NIH_SPENDING_CATS: Behavioral and Social Science;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will elucidate fundamental cellular and circuit-level mechanisms that underlie photoreceptor death. The rationale is to enable the prediction of degrees of cone loss and estimation of health across ganglion cell populations by using a visual reflex as a diagnostic into the overall state of the degenerating retina. Results will be critical to identifying biomarkers for early photoreceptor death and to improving diagnostics and treatments for degenerative retinal diseases where photoreceptors die first, such as macular dystrophy and retinitis pigmentosa.

PI_NAMEs: DUNN, FELICE A (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Address;Affect;Behavior;Behavioral;Biological Markers;biomarker identification;Cell Physiology;Cell Size;cell type;Cells;Cessation of life;Compensation;Computer Models;Cone;Conscious;Data;design;Detection;detection sensitivity;Diagnosis;Diagnostic;Diagnostic tests;Disease;early detection biomarkers;Early Diagnosis;Early identification;Early treatment;Enabling Factors;Evaluation;Exhibits;Eye Movements;ganglion cell;Goals;Health;Human;Image;Impairment;improved;Inferior;insight;Knowledge;Link;macular dystrophy;Measures;Modeling;Monitor;motor behavior;Optics;Pathway interactions;Perception;photoreceptor degeneration;Photoreceptors;Physiological;Physiology;Population;prediction algorithm;prevent;Property;Psychophysics;Public Health;Reaction;Reflex action;Research;resilience;response;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;Retinal Ganglion Cells;Retinitis Pigmentosa;Sensitivity and Specificity;Specific qualifier value;Stereotyped Behavior;Synapses;System;Testing;Vision;Visual;Visual Pathways;Visual System;Work

PROJECT_TITLE: Synaptic and circuit mechanisms of compensation following loss of cone inputs in the mature retina

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Human Genome;Liver Disease;Microbiome;Natural Products

ORG_CITY: LOS ANGELES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative Non-alcoholic steatohepatitis (NASH) is emerging as a significant health problem in modern societies, yet the underlying molecular mechanisms remain poorly understood, preventing effective diagnostic and therapeutic strategies. Using innovative systems genetics approaches, we will elucidate the tissue-specific and cell-type specific mechanisms for NASH to identify potential therapeutic targets.

PI_NAMEs: LUSIS, ALDONS JAKE (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: 3-Dimensional;Ablation;Adipose tissue;Affect;Bacteria;bariatric surgery;Candidate Disease Gene;candidate validation;causal variant;Cell Communication;Cell Culture System;Cell Physiology;cell type;Cells;chronic liver disease;Cirrhosis;Clinical;Data;data integration;Data Set;Development;Diagnosis;Diagnostic;Dietary Supplementation;Disease;disease phenotype;Disease Progression;Dissection;effective therapy;end stage liver disease;Environmental Risk Factor;Enzymes;Exhibits;Fatty Liver;Fibrosis;Four Core Genotypes;Funding;Genes;Genetic;genetic analysis;genetic approach;Genetic Engineering;Genetic Variation;genome wide association study;Germ-Free;Gnotobiotic;Goals;Gonadal Hormones;Grant;gut microbes;gut microbiome;gut microbiota;Health;Heavy Drinking;Hepatic;Hepatic Stellate Cell;Hepatocyte;Human;human data;human disease;humanized mouse;Hybrids;IGFBP4 gene;improved;in vivo;Indoles;Inflammation;innovation;insight;Insulin-Like Growth Factor Binding Protein 4;intercellular communication;Investigation;Knock-out;Knockout Mice;Laboratories;Ligands;Link;Liver;Liver Fibrosis;loss of function;matrix Gla protein;metabolomics;microbiome composition;Modeling;Modernization;Molecular;molecular phenotype;mouse model;Mouse Strains;Mus;network models;Niacinamide;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;overexpression;Pathogenesis;Pathway interactions;Patients;Phenotype;Plasma;Population;Predisposition;prevent;Primary carcinoma of the liver cells;Process;Production;Propionic Acids;protective factors;Protein Secretion;Proteins;receptor;Regulation;resistant strain;Resolution;Resources;Risk;Role;sex;Sex Chromosomes;Sex Differences;Signal Transduction;simple steatosis;single cell sequencing;single-cell RNA sequencing;Societies;spheroids;Statistical Data Interpretation;Steatohepatitis;stellate cell;Study models;System;Technology;Testing;Therapeutic;therapeutic target;Tissues;trait;Transcript;transcriptome;transcriptomics;Transferase;Transforming Growth Factor beta;Transplantation

PROJECT_TITLE: Systems Genetics Dissection of Non-alcoholic Steatohepatitis

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Lung;Pulmonary Fibrosis

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE While the clearance of dying cells (efferocytosis) by macrophages is a fundamental mechanism of lung tissue homeostasis, efferocytosis is significantly reduced in lungs of patients with idiopathic pulmonary fibrosis (IPF) and mice with established lung fibrosis. The primary goal of the proposed studies is to delineate the feasibility of AMPK activators to recover efferocytosis and thereby promote fibrosis resolution in aging. The proposed studies will not only provide fundamental information concerning the pathological events associated with immune dysregulation, but also suggest novel therapeutics to stimulate resolution via modulation of the macrophage fibrogenic phenotype.

PI_NAMEs: THANNICKAL, VICTOR J.;ZMIJEWSKI, JAROSLAW WALDEMAR (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: 5'-AMP-activated protein kinase;Adoptive Transfer;Adverse effects;Affect;age related;Aging;alveolar epithelium;Apoptosis;Apoptotic;Area;Biogenesis;CD47 gene;Cells;Chronic;Clinical Research;Competence;design;Development;Disease;Eating;Epithelial Cells;Event;Extracellular Matrix;Fibroblasts;Fibrosis;functional outcomes;geroprotector;Goals;Homeostasis;idiopathic pulmonary fibrosis;Immune;Immune System Diseases;immunodeficiency;Impairment;Inflammation;Investigation;Left;Link;Lung;lung development;Lung Diseases;Lysosomes;Macrophage;Mediating;Mediator;Metformin;Mitochondria;Modeling;monocyte;Mus;Myeloid Cells;Myofibroblast;Natural regeneration;novel therapeutic intervention;novel therapeutics;old mice;Organ;organ growth;Pathologic;Patients;Phagocytes;Phenotype;Population;Population Dynamics;Pre-Clinical Model;Process;Pulmonary Fibrosis;Recovery;Regulation;Resolution;restoration;Risk Factors;Role;senescence associated secretory phenotype;senescent cell;senomorphic;Signal Transduction;Specificity;Structure of parenchyma of lung;Testing;Therapeutic;tissue repair;Tissues;transcriptomics;wound healing;young adult

PROJECT_TITLE: AMPK in the Development and resolution of Lung Fibrosis

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Neurosciences;Women's Health Research

ORG_CITY: FAYETTEVILLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE

ORG_STATE: AR

PHR: PROJECT NARRATIVE Recent clinical analyses have shown that increased infiltration of nerve fibers into breast tumors, also known as tumor innervation, is highly correlated with metastatic potential. Importantly, a wealth of literature suggests that metabolic dysregulation could in fact be linked to tumor innervation and metastasis. Therefore, the overall goal of this project is to investigate metabolic regulation of breast tumor innervation and potential impact it may have on metastasis.

PI_NAMEs: SONG, YOUNGHYE  (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;addiction;Address;Adipose tissue;aerobic glycolysis;afferent nerve;Blocking Antibodies;Brain-Derived Neurotrophic Factor;Breast Cancer Cell;breast cancer metastasis;breast cancer progression;Breast Epithelial Cells;cancer addiction;cancer cell;cancer type;Cause of Death;Cell Communication;Cell Line;Cell model;cell type;Cells;Cellular Metabolic Process;Clinical;clinical translation;clinically significant;Coculture Techniques;Collagen Fiber;Colorectal;Complex;Consumption;CRISPR/Cas technology;Data;Enzymes;Extracellular Matrix;Fatty acid glycerol esters;Fibroblasts;Formalin;Freezing;Frequencies;Future;Gene Modified;Genetic;Glutamates;Glutaminase;Glutamine;Glycolysis;Goals;Growth Factor;Head and neck structure;Human;Hydrogels;Image;Implant;In Vitro;in vitro Model;in vivo;Infiltration;inhibitor;innovation;insight;interest;Invaded;Investigation;Knock-out;Knowledge;lactate dehydrogenase A;Link;Literature;Lung;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;MCF10A cells;Metabolic;metabolic abnormality assessment;Metabolic Control;metabolic profile;Metabolism;Metastatic breast cancer;Metastatic Neoplasm to the Breast;mimetics;Modeling;Molecular;Monitor;multiphoton microscopy;Mus;NADH;Neoplasm Metastasis;neoplastic cell;Nerve;Nerve Fibers;Nerve Growth Factor Receptors;Nerve Growth Factors;nerve supply;Neurites;neurotrophic factor;Neurotrophic Tyrosine Kinase Receptor Type 1;Neurotrophic Tyrosine Kinase Receptor Type 2;new therapeutic target;NGFR Protein;Noninfiltrating Intraductal Carcinoma;novel strategies;Optics;Organ;Outcome;Oxidation-Reduction;Pancreas;Paraffin Embedding;Pathologic;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Plasma;premalignant;prevent;Rattus;receptor;Regulation;Research;Role;Sampling;Series;Site;Skin;Spinal Ganglia;Stains;Stromal Cells;Temperature;Testing;Therapeutic;Thick;three dimensional cell culture;three-dimensional modeling;Tissue Engineering;Tissues;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Tissue;Validation;Work

PROJECT_TITLE: Investigating the role of metabolic rewiring in breast tumor innervation

STUDY_SECTION: THI

STUDY_SECTION_NAME: Tumor Host Interactions Study Section[THI]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SANTA BARBARA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: We study cell behaviors that contribute to normal processes like embryonic development and that are coopted in diseases like cancer. We have developed a powerful experimental model, which we exploit to derive deep insights into how genes control cell behaviors. In this work we will uncover how groups of cells squeeze in between other cells, a process that both immune cells and cancer cells use to move around the body.

PI_NAMEs: MONTELL, DENISE J. (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actins;Address;Automobile Driving;Behavior;Blood;cancer cell;cell behavior;Cell membrane;Cell model;cell motility;Cell Nucleus;Cell surface;Cells;Chemotaxis;Classification;Complex;Connexins;Contracts;Cytoplasm;Cytoskeleton;Data;Destinations;Development;Disease;Drosophila genus;Dynein ATPase;Elements;Embryonic Development;Environment;Epithelial Cells;epithelial to mesenchymal transition;Epithelium;Experimental Models;Filament;flexibility;follow-up;Funding;gain of function;Gap Junctions;Genes;Genetic;genetic manipulation;Geometry;Image;Immune;In Vitro;in vivo;in vivo evaluation;in vivo Model;Individual;innovation;insight;Intercellular Junctions;Intermediate Filaments;Lamins;Lead;Location;loss of function;Lymph;Malignant Epithelial Cell;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mechanics;Membrane;Metastatic Neoplasm to the Lung;Methods;Microtubules;migration;Modeling;Molecular;Motor;Movement;Myosin ATPase;Neocortex;Neoplasm Metastasis;nerve stem cell;novel;Nuclear;Nuclear Lamin;Oocytes;optogenetics;Organ Culture Techniques;Organelles;Ovary;Pathway interactions;Phenotype;Play;Post-Translational Protein Processing;Process;programs;Proteins;recruit;Resolution;rho;rho GTP-Binding Proteins;Role;Shapes;Site;Source;Surface;Techniques;Testing;Text;Texture;tissue repair;Tissues;tumor;Work;wound healing

PROJECT_TITLE: Making and breaking cell-cell contacts in development

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ADMINISTERING_IC: AA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Substance Misuse

ORG_CITY: SAN JOSE

ORG_DEPT: BIOLOGY

ORG_NAME: SAN JOSE STATE UNIVERSITY

PHR: Project Narrative This application requests funds for the purchase of an Andor BC43 spinning disc confocal microscope to add new capabilities for visualizing dynamic biological systems, and enable imaging of live mammalian cells, whole mount dissected tissues and organisms. This instrument will enhance research in 11 labs across three departments in the Colleges of Science and Engineering, and will provide outstanding educational benefits for hundreds of students at San José State University.

PI_NAMEs: GRILLO-HILL, BREE K. (contact)

PROGRAM_OFFICER_NAME: POWELL, ELIZABETH

PROJECT_TERMS: 11 year old;Active Learning;Biological Process;biological systems;Biomedical Research;Charge;college;Contract Services;Core Facility;Education;empowerment;Engineering;Event;experimental study;faculty research;Funding;Future;graduate student;Image;instrument;Laboratories;learning strategy;Life;Mammalian Cell;Microscope;Modeling;novel;Organism;Performance;Photobleaching;repaired;Request for Applications;Research;Reservations;Sampling;Scanning;Science;System;Testing;Training;undergraduate student;Underrepresented Minority;Underrepresented Populations;Universities;Visualization;Work

PROJECT_TITLE: Spinning Disk Confocal Microscope

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-L (30)]


NIH_SPENDING_CATS: Cancer;Cervical Cancer;Genetics;Precision Medicine;Radiation Oncology;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE Two thirds of cervical cancers have high levels of SERPINB3 and this is a biomarker for therapeutic resistance, recurrence, and death. This proposal aims to determine the effect of targeting SERPINB3 on cervical tumor cells and normal cells when treated with radiation and chemotherapy. Improving response to radiation and standard chemotherapy will improve overall survival for patients with cervical cancer and has the potential for broad impact for countless patients receiving these therapies.

PI_NAMEs: MARKOVINA, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Address;Aftercare;Aggressive behavior;Apoptosis;Apoptosis Promoter;Binding;Biochemical;Biological Assay;Biological Markers;Brachytherapy;candidate identification;Cathepsins;Cell Death;Cell Death Induction;Cell Line;Cell Membrane Permeability;Cell Nucleus;Cells;Cervical;Cervix Neoplasms;Cessation of life;chemoradiation;chemotherapy;Chemotherapy and/or radiation;Clinic;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Cytoplasm;Cytoprotection;Cytotoxic agent;Data;DNA Damage;effective therapy;Endocytosis;Epithelial Cells;Event;experimental study;Extravasation;Gene Expression Profile;genetic approach;Goals;Immunoprecipitation;improved;In Vitro;in vivo;in vivo evaluation;in vivo Model;inhibitor;innovation;irradiation;knock-down;Knock-out;Knowledge;Lead;Lysosomes;Malignant neoplasm of cervix uteri;Mediating;member;Mitochondria;Modeling;Molecular;Molecular Profiling;Morphology;mouse model;Mus;Necrosis;neoplastic cell;Normal Cell;Normal tissue morphology;novel;novel therapeutic intervention;Nuclear;Organelles;Pathway interactions;patient derived xenograft model;Patients;Peptide Hydrolases;personalized medicine;Phagocytosis;pharmacologic;pre-clinical;predictive marker;Predisposition;Publishing;Radiation Dose Unit;radiation resistance;radiation response;Radiation therapy;radioresistant;Radiosensitization;Recurrence;Regimen;Resistance;response;Role;Rupture;screening;Serine Proteinase Inhibitors;Signal Induction;Signal Transduction;Small Interfering RNA;small molecule;small molecule libraries;Specificity;Stimulus;Stress;success;System;Testing;Therapeutic;therapeutic target;therapy resistant;Time;Translating;treatment strategy;tumor;Tumor Cell Line;tumor microenvironment;Validation;vesicle transport;Work

PROJECT_TITLE: The role of SERPINB3 in cervical cancer therapeutic resistance

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative Circular RNAs (circRNAs) are highly relevant for public health due to their implicated role in many different disease settings and their potential as powerful biomarkers owed to their stability. This project will empower researchers to perform comprehensive computational circRNA analyses without requiring bioinformatics expertise by developing a modern, scalable, web-portal allowing them to improve human health at the forefront of genomics. These proposed advances are essential to perform robust circRNA analyses that are currently impossible due to missing infrastructure, computational expertise, or access to datasets.

PI_NAMEs: JAKOBI, TOBIAS  (contact)

PROGRAM_OFFICER_NAME: WELLINGTON, CHRISTOPHER

PROJECT_TERMS: Address;algorithm development;Algorithms;analysis pipeline;Benchmarking;Bioinformatics;bioinformatics infrastructure;Biological Markers;Biological Process;Cardiovascular Diseases;circular RNA;Circulation;cloud platform;Collaborations;Computer software;Computing Methodologies;Data;Data Analyses;Data Set;Data Sources;Dedications;design;Detection;detection sensitivity;Development;Disease;empowerment;Event;experience;Face;Familiarity;Feedback;Genomics;Goals;Health;Human;human disease;Improve Access;improved;Infrastructure;innovation;insight;Knowledge;Laboratories;Length;Letters;Libraries;Literature;Location;Malignant Neoplasms;Measures;method development;Methods;Modernization;mRNA Precursor;nanopore;Nervous System Disorder;Neurologic;novel;novel strategies;potential biomarker;Privacy;Process;Public Health;PubMed;Pythons;Regulation;Research;research and development;Research Personnel;RNA;RNA analysis;RNA primers;RNA Processing;RNA Sequences;Role;Sensitivity and Specificity;Small Interfering RNA;Software Tools;Source;Structure;success;Testing;Time;tool;transcriptome sequencing;usability;user-friendly;web app;web portal

PROJECT_TITLE: Enabling comprehensive and user-friendly circular RNA analyses with circtools.cloud

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: LONG BEACH

ORG_NAME: CALIFORNIA STATE UNIVERSITY LONG BEACH

PHR: Maldonado, Maricela; Confocal Microscope Project Narrative The versatility of using an Echo Confocal Microscope for the imaging of three-dimensional constructs has powerful implications in biomedical research and education at California State University, Long Beach (CSULB). Faculty and students will have access to an instrument that allows for live imaging of cells in the lab and/or examining 3D cell aggregate or tissue architecture which is essential for enhancing the cutting-edge research at CSULB. Importantly, the confocal microscope will provide additional hands-on educational experiences for students interested in biological/biomedical research fields.

PI_NAMEs: MALDONADO, MARICELA  (contact)

PROGRAM_OFFICER_NAME: BECKETT, DOROTHY

PROJECT_TERMS: 3-Dimensional;Acceleration;Biocompatible Materials;Biological;Biomedical Engineering;Biomedical Research;California;Cells;Core Facility;data acquisition;Development;Discipline;Education Projects;Faculty;hands-on learning;high resolution imaging;Housing;Hydrogels;Image;imaging capabilities;imaging facilities;Immunofluorescence Immunologic;instrument;laboratory curriculum;Lasers;Light;member;Microfluidics;Microscope;Microscopy;Optics;Organoids;Pancreas;Photobleaching;reconstruction;Research;Research Project Grants;Resolution;Resource Sharing;Sampling;Scanning;Students;Technology;Thinness;three dimensional structure;three-dimensional visualization;Tissues;tool;Training;Universities;user-friendly

PROJECT_TITLE: Confocal Microscope


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Dietary Supplements;Kidney Disease;Nutrition;Prevention

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE  Chronic kidney disease (CKD) affects approximately 37 million (1 in 7) U.S. adults, many of whom experience mineral and bone disorders (CKD-MBD) that increases risk for cardiovascular events, bone fractures, and death. Dietary and pharmaceutical treatments for CKD-MBD have diverse effects on serum calcium and phosphorus levels, but their effects on the underlying physiological processes of calcium and phosphorus balance are largely unknown. This project aims to determine the effects of two common CKD-MBD interventions, dietary phosphorus restriction and calcitriol (active vitamin D), on whole-body calcium and phosphorus balance, intestinal absorption, renal excretion, and bone turnover in two human clinical trials, with the overall goal of advancing foundational knowledge of calcium and phosphorus physiology in CKD that will support progress towards preventing morbidity and mortality associated with CKD-MBD.

PI_NAMEs: GALLANT, KATHLEEN M HILL (contact)

PROGRAM_OFFICER_NAME: GIPSON, DEBBIE SUE

PROJECT_TERMS: absorption;Address;Adult;Adverse effects;Affect;analog;Animal Feed;Area;bone;Bone Diseases;bone fragility;Bone Resorption;bone turnover;Calcitriol;Calcium;calcium absorption;Calcium Isotopes;calcium metabolism;cardiovascular disorder risk;cardiovascular risk factor;Cessation of life;Chronic Kidney Failure;Clinical;Clinical Research;Clinical Trials;Collection;comorbidity;Complex;Crossover Design;Data;design;Development;Diet;dietary;Dietary Phosphorus;Disease;Equilibrium;Event;Excretory function;experience;Feces;feeding;fibroblast growth factor 23;Fracture;fragility fracture;Future;Goals;Guidelines;Health;Homeostasis;Hormonal;Hormones;Human;Hypercalcemia;Hyperparathyroidism;improved;in vivo;innovation;Intake;Intervention;Intestinal Absorption;Intestines;intravenous administration;Isotopes;Kidney;Kidney Diseases;kinetic model;Kinetics;Knowledge;Link;Measurement;Measures;Metabolic;Metabolism;Methods;Minerals;Mission;Modeling;Morbidity - disease rate;mortality;Movement;National Institute of Diabetes and Digestive and Kidney Diseases;Oral Administration;Osteogenesis;Outcome;Patients;Pharmacologic Substance;Phase;Phosphorus;Physiologic calcification;Physiological;Physiological Processes;Physiology;Placebos;Plants;prevent;Prevention;PTH gene;Quality of life;Randomized;Rattus;Recommendation;renal calcium;Renal clearance function;Reporting;Research;Research Support;response;Risk;Role;Running;Serum;Source;Tissues;Tracer;Translational Research;treatment response;Urine;Vitamin D;Vitamin D Analog;Work

PROJECT_TITLE: Effects of Dietary Phosphorus Bioaccessibility and Calcitriol onPhosphorus and Calcium Whole-Body Balance and Kinetics in Moderate CKD

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ADMINISTERING_IC: OH

FUNDING_MECHANISM: OTHERS

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: SANTA FE

ORG_NAME: NEW MEXICO STATE DEPARTMENT OF HEALTH

ORG_STATE: NM

PHR: Project Narrative Occupational injuries and illnesses pose a substantial burden on communities, both financially and in terms of quality of life and mortality. Alleviating this burden requires an understanding of the nature, causes, victims and impacts of these injuries and illnesses. This understanding is achieved via occupational health surveillance activities, and can then be leveraged to effect positive change.

PI_NAMEs: KHAN, NAYEEM HASSAN  (contact)

PROGRAM_OFFICER_NAME: O'NEILL, EDUARDO

PROJECT_TITLE: New Mexico Occupational Health Surveillance Program


ED_INST_TYPE: OVERALL MEDICAL

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PI_NAMEs: HURTADO, DAVID ALEJANDRO (contact)

PROJECT_TITLE: Improving Occupational Health in Oregon: Turning Data to Action


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: FORT COLLINS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: RELEVANCE The proposed HICAHS Center includes cohesive and complementary research, intervention, outreach and translation efforts that address multiple NIOSH Strategic Objectives, NORA Strategic Goals, and CDC Healthy People 2030 Goals. The Center promotes health and reduces work hazards among high-risk industries within agriculture and forestry in Public Health Service Region VIII and beyond.

PI_NAMEs: STALLONES, LORANN  (contact)

PROJECT_TITLE: High Plains Intermountain Center for Agricultural Health and Safety (HICAHS)


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: DURHAM

ORG_NAME: UNIVERSITY OF NEW HAMPSHIRE

ORG_STATE: NH

PHR: PROJECT NARRATIVE Successful approaches to making the workplace safer begin with having the most accurate and current occupational health surveillance data. This often involves a unique and creative approach to data collection, data linkage and data analysis. The proposed activities will contribute to fundamental knowledge and the application of that knowledge to enhance worker well-being and reduce injury, illness, disability, and death.

PI_NAMEs: YANG, LIU  (contact)

PROJECT_TITLE: Expansion of the New Hampshire Occupational Health Surveillance Program VTF


ORG_CITY: BALTIMORE

ORG_NAME: MARYLAND STATE DEPARTMENT OF HEALTH

ORG_STATE: MD

PHR: Maryland Department of Health  FOA: PAR-20-312 State Occupational Safety and Health Surveillance Surveillance Program (U60) Maryland Title: Maryland Occupational Health and Safety Surveillance Project  CFDA: 93.262 PROJECT NARRATIVE The Maryland Occupational Health and Safety Surveillance project of the Maryland Department of Health (OHSSP) provides data on injury and illness in Maryland through existing occupational health indicators, and identifies important gaps in occupational safety and health data in specific worker populations. The new proposal focuses on an underserved population (migrant teenage workers) with an innovative approach that looks at an important health condition (asthma), pairing existing health department home visiting programs for asthma with a new complementary approach to employers to identify and reduce triggers in the workers’ occupational and home environments. The proposal also builds on pre-existing work to address the state’s opioid crisis with an innovative project to develop toolkits for employers and other stakeholders to improve management of opioids in Maryland workplaces.

PI_NAMEs: MITCHELL, CLIFFORD S (contact)


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: Basal cell carcinoma, the most prevalent cancer type worldwide, is particularly common in Veterans due to harsh environmental exposures encountered on active duty. Despite the significant global health and treatment cost burdens that this cancer imposes, a thorough understanding of the mechanisms that underlie its pathogenesis remains elusive. The stromal components of tumors, which include cancer-associated fibroblasts, have been shown to promote tumorigenesis. The proposed studies, which address a major gap in the skin cancer field, will investigate the direct role of dermal cancer-associated fibroblasts in basal cell carcinoma development. This research is critical for devising targeted skin cancer therapies to significantly improve Veteran healthcare.

PI_NAMEs: SELDIN, LINDSEY NICOLE (contact)

PROJECT_TERMS: 3-Dimensional;Ablation;active duty;Address;agent orange;Aging;Award;Basal cell carcinoma;Behavior;Biological Assay;Burn injury;Cancer Burden;cancer prevention;cancer therapy;cancer type;Carcinoma;career development;cell behavior;Cells;Characteristics;Chemicals;Coculture Techniques;Coupled;CRISPR/Cas technology;Cutaneous;Cytometry;Data;Dermal;Development;Disease;DNA Damage;Environment;Environmental Exposure;Epidermis;Epithelial Cell Proliferation;Epithelial Cells;Epithelium;Exhibits;Exposure to;Failure;Fibroblasts;Fluorescence-Activated Cell Sorting;Foundations;Funding;Gene Expression;Gene Expression Profile;General Population;genetic signature;global health;Goals;Growth;Health;Health Care Costs;Healthcare;Heterogeneity;Human;Hyperplasia;Image;improved;in vivo;Individual;Inflammasome;Inflammatory;inhibitor;insight;Institution;Interleukin-1 beta;intravital imaging;knockout gene;Maintenance;Malignant Neoplasms;Medical;military veteran;mouse model;Mutagens;Neoplasms;NOD/SCID mouse;Normal Cell;novel;novel therapeutics;Organoids;Outcome;Pathogenesis;patient derived xenograft model;Patients;pharmacologic;Phase;Prevalence;prevent;Process;programs;Proliferating;protein expression;Proteins;Proteomics;Quality of life;Radiation;repaired;Research;Research Proposals;response;Role;Sampling;Secure;Signal Pathway;Signal Transduction;single cell analysis;single cell technology;single-cell RNA sequencing;skill acquisition;Skin;Skin Cancer;Skin Carcinoma;skin disorder;Skin tumorigenesis;Sorting;Source;Specific qualifier value;Specimen;Squamous cell carcinoma;targeted treatment;Technical Expertise;Testing;Therapeutic;Time;Tissues;Toxic Environmental Substances;Training;Transcript;Transgenic Mice;Transplantation;Treatment Cost;tumor;tumor progression;tumorigenesis;tumorigenic;Ultraviolet Rays;Veterans;Vietnam;Work;World War II;wound;Xenograft procedure

PROJECT_TITLE: The Role of Dermal Fibroblasts in Skin Cancer


PHR: Project Narrative This application proposes to define the role and mechanisms of Slit/Roundabout (Robo)- GTPase activating protein 1(srGAP1) in its reciprocal regulations with both androgen receptor signaling and Wnt signaling during progression to castration-resistant prostate cancer (CRPC) and in resistance to Enzalutamide treatment, and to determine whether the expression of srGAP1 will be a good predictor for disease progression and overall survival of CRPC patients.

PI_NAMEs: ZI, XIAOLIN  (contact)

PROJECT_TERMS: abiraterone;Acetates;Affect;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgen sensitive;Androgens;Anti-androgen Therapy;Area;Behavior;Benign Prostatic Hypertrophy;beta catenin;Binding;Biological;Biological Assay;Biological Markers;cancer diagnosis;Cancer Patient;Carcinoma;chromatin immunoprecipitation;cohort;Databases;deprivation;Diagnosis;Disease;Disease Progression;Early Detection Research Network;enzalutamide;Family;Fibroblasts;follow-up;Generations;Genes;Genetic Transcription;Growth;GTPase-Activating Proteins;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate Phosphohydrolases;healthcare burden;Human;Immunohistochemistry;implantation;in silico;in vivo;Individual;Invaded;Length;Link;Luciferases;lymphoid enhancer-binding factor 1;Malignant neoplasm of prostate;Medical center;migration;military veteran;mutant;Neoplasm Metastasis;Neoplasms;new therapeutic target;novel;novel strategies;Nuclear;Oncogenes;overexpression;palliative;Patients;Pharmaceutical Preparations;Play;precision medicine;Prognosis;Prognostic Marker;programs;promoter;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer metastasis;prostate cancer progression;prostate transurethral resection;Radical Prostatectomy;Receptor Signaling;Regulation;Reporter;Research Priority;Resistance;Resistance development;Resources;rho GTPase-activating protein;Role;SCID Mice;Signal Transduction;small hairpin RNA;Specimen;Testing;Tissue Microarray;Tissues;transdifferentiation;treatment response;tumor;tumorigenesis;United States Department of Veterans Affairs;Variant;Veterans;WNT Signaling Pathway;Work;Xenograft Model

PROJECT_TITLE: A novel targetable mechanism for castration-resistant prostate cancer


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: The goal of this proposal is to develop novel chemotherapeutic drugs that target the mitochondria and can be used for the treatment of high grade serous ovarian cancer. With a growing number of women Veterans, it is anticipated that the number of patients with ovarian cancer and other gynecologic malignancies will increase in the coming years. The development of novel chemotherapeutic agents against ovarian cancer will therefore lead to effective and novel strategies for the management and treatment of this malignancy in women Veterans.

PI_NAMEs: PATANKAR, MANISH S (contact)

PROJECT_TERMS: Active Learning;Address;aerobic glycolysis;Age;age group;Age Years;aging population;Apoptosis;atovaquone;Benzoquinones;Biochemical;Biological;Biological Assay;Biological Response Modifier Therapy;Biology;Biometry;Cancer Biology;cancer cell;Cancer cell line;Cancer Model;cancer stem cell;cancer therapy;candidate identification;carbonyl compound;Cell Death;Cell Death Inhibition;Cells;Characteristics;Chemicals;cheminformatics;chemotherapeutic agent;chemotherapy;citral;Clinical Management;Clinical Trials;cohort;cost effective;Curcumin;Data;data mining;Development;Diagnosis;Disease;DNA Damage;DNA Repair;DNA strand break;Dose;drug candidate;Drug Targeting;effective therapy;Electron Transport;Exhibits;experimental study;FADH2;Female;Female Genital Neoplasms;functional group;Future;Genetic Complementation Test;Goals;Healthcare Systems;high standard;high throughput screening;in vivo;Incidence;Induction of Apoptosis;inhibitor;innovation;interest;Lead;machine learning model;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Metabolic;Metabolic Pathway;metabolic rate;Methods;military veteran;mimetics;Mitochondria;model building;Modeling;Modernization;Molecular;mouse model;NADH;neoplastic cell;Non-Malignant;novel;novel anticancer drug;novel strategies;Ovarian;ovarian neoplasm;Ovarian Serous Tumor;oxidative damage;Oxidative Phosphorylation;Oxidative Stress;Oxygen;Patients;Periodicity;Pharmaceutical Preparations;pharmacokinetic characteristic;pharmacologic;plumbagin;Poly(ADP-ribose) Polymerase Inhibitor;Population;Postmenopause;pre-clinical;preclinical study;Predisposition;Property;protein complex;PubChem;public repository;Reactive Oxygen Species;Records;Recurrent tumor;Reporting;Research;scaffold;screening;Screening procedure;Serous;Site;small molecule;small molecule inhibitor;Standardization;synergism;targeted agent;Testing;Therapeutic;Tissues;Toxic effect;TP53 gene;Treatment Protocols;tumor;tumor growth;tumor metabolism;tumor microenvironment;Ubiquinone;Veterans;Woman;Work

PROJECT_TITLE: Using a chemical biology approach to develop novel inhibitors of mitochondrial oxidative phosphorylation for the treatment of ovarian cancer


ORG_CITY: NORTHPORT

ORG_NAME: NORTHPORT VA MEDICAL CENTER

ORG_STATE: NY

PHR: Project Narrative The proposed project is aimed to develop a miRNA based therapeutic strategy to eliminate 5- FU resistant colon cancer stem cells and to inhibit colorectal cancer metastasis. We have created new miR-15a mimics with potent therapeutic efficacy to eliminate colorectal cancer metastasis in mouse model. As a result, the new therapeutic molecules may have a potential to extend patient life and to improve quality of life of patient with advanced metastatic colorectal cancer.

PI_NAMEs: JU, JINGFANG  (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Apoptosis;appetite loss;base;BCL2 gene;BMI1 gene;cancer cell;cancer diagnosis;cancer recurrence;cancer stem cell;CD44 gene;Cell Cycle Regulation;Cell Line;Cessation of life;Chemoresistance;chemotherapy;Colon;colon cancer metastasis;Colon Carcinoma;Colorectal Cancer;colorectal cancer metastasis;Complex;delivery vehicle;design;Development;Drug Kinetics;Drug or chemical Tissue Distribution;Early Diagnosis;Enzymes;Epigenetic Process;Epithelial Cells;Failure;Female;fluoropyrimidine;Fluorouracil;Gene Expression Regulation;Genes;Goals;Growth;Hair;Human;improved;in vivo;Incidence;knock-down;Laboratories;Life;lipid nanoparticle;Location;loss of function;Magnetic nanoparticles;male;men;metastatic colorectal;MicroRNAs;military veteran;Modeling;Modification;mouse model;mRNA Translation;Mus;novel;novel strategies;novel therapeutics;oligofectamine;Organoids;Pathway interactions;patient derived xenograft model;Patients;Play;Population;posttranscriptional;Proliferating;Protein Biosynthesis;protein expression;Quality of life;Resistance;resistance mechanism;RNA Degradation;Role;Specificity;stem cell growth;subcutaneous;synergism;Therapeutic;therapeutic development;therapeutic miRNA;therapeutic target;Thymidylate Synthase;Toxic effect;Treatment Efficacy;treatment strategy;tumor;Tumor Suppressor Proteins;tumorigenesis;TYMS gene;United States;Untranslated RNA;Uracil;Veterans;Weight;Woman

PROJECT_TITLE: Development of novel miRNA based novel therapeutics for metastatic colorectal cancer


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Ongoing research projects focus on brain injury (traumatic brain injury and stroke) and transplant rejection (face, limb and heart). Studies investigate mechanisms of injury and therapeutic strategies. These are areas of research highly relevant to Veteran health and healthcare. Traumatic Brain Injury (TBI) is a major cause of death and disability, and for military personnel, between 14-20% of surviving casualties had a TBI. Stroke is the main cause of long- term disability, and the risk of stroke increases significantly with age. The proportion of veterans who are older than 65 continues to increase. Explosive devices and blast trauma often result in debilitating injuries to unprotected areas such as the face and limbs. Restoring facial appearance or providing new limbs via transplantation can provide mobility and function, can dramatically improve quality of life, and can restore the mental health of a traumatized soldier.

PI_NAMEs: TOMLINSON, STEPHEN  (contact)

PROJECT_TERMS: Academy;activation product;Acute;acute stroke;adaptive immunity;addiction;Affect;Age;age effect;allograft rejection;Allografting;American;Antibodies;Appearance;Appointment;Area;Autoimmunity;Award;Biological Markers;Biotechnology;blast trauma;Blood;Brain;Brain Death;Brain Injuries;career;Cause of Death;Cells;Central Nervous System Diseases;central nervous system injury;Chronic;Circulation;Clinical;clinically relevant;Collaborations;Collection;comorbidity;Complement;Complement Activation;Complement Inactivators;complement pathway;complement system;Country;dementia risk;Deposition;Development;Devices;disability;Disclosure;Disease;Doctor of Philosophy;doctoral student;effective therapy;Eligibility Determination;experience;exposure to cigarette smoke;Face;facial transplantation;Faculty;Foundations;Funding;Future;Goals;Graft Rejection;Grant;Health;Healthcare;Heart;Hepatology;high risk;Hindlimb;HIV;Host Defense;human old age (65+);Immune system;Immunoglobulin M;Immunology;Immunosuppression;Immunosuppressive Agents;Impaired cognition;improved;Inflammation;Injury;injury and repair;interest;International;invention;Investigation;Investments;isoimmunity;Jail;Joints;Journals;Laboratories;Legal patent;Licensing;Limb structure;limb transplantation;Long term disability;Malignant Neoplasms;Mediating;Mental Health;Mentors;Mentorship;Military Personnel;military veteran;Molecular;mouse model;Names;Natural Immunity;Nature;Nerve Degeneration;neuroinflammation;neuron loss;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Outcome;Paper;Participant;pathogen;Pathologic;Pattern;Population;post stroke;Post-Traumatic Stress Disorders;Postdoctoral Fellow;prevent;Process;programs;Proteins;Publications;Publishing;Quality of life;Recovery;Recovery of Function;Regulation;rehabilitation research;Rehabilitation therapy;repaired;Reperfusion Injury;Reperfusion Therapy;Research;Research Activity;research and development;Research Project Grants;response;Review Committee;Role;San Francisco;Science;Scientist;Series;Serum;Services;Sheep;Site;Smoking;Soldier;spatiotemporal;Spinal cord injury;standard of care;Stroke;stroke model;stroke outcome;stroke patient;stroke risk;stroke therapy;symposium;Synapses;Therapeutic;therapeutically effective;Tissues;tool;Training;Transplantation;Transplantation Immunology;Trauma;Traumatic Brain Injury;treatment strategy;United States National Institutes of Health;Vascularization;Veterans;Vietnam;Visit;visual dysfunction;Work

PROJECT_TITLE: BLR&D Research Career Scientist Award Application for Dr. Stephen Tomlinson


ORG_CITY: NASHVILLE

ORG_STATE: TN

PHR: End stage renal disease (ESRD) is a major cause of morbidity and mortality for our Veterans. One of the hallmarks of ESRD is fibrosis, characterized by abnormal accumulation of extracellular matrix leading to the loss of kidney function. The PI’s goal is to identify the mechanisms that control the modulation of matrix turnover in injured kidneys to devise more effective anti-fibrotic therapies. The PI studies how the matrix receptor integrin α1β1 controls matrix homeostasis in health and disease. She found that integrin α1β1 plays an anti-fibrotic role by negatively regulating tyrosine phosphorylation levels and consequent nuclear localization of the ribonucleoprotein Fused in Sarcoma (FUS). She also found that FUS promotes collagen transcription and its downregulation reduces collagen synthesis. Her goal is to develop strategies to prevent FUS nuclear translocation thus reducing its pro- fibrotic action in a preclinical model. This work will lead to the development of novel strategies to halt/ prevent kidney fibrosis and, hence, improve the quality of lives of our Veterans.

PI_NAMEs: POZZI, AMBRA  (contact)

PROJECT_TERMS: active duty;Affect;American;Animal Model;antifibrotic treatment;Area;Award;base;Binding;Biology;career;CCL2 gene;Cell Nucleus;Cells;Cessation of life;Chromatin;Chronic Kidney Failure;clinical investigation;Clinical Management;Collagen;Collagen Receptors;Collagen Type IV;DDR1 gene;Deposition;Development;discoidin receptor;Disease;DNA;Doctor of Philosophy;Down-Regulation;ECM receptor;editorial;End stage renal failure;Epidermal Growth Factor Receptor;Etiology;Extracellular Matrix;Fibrosis;Funding;Funding Agency;fused in sarcoma;Generations;Genetic;Genetic Transcription;Goals;Health;Healthcare;Homeostasis;Human;improved;In Vitro;in vivo;indexing;Inflammatory;inhibitor;Injury;Injury to Kidney;Integrin Inhibition;Integrins;International;Journals;Kidney;Kidney Diseases;kidney fibrosis;Ligands;Mediating;medical schools;Medicine;Military Personnel;Mission;Morbidity - disease rate;mortality;mouse development;NADPH Oxidase;Names;National Institute of Diabetes and Digestive and Kidney Diseases;Nephrology;novel;novel strategies;Nuclear;Nuclear Translocation;Outcome;Oxidative Stress;Pathology;Pathway interactions;Peer Review;Penetration;Peptides;Pharmaceutical Preparations;Phosphorylation;Play;Pre-Clinical Model;prevent;Privatization;Production;professor;Profibrotic signal;programs;promoter;Protein Tyrosine Phosphatase;Publications;Publishing;Quality of life;Reactive Oxygen Species;receptor;Receptor Activation;recruit;Regulation;Renal function;Research;Ribonucleoproteins;RNA-Binding Proteins;Role;Scientist;Sclerosis;Signal Transduction;Site;small molecule;small molecule inhibitor;Societies;T-cell protein tyrosine phosphatase;Therapeutic;transcription factor;Transforming Growth Factor beta Receptors;Tyrosine Phosphorylation;United States National Institutes of Health;Universities;Veterans;Work

PROJECT_TITLE: BLR&D Merit Review Research Career Scientist (RCS) Award (IK6)


PHR: TBI is a major health problem in Veterans of all ages. The negative impact of this devastating condition on Veterans will increase enormously unless new therapies that can minimize the secondary brain damage after TBI are tested and propagated to clinical trials. Oxidative stress and endoplasmic reticulum (ER) stress are controllable pathologic events that promoter neuronal death after TBI. In a current Merit Review Grant, the Vemuganti Lab is testing the long-term effects of a combo therapy that curtails oxidative stress and ER stress in rodents subjected to TBI. Stroke is also a major health problem of Veterans. Dr. Vemuganti’s pending Merit Review Grant will test the functional significance of a small RNA 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.

PI_NAMEs: VEMUGANTI, RAGHU  (contact)

PROJECT_TERMS: Acute;Age;alpha synuclein;Animals;Anti-Inflammatory Agents;Antioxidants;Apoptotic;Award;Brain;Brain Injuries;Brain Ischemia;career;Central Nervous System;Cerebral Ischemia;Cerebrovascular Circulation;circular RNA;Clinical Trials;Cognitive;cognitive function;Combined Modality Therapy;comorbidity;controlled cortical impact;Cortical Contusions;Data;derepression;Diabetes Mellitus;disability;DNA;dysbiosis;efficacious treatment;endoplasmic reticulum stress;Epigenetic Process;epitranscriptomics;Event;Family;Functional disorder;functional gain;functional outcomes;Funding;Genes;Goals;Grant Review;gut dysbiosis;gut inflammation;gut microbiome;Health;Hour;Human Resources;improved;indexing;Industry;Inflammation;Injury;Ischemic Brain Injury;Ischemic Stroke;Journals;Long-Term Effects;Mediating;Metabolism;MicroRNAs;Middle Cerebral Artery Occlusion;Modification;Molecular;Motor;mouse model;Mus;Neurobiology;neurochemistry;Neurologic Deficit;Neurologic Dysfunctions;neurological recovery;neuron loss;Neurons;neuroprotection;neuropsychiatry;Neurosciences;neurotoxicity;new therapeutic target;novel therapeutics;Outcome;Oxidative Stress;Paper;Parkinson Disease;Pathologic;Pathology;Pharmaceutical Preparations;Phosphorylation;Play;polyphenol;post stroke;prevent;Prevention;programs;promoter;prophylactic;Protein Family;Proteins;Publications;Publishing;Quality of life;Recovery of Function;Research;Resveratrol;Rodent;Role;Science;Scientist;Seminal;Services;sex;Signal Transduction;Small RNA;Societies;Source;Stroke;stroke model;Stroke prevention;stroke therapy;Testing;Toxic effect;transcription factor;Transcriptional Regulation;Translations;Traumatic Brain Injury;Traumatic Brain Injury recovery;Treatment Efficacy;Ubiquitination;Untranslated RNA;Veterans

PROJECT_TITLE: BLRD Research Career Scientist Award Application


ORG_CITY: PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Stroke remains as the 5th leading cause of death and long-term adult disability in the USA. Moreover, hypertension and pre-hypertension are common in active US military personnel. Moreover, post-traumatic stress disorder is associated with different cardiovascular and cerebrovascular diseases in older veterans, including hypertension and ischemic stroke. Traumatic brain injury (TBI)-induced white matter brain tissue damage contributes to motor, cognitive, behavioral, and psychiatric deficits. Our research program has two objectives: 1) to investigate cellular mechanisms underlying worsened ischemic stroke in hypertensive brains and to develop a novel therapeutic strategy for ischemic stroke with comorbid hypertension; 2) to investigate the roles of microglia-oligodendrocyte interactions in white matter injury and tissue repair in experimental TBI models and to explore glia-oriented therapeutic strategies for treating TBI.

PI_NAMEs: SUN, DANDAN  (contact)

PROJECT_TERMS: Acceleration;Achievement;Acute;Adult;Affect;Alanine;Alteplase;Animal Model;Anti-Hypertensive Agents;Attenuated;Autopsy;Award;Behavioral;Brain;Brain Diseases;Brain Injuries;brain tissue;burden of illness;Cardiovascular Diseases;career;Carrier Proteins;Cause of Death;cell injury;Central Nervous System;Cerebral Edema;Cerebrospinal Fluid;Cerebrovascular Disorders;chloride-cotransporter potassium;Clover;Cognitive;Collaborations;Communication;comorbidity;controlled cortical impact;cytokine;cytotoxic;Development;disability;Disclosure;Disease;Edema;excitotoxicity;Exhibits;Free Radicals;Functional disorder;Funding;Grant;Health;health care service;Healthcare;Hemorrhage;High Prevalence;Homeostasis;Human;Hybrids;Hydrocephalus;Hypertension;hypertensive;Impairment;improved;improved outcome;Inbred SHR Rats;Inbred WKY Rats;inclusion criteria;Inflammation;Inflammatory;inhibitor;injury and repair;innovation;International;invention;Ion Transport;Ions;Ischemia;Ischemic Brain Injury;Ischemic Stroke;Kidney;Knockout Mice;Legal patent;LoxP-flanked allele;Lysine;Macrophage;Maintenance;Malignant - descriptor;Mediating;Membrane;Microglia;Middle Cerebral Artery Infarction;Military Personnel;Mission;Modeling;Motor;Mus;NADPH Oxidase;Nature;Nervous System Disorder;Nervous System Physiology;Neuroglia;neuroprotection;Neuroprotective Agents;normotensive;novel;novel therapeutic intervention;Oligodendroglia;Oxidative Stress;Pathogenesis;Patients;Persons;pH Homeostasis;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Play;Post-Traumatic Stress Disorders;Predisposition;prehypertension;preservation;Production;programs;Proline;protein expression;Protein Isoforms;Proteins;Rattus;Recovery of Function;Regulation;remyelination;Reporting;Research;Research Project Grants;Rights;Role;scaffold;Scientist;Sensorimotor functions;Signal Transduction;social;Sodium Chloride;Stroke;stroke intervention;stroke model;stroke therapy;Structure of choroid plexus;Superoxides;symporter;Synapses;Technology Transfer;Therapeutic;therapeutic target;tissue repair;translational approach;Translational Research;Traumatic Brain Injury;United States Department of Veterans Affairs;Veterans;white matter;white matter injury


ORG_CITY: COLUMBIA

ORG_NAME: HARRY S. TRUMAN MEMORIAL VA HOSPITAL

PHR: Project Narrative Eye trauma and injury are the major causes of vision loss among our veterans and troops engaged in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), New Dawn, and fighting terrorism. Despite using protective gear, eye injuries have risen from 2% in World Wars to 13% in OIF and OEF. Presently, >167,000 Veterans are legally blind, 1.5 million have significantly compromised vision, and >7000 veterans become blind each year. Our research is focused on studying the effects of traumatic eye and brain injury on vision loss. Both injuries are becoming more common among Veterans, active military personnel, and civilians. Our projects are focussed on developing novel nanomedicine and gene-based therapies for treating corneal scars/ fibrosis, and studying pathophysiologic mechanisms causing blindness after chemical or surgical injury. Our goal is to establish efficacious and safe molecular therapies to treat blindness and restore vision in humans and service dogs and advance the mechanistic understanding of corneal wound healing and diabetic retinopathy.

PI_NAMEs: MOHAN, RAJIV RAVINDRA (contact)

PROJECT_TERMS: Academy;Acrolein;active duty;Acute;Affect;Animal Model;Animals;Area;Asia;Automobile Driving;Award;Bilateral;blind;Blindness;Book Chapters;Brain Injuries;Canada;Canis familiaris;career;Chemical Injury;Chemicals;Chlorine;Chronic;Cicatrix;Complement Factor H;Congresses;Cornea;Corneal Diseases;Corneal dystrophy;corneal epithelial wound healing;Corneal Neovascularization;corneal scar;Data;Defect;delivery vehicle;Dependovirus;design;Development;Diabetic Retinopathy;disabled;Drops;effective therapy;Elderly;Ensure;Epigenetic Process;European;Event;Eye;Eye diseases;Eye Enucleation;Eye Injuries;Family suidae;Fibrosis;fighting;Formulation;Foundations;France;Freedom;Functional disorder;Funding;gene therapy;General Population;Genes;Goals;Grant;Health;health care delivery;health care quality;high risk;Human;Hydrogen Sulfide;In Vitro;in vivo;indexing;Industry;injured;Injury;insight;Institution;International;Interruption;Italy;Journals;Keratoplasty;Koreans;Laboratories;Lasers;Law Enforcement;Laws;Lead;Legal Blindness;legally blind;Lentivirus;Link;Long term disability;Mediating;medical countermeasure;medical schools;meetings;Military Personnel;minimally invasive;Mission;Modeling;Modification;Molecular;multimodality;Mustard Gas;Myopia;nanomedicine;nanoparticle;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;operation;Ophthalmologic Surgical Procedures;Ophthalmology;Organ Culture Techniques;Oryctolagus cuniculus;Pathogenesis;Pathologic;Patients;Peer Review;Persons;Photorefractive Keratectomy;Pilot Projects;Plasmids;Poison;Population;porcine model;pre-clinical;precision medicine;prevent;Process;Productivity;programs;Publications;Publishing;Quality of life;Refractive Errors;Research;response;Retina;Rodent;Role;Safety;Scientist;Security;Service animal;side effect;sight restoration;Signal Pathway;Societies;South Africa;Surgical Injuries;Techniques;Terrorism;Testing;therapeutic gene;therapeutic target;Time;Tissues;Toxic effect;Translational Research;Trauma;Traumatic Brain Injury;Traumatic injury;United States Department of Veterans Affairs;United States National Institutes of Health;vector;Veterans;Vietnam;Vision;War;wound healing

PROJECT_TITLE: BLR&D Research Career Scientist Award Application (Renewal)


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: The prevalence of obesity and the metabolic syndrome has increased dramatically in developed countries over the last three decades. Obesity is a strong risk factor for a number of cancers including breast, liver and colorectal cancer. The goal of our research is to understand how obesity alters the liver metabolism and the metabolic milieu to promote cancer development.

PI_NAMEs: WEBSTER, NICHOLAS J (contact)

PROJECT_TERMS: Acceleration;Accounting;Address;Adipose tissue;Aging;Alcohol consumption;Alcoholism;American Cancer Society;Apoptosis;Area;Astronomy;aurora B kinase;Award;Biochemical;Biological;Biological Process;Breast Cancer Risk Factor;Cancer Center Support Grant;career;Cell Culture Techniques;Cells;Chronic;Chronic Disease;chronic liver disease;Cirrhosis;clinical investigation;Colon Carcinoma;Colorectal Cancer;Communication;cost;Cyclic AMP;Dendritic Cells;design;Developed Countries;Development;Diabetes Mellitus;Diagnosis;diet-induced obesity;Dietary Intervention;Direct Costs;Disease;DNMT3B gene;effective therapy;Endocrinology;Epidemiology;Etiology;Event;experimental study;Exposure to;Facilities and Administrative Costs;Fatty Acids;Fibrosis;FN1 gene;Functional disorder;Funding;glucose metabolism;Goals;Grant;Growth;Health;Health Care Costs;heart disease risk;Hepatitis B Virus;Hepatitis C virus;Hepatocarcinogenesis;Hepatocyte;Hepatology;High Fat Diet;high risk;Hormonal;Human;Hyperglycemia;Hyperinsulinism;hypothalamic pituitary axis;IL17 gene;Impairment;Incidence;indexing;Inflammation;Insulin Resistance;interest;Interruption;Journals;Knock-out;Life Style;Link;lipid metabolism;Liver;Liver diseases;liver function;liver inflammation;liver injury;liver metabolism;Malignant Breast Neoplasm;Malignant neoplasm of liver;Malignant neoplasm of lung;Malignant Neoplasms;MDM2 gene;Medicine;Metabolic;Metabolic syndrome;Metabolism;military service;military veteran;Modeling;Molecular;Molecular Profiling;Morbidity - disease rate;mortality;Mus;MXD1 gene;Nature;neoplastic cell;new therapeutic target;non-alcoholic;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;nutrition;Nutritional;obese person;Obesity;Obesity associated liver disease;obesity risk;Omega-3 Fatty Acids;Oncogenes;Overnutrition;Overweight;Paper;Pathogenesis;patient population;Patients;Persons;Phenotype;Physiological;Physiology;Population;Postmenopause;Predisposition;Prevalence;prevent;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;Proliferating;proteostasis;Publishing;Regulation;Reporting;Reproductive Medicine;Reproductive Sciences;Research;Resource Sharing;response;Risk;Risk Factors;Risk Reduction;RNA Splicing;Scientist;Signal Transduction;Smoking;Stimulus;Survival Rate;System;T-Lymphocyte;targeted treatment;tensin;Time;Time-restricted feeding;Tissues;toxicant;Toxicant exposure;TP53 gene;TP73 gene;Training;tumor;tumor growth;Tumor Suppressor Genes;United States National Academy of Sciences;United States National Institutes of Health;Veterans;Virus Diseases;Woman;Women's Health;Writing

PROJECT_TITLE: BLR&D Research Career Scientist Award Application


ORG_CITY: INDIANAPOLIS

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: The focus of my VA Merit is to understand (i) how mast cells migrate to the liver during damage and (ii) which molecular and/or cellular signals are involved in mast cell migration. During cholestatic liver injury, cholangiocytes express and secrete a number of neuroendocrine factors that influence liver damage, inflammation and hepatic fibrosis. Work from my collaborator, Dr. Gianfranco Alpini, SR VA RCS, RLR VA Medical Center, has shown that cholangiocytes become senescent during liver damage and take on a senescence-associated secretory phenotype (SASP) causing them to secrete mediators which are also considered to be chemoattractants for mast cell migration. The overall hypothesis of this application is that during liver injury, damaged, senescent cholangiocytes secrete SASP factors which serve as chemoattractants for mast cells inducing their migration into the liver where they reside near damaged cholangiocytes.

PI_NAMEs: FRANCIS, HEATHER L (contact)

PROJECT_TERMS: Abdominal Pain;Ablation;Aging;American;angiogenesis;Antihistamines;Area;autocrine;Award;Bile Acids;bile duct;Bile fluid;Biliary;biliary tract;Biology;biomarker identification;career;Cell Communication;Cell Count;cell motility;cell transformation;cell type;Cells;Chemotactic Factors;Cholangiocarcinoma;cholangiocyte;Cholestasis;Chronic;Cicatrix;Cirrhosis;Clinical;Collaborations;Colorectal Cancer;Cromolyn Sodium;Data;Development;Diagnosis;Disease;Disease Progression;Ductal Epithelial Cell;editorial;Epithelium;Fibrosis;Functional disorder;Funding;Gall Bladder Diseases;Gallbladder;Gallbladder Carcinoma;Gastroenterology;Genetic;Goals;graduate student;Grant;gut microbiota;Healthcare Systems;Hepatic;Hepatic Stellate Cell;Hepatobiliary;Hepatocyte;Hepatology;Heterogeneity;High Fat Diet;high risk;Histamine;Histamine Agents;Histamine Receptor;human model;Icterus;Immune system;In Vitro;in vivo;Incidence;Indiana;Inflammation;Inflammatory Bowel Diseases;Injury;interest;Internal Medicine;International;Investigation;Investments;Journals;K-Series Research Career Programs;Knockout Mice;Laboratories;Left;Leptin;Ligation;Link;Liver;Liver diseases;Liver Fibrosis;liver injury;liver transplantation;Malignant neoplasm of liver;Manuscripts;mast cell;Mediator;Medical center;Medical Students;Medicine;member;Mentors;Mesenchymal;migration;Mission;Molecular;mouse model;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;Neurosecretory Systems;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutics;Operative Surgical Procedures;patient subsets;Patients;Play;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;Preparation;primary sclerosing cholangitis;Printing;programs;Progressive Disease;Pruritus;Publications;Publishing;Reaction;receptor;recruit;Recurrence;reduce symptoms;release factor;Research;Research Personnel;Research Support;Risk;Rodent;Rodent Model;Role;Scientist;Seminal;senescence;senescence associated secretory phenotype;senior faculty;Signal Pathway;Signal Transduction;Study Section;symposium;Symptoms;Texas;therapeutic target;Time;Training;Transforming Growth Factor beta Receptors;Transplantation;treatment strategy;tumor;Tumor Angiogenesis;tumor growth;tumor progression;Ulcerative Colitis;undergraduate student;United States;United States National Institutes of Health;Universities;Veterans;Work

PROJECT_TITLE: BLR&D Research Career Scientist Award


PHR: Lung infections such as bacterial pneumonia are the fourth leading cause of death in the world and the most common cause of the acute respiratory distress syndrome. Veterans have an increased risk of mortality due to pneumonia, so it is important to identify new ways to prevent and treat pneumonia. Platelet deficiency is an independent risk factor for mortality in severe pneumonia and the acute respiratory distress syndrome yet the mechanisms by which platelets may provide protection during lung infections are poorly understood. The goal of this project is to identify mechanisms by which platelets protect the lung during infection, which could lead to new treatment options and better patient outcomes for veterans and other patients.

PI_NAMEs: BAIN, WILLIAM G (contact)

PROJECT_TERMS: Acids;Acute;acute infection;Acute Lung Injury;Acute Respiratory Distress Syndrome;Alveolar;alveolar epithelium;Antibodies;Apoptosis;Apoptotic;Area;aspirate;Attenuated;attenuation;Bacterial Pneumonia;Blood capillaries;Blood Platelets;career;CASP3 gene;Cause of Death;Cell Death;Cell Death Inhibition;Cells;Clinical;clinical center;combat;Critical Illness;Cytoprotection;cytotoxicity;Death Rate;Development;Diffuse;Elements;Epithelial Cells;epithelial repair;Epithelium;Exposure to;Gases;Gene Expression Profile;Genetic Transcription;Goals;Gram-Positive Bacteria;Hospitalization;Human;Immune response;improved;In Vitro;in vivo;Infection;Injury;Lower Respiratory Tract Infection;Lung;Lung infections;lung injury;Mediating;Mitochondria;Modeling;Morbidity - disease rate;mortality;mortality risk;mouse model;MPL gene;Mus;Natural Immunity;novel;novel therapeutics;Outcome;pathogen;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Physicians;Platelet Count measurement;Pneumonia;pneumonia treatment;Predisposition;prevent;Proliferating;protective effect;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pseudomonas aeruginosa pneumonia;Pulmonology;reconstitution;release factor;repaired;Reporter;Research;response;Risk Factors;Role;Scientist;Site;Staphylococcus aureus;Surveys;Therapeutic;Thrombocytopenia;Toxin;Transfusion;translational applications;translational potential;United States Department of Veterans Affairs;Veterans;Veterans Health Administration

PROJECT_TITLE: Platelet factors attenuate alveolar injury during severe pneumonia


ADMINISTERING_IC: OD

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Relevance to Public Health Pigs are the model of choice for many human diseases, and as such, they play an important role in understanding of human disease and the development of drugs and therapeutics. The National Swine Resource and Research Centers (NSRRC) provides a unique one-stop-shop for creating, curating and distributing these valuable genetics. The NSRRC supports biomedical researchers by providing animals, or assisting with innovative research to ensure reproducibility of their results.

PI_NAMEs: LEE, KIHO  (contact);WELLS, KEVIN DALE

PROGRAM_OFFICER_NAME: CONTRERAS, MIGUEL A

PROJECT_TERMS: Anatomy;animal care;Animal Model;Animals;Applied Research;Area;Arteriosclerosis;Biomedical Research;biosecurity;Cardiovascular Diseases;Cells;Characteristics;Client;clinical practice;Communicable Diseases;Communities;Country;Critical Pathways;Cryopreservation;Dedications;Derivation procedure;Development;Diabetes Mellitus;Discipline;Disease;drug development;Educational Activities;Educational workshop;Embryo;embryo cell;Ensure;Equipment and supply inventories;Europe;experience;Family suidae;Female;Future;gene editing technology;Genetic;Genetic Diseases;Genetic Engineering;Genetic Materials;Germ Cells;germ free condition;Germ Lines;Goals;Grant;Health;Human;human disease;human model;improved;Individual;Infrastructure;innovation;Laboratories;Maintenance;male;Manuscripts;Medical Device;Medical Research;meetings;Methods;Modeling;Modification;Molecular;Monitor;National Center for Advancing Translational Sciences;nonhuman primate;novel therapeutic intervention;novel therapeutics;operation;Optics;Organ;pathogen;Pharmaceutical Preparations;Physiological;Physiology;pig genome;Play;porcine model;pre-clinical;predictive modeling;prevent;Production;Public Health;Publishing;Quality Control;Reagent;recruit;repository;Reproducibility;Research;Research Personnel;Research Project Grants;Resources;Role;Scientist;Services;Site;Somatic Cell;sperm cell;Study models;Therapeutic;Therapeutic Agents;Tissues;tool;Training;Training and Education;United States;United States National Institutes of Health;web-accessible;Work;Xenograft procedure

PROJECT_TITLE: National Swine Resource and Research Center (NSRRC) Years 21-25

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-A(50)S]


PI_NAMEs: PRATHER, RANDALL S (contact)

PROJECT_TERMS: Anatomy;animal care;Area;Arteriosclerosis;Biological;biosecurity;Cardiovascular Diseases;Cells;Characteristics;Client;Communicable Diseases;Communities;Country;Cryopreservation;Dedications;Derivation procedure;Development;Diabetes Mellitus;Discipline;Disease;Educational Activities;Educational workshop;Embryo;Ensure;Equipment and supply inventories;Europe;experience;Family suidae;Female;Funding;Future;gene editing technology;Genetic;Genetic Engineering;Genetic Materials;Germ Cells;germ free condition;Germ Lines;graduate student;Health;Human;human disease;human model;improved;Individual;Infrastructure;Institution;Laboratories;Maintenance;male;Medical Research;meetings;Methods;Modeling;Modification;Monitor;operation;Optics;Organ;pathogen;Physiological;Physiology;pig genome;Plasmids;porcine model;preservation;prevent;Quality Control;Reagent;recruit;repository;Research;Research Personnel;Resource Sharing;Resources;Sampling;Scientist;Seminal fluid;Services;Site;Somatic Cell;sperm cell;Study models;Techniques;Tissues;Training and Education;training opportunity;undergraduate student;United States;United States National Institutes of Health;Veterinarians;Visit;web-accessible;Work;Xenograft procedure

PROJECT_TITLE: Resource Core for National Swine Resource and Research Center (NSRRC) Years 21-25

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-A]


ORG_CITY: TAMPA

ORG_NAME: JAMES A. HALEY VA MEDICAL CENTER

ORG_STATE: FL

PHR: Dr. Bickford is a recognized leader in research as she has received numerous awards including being a Fellow of the American Association for the Advancement of Science and a Fellow of the American Institute for Medical and Biological Engineering. Her work is in the area of aging and neurodegenerative diseases. Millions of Veteran’s over the age of 65 are seeking care in our VA healthcare system, and aging is a critical, yet often overlooked risk factor for many diseases. Dr. Bickford’s work promises to unlock new and improved interventions in memory loss in aging as well as in Parkinson’s disease.

PI_NAMEs: BICKFORD, PAULA C (contact)

PROJECT_TERMS: age effect;age related changes;aged;Aging;aging brain;American;American Association for the Advancement of Science;Animal Disease Models;Area;Award;Basic Science;Biological Process;Biomedical Engineering;Blueberries;Brain;Brain Injuries;care seeking;career;Cell Survival;Cell Therapy;chemokine;Clinical Sciences;Cognitive aging;cognitive function;comorbidity;Complex;CX3CL1 gene;cytokine;Data;design;detection of nutrient;Diet;Discipline;Disease;disease model;Energy Metabolism;examination questions;Flowers;Food;Fractalkine;Funding;gene therapy;Gerontology;Goals;Grant;Healthcare Systems;Hospitals;human old age (65+);immune system function;Impaired cognition;improved;Inflammatory;inflammatory milieu;Influentials;Innate Immune System;interest;Intervention;juvenile animal;Knock-out;Laboratories;Manuscripts;Mediator;Medical;meetings;Memory Loss;Microglia;Modeling;Natural Products;Neurodegenerative Disorders;Neuroglia;Neurons;neuroprotection;Neurosciences;novel therapeutics;Paper;Parkinson Disease;Pathway interactions;Phenotype;Process;Productivity;programs;promote resilience;Proteomics;Publications;Publishing;Rattus;receptor;Research;Research Personnel;response;Risk Factors;Scientist;Seminal;small molecule;stem cell therapy;stem cells;Tauopathies;Therapeutic;Therapeutic Intervention;therapy design;tool;Traumatic Brain Injury;Untranslated RNA;Veterans;Veterans Hospitals;Work

STUDY_SECTION: RCSR

STUDY_SECTION_NAME: Research Career Scientist[RCSR]


PHR: Sleep disturbance is a frequent and common complaint among our Veterans and within the general population. Veterans suffering from post-traumatic stress disorder (PTSD) and depression have severe sleep disorders. In PTSD, there is a marked hyperarousal that makes it difficult for patients to fall asleep. The cause of the insomnia in PTSD is not known because we do not have a clear understanding of the brain circuits that induce sleep. I am using new genetically engineered tools such as optogenetics, pharmacogenetics, deep-brain imaging and CLARITY to identify the brain circuits responsible for specific behaviors, such as sleep. My laboratory is actively engaged in mapping neural circuits, and training a new generation of scientists in the use of cutting-edge neuroscience tools and methods.

PI_NAMEs: SHIROMANI, PRIYATTAM J. (contact)

PROJECT_TERMS: 3-Dimensional;Aging;American;Anxiety;Area;Arousal;Atypical depressive disorder;Autopsy;awake;Award;Behavior;Behavioral Symptoms;Books;Brain;Brain imaging;Brain Mapping;brain tissue;calcium indicator;career;cell type;Collaborations;Complex;conditioned fear;Data;Defect;Deterioration;Development;Disease;Drowsiness;Education;Educational process of instructing;Emotional;emotional behavior;Environment;experience;experimental study;falls;FDA approved;Fluorescence;Funding;Gene Transfer;General Population;Generations;Genetic Engineering;Genetically Engineered Mouse;Goals;Grant;Grant Review;Growth;Heart;hypnotic;hypocretin;Hypothalamic structure;Image;imaging modality;Individual;Induced Neurons;Injury;Institution;interest;International;Jet Lag Syndrome;Journals;Kidney;Laboratories;Laboratory Research;Life;Light;Limbic System;Link;Liver;liver imaging;Magnetic Resonance Imaging;Malignant Neoplasms;Mammals;Maps;Measures;Memory;Mental Depression;Mentors;Methodology;Methods;microendoscope;Microscope;Microtomy;mild traumatic brain injury;Modern Medicine;Molecular;Moods;mouse model;Mus;Narcolepsy;Nerve Degeneration;neural circuit;Neuroanatomy;Neurobiology;Neurodegenerative Disorders;neuronal circuitry;Neurons;Neurosciences;non-alcoholic fatty liver disease;Obstructive Sleep Apnea;optogenetics;Pathology;Patients;Peer Review;Pharmacogenetics;Phenotype;Philosophy;Post-Traumatic Stress Disorders;programs;Prosthesis;Proteins;Publishing;Rattus;reconstruction;Research;Research Personnel;Resolution;Review Committee;Rodent Model;Science;Scientist;Series;Services;Signal Transduction;skills;Sleep;Sleep Deprivation;Sleep Disorders;Sleep disturbances;Sleeplessness;Slice;Spinal Cord;Stroke;Students;Substance abuse problem;Symptoms;Testing;Time;Tissues;tool;Training;translational potential;Trauma;Traumatic Brain Injury;United States National Institutes of Health;Veterans;Visual;Visualization;Wakefulness;Work;wound healing


NIH_SPENDING_CATS: Biotechnology

ORG_STATE: MO

PROJECT_TERMS: Anatomy;Applied Research;Arteriosclerosis;Biological Assay;Biomedical Research;Cardiovascular Diseases;Characteristics;Client;Communicable Diseases;Communities;Country;Cryopreservation;Development;Diabetes Mellitus;Disease;Domestic Pig;Embryo;embryo cryopreservation;Embryo Transfer;Ensure;Equipment and supply inventories;experience;Family suidae;Funding;Future;Genetic Engineering;Genetic Materials;Germ Cells;Germ Lines;Goals;Health;Human;human disease;improved;innovation;Knock-out;Medical Device;Medical Research;method development;Methods;Modeling;Modification;Molecular;Monitor;novel therapeutic intervention;operation;Optics;Organ;Performance;Pharmaceutical Preparations;Physiological;Physiology;pig genome;porcine model;pre-clinical;prevent;Production;Reagent;repository;reproductive;Research;Research Personnel;Research Project Grants;Resources;Scientist;sex;somatic cell nuclear transfer;sperm cell;Study models;Technology;Tissues;tool;United States;web-accessible;Work;Xenograft procedure

PROJECT_TITLE: Research Project for NSRRC Renewal Year 21-25


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Dr. Tsukamoto’s ongoing research is aimed at better understanding of molecular mechanisms underlying activation of the liver cell type called hepatic stellate cells (HSCs) which cause cirrhosis and promote liver cancer. His research has discovered HSCs promote both liver fibrosis and tumor development by actions of the enzyme called stearoyl Co-A desaturase (SCD). Proposed research will aim to elucidate how this tumor promotion takes place using the genetic mouse models, global screening for lipids in tumor microenvironment, and analysis of gene regulation. These efforts will help identify new therapeutic targets for cirrhosis and liver cancer which are common complications of chronic liver disease among veteran patients. !

PI_NAMEs: TSUKAMOTO, HIDEKAZU  (contact)

PROJECT_TERMS: 3' Untranslated Regions;Ablation;Alcoholic Liver Diseases;Alcoholic steatohepatitis;Alcohols;Animals;Attenuated;Award;beta catenin;Binding;California;career;Caspase;Cell Death;Cell Fate Control;cell type;Cellular biology;Chronic;chronic liver disease;Cirrhosis;Citric Acid Cycle;Clinical;Collaborations;Core Grant;desaturase;Development;Direct Costs;Disease;Environment;Environmental Risk Factor;Enzymes;Epigenetic Process;epigenetic regulation;Ethanol;Event;Faculty;Fibrosis;Funding;gain of function;Gastroenterology;Gene Expression Regulation;Genes;Genetic;genetic risk factor;Genetic Transcription;Grant;Growth;Healthcare Systems;Hepatic;Hepatic Fibrogenesis;Hepatic Stellate Cell;Hepatitis;Hepatocyte;Hepatology;Impairment;in vivo;Individual;Inflammation;Inflammatory;Infusion procedures;International;Investigation;Investments;Knowledge;Kupffer Cells;Laboratories;Link;Lipids;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver inflammation;Liver neoplasms;Los Angeles;loss of function;Macrophage;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;Medical Research;member;Mentors;Messenger RNA;Metabolic;Methyl-CpG-Binding Protein 2;Mitochondria;Modeling;Molecular;Monounsaturated Fatty Acids;morphogens;mouse model;Mus;National Institute on Alcohol Abuse and Alcoholism;neutrophil;new therapeutic target;notch protein;novel;novel therapeutic intervention;Nuclear Import;Outcome;overexpression;Oxidative Phosphorylation;Pancreatic Diseases;Pathogenesis;Pathway interactions;Patients;Peer Review;Philosophy;Play;Post-Translational Regulation;PPAR gamma;problem drinker;programs;Protein Dephosphorylation;Publications;Publishing;pyruvate dehydrogenase;Pyruvate Dehydrogenase (Lipoamide)-Phosphatase;R24;receptor;Regulation;Repression;Research;Research Personnel;Respiration;Respiratory Chain;Respiratory physiology;Role;Science;Scientist;screening;Services;Site;Stearoyl-CoA Desaturase;stem-like cell;Techniques;therapeutic target;Time;Transcriptional Activation;tumor initiation;tumor microenvironment;tumor progression;Tumor Promotion;United States Department of Veterans Affairs;United States National Institutes of Health;Up-Regulation;Veterans


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Mitochondria are the powerhouse of the cell providing most of the energy needed for the human body to function. A number of diseases prevalent in Veteran patient populations are associated with the malfunction of mitochondria. Diseases like Parkinson's, Alzheimer's, neurodegeneration, diabetes, heart disease, and cancer all are associated with a decline in mitochondrial function. Our laboratory studies the architecture and function of essential mitochondrial proteins. We are developing methods to identify how mitochondrial proteins assemble with their essential vitamin and mineral cofactors that are needed for proper function. These studies will lead to methods for early detection of changes in mitochondria that can lead to diagnoses and treatment of disease. Early warning of changes in mitochondrial function will lead to the development of ways to intervene to protect patients from these debilitating diseases.

PI_NAMEs: CECCHINI, GARY  (contact)

PROJECT_TERMS: Alzheimer's Disease;Amino Acids;Apoptosis;Architecture;Area;Award;Bacterial Model;Binding;Binding Proteins;Biochemical;Biochemistry;Bioenergetics;Brain Injuries;Cardiac;career;Cells;Clinical;Coenzyme Q10;cofactor;Complex;Dedications;design;Development;Diabetes Mellitus;Diagnosis;Disease;DNA;Early Diagnosis;Enzymes;Epigenetic Process;Ethics;Family;Fumarates;Functional disorder;Gene Expression;Generations;Genes;Genetic Polymorphism;Genetic Transcription;healing;Health;Heart Diseases;Heme;histone demethylase;Homeostasis;Human;Human body;Hypoxia Inducible Factor;in vivo;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Injury;insight;Investigation;Ischemia;Kidney Diseases;Laboratories;Laboratory Study;Lipids;Maintenance;Malignant Neoplasms;Malonates;member;Membrane;method development;Methods;Minerals;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;mitochondrial metabolism;Mitochondrial Proteins;mitochondrial therapeutics;Modeling;mouse model;Multienzyme Complexes;Multiple Sclerosis;Muscle Weakness;Mutation;Myocardial Infarction;NADH;NADH dehydrogenase (ubiquinone);Nerve Degeneration;Nerve Regeneration;Neurodegenerative Disorders;news;Nobel Prize;nuclear factor-erythroid 2;nucleotide metabolism;Organelles;Oxidation-Reduction;Oxidative Phosphorylation;Paper;Parkinson Disease;Pathway interactions;patient population;Patients;Permeability;Pharmaceutical Preparations;Philosophy;Physiology;Play;Point Mutation;Poison;prevent;Process;Procollagen-Proline Dioxygenase;programs;protein complex;protein function;protein metabolism;Protein Region;protein structure;Protons;Psoriasis;Publishing;Quinone Reductases;Reactive Oxygen Species;Regulatory Element;Relapse;Reperfusion Therapy;Research;research and development;Resolution;Respiration;respiratory;Respiratory Chain;response;Roentgen Rays;Role;Science;Scientist;Series;Severities;Signal Transduction;Signaling Molecule;small molecule inhibitor;Stress;Stroke;Structure;Study models;success;Succinate Dehydrogenase;Succinates;System;Therapeutic Uses;three dimensional structure;Time;Traumatic Brain Injury;tumor;Ubiquinone;United States National Academy of Sciences;Vascular remodeling;Veterans;Vitamins;Work


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: The Peachey lab focuses on outer retinal biology and disorders that impact the function of rod and cone photoreceptors, which initiate vision. The power of mouse genetics, whereby the activity of specific genes of interest can be controlled, is used to understand fundamental aspects of the visual system, to define mouse models of human retinal diseases, and to evaluate experimental therapies in these models. The Million Veteran Program (MVP) biobank is used for studies of human genetics, where genes that confer susceptibility to an eye disease such as age-related macular degeneration (AMD) are identified and compared across the different ethnic groups that comprise the Veteran population. This information is important towards development of treatments that will maintain useful vision by slowing or halting disease progression, and towards the reduction of healthcare costs associated with these conditions.

PI_NAMEs: PEACHEY, NEAL S. (contact)

PROJECT_TERMS: Activities of Daily Living;African American;age difference;Age related macular degeneration;Algorithms;American;Anatomy;Area;Automobile Driving;Award;biobank;Biochemical;Biochemistry;Biological;Biological Assay;Biology;Blindness;Candidate Disease Gene;career;case control;Cataract;CD147 antigen;Cell membrane;cell type;Cells;Cellular Metabolic Process;Chromosome Mapping;Code;cohort;Collaborations;conditional knockout;Cone;Coupled;Data;Databases;design;Development;Diabetic Retinopathy;Disease;disease phenotype;Disease Progression;DNA Sequence Alteration;Electrophysiology (science);Equilibrium;Ethnic Origin;Ethnic Population;European;Exposure to;Eye diseases;forward genetics;Fright;Funding;Genes;Genetic;genetic analysis;genetic approach;Genetic Risk;Genetic study;genome wide association study;Glaucoma;glucose transport;Glucose Transporter;Health;Health Care Costs;Healthcare;Hispanic;Hispanic Americans;Human;human disease;Human Genetics;human model;imaging study;improved;interest;International;International Classification of Disease Codes;Investigational Therapies;Knock-out;Laboratories;Laboratory Research;Light;Link;Maintenance;Manuscripts;Measures;meetings;Meta-Analysis;Metabolism;military veteran;Modeling;Monitor;mouse genetics;mouse model;multi-ethnic;multidisciplinary;Mus;Mutagenesis;mutant;Mutant Strains Mice;Mutation;Nature;ocular imaging;Patients;pharmacologic;Phenotype;Photoreceptors;Play;Predisposition;Prevalence;procedure cost;programs;Proteins;Psychophysics;Publishing;Reading;Reporting;Research;Research Project Grants;Retina;Retinal Cone;Retinal Diseases;reverse genetics;Risk;risk variant;Rod;Role;RPE65 protein;Running;Scientist;Site;SLC2A1 gene;Structure of retinal pigment epithelium;success;The Jackson Laboratory;therapy development;Transgenic Organisms;Translations;Vertebrate Photoreceptors;Veterans;Veterans Health Administration;Vision;Vision Disorders;Vision research;visual cycle;visual processing;Visual System;Work;XLRS1 protein


ADMINISTERING_IC: NS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Rett Syndrome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE Rett syndrome (Rett) is a severe, genetically diverse neurodevelopmental disease with no curative treatments. This study seeks to develop a therapeutic approach to correct the underlying genetic cause of Rett in neurons. If successful, this work will inform the development of a gene-editing platform to treat almost any case of Rett as well as other neurological disorders.

PI_NAMEs: KEENER, DAVID G. (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Affect;Age Months;Binding;Bioinformatics;Biological Assay;Biology;Brain;career;Cells;chemical synthesis;Chemicals;Chemistry;Chimeric Proteins;Chromatin;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;curative treatments;Defect;design;Development;DNA delivery;DNA Integration;DNA Methylation;DNA sequencing;Effectiveness;Encapsulated;Engineering;flexibility;Flow Cytometry;Functional disorder;gene editing technology;Gene Expression;Gene Expression Regulation;Genes;Genetic;genome sequencing;Genomic DNA;Guide RNA;immunogenic;Impairment;improved;In Vitro;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Infant;insight;Interphase Cell;Length;Lentivirus;Ligation;lipid nanoparticle;Liver;loss of function mutation;Luciferases;Measures;Mediating;Messenger RNA;Methods;Methyl-CpG-Binding Protein 2;Missense Mutation;model organism;Modification;Molecular;molecular phenotype;mRNA delivery;Mus;mutant;Mutation;Nervous System Disorder;neurite growth;Neurites;Neurobiology;Neurodevelopmental Disorder;Neurologic;neuron development;Neuronal Differentiation;Neurons;Nonsense Mutation;novel;Nuclear;nuclease;Nucleic Acids;patient derived induced pluripotent stem cells;Patients;Pattern;Phenotype;postmitotic;prime editing;prime editor;Primer Extension;Productivity;Quality of life;Reading Frames;Regulator Genes;Research;Rett Syndrome;RNA chemical synthesis;RNA Sequences;RNA-Directed DNA Polymerase;Severities;Symptoms;System;Technology;technology platform;Testing;Therapeutic;Time;Training;transcriptome;Transfection;Viral Vector;whole genome;Work

PROJECT_TITLE: Establishing and Optimizing a Prime Editing Method in Neurons for Treatment of Rett Syndrome


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: Project Narrative. Sarcopenia is a major contributor to the decline in physical function and disability in older adults and a highly relevant problem for the veteran population, as more than half of veterans are over age 60. The weakness associated with sarcopenia contributes to falls and fractures, frailty, deconditioning and institutionalization and the consequent decline in physical function also contributes to obesity and diabetes. All of these are major problems in older veterans (falls, fractures, frailty, institutionalization, obesity and diabetes) and all could be significantly prevented/improved by successfully targeting sarcopenia. As long as the underlying causes of the muscle atrophy, declining strength and physical frailty that occur with age are not known, it will be difficult to design effective interventions. My research program will provide important new insights into targets for interventions to prevent or reduce muscle atrophy during aging.

PI_NAMEs: VAN REMMEN, HOLLY  (contact)

PROJECT_TERMS: Address;Age;age acceleration;age related;age related changes;Age Years;age-related disease;age-related muscle loss;Aging;aging population;aging related;Amyotrophic Lateral Sclerosis;Atherosclerosis;ATP phosphohydrolase;Atrophic;Award;Biology;Cachexia;Calcium;career;Caring;copper zinc superoxide dismutase;Coupling;Cytosol;Data;deconditioning;Degenerative Disorder;demographics;Denervation;design;Deterioration;Diabetes Mellitus;Disease;effective intervention;Elderly;fall risk;falls;Fracture;frailty;Functional disorder;Funding;Gastrocnemius Muscle;General Population;Generations;Goals;Grant;Health;healthspan;Homeostasis;human old age (65+);Impairment;improved;Injury;insight;Institutionalization;Intervention;Journals;Knockout Mice;Maintenance;Malignant Neoplasms;Measures;Mediating;Mediator;military veteran;Mission;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;Motor Neurons;mouse model;Mus;Muscle;Muscle Fibers;muscle form;Muscle function;Muscle Weakness;Muscular Atrophy;muscular structure;Myopathy;Nerve;nerve supply;Neurodegenerative Disorders;neuromuscular;Neuromuscular Junction;Neurons;novel;Obesity;older adult;Older Population;Oxidation-Reduction;oxidative damage;Oxidative Stress;Pathway interactions;Persons;pharmacologic;Phenotype;Physical Function;physically handicapped;Physiology;Play;Population;postsynaptic;preservation;presynaptic;Prevalence;prevent;Process;programs;Publishing;Pulmonary Emphysema;Pump;Quality of life;Reactive Oxygen Species;Research;Research Support;restoration;Role;sarcopenia;Sarcoplasmic Reticulum;Scientist;Skeletal Muscle;SOD2 gene;superoxide dismutase 1;Superoxides;synaptic function;Testing;Therapeutic;therapeutic target;Tissues;United States Department of Veterans Affairs;Veterans;Wild Type Mouse;Work


ORG_NAME: BALTIMORE VA MEDICAL CENTER

PHR: Dr. Jian-Ying Wang is a Senior Research Career Scientist and his research program directly addresses an important health issue relevant to VA health care. Ongoing studies in Wang lab are to fully investigate the mechanism underlying rapid gut mucosal repair after injury, and to search for new therapies to maintain the intestinal epithelial integrity in patients with critical illness. Mucosal injury-related disorders such as: stress/peptic ulcerations, Crohn's disease/ulcerative colitis, trauma, and sepsis occur commonly in our Veteran population, but the effective therapies in clinic are limited. Because improving our understanding of the mechanism involved in mucosa repair is the first step towards therapeutic initiatives, Dr. Wang's research program will strengthen our long-term goal to develop more effective therapeutic approaches for gut mucosal injury-related diseases for our VA patients.

PI_NAMEs: WANG, JIAN-YING  (contact)

PROJECT_TERMS: Acute;Address;Affect;Animal Model;Apoptosis;Area;Award;Bacteria;Baltimore;base;Binding Proteins;Blood;career;Cell membrane;cell motility;Cell Survival;Cells;Clinic;Clinical;Collaborations;Critical Illness;Crohn's disease;Development;Disease;effective therapy;Elements;Environment;Epithelial Cells;epithelial repair;Epithelium;Event;Exhibits;Faculty;Functional disorder;Funding;gain of function;gastrointestinal epithelium;Gene Expression;Gene Expression Profile;Genes;genetic regulatory protein;Genetically Modified Animals;Goals;Grant;Gut Mucosa;Health;Healthcare;Healthcare Systems;Hemorrhage;Homeostasis;HuR protein;Impaired healing;improved;Inflammation;Injury;innovation;intestinal epithelium;Intestinal Mucosa;K-Series Research Career Programs;Knock-out;Laboratories;laboratory development;Laboratory Research;Link;Maintenance;Mammalian Cell;Maryland;Mediating;Medical center;medical schools;Mentors;microorganism;MicroRNAs;migration;military veteran;Mission;Molecular;Mucous Membrane;Natural regeneration;novel;novel therapeutics;Nucleic Acids;operation;Operative Surgical Procedures;Pathologic;Pathology;patient population;Patients;Peer Review;Peptic Ulcer;Permeability;Physiological;Poison;Polyamines;Positioning Attribute;posttranscriptional;preservation;Process;professor;programs;Proliferating;Publishing;re-epithelialization;receptor;Regulation;repaired;Repression;Research;research and development;Research Personnel;Research Project Grants;response;restoration;RNA;Scientist;self-renewal;Seminal;Sepsis;Services;Shock;Signal Transduction;STIM1 gene;Stream;Stress;systems research;Techniques;Testing;Therapeutic;therapeutically effective;Tissues;Trans-Activators;Transcription Process;Transgenic Organisms;Translations;Trauma;Ulcer;Ulcerative Colitis;United States National Institutes of Health;Universities;Untranslated RNA;Veterans;WNT Signaling Pathway


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: Cancer is the second leading cause of death among veterans, and there are an estimated 170,000 cancer patients within in the VA system. To address this issue, the research of the Chalfant Laboratory focuses on non- small cell lung cancer (NSCLC), which represents the majority of lung cancers, and carries a poor outcome (e.g. five-year survival rate of ~15%). The applicant’s research is tailored to identify new cellular targets for the development of new treatments for this deadly disease, which are thus, directly relevant to the patient care mission of the Department of Veterans’ Affairs. To accomplish the goal for new therapeutics for NSCLC, the applicant is supported by several NIH/VA funded grants. The applicant has also been very productive with >100 peer-reviewed publications and is a distinguished member of the VA system for 17 years. He has trained > 40 trainees at various levels with many of them faculty members at various institutions with funded research programs. In summary, the applicant’s scientific contributions are vitally important to the VA mission.

PI_NAMEs: CHALFANT, CHARLES E. (contact)

PROJECT_TERMS: acute wound;Address;Affinity;agent orange;Aging;American;Anabolism;Anoikis;anti-cancer research;Appointment;Area;Arts;Asbestos;Award;Basic Science;Binding;Binding Sites;Biochemistry;Biology;Biomedical Research;cancer cell;cancer diagnosis;Cancer Etiology;Cancer Patient;Carcinogens;career;Caring;Cause of Death;Cell Survival;Cellular biology;cellular targeting;ceramide 1-phosphate;ceramide kinase;Cessation of life;chronic wound;Clinical;clinical predictors;clinical translation;Collaborations;college;Communication;Communities;Department chair;Developed Countries;Development;Disease;editorial;Eicosanoid Production;Eicosanoids;Elements;Endowment;Event;Exposure to;Faculty;Florida;former smoker;Funding;Glycerol;Goals;Grant;Head;Healthcare;Healthcare Systems;Heart Arrest;Heterogeneous-Nuclear Ribonucleoprotein L;high risk;Human;human disease;Individual;Inflammatory;Inflammatory Response;innovation;Inorganic Phosphate Transporter;Institution;Ionizing radiation;Journals;Laboratories;Laboratory Study;Link;lipidomics;Lipids;Lung;lung cancer cell;lung development;Maintenance;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Manuscripts;Mediating;member;men;Mentors;Microbiology;Military Personnel;military service;military veteran;Mission;Molecular;Molecular Biology;molecular targeted therapies;N-terminal;Natural Sciences;Nature;new therapeutic target;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;Oncology;Outcome;Patient Care;Patient-Focused Outcomes;Peer Review;Peripheral;phenome;Phospholipase;Phosphorylation Site;preference;Productivity;Prognosis;programs;Proteins;Publications;Publishing;Reporting;Research;Research Personnel;Resistance;Resources;RNA;RNA Recognition Motif;RNA Sequences;RNA Splicing;Role;Science;Scientist;senior faculty;Sepsis;Series;Services;Signal Transduction;Smoke;Societies;Sphingolipids;Study Section;Survival Rate;System;Therapeutic;tobacco abuse;Tobacco Dependence;Training;transcriptome sequencing;Traumatic injury;tumor;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;Veterans;Veterans Health Administration;Veterans Hospitals;Woman;Work;wound healing


PHR: Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome (MODS) following sepsis; however, few specific targets have yet been identified that predispose septic patients to MODS and ALI, rendering mortality rates high and effective treatment lacking. Innate lymphoid cells (ILCs) are a new member of the lymphoid population playing important roles in host response to inflammation and infection. Group 2 ILCs (ILC2) are a main ILC subtype in the lungs. Gaining insight into the regulatory role of ILC2 in ALI and the mechanism of ILC2 mobilization, migration, and expansion in the lungs in sepsis will provide us with novel targets for preventive and therapeutic interventions for ALI in septic patients. Furthermore, in a broader sense, the proposed studies will contribute to a greater understanding of the pathogenesis of a number of human diseases in which innate immune cells are involved in the inflammatory process.

PI_NAMEs: FAN, JIE  (contact)

PROJECT_TERMS: Acute;Acute Lung Injury;Address;Affect;alveolar epithelium;Automobile Driving;Bone Marrow;CASP1 gene;Cause of Death;Cell Death;Cell surface;Cells;Cessation of life;chemokine receptor;CXC Chemokines;cytokine;Death Rate;Development;effective therapy;Emigrations;Endothelial Cells;Epithelial Cells;Exhibits;Foundations;G protein coupled receptor kinase;GATA3 gene;Goals;Hematogenous;HMGB1 gene;Homeostasis;Human;human disease;IL17 gene;Immune;Immune response;Individual;Infection;Inflammation;Inflammatory;insight;Interferon Type II;Interleukin-13;interleukin-22;Interleukin-9;Intervention;Lung;Lymphoid;Lymphoid Cell;Macrophage;Mediating;member;migration;Molecular;Multiple Organ Failure;Mus;Myeloid Cells;Natural Immunity;neutrophil;novel;Orphan;Pathogenesis;Pathologic;Patients;Peripheral;Persons;Physiological;Play;Population;prevent;preventive intervention;Process;progenitor;Proliferating;prophylactic;Pulmonary Inflammation;receptor;receptor for advanced glycation endproducts;recruit;Research Project Grants;Retinoic Acid Receptor;Role;Sepsis;septic;septic patients;Signal Transduction;Site;Structure of parenchyma of lung;Subgroup;Testing;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissue Expansion;Tissues;transcription factor;TSLP gene;Virus Diseases

PROJECT_TITLE: Regulatory Role of ILC2 in Acute Lung Injury in Sepsis