PHR: Stroke is a leading cause of death and disability in Veterans, with approximately 15,000 suffering from a stroke annually. Studying the molecular mechanisms of post-stroke brain damage and testing new drugs will help to minimize neurological dysfunction in the affected. The present project is to evaluate the functional significance of a microRNA called miR-21 in protecting post-stroke brain and providing better functional outcome. We will further test if miR-21 prevents stroke-induced gut dysbiosis and the resulting inflammation which might be a mechanism of its neuroprotective efficacy. The long-term goal is to develop miR-21 as a therapy to minimize post-stroke brain damage and improve outcomes for Veterans who have undergone a stroke.

PI_NAMEs: VEMUGANTI, RAGHU  (contact)

PROJECT_TERMS: Adult;Affect;Age;Body Weight decreased;Brain;Brain Injuries;Brain Ischemia;Cause of Death;Cerebral Ischemia;Chemistry;Cognitive;comorbidity;Curiosities;Data;Diabetes Mellitus;disability;dysbiosis;effective therapy;efficacious treatment;efficacy evaluation;Event;Family;Female;Functional disorder;functional outcomes;Genes;Goals;gut dysbiosis;gut inflammation;gut microbiome;Human Resources;improved;improved outcome;Industry;Infarction;Inflammation;Inflammatory;Intravenous;Ischemia;Ischemic Preconditioning;Lead;male;Mediating;MicroRNAs;Middle Cerebral Artery Occlusion;Mission;Molecular;mortality;Motor;motor function recovery;Mus;Neurologic Deficit;Neurologic Dysfunctions;neurological recovery;neuroprotection;neuropsychiatry;novel therapeutics;Outcome;Patient Care;Peripheral;post stroke;Pre-Clinical Model;preconditioning;prevent;Prevention;Proteins;Quality of life;Reagent;Recovery of Function;Reperfusion Therapy;Rodent;Services;sex;Societies;Stroke;stroke model;Stroke prevention;stroke therapy;Testing;Therapeutic;therapeutic development;therapeutic evaluation;Toxic effect;Treatment Efficacy;Untranslated RNA;Veterans;Work

PROJECT_TITLE: miR-21 induced neuroprotection after stroke


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: PITTSBURGH

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: PA

PHR: Despite aggressive therapy, Veterans with squamous cell carcinoma of the upper aerodigestive tract (UADT) including cancer of the head and neck have a dismal prognosis. Although we have identified novel targets to treat this disease, the improvements in outcomes have been relatively modest. We propose to study how these cancers develop from pre-cancerous lesions. If we can prevent or slow the progression to cancer, we may be able to treat these patients before they develop cancer. The calcium-activated chloride channel TMEM16A/ ANO1 is frequently overexpressed in these cancers and contributes to tumor cell growth. TMEM16A appears to promote carcinogenesis by driving cellular signaling. Interestingly, we find that TMEM16A is increased in pre-cancerous lesions. This proposal outlines studies that will elucidate the fundamental biology of TMEM16A and how it promotes carcinogenesis. We will address the unmet need by implicating TMEM16A as a potential therapeutic target for the treatment of Veterans with cancer of the UADT, and head & neck in particular.

PI_NAMEs: DUVVURI, UMAMAHESWAR  (contact)

PROJECT_TERMS: 11q13;Aerodigestive Tract;aggressive therapy;Alcohols;Animal Model;Automobile Driving;Bioinformatics;biological adaptation to stress;Biological Assay;Biological Markers;Biological Process;Biology;Calcium;cancer cell;cancer diagnosis;cancer invasiveness;cancer therapy;Carcinogen exposure;carcinogenesis;carcinogenicity;Carcinogens;Carcinoma;Caring;Cell Culture Techniques;cell growth;Cell Survival;cell transformation;Chloride Channels;Chlorides;Chromosomal Duplication;Cisplatin;Clinical Trials;Cytotoxic agent;Data;Development;Disease;Dysplasia;Enhancers;Epidermal Growth Factor Receptor;Epithelium;ERBB2 gene;ERBB3 gene;Esophagus;Event;Excision;experimental study;Exposure to;Family member;Funding;Gene Amplification;Gene Expression;Genes;Genetic;genetic manipulation;Genetic Transcription;Genomics;Goals;Growth;Head;Head and Neck Cancer;Head and neck structure;Histologic;Human;human tissue;improved;In Vitro;inhibitor;insight;Investigation;Investments;Ion Channel;keratinocyte;Knockout Mice;Larynx;Lesion;Leukoplakia;Malignant - descriptor;malignant mouth neoplasm;Malignant neoplasm of esophagus;Malignant neoplasm of lung;Malignant Neoplasms;MAP Kinase Gene;MAPK Signaling Pathway Pathway;MAPK3 gene;Mediating;Methods;Modeling;Molecular;mouse model;Mus;Neck Cancer;neoplastic;neoplastic cell;new therapeutic target;novel;Oncogenic;Operative Surgical Procedures;Oral cavity;oral tissue;Outcome;Oxidative Stress;Oxides;Pathway interactions;Patients;pharmacologic;Physiological;Play;Precancerous Conditions;premalignant;prevent;Process;Prognosis;progression risk;Proliferating;promoter;Proto-Oncogene Proteins c-akt;Reactive Oxygen Species;Resistance;Resources;Role;Runaway;Sampling;Services;Signal Pathway;Signal Transduction;Specimen;Squamous cell carcinoma;Testing;Therapeutic;therapeutic target;Tissues;Tobacco;tobacco exposure;transcription factor;Transcriptional Regulation;Translating;tumor;Tumor Promotion;tumorigenesis;Up-Regulation;Upper aerodigestive tract cancer;Veterans;Work

PROJECT_TITLE: Novel Targets to Treat Head & Neck Cancer in Veterans


ORG_CITY: INDIANAPOLIS

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: PROJECT NARRATIVE Diabetes mellitus is a disorder of glucose homeostasis that affects nearly one in four Veterans and is a leading cause of blindness, kidney failure, and cardiovascular disease. Female veterans are at high risk for the development of diabetes, and the number of females receiving care in the VA is growing, suggesting that increased expenditures will be needed to care for this population. Pancreatic β cell dysfunction plays a central role in the pathogenesis of diabetes, yet current therapies do little to improve β cell health. The goal of this proposal is to define how impaired store operated calcium entry interacts with estrogen signaling to cause β cell de-differentiation and to test how alterations in these pathways contribute to diabetes development. The translational impact of this work will be the identification of novel pathways that can be targeted clinically as a means of preserving β cell function, survival, and identity in diabetes.

PI_NAMEs: EVANS-MOLINA, CARMELLA  (contact)

PROJECT_TERMS: Affect;Agonist;Alpha Cell;Award;Beta Cell;Biological Models;Biosensor;Blindness;blood glucose regulation;Ca(2+)-Transporting ATPase;Calcium;Calcium Channel;Calcium Oscillations;Cardiovascular Diseases;Caring;cell dedifferentiation;Cell Differentiation process;Cell membrane;Cell Physiology;Cells;Clinical;Complex;Cyclic AMP;Data;Development;Diabetes Mellitus;diabetes pathogenesis;diet-induced obesity;directed differentiation;Disease;Dissociation;Endoplasmic Reticulum;endoplasmic reticulum stress;Equilibrium;Estradiol;Estrogens;Exhibits;Expenditure;experimental study;Extracellular Space;Failure;Female;Fluorescence Resonance Energy Transfer;Functional disorder;functional loss;Funding;Generations;Genetic;Genetic Transcription;Glucose;glucose tolerance;Goals;GPER gene;Health;Healthcare Systems;High Fat Diet;high risk;Homeostasis;Human;human induced pluripotent stem cells;human model;Hyperglycemia;Image;impaired glucose tolerance;Impairment;improved;in vivo;Individual;induced pluripotent stem cell;Inositol;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;Ion Channel;islet;Kidney Failure;Lead;Link;loss of function mutation;Maintenance;male;Mediating;Modeling;Molecular;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Organ Donor;Organelles;Ovariectomy;Overnutrition;Pancreas;Pathway interactions;personalized therapeutic;pharmacologic;Phenotype;Physiological;Play;Population;Postmenopause;Predisposition;Premenopause;preservation;Process;Production;programs;Pump;receptor;Receptor Activation;receptor expression;Receptor Signaling;receptor-mediated signaling;Regulation;Reporter;Research;response;reticulum cell;Rodent Model;Role;Ryanodine Receptor Calcium Release Channel;Second Messenger Systems;sensor;sexual dimorphism;Signal Transduction;STIM1 gene;Stress;Structure of beta Cell of islet;Testing;Translating;translational impact;tripolyphosphate;Veterans;Wild Type Mouse;Work

PROJECT_TITLE: Regulation of calcium homeostasis in the pancreatic beta cell


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

ORG_STATE: CA

PHR: Osteoporotic bone fractures cause dramatic morbidity and mortality that greatly impact the survival and quality of the life of our veterans along with steep socioeconomical burdens to their families and the VA Healthcare Systems. The current parathyroid hormone (PTH)-based therapies are suboptimal in rehabilitating osteoporotic skeletons due to its propensity to produce adverse side effects with higher doses. This new proposal aims to understand the molecular and cellular mechanisms underlying the skeletal actions and the adverse effects of the PTH therapy, establish the utility of a long-acting PTH analog (i.e., LAPTH) to enhance anabolic bone actions, and devise a novel regimen to build bone without unwanted side effects by concurrently targeting the PTH1R and CaSR receptors. Successful completion of this highly translational and clinically relevant project will generate an essential blueprint for designs of clinical trials using combined LAPTH and CaSR activators to more efficiently restore weakened bones in many VA patients afflicted with osteoporotic bone diseases of different etiologies.

PI_NAMEs: CHANG, WENHAN  (contact)

PROJECT_TERMS: Ablation;Acceleration;Address;Adverse effects;Affect;Aging;Anabolism;analog;Award;bone;Bone callus;Bone Diseases;bone fracture repair;bone health;bone loss;bone mass;Bone Regeneration;bone repair;Bone Resorption;Calcium-Sensing Receptors;Cartilage;Cells;Clinical;Clinical Management;Clinical Trials;Clinical Trials Design;clinically relevant;Collaborations;Combined Modality Therapy;common treatment;cortical bone;cost;Cyclic AMP;design;Development;Diagnosis;Disease;disease model;Dose;Early Diagnosis;Economic Burden;effective therapy;Endosomes;Ensure;Estrogen deficiency;Etiology;extracellular;Family;first-in-human;Fracture;fracture risk;fragility fracture;Funding;Genes;Goals;Growth;healing;Health;Healthcare Systems;high risk;Homeostasis;hormonal signals;hormone analog;hormone therapy;Hospitals;Hybrids;Hypercalcemia;Imaging technology;improved;in vitro Model;in vivo;Individual;Injectable;Injections;innovation;insight;Investigation;knock-down;knockout gene;live cell imaging;male;Mediating;mineralization;Minerals;Molecular;Morbidity - disease rate;mortality;Mus;Musculoskeletal Pain;novel;novel strategies;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;Osteoporosis;Osteoporosis prevention;Osteoporotic;osteoporotic bone;Outcome Measure;Ovariectomy;overexpression;parathyroid hormone-related protein;Patients;Peptides;Pharmaceutical Preparations;Pilot Projects;Population;positive allosteric modulator;Pre-Clinical Model;prevent;Prevention approach;Proliferating;PTH gene;Quality of life;receptor;Receptor Activation;Regimen;Rehabilitation therapy;Research;Research Personnel;research study;Role;side effect;Signal Pathway;Signal Transduction;skeletal;Skeleton;socioeconomics;substantia spongiosa;Technical Expertise;Testing;Therapeutic;therapy adherence;Time;tool;treatment effect;treatment strategy;Veterans;young adult

PROJECT_TITLE: BCCMA: Foundational Research to Act Upon and Resist Conditions Unfavorable to Bone (FRACTURE CURB): Combined long-acting PTH and calcimimetics actions on skeletal anabolism


FUNDING_MECHANISM: OTHERS

ORG_CITY: NASHVILLE

ORG_STATE: TN

PHR: C. difficile infection is the most common hospital-acquired infection in the United States. Recent epidemiological data show an increasing incidence of C. difficile infection in Veterans, particularly non-hospital, community- acquired disease. This alarming trend illustrates the need for more knowledge about this potentially deadly bacterial infection. A better fundamental understanding of how C. difficile toxins target the human colon, and how the human cells and molecules respond to damage, is required for identifying new therapeutic and preventive opportunities. This proposal addresses this need by defining the molecular actions responsible for C. difficile infection. This innovative proposal will advance the science of gastrointestinal microbiology, and ultimately, the results are expected to reveal novel targets for treatments to ease the suffering of our nation’s Veterans.

PI_NAMEs: MARKHAM, NICHOLAS O (contact)

PROJECT_TERMS: Address;Affect;Antibiotic Therapy;antibiotic-associated diarrhea;Antibodies;Bacterial Infections;base;beta catenin;cell behavior;Cell Death;Cell Death Induction;cell injury;cell killing;Cell Surface Receptors;cell type;Cells;Cessation of life;chronic infection;Clinical;Clostridium;Clostridium difficile;Colon;Colon Injury;colonic crypt;Communities;CSPG4 gene;Data;disabled;Disease;disorder prevention;Drug resistance;epidemiologic data;epidemiology study;Epidermal Growth Factor Receptor;Epithelial Cells;epithelial stem cell;Epithelium;ERBB2 gene;experimental study;Exposure to;Family;fecal transplantation;fluorophore;gastrointestinal;gastrointestinal epithelium;Genes;Genetic Transcription;Goals;Growth Factor Receptors;Healthcare Systems;Homeostasis;Hospitals;Human;Human Cell Line;human disease;Immunofluorescence Immunologic;In Situ;In Vitro;in vivo;Incidence;Infection;Infection Control;Inflammatory Response;injury and repair;innovation;knock-down;Knowledge;lentivirally transduced;Ligands;Link;Measures;Mediating;Mediator;member;Microbiology;Modeling;Molecular;mouse model;Mucous Membrane;Mus;mutant;nectin-3;neutralizing antibody;new therapeutic target;Nosocomial Infections;novel;novel therapeutics;Oncogenes;Oral;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phosphorylation;prevent;Preventive;programs;protein expression;receptor;receptor binding;receptor expression;Receptor Signaling;Recombinants;reconstitution;Rectal Administration;Recurrence;Reproduction spores;Resolution;response;Role;Science;self-renewal;Signal Pathway;Signal Transduction;small hairpin RNA;Small Interfering RNA;small molecule inhibitor;Specificity;Standardization;stem;stem cell function;stem cells;success;Targeted Toxins;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;three dimensional cell culture;Tissues;Toxin;Transgenic Mice;Translating;trend;Tyrosine Kinase Inhibitor;Tyrosine Phosphorylation;United States;Veterans;Virulence;Work

PROJECT_TITLE: Gastrointestinal cell type-specific signaling and C. difficile toxin pathogenesis


ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

ORG_STATE: NY

PHR: Major depressive disorder (MDD) is a neuropsychiatric illness with considerable morbidity, mortality (including suicide), and personal and societal cost. Available treatments are ineffective for a large subset of MDD patients, and even among patients who respond to treatment only a fraction show long-time remission. Thus, there is the strong need to use novel approaches to advance our understanding of the biological bases of MDD in order to develop more efficacious treatments, which is an overarching goal of this application.

PI_NAMEs: DRACHEVA, STELLA  (contact)

PROJECT_TERMS: Adult;Affect;Autopsy;base;Biochemical;Biological;Biological Assay;Blood;Brain;brain cell;candidate identification;candidate validation;case control;causal variant;Cell Differentiation process;Cell Nucleus;Cell Separation;cell type;Cells;Cessation of life;Chromosome Mapping;Chronic;cohort;Complex;cost;Data;Development;disability;Disease;Disease remission;disorder risk;efficacious treatment;Elements;Enhancers;Epigenetic Process;Etiology;Fluorescence;Freezing;Functional disorder;Gene Expression;Genes;Genetic;Genetic Predisposition to Disease;Genetic Risk;Genetic Transcription;Genome;genome wide association study;genome-wide;Genotype;Goals;Hospitalization;Human;Human Genome;human induced pluripotent stem cells;Immune;ineffective therapies;Libraries;Link;Major Depressive Disorder;Maps;Mental Depression;Mental disorders;Microglia;military veteran;Morbidity - disease rate;mortality;Myeloid Cells;Neurobiology;Neuronal Dysfunction;neuropsychiatry;novel;novel strategies;novel therapeutic intervention;Pathogenesis;Patients;Persons;Play;Population;Predisposition;Prefrontal Cortex;Prevalence;promoter;protective allele;Protocols documentation;Quality of life;Quantitative Trait Loci;recruit;Recurrence;Regulatory Element;Reporter;Risk;risk variant;Role;Signal Transduction;societal costs;Sorting;Specimen;suicidal risk;Suicide;Testing;Time;Tissues;transcription factor;transcriptome;transcriptome sequencing;treatment strategy;Untranslated RNA;Validation;Variant;Veterans;whole genome

PROJECT_TITLE: The role of microglia in major depressive disorder


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Inflammatory bowel disease (IBD) encompasses both ulcerative colitis and Crohn’s disease, which are multifactorial, chronic conditions that result in numerous perturbations in the GI mucosa. The incidence of IBD has been steadily increasing, with over 1 million Americans currently affected. The economic impact of IBD was roughly $31.6 billion in 2014. Importantly, IBD represents a disease with one of the highest hospitalization rates among veterans (>100,000 hospitalizations from 1975-2006), with psychosocial conditions (PTSD, depression, anxiety) contributing to IBD severity. In addition, IBD-associated cancer is on the rise in some veteran populations. Currently, less than 50% of IBD patients respond to the current biological therapies, thus, a better understanding of IBD pathogenesis and the development of more effective therapies could significantly impact the veteran population.

PI_NAMEs: CARTWRIGHT, IAN MICHAEL (contact)

PROJECT_TERMS: Acidity;Acidosis;Acids;Acute;Affect;American;Anxiety;Bacteria;Bicarbonates;Biological Assay;Biological Response Modifier Therapy;Buffers;career development;Cell Physiology;Cells;chemically induced colitis;Chemicals;Chronic;Colitis;Colonic inflammation;commensal bacteria;Crohn's disease;cytokine;Data;design;Development;Disease;Disease Outcome;economic impact;effective therapy;Epithelial Cells;Escherichia coli;Escherichia coli K12;experience;Exposure to;extracellular;Family;Funding;gastrointestinal;Gastrointestinal tract structure;Gene Expression Regulation;Generations;Genetic;genetic approach;genetic signature;Genetic Transcription;Germ-Free;Glycolysis;Goals;gut inflammation;Home;Hospitalization;hospitalization rates;host-microbe interactions;Hypochlorous Acid;Ileitis;Immune response;Immunology;improved;In Vitro;in vivo;Incidence;Indoles;Infiltration;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;inhibitor;intestinal epithelium;intestinal homeostasis;Intestines;Invaded;knock-down;Knowledge;Lactic acid;Malignant Neoplasms;member;Mental Depression;Mentorship;metabolomics;microbial;microbial host;microbiota;microbiota metabolites;migration;military veteran;Modeling;Modification;Molds;Monitor;mouse model;Mucositis;Mucous Membrane;murine colitis;Mus;neutrophil;novel;novel therapeutics;Pathogenesis;Pathology;Patients;Peroxidases;pH Homeostasis;pharmacologic;Phenotype;Post-Traumatic Stress Disorders;Production;psychosocial;Regulation;Reporting;Research Personnel;Resolution;response;Role;Severity of illness;Signal Transduction;Site;SLC26A3 gene;Source;Surface;symposium;Testing;Time;Tissues;Training;transcriptome sequencing;Ulcerative Colitis;Veterans;Work;wound healing

PROJECT_TITLE: Control of Inflammatory Acidity in Mucosal Inflammation


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: There are over 2.2 million women Veterans and 32% are enrolled to receive VA health care. Female Veterans of childbearing age are seeking care at VA facilities in record numbers. Frequent reproductive health diagnoses in VA include menstrual disorders, endometriosis and infertility, menopausal disorders, osteoporosis and ovarian cancers; conditions which rely on adequate control of steroid hormone production. This program of research will explore the role of recently discovered molecular pathways that control cell and tissue homeostasis in ovarian development, endocrine function, and pathology. This research will lead to new understanding of steroid secretion, fertility, and ultimately woman’s health. New knowledge that informs approaches to control ovarian function can translate into approaches that improve not only reproductive health, but overall health and longevity.

PI_NAMEs: DAVIS, JOHN S (contact)

PROJECT_TERMS: Acute;Address;Adult;Affect;Age;age related;age related changes;aged;Aging;Amenorrhea;Automobile Driving;Award;Basic Science;Biological;Bone Density;bone loss;cancer cell;cancer initiation;Carbohydrates;Carcinoma;cardiovascular health;care seeking;career;Cattle;Cell Proliferation;Cells;Centers for Disease Control and Prevention (U.S.);child bearing;cholesterol trafficking;Clinical Endocrinology;Contraceptive methods;corpus luteum;cost;Cyclic AMP-Dependent Protein Kinases;Development;Diabetes Mellitus;Diagnosis;Disease;Endocrine;Endocrinology;endometriosis;Enrollment;Event;Exhibits;experience;Feedback;Female;Female infertility;Fertility;Follicle Stimulating Hormone Receptor;Genetic Transcription;glycosylation;Goals;gonad function;granulosa cell;granulosa cell tumor;Health;Healthcare;Healthcare Systems;Homeostasis;Hormones;Human;Human Follicle Stimulating Hormone;human old age (65+);Hyperinsulinism;Hypertension;improved;In Vitro;in vitro Model;in vivo;Infertility;Inflammation Mediators;insight;Journals;Knowledge;Laboratories;LATS2 gene;Life Cycle Stages;Lipids;Longevity;Luteal Cells;Maintenance;male;Malignant neoplasm of cervix uteri;Malignant neoplasm of ovary;Malignant Neoplasms;Mammary Neoplasms;Manuscripts;Mediating;member;men;Menopause;Menstruation Disturbances;mental function;Metabolic;Metabolic Diseases;Metabolic Pathway;migration;Military Personnel;military veteran;military women;Mitochondria;Molecular;Molecular Medicine;Molecular Weight;Neurophysiology - biologic function;Obesity;older women;Oncogenes;Oocytes;operation;Osteoporosis;Outcome;Ovarian;Ovarian Diseases;Ovarian Follicle;ovarian neoplasm;Ovary;Pathology;Pathway interactions;Patient-Centered Care;Pituitary Gland;pituitary gonadal axis;Polycystic Ovary Syndrome;Population;Pregnancy Maintenance;Premature Ovarian Failure;primary amenorrhea;Process;Production;Progesterone;programs;Proliferating;Proteomics;Publications;Publishing;Quality of life;receptor binding;Reporting;Reproduction;reproductive;Reproductive Health;Reproductive History;Reproductive system;Research;response;Rodent;Role;Science;Scientist;senescent cell;Serous;Services;Shapes;Signal Pathway;Signal Transduction;Steroid biosynthesis;steroid hormone;Steroids;theca cell;Time;Tissues;transcriptomics;Translating;tumor progression;United States;United States Department of Agriculture;United States National Institutes of Health;Uterine Neoplasms;Variant;Veterans;Woman;Women's Health;Work;young woman

PROJECT_TITLE: BLRD Research Career Scientist Award Application


PHR: Musculoskeletal disease affects millions of veterans and can result from service-related injuries as well as inflammatory disorders such as rheumatoid arthritis (RA) and postmenopausal osteoporosis. Factors produced by cells in the bone marrow play a causal role in driving bone loss (thereby increasing the risk of fracture) in these disorders, but the identify of these factors and how their production is orchestrated remain unclear. If we knew more about these factors, it would be possible to develop therapeutics that neutralize their activity and prevent bone loss. In the present study, we will test the hypothesis that a specific factor, progranulin, is an orchestrator of bone loss in RA and in estrogen deficiency-induced bone loss and is thus a potential therapeutic target. We will also investigate the mechanism by which progranulin negatively affects bone mass. Successful completion of these studies will increase our knowledge of the control of bone mass and will reveal new opportunities for treatments to prevent fractures.

PI_NAMEs: NISSENSON, ROBERT  (contact)

PROJECT_TERMS: Adult;Adult women;Affect;Age-Related Bone Loss;Aging;Amyloid;Anabolism;Automobile Driving;beta catenin;bone;Bone Diseases;bone erosion;Bone Formation Inhibition;bone loss;Bone Marrow;Bone Marrow Transplantation;bone mass;Bone Resorption;Bone Resorption Stimulation;bone turnover;Cell Lineage;Cells;Coupled;Cyclic AMP;cytokine;Defect;Deficiency Diseases;Disease;Estrogen deficiency;Female;Fracture;fracture risk;Galectin 3;Gene Deletion;Gene Expression;Genes;Genetic;Genetic Suppression;GTP-Binding Proteins;In Vitro;in vivo;Inflammation;Inflammatory;Injury;Innate Immune Response;Innate Immune System;interest;Joints;K/BxN model;Knockout Mice;Knowledge;Link;Macrophage;Maintenance;Mediating;Menopause;Modeling;mouse model;Mus;Musculoskeletal Diseases;Natural Immunity;new therapeutic target;novel;Osteoblasts;osteoclastogenesis;Osteoclasts;Osteocytes;Osteogenesis;osteogenic;Osteoporosis;Ovariectomy;Pathogenesis;Pathology;Pathway interactions;Patients;PGRN gene;Phenotype;Play;Population;Postmenopausal Osteoporosis;prevent;Production;progenitor;repaired;Reporting;response;Rheumatoid Arthritis;Role;Serum;Services;Signal Pathway;Signal Transduction;Signaling Protein;skeletal;Skeletal Development;Skeleton;Testing;Therapeutic;therapeutic target;TNF gene;Transplantation;Veterans;WNT Signaling Pathway

PROJECT_TITLE: Control of Bone Mass by Progranulin


ORG_CITY: AUGUSTA

ORG_NAME: CHARLIE NORWOOD VA MEDICAL CENTER

ORG_STATE: GA

PHR: In the United States, over 300,000 cases of acute kidney injury (AKI) are diagnosed each year with high mortality and staggering medical expense. Veterans are highly susceptible to AKI as shown by the Austin Automation Center Patient Files. AKI is also a common complication among military casualties in battle-fields. Moreover, even if the AKI patients have survived the acute injury, maladaptive kidney repair after AKI may result in chronic kidney disease (CKD) that contributes significantly to cardiovascular disease and mortality in aging patients including veterans. In the general population, 15-20% of AKI cases progress to CKD within 24 months; however, AKI-CKD transition in veterans is markedly higher and faster, reaching 31.8% in 12 months (Heung et al. Am J Kidney Dis 2016, 67:742-52). By elucidating stress granules in AKI and post-AKI kidney repair, this application may lead to new strategies for the prevention and treatment of this devastating disease, contributing significantly to the improvement of veterans’ health.

PI_NAMEs: DONG, ZHENG  (contact)

PROJECT_TERMS: Ablation;Acute;Acute Renal Failure with Renal Papillary Necrosis;Aging;aging population;Area;Automation;Binding;Binding Proteins;biological adaptation to stress;Cardiovascular Diseases;Cell Death;cell injury;Cell Survival;Cells;Cellular Stress;Chronic;Chronic Kidney Failure;Complication;Cytoplasmic Structures;Development;Diagnosis;Disease;effective therapy;Eukaryotic Cell;field study;G3BP1 gene;General Population;Goals;Health;improved;Injury;injury and repair;Injury to Kidney;insight;Ischemia;Kidney;kidney cell;Kidney Diseases;kidney repair;knockout gene;Knockout Mice;Mediating;Medical Care Costs;Military Personnel;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;new therapeutic target;novel;Pathogenesis;Pathologic;Pathology;patient oriented;Patients;Play;Positioning Attribute;Predisposition;Prevalence;Prevention strategy;Preventive;Proximal Kidney Tubules;Recovery;Regulation;renal damage;renal ischemia;Renal tubule structure;repaired;Reporting;Research;response to injury;RNA;RNA-Binding Proteins;Role;Severities;Site;Stress;stress granule;Testing;Therapeutic;Time;Tissues;Tubular formation;United States;Veterans;Work

PROJECT_TITLE: Ischemic Kidney Injury and Kidney Repair: Stress Granules


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: The ability of the HIV to become silent and establish persistent latent reservoir is the major obstacle to cure from this virus. Because of the these latent reservoirs, discontinuation of antiretroviral treatment results in virus rebound within weeks, requiring the chronic, lifelong adherence to therapy. The number of people living with HIV infection in the United States is increasing every year, with the number of HIV-infected Veterans enrolled in VA Healthcare System reaching nearly 31,000 in 2019. The Center for Disease Control and Prevention estimates that 14% of the infected individuals are not aware of their infection, which leads to late diagnosis and increase in the size of latent reservoir. To reduce the number of Veterans living with HIV infection and the costs associated with lifelong antiviral treatment as well as therapy- related toxicities, continued research aiming at purging HIV latent reservoir is required.

PI_NAMEs: BELIAKOVA-BETHELL, NADEJDA S (contact)

PROJECT_TERMS: Address;Adherence;Antibodies;antiretroviral therapy;Biological Assay;Biological Markers;Biological Specimen Banks;biomarker identification;biomarker selection;Blood;Blood specimen;CCR5 gene;CD4 Positive T Lymphocytes;Cell model;cell type;Cells;Centers for Disease Control and Prevention (U.S.);Chronic;Clinical;cohort;Collaborations;cost;Coupled;CXCR4 gene;Data;Development;Diagnosis;DNA;Enrollment;Experimental Designs;Flow Cytometry;Future;Gene Expression;Genes;Genetic Transcription;Gifts;Goals;Healthcare Systems;Heterogeneity;HIV;HIV Infections;Human body;Immunophenotyping;improved;In Vitro;in vivo;Individual;Infection;innovation;latent HIV reservoir;Length;Lymphoid Tissue;Membrane Proteins;Memory;Outcome;Pathway interactions;Patients;Persons;Phenotype;Population;protein biomarkers;Proteins;Proviruses;purge;Research;response;RNA;RNA Splicing;Sampling;single-cell RNA sequencing;Stimulus;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Tissue Sample;Tissues;Transcript;transcriptome sequencing;transcriptomics;Translating;Treatment-related toxicity;Tropism;United States;Variant;Veterans;Viral;viral rebound;Virus

PROJECT_TITLE: Cellular and viral determinants of the persistent HIV reservoir


ORG_CITY: ALBUQUERQUE

ORG_NAME: ALBUQUERQUE VA MEDICAL CENTER

ORG_STATE: NM

PHR: Diabetic retinopathy (DR), that affects more than 40% of diabetics, is a leading cause of vision loss in middle aged adults. Although a class of new drugs (anti-vascular endothelial growth factor, VEGF) is effective in treatment of vision loss in DR patients, only 40% of patients respond well to these drugs. Thus, there is an unmet demand for the development of new drugs other than anti-VEGF drugs. The proposed research will advance our understanding of the role of specific immune cells of the retina, namely microglia and their secretion of different molecular factors that cause leakage of blood vessels and results in blindness. The studies will utilize novel genomic technology to identify these molecular mediators secreted by these cells. Perhaps, this study will lead to the development of new improved therapeutics in diabetics who respond poorly to the standard anti-VEGF drugs.

PI_NAMEs: DAS, ARUP  (contact)

PROJECT_TERMS: Adult;Affect;aggressive therapy;Animal Model;Astrocytes;Atlases;Bed Occupancy;Blindness;Blood Vessels;Blood-Retinal Barrier;Candidate Disease Gene;candidate validation;Cell Culture Techniques;Cell Physiology;Cell secretion;Cells;Chemicals;Chronic;Communication;Complex;cost;cytokine;Data;design;Development;Diabetes Mellitus;diabetic;Diabetic Angiopathies;Diabetic mouse;Diabetic Retinopathy;Diagnosis;differential expression;Disease;Endothelial Cells;Endothelium;Epidemic;Event;Extravasation;Functional disorder;Gene Expression;Gene Expression Profile;Gene Targeting;General Population;Genes;genetic signature;Genomics;Goals;high throughput screening;hospital bed;human genomics;Immune;improved;In Vitro;in vivo;in vivo Model;Inflammation;Inflammation Mediators;Inflammatory;innovation;Insulin-Dependent Diabetes Mellitus;Intercellular Junctions;intravitreal injection;macular edema;Mediator;Microglia;middle age;Modeling;Molecular;Molecular Profiling;monocyte;Muller's cell;new therapeutic target;next generation;Non-Insulin-Dependent Diabetes Mellitus;novel;novel drug class;novel marker;novel therapeutics;off-patent;participant enrollment;Pathway interactions;Patient Selection;Patients;Pericytes;Permeability;Persons;Pharmaceutical Preparations;Pharmacy facility;Phenotype;Play;Population;Prevalence;prevent;Process;Public Health;Research;Research Proposals;Rest;Retina;retinal neuron;RNA;Role;Severity of illness;small molecule;small molecule libraries;Structure;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;Therapeutic Uses;trafficking;transcriptome;transcriptomic profiling;Vascular Endothelial Growth Factors;Vascular Permeabilities;Veterans Health Administration;Vision;Work

PROJECT_TITLE: Microglia-Vascular Interaction in Alteration of Blood-Retinal Barrier in Diabetic Retinopathy


PHR: Traumatic brain injury (TBI) is a complex neurological condition, and there are currently no FDA-approved treatments to directly treat cognitive deficits. The proposed study will delineate a mechanistic role of Neurogranin (Ng) in the pathophysiology of experimental TBI and use systemic delivery of retinoic acid and adeno-associated viral (AAV) vector-mediated overexpression to elucidate the therapeutic impact of increased Ng expression on restoring synaptic plasticity and functional outcomes after TBI. Successful completion of this study will further our understanding of molecular mechanisms of cognitive dysfunction after TBI.

PI_NAMEs: DIXON, C EDWARD (contact)

PROJECT_TERMS: Acute;adeno-associated viral vector;Alzheimer's Disease;Anatomy;Animal Model;Animals;Attention;Attenuated;Behavior;Behavioral;behavioral outcome;Biological Markers;Blood;Ca(2+)-Calmodulin Dependent Protein Kinase;Calcium;Calcium Binding;Calmodulin;calmodulin-dependent protein kinase II;Chronic;Circulation;Cognition;Cognitive deficits;cognitive function;cognitive task;combat;Communication;Complex;controlled cortical impact;Data;Dendritic Spines;density;disability;Economic Burden;Electrophysiology (science);emotional functioning;exosome;experience;Experimental Models;FDA approved;Functional disorder;functional outcomes;high risk;Hippocampus;Hospitalization;Impaired cognition;Impairment;improved;injured;Injury;Investigation;ischemic injury;Learning;Mediating;Medical Care Costs;Memory;mild traumatic brain injury;Military Personnel;Modeling;Molecular;Molecular Conformation;Molecular Target;Morphology;Nerve Degeneration;Nervous System Disorder;Neurocognitive;Neurodegenerative Disorders;neurogranin;Neurologic;neuron loss;Neurons;neuropathology;overexpression;Pathologic;Pathway interactions;Performance;Pharmacotherapy;Phosphorylation;Physical Function;Plasma;postsynaptic;pre-clinical;protein expression;Protein Kinase C;Proteins;Rattus;Regulation;Reporting;Research;Role;Serum;Severities;Signal Transduction;Symptoms;Synapses;Synaptic plasticity;Syndrome;Therapeutic;therapeutic biomarker;therapeutic target;Time;Traumatic Brain Injury;Tretinoin;Veterans;Viral;Vitamin A

PROJECT_TITLE: Neurogranin and Traumatic Brain Injury


ORG_CITY: KANSAS CITY

ORG_NAME: KANSAS CITY VA MEDICAL CENTER

ORG_STATE: MO

PHR: 8. Project Narrative Women are a vital part of the armed forces and veterans' community. The population of women veterans has risen and is projected to continue to rise. In the United States, one in seven women has or will develop breast cancer (BC). Therefore, we can anticipate that approximately 237,500 female veterans will be affected by BC in their lifetimes. The triple-negative breast cancer (TNBC), a sub-type of BC lacking estrogen, progesterone, and HER2 receptors, has a dismal prognosis. New insights into the disease and new therapeutic options thus must be developed. By revealing its mechanism of action, the proposed study aims to demonstrate CCN5 as a novel for TNBC. Our findings will directly inform the design and help interpret the results of potential clinical trials of CCN5-activation therapy in TNBC patients.

PI_NAMEs: BANERJEE, SUSHANTA K. (contact)

PROJECT_TERMS: active duty;Address;Affect;Aftercare;aggressive breast cancer;American;American Association for the Advancement of Science;Animals;anti-cancer research;Apoptosis;Area;Aspirin;Award;Back;Breast Cancer Cell;Breast Cancer Patient;breast cancer progression;Breast Cancer therapy;Breast Epithelial Cells;cancer cell;cancer initiation;cancer prevention;Cardiac;career;Cells;Censuses;Chemicals;chemotherapy;Classification;Clinic;Clinical;Clinical Trials;Collaborations;Communities;connective tissue growth factor;cyclin-dependent kinase inhibitor 1B;design;Detection;Diagnosis;differential expression;Disease;Distant;Dose;drug development;drug discovery;drug relapse;drug repurposing;Drug resistance;Drug Targeting;Enrollment;epithelial to mesenchymal transition;Epithelium;ERBB2 gene;ESR1 gene;Estrogens;falls;Family;Female;Funding;Genes;Genetic;Genetic Engineering;Goals;Growth;Growth Factor;health care delivery;Healthcare;Healthcare Systems;Hormone Receptor;hormone therapy;Human;Immune checkpoint inhibitor;improved;Industry;innovation;insight;Invaded;Investments;Knowledge;Laboratories;Laboratory Finding;Letters;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;member;Mesenchymal;migration;Military Personnel;Modification;mouse model;multidisciplinary;Mus;Mutation;Neoplasm Metastasis;Neoplasms;neoplastic;neoplastic cell;novel;novel marker;novel therapeutics;Oncogenes;Organ;overexpression;Paclitaxel;Pain;pancreatic cancer cells;Peer Review;Phenotype;Play;Polyethylene Glycols;Population;pre-clinical;prevent;Printing;Privatization;Process;Progesterone;Prognosis;programmed cell death ligand 1;programmed cell death protein 1;programs;Property;Protein Family;Proteins;receptor;Recombinant Proteins;Recombinants;recruit;Recurrence;Regimen;Regulation;Research;Research Personnel;Residual Cancers;Resistance;response;Role;Scientist;Seminal;stem;stem cells;stemness;Surface;System;systemic toxicity;Tamoxifen;targeted treatment;Techniques;Testing;Therapeutic;therapy outcome;Time;TP53 gene;trafficking;Translating;triple-negative invasive breast carcinoma;tumor growth;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;United States;Veterans;Woman


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: Cancer stem cells (CSCs) comprise a sub-set of cancer cells that are capable of self- regeneration, self-renewal, and de-differentiation. CSCs are felt to be responsible for the relapse of cancer patients that initially have a promising response to chemotherapy and targeted therapy. High dose acetaminophen (AAP) with delayed n-acetylcysteine (NAC) rescue has demonstrated promising evidence of anti-cancer activity in early phase clinical trials. However, the mechanism of anti-tumor activity of high dose AAP is incompletely understood. In this proposal, we outline preliminary data that high dose AAP acts as a novel anti-CSC drug and STAT3 modulator in human non-small cell lung cancer models. We outline a series of experiments to test the hypothesis that high dose AAP synergizes with chemotherapy and targeted therapy via a STAT3-dependant mechanism.

PI_NAMEs: NEUWELT, ALEXANDER  (contact)

PROJECT_TERMS: Acetaminophen;Acetylcysteine;Analgesics;anti-cancer;anticancer activity;Antidotes;antitumor effect;Award;Binding;Biological Assay;cancer cell;Cancer Model;Cancer Patient;Cancer Relapse;cancer stem cell;career;Caring;Cells;Chemoresistance;chemotherapy;Cisplatin;Clinical;Clinical Research;Collaborations;Computer software;Data;Dedications;Disease;Doctor of Philosophy;Dominant-Negative Mutation;Dose;driver mutation;Drug Targeting;Drug usage;early phase clinical trial;Education;Enrollment;Epidermal Growth Factor Receptor;Exhibits;experience;experimental study;Foundations;Free Radicals;Funding;Genes;Genetic Transcription;Glutathione;Goals;Head;Hepatoblastoma;Hepatotoxicity;Human;Hydrogen Bonding;In complete remission;in silico;In Vitro;in vivo;inhibitor;Injury;insight;Invaded;K-Series Research Career Programs;Knock-out;Knowledge;Laboratory Research;Length;Liver;lung cancer cell;Maintenance;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Mentors;Methods;Mitochondria;Modeling;Molecular;Mus;Natural regeneration;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Overdose;patient derived xenograft model;Patient Selection;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phenotype;Phosphorylation;Physicians;Physiology;Play;Population;pre-clinical;predictive marker;Process;Prognosis;Proliferating;Property;Proteins;Regulation;Research;Research Personnel;Resistance;Resources;response;Role;Scientist;self-renewal;Series;Signal Transduction;Site-Directed Mutagenesis;skills;spheroids;src Homology Region 2 Domain;STAT3 gene;Stat3 protein;stem cell biology;stem cell biomarkers;stem cell growth;stem cell population;symposium;synergism;targeted treatment;Testing;Time;Toxic effect;Transfection;tumor;tumor growth;tumor microenvironment;Tumorigenicity;Universities;vector;Virginia;Work;Xenograft procedure

PROJECT_TITLE: High dose acetaminophen with n-acetylcysteine rescue as a novel STAT3 inhibitor with anti-cancer stem cell properties


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: Decatur

PHR: PROJECT NARRATIVE The overarching mission of this project is to develop a Center entitled PRE-Clinical Interagency reSearch resourcE-Traumatic Brain Injury (PRECISE-TBI) with the mission of accelerating the development of therapies for TBI. PRECISE-TBI will achieve this mission by utilization of an enterprise approach to meet key objectives with targeted strategies and by leveraging previous collaborative efforts. The strategic missions of the Center are divided into five Cores and milestones will be achieved by activities of Core Directors and members. Leadership of PRECISE-TBI will be the Core Directors (Drs. C. Edward Dixon, Gene Gurkoff, Pamela VandeVord, Maryann Martone, Michelle LaPlaca, Neil Harris, Candace Floyd) and the Steering Committee Chair, Dr. Adam Ferguson. Leadership will interact with the Steering Committee and a Community Committee to set objectives, milestones, and deliverables.

PI_NAMEs: DIXON, C EDWARD;FERGUSON, ADAM R;FLOYD, CANDACE L. (contact);GURKOFF, GENE GABRIEL;HARRIS, NEIL ;LAPLACA, MICHELLE C;MARTONE, MARYANN E;VANDEVORD, PAMELA J.

PROJECT_TERMS: Acceleration;Acute;Addendum;Benchmarking;Businesses;Catalogs;Chronic;Clinical;Committee Members;Common Data Element;Communication;Communities;Consensus;Data;data sharing;Databases;Development;diversity and inclusion;Elements;Employee;FAIR principles;Friends;Funding;Gender Identity;Genes;Geographic Locations;Goals;Home;Human;Industry;Informatics;Infrastructure;Instruction;Knowledge;Knowledge Discovery;Leadership;Length;Maintenance;member;Mission;Modeling;Nonprofit Organizations;Ontology;organizational structure;Outcome;Pathology;pediatric traumatic brain injury;Persons;pre-clinical;Pre-Clinical Model;programs;Recording of previous events;Research;Research Personnel;Resources;Role;software systems;TBI treatment;therapy development;Traumatic Brain Injury

PROJECT_TITLE: PRECISE-TBI: PRE Clinical lnteragency research resourcE-TBI


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Anal cancer is caused mainly by sexually transmitted human papillomaviruses and has been increasing in incidence for many years—especially in adults living with HIV. In fact, people living with HIV have a 100x increased risk for anal cancer compared with HIV-negative patients. The VA cares for the largest population of patients living with HIV of any healthcare system in the United States, over 25,000 Veterans in 2019. One opportunity for preventing this deadly cancer in high-risk individuals lies in the effective treatment of precancerous lesions. The proposed research uses several novel preclinical models of anal cancer to examine the efficacy of targeted, topical therapies.

PI_NAMEs: CARCHMAN, EVIE  (contact)

PROJECT_TERMS: 3-Dimensional;Adult;Advanced Development;Affect;Anal carcinoma;Anal Intraepithelial Neoplasia;anti-cancer;Anus;Autophagocytosis;Back;Biological Assay;carcinogenesis;Carcinoma;Caring;CD4 Positive T Lymphocytes;Cell Culture Techniques;Cell Line;Cell Survival;Cells;Cervical dysplasia;chronic infection;Clinic;Clinical;Clinical Research;Collaborations;Data;Development;Diagnosis;Disease;Drug Screening;Drug Targeting;Dysplasia;effective therapy;efficacy evaluation;Epithelium;FRAP1 gene;Functional disorder;Goals;Green Fluorescent Proteins;Healthcare Systems;high risk;high risk population;HIV;HIV Infections;HIV Protease Inhibitors;HIV Seronegativity;HIV Seropositivity;HIV-1 protease;HIV/AIDS;HPV E7;HPV positive;Human;Human papilloma virus infection;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papillomavirus 16;Immune response;Immune system;Immunologic Stimulation;immunoregulation;Incidence;innovation;Knowledge;Laboratories;Laboratory Study;Lesion;Link;Lopinavir/Ritonavir;Malignant neoplasm of anus;Malignant Neoplasms;Mediating;Methodology;Modeling;Molecular;molecular targeted therapies;mortality;mouse model;multicatalytic endopeptidase complex;novel;novel therapeutic intervention;novel therapeutics;Oncoproteins;Papillomavirus Transforming Protein E6;Pathway interactions;patient population;Patients;Peripheral;Persons;pharmacologic;PIK3CG gene;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;preclinical study;premalignant;prevent;Prevention;Process;Property;Protease Inhibitor;Proteome;Recurrence;Research;Risk;Risk Factors;Serotyping;Sexual Transmission;side effect;Squamous cell carcinoma;Study models;T-Cell Depletion;Testing;Therapeutic;Therapeutic Agents;therapeutic evaluation;therapeutically effective;Tissues;Topical agent;Topical application;TP53 gene;transcriptome;Transgenic Mice;Transgenic Model;United States;United States Department of Veterans Affairs;Universities;Veterans;Viral;Wisconsin;Work

PROJECT_TITLE: Prevention of anal cancer in People Living with HIV (PLWH)


ORG_CITY: EAST ORANGE

ORG_NAME: VA NEW JERSEY HEALTH CARE SYSTEM

ORG_STATE: NJ

PHR: Project Narrative The prevalence of chronic liver diseases, including alcoholic liver diseases, non-alcoholic fatty liver diseases, drug-induced liver injury, hepatocellular carcinoma, has increased rapidly during the last two decades and become a huge medical burden in the US, especially to the veteran population. To discover novel mechanisms, diagnostic biomarkers, and treatments to these chronic liver diseases especially hepatocellular carcinoma, will provide a great health benefit to the veteran patient population.

PI_NAMEs: GUO, GRACE L (contact)

PROJECT_TERMS: Alcoholic Liver Diseases;Animal Model;Animals;Apoptosis;Automobile Driving;Bile Acid Biosynthesis Pathway;Bile Acids;Biological Markers;Cancer Etiology;cell injury;Cell Proliferation;Cessation of life;Cholestasis;Cholic Acids;chronic liver disease;Cirrhosis;cytotoxic;Data;Deoxycholic Acid;Detergents;Development;diagnostic biomarker;drug induced liver injury;Early Diagnosis;effective therapy;Endocrine;Enterohepatic Circulation;Event;FGF19 gene;Fibroblast Growth Factor;Future;Goals;Growth;Health Benefit;Homeostasis;hormonal signals;Hormones;Human;in vivo;innovation;Intestines;Knock-out;Knockout Mice;Liver;Liver diseases;liver injury;Liver Regeneration;Mediating;Medical;military veteran;Molecular;mouse model;Mus;non-alcoholic fatty liver disease;novel;overexpression;Pathogenesis;Pathology;Pathway interactions;patient population;Patients;Physiology;Prevalence;prevent;Prevention;Primary carcinoma of the liver cells;Property;receptor;receptor expression;receptor function;Research;Rodent;Role;Signal Transduction;Somatotropin;Testing;TG gene;Time;Transgenic Mice;Transgenic Organisms;Tumor Promotion;Tumor Suppressor Proteins;Veterans

PROJECT_TITLE: Role of Intestinal Bile Acid Signaling in Liver Diseases


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Kidney Disease;Patient Safety

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Patients with end-stage kidney disease (ESKD) suffer high rates of hospitalization and death. Opinion-based clinical practice guidelines recommend lowering serum phosphate in patients with ESKD, but no randomized clinical trial tested whether phosphate reduction improves or worsens outcomes. “HiLo” is a randomized pragmatic clinical trial that is testing the effects of higher versus lower serum phosphate targets on rates of mortality and hospitalization in 4000 patients with ESKD being treated with hemodialysis at >150 DaVita dialysis across the US.

PI_NAMEs: CHAKRABORTY, HRISHIKESH  (contact)

PROGRAM_OFFICER_NAME: MENDLEY, SUSAN RUTH

PROJECT_TERMS: adverse outcome;analytical method;arm;Award;Cardiovascular Diseases;Cessation of life;Characteristics;Clinical;Clinical Practice Guideline;Clinical Research;Clinical Trials Data Monitoring Committees;Cluster randomized trial;collaboratory;Complication;Consent;COVID-19;Data;data exchange;Death Rate;Decision Making;design;Dialysis procedure;End stage renal failure;Enrollment;Equipoise;Futility;Guidelines;Healthcare Systems;Hemodialysis;Hospitalization;hospitalization rates;improved;Individual;inorganic phosphate;Intervention;invention;Manuscripts;Measures;mortality;National Institute of Diabetes and Digestive and Kidney Diseases;Outcome;Participant;Patient-Focused Outcomes;Patients;Pragmatic clinical trial;pre-clinical;primary outcome;Provider;Randomized;randomized trial;randomized, clinical trials;Recommendation;recruit;Reporting;Research Institute;response;secondary outcome;Serum;systems research;Testing;United States National Institutes of Health;Work

PROJECT_TITLE: HiLo Competitive Renewal

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-3 (M2)]


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: The current barrier to delivering optimal health care to patients with urinary stone disease (USD) is the lack of evidence supporting the efficacy of current guidelines for prevention of USD. This lack of evidence likely drives unwanted variability in how providers diagnose and treat USD. The proposed research has two main objectives: 1) determine which guideline recommendations are associated with better outcomes for USD in the Veterans Health Administration (VHA); and 2) identify current barriers to implementation of effective guidelines for USD in the VHA. The anticipated impact of the proposed work will be to define more clearly best practice management of USD and inform future quality improvement efforts to facilitate diffusion of best USD care practices in both the VA and civilian health care systems.

PI_NAMEs: LEPPERT, JOHN THOMAS;PAO, ALAN C (contact)

PROJECT_TERMS: Address;Adoption;American;American College of Physicians;care providers;Caring;Chronic Disease;Clinic;Clinical;clinical practice;Clinical Trials;cohort;comparative effectiveness study;Complex;Data;design;Diagnosis;Diffuse;Diffusion;Disease;disorder prevention;disorder risk;Drug Prescriptions;Economics;effective intervention;effectiveness evaluation;Emergency department visit;Event;evidence base;evidence based guidelines;experience;Expert Opinion;Face;Future;Geographic Locations;Guidelines;Health;Health Care Costs;Healthcare;Healthcare Systems;Hour;Hyperparathyroidism;implementation barriers;improved;indexing;Injury to Kidney;innovation;Lead;Measurement;Measures;medical specialties;Methodology;Methods;Morbidity - disease rate;Nephrology;Operative Surgical Procedures;Outcome;Pain;Patients;Pattern;Pharmaceutical Preparations;Positioning Attribute;Practice Guidelines;Practice Management;prevent;Prevention;Prevention Guidelines;Prevention Measures;Prevention strategy;Primary Care;primary care practice;primary care provider;Process Measure;prospective;Provider;Quality of Care;randomized, clinical trials;Recommendation;Recurrence;Recurrent disease;Research;screening;Secondary Prevention;Surveys;Testing;Time;treatment strategy;United States;Urinary Calculi;Urinary tract;Urinary tract infection;Urine;urologic;Urology;Variant;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Defining Optimal Care for Urinary Stone Disease in the Veterans Health Administration

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Antibiotic-resistant bacteria cause over 23,000 deaths annually in the US. The primary risk for this is antibiotic exposure. Up to half of all antibiotic use is unnecessary, much due to treating over-diagnosed urinary tract infection (UTI). Recent efforts to improve unnecessary antibiotic use focus on a highly trained physician ‘steward’ who reviews cases or restricts the use of specific antibiotics. A novel approach we defined in JAMA, diagnostic stewardship, aims to streamline test ordering, processing and reporting to make appropriate testing and interpretation easier for clinicians. Small-scale studies indicate this type of electronic medical record/laboratory intervention can significantly reduce antibiotic overuse without apparent harms and is easy to implement. This award will develop literature/expert based criteria for UTI diagnostic stewardship and tools that are acceptable to clinicians. Next, a proof-of-concept study in three VA healthcare systems will implement and measure impact on cultures and antibiotic use across acute-ambulatory-and long-term care.

PI_NAMEs: MORGAN, DANIEL J (contact)

PROJECT_TERMS: Acute;acute care;Address;Adverse event;adverse outcome;Ambulatory Care;American;Antibiotics;antimicrobial;Antimicrobial Resistance;Area;Award;Bacterial Antibiotic Resistance;behavioral economics;Bladder;Caring;catheter associated UTI;Centers for Disease Control and Prevention (U.S.);Cessation of life;Clostridium difficile;Collaborations;Combating Antibiotic Resistant Bacteria;Communicable Diseases;Computerized Medical Record;Consensus;cost;Data;data warehouse;design;Diagnosis;Diagnostic;Diagnostic tests;effective intervention;effectiveness/implementation study;Focus Groups;Funding;Goals;Health system;Healthcare;Healthcare Systems;Hospitals;implementation barriers;implementation facilitators;implementation research;implementation science;implementation strategy;implementation tool;improved;improved outcome;Infection;Infection prevention;Inflammation;innovation;interest;Intervention;intervention refinement;Interview;Laboratories;Learning;Life;Literature;Long-Term Care;Maryland;Measures;Medical center;Methods;novel strategies;Nurses;Outcome;Patient Care;Physicians;Pilot Projects;Population;prevent;Process;programs;Protocols documentation;provider behavior;Psychology;Quasi-experiment;Reporting;Research;Research Priority;response;Risk;Safety;Sampling;Technology;Testing;tool;Training;United States Centers for Medicare and Medicaid Services;Universities;uptake;urinary;Urinary tract infection;Urine;user centered design;Veterans;Work

PROJECT_TITLE: Diagnostic Stewardship as a 'nudge' to reduce inappropriate antibiotic use for urinary tract infections


ORG_CITY: HOUSTON

ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

ORG_STATE: TX

PHR: ACEI/ARB therapy reduces cardiovascular events and progression to end-stage kidney disease in patients with chronic kidney disease (CKD) and albuminuria. We have shown that ACEI/ARB therapy is underused in veterans with CKD. This could be related to clinical inertia but could also be related to ACEI/ARB associated side effects which may not be well captured in structured VA datasets. The objectives of this proposal are to (a) identify reasons for suboptimal ACEI/ARB in CKD patients use using both structured data and provider text notes using novel informatics techniques (Aim 1) (b) understand patient and provider perspective on ACEI/ARB use in CKD and refine a communication aid targeting providers to improve ACEI/ARB use in CKD patients (Aim 2) and (c) pilot test an intervention (Aim 3) to improve ACEI/ARB use in veterans with CKD using the communication aid refined in Aim 2. Our results will identify strategies to improve ACEI/ARB use in high-risk veterans with CKD, who stand to derive the most benefit from this life saving therapy.

PI_NAMEs: NAVANEETHAN, SANKAR DASS  (contact);VIRANI, SALIM S

PROJECT_TERMS: Address;Adverse event;Albuminuria;Algorithms;Ambulatory Care Facilities;Angioneurotic Edema;Angiotensin II Receptor;Angiotensin-Converting Enzyme Inhibitors;Anti-Hypertensive Agents;Cardiovascular Diseases;Cardiovascular system;care costs;Caring;Cessation of life;Chronic Disease;Chronic Kidney Failure;Clinical;Cognitive;communication aid;Communities;cost;Cost Analysis;cost effectiveness;Cost Savings;Coughing;Creatinine;Data Set;Department of Defense;design;Diabetes Mellitus;diabetic;Dialysis procedure;Diet Modification;Disease Progression;Diuretics;Dose;End stage renal failure;Event;follow-up;General Population;Guidelines;Health care facility;Health Services Research;Healthcare Systems;High Prevalence;high risk;high risk population;Human;hyperkalemia;Hypertension;Hypotension;improved;Informatics;Information Retrieval;inhibitor;innovation;Intervention;Interview;Kidney Diseases;Learning;Life;Manuals;Medical center;Methodology;Morbidity - disease rate;mortality;mortality risk;Myocardial Ischemia;Natural Language Processing;New Agents;non-diabetic;novel;Outcome;Patients;Pharmaceutical Preparations;Physiological;Pilot Projects;pilot test;pilot trial;point of care;Population;Potassium;Prevalence;primary care provider;primary outcome;Provider;provider behavior;Qualitative Research;Quality of life;Recommendation;Renin-Angiotensin System;Renin-Angiotensin-Aldosterone System;Reporting;Research Methodology;Research Priority;Risk;Risk Reduction;Secondary to;Sensitivity and Specificity;Serum;side effect;Site;sound;standard of care;Structure;structured data;System;Techniques;tertiary care;Testing;Text;Time;Training;treatment as usual;Treatment Side Effects;United States;United States Department of Veterans Affairs;unstructured data;Variant;Veterans;Veterans Health Administration

PROJECT_TITLE: Optimizing Renin Angiotensin System Blocker Use among Veterans with Kidney Disease


ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Every day, thousands of Veterans are treated urgently for unexpected problems. They present to acute outpatient settings such as the emergency department, urgent care clinics, and primary care offices for infectious and pain-related complaints, and in many cases, are treated with antibiotics and non-steroidal anti- inflammatory drugs (NSAIDs). Unfortunately, 30% of these medications are inappropriately prescribed and may cause patient harm. Without a systematic process to give providers feedback on their prescribing, the opportunity to learn from experience and prevent future adverse events is lost. By placing the provider at the center of the design of a feedback system, this study seeks to develop a feedback system using potentially inappropriate antibiotic and NSAID prescribing as two primary opportunities to improve acute outpatient care delivery. This project will examine the performance of an automated system to enhance the quality and safety of medication prescribing for Veterans who seek acute care.

PI_NAMEs: MATHENY, MICHAEL E.;WARD, MICHAEL J. (contact)

PROJECT_TERMS: Academic Detailing;Academic Medical Centers;Accident and Emergency department;Acute;acute care;Address;Adverse drug event;Adverse event;Advisory Committees;Ambulatory Care;Antibiotics;antimicrobial;Behavior;behavior change;Calibration;Cardiovascular system;care delivery;care providers;Caring;Clinic;clinical center;comorbidity;Complex;Consolidated Framework for Implementation Research;cost;Coupled;Data;design;Development;Drug Interactions;Drug Prescriptions;Education;Educational workshop;effectiveness evaluation;Elderly;Electronics;Emergency Care;Engineering;Environment;Evaluation;experience;Familiarity;Feedback;field study;Future;gastrointestinal;Goals;Guidelines;Health;health care service utilization;Healthcare;Healthcare Systems;Human;hybrid type 1 design;iatrogenic injury;Ibuprofen;implementation intervention;implementation outcomes;implementation science;implementation strategy;improved;Incentives;Individual;Informatics;innovation;Inpatients;Institution;Intervention;Interview;Intuition;Joints;Kidney;Knowledge;Learning;Machine Learning;medication safety;Methods;multi-component intervention;Musculoskeletal Pain;Non-Steroidal Anti-Inflammatory Agents;Operations Research;Outcome;Outpatients;Pain;patient safety;Patient-Focused Outcomes;Patients;Performance;Pharmaceutical Preparations;Planning Theory;prescription opioid;pressure;prevent;Prevention;Primary Care;primary care clinic;primary care setting;primary care visit;Process;programs;Provider;Qualifying;Qualitative Methods;Qualitative Research;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Registries;Research;Risk;Risk Adjustment;risk prediction model;Safety;Sampling;satisfaction;Site;Source;Structure;System;Tennessee;therapy design;tool;uptake;urgent care;user centered design;Vacuum;Variant;Veterans;Veterans Health Administration;Visit;Visual;Writing

PROJECT_TITLE: Evaluating a Prescribing Feedback System for Acute Care Providers


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: PEDIATRICS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Neutrophils are critical first-responders of the innate immune system, yet aberrant or prolonged neutrophil activity causes tissue damage in a wide array of acute and chronic inflammatory diseases. This proposal aims to investigate the intracellular signaling pathways that guide neutrophil activation, and how these processes adapt during neutrophil development and inflammation. These studies are anticipated to identify new mechanisms to strategically modulate neutrophil function to impact disease.

PI_NAMEs: CLEMENS, REGINA  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Acute;Acute Lung Injury;Bacteria;Bacterial Infections;Biological;Biology;Calcium;Calcium Channel;Calcium ion;Calcium Signaling;Calcium-Activated Potassium Channel;Cell membrane;Cell Physiology;Cells;Charge;chronic inflammatory disease;Clinical;Communicable Diseases;Coupling;Cytoplasmic Granules;Cytotoxin;Data;Development;Disease;driving force;Emergency Situation;Enzymes;Event;extracellular;first responder;Functional disorder;Genetic;Goals;Gout;Granulopoiesis;Hemolysin;Host Defense;Human;Immune;immune system function;Infection;Inflammation;Inflammatory;Innate Immune System;insight;Ion Channel;Knowledge;Laboratories;Lymphocyte;mast cell;Mediating;Mediator;Membrane Potentials;Molecular;mouse model;Mus;Mycoses;Neutropenia;neutrophil;Neutrophil Activation;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Patients;Predisposition;Process;Reactive Oxygen Species;Regulation;response;Rheumatoid Arthritis;Role;Sepsis;Signal Pathway;Signal Transduction;Staphylococcus aureus;Stimulus;Testing;Therapeutic Intervention;Tissues;Toxic Neutrophil;Toxin;Virulence

PROJECT_TITLE: Membrane potential and Calcium Signaling in Neutrophil Development and Inflammation

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Microglia, the innate immune cells of the brain, play a critical role in Alzheimer’s Disease pathophysiology by responding to amyloid-ß plaques through the induction of a unique transcriptional and functional phenotype. Our data suggests that the polycomb repressive complex 2 (PRC2), a known regulator of microglial transcriptional state, is required for the proper induction of this phenotype. In this proposal, I will address the mechanism through which PRC2 controls the microglial response to amyloid-ß plaques by characterizing its regulation of transcription as well as its role in microglial function.

PI_NAMEs: CHALLMAN, MATTHEW FRANCIS (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta accumulation;Ablation;Actins;Address;Affinity Chromatography;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Biological Assay;Brain;brain cell;Brain region;Cell Maintenance;Cell Nucleus;Cell Proliferation;Cell Survival;cell type;Cells;Cessation of life;Chemotaxis;Cleavage Under Targets and Release Using Nuclease;Complex;Cytoplasm;Data;Development;Disease;Disease associated microglia;effective therapy;Environment;Epigenetic Process;experimental study;Fibroblasts;Functional disorder;Gene Expression;Gene Expression Profile;gene repression;Gene Silencing;Genes;Genetic;genetic approach;genetic risk factor;Genetic study;Genetic Transcription;glial activation;histone methylation;Immune;In Vitro;in vivo;Inflammatory Response;Late Onset Alzheimer Disease;loss of function mutation;Lysine;Maintenance;Measures;Mediating;Metabolism;Microglia;migration;Modeling;mouse model;Mus;Myelogenous;Neurodegenerative Disorders;neuron loss;Pathway interactions;Phagocytosis;pharmacologic;Phenotype;Play;Polycomb;polymerization;Polymers;Proliferating;Property;Prosencephalon;receptor;Receptor Activation;Regulation;response;Ribosomes;Risk Factors;risk variant;Role;Senile Plaques;Signal Induction;Signal Pathway;Signal Transduction;Specific qualifier value;tau aggregation;Toxic effect;Transcriptional Regulation;Translating;TREM2 gene;virtual

PROJECT_TITLE: The regulation of the microglial response to amyloid-beta plaques by the polycomb repressive complex 2


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE Antibiotic resistant bacterial infections cause hundreds of thousands of deaths each year, while the lack of new antimicrobials poses a threat to modern medicine. The development of new drugs against Gram-negative bacteria, organisms that are responsible for most of the societal burden of resistant infections, is primarily hampered by the protective action of their cell envelope compartment. We propose to systematically investigate the interaction between resistance proteins and biochemical pathways that maintain the integrity of the cell envelope proteome, with the goal to evaluate whether targeting protein folding in the cell envelope could be exploited in future attempts to overcome antibiotic resistance.

PI_NAMEs: MAVRIDOU, DESPOINA  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acinetobacter baumannii;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;antimicrobial;Antimicrobial Resistance;Bacterial Antibiotic Resistance;bacterial genetics;Bacterial Infections;beta-Lactamase;Biochemical;Biochemical Pathway;Biochemistry;Biogenesis;catalyst;cell envelope;Cell Membrane Permeability;Cessation of life;Chemicals;chronic infection;Clinical;clinically relevant;colistin resistance;comparative;Complex;CRISPR interference;Cytoplasm;Data;Development;disease model;disulfide bond;efflux pump;Enzymes;Epidemiology;Escherichia coli;Evolution;Foundations;Functional impairment;Future;Genetic Transcription;global health;Goals;Gram-Negative Bacteria;Healthcare Systems;holistic approach;Home;human disease;Impairment;Infection;innovation;Investigation;Klebsiella pneumoniae;Knowledge;Laboratories;Light;Link;Mechanical Stress;Mediating;Microbiology;Modeling;Modern Medicine;Multi-Drug Resistance;multidrug-resistant Pseudomonas aeruginosa;Mus;mutant;Natural regeneration;Nature;next generation;novel;novel therapeutics;Organism;pathogen;pathogenic bacteria;Pathway interactions;Performance;periplasm;Permeability;Process;programs;protein folding;Proteins;Proteome;Proteomics;proteostasis;proteostasis loss;Pseudomonas aeruginosa;Research;Resistance;resistance mechanism;resistome;Role;Stress;System;Testing

PROJECT_TITLE: The interplay between cell envelope protein homeostasis and antibiotic resistance in Gram-negative bacteria

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Clinical Research;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: LEXINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: The proposed studies investigate structure, biosynthesis pathway and function of cell wall in the important human pathogen Streptococcus pyogenes. The outcomes of this research are expected to have a positive impact on the development of highly targeted therapeutics to control S. pyogenes infections. !

PI_NAMEs: KOROTKOVA, NATALIA  (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Acetylation;Anabolism;analog;Analytical Chemistry;anti-microbial peptide;Antibiotic Therapy;Antibiotics;antimicrobial;Antimicrobial Cationic Peptides;Antimicrobial Resistance;Bacterial Physiology;Binding;Biochemical;Biogenesis;Biological;Biological Assay;carbohydrate biosynthesis;Carbohydrates;Cations;cell envelope;Cell membrane;Cell Physiology;Cell Wall;Cells;Cellulitis;Charge;Chemicals;combat;Communicable Diseases;Control Groups;Data;Deacetylase;density;Dental;design;Development;Diagnostic;Disease;Drug Design;drug development;Drug Targeting;Electrostatics;Enzymatic Biochemistry;Enzymes;Epitopes;Erysipelas;extracellular;Freeze Substitution;Gene Cluster;Genetic;Glycerol;Goals;Histones;Homologous Gene;Human;human pathogen;improved;in vivo;in vivo Model;Infection;inorganic phosphate;insight;Knowledge;Link;Mass Spectrum Analysis;Methods;Modeling;Modification;Molecular;Molecular Genetics;molecular size;Molecular Structure;mortality;mouse model;Muramidase;mutant;Necrotizing fasciitis;neglect;neutrophil;novel;Outcome;Outcome Study;Outcomes Research;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Peptidoglycan;Permeability;Pharyngeal structure;Phospholipase A2;Polymers;Polysaccharides;Predisposition;Proteins;Publishing;resistance mechanism;Rhamnose;Role;Scarlet Fever;Serotyping;Serum;Skin;Streptococcal Infections;Streptococcal Vaccines;Streptococcus;Streptococcus mutans;Streptococcus pyogenes;Structure;Surface;Syndrome;targeted treatment;Techniques;Testing;Therapeutic Intervention;Thick;Vaccine Antigen;vaccine candidate;Vaccine Design;Vaccines;Vertebral column;Work

PROJECT_TITLE: Biogenesis and Function of Streptococcus Pyogenes Cell Wall

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


PHR: PROJECT NARRATIVE Over 100,000 VA patients are diagnosed every year with carpal tunnel syndrome and 11,000 receive surgical carpal tunnel release to treat this common and disabling syndrome. Healthcare quality measures are used by policy makers, VA administrators, and other healthcare professionals to identify high and low performing facilities, measure the effects of quality improvement interventions, and for performance-based reimbursement. Currently, no feasible and valid measures of treatment quality exist for carpal tunnel syndrome. This project aims to develop and validate measures of carpal tunnel syndrome treatment quality so that all stakeholders, including Veterans, have valid measures to distinguish excellent from substandard care. With VA's increasing role as a purchaser of healthcare, as well as increasing interest in making between-system comparisons, VA needs quality measures that are rigorously evaluated for both VA-internal use and value-based purchasing of community care.

PI_NAMEs: SOX-HARRIS, ALEX  (contact)

PROJECT_TERMS: Academy;Address;Administrator;Affect;American;Caring;Carpal Tunnel Syndrome;Case-Mix Adjustments;Characteristics;Clinical Practice Guideline;Code;Collaborations;Communities;Community Health;Community Healthcare;Consultations;cost;Data;Data Set;Development;Diagnosis;Disabling;Future;Guidelines;Hand;health care quality;health care settings;Health Personnel;Health Professional;Healthcare;Healthcare Systems;Hospitals;ICD-9;improved;Incentives;innovation;interest;Intervention;Link;Logistics;Measurement;Measures;Medical center;medical specialties;Medicare;Methodology;Methods;Michigan;Modeling;Monitor;Musculoskeletal Diseases;Operative Surgical Procedures;Orthopedics;Outcome;Outcome Measure;Patient Outcomes Assessments;Patients;payment;Performance;Persons;pilot test;Policy Maker;Privatization;Process;Process Measure;Property;Provider;Publishing;Reporting;Research;Role;Safety;Science;Societies;Specific qualifier value;statistics;Surgeon;Symptoms;Syndrome;System;Testing;United States;Universities;Validation;Variant;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Addressing the Gap in Feasible, Valid, and Important Quality Measures for the Treatment of Carpal Tunnel Syndrome


ORG_CITY: ANN ARBOR

ORG_STATE: MI

PHR: Sepsis is a common cause of hospitalization that is associated with long-term challenges in survivors, such as weakness, cognitive difficulties, and worsening of chronic medical problems. This study will help us understand why some hospitals and clinics have better long-term outcomes from sepsis. By identifying strategies used by top-performing sites, we will be able to share these “best practices” to improve survivorship from COVID-related and non-COVID- related sepsis.

PI_NAMEs: PRESCOTT, HALLIE CHRISTINE (contact);SUSSMAN, JEREMY BRODER

PROJECT_TERMS: 2019-nCoV;Acute;Address;Administrator;Adopted;Awareness;Caregivers;Caring;Censuses;Characteristics;Chronic;Clinical;clinical implementation;clinical practice;Clinical Research;Clinics and Hospitals;Cognitive;cohort;COVID-19;COVID-19 pandemic;Creativeness;Critical Care;Data;design;Diffusion;disability;Disasters;Electronic Health Record;Epidemiology;epidemiology study;experience;Family;Functional disorder;Future;Goals;Guidelines;Health system;hospital readmission;Hospitalization;Hospitals;Impaired cognition;implementation strategy;improved;Incidence;Infection;informant;innovation;Intervention;Interview;Learning;Life;long term recovery;Managed Care;Marketing;Measures;Medical;Methodology;Methods;Modeling;Morbidity - disease rate;multidisciplinary;Nursing Research;Organ;Outcome;pandemic disease;Patients;Pharmaceutical Preparations;physical impairment;Prevalence;Primary Care;primary caregiver;Professional Organizations;Proxy;Public Health;Qualitative Research;Quality of life;Recommendation;Recovery;Research;Resolution;Respondent;Review Literature;Risk;Sepsis;Sepsis Syndrome;Series;Site;Site Visit;Standardization;Structure;Surveys;Survivors;survivorship;Telephone;tool;treatment guidelines;treatment research;Veterans;Viremia;virtual;Work;World Health Organization;World Health Organization Disability Assessment Schedule

PROJECT_TITLE: Optimizing Veteran Recovery from Sepsis (OVeR-Sepsis)


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Despite intense and ongoing investigations, there are no established biomarkers to identify the optimal location, intensity, or parameters for emerging DBS device technologies. Here we will use a novel 16-contact directional lead in tandem with advanced stimulation and acquisition hardware to create detailed spatiotemporal maps of globus pallidus interna and subthalamic nucleus electrophysiology in patients with advanced Parkinson’s disease. Our vision is for this work to advance the design of future DBS systems that can stimulate and sense interactions between DBS and human brain circuits and inform clinical decision-making related to directional stimulation for Parkinson’s disease and other complex neurocognitive disorders.

PI_NAMEs: WALKER, HARRISON CARROLL (contact)

PROGRAM_OFFICER_NAME: ROBINSON SCHWARTZ, SARAH ELIZABETH

PROJECT_TERMS: Algorithms;analytical method;Anesthesia procedures;Architecture;Attention;awake;Biological Markers;biomarker validation;Boston;Brain;Clinic;Clinical;clinical decision-making;clinical efficacy;clinical predictors;clinically relevant;Collaborations;Complex;Coupling;Deep Brain Stimulation;design;Devices;Disease;Electrophysiology (science);Evoked Potentials;Excision;experimental study;Frequencies;Future;General Anesthesia;Generations;Globus Pallidus;Goals;Human;implantable device;improved;Individual;Industry Collaboration;industry partner;interest;Investigation;Lead;Link;Location;Maps;Measures;Methods;Morphologic artifacts;Motor;motor symptom;Movement Disorders;neural;neurocognitive disorder;Neurons;neuroregulation;new technology;next generation;novel;novel marker;Operative Surgical Procedures;Outcome;Parkinson Disease;Patients;Phase;Physiologic pulse;Physiological;Physiology;point of care;Population;prediction algorithm;predictive marker;predictive modeling;prospective;Radial;recruit;Refractory;Research;response;Severity of illness;Shapes;Signal Transduction;Site;spatiotemporal;Specific qualifier value;Stimulus;Structure;Structure of subthalamic nucleus;Symptoms;System;Technology;Testing;Thalamic structure;Vision;Visualization;Work

PROJECT_TITLE: Stimulus-evoked directional field potentials to guide subthalamic and pallidal DBS for PD

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-G (59)]


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Patient Safety;Rehabilitation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: We propose a neurotechnology development project entailing pre-clinical and human intra-operative testing of a speech neuroprosthetic device intended to benefit patients with paralysis and loss of speech resulting from stroke, amyotrophic lateral sclerosis (ALS) and progressive muscle disorders. This work will pave the way for chronic studies and real-world implementation of speech neuroprosthesis device technology that restores communication and quality of life for affected individuals.

PI_NAMEs: CHANG, EDWARD ;CONG, PENG  (contact)

PROGRAM_OFFICER_NAME: WU, GUANGYING

PROJECT_TITLE: A fully implantable speech neuroprosthesis

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-A (04)]


ORG_CITY: PITTSBURGH

ORG_STATE: PA

PHR: Stroke is the leading cause of neurological disability in the veteran population and problems with arm movement are a major cause of loss of functional ability. Strokes affect a network of brain regions that control movement and restoring ability to move requires knowledge about how brain connections are changed. We propose studying the changes in connections between a few of these regions in people with and without a stroke. The goal is a method to improve movement by combining brain stimulation with practice of movement, a method that we will test, using some of the knowledge we will have gained by studying how brain connections affect movement before and after stroke.

PI_NAMEs: WITTENBERG, GEORGE F. (contact)

PROJECT_TERMS: Activities of Daily Living;Affect;Anatomy;Area;arm movement;arm paresis;Behavior;Behavioral;Bilateral;Brain;Brain region;causal model;Clinical;Clinical Trials;Coupled;Data;design;Diffusion;disability;Dorsal;experience;functional loss;Functional Magnetic Resonance Imaging;Goals;Human;Impairment;improved;Individual Differences;Infarction;innovation;Internal Capsule;Intervention;Knowledge;Learning;Lesion;lifetime risk;Magnetic Resonance Imaging;Measures;Methods;military veteran;Motor;motor behavior;motor control;Motor Cortex;motor function improvement;motor impairment;Motor output;Movement;movement practice;Neurological disability;neurological rehabilitation;Neuronal Plasticity;neuroregulation;novel;Participant;Patients;Performance;Persons;Population;post stroke;Procedures;Productivity;Quality of life;Recovery;repetitive transcranial magnetic stimulation;Resources;Rest;robot exoskeleton;Robotics;Role;Shapes;Side;Stroke;stroke patient;stroke risk;stroke survivor;Techniques;Testing;Training;transcranial direct current stimulation;Transcranial magnetic stimulation;Translations;Treatment Protocols;Upper Extremity;Veterans;white matter damage;Work

PROJECT_TITLE: Brain areas that control reaching movements after stroke: Task-relevant connectivity and movement-synchronized brain stimulation

STUDY_SECTION_NAME: Brain Health and Injury[RRD1]


ORG_CITY: GAINESVILLE

ORG_STATE: FL

PHR: Post-traumatic stress disorder (PTSD) is a major source of quality of life decline in Veterans. Sleep disruption in PTSD is very common and hyperarousal features of PTSD have a bidirectional relationship to sleep problems. Current treatment options have limited efficacy. Further, pharmacological treatments for poor sleep quality often deleteriously affect sleep architecture and may also be addictive. We will examine the efficacy of a non-invasive treatment option called transcutaneous vagal nerve stimulation (tVNS) to improve sleep architecture (aim 1), hyperarousal symptoms of PTSD (aim 2), and predictors of individual differences in response (e.g., mild TBI features) (aim 3). tVNS is promising because the vagus nerve affects brain structures that underlie core hyperarousal PTSD symptoms. Preliminary data in animals and humans suggest efficacy in reducing hyperarousal symptoms and increasing restorative sleep quality. Data gleaned from this investigation will substantially move this technology towards becoming a viable treatment.

PI_NAMEs: WILLIAMSON, JOHN B (contact)

PROJECT_TERMS: actigraphy;addiction;Address;Adherence;Affect;alcohol and other drug;Alcohol consumption;Amygdaloid structure;Animals;Apnea;Arthritis;Attenuated;attenuation;Autonomic nervous system;Behavior;Behavioral;Brain;Cardiovascular Diseases;Chronic;clinical care;clinically relevant;cognitive performance;Complex;Continuous Positive Airway Pressure;Crossover Design;Data;debilitating symptom;Dependence;Development;Diabetes Mellitus;Disease;Dose;Ear;effective therapy;efficacy evaluation;Emotional;Environment;Evaluation;Event;experience;falls;fighting;Fostering;Frequencies;Glean;Heart Rate;heart rate variability;Heterogeneity;Home;Hour;Human;Impairment;Implant;improved;improvement on sleep;Individual Differences;Inflammatory;Injury;innovation;Investigation;Knowledge;Literature;Measures;Methods;mild traumatic brain injury;Monitor;Moods;multimodality;Nerve;neurophysiology;neurosurgery;Neurotransmitters;Nightmare;non rapid eye movement;novel;Operative Surgical Procedures;Parasympathetic Nervous System;Participant;Patient Self-Report;Patients;pharmacologic;Pharmacological Treatment;Phase;poor health outcome;poor sleep;Population;Post-Traumatic Stress Disorders;Publishing;Quality of life;Recording of previous events;Recovery;reduce symptoms;Regulation;REM Sleep;Reporting;response;Rest;Risk;Role;Safety;Self Assessment;Severities;side effect;Sleep;Sleep Architecture;Sleep Deprivation;Sleep Disorders;Sleep disturbances;sleep onset;sleep quality;Sleeplessness;Slow-Wave Sleep;Source;Structure;success;Sympathetic Nervous System;Symptoms;System;Technology;Testing;Time;tool;translational potential;treatment response;Up-Regulation;Vagus nerve structure;Veterans;Visual;white matter;Work

PROJECT_TITLE: Transcutaneous vagal nerve stimulation improvement of sleep quality in veterans with PTSD with or without history of mild TBI


NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases

ORG_CITY: BOSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: In order to exert their protective effector functions during viral infections, T lymphocytes must migrate actively within the body to engage in physical contacts with their target cells. This project focuses on one major subpopulation of anti-viral T cells that are defined by high expression of a diagnostic surface molecule, CX3CR1, and were found to crawl within the lumen of small blood vessels in peripheral tissues. The goals of this project are to investigate the mechanisms of intravascular crawling of anti-viral CX3CR1-high T cells and to elucidate the immunological consequences of this unprecedented form of cellular immune surveillance.

PI_NAMEs: VON ANDRIAN, ULRICH H (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Acute;adaptive immune response;Address;Adhesions;Affect;Anti-viral Response;Antigens;arteriole;Behavior;Biological;Blood;Blood capillaries;Blood flow;Blood Vessels;capillary bed;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Adhesion Molecules;Cell Communication;cell motility;Cells;chemokine receptor;Data;density;Diagnostic;differential expression;Effector Cell;Endothelial Cells;Endothelium;engineered T cells;Environment;Exclusion;experience;experimental study;Frequencies;Gene Expression Profiling;Generations;Germ Cells;Goals;Image;Immunologic Surveillance;Immunologics;in vivo;Infection;intravital microscopy;Kinetics;life span;Long-Term Effects;Lymphocyte Homing Receptors;Lymphoid Tissue;Malignant Neoplasms;Mediating;Memory;microbial;migration;Molecular;multi-photon;Names;Nature;pathogen;Peripheral;Phase;Phenotype;Physiological;Population;Process;Proliferating;Property;Proteins;recruit;Research;response;Role;Series;Shapes;Signal Transduction;Spleen;Stream;Surface;Surveys;T-cell inflamed;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Textbooks;Tissues;tool;TRAF6 gene;transcriptome sequencing;Vascular Endothelial Cell;venule;Viral;Viral Antigens;Virus;Virus Diseases;Work

PROJECT_TITLE: Intravascular Immune Surveillance by Anti-viral T Cells

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Dissemination and Implementation Research;HIV/AIDS;Health Services;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention;Social Determinants of Health

ORG_CITY: PROVIDENCE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project narrative Retention in care and viral suppression via antiretroviral therapy are critical for continuing progress toward global elimination of HIV. This proposal develops and evaluates data-driven clinical decision support tools that are designed to maximize retention and viral suppression by identifying patients who will benefit from proactive support and other interventions. The tools utilize data from electronic health records and are customized to low- and middle-income country settings; successful implementation will maximize patient engagement in care, further reduce HIV incidence, and enable continued progress toward worldwide elimination of HIV.

PI_NAMEs: FRASER, HAMISH SF;HOGAN, JOSEPH W (contact);MWANGI, ANN

PROGRAM_OFFICER_NAME: GEZMU, MISRAK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Aftercare;Algorithms;Anti-viral Therapy;antiretroviral therapy;Architecture;Benchmarking;care outcomes;Caring;Case-Mix Adjustments;Client;Clinic;Clinical;Clinical Data;clinical decision support;Clinical Decision Support Systems;clinical implementation;clinical predictive model;Clinical Trials;Communication;Country;Data;Data Science;Data Set;Data Sources;data visualization;Databases;Decision Making;design;Development;Diagnosis;Drug resistance;Early identification;efficacy evaluation;electronic health data;Electronic Health Record;electronic health record system;Emergency Situation;Environment;Failure;Fast Healthcare Interoperability Resources;Feedback;field study;follow-up;Geographic Locations;Guidelines;Health;health care availability;Health care facility;Health system;Healthcare;high risk;HIV;HIV/AIDS;Impact evaluation;improved;Incidence;Individual;Infection;Intervention;Investments;Kenya;Learning;low and middle-income countries;machine learning algorithm;machine learning model;Measures;Methods;Modeling;Modern 1601-history;Motivation;Observational Study;Outcome;Output;pandemic disease;patient engagement;patient retention;Patients;Persons;Phase;Physicians;point of care;predictive modeling;Predictive Value;Prevalence;prevent;Process;programs;Public Health;public health intervention;Quality of Care;Randomized;Research;research clinical testing;Research Personnel;response;retention rate;Schedule;Social support;Specific qualifier value;statistical and machine learning;support tools;System;Technology;Testing;Time;tool;tool development;transmission process;Uncertainty;Update;Viral;Viral load measurement;Viral Load result;Visualization software;Work

PROJECT_TITLE: Data Science for Decision Support in the HIV Care Cascade

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ADMINISTERING_IC: HD

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Nutrition;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Wound Healing and Care

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Project Narrative While a great deal is known about how the transcriptional and signaling pathways that regulate the stem cell response to tissue regeneration, it is currently unknown whether stem cells integrate metabolic inputs into this process. Based on previous studies and my preliminary data, I propose that serine metabolism controls stem cell fate decisions during tissue regeneration. Successful completion of my aims will be of particular utility to promote wound repair and possibly enable dietary or metabolic interventions in the prevention and treatment of SCC in ways that do not impair normal regenerative processes.

PI_NAMEs: NOVAK, JESSE STEPHEN SWYER (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Ablation;Acceleration;Affect;alpha ketoglutarate;Anabolism;Apoptosis;ATAC-seq;cell behavior;Cell Lineage;cell type;Cells;ChIP-seq;Chromatin;chromatin modification;Clinical;Data;deprivation;Diet;dietary;Disease;endogenous stem cells;Environment;Enzymes;epidermal stem cell;Epidermis;epidermis cell;Equilibrium;EZH2 gene;fitness;Genetic;Genetic Transcription;Genus Mentha;Glycine;Goals;Hair;Hair follicle structure;hair regeneration;Hair Removal;healing;histone demethylase;histone modification;Histones;Immune;Immunofluorescence Microscopy;improved;Inflammation;Inflammatory;Intervention;knock-down;Knowledge;loss of function;Malignant Epithelial Cell;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Methyltransferase;Monitor;Morbidity - disease rate;mortality;Mus;Natural regeneration;novel;novel therapeutics;overexpression;Phase;Phenocopy;Phenotype;Prevention;Process;Production;Proliferating;re-epithelialization;regenerative;response;Role;Serine;Signal Pathway;Skin;skin barrier;skin squamous cell carcinoma;Specific qualifier value;Squamous cell carcinoma;stem cell fate;stem cells;Testing;Therapeutic;therapeutic candidate;Therapeutic Intervention;Time;tissue regeneration;tissue stem cells;Tissues;transcriptome sequencing;Translating;uptake;Work;wound;wound healing

PROJECT_TITLE: Dissecting the role of serine metabolism in stem cell fate and tissue regeneration


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Prevention

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Many enteric pathogens that cause high levels of morbidity and mortality are spread via the fecal oral route. Thus, an increased understanding of the molecular mechanisms that influence pathogen persistence within granulomas and their impact on host-to-host transmission will have a large impact on human health.

PI_NAMEs: MONACK, DENISE M (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Anti-Inflammatory Agents;Bacteria;Bacterial Infections;Biochemical;Carrier State;Cells;Chronic;chronic infection;Clinical;Critical Pathways;Data;Disease Progression;Disease Reservoirs;disease transmission;enteric pathogen;Gene Expression Profiling;Genetic;Goals;Granuloma;Health;Human;Immune;Immune response;Immunity;Immunologics;immunopathology;Infection;Inflammatory;Inflammatory Response;innovation;insight;Knowledge;Macrophage;man;MAPK8 gene;Mediating;Metabolic;microbial;Molecular;Monitor;Morbidity - disease rate;Morphology;mortality;Mus;Nature;NF-kappa B;novel marker;Oral;pathogen;Pathogenesis;Pathway interactions;persistent bacterial infection;pharmacologic;Phenotype;Preventive;preventive intervention;Publishing;Regulation;Research;Risk;Role;Route;Salmonella;Salmonella enterica;Salmonella infections;Salmonella typhimurium;Signal Pathway;Signal Transduction;Sorting;STAT3 gene;System;Systemic infection;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;TLR4 gene;TNF gene;transcription factor;transcriptomics;transmission process;Type III Secretion System Pathway;Virulence Factors;Visualization

PROJECT_TITLE: Mechanisms of persistent Salmonella infection

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


ORG_CITY: Decatur

ORG_STATE: GA

PHR: Mild Traumatic Brain Injury (mTBI) is an important priority for the Veterans Administration which affects many veterans of the conflicts in Iraq and Afghanistan, and when it co-occurs with posttraumatic stress disorder (PTSD) is associated with increased symptoms of post-concussion syndrome and suicidality, as well as worse health and cognitive outcomes. Currently there is no single effective treatment or rehabilitation for co-morbid mTBI and PTSD that addresses all the symptoms and the potential risk of progression of neurotrauma in these veterans. This project will look at a novel and newly available treatment for mTBI and PTSD called non-invasive Vagal Nerve Stimulation (nVNS) and how it affects brain and physiological responses to memory tasks and stress in veterans with mTBI and PTSD.

PI_NAMEs: BREMNER, JAMES DOUGLAS (contact)

PROJECT_TERMS: Address;Affect;Afghanistan;Anesthetics;Anterior;Area;biological adaptation to stress;Biological Markers;Blood;Brain;Brain imaging;Brain region;Cardiovascular system;Cerebrovascular Circulation;Cognition;Cognitive;cognitive function;combat;combat veteran;comorbidity;cost;Data;Devices;Disease;Economics;effective therapy;Exposure to;Feeling suicidal;follow-up;Future;Generations;Government;Guidelines;Headache;Health;Health Care Costs;Healthcare;Hippocampus;Home;Image;Immune response;Immunologic Markers;Impaired cognition;Implant;implantation;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Insula of Reil;Insurance;Interleukin-6;Intervention;Iraq;Learning;Measurement;Measures;Mediating;Memory;memory encoding;memory recall;mild traumatic brain injury;Morbidity - disease rate;Nerve;Nervous System Trauma;Neurobiology;Neuronal Plasticity;neuroregulation;novel;Operative Surgical Procedures;Outcome;pain reduction;Patients;Peripheral;Pharmaceutical Preparations;Photoplethysmography;Physiological;Physiology;Placebos;Positron-Emission Tomography;Post-Concussion Syndrome;Post-Traumatic Stress Disorders;prevent;Procedures;Productivity;progression risk;Publishing;Radiolabeled;Randomized;reduce symptoms;Rehabilitation therapy;Resistance;Resolution;response;restoration;Stress;suicidal;Surgical complication;Sympathetic Nerve Block;Symptoms;Syndrome;System;United States Department of Veterans Affairs;Vagus nerve structure;vasoconstriction;Veterans;Water;wearable device

PROJECT_TITLE: Non-Invasive Vagal Nerve Stimulation in Veterans with Mild Traumatic Brain Injury (mTBI)


NIH_SPENDING_CATS: Asthma;Genetics;Lung

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Interleukin-9 is a cytokine used by inflammatory cells to communicate with each other and target tissues during immune responses that range from allergic inflammation and inflammatory bowel disease to anti-tumor immunity. In this application, we are defining how IL-9 promotes inflammation from an allergic memory population, and examining the development of that IL-9-secreting T cell population.

PI_NAMEs: KAPLAN, MARK H (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Acute;Allergens;Allergic;allergic airway disease;Allergic Disease;Allergic inflammation;Anaphylaxis;Aspergillus fumigatus;Asthma;ATAC-seq;Attenuated;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;cell type;Cells;Chronic;Chronic Disease;Clinical Trials;Communication;conditional mutant;Cost of Illness;cytokine;Data;Development;differentiation in vitro;disease model;Effector Cell;Environment;Eye;Food Hypersensitivity;Funding;Gene Expression;Genetic Transcription;Goals;Grant;Health;Health Care Costs;Helper-Inducer T-Lymphocyte;Hematopoietic;human model;Hypersensitivity;IL9 gene;Immune response;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;Interleukin-13;Interleukin-4;Interleukin-9;IRF4 gene;Lung;Lymphoid Cell;Maintenance;Mediating;Memory;Modeling;mouse model;Mutant Strains Mice;Organ;Pathogenicity;Patients;Phenotype;Population;Production;Productivity;Regulation;Regulatory Element;response;Rest;Role;seasonal allergies;single-cell RNA sequencing;Source;Structure of parenchyma of lung;Symptoms;System;T cell response;T memory cell;T-Lymphocyte;Testing;Th2 Cells;Tissues;tool;transcription factor;Transcriptional Regulation;transcriptome;Tumor Immunity;Ulcerative Colitis;United States

PROJECT_TITLE: Allergic inflammation and Transcriptional Regulation in Th9 cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)S]