid pharmacologic development.","9147977; ","BROWN, RITCHIE EDWARD;","","10/01/2011","09/30/2020","Action Potentials; adeno-associated viral vector; Anatomy; Appearance; Auditory; Autopsy; basal forebrain; base; Basic Science; Bilateral; Budgets; Calcium-Binding Proteins; Cell Nucleus; Cells; Chlorides; Cognition; Cognitive; Cognitive deficits; cognitive performance; Consumption; Data; Development; Disease; Down-Regulation; Eszopiclone; experimental study; Exposure to; Fiber; Fire - disasters; Frequencies; GABA Receptor; gain of function; gamma-Aminobutyric Acid; Healthcare; Human; hypnotic; Impairment; improved; In Vitro; in vivo; Injections; Lasers; Lead; Light; Link; loss of function; Mediating; Mediation; memory consolidation; Memory impairment; memory recall; Methods; Modeling; mouse model; Mus; Neurobiology; Neurons; non rapid eye movement; novel; novel therapeutics; object recognition; Optics; optogenetics; Parvalbumins; Pathway interactions; Patients; Pattern; Performance; Pharmacological Treatment; Pharmacology; Physiologic pulse; programs; Proton Pump; Psyche structure; public health relevance; receptor; Research; response; Role; Schizophrenia; Sensory; sensory input; Sleep; sleep spindle; Techniques; Testing; Thalamic structure; Time; transmission process; Veterans; Viral; voltage clamp; Waxes; Work; zolpidem; ","Sleep Spindles: Role of Thalamic Reticular Nucleus and Parvalbumin GABA Neurons","001356","NURR","Neurobiology R ","","","09","","","",""
"10001425","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002495","","RFA-BX-13-001","5I01BX002495-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","PITTSBURGH","UNITED STATES","","18","033127569","US","481080","VETERANS HEALTH ADMINISTRATION","PA","152401003","PUBLIC HEALTH RELEVANCE:         Stroke is a devastating clinical condition for which an effective neuroprotective treatment is currently unavailable. We have identified HSP27 as a promising therapeutic agent for the treatment of ischemic stroke. The objective of this proposal is to investigate whether and how HSP27 protects against the loss of blood brain barrier integrity after ischemic/reperfusion brain injury in both young and aged rodents. This information will be valuable for future development of new therapeutic strategies for the treatment of stroke and, possibly, other neurological disorders.","2084976; ","CHEN, JUN ;","","10/01/2014","09/30/2020","actin depolymerizing factor; Actins; Adult; aged; Apoptotic; base; Blood - brain barrier anatomy; Blood Preservation; Brain; brain endothelial cell; Brain Injuries; brain parenchyma; cell type; Cells; Cellular Structures; Central Nervous System Diseases; Cerebral Ischemia; Cerebrum; Clinical; Cytoskeletal Modeling; Cytoskeleton; Data; deprivation; Development; disability; Disabled Persons; Disease; Edema; Endothelial Cells; Endothelium; Event; Exhibits; Extravasation; Future; Gelatinase A; Gene Targeting; Genes; Glucose; Heat shock proteins; Hemorrhage; HSPB1 gene; Immune; Impairment; improved; improved outcome; In Vitro; in vivo; Infarction; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; innovation; intravenous administration; intravenous injection; Ischemia; Ischemic Stroke; knock-down; Lentivirus Vector; Liquid substance; Mediating; Medical; member; Middle Cerebral Artery Occlusion; Military Personnel; MMP2 gene; Modeling; Molecular Chaperones; Mus; nervous system disorder; Nervous System Physiology; Neurologic; Neurological outcome; neuroprotection; NF-kappa B; novel; novel therapeutic intervention; overexpression; Oxygen; Pathogenesis; Pathologic; Patients; Permeability; Plasma Proteins; polymerization; post stroke; prevent; Production; Protective Agents; protective effect; Protein Family; Proteins; public health relevance; Quality of life; Reperfusion Injury; Reperfusion Therapy; Rodent; Role; Signaling Molecule; Stroke; stroke survivor; stroke therapy; stroke victims; Structure; Testing; Therapeutic; Therapeutic Agents; Thrombolytic Therapy; Time; Transfection; Transgenic Mice; Transgenic Organisms; United States; Veterans; white matter injury; young adult; ","Heat shock proteins and neuroprotection in cerebral ischemia","002495","NURC","Neurobiology C ","","","05","","","",""
"10044415","I01","VA","5","N","10/23/2019","07/01/2018","06/30/2019","999","I01HX001284","","RFA-HX-12-019","5I01HX001284-05","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NASHVILLE","UNITED STATES","","05","156385783","US","481084","VETERANS HEALTH ADMINISTRATION","TN","372122637","The VA is facing an increasing burden of chronic liver disease due to substance use disorders, chronic viral hepatitis, and  increasing numbers of patients with non-alcoholic steatohepatitis , and is the largest single provider of hepatitis C  care  in the US.  Complications of cirrhosis frequently require hospital admission, and each year, cirrhosis is responsible for  >150,000 hospitalizations at a cost of approximately $4 billion. Among patients who survive the initial hospitalization,  nearly half are rehospitalized within 1 year.  The use of clinical decision support (CDSS) in clinical dashboards has great  potential for facilitating more robust risk stratification and tailored clinical care interventions as well as providing a  platform for effective use of NLP technologies in clinical care.  This project seeks to highlight the development and  evaluation of a framework to manage structured and unstructured information flow, development of predictive  modeling and risk stratification, and presentation of clinical information through a population and patient visualization  tools within the compelling use case of advanced liver disease care to directly impact and improve Veteran care.","9585547; 9346188 (contact); ","HO, SAMUEL BENJAMIN; MATHENY, MICHAEL E. (contact);","","07/01/2014","06/30/2019","Acute; Admission activity; Adoption; Adult; Advanced Development; Alcohol consumption; Ambulatory Care; Area; base; Calibration; care delivery; Caring; case finding; Characteristics; Chronic Disease; chronic liver disease; Chronic Obstructive Airway Disease; Chronic viral hepatitis; Cirrhosis; Clinic; Clinical; clinical care; clinical decision support; Clinical effectiveness; clinical practice; clinically relevant; cohort; Complex; Congestive Heart Failure; Continuity of Patient Care; cost; dashboard; Data; data visualization; design; Development; Discrimination; Disease; Economics; electronic data; Electronic Health Record; End stage renal failure; Engineering; Evaluation; evidence base; Face; Family; Fibrosis; General Population; Goals; health information technology; Healthcare; Hepatitis C; high risk; hospital readmission; Hospitalization; Human; implementation science; improved; informatics infrastructure; informatics tool; Information Management; inpatient service; Inpatients; Intervention; Interview; Liver Cirrhosis; liver development; Liver diseases; Logistic Regressions; Measurement; Medical; Medicare; Methods; Modeling; Modernization; modifiable risk; Modification; mortality; mortality risk; Natural Language Processing; Natural Language Processing pipeline; next generation; nonalcoholic steatohepatitis; Outcome; Outpatients; Paper; Patient Care; patient population; Patient risk; Patients; Pattern; Performance; Population; predictive modeling; Prevalence; Process; prototype; Provider; Quality Indicator; Quality of Care; Recommendation; Recording of previous events; Retrospective cohort; Risk; Risk Factors; Risk stratification; simulation; social; Specific qualifier value; Structure; Substance Use Disorder; System; Techniques; Technology; Time; tool; treatment as usual; usability; user centered design; Validation; Veterans; Visualization software; Work; ","Automated Surveillance and Intervention among Patients with Liver Cirrhosis","001284","HSR3","HSR-3 Methods and Modeling for Research, Informatics, and Surveillance ","","","05","","","",""
"10045918","IK2","VA","5","N","10/23/2019","10/01/2018","09/30/2019","999","IK2HX001775","","RFA-HX-16-011","5IK2HX001775-03","","OTHERS","2020","Veterans Affairs","","PROVIDENCE","UNITED STATES","","02","182465745","US","10018779","PROVIDENCE VA  MEDICAL CENTER","RI","029084734","The proposed research is relevant to VHA's mission to ?honor America's Veterans by providing exceptional healthcare that improves their health and well-being.? Patient-directed cash benefit programs, like Veteran- Directed Home and Community Based Services and VBA's Aid and Attendance and Housebound benefits, employ personalized strategies that consider Veterans' unique conditions, needs, and circumstances. These cash benefits are expected to affect Veterans' use of, unmet need for, and satisfaction with supportive services. As a result, they may also affect their health and functioning. However, there remains no evidence on reasons for their variability in utilization or their effectiveness in meeting Veteran's long-term care (LTC) needs and controlling escalating spending on long-term services and supports (LTSS). Therefore, it is important that we understand the utilization and effectiveness of these programs, as well as Veterans' experiences with these programs, to both inform the delivery of LTSS within VA and improve Veterans' health and well-being.","10381499; ","THOMAS, KALI ST. MARIE;","","10/01/2016","09/30/2021","Accident and Emergency department; Admission activity; Affect; Age; aged; Americas; Award; base; Behavioral Model; Budgets; care delivery; care systems; career; Caring; Case Manager; Characteristics; Communities; community based service; comparative effectiveness; Consumption; cost; cost effective; Data; Data Collection; disability; Disabled Persons; Effectiveness; effectiveness research; Enrollment; Ensure; Evaluation Research; evidence base; experience; Financial compensation; Foundations; Future; Goals; Health; health administration; Health Care Costs; health care service utilization; Healthcare; Home environment; Home Health Aides; Hospitalization; Human Resources; implementation research; Improve Access; improved; innovation; insight; Intervention; Interview; K-Series Research Career Programs; Knowledge; Leadership; Long-Term Care; Medical; Medical center; meetings; Methodology; Methods; Mission; Monitor; Nursing Homes; Outcome; Participant; Patient Care; Patients; Pensions; Perception; person centered; Personal Satisfaction; personalized strategies; Policies; Population; Positioning Attribute; Primary Health Care; Process; Program Effectiveness; Program Evaluation; programs; Qualitative Research; Quality of life; Research; Research Methodology; residence; Role; satisfaction; Scientist; Self Care; service delivery; service programs; Services; skills; Structure; Suggestion; System; Training; United States Department of Veterans Affairs; Variant; Veterans; Vulnerable Populations; Waiting Lists; ","Evaluating Cash Benefit Programs for Veterans' Long Term Care","001775","CDA0","HSR&D Career Development Award  ","","","03","","","",""
"9721161","I01","VA","1","N","10/21/2019","05/01/2019","04/30/2020","999","I01RX002789","","RFA-RX-18-013","1I01RX002789-01A2","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","CLEVELAND","UNITED STATES","","14","093016124","US","481118","LOUIS STOKES CLEVELAND VA MEDICAL CENTER","OH","441413204","Advanced peripheral neuroprostheses will require high-density (HD) interconnections that are enabled by our proposed research effort. These systems will contribute to the distribution of new clinical interventions for Veterans based on effective life enhancing technology to the veteran population, in whom lower extremity paralysis or weakness is common. Specifically, motor nerve dysfunction due to stroke or incomplete spinal cord injury can create debilitating conditions that affect a Veteran's ability to walk and engage in physical activity. HD stimulation and in-line connector technology for walking assistance has the potential to enhance functional independence by providing patients with a means to maneuver. Combat- related amputations have been steady, too, and new prosthetic technology for amputees can restore natural sensations in amputated limbs; our connectors help miniaturize such systems.","9215685; ","SHIRE, DOUGLAS B.;","","05/01/2019","04/30/2021","Address; Affect; Amendment; Amputation; Amputees; Animal Model; Animals; base; biomaterial compatibility; Chronic; Clinical; Clinical Research; Clinical Trials; combat; Custom; Data; density; design; Development; Devices; devices for disabled persons; Documentation; electric impedance; Electrodes; Encapsulated; Enhancement Technology; Equipment Malfunction; Esthesia; experimental study; Exposure to; Family Felidae; FPS-FES Oncogene; Functional disorder; functional electrical stimulation; functional independence; Funding; Future; gait rehabilitation; Generations; Goals; Health; Hip region structure; Histologic; Implant; implantable device; implantation; improved; In Vitro; in vitro testing; interoperability; Intervention; Investigation; Knee; Laboratories; Life; limb amputation; Location; Mechanics; Medical Device; Methods; miniaturize; Mission; Modeling; Monitor; Motor; Muscle; nanoscale; Nerve; neural prosthesis; Neurologic Deficit; Neurological rehabilitation; neuroprosthesis; next generation; Operative Surgical Procedures; Paraplegia; Partner in relationship; Pathologic; Patient Care; Patients; Peripheral; Peripheral Nerves; Peripheral Nervous System Diseases; Phantom Limb; Physical activity; Population; post stroke; Postoperative Period; Preclinical Testing; Process; process optimization; programs; Prosthesis; Publishing; recruit; Rehabilitation therapy; relating to nervous system; Research; Research Personnel; Running; Safety; Saline; Science; seal; Sensory; sensory feedback; sensory system; silicon carbide; Site; Solid; Spinal cord injury; Sterilization; Stroke; System; Techniques; Technology; Test Result; Testing; Tissues; Update; Upper Extremity; Validation; Variant; Vendor; Veterans; Walking; Work; ","Optimization & Pre-clinical Testing of Implantable, In-Line High Density 32-Channel Connector","002789","RRD5","Rehabilitation Engineering & Prosthetics/Orthotics  ","","A2","01","","","",""
"9814684","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003272","","RFA-BX-16-001","5I01BX003272-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BIRMINGHAM","UNITED STATES","","07","082140880","US","481003","BIRMINGHAM VA MEDICAL CENTER","AL","352331927","Solid organ transplantation has revolutionized the care of individuals with organ failure. The VA National Transplant Program, established in 1962, provides transplants, including bone marrow, heart, liver, pancreas, lung and kidneys, to Veterans at 12 VA Medical Centers across the continental US. These individuals all require immunosuppressive medications for their lifetime to avoid rejection of the transplanted organ. Nearly all of these recipients are placed on drugs known as calcineurin inhibitors (CNI). While these drugs are potent immunosuppressives, they are highly toxic to the kidney and lead to kidney failure over time. Current clinical management has included dose reduction or avoidance, but sadly, such strategies have negligible success. This application proposes to study a new mechanism for CNI-caused kidney injury. The study uses both laboratory and mouse models to find a novel and effective therapy to minimize the nephrotoxic effects of these critical immunosuppressive agents and to improve patient outcomes after transplant.","1899136; ","MANNON, ROSLYN B;","","10/01/2016","09/30/2020","5'-AMP-activated protein kinase; Acute Renal Failure with Renal Papillary Necrosis; adenylate kinase; Adverse effects; Affect; Allografting; Apoptosis; Atrophic; Autophagocytosis; Biochemical; Bioenergetics; Biogenesis; Bone Marrow; Calcineurin inhibitor; Caring; cell injury; Cellular Metabolic Process; Chronic; Clinical; clinical application; Clinical Management; clinically relevant; Complement; Coupled; Creatinine; Cyclic AMP-Dependent Protein Kinases; Cyclosporine; Data; Diabetic Nephropathy; Dose; Duct (organ) structure; effective therapy; Epithelial; Epithelial Cells; Epithelium; exhaustion; Exposure to; Failure; Fibrosis; Functional disorder; Goals; Graft Survival; Half-Life; Health; Heart; Histologic; HMGB1 gene; Homeostasis; Human; Immune; Immunosuppression; Immunosuppressive Agents; improved; In Vitro; in vivo; Individual; Inflammation; Inflammation Mediators; Inflammatory; inflammatory marker; Injury; injury and repair; insight; interstitial; Intervention; Kidney; kidney cell; Kidney Diseases; kidney dysfunction; Kidney Failure; kidney preservation; Kidney Transplantation; knock-down; Laboratories; Laboratory mice; Lead; Link; Liver; Lung; macrophage; Mediating; Mediator of activation protein; Medical center; Metabolic; Metformin; Mitochondria; mitochondrial dysfunction; mouse model; mRNA Expression; Mus; NADPH Oxidase; nephrotoxicity; novel; novel therapeutic intervention; novel therapeutics; Organ; Organ failure; organ transplant rejection; Organ Transplantation; Outcome; Oxidation-Reduction; Oxidative Stress; Pancreas; paracrine; Paracrine Communication; Pathway interactions; Patient-Focused Outcomes; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Polycystic Kidney Diseases; Population; preservation; prevent; Production; programs; Property; Protein Kinase; Reactive Oxygen Species; Renal function; RNA Interference; Role; Series; Serum; Solid; success; Testing; Therapeutic; Therapeutic Agents; Therapeutic immunosuppression; Time; Tissues; Toxic effect; Translations; Transplant Recipients; Transplantation; Tubular formation; United States; Veterans; Whole Organism; ","AMP Kinase Activation in Calcineurin Inhibitor Nephrotoxicity","003272","NEPH","Nephrology ","","","04","","","",""
"9815312","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX003198","","RFA-BX-15-001","5I01BX003198-04","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","OKLAHOMA CITY","UNITED STATES","","05","020719316","US","481072","OKLAHOMA CITY VA MEDICAL CENTER","OK","731045007","PUBLIC HEALTH RELEVANCE        Every year 150,000 Americans are diagnosed with colorectal cancer (CRC), the second leading cause of cancer-related mortality in the US and is a major health problem among the Veterans. Approximately 4,000 veterans being diagnosed with the CRC each year within VA facilities. NSAIDs are promising CRC preventive agents. However, Veterans, as a group on NSAIDs therapy, are at high risk for both gastrointestinal and cardiovascular NSAID-induced complications. Therefore, to reduce the risk of CRC in Veterans, potential early intervention with novel and safer drugs for prevention are warranted. In this project we propose to develop a novel drug with efficacious and safe profile for the high-risk CRC patients. Toward this end, we have discovered a novel drug with promising CRC preventive effects. Further development of this drug in this project will significantly improve clinical and translational research towards prevention and treatment of VA-CRC patients.","1900139; ","RAO, CHINTHALAPALLY V.;","","04/01/2016","09/30/2020","Adoptive Transfer; Alcohol consumption; alcohol exposure; American; Animal Model; Antineoplastic Agents; ApcMin/+ mice; Arachidonate 5-Lipoxygenase; Arachidonic Acids; Azoxymethane; base; Biological Assay; Biological Markers; Bone Marrow; Cancer Etiology; cardiovascular risk factor; Cardiovascular system; Chemopreventive Agent; chemotherapy; Clinical Research; Clinical Trials; colon cancer patients; colon cancer risk; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; colorectal cancer prevention; colorectal cancer risk; colorectal cancer treatment; cyclooxygenase 1; cyclooxygenase 2; Data; Development; Diagnosis; Diet Habits; Dinoprostone; Dose; drug development; Drug resistance; Early Intervention; efficacy study; Eicosanoids; Enzyme Kinetics; Epidemiology; Epoprostenol; Event; Excision; experimental study; Female; gastrointestinal; Gene Expression Profiling; Health; high risk; Histopathologic Grade; improved; in vivo; Inbred F344 Rats; Individual; Inflammation; Inflammation Mediators; inhibitor/antagonist; Intestinal Neoplasms; ITGAM gene; Laboratories; Leukotrienes; LOX gene; macrophage; male; Modeling; Modification; mortality; mouse model; mouse PGE synthase 1; Mus; Non-Steroidal Anti-Inflammatory Agents; novel; novel therapeutics; Operative Surgical Procedures; Outcomes Research; Patients; Pharmaceutical Preparations; Pharmacotherapy; Population; Prevention; Preventive; Property; Prostaglandin-Endoperoxide Synthase; PTGS2 gene; public health relevance; Relapse; relapse risk; Research; response; Risk; Role; Safety; Series; Serum; side effect; Smoking; Survival Rate; targeted agent; Testing; Therapeutic; Tissues; Toxic effect; transcriptome; Translational Research; tumor; tumor progression; tumorigenic; Veterans; Xenograft procedure; ","Targeting mPGES-1/5-LOX for Prevention of CRC in High-Risk Veterans","003198","ONCC","Oncology C ","","","04","","","",""
"9815316","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004044","","RFA-BX-17-004","5I01BX004044-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SEATTLE","UNITED STATES","","09","020232971","US","481094","VA PUGET SOUND HEALTHCARE SYSTEM","WA","981081532","The National Academy of Sciences Institute on Medicine has found an association between service in the U.S. military and ALS. American Veterans as a whole are at about 60% greater risk than U.S. civilians. Pathological TDP-43 occurs in the majority of ALS cases resulting in severe disability and premature death in American Veterans. Furthermore, ALS has been designated a service connected condition by the Department of Veterans Affairs. The burden placed on America Veterans afflicted with ALS is incalculable as this life ending neurologic condition causes rapid and severe disability ultimately leading to death. Here we propose to devise and test neuroprotective strategies targeting genes causing and contributing to disease using simple models of ALS. This in turn may ultimately lead to potential therapeutic interventions for the benefit of all those affected by ALS including Veterans.","10420415; ","LIACHKO, NICOLE FARON;","","10/01/2018","09/30/2022","Affect; American; Americas; Amyotrophic Lateral Sclerosis; Binding; Brain; Caenorhabditis elegans; Calcineurin; calcineurin phosphatase; Calmodulin; Cell Culture Techniques; Cessation of life; Code; Data; Degenerative Disorder; design; Diagnostic; disability; Disease; disease phenotype; Disease Progression; effective therapy; Event; experimental study; FDA approved; gain of function mutation; Genes; Genetic; genome editing; genomic tools; Health; illness length; Innate Immune Response; Institutes; Lead; Life; Mammalian Cell; Medicine; Military Personnel; Modeling; Molecular; motor neuron degeneration; Motor Neurons; Muscular Atrophy; mutant; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neuroglia; Neurologic; Neuronal Dysfunction; Neurons; neurotoxic; neurotoxicity; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; Paralysed; Pathologic; Pathology; Pathway interactions; Peptide aptamers; Pharmaceutical Preparations; Phosphorylation; Post-Translational Protein Processing; pre-clinical; premature; Process; Protein Dephosphorylation; protein TDP-43; Proteins; Recovery; Regulation; response; Risk; RNA Interference; Role; Serine; Services; Signal Transduction; Spinal Cord; Stress; targeted treatment; Testing; therapeutic development; Therapeutic Intervention; therapeutic target; translational approach; United States National Academy of Sciences; Validation; Vertebrates; Veterans; Work; ","Investigating calcineurin regulation of pathological TDP-43 phosphorylation in ALS","004044","NURE","Neurobiology E ","","","02","","","",""
"9815428","IK2","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","IK2BX003518","","RFA-BX-17-008","5IK2BX003518-03","","OTHERS","2020","Veterans Affairs","","LONG BEACH","UNITED STATES","","47","625399951","US","481011","VETERANS HEALTH ADMINISTRATION","CA","908225201","Inflammatory conditions in the GI tract like Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis) represent a burden to our Veterans and our healthcare system because these are chronic conditions which dramatically affect quality of life and are expensive to treat. In general, these diseases arise when the immune system malfunctions and cannot distinguish between infectious agents and normal tissue. Approximately 1 in 2,000 people in the US will develop disease in any given year and studies show more than a 2-fold increase in the number of Veterans with these problems since 1998. The direct medical cost is estimated to be over $18,000 per person per year and is likely to keep increasing. In this proposal, we will be studying three potential treatments as well as the underlying immune process that leads to disease. Our hope is that with a better understanding of the disease, we will be able to develop more effective and safer treatments.","9047123; ","SKUPSKY, JONATHAN ;","","10/01/2017","09/30/2022","Adoptive Transfer; Affect; Agonist; analog; Autoimmune Process; Biotin; Calcium; Calcium Channel; Calcium Signaling; cell motility; Cells; channel blockers; Characteristics; Chronic; Clinic; Clinical; clinical implementation; Clinical Trials; Colitis; Colon; Crohn's disease; Data; Dendritic cell activation; Dendritic Cells; design; Development; Disease; Disease remission; effective therapy; effector T cell; Equilibrium; Eragrostis; Event; experimental study; Frequencies; functional status; Gastrointestinal tract structure; Goals; Healthcare Systems; Image; Imagery; Immune; Immune response; Immune system; immunological synapse; immunological synapse formation; Immunologics; immunoregulation; In Vitro; in vivo; Infectious Agent; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestines; Link; Lymph Node Sinus; lymph nodes; Lymphatic Endothelium; Lymphocyte; Mediating; Medical Care Costs; Mentors; Mesentery; Methods; migration; Modeling; Molecular; mouse model; Mucosal Immunity; Mus; Normal tissue morphology; novel; novel therapeutics; Pathogenesis; Pathogenicity; Pathway interactions; Persons; Pharmaceutical Preparations; Pharmacology; Phenotype; Physiology; Play; Preparation; prevent; Process; Proliferating; Publishing; Quality of life; real time monitoring; real-time images; Regulatory T-Lymphocyte; Reporter; Reporting; Resolution; Role; side effect; Signal Transduction; Sphingosine-1-Phosphate Receptor; Supplementation; Symptoms; System; T-Lymphocyte; Techniques; Therapeutic; Therapeutic Agents; Time; Tissues; tool; trafficking; Translations; Travel; Treatment Cost; two photon microscopy; Ulcerative Colitis; Veterans; Work; ","Functional Immunoimaging in the GI Tract","003518","GAST","Gastroenterology ","","","03","","","",""
"9815446","I01","VA","5","N","10/23/2019","10/01/2019","09/30/2020","999","I01BX002741","","RFA-BX-16-001","5I01BX002741-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","EAST ORANGE","UNITED STATES","","10","087286308","US","10018809","VA NEW JERSEY HEALTH CARE SYSTEM","NJ","070181023","PROJECT NARRATIVE Management of liver failure after chemical exposure or behavioral disruptions and prevention and treatment of liver tumors represent a major challenge for the Veterans Administration. These diseases commonly cause hospitalization and mortality in American Veterans. The current study, once successfully completed, will shed mechanistic light into understanding a fundamental aspect of liver regeneration, initiation, and provide scientific strategy to promote liver growth with liver failure and liver resection by enhancing this pathway or to prevent liver tumor development by blocking this pathway.","8250103; ","GUO, GRACE L;","","10/01/2017","09/30/2020","American; Amino Acid Sequence; base; Behavioral; Bile Acid Biosynthesis Pathway; Bile Acids; Blood; Blood Circulation; Cell Proliferation; Chemical Exposure; Data; Development; Disease; Endocrine; Excision; FGF19 gene; Fibroblast Growth Factor; fibroblast growth factor receptor 4; Future; gain of function; Goals; Growth; Health; hepatic necrosis; Hepatocyte; Hospitalization; Human; ileum; improved; In Vitro; in vivo; injury prevention; innovation; insight; Intestines; Knockout Mice; Ligands; Light; Liver; liver cell proliferation; Liver diseases; Liver Failure; liver function; liver injury; Liver neoplasms; Liver Regeneration; MAP Kinase Gene; MAPK8 gene; Mediating; Medical; Mitogens; Molecular; mortality; Mus; Nature; novel; novel strategies; Operative Surgical Procedures; Partial Hepatectomy; Pathway interactions; Pharmaceutical Preparations; Population; prevent; Prevention; Process; Proteins; Publishing; receptor; Regulatory Pathway; Role; Signal Pathway; STAT3 gene; Stimulation of Cell Proliferation; Tertiary Protein Structure; Testing; Transgenic Mice; United States Department of Veterans Affairs; Veterans; ","Role of FGF15 in liver regeneration","002741","GAST","Gastroenterology ","","","03","","","",""
"9815462","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX003934","","RFA-BX-17-001","5I01BX003934-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","SAN DIEGO","UNITED STATES","","52","073358855","US","481156","VA SAN DIEGO HEALTHCARE SYSTEM","CA","921610002","Insulin resistance is the underlying cause for the development of diabetes, obesity and cardiovascular diseases, collectively known as metabolic disorders. Obesity and diabetes, aggravated by hypertension, are global public health challenges. The stress factors associated with the U.S. veteran population contribute to these diseases. These calamities all arise from the development of insulin resistance in peripheral tissues. Insulin resistance, in turn, is a byproduct of a complex network of problems that include genetic, environmental, and lifestyle related factors. Our challenge is to restore insulin sensitivity by manipulating the major molecular contributors to these diseases. The applicant proposes that an endogenous peptide, catestatin may serve as an appropriate therapeutic agent by performing dual jobs of (i) minimizing metabolic disorders and (ii) reducing hypertension and associated disorders.","1860487; ","MAHATA, SUSHIL K;","","10/01/2017","09/30/2021","Adipose tissue; Affect; AKT Signaling Pathway; AMP Deaminase; Anti-inflammatory; Antiinflammatory Effect; Attenuated; base; blood glucose regulation; Body Weight decreased; Cardiovascular Diseases; Cells; CHGA gene; Chromogranin A; Chronic; combat; Complex; CREB1 gene; cytokine; Data; Deposition; Development; Diabetes Mellitus; diabetic; Diet; Disease; Dose; effective therapy; Endogenous Factors; Fasting; Fatty acid glycerol esters; Fatty Liver; FOXO1A gene; Gene Expression Profiling; gene product; Genes; Genetic; Gluconeogenesis; glucose 1 phosphate; glucose metabolism; glucose production; glucose tolerance; Glucose-6-Phosphate; Glycogen; Hepatic; Hepatocyte; Hypertension; improved; Infiltration; Inflammation; Inflammatory Response; Insulin; Insulin Resistance; insulin sensitivity; insulin signaling; insulin tolerance; Investigation; knock-down; Knockout Mice; Lead; Life Style; lipid biosynthesis; Lipids; Liver; macrophage; MAPK8 gene; Mediating; Metabolic Diseases; Modeling; Molecular; monocyte; mouse model; Mus; Non-Insulin-Dependent Diabetes Mellitus; novel; Obese Mice; Obesity; Occupations; Outcome; Pathway interactions; Peptides; Peripheral; Permeability; Pharmacology; Phosphorylation; Phosphotransferases; Play; Population; Production; Proteins; Proto-Oncogene Proteins c-akt; Public Health; recruit; Regulation; Signal Transduction; Stimulus; STK11 gene; Stress; Testing; Therapeutic Agents; Tissues; Transmission Electron Microscopy; Veterans; ","Catestatin improves glucose homeostasis and insulin sensitivity in diet-induced obese mice","003934","ENDA","Endocriniology A ","","","03","","","",""
"9815465","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004047","","RFA-BX-17-001","5I01BX004047-03","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","BIRMINGHAM","UNITED STATES","","07","082140880","US","481003","BIRMINGHAM VA MEDICAL CENTER","AL","352331927","Acute kidney injury (AKI) is a common and serious complication in hospitalized Veterans. Patients with AKI are at significant risk for the subsequent development of chronic kidney disease (CKD). This proposal will focus on the lymphatic system, which is crucial for maintaining fluid balance, transporting lipids, and aiding in immune function, within the kidney particularly during AKI and the AKI to CKD transition. Successful completion of the aims of this project will help better understand the pathogenesis of AKI during both injury and repair and could provide new avenues targeting the lymphatic system for therapeutic interventions in AKI.","1867506; ","AGARWAL, ANUPAM ;","","10/01/2017","09/30/2021","Acute Renal Failure with Renal Papillary Necrosis; Affect; Bilateral; Blocking Antibodies; CD44 Antigens; Cell Surface Receptors; Cells; Chronic Kidney Failure; Clinical; Clinical Trials; Complication; Critical Illness; Data; Data Reporting; density; design; Development; Dialysis procedure; Disease; Endothelium; Epithelial Cells; Fibrosis; Fluid Balance; Galectin 3; Goals; Health; Hospitalization; immune function; Impairment; Inflammation; Inflammatory; Injury; injury and repair; Injury to Kidney; Intensive Care Units; Ischemia; Kidney; kidney fibrosis; Knockout Mice; Knowledge; Link; lipid transport; Liquid substance; Lymphangiogenesis; Lymphatic; Lymphatic Endothelial Cells; Lymphatic System; Lymphatic vessel; Magnetic Resonance Imaging; Mediating; medical complication; Modality; Modeling; Morbidity - disease rate; mortality; Mus; Myelogenous; Myeloid Cells; Myocardial Ischemia; Operative Surgical Procedures; Organ; Participant; Pathogenesis; Pathologic; Patients; Phase; Proteins; receptor; Recombinant Vascular Endothelial Growth Factor; recombinase-mediated cassette exchange; Recovery; Renal Replacement Therapy; Reperfusion Injury; Reperfusion Therapy; Resolution; Risk; Role; Serum; Severities; Structure; Supportive care; Testing; Therapeutic Intervention; tissue repair; Transgenic Mice; Tubular formation; Up-Regulation; Ureteral obstruction; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor D; Vascular Endothelial Growth Factors; Veterans; ","Lymphangiogenesis in the pathogenesis of Acute Kidney Injury","004047","NEPH","Nephrology ","","","03","","","",""
"9871460","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004855","","RFA-BX-19-022","1IK6BX004855-01","","OTHERS","2020","Veterans Affairs","","CHICAGO","UNITED STATES","","07","010299204","US","481026","JESSE BROWN VA MEDICAL CENTER","IL","606123728","Pancreatic and breast cancer are common ailments in our veterans. These cancers are lethal and therefore, it is important to understand the detail underlying mechanisms of the disease to identify new drug targets. The pancreatic cancer is the most difficult to treat and the patient survive for few months, after detection. We have identified new targets and seen that inhibitors of a protein (i.e. MLK3/MLKs) can inhibit pancreatic cancer tumor growth in animal models. The other projects in the laboratory deals with breast cancer. With increasing numbers of female veterans, the incidence of breast cancer and developing resistance to current therapies are quite frequent. Our investigation shows that inhibitors of MLK3/MLKs can also be used to treat Triple Negative Breast Cancer, a deadly sub-type that lacks drug target. Similarly, we have observed that the activator of MLK3/MLKs can serve as a therapeutic for ER+ and HER2+ breast cancer, and can overcome therapy resistance. We are highly encouraged with our research and hope to take our discoveries to clinical trials in future.","1973958; ","RANA, AJAY NMN;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award Application","004855","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9871720","IK6","VA","1","N","10/25/2019","10/01/2019","09/30/2020","999","IK6BX004853","","RFA-BX-19-022","1IK6BX004853-01","","OTHERS","2020","Veterans Affairs","","OMAHA","UNITED STATES","","02","844360367","US","481160","OMAHA VA  MEDICAL CENTER","NE","681051850","This proposal addresses a significant healthcare issue that affects Veterans, military personnel, and their families disproportionately to the general population. Here, work from Dr. Casey?s research program is focused on the investigation of alcoholic and non-alcoholic fatty liver disease (AFLD and NAFLD, respectively). Both AFLD and NAFLD represent a major clinical challenge in the VA, since there are no current, effective therapeutic interventions, and progression of liver injury can result in liver transplantation, or death. Work from our lab aims to provide a better understanding of AFLD and NAFLD progression and to increase opportunities for the development of novel treatment paradigms for the management of chronic liver diseases.","1860813; ","CASEY, CAROL A;","","10/01/2019","09/30/2024","","BLR&D Research Career Scientist Award","004853","ZRD1","Special Emphasis Panel ","","","01","","","",""
"9924242","I01","VA","5","N","10/24/2019","10/01/2019","09/30/2020","999","I01BX004299","","RFA-BX-18-001","5I01BX004299-02","","Non-SBIR/STTR RPGs","2020","Veterans Affairs","","NASHVILLE","UNITED STATES","","05","156385783","US","481084","VETERANS HEALTH ADMINISTRATION","TN","372122637","PROJECT NARRATIVE Allergic diseases are a major burden to public health in the United States. This is of particular relevance to Veterans of the U.S. Military in whom the prevalence of allergic rhinitis is approximately 30% and allergic asthma is approximately 6%. Thus, allergic diseases are an important cause of morbidity among Veterans. Very recently, Group 2 innate lymphoid cells (ILC2) were discovered in both in mice and in people. ILC2 produces large quantities of specific proteins called cytokines that are important in the development of allergic inflammation. Our preliminary data suggests that a medication that is currently being used for the treatment of patients with pulmonary hypertension, prostaglandin (PG)I2, may be an important inhibitor of the inflammatory function of ILC2. Our proposal will define the mechanisms by which PGI2 blocks the initial phases of allergic airway inflammation and may be a novel and effective treatment for asthma.","1903042; ","PEEBLES, RAY STOKES;","","10/01/2018","09/30/2022","adaptive immunity; Agonist; airborne allergen; airway epithelium; Allergens; Allergic; allergic airway inflammation; Allergic Disease; Allergic inflammation; Allergic rhinitis; Alternaria; analog; Antiinflammatory Effect; Arachidonic Acids; Asthma; asthma exacerbation; Award; Binding; Cell physiology; Cell Proliferation; cell type; Cells; Cellular Structures; Chronic Disease; clinically relevant; clinically significant; constriction; cytokine; Data; Development; Disease; effective therapy; Eosinophilia; Epithelial; Epithelial Cells; Epithelium; Epoprostenol; experimental study; Extrinsic asthma; FDA approved; Funding; Fungal Antigens; Gene Expression; Genes; genome wide association study; Glucocorticoids; Human; Hypersensitivity skin testing; hypertension control; IL2RA gene; Immediate hypersensitivity; Immune response; In Vitro; in vivo; Inflammatory; Inflammatory Response; Inhalation; inhibitor/antagonist; Interleukin-13; Interleukin-2; Interleukin-5; Interleukin-9; intraperitoneal; IRF4 gene; Lead; Link; Lung; Lung diseases; Lymphoid Cell; Mediating; Metabolic; Metabolism; Metaplasia; microbial; Military Personnel; Modeling; Molecular; Morbidity - disease rate; Mucous body substance; Mus; Natural Immunity; novel; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Prevalence; Production; programs; Prostaglandin-Endoperoxide Synthase; Proteins; Public Health; Pulmonary Hypertension; Reaction; reagent testing; receptor; receptor expression; Regulation; Reporting; Research; Role; Signal Transduction; Smooth Muscle; STAT1 gene; Susceptibility Gene; Testing; Th2 Cells; Therapeutic Uses; United States; United States National Institutes of Health; Veterans; ","PGI2 inhibition of pulmonary innate allergic immune responses","004299","ZRD1","Special Emphasis Panel ","","","02","","","",""
"9963029","Y01","HL","","N","","","","","Y01HL160050","","","AHL16005001-1-0-1","NHLBI:239052\","INTERAGENCY AGREEMENTS","2019","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","","","","","","NATIONAL HEART, LUNG, AND BLOOD INSTITUTE","","","","; ",",  ;","","","","Evaluation of Risk Factors; Funding; Hepatitis B; Hepatitis C; HIV; infection risk; Monitor; Risk Factors; Time trend; Transfusion; Vascular blood supply; ","Temporal Trends in Transfusion ?Transmissible Infections Risks and Monitoring of Donor Risk Factors in the US Blood Supply Project (TTIMS)-Non-AIDS","","","","","","","","","239052",""
"10045516","IK2","VA","5","N","10/22/2019","10/01/2017","09/30/2018","999","IK2HX001775","","RFA-HX-16-011","5IK2HX001775-02","","OTHERS","2020","Veterans Affairs","","PROVIDENCE","UNITED STATES","","02","182465745","US","10018779","PROVIDENCE VA  MEDICAL CENTER","RI","029084734","The proposed research is relevant to VHA's mission to ?honor America's Veterans by providing exceptional healthcare that improves their health and well-being.? Patient-directed cash benefit programs, like Veteran- Directed Home and Community Based Services and VBA's Aid and Attendance and Housebound benefits, employ personalized strategies that consider Veterans' unique conditions, needs, and circumstances. These cash benefits are expected to affect Veterans' use of, unmet need for, and satisfaction with supportive services. As a result, they may also affect their health and functioning. However, there remains no evidence on reasons for their variability in utilization or their effectiveness in meeting Veteran's long-term care (LTC) needs and controlling escalating spending on long-term services and supports (LTSS). Therefore, it is important that we understand the utilization and effectiveness of these programs, as well as Veterans' experiences with these programs, to both inform the delivery of LTSS within VA and improve Veterans' health and well-being.","10381499; ","THOMAS, KALI ST. MARIE;","","10/01/2016","09/30/2021","Accident and Emergency department; Admission activity; Affect; Age; aged; Americas; Award; base; Behavioral Model; Budgets; care delivery; care systems; career; Caring; Case Manager; Characteristics; Communities; community based service; comparative effectiveness; Consumption; cost; cost effective; Data; Data Collection; disability; Disabled Persons; Effectiveness; effectiveness research; Enrollment; Ensure; Evaluation Research; evidence base; experience; Financial compensation; Foundations; Future; Goals; Health; health administration; Health Care Costs; health care service utilization; Healthcare; Home environment; Home Health Aides; Hospitalization; Human Resources; implementation research; Improve Access; improved; innovation; insight; Intervention; Interview; K-Series Research Career Programs; Knowledge; Leadership; Long-Term Care; Medical; Medical center; meetings; Methodology; Methods; Mission; Monitor; Nursing Homes; Outcome; Participant; Patient Care; Patients; Pensions; Perception; person centered; Personal Satisfaction; personalized strategies; Policies; Population; Positioning Attribute; Primary Health Care; Process; Program Effectiveness; Program Evaluation; programs; Qualitative Research; Quality of life; Research; Research Methodology; residence; Role; satisfaction; Scientist; Self Care; service delivery; service programs; Services; skills; Structure; Suggestion; System; Training; United States Department of Veterans Affairs; Variant; Veterans; Vulnerable Populations; Waiting Lists; ","Evaluating Cash Benefit Programs for Veterans' Long Term Care","001775","CDA0","HSR&D Career Development Award  ","","","02","","","",""