ORG_CITY: SALISBURY

ORG_NAME: W G HEFNER VA MEDICAL CENTER

ORG_STATE: NC

PHR: Project Narrative Regardless of family history, site of onset, and sequence of symptoms and progression, all Amyotrophic Lateral Sclerosis (ALS) patients lose muscle function as central nervous system cells stop working and eventually die. This proposal will perform comprehensive analyses on 1000s of individual cells from dozens of central nervous system tissues donated by veterans with ALS. The results will provide an unprecedented depth of information on stresses experienced at the cellular level and how this stress relates to the health of the tissue. Data derived from this project will unveil numerous new directions of research to better understand ALS disease processes with the goal of developing effective therapies.

PI_NAMEs: ORR, MIRANDA ETHEL (contact)

PROJECT_TERMS: Affect;ALS patients;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;analytical method;Apoptosis;Area;Autopsy;Back;biobank;biological adaptation to stress;biomarker discovery;biomarker validation;Blood Vessels;Brain;Brain Diseases;brain tissue;candidate identification;candidate marker;case control;Cell Aging;Cell Death;Cell Death Process;cell injury;cell type;Cells;Cellular Morphology;cellular resilience;Cellular Stress;Central Nervous System;Chronic;Communities;Complex;Cytoplasm;Data;Data Set;Deposition;Development;Diagnosis;digital;Disease;Disease Progression;effective therapy;Environment;experience;experimental study;extracellular;Family history of;Functional disorder;Future;Goals;Health;Histologic;Human;human tissue;Immunohistochemistry;improved;Individual;Investigation;Lateral;Limb structure;Link;Location;Maps;method development;military veteran;Mitochondria;Molecular;Molecular Profiling;Motor;Motor Cortex;Motor Neurons;mouse model;Movement;Muscle;muscle form;Muscle function;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;Neuronal Dysfunction;Neurons;neuropathology;new therapeutic target;novel;Nuclear;Outcome;Pathogenicity;Pathologic;Pathology;Pathway interactions;pharmacologic;preservation;Process;protein expression;protein TDP-43;Proteins;proteostasis;Research;research clinical testing;Research Proposals;Resolution;RNA;Role;screening;senescence;senescent cell;single cell analysis;Site;Spinal Cord;Spinal Cord Column;Spinal Diseases;Stress;stress resilience;Structure;Symptoms;tau aggregation;tau Proteins;Technology;Testing;Therapeutic Intervention;therapeutic target;Time;tissue degeneration;Tissue Donors;Tissues;Transcript;transcriptomics;Transgenic Mice;Validation;Veterans

PROJECT_TITLE: High Resolution Profiling of Senescent Cells in ALS Brain and Spinal Cord


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: SAN ANTONIO

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: Project Narrative Candida-associated denture stomatitis (CADS) is one of the most common oral diseases among our aging veterans, seriously affecting their nutrition, speech, appearance, and quality of life. Previously described animal models for CADS are not well-established and do not recapitulate infections as seen in humans. This project will optimize a novel CADS rat model using computer aided design/manufacturing (CAD/CAM) technology, special UME6 overexpressing Candida strains and immunocompetent animals. We will further validate the rat CADS model to test the feasibility of treating CADS with a novel cell binding antifungal drug release system. This proposal represents a major breakthrough in CADS research and provides an easy and reproducible system for testing anticandidal drugs/devices and studying the pathogenesis of oral Candida infections.

PI_NAMEs: YEH, CHIH-KO  (contact)

PROJECT_TERMS: Address;Affect;Aging;Animal Model;Animals;anti-fungal agents;Appearance;Binding;Body Weight;Candida;Candida albicans;Cells;Cessation of life;Characteristics;Clinic;Clinical;Color;Computer-Aided Design;Computer-Assisted Manufacturing;Control Groups;Custom;Data;Dental caries;Dental Cements;Dental Implants;Denture Stomatitis;Denture Wear;Dentures;design;Development;Devices;Diabetes Mellitus;Diet;Disease;Dose;Drug Delivery Systems;Edentulous Mouth;effectiveness evaluation;fabrication;feasibility testing;Financial Hardship;fungus;gastrointestinal;Health;histological studies;Human;Hyphae;Immune;Immunocompetent;Immunocompromised Host;In Vitro;in vivo;in vivo Model;Infection;Inflammation;Injections;Invaded;Liquid substance;manufacture;manufacturing technology;Maxilla;Medical;Methods;Microbial Biofilms;microbial colonization;microorganism;military veteran;Modality;Modeling;Monitor;Mouth Diseases;Mucous Membrane;Mycoses;Natural Resistance;novel;novel strategies;novel therapeutic intervention;novel therapeutics;nutrition;Nutritional status;Oral;Oral candidiasis;Oral cavity;oral fungal;Oral mucous membrane structure;oral tissue;Organ;Outcome;overexpression;Palate;Pathogenesis;Patients;Periodontal Diseases;Pharmaceutical Preparations;Pharmacotherapy;Pilot Projects;Property;Quality of Care;Quality of life;Rattus;Reagent;Recurrent disease;Reproducibility;Research;Risk Factors;Rodent;Rodent Model;Scheme;Secure;Smoking;Speech;Study models;Surface;System;Systemic infection;Testing;Therapeutic;Time;Tissues;Tongue;Tooth Diseases;Tooth Loss;Tooth structure;treatment choice;treatment group;Validation;Veterans

PROJECT_TITLE: Validation of a novel rodent Candida-associated denture stomatitis model for studying pathogenesis and therapeutic management


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: TAMPA

ORG_NAME: JAMES A. HALEY VA MEDICAL CENTER

ORG_STATE: FL

PHR: Traumatic brain injury (TBI) is a major health issue for both military and civilian populations. Currently, there are no drugs available to treat TBI. While TBI severity ranges from mild to severe, moderate TBI is clinically most relevant, and If not treated immediately the secondary injury in these patients could spread quickly and may lead to long-term consequences including cognitive and memory loss. Hence, there is a genuine need to discover new therapeutic agents for moderate TBI. This proposal is based on the discovery of a novel target of TBI, CCL20, a chemokine protein that plays a critical role in increasing inflammation in acute TBI and memory loss. Our proposed studies focus on evaluating the long-term effects and mechanism of actions of the combinatorial anti-inflammatory and stem cell therapy for moderate TBI, which involves nanoparticle driven anti-chemokine therapy to reduce acute inflammation followed by stem cell therapy to remodel neurogenesis of parenchymal cells in the injured brain.

PI_NAMEs: MOHAPATRA, SHYAM S;MOHAPATRA, SUBHRA  (contact)

PROJECT_TERMS: Acute;Address;adult stem cell;Anti-Inflammatory Agents;Anxiety;anxiety reduction;anxiety-like behavior;Astrocytes;astrogliosis;Attenuated;Behavioral;behavioral outcome;Brain;Brain Injuries;Brain-Derived Neurotrophic Factor;Cause of Death;CCL20 gene;CCR6 gene;Cells;chemokine;chemokine therapy;Clinical;clinical translation;Closed head injuries;Cognitive deficits;Collaborations;combat;combinatorial;Combined Modality Therapy;Communication;Consensus;Data;Dendrimers;depressive behavior;disability;Dose;Drug Targeting;effective therapy;Encephalitis;Engraftment;evidence base;FDA approved;Functional disorder;Funding;Future;Genes;glial activation;Gliosis;Goals;Health;Human;Human Resources;Immune;Impaired cognition;improved;Infiltration;Inflammasome;Inflammation;Inflammatory;inhibitor;Injury;innovation;Integral Membrane Protein;Interferons;Interleukin-1 beta;Intravenous;Lateral;learned behavior;Lesion;Ligands;Liquid substance;Long-Term Effects;Memory Loss;Mesenchymal Stem Cell Transplantation;Mesenchymal Stem Cells;Methods;Microglia;Military Personnel;Modeling;motor behavior;mouse model;Mus;nano;nanoformulation;nanoparticle;Nerve Degeneration;Nerve Regeneration;Nervous System Trauma;neurogenesis;Neurogenic Inflammation;Neurologic;Neurons;neuropathology;novel;novel therapeutics;Outcome;Pathogenesis;Pathology;Patients;Percussion;Peripheral;Pharmaceutical Preparations;Phase;Pioglitazone;Plasmids;Play;Population;pre-clinical research;Prevalence;programs;Proteins;rational design;Rattus;Reagent;receptor;Regimen;Reporting;Research;response;Role;Severities;Signal Transduction;small hairpin RNA;Spleen;stem cell therapy;Stimulus;Surrogate Markers;systemic inflammatory response;targeted treatment;TBI treatment;Testing;Therapeutic;Therapeutic Agents;therapy outcome;Translational Research;Traumatic Brain Injury;Uncertainty;Work

PROJECT_TITLE: Anti-inflammatory and hMSC combination therapy for traumatic brain injury


FUNDING_MECHANISM: OTHERS

ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Pancreatic adenocarcinoma is a significant health burden with poor survival, especially among Blacks. To improve survival, we must identify individuals at high risk for further targeted screening, as universal screening is unfeasible. Current prediction tools to identify these individuals are inadequate as they were developed in mostly Whites or lack genetic data from a trans-ancestry population. This proposal will use population-level data to accurately identify cases of pancreatic adenocarcinoma, improve risk prediction by incorporating genetics with clinical factors in the Veterans Affairs electronic health record-linked biobank, and identify genetic risk factors in diverse, underrepresented populations to improve future risk prediction. This new knowledge will not only make early detection of pancreatic adenocarcinoma possible in the multiethnic population of Veterans, but also understand and ultimately bridge the disparities seen in Blacks.

PI_NAMEs: WANG, LOUISE L (contact)

PROJECT_TERMS: Address;Adult;African ancestry;ancestry analysis;Award;biobank;Bioinformatics;Biometry;Black Populations;career;career development;causal variant;Clinical;clinical center;Clinical Data;clinical epidemiology;clinical predictive model;clinical predictors;clinical risk;Code;Communities;Computational Biology;Data;Data Set;data warehouse;Development;Development Plans;Diagnosis;Disease;Disparity;Disparity in diagnosis;Early Diagnosis;Electronic Health Record;Epidemiology;European ancestry;Foundations;Funding;Future;Gastroenterology;General Population;Genetic;Genetic Risk;genetic risk factor;genome wide association study;Genomics;Genotype;Goals;Grant;hazard;Health;health disparity;Hereditary Malignant Neoplasm;Heritability;high risk;high risk population;Histologic;improved;Incidence;Individual;Informatics;Inherited;Institution;International;Investigation;Investments;Knowledge;Laboratories;Link;Logistic Regressions;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of pancreas;Malignant Neoplasms;Manuals;Maps;Medical;Medicine;meetings;Mentorship;Meta-Analysis;military veteran;Mission;Modeling;Morbidity - disease rate;mortality;multi-ethnic;Natural Language Processing;neglect;novel;Outcome;Pancreatic Adenocarcinoma;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Patients;Pennsylvania;personalized strategies;Phenotype;phenotypic data;phenotyping algorithm;Physicians;polygenic risk score;Population;Positioning Attribute;precision medicine;predictive modeling;predictive tools;Predisposition;prevent;Procedures;programs;prototype;racial disparity;racial diversity;Research;Research Infrastructure;Risk;Risk Factors;risk prediction;Scientist;screening;Signal Transduction;skills;Statistical Methods;Structure;structured data;Survival Rate;symposium;Technical Expertise;Testing;Text;tool;Training;trait;Underrepresented Populations;United States Department of Veterans Affairs;Universities;unstructured data;Variant;Veterans;Visualization

PROJECT_TITLE: Pancreatic Cancer Risk Prediction: Integrating Individual-Level Clinical and Genetic Data


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: Heart failure is a very common disease of the aging population with the highest incidence and prevalence in the age group above 65, which is also the largest Veteran population group. Ischemic heart disease and myocardial infarction (MI) are the primary cause or a major contributor in 2/3rds of all cases of heart failure in Veterans. Infiltration of inflammatory macrophages has been implicated in adverse remodeling of the heart muscle leading to post-MI heart failure. We and others have identified macrophage lysosome function as a key determinant of the pro-inflammatory response. In this proposal, we will explore the role of mitophagy pathways in macrophages as a determinant of cardiac myocyte homeostasis and evaluate translational approaches to stimulate mitophagy in cardiac myocytes to prevent development of post-MI cardiomyopathy.

PI_NAMEs: DIWAN, ABHINAV  (contact)

PROJECT_TERMS: 25-hydroxycholesterol;Ablation;Acute;Adult;Affect;age group;Aging;aging population;aging related disease;Anti-Inflammatory Agents;Attenuated;Automobile Driving;Autophagocytosis;Biogenesis;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cd68;Cell Death;cell type;Cells;Cellular Infiltration;Chest;Cholesterol;Collaborations;Data;Defect;Degradation Pathway;Development;enantiomer;Enzymes;Excision;Functional disorder;Generations;genetic approach;Genetic Transcription;Germ Lines;healing;Heart failure;Homeostasis;Hypertrophy;Immune;Impairment;Incidence;Induced Cardiomyocytes;Infiltration;Inflammasome;Inflammation;Inflammatory;Inflammatory Infiltrate;Inflammatory Response;Injury;Ischemia;ischemic cardiomyopathy;knock-down;Left;Left Ventricular Hypertrophy;LoxP-flanked allele;Lysosomes;Macrophage;Maintenance;Mediating;military veteran;Mitochondria;Mitochondrial DNA;Mixed Function Oxygenases;Molecular;monocyte;Morbidity - disease rate;mortality;Mus;Muscle Cells;Myocardial;Myocardial Infarction;Myocardial Ischemia;Myocardium;Pathogenesis;Pathway interactions;Peripheral;Phagocytes;Phase;Phenotype;Physiological;Play;Population;Population Group;Prevalence;prevent;Production;programs;Publishing;Reagent;Reperfusion Injury;Reperfusion Therapy;restoration;restraint;Role;Shapes;Signal Transduction;Sterility;Stress;Structure;Tamoxifen;Testing;Therapeutic;TRAF2 gene;translational approach;United States;Ventricular;Ventricular Remodeling;Veterans;Wild Type Mouse

PROJECT_TITLE: Mitophagy pathways in cellular cross-talk in the myocardium


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: Alcohol-related liver disease affects several million people in the United States and is the most important cause of liver cirrhosis among Veterans. Results from this innovative study will benefit Veterans health by increasing our understanding of the role that specific gut bacteria play in the progression of alcohol-related liver disease. We will also identify innovative intervention strategies to prevent or ameliorate these diseases in Veterans. Our novel findings can easily be translated into Veteran patients suffering from alcohol abuse and liver disease.

PI_NAMEs: SCHNABL, BERND G. (contact)

PROJECT_TERMS: Affect;Alcohol abuse;alcohol use disorder;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcoholism;Alcohols;Bacteria;Bacteriophages;capsule;Cessation of life;Chronic;Clinical;Cytolysins;Data;Development;Disease;disease model;dysbiosis;Endotoxins;Enterococcus;Enterococcus faecalis;Escherichia;Escherichia coli;Etiology;Exotoxins;Experimental Models;Feces;Genes;Genome;Germ-Free;Gnotobiotic;Grant;Growth;gut bacteria;gut metagenome;gut microbiota;Health;Hepatocyte;humanized mouse;improved;in vivo;innovation;insight;Intervention;Intestinal permeability;Intestines;Klebsiella;Kupffer Cells;Laboratories;Lipopolysaccharides;Liver Cirrhosis;Liver diseases;liver inflammation;liver injury;Mediating;Medical;metagenome;metagenomic sequencing;microbial products;microbiome;microbiome research;microbiota;Molecular;Morbidity - disease rate;mortality;Mus;Nature;non-alcoholic;novel;novel strategies;Outcome;pathobiont;Patients;Persons;Phagocytosis;Play;Polysialic Acid;Pre-Clinical Model;prevent;Publications;Research;Role;Severity of illness;Shigella;Testing;Translating;United States;Veterans;Virulence;Virulence Factors;virulence gene;Yersinia

PROJECT_TITLE: The role of pathobionts in alcoholic liver disease


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: PROJECT NARRATIVE This VA Merit Review research will help understand how one liver cell type called hepatic stellate cell (HSC), promotes liver tumor development under alcohol drinking and Western diet consumption, the conditions which are prevalent among veteran patients. Our research has identified a lipid molecule produced by HSC as a novel driver for liver tumor development via a newly revealed tumor promotion pathway. Proposed research will pin-point a subset of HSC responsible for this pathway and test if its intervention reduces liver tumor development in a mouse model and in mice bearing human liver cancer. Findings from these studies will help develop a new therapeutic approach for liver cancer which continues to plague veteran patients.

PI_NAMEs: TSUKAMOTO, HIDEKAZU  (contact)

PROJECT_TERMS: Ablation;Acids;ADD-1 protein;Affinity;Alcohol consumption;Alcohols;Arachidonic Acids;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Attenuated;Behavior;beta catenin;Binding Proteins;cancer cell;Cell Line;cell type;Cells;Cholestasis;combinatorial;Consumption;CTNNB1 gene;CYP1B1 gene;desaturase;design;Development;Diet;Eicosanoids;Enhancers;Event;Extracellular Matrix;Fibroblasts;Gene Expression;Generations;Genes;Genetic Transcription;glycogen synthase kinase 3 beta;Goals;Growth;Hepatic Stellate Cell;Hepatocarcinogenesis;hepatocellular carcinoma cell line;Hepatocyte;Hepatotoxicity;Human;HuR protein;Impairment;in vivo;innovation;Intervention;knock-down;Knock-out;Knockout Mice;Ligands;lipidomics;Lipids;Liver;Liver Fibrosis;Liver neoplasms;LTB4R gene;Malignant neoplasm of liver;Malignant Neoplasms;MAPK3 gene;Mediating;Messenger RNA;Metabolism;Modality;Molecular;Monounsaturated Fatty Acids;mouse model;Mus;neoplastic cell;Nitrosamines;novel;novel therapeutic intervention;Nuclear;nucleocytoplasmic transport;Pathway interactions;patient derived xenograft model;Patients;prevent;Primary carcinoma of the liver cells;Production;programs;Proteins;PTGS2 gene;receptor;Regulation;release factor;Repression;Research;Response Elements;selective expression;single-cell RNA sequencing;Site;Stearoyl-CoA Desaturase;stellate cell;success;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;Therapeutic Intervention;therapeutically effective;Tissues;Transcriptional Activation;transcriptomics;Treatment Efficacy;tumor;tumor microenvironment;Tumor Promoters;Tumor Promotion;Tumor Suppression;Up-Regulation;Veterans;western diet;Wild Type Mouse;Xenobiotics

PROJECT_TITLE: Molecular Mechanisms of Stellate Cell Activation in Liver Fibrosis


PHR: The Department of Veteran Affairs is the single largest health care system in the world to provide comprehensive lifelong care after spinal cord injury (SCI). Most SCI patients experience bone health decline, which involves not only a decrease in the amount of bone but changes to the structure, vascularity, and chemical environment. As a result, patients are predisposed to fractures, anemia, and infections after SCI. Current bone imaging techniques, such as those that use x-rays, are limited in their capability to evaluate changes to bone health. In this project, we propose to optimize novel quantitative magnetic resonance imaging (MRI) techniques to comprehensively assess bone. We validate these techniques in an animal model to show how much bone recovery can be expected by restoring movement and loading after SCI, with and without sympathetic inhibition.

PI_NAMEs: CHANG, ERIC Y (contact)

PROJECT_TERMS: acquired bone marrow failure;Alkalinization;Anemia;Animal Model;behavioral outcome;Binding;Biological Markers;Biology;biomarker panel;biomechanical test;Biomechanics;Blood Vessels;bone;Bone Density;Bone Diseases;bone health;bone imaging;Bone Marrow;bone marrow failure syndrome;bone quality;Bone remodeling;Bone structure;Bone Tissue;Cadaver;Caring;chemical property;Chemicals;Chronic;Clinic;Clinical;clinically relevant;Collagen;density;designer receptors exclusively activated by designer drugs;Deterioration;Development;Diffusion;Dual-Energy X-Ray Absorptiometry;Effectiveness;effectiveness testing;Electrodes;Environment;Evaluation;experience;extracellular;Fracture;Functional disorder;Goals;Grant;Healthcare Systems;Hindlimb;Histology;Hypertension;imaging modality;Imaging Techniques;Immune System Diseases;in vivo;Infection;insight;interest;Investigation;Knee;Life;Locomotion;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maps;Measurement;Measures;mechanical properties;Mechanics;military veteran;Modality;Modeling;molecular scale;morphometry;Motor Activity;Movement;Neurons;neuroregulation;novel;Osteoporosis;osteoporosis with pathological fracture;Paralysed;Pathogenesis;Pathologic;Pathological fracture;Patients;Physiological;Physiology;Property;Protons;Rattus;Recovery;Reference Standards;Relaxation;restoration;Risk;Roentgen Rays;Role;Sampling;Series;Site;skeletal;Spinal;Spinal cord injury;Spinal cord injury patients;Structure;Sympathetic Nervous System;Techniques;Technology;Testing;Thoracic spinal cord structure;Time;Tissues;tool;Translating;Treatment Effectiveness;United States Department of Veterans Affairs;Use of New Techniques;Venous Engorgements;Water;X-Ray Computed Tomography

PROJECT_TITLE: Multi-scale MRI Assessment of Bone Quality and Function in a Chronic Rat Spinal Cord Injury Model


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: HADLEY

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: Project Narrative The “brain-eating amoeba” Naegleria fowleri causes a deadly disease that lacks safe and reliable treatment. To identify new leads for therapeutic development, this proposal will reveal mechanisms responsible for assembling and organizing the mitotic spindle, a cellular structure essential for cell division and thus disease progression. By identifying proteins and processes that are required to assemble a functional spindle, this proposal will provide training in super-resolution microscopy and high throughput sequencing and identify new avenues to develop therapies for combating the devastating infection caused by Naegleria.

PI_NAMEs: KENNARD, ANDREW STEVEN (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Affect;Amoeba genus;Animals;antimicrobial;Architecture;Automobile Driving;Biochemical;Biological;Biology;Brain;Brain Injuries;career;career development;Case Fatality Rates;Category B pathogen;cell assembly;Cell division;Cell Proliferation;Cells;Cellular biology;Cellular Structures;Chromosomes;Data;Development;Disease;Disease Progression;Drug Targeting;Eating;effective therapy;Electron Microscopy;Ensure;experience;Fatality rate;Future;Gene Expression;Gene Proteins;Genes;Goals;Heat-Shock Response;High-Throughput Nucleotide Sequencing;Human;Image;Infection;inhibitor;knock-down;Knowledge;Learning;Length;Measurement;Measures;Mentors;Methods;Microscopy;Microtubule Stabilization;Microtubule stabilizing agent;Microtubules;Mitosis;Mitotic;Mitotic spindle;Molecular;Molecular Motors;Morphology;Motor;Naegleria;Naegleria fowleri;National Institute of Allergy and Infectious Disease;Organism;Pharmaceutical Preparations;Phenotype;Play;Population;Process;Proteins;Protocols documentation;Quantitative Microscopy;Research Personnel;Resolution;Risk;RNA Splicing;Role;Running;Sequence Analysis;side effect;skill acquisition;Source;Structure;success;superresolution microscopy;Techniques;temporal measurement;Testing;Therapeutic;therapeutic development;therapeutically effective;therapy development;Training;transcriptome sequencing;transcriptomics;Tubulin

PROJECT_TITLE: Defining mechanisms of mitotic spindle organization in Naegleria

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-D(21)L]


ORG_CITY: MIAMI

ORG_NAME: MIAMI VA HEALTH CARE SYSTEM

PHR: Dry eye (DE) is a complex disease that manifests with multiple symptoms and signs, affects 1 in 5 veterans, causes significant morbidity, and impacts quality of life. Given the heterogeneous nature of DE, it is necessary to understand mechanisms and contributors to the different disease sub-types in order to optimize treatments. This research focuses on the contribution of bioactive lipid mediators in meibum and tears and their relationship to ocular surface inflammation and clinical manifestations of meibomian gland dysfunction and DE.

PI_NAMEs: GALOR, ANAT  (contact);MANDAL, NAWAJES

PROJECT_TERMS: Affect;Age;Anti-Inflammatory Agents;aqueous;Arachidonic Acids;base;Biological;Biological Assay;Cell Death;Cell Line;Cell Survival;ceramide 1-phosphate;Ceramides;Clinical;Clinical Data;Complex;Cytoplasm;Dinoprostone;Disease;disorder subtype;Docosahexaenoic Acids;Eicosanoids;Eicosapentaenoic Acid;Epithelial Cells;Evaluation;evaporation;Eye;eye dryness;Female;Film;Foundations;Frequencies;Functional disorder;Goals;Human;improved;In Vitro;in vitro Model;in vivo Model;Individual;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Knowledge;Laboratories;Link;lipid mediator;Lipids;male;Measures;Mediating;meibomian gland;meibomian gland dysfunction;military veteran;model building;Modeling;Molecular;molecular targeted therapies;Morbidity - disease rate;multiplex assay;Nature;novel;ocular surface;Omega-3 Fatty Acids;Omega-6 Fatty Acids;Pain;Pathway interactions;Patients;Phospholipase A2;Pilot Projects;Polyunsaturated Fatty Acids;Production;prospective;Prostaglandins;Proteins;Publishing;Quality of life;Regression Analysis;Research;Role;Sample Size;Sampling;Signal Transduction;Signs and Symptoms;Sphingolipids;Sphingomyelinase;Sphingomyelins;sphingosine 1-phosphate;Stress;Symptoms;Testing;therapeutic development;therapeutic target;Time;treatment optimization;Veterans;Visual;Work

PROJECT_TITLE: Lipid mediators and their signaling in ocular surface inflammation and meibomian gland dysfunction


PHR: Veterans of war are more prone to be affected by depression, chronic fatigue and anxiety. Posttraumatic stress disorder (PTSD) is common among former soldiers who have experienced traumatic battlefield combat experiences, such as witnessing suffering and death. Although there are several factors that predict the severity of symptoms and recovery, PTSD is undoubtedly a widespread condition among soldiers. Research suggests that there is a specific link between PTSD and cocaine abuse and that patient treatment should approach both disorders in order to be successful. This proposal focuses on characterizing the molecular mechanisms involved in the effects of cocaine in the cardiovascular system. This will help inform patient care and facilitate the development of novel therapeutic treatments for cocaine-induced cardiovascular toxicities for veterans in particular, among whom cocaine abuse is more prevalent.

PI_NAMEs: DONG, CHUNMING  (contact)

PROJECT_TERMS: Accounting;Acetylcysteine;Adrenergic Agents;Affect;Aging;analog;Anxiety;Aorta;Arrhythmia;Atherosclerosis;Biological Process;Blood Pressure;blood pressure elevation;Blood Vessels;Calcium;Calcium Channel;Cardiac Catheterization Procedures;Cardiovascular Diseases;cardiovascular effects;Cardiovascular Pathology;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;Catecholamines;Cause of Death;Cell Physiology;Cells;Central Nervous System;Cessation of life;Chronic;clinical practice;Cocaine;Cocaine Abuse;cocaine exposure;cocaine use;combat;Complex;Coronary Arteriosclerosis;Data;Development;Disease;Emergency department visit;Ensure;Epidemiology;experience;experimental study;Fatigue;FDA approved;Florida;Funding;General Population;Genes;Genomic approach;genomic data;Guidelines;Heart failure;Hypertension;illicit drug use;Illicit Drugs;In Vitro;in vitro Model;in vivo;in vivo Model;innovation;Journals;Link;malic enzyme;Measures;Mediating;Mental Depression;Messenger RNA;MicroRNAs;Modification;Molecular;Mus;Muscle Contraction;Nerve;Nerve Endings;Nimodipine;Norepinephrine;novel therapeutics;Opioid;opioid epidemic;opioid overdose;Outcome;overexpression;Pathogenesis;Pathologic;Pathway interactions;Patient Care;Patients;pharmacologic;Play;Post-Traumatic Stress Disorders;Prazosin;Predictive Factor;Prevalence;Publishing;Reactive Oxygen Species;Recovery;Regulation;Reporting;Research;Research Design;Resources;respiratory;Respiratory Failure;reuptake;Role;Saline;Severities;Signal Transduction;Small RNA;Smooth Muscle Myocytes;Soldier;Solid;Sympathetic Nervous System;Symptoms;Testing;Toxic effect;transcriptome sequencing;translational potential;Treatment-related toxicity;United States National Institutes of Health;Up-Regulation;Vascular Endothelial Cell;Vascular Smooth Muscle;Veterans;Visit;War;Work

PROJECT_TITLE: microRNA Regulation of The Cocaine Effects on the Cardiovascular System


PHR: Patients with esophageal adenocarcinoma have a poor survival rate and limited treatment options, making this tumor a serious health problem. The proposed research will provide new insights into esophageal tumorigenesis and lay the groundwork for development of novel chemopreventive and chemotherapeutic agents.

PI_NAMEs: ZAIKA, ALEXANDER I. (contact)

PROJECT_TERMS: adduct;Affect;Animal Model;Animal Testing;Animals;Apoptosis;Bile fluid;Biological Process;Cell Cycle Arrest;Cell Proliferation;Cells;Chemicals;Chemopreventive Agent;chemotherapeutic agent;Chronic;Clinical;Data;Development;DNA;DNA Damage;DNA Repair;DNA Sequence Alteration;drug testing;Duodenum;Epithelium;Esophageal Adenocarcinoma;Esophageal Intraepithelial Neoplasia;Esophageal mucous membrane;Esophageal Tissue;Esophagus;Exposure to;free radical oxygen;Frequencies;Gastroesophageal reflux disease;genome integrity;Genomic Instability;Health;High Prevalence;Histologic;Human;in vivo;Incidence;Individual;Inflammatory;Injury;Innate Immune Response;innovation;insight;interest;Laboratories;Lesion;Malignant - descriptor;Malignant neoplasm of esophagus;Malignant Neoplasms;Mediating;member;Metaplasia;Molecular;mouse model;Mutation;Neoplasms;Neoplastic Cell Transformation;novel;novel therapeutic intervention;Pathway interactions;Patients;Play;Population;premalignant;prevent;Prevention;Protein Family;Proteins;PTGS2 gene;Reflux;Regulation;Reporting;Research;response;Risk;Risk Factors;Role;screening;Specimen;Stomach Content;Survival Rate;Testing;tissue injury;Tissues;TP53 gene;tumor;Tumor Suppression;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;Veterans

PROJECT_TITLE: Regulation of DNA damage response in esophageal cells exposed to reflux


ADMINISTERING_IC: DC

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE During development, neural circuits self-assemble to form the connectivity patterns governing all brain functions. This proposal seeks to elucidate conserved cellular strategies that underly neural circuit formation in the intact brain. Thus, this work will provide key mechanistic insight into an important neurodevelopmental process, which will be crucial for creating therapeutic strategies to regenerate circuits following ageing, disease, or injury.

PI_NAMEs: MCLAUGHLIN, COLLEEN  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Afferent Neurons;Aging;Axon;Biological;Brain;career;Cell Physiology;Cell surface;Cell Surface Proteins;cell type;Cells;Central Nervous System;Collaborations;Color;Complex;Cytosol;Data;Defect;Dendrites;Development;Disease;Drosophila genus;Endocytosis;Endosomes;Ensure;Environment;Enzymes;Equilibrium;Esthesia;Event;Exhibits;Family;fly;Genetic;Guanosine Triphosphate Phosphohydrolases;Impairment;in vivo;in vivo Model;Injury;insight;Label;Lobe;Mass Spectrum Analysis;Maxilla;Membrane;Membrane Proteins;Mentors;migration;Mission;National Institute on Deafness and Other Communication Disorders;Natural regeneration;neural circuit;Neurites;neurodevelopment;Neuronal Differentiation;Neurons;Olfactory dysfunction;Olfactory Pathways;Olfactory Receptor Neurons;Pathway interactions;Pattern;Phase;Physiological;Process;Protein Array;protein degradation;Protein Dynamics;Proteins;Proteomics;Recycling;Regulation;Research;Role;self assembly;Sensory;Sensory Disorders;sensory system;Series;Shapes;Signal Transduction;Signaling Protein;Stereotyping;Structure;Synapses;synaptogenesis;System;temporal measurement;Testing;Therapeutic;tool;trafficking;Training;Work

PROJECT_TITLE: Cell surface protein dynamics in neural circuit assembly

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer

ORG_CITY: WORCESTER

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project Narrative The ability to functionally characterize all human kinases, understand potential mechanisms leading to drug resistance in cancer therapy and identify new compounds targeting them for degradation is severely hampered by technological limitations to interrogate all expressed human kinases in a single assay. The objectives of this proposal are to develop a new targeted kinome assay to enable simultaneous relative and absolute quantification of all human kinases and then to apply the assay to chemical library screening.

PI_NAMEs: YU, QING  (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: Abnormal Cell;Accounting;Address;Aging;amyloid precursor protein processing;application programming interface;Automation;Automobile Driving;Benchmarking;Biochemical;Bioinformatics;Biological Assay;Biological Process;Biology;Body part;Bypass;Calibration;Cancer cell line;cancer therapy;carcinogenicity;career;Categories;Cause of Death;Cell Proliferation;Cells;Cessation of life;Chemicals;Chemistry;Clinical;Collaborations;Computer software;Core Facility;Cytolysis;Darkness;Data;Decision Making;Development;Digestion;drug candidate;drug discovery;Drug resistance;Drug Targeting;Enzymes;experimental study;Family;Fulvestrant;Genetic Variation;Goals;Human;Human Cell Line;Informatics;inhibitor;innovation;instrument;interest;Investigation;kinase inhibitor;Knowledge;Label;Libraries;lipid metabolism;Malignant neoplasm of ovary;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Measurement;Measures;medical schools;member;Mentors;millisecond;next generation;novel;novel therapeutics;overexpression;Pathologic Processes;Pathology;Pharmaceutical Preparations;Phosphotransferases;Platinum;Play;Postdoctoral Fellow;Preparation;pressure;programs;protein degradation;protein expression;Protein Kinase;protein protein interaction;Proteins;Proteome;Proteomics;Protocols documentation;Reagent;Reproducibility;Research;Resistance;resistance mechanism;Resources;response;Role;Sampling;screening;selected ion monitoring;Signal Transduction;small molecule libraries;stoichiometry;success;System;targeted agent;Technology;technology development;Thalidomide;Therapeutic;therapeutic biomarker;therapeutic development;Time;Tissues;tool;Training;transcription factor;Work

PROJECT_TITLE: New Proteomics Approaches to Study the Full Human Kinome, Inhibitor Resistance, and Kinase Degraders

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-R (M1)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pediatric;Substance Misuse;Underage Drinking

ORG_CITY: CHARLESTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE The K24 Mid-Career Investigator Award will allow Dr. Squeglia to bolster her dedication to patient-oriented adolescent alcohol research and mentorship. She will also develop her own skill set through proposed structured trainings in inflammation markers, advanced neuroimaging, and statistical analysis. Dr. Squeglia is committed to training the new generation of patient-oriented adolescent alcohol researchers and will continue to concentrate on efforts to diversify the pool of junior alcohol researchers.

PI_NAMEs: SQUEGLIA, LINDSAY  (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: Acetylcholine;Adolescence;Adolescent;adolescent alcohol treatment;adolescent substance use;Adult;Affect;Age;age group;alcohol abuse therapy;Alcohol consumption;alcohol effect;alcohol research;alcohol use disorder;Alcohols;Alternative Medicine;Anterior;Anti-Inflammatory Agents;Antiinflammatory Effect;Arachidonic Acids;Area;Attention;attentional control;Award;Behavioral;Biological Markers;Blood;Brain;candidate identification;career;career development;Cell Death;Cells;Central Nervous System;Choline;Clinical Investigator;Clinical Trials;Cocaine use disorder;Cognition;Cognitive;cognitive control;cognitive enhancement;cognitive function;cognitive testing;craving;critical period;Cytidine Diphosphate Choline;cytokine;Dedications;Development;Dopamine;drinking;Educational workshop;efficacious treatment;Ensure;Enzymes;Evaluation;experience;Fetal Alcohol Exposure;Funding;Future;Generations;Glutamates;Goals;Grant;Growth and Development function;hands on research;Health;Impaired cognition;improved;Impulsivity;indexing;Inflammation;Inflammatory;inflammatory marker;interest;Interleukin-6;International;Intervention;Link;Magnetic Resonance Spectroscopy;Measures;Membrane;membrane synthesis;Mentors;Mentorship;Methamphetamine use disorder;Methods;Minority Groups;N-acetylaspartate;Nervous System Disorder;neural;Neurocognition;Neurocognitive;neuroimaging;neuroinflammation;Neurons;neuroprotection;Neurosciences;Neurotransmitters;neurotrophic factor;next generation;Outcome;Participant;patient oriented;patient oriented research;Peripheral;Peripheral Nervous System;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phenotype;Phospholipase A2;Phospholipids;Placebos;Play;Prevalence;Production;Property;psychosocial outcome;Publications;Randomized;reduced substance use;Research;Research Personnel;Role;Signal Transduction;skills;Speed;Statistical Data Interpretation;Stroke;Structure;substance use;success;Supplementation;symposium;System;Testing;therapy development;Time;TNF gene;Training;Traumatic Brain Injury;Treatment Efficacy;treatment research;underage drinking;Withdrawal;young adult;Youth

PROJECT_TITLE: Mentoring Clinical Investigators in Patient-Oriented Adolescent Alcohol Research

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 GG (01)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Social Determinants of Health

ORG_CITY: IRVINE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Many studies now firmly support the idea that diversity makes teams and organizations stronger. Moreover, in order for taxpayer money to be equitably utilized there should be equal opportunities for individuals from every type of background to engage in research supported by taxpayer money and for their communities to benefit from such research. Here, we propose to provide educational and personal development activities to encourage individuals from diverse backgrounds to enter academia. We propose to create a new form of mentoring ecosystem to support their inclusiveness and promote their involvement and success within scientific and academic communities. The goal of this program is quite simply to train graduate students for successful careers to diversify the biomedical research workforce and to be active future leaders with skills that will enable them to further promote diversity, equity, inclusion and accessibility.

PI_NAMEs: DONOVAN, PETER JOHN (contact);FOWLER, CHRISTIE D

PROGRAM_OFFICER_NAME: ULLRICH, LAUREN ELIZABETH

PROJECT_TERMS: Academia;Address;Alzheimer's Disease;American;Awareness;Back;Behavior;Behavioral Sciences;Biomedical Research;Brain;brain fog;brain health;career;Centers for Disease Control and Prevention (U.S.);cohort;Collaborations;college;Communication;Communities;Country;Coupled;COVID-19 pandemic;Data;Development;Domestic Violence;Drug Addiction;Ecosystem;Education;Educational Activities;Educational process of instructing;Ensure;Epilepsy;Equity;equity, diversity, and inclusion;Faculty;faculty mentor;Family;Fellowship;Fright;Funding;Future;Goals;graduate school;graduate student;Health;Health Care Costs;health goals;Healthcare Systems;Heart Diseases;Home;Human;Humanities;Individual;Inequity;Institution;Leadership;Learning;Long COVID;Malignant Neoplasms;Mental Depression;Mental Health;Mentors;Methods;Minority-Serving Institution;Neurobiology;Neurosciences;Neurosciences Research;novel;Oral;Outreach Research;peer coaching;Population;programs;Qualifying;Recruitment Activity;Research;Research Personnel;Research Support;Resources;Scientist;Services;skills;Social isolation;Societies;Stroke;student training;Students;success;symposium;Syndrome;Techniques;Testing;Time;Training;Training Support;undergraduate student;underrepresented minority student;Underrepresented Populations;Underrepresented Students;underserved community;United States;United States National Institutes of Health;Universities;Visit;Writing

PROJECT_TITLE: Enhancing Neuroscience Research through Inclusiveness, Culture and Health (ENRICH)

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-F (10)]


ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

PHR: Stroke is a major cause of disability in the US and among our Veterans. High blood pressure and diabetes, which occurs in 37% and 25% of our Veterans, respectively, are two major diseases that increase the risk of having a stroke. There are NO approved treatments because we do not know the underlying mechanisms that contribute to poor brain repair and functional recovery after stroke in these diseases. Most research has been conducted in males and we do not know the disease process in females. We will use disease models that are common in stroke patients and determine the mechanisms contributing to post stroke functional and cognitive recovery in both sexes. Since a high percentage of Veterans suffer from diabetes and stroke and female Veterans are rapidly increasing, this project is highly relevant to the mission of Veterans Affairs.

PI_NAMEs: ERGUL, ADVIYE  (contact)

PROJECT_TERMS: acute stroke;Address;Administrative Supplement;Affect;American;American Heart Association;Animal Model;Animals;Appointment;arteriole;Award;Biology;Blood flow;blood vessel occlusion;Blood Vessels;Brain;Brain Diseases;brain dysfunction;brain repair;Cardiometabolic Disease;Cardiovascular Diseases;career;Cerebrovascular Disorders;Cerebrovascular system;Cerebrum;Chronic;Coagulation Process;cognitive recovery;Collaborations;Complications of Diabetes Mellitus;Dementia;dementia risk;Diabetes Mellitus;diabetic;disability;Disease;disease model;Endocrinology;Extramural Activities;Failure;Female;Funding;Grant;Healthcare;Hypertension;Impaired cognition;Impairment;improved;Injury;innovation;Intervention;Ischemic Brain Injury;Ischemic Neuronal Injury;Ischemic Stroke;Journals;juvenile animal;male;Mentors;Microvascular Dysfunction;military veteran;Mission;Molecular;multidisciplinary;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Neurological Disorders and Stroke;neovascularization;Neurons;next generation;Paper;Pathologic;Patients;Pattern;peer;Pericytes;Pharmaceutical Preparations;Pharmacology;physical impairment;Physiology;post stroke;post stroke cognitive impairment;post stroke dementia;Postdoctoral Fellow;Process;professor;Program Research Project Grants;programs;Publications;Publishing;Quality of life;Recovery;Recovery of Function;repaired;Research;Research Personnel;Risk;Risk Factors;Role;Scientist;Senior Scientist;sex;Societies;Stroke;stroke patient;stroke recovery;stroke therapy;Structure;success;System;Training;Training Programs;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;vascular injury;vascular risk factor;Veterans;Wages;Women's Health;working group

PROJECT_TITLE: BLR&D Research Career Scientist Award Application

STUDY_SECTION: RCSR

STUDY_SECTION_NAME: Research Career Scientist[RCSR]


ORG_CITY: BUFFALO

ORG_NAME: VA WESTERN NEW YORK HEALTHCARE SYSTEM

ORG_STATE: NY

PHR: Ischemic heart disease continues to be the leading cause of mortality and morbidly in the United States, impacting the lives of millions of Veterans each year. This project seeks to identify novel therapeutic approaches and targets to simulate heart muscle regeneration, including those that would not require the administration of stem cell populations. This would enhance the treatment of Veterans with a wide spectrum of cardiac disease including heart failure and myocardial infarction.

PI_NAMEs: LANG, JENNIFER K (contact)

PROJECT_TERMS: Acute myocardial infarction;Address;Anti-Inflammatory Agents;Apoptotic;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiac repair;cardioprotection;Cell membrane;cell preparation;Cell secretion;Cell Therapy;Cells;Cellular Membrane;Clinical Research;conditioning;Data;Diameter;Engraftment;Environment;Enzymes;exosome;experimental study;extracellular;Fibroblasts;Fibrosis;functional decline;functional improvement;Genes;Genetic;Goals;Heart;Heart Diseases;Heart failure;heart function;Human;In Vitro;in vivo;Infarction;Inflammation;injured;intercellular communication;Ischemia;knock-down;late endosome;Left Ventricular Function;Macrophage;Mediating;Mediator;Membrane Lipids;Messenger RNA;MicroRNAs;mortality;mouse model;Multivesicular Body;muscle regeneration;Myocardial Infarction;myocardial injury;Myocardial Ischemia;Myocardium;Natural regeneration;novel;novel therapeutic intervention;paracrine;Paracrine Communication;Patient Care;Patients;pharmacologic;Phenotype;Physiological;prevent;Proteins;Recovery;repaired;Reporting;response;restoration;Role;Sphingomyelinase;stem cell population;stem cells;success;Testing;tool;United States;Up-Regulation;vector;Vesicle;Veterans;Work

PROJECT_TITLE: The Functional Role of Exosomes in Stem Cell Mediated Cardiac Repair

STUDY_SECTION: CARA

STUDY_SECTION_NAME: Cardiovascular Studies A[CARA]


ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: We have an established research program that focuses on understanding the pathogenesis of intestinal inflammation, mucosal immunity and formulating treatment strategies for intestinal inflammatory diseases. We have made seminal observations on alterations in peptide transporters during intestinal inflammation and utilized peptide transporters to deliver anti-inflammatory molecules to treat intestinal inflammation and colitis associated cancer. Impact on Veterans Health care: Over one million adults in the US, including members of the VA population, suffer from IBD, and about 50,000 new cases are diagnosed each year (according to the Crohn’s and Colitis Foundation of America. The VA IBD patients have a much higher rate of colorectal cancer compared to the general population (2.9% vs. 0.1%; from National Center for Health Statistics data). Thus, attaining an understanding of the etiology of IBD and the relevant pathological mechanisms are major aims of research seeking to develop effective future treatments will directly benefit the veteran population.

PI_NAMEs: MERLIN, DIDIER  (contact)

PROJECT_TERMS: Adult;Affect;Anti-Inflammatory Agents;Award;candidate selection;career;Cellular biology;Child;clinical care;Colitis;colitis associated cancer;Collaborations;Colorectal Cancer;Crohn's disease;Data;Development;Diagnosis;Digestive System Disorders;Discipline;Disease;Doctor of Philosophy;Environment;Etiology;Faculty;Focus Groups;Fostering;Foundations;Future;Gastroenterology;General Population;Grant;gut inflammation;Healthcare;improved;indexing;Inflammatory Bowel Diseases;Interdisciplinary Study;interest;Intestines;Journals;K-Series Research Career Programs;Laboratories;lectures;Medical center;meetings;member;military veteran;Mission;Molecular Biology;Mucosal Immunity;Nanotechnology;Neurofibromin 2;next generation;novel;novel therapeutic intervention;Pathogenesis;Pathologic;Patients;Peptides;Physicians;Population;Productivity;programs;Publishing;Research;Research Personnel;Science;Scientist;Seminal;Series;Structure;symposium;Techniques;Training;training opportunity;Transcend;treatment strategy;United States National Center for Health Statistics;Universities;Veterans;Work


ADMINISTERING_IC: HD

ED_INST_TYPE: UNIVERSITY-WIDE

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

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Congenital Structural Anomalies;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Pediatric;Pregnancy

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative Mutations in the most evolutionarily conserved regions of the human genome have been shown to be strong risk factors for many developmental anomalies in humans. In this proposal, I will leverage whole-genome sequencing data from an unprecedented trio cohort ascertained for intrauterine fetal death, one of the most extreme developmental disorders, to discover mutationally intolerant loci in the human genome, define functional features that are predictive of these loci, and evaluate these predictors against a continuum of severe developmental disorders. This work will establish a statistical framework for disease association capable of integrating evidence from all variation classes weighted by metrics of evolutionary constraint, and will yield new insights into the roles that mutationally intolerant loci play in the etiologies of fetal loss and other severe developmental anomalies.

PI_NAMEs: WANG, LILY  (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: Atlases;Automobile Driving;Autopsy;Biological;Birth;career;cell type;Cells;Childhood;Chromatin;Clinical;Code;cohort;congenital anomaly;Data;Data Set;Development;developmental disease;Developmental Process;Discipline;Disease;disease model;Doctor of Philosophy;dosage;Etiology;Exhibits;exome;Family member;Fellowship;Fertility;fetal;Fetal Death;fetal loss;Fetus;First Pregnancy Trimester;gene discovery;Gene Frequency;gene function;General Population;Genes;genetic architecture;Genetic Predisposition to Disease;Genetic Risk;Genetic study;Genetic Transcription;Genetic Variation;Genome;genome sequencing;genome-wide;Genomic Segment;genomic variation;Genomics;hands on research;Human;human data;Human Development;Human Genome;Individual;Inherited;insertion/deletion mutation;insight;Institution;International;Laboratories;laboratory experience;loss of function;Maternal-fetal medicine;Measures;Mentors;Mentorship;Mus;Mutation;Natural Selections;Neurodevelopmental Disorder;novel;Outcome;Parents;Pathway interactions;Pattern;Play;Point Mutation;Population;Positioning Attribute;programs;Property;protein protein interaction;Publishing;purge;Recurrence;Regulatory Element;reproductive;Research;Research Support;Resources;Risk Factors;Role;Sampling;sex;skill acquisition;Source;Statistical Models;stillbirth;Structural defect;symposium;Testing;tool;Training;training opportunity;Untranslated RNA;Variant;whole genome;Work

PROJECT_TITLE: Illuminating the distribution of extreme evolutionary constraint in the human genome from fetal demise to severe developmental disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: Infection with HCV is particularly prevalent in the veteran population. Roughly 80% of veterans are at sufficient risk as to qualify for screening, and approximately 10% are infected. Infection with HCV constitutes the most common cause of chronic hepatitis in the United States. Many infected patients develop cirrhosis, end stage liver disease, and liver cancer. Liver cancer, and geriatric age are developing issues expected to peak in 2030, though screening and treatment of liver cancer is only modestly effective. Because of these issues, and because Natural Killer (NK) cells are capable of controlling cancer, investigation of the role of NK cells in control of HCV associated hepatocellular carcinoma is needed to guide new screening, monitoring, and treatment strategies.

PI_NAMEs: ANTHONY, DONALD D (contact)

PROJECT_TERMS: Age;Aging;anti-cancer;Biological Assay;Biological Markers;Blood;Cancer Control;cancer therapy;case control;Cause of Death;Cellular Assay;Chronic Hepatitis;Chronic Hepatitis C;Cirrhosis;Clinical Trials;Clinical Trials Design;Cryopreservation;Cytolysis;Data;design;Diagnosis;diagnostic strategy;disorder risk;Doctor of Philosophy;Elderly;end stage liver disease;epidemic virus;Funding;Genes;Granzyme;Hepatitis C;Hepatitis C Therapy;Hepatitis C virus;hepatocellular carcinoma cell line;high risk;Host Defense;human old age (65+);immune function;Immune response;Immunity;improved;In Vitro;in vivo;Incidence;Individual;Infection;Interferon alpha;Interferon Type II;Interferons;Investigation;knock-down;Liver;Liver diseases;liver transplantation;Lymphocyte;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;metastatic colorectal;Metastatic Neoplasm to the Liver;military veteran;Monitor;Morbidity - disease rate;mortality;Natural Killer Cells;NK Cell Activation;NK cell therapy;novel diagnostics;novel therapeutic intervention;Onset of illness;Outcome;Participant;Pathway interactions;patient population;Patients;PD-1 blockade;PD-1 pathway;Peripheral Blood Mononuclear Cell;Phenotype;Plasma;Plasma Cells;Play;Population;predictive marker;Prevention strategy;Primary carcinoma of the liver cells;programmed cell death protein 1;Qualifying;Recording of previous events;Regimen;Regulatory Pathway;response;Risk;Role;Running;screening;Signal Transduction;T-Lymphocyte;targeted treatment;Therapeutic;Time;TNF gene;transcriptomics;treatment strategy;tumor;United States;Untranslated RNA;Veterans;Viral;Work

PROJECT_TITLE: Role of NK cells in control of HCV infection associated hepatocellular carcinoma


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Biotechnology;Obesity;Sarcopenia

ORG_CITY: BATON ROUGE

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

ORG_STATE: LA

PHR: PROJECT NARRATIVE Sarcopenic obesity is strongly associated with a decline in physical function and less independence in older adults. As such, there is immense value in determining strategies to mitigate sarcopenic obesity to improve the quality of life in older adults. The proposed study will pave the way for novel mechanistic insights and the discovery of new therapeutics for healthspan during aging with obesity.

PI_NAMEs: DANTAS, WAGNER SILVA (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Acute;Address;Affect;age-related disease;aged;Aging;Antioxidants;Apoptosis;Area;Attenuated;Award;Behavior Therapy;Biogenesis;Biology;biomedical profession;career;Career Transition Award;Cell Culture Techniques;Cells;Cessation of life;Chloroquine;Chronic Disease;Dedications;Defect;Development;Dynamin;effective therapy;Elderly;energy efficiency;Equilibrium;Erythroid;experimental study;Extramural Activities;fitness;frailty;Fumarates;Funding;Future;Generations;Genetic;genetic manipulation;Geroscience;Goals;graduate student;Health;Health Care Costs;healthspan;high risk;Hospitalization;Impairment;implementation facilitation;improved;In Vitro;inhibitor;insight;Institutionalization;Knowledge;Learning;life span;Life Style;Link;Lipids;loss of function;Mediating;Metabolic;MG132;Mitochondria;mitochondrial DNA mutation;Mitochondrial RNA;Modeling;Molecular;Morbidity - disease rate;mRNA Decay;Mus;Muscle;Muscle Fibers;muscle form;Muscle function;Muscle Mitochondria;muscle strength;Muscular Atrophy;new therapeutic target;novel;novel therapeutics;Nuclear;nuclear factor-erythroid 2;obese patients;Obesity;old mice;older adult;older patient;Organelles;oxidation;Oxidation-Reduction;oxidative damage;Oxidative Stress;Oxidative Stress Induction;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Phosphorylation;Physical Function;Positioning Attribute;Postdoctoral Fellow;prevent;Probability;Production;programs;Protein Biosynthesis;protein expression;Protein Import;Proteins;proteostasis;Public Health;Quality Control;Quality of life;Reactive Oxygen Species;Regulation;Research;Research Design;Risk;RNA;RNA Interference;Role;sarcopenia;sarcopenic obesity;Scientist;Series;Signal Transduction;Skeletal Muscle;skills;Small Interfering RNA;Syndrome;System;Techniques;Testing;Therapeutic;Time;trafficking;Training;Transgenic Mice;treatment strategy;Underrepresented Minority;United States National Institutes of Health;Weight

PROJECT_TITLE: The Role of Nuclear Factor Erythroid 2-related factor 2 in Sarcopenic Obesity

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-B (MK)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Eating Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Nutrition;Pediatric;Social Determinants of Health

ORG_CITY: RICHMOND

ORG_DEPT: PEDIATRICS

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE Transgender and gender-diverse (TGD) youth are at higher risk of disordered eating behaviors in comparison to cisgender youth and engage in disordered eating behaviors (DEB) for unique factors related to their gender dysphoria, yet there are no specific measures tailored to this population. This Career Development Award will implement community-engaged research methods to improve recruitment of subpopulations of TGD youth who have historically been excluded from research and then develop and evaluate a culturally specific DEB measure using a high degree of TGD youth input. This proposal will advance the clinical practice for a highly stigmatized population by developing a measure that will inform interventions for specific behaviors, attitudes, and cognitions that contribute to DEB in TGD youth.

PI_NAMEs: PHAM, AN H (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Address;Adolescent Medicine;Adult;Affect;Age;Anxiety;Applications Grants;Assessment tool;Attitude;Beauty;Behavior;Binge Eating;Birth;body dissatisfaction;Caring;Characteristics;children of color;cisgender;Clinical;clinical care;clinical practice;Cognition;cognitive interview;Communities;community engaged research;community partners;Data;Death Rate;design;Development;direct application;Discrimination;Distress;Eating;Eating Behavior;Eating Disorders;Ensure;Equity;Estrogens;ethnic diversity;ethnic minority;Ethnic Origin;Evaluation;Exclusion;Exercise;expectation;experience;Exposure to;Family member;Fasting;Feeling suicidal;Female;Focus Groups;Future;Gender;gender affirmation;gender affirming care;gender affirming medical care;gender diverse;gender dysphoria;Gender Identity;gender minority community;gender minority group;General Population;Goals;Group Interviews;Health;health disparity;high risk;Impairment;improved;Individual;innovation;Intervention;Intervention Studies;Interview;K-Series Research Career Programs;Knowledge;Literature;Lived experience;Longitudinal Studies;marginalization;marginalized population;Measurement;Measures;member;Mental Depression;Mental Health;Mentorship;Methods;National Institute of Mental Health;nonbinary;novel strategies;Onset of illness;Participant;peer;Persons;Pharmaceutical Preparations;Physicians;Population;Property;protective factors;Protocols documentation;Psychometrics;Puberty;puberty blocker;purge;Qualitative Methods;Qualitative Research;Questionnaires;Race;racial diversity;racial minority;recruit;Reporting;Research;Research Activity;Research Methodology;Research Personnel;Research Training;Resources;Risk Factors;Sampling;sex assigned;Sexual and Gender Minorities;sexual minority group;sexual minority youth;skills;social expectations;social stigma;Societies;Stigmatization;Structure;Suicide attempt;Surveys;symptomatology;Testing;Testosterone;Training;Training Activity;transgender;Vulnerable Populations;Work;young adult;Youth

PROJECT_TITLE: Using youth-engaged methods to develop and evaluate a measure for disordered eating behaviors in transgender and gender-diverse youth

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


ADMINISTERING_IC: AI

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: Chicago

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: PROJECT NARRATIVE Cytokines are powerful modulators of the immune system, but cytokine therapies have had limited clinical success due to off-target side effects. To circumvent these limitations, this research proposes to engineer a platform technology that delivers these protein drugs where they are needed in multiple different immune- mediated diseases.

PI_NAMEs: VOLPATTI, LISA R (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Advanced Development;Affect;Affinity;Anti-Inflammatory Agents;Antibodies;antigen binding;Antiinflammatory Effect;Arterial Fatty Streak;Atherosclerosis;Avidity;Binding;Binding Sites;Biological;career development;cell type;Cells;Chimeric Proteins;Cholesterol Homeostasis;chronic inflammatory disease;Clinical;cytokine;cytokine therapy;Data;design;Development;Development Plans;Disease;disease model;Disease Outcome;Disease Progression;Drug Kinetics;Engineering;Environment;Epitopes;extracellular;Foam Cells;Future;Grant;Half-Life;High Prevalence;hypercholesterolemia;Immune;Immune system;Immune System Diseases;Immunoglobulin Fragments;Immunomodulators;immunoregulation;improved;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;Injections;insight;interest;Interleukin-10;interleukin-19;Learning;Lipid-Laden Macrophage;Lipids;Lipoprotein Binding;Low-Density Lipoproteins;Macrophage;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;Metabolism;Molecular Mechanisms of Action;mouse model;Mus;Nature;neonatal Fc receptor;next generation;non-alcoholic fatty liver disease;NUP214 gene;optimal treatments;Pharmaceutical Preparations;Phenotype;Play;pleiotropism;Population;prevent;professor;Protein Engineering;Proteins;receptor;Recycling;Reporting;Research;Research Proposals;response;Role;scavenger receptor;Side;side effect;Signal Transduction;single-cell RNA sequencing;skills;Solid;Specificity;Stimulus;success;Technology;technology platform;tenure track;Testing;Tissues;tool;transcriptome;treatment effect;uptake;vascular inflammation;Work

PROJECT_TITLE: Engineered Cytokines Targeting Lipid-Laden Macrophages

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Immunotherapy;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative NK cells are a type of lymphocyte with a specialized capacity to kill cancer cells through engagement of activating receptors. Memory-like NK cells develop after a brief cytokine stimulation resulting in an increased ability to kill leukemia, and when transferred into patients have an excellent safety profile; however, clinical responses in difficult-to-treat acute myeloid leukemia patients are not durable. The goal of this application is to understand how leukemia resists and evades memory-like NK cells with the goal of improving clinical outcomes to NK cell therapy.

PI_NAMEs: FOLTZ-STRINGFELLOW, JENNIFER ANN (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Activated Natural Killer Cell;Acute Myelocytic Leukemia;acute myeloid leukemia cell;antileukemic activity;Apoptotic;Automobile Driving;Binding;Biological Assay;Blocking Antibodies;cancer cell;Cancerous;career;career development;cell killing;Cell Physiology;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cessation of life;chimeric antigen receptor T cells;Clinic;Clinical;clinical efficacy;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Collaborations;cytokine;Cytokine Signaling;Cytoplasmic Granules;cytotoxic;cytotoxicity;Data;Development Plans;differentiation in vitro;Disease remission;Dominant-Negative Mutation;Down-Regulation;Educational workshop;Effector Cell;Epigenetic Process;epigenome;epigenomics;exhaustion;Flow Cytometry;Future;Genetic Transcription;Genomics;Goals;Grant;Granzyme;Immune;immunoglobulin receptor;improved;In Vitro;in vivo;Interleukin-12;Interleukin-15;Interleukin-2;International;Journals;Laboratory Research;Lead;Leadership;leukemia;Leukemic Cell;Ligands;Ligation;Literature;loss of function;Lymphocyte;Malignant - descriptor;Malignant Neoplasms;Measurement;member;Memory;Mentors;MHC Class I Genes;MHC Class II Genes;Molecular;mouse model;multiple omics;Mus;Natural Killer Cells;neoplastic cell;NK Cell Activation;NK cell therapy;novel;Outcome;Pathway interactions;Patients;perforin;Phenotype;Positioning Attribute;post-doctoral training;Predisposition;pressure;programs;receptor;receptor sensitivity;Regulation;Research;Research Personnel;Research Project Grants;Resistance;resistance mechanism;response;Role;Running;Safety;Sampling;Shapes;skills;symposium;T-Lymphocyte;tenure track;Therapeutic;TNF gene;TNFSF10 gene;Training;transcription factor;Translating;tumor;Up-Regulation;Work;Writing;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Mechanisms of NK cell activation and immune-editing of leukemia


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

ORG_CITY: HOUSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE The pathogenic bacterium Staphylococcus aureus can evade effective clearance by host cells or antibiotics by adopting a heterogeneous mixture of states during infection that balance growth and tolerance. Since this represents a significant hurdle to curative treatment, understanding cell-to-cell heterogeneity in responses to these challenges would not only help identify the drivers of this variation, but also reveal fundamental insights into how these responses are regulated. In this proposal, I will capture the responses of individual S. aureus cells to the antibiotic vancomycin and to the complex environment within human cells to understand what determines the outcome of these interactions, helping to overcome this inherent variation and allow eradication of this resilient pathogen from infection sites.

PI_NAMEs: POUNTAIN, ANDREW WILLIAM (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;Adopted;Adoption;analytical tool;Antibiotic Resistance;Antibiotic Therapy;antibiotic tolerance;Antibiotics;Antimicrobial Resistance;Automobile Driving;Bacteria;bactericide;Behavior;Biology;Candida;Cell Cycle;Cell model;Cell Survival;Cell Wall;Cells;Cessation of life;Complex;Coupled;curative treatments;Cytoplasm;Development;Drug Tolerance;Endothelial Cells;Environment;environmental adaptation;Equilibrium;Escherichia coli;Event;Face;flexibility;fungus;Future;Gene Expression Profile;Gene Expression Regulation;Genetic Transcription;Genomics;Goals;Gram-Positive Bacteria;Growth;Heterogeneity;Human;Immune;in vivo;individual response;Infection;innovation;insight;Leishmania;lens;Link;Lytic;Macrophage;Medical;Metabolic;Metabolism;methicillin resistant Staphylococcus aureus;Methodology;Methods;microbial;Modeling;Morbidity - disease rate;mortality;novel;Nutrient availability;Organism;Outcome;Parasites;pathogen;Pathogenesis;pathogenic bacteria;pathogenic microbe;Phagosomes;Pharmaceutical Preparations;Phenotype;Population;Postdoctoral Fellow;Proliferating;Regulation;Regulatory Pathway;Reporter;Research Personnel;resilience;Resolution;response;Role;Shapes;Signal Transduction;single-cell RNA sequencing;Site;Source;Staphylococcus aureus;Staphylococcus aureus infection;Stimulus;Stress;stress tolerance;stressor;Techniques;Technology;Testing;Time;Tissues;tool;Training;Transcript;Transcriptional Regulation;transcriptome;transcriptome sequencing;Vancomycin;Variant;Virulence;Virulence Factors;Work

PROJECT_TITLE: Developing a single cell resolution understanding of pathogenesis and antibiotic tolerance in Staphylococcus aureus

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Research Study Section[MID]


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

PHR: Our lab primarily focuses on central nervous system (CNS) cell signaling that leads to neuronal death in Parkinson's disease (PD) and Alzheimer's disease (AD) and demyelination in multiple sclerosis (MS). We will try to suppress neurotoxic signaling pathways and/or boost neuroprotective signaling pathways in different animal models of neurodegenerative diseases by nontoxic drugs in order to achieve neuroprotection and functional recovery. 1

PI_NAMEs: PAHAN, KALIPADA  (contact)

PROJECT_TERMS: Address;agent orange;Alzheimer's Disease;Alzheimer's disease pathology;Animal Model;Aspirin;Astrocytes;Attenuated;Autoimmune;Binding;Biogenesis;Brain;brain cell;Brain region;career;Cell Death;Cells;Cellular Metabolic Process;Central Nervous System;Cessation of life;Chemicals;Cholesterol;Clinical Trials;CNS autoimmune disease;CNS Demyelinating Autoimmune Diseases;combat;Dementia;Demyelinations;Disease;Exhibits;Exposure to;Fatty acid glycerol esters;Gender;Gliosis;Health;Hippocampus;Human;Hydroxymethylglutaryl-CoA Reductase Inhibitors;improved;Incidence;Induction of Apoptosis;Inflammation;Inflammatory;Integrins;Interferon Type II;Interleukin-12;Investments;Knowledge acquisition;Lesion;Ligands;Link;Lovastatin;Magnetic Resonance Imaging;Mediating;Memory;Microglia;monomer;Multiple Sclerosis;Mus;Myelin;Nature;Nerve Degeneration;nerve stem cell;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurology;neuron apoptosis;neuron loss;Neurons;neuroprotection;neurotoxic;Neurotoxins;neurotrophic factor;Nitric Oxide;Oligodendroglia;Parkinson Disease;Pathway interactions;Pharmaceutical Preparations;Poison;PPAR alpha;Process;Production;prostate cancer cell;Proteolysis;Recovery of Function;Regulation;Regulatory T-Lymphocyte;Research;Risk;Safety;Scientist;Services;Signal Pathway;Signal Transduction;T-Lymphocyte;Therapeutic;Therapeutic Agents;Time;TLR2 gene;Veterans;Vietnamese;War

PROJECT_TITLE: BLR&D Research Career Scientist Application


PHR: Age-related macular degeneration (AMD) is an age-related disease with genetic and environmental risk factors that is significantly affected by smoking. AMD has two outcomes, wet AMD or dry AMD; and while there are treatments for the former, none are available for the latter. Developing novel treatment strategies, is therefore essential to reduce the incidence and progression of AMD and improve quality of life for veterans with AMD. The goal of our research is to study mechanisms underlying AMD in cell- and animal- based experiments and develop novel diagnostic and treatment strategies to reduce the damage produced by the disease or help repair the tissues affected. Our long-term goal is to translate our treatment strategies from animal models to our veterans, which makes this research highly relevant to the VA mission.

PI_NAMEs: ROHRER, BAERBEL  (contact)

PROJECT_TERMS: Affect;Age;age related;Age related macular degeneration;age-related disease;Alternative Complement Pathway;American;Animal Model;Animals;Applications Grants;Award;Barbus;Blindness;Book Chapters;Bruch's basal membrane structure;Bystander Effect;career;Caring;Cell Therapy;Cells;Choroid;Choroidal Neovascularization;cilium biogenesis;Clinical;clinical application;Clinical Trials;Collaborations;Committee Members;Communication;Communication impairment;Complement;Complement 3d Receptors;Complement Activation;Complement Factor D;Complement Factor H;Data;design;diagnostic strategy;Disease;Disease Progression;early phase clinical trial;Early treatment;Educational process of instructing;effective therapy;efficacy testing;Electrophysiology (science);Employee;Environmental Risk Factor;experience;experimental study;Eye;Faculty;Funding;Future;gene therapy;Generations;Genetic Polymorphism;genetic risk factor;Genetic study;geographic atrophy;Goals;graduate school;Grant;Hematopoietic stem cells;high resolution imaging;Histologic;improved;in vivo imaging;Incidence;indexing;induced pluripotent stem cell;Inflammation;inhibitor;innovation;Intervention;Joints;K-Series Research Career Programs;Knock-in Mouse;Laboratories;Liquid substance;Location;Macular degeneration;Manuscripts;Medical;Medical center;Medical Students;member;Mentors;Mission;Modeling;Molecular;Molecular Abnormality;mouse model;Multiple Sclerosis;Mus;Mutation;Nonexudative age-related macular degeneration;nonhuman primate;novel;novel diagnostics;Ocular Pathology;Ophthalmologist;Ophthalmology;Outcome;Participant;Pathology;Pathway interactions;Patients;Penetration;Pharmaceutical Preparations;Phase II/III Trial;Photoreceptors;Population;Postdoctoral Fellow;Prevalence;Productivity;professor;Publications;Publishing;Quality of life;Recovery;recruit;Rehabilitation therapy;Research;Research Assistant;Research Personnel;Retina;Retinal Degeneration;Retinal Diseases;Risk;Risk Factors;Role;Rotation;Science;Scientist;Sensory impairment;sensory system;Services;Side;Site;Smoke;Smoking;South Carolina;Students;symposium;System;Technology;Therapeutic;Time;tissue repair;Tissues;Translating;Traumatic Brain Injury;treatment strategy;United States National Institutes of Health;Universities;vector;Veterans;Vision;Vision research;Visit;wasting;Work;wound healing;Writing

PROJECT_TITLE: BLR&D Research Career Scientist Award for Dr. Barbel Rohrer


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: The loss of muscle mass and function associated with obesity is known as “sarcopenic obesity”. This condition is very common in the elderly and is over-represented in the veteran population, reducing functionality and quality of life, and increasing mortality. We have generated exciting preliminary data suggesting that the hormone ghrelin and its receptor GHSR-1a may play a role in the development of “sarcopenic obesity”. This proposal will determine their effects and mechanisms of action in this setting. The results generated by these studies are expected to help us develop new treatments for this condition; thereby improving quality of life by allowing veterans to stay home longer, decreasing the need for hospitalizations and reducing the cost of healthcare.

PI_NAMEs: GARCIA, JOSE M. (contact)

PROJECT_TERMS: Adipocytes;Adipose tissue;Adult;Age;age group;age related;Aging;Agonist;antagonist;Appetite Stimulants;Area;Attenuated;Biogenesis;Body Composition;Brown Fat;C57BL/6 Mouse;Cardiovascular Diseases;Chronic;Clinical;clinical development;Data;Deposition;Development;Diabetes Mellitus;disability;disability risk;Eating;effective therapy;Elderly;Energy Metabolism;Epidemic;fall risk;Fatigue;Fatty acid glycerol esters;fatty acid metabolism;fatty acid oxidation;feeding;Fiber;frailty;Functional disorder;General Population;ghrelin;GHS-R1a;Goals;hallmarks of aging;Hand Strength;Health Care Costs;High Prevalence;high risk;Home;Hormones;Hospitalization;human old age (65+);improved;in vivo;Individual;Injury;Kinetics;Knockout Mice;Knowledge;Lead;Length of Stay;Ligands;lipid biosynthesis;lipid metabolism;Lipids;Lipolysis;Mediating;Mediator;middle age;military veteran;mimetics;Mitochondria;mitochondrial dysfunction;Molecular;molecular marker;Morbidity - disease rate;mortality;Motor Activity;Muscle;Muscle Fibers;muscle form;Muscle function;muscle strength;Muscular Atrophy;novel;novel therapeutics;Obesity;obesity prevention;old mice;older adult;Older Population;Outcome;Pathway interactions;Performance;pharmacologic;Physical Performance;Population;prevent;Quality of life;Reactive Oxygen Species;receptor;Relaxation;Resistance;Rodent Model;Role;sarcopenia;sarcopenic obesity;Skeletal Muscle;Stains;targeted treatment;Testing;Therapeutic;therapy development;Thermogenesis;Transgenic Mice;Triglycerides;Veterans;Weight;Work

PROJECT_TITLE: The Role of Ghrelin and the GHSR-1a receptor in Sarcopenic Obesity


ORG_CITY: NORTH LITTLE ROCK

ORG_NAME: CENTRAL ARKANSAS VETERANS HLTHCARE SYS

ORG_STATE: AR

PHR: This research is highly relevant to the healthcare of veterans, who comprise an aging population with elevated incidence of traumatic brain injury (TBI). Both age and TBI increase the risk of AD, PD, and other neurodegenerative diseases. By seeking basic principles that govern protein aggregation across many neuropathies, we hope to gain insights and develop novel interventions (e.g., drugs) that apply to diverse neurological pathologies including “orphan diseases” that are too rare or underfunded to attract substantial research effort aimed at their prevention or cure.

PI_NAMEs: SHMOOKLER REIS, ROBERT JOSEPH (contact)

PROJECT_TERMS: Address;Adhesions;Affinity;Age;Age Distribution;age related;Age Years;age-related disease;Aging;aging population;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Amyloidosis;analog;Award;Binding;Binding Proteins;Bioinformatics;Brain;Cachexia;Caenorhabditis elegans;career;Cell Aging;Cell Culture Techniques;Cell model;Cells;Chemistry;Chinese population;Chronic;cohesion;crosslink;cytotoxicity;Data;design;Disease;disorder risk;Drug Screening;Drug Targeting;Environmental Risk Factor;Etiology;Exposure to;extracellular;Family;gene network;Generations;Genes;Genetic;Genetic Variation;Healthcare;Healthcare Systems;Heart Diseases;high risk;Hippocampus;homologous recombination;Human;Huntington Disease;hyperphosphorylated tau;Hypertension;improved;in silico;in vivo;in vivo evaluation;Incidence;inhibitor;insight;Intervention;Laboratories;Legal patent;Libraries;Link;link protein;Location;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Mammalian Genetics;Mediating;military veteran;Modeling;Molecular;Molecular Genetics;Multiple Myeloma;Mus;Muscular Atrophy;Nematoda;Nerve Degeneration;neural;Neurodegenerative Disorders;Neurofibrillary Tangles;neurological pathology;Neuropathy;novel;novel strategies;novel therapeutics;Oncogenic;Orthologous Gene;Oxidation-Reduction;Oxidative Stress;Paper;Parkinson Disease;Pathology;Peptides;Pharmaceutical Preparations;Phosphorylated Peptide;Play;Post-Translational Protein Processing;Postmenopausal Osteoporosis;potency testing;prevent;Prevention;Process;Progressive Disease;Property;protein aggregation;protein protein interaction;Proteins;Publishing;Rare Diseases;Reagent;Reporting;Research;Research Priority;Resistance;Risk Factors;Role;Scientist;screening;senescence;Senile Plaques;Signal Pathway;Specificity;Spinal Cord;Stress;Structure;Testing;Time;Traumatic Brain Injury;Universities;Veterans;Woman

PROJECT_TITLE: BLR&D Research Career Scientist Award


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Aging;Cancer;Cardiovascular;Radiation Oncology;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: PROJECT NARRATIVE Life-threatening vascular toxicities reduce long-term quality of life in cancer patients after treatment and although this phenomenon has long been observed in the clinic, the mechanisms that cause this to occur remain unclear. We propose to investigate the mechanisms behind vascular toxicities by modulating the apoptotic machinery in cells within the vasculature and identify the contributions of each vascular cell type in response to various chemotherapies and radiation therapy. Our studies will ultimately lead to improved therapeutic strategies that will reduce vascular toxicity and improve health outcomes in cancer patients.

PI_NAMEs: FLORIDO, MARY HEATHER CELINE  (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Acute;Adolescent;Adult;Affect;Aftercare;Age;age effect;Aging;animal old age;Antineoplastic Agents;Apoptosis;Apoptotic;ARHGEF5 gene;Atherosclerosis;Automobile Driving;BAX gene;Bax protein;BCL1 Oncogene;Biological Models;Birth;Blood capillaries;Blood Vessels;cancer cell;Cancer Patient;cancer therapy;carcinogenesis;Cell Death;cell injury;Cell Physiology;cell type;Cells;Cellular Morphology;Cellular Stress;chemotherapy;Chemotherapy and/or radiation;Cisplatin;Clinic;Clinical;curative treatments;Cytochrome P450;cytotoxic;Cytotoxic agent;Databases;Detection;Development;differentiation protocol;disease model;DNA;Doxorubicin;effective therapy;Elderly;Endothelial Cells;endothelial stem cell;experience;experimental study;Exposure to;External Beam Radiation Therapy;FDA approved;Future;Gene Expression;Gene Family;Genes;Health;Heart failure;high risk;human induced pluripotent stem cells;human model;Hypertension;Impairment;improved;In Vitro;in vivo;induced pluripotent stem cell;Induction of Apoptosis;innovation;International;Ionizing radiation;Irreversible Toxicity;Ischemia;juvenile animal;Knockout Mice;Knowledge;Laboratories;Life;life span;Link;Malignant Neoplasms;Measurement;Measures;Migration Assay;mimetics;Mitochondria;Molecular;Morphology;Mus;neonate;neoplastic cell;Normal tissue morphology;Outcome;Patients;Peripheral;Pharmaceutical Preparations;pharmacovigilance;Predisposition;prevent;Prevention;pro-apoptotic protein;Proliferating;Protein Family;Proteins;Quality of life;quality of life for cancer survivors;Radiation therapy;Regimen;Regulation;response;Role;screening;Signal Pathway;Smooth Muscle Myocytes;targeted agent;Testing;Therapeutic;therapy development;Thrombosis;Tissues;Toxic effect;transcriptomics;Tube;tumor;tumor xenograft;Tyrosine Kinase Inhibitor;Vascular Diseases;Vascular Endothelial Cell;Vascular Endothelium;Vascular Smooth Muscle;vascular stress;VDAC1 gene;Vegf Inhibitor;venous thromboembolism;Work

PROJECT_TITLE: Investigating the role of apoptosis regulation in cancer therapy-induced vascular toxicities


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: This proposal addresses a significant healthcare issue that affects Veterans, military personnel, and their families disproportionately to the general population. Here, work from Dr. Casey’s research program is focused on the investigation of alcoholic and non-alcoholic fatty liver disease (AFLD and NAFLD, respectively). Both AFLD and NAFLD represent a major clinical challenge in the VA, since there are no current, effective therapeutic interventions, and progression of liver injury can result in liver transplantation, or death. Work from our lab aims to provide a better understanding of AFLD and NAFLD progression and to increase opportunities for the development of novel treatment paradigms for the management of chronic liver diseases.

PI_NAMEs: CASEY, CAROL A. (contact)

PROJECT_TERMS: Address;Admission activity;Affect;Alcohol abuse;alcohol consequences;alcohol effect;alcohol exposure;Alcoholic Fatty Liver;Alcoholic Liver Diseases;Alcohols;American;Animal Model;Apoptotic;Area;Asialoglycoprotein Receptor;Autophagocytosis;Autophagosome;Award;Basic Science;Binding;Biochemical;Biology;Book Chapters;Carcinoembryonic Antigen;career;Cells;Cellular biology;Cessation of life;Chronic;chronic liver disease;Clinical;Collaborations;Country;Cytolysis;Data;Defect;Destinations;Development;Disease Progression;Endocytosis;Ethanol;Ethanol Metabolism;Exocytosis;Experimental Designs;experimental study;Family;fatty liver disease;Fibronectins;Functional disorder;General Population;Goals;Golgi Apparatus;Grant Review;Guanosine Triphosphate Phosphohydrolases;Healthcare;Heavy Drinking;Hepatic;Hepatocyte;Hepatotoxicity;Impairment;improved;In Vitro;in vivo;Incidence;Inflammatory Response;Injury;insight;Investigation;Journals;knowledge translation;Laboratories;Ligands;Link;Lipids;Liver;Liver Carbohydrate-Binding Protein;Liver diseases;liver injury;liver transplantation;Manuscripts;Mediating;Medical;Medical center;member;Membrane;Mentors;Military Personnel;military veteran;Mission;Monitor;Monomeric GTP-Binding Proteins;Morphology;National Institute on Alcohol Abuse and Alcoholism;non-alcoholic;non-alcoholic fatty liver disease;novel;Organelles;Pathogenesis;Pathway interactions;Patients;Peer Review;Physiological;Play;population health;problem drinker;Process;Productivity;Program Development;programs;Protein Secretion;protein transport;Proteins;Publishing;receptor;receptor mediated endocytosis;receptor recycling;Recycling;Research;Research Personnel;Role;Scientist;Seminal;Signal Transduction;Societies;special interest group;symposium;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;therapeutically effective;therapy development;Toxic effect;Toxin;trafficking;Training;trans-Golgi Network;undergraduate student;United States National Institutes of Health;uptake;Vesicle;Veterans;Work;World Health


ORG_CITY: TAMPA

ORG_NAME: JAMES A. HALEY VA MEDICAL CENTER

PHR: Over 200,000 veterans are diagnosed with dementia, of which, Alzheimer's disease (AD) is the major form. Veterans who have experienced traumatic brain injury (TBI) or post-traumatic stress disorder (PTSD) are at a higher risk of developing AD later in life, particularly those carrying the apolipoprotein E (APOE) ε4 allele. There is strong evidence that low dietary omega-3 docosahexaenoic acid (DHA) contributes to brain inflammation and amyloid burden in AD. Studies of veterans with TBI/PTSD show that those with the ε4 allele have an abnormal accumulation of a DHA form that is directly transported from blood to the brain. Individuals with an ε4 allele have deficiencies in transporting DHA to the brain. In this proposal, we will identify mechanisms of how the ε4 allele contributes to DHA transport deficiencies into the brain with the purpose of developing therapeutic strategies to enhance brain DHA levels in AD patients with the ε4 allele.

PI_NAMEs: ABDULLAH, LAILA  (contact);BACHMEIER, CORBIN

PROJECT_TERMS: Address;Affect;Afghanistan;Age;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapy;Amyloid;Amyloid beta-Protein;Animals;Antiinflammatory Effect;Apolipoprotein E;apolipoprotein E-4;Astrocytes;Biological Availability;Blood;Blood - brain barrier anatomy;blood-brain barrier function;Brain;brain endothelial cell;brain parenchyma;Cerebrovascular system;Chronic;Circulation;combat injury;cytokine;Data;Dementia;Development;Diagnosis;dietary;Disease;Docosahexaenoic Acids;Encephalitis;Environment;experience;Exposure to;Extracellular Matrix;Gelatinase B;General Population;Genes;genetic risk factor;Genotype;High Prevalence;high risk;high risk population;Human;Impaired cognition;Impairment;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Inhibition of Matrix Metalloproteinases Pathway;Integral Membrane Protein;Investigation;Iraq;Lecithin;Life;lipid transport;Lipids;Lysophosphatidylcholines;Mediating;Membrane;Microglia;military veteran;mouse model;Mus;Neurofibrillary Tangles;neuroinflammation;neurotransmission;Nuclear;Omega-3 Fatty Acids;Patients;Pattern;Pericytes;Peripheral;Peroxisome Proliferator-Activated Receptors;pharmacologic;Plasma;Play;Population;Post-Traumatic Stress Disorders;pre-clinical;prevent;Protein Isoforms;Proteins;repaired;Resistance;Risk;Role;Senile Plaques;Signal Pathway;Signal Transduction;Soldier;Therapeutic;Transgenic Mice;Traumatic Brain Injury;Up-Regulation;uptake;Veterans;War;Work;β-amyloid burden

PROJECT_TITLE: Influence of APOE genotypes on blood brain barrier transport of DHA by mfsd2a in Alzheimer's Disease


PHR: Pancreatic and breast cancer are common ailments in our veterans. These cancers are lethal and therefore, it is important to understand the detail underlying mechanisms of the disease to identify new drug targets. The pancreatic cancer is the most difficult to treat and the patient survive for few months, after detection. We have identified new targets and seen that inhibitors of a protein (i.e. MLK3/MLKs) can inhibit pancreatic cancer tumor growth in animal models. The other projects in the laboratory deals with breast cancer. With increasing numbers of female veterans, the incidence of breast cancer and developing resistance to current therapies are quite frequent. Our investigation shows that inhibitors of MLK3/MLKs can also be used to treat Triple Negative Breast Cancer, a deadly sub-type that lacks drug target. Similarly, we have observed that the activator of MLK3/MLKs can serve as a therapeutic for ER+ and HER2+ breast cancer, and can overcome therapy resistance. We are highly encouraged with our research and hope to take our discoveries to clinical trials in future.

PI_NAMEs: RANA, AJAY NMN (contact)

PROJECT_TERMS: African American Women;Aging;Animal Model;Animals;anti-cancer research;Area;Award;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Treatment;Cancer Cell Growth;Cancer cell line;career;Cell Death;Cell Death Induction;cell growth;Cell Proliferation;Cell Survival;Cells;Ceramides;chemotherapy;Clinical;Clinical Trials;Communication;Cyclic AMP-Dependent Protein Kinases;Cytotoxic agent;Data;Death Rate;Detection;Disease;Drug Targeting;Epidermal Growth Factor Receptor;Estrogen receptor positive;Estrogen Receptors;Estrogens;Extracellular Matrix;Failure;Family;Family member;Female;Funding;Future;Goals;Grant;Healthcare;Human;human tissue;Immunity;improved;Incidence;inhibitor;inhibitor therapy;interest;Investigation;Journals;kinase inhibitor;Laboratories;Life;Link;Lipids;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;MAP Kinase Modules;Mediating;Molecular;mortality;Mus;nanoparticle;Nature;neoplastic cell;new therapeutic target;novel;novel therapeutic intervention;Oncogenes;overexpression;pancreatic cancer cells;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;Paper;Parkinson Disease;Pathogenesis;Pathway interactions;Patients;Phosphotransferases;Physiological;Play;Protein Kinase;Proteins;Publishing;receptor;Regimen;Reporting;Research;Resistance;Resistance development;Role;Scientist;Seminal;Signal Transduction;Site;small molecule;standard of care;Structure;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapy resistant;Thick;Time;transcription factor;translational cancer research;Transplantation;Trastuzumab;triple-negative invasive breast carcinoma;tumor;Tumor Burden;tumor growth;uncontrolled cell growth;United States National Institutes of Health;Veterans;Vietnam;War;Woman


PHR: The number of veterans afflicted with MS is estimated at about 30,000; and some studies have suggested that the incidence of MS is higher in certain veteran populations than in civilian populations. Knowledge of specific genetic factors that are a risk for MS, as well as finding new treatments could help reduce minimize MS rate and symptom severity in patients. With increasing age, more and more veterans will develop AD, possibly at higher rates due to environmental factors or dietary factors, which will create new challenges for the VA healthcare systems. Our studies on the relationships between alcohol consumption and AD, or exposure to warfarins or superwarfarins and development of treatments to minimize their detrimental effects, could therefore help prevent the overall increase in AD rates.

PI_NAMEs: FEINSTEIN, DOUGLAS L. (contact)

PROJECT_TERMS: Affect;African American;African American population;Age;Aging;Agonist;Alcohol abuse;Alcohol consumption;alcohol effect;Alcohols;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Animal Model;Anticoagulants;Area;Award;Behavior;Blood specimen;Brain;Calcium;career;Caucasians;Cell Culture Techniques;Cells;Clinic;Clinical;Clinical Trials;Cognitive deficits;cohort;comorbidity;Craniocerebral Trauma;Deposition;design;Development;Developmental Therapeutics Program;Diagnosis;Dietary Factors;Disease;disorder risk;DNA;DNA sequencing;Down-Regulation;drug repurposing;drug testing;Economic Burden;Environmental Risk Factor;Ethanol;Experimental Autoimmune Encephalomyelitis;Exposure to;Family;FDA approved;Frequencies;Funding;Genes;Genetic;genetic risk factor;Goals;Grant;Healthcare Systems;Heavy Drinking;High Prevalence;Hispanic;Human;In Vitro;in vivo;Incidence;Inflammation;Inflammatory Response;interest;Intervention;Knowledge;LAMC2 gene;Lesion;locus ceruleus structure;Mediating;Metformin;Methods;Microglia;Military Personnel;military veteran;Modeling;mouse model;Multiple Sclerosis;multiple sclerosis patient;Myelin Sheath;Nervous System Trauma;Neurobiology;Neurodegenerative Disorders;Neuroglia;neuroinflammation;Neurologic;Neurons;neuropathology;neuroprotection;Neurosciences;Nitric Oxide Synthase;noradrenergic;Norepinephrine;novel;Nucleotides;Paper;Pathology;Patients;Phagocytosis;Pharmaceutical Preparations;phase I trial;Pilot Projects;pilot test;Pioglitazone;Population;Post-Traumatic Stress Disorders;prevent;Protein-Serine-Threonine Kinases;Proteins;Rattus;recruit;reduce symptoms;Relapsing-Remitting Multiple Sclerosis;remyelination;Research;Risk;Risk Factors;Risk Reduction;Rodent Model;Rodenticides;Role;Sampling;Scientist;Seminal;Senile Plaques;Services;Severities;Siblings;Signal Transduction;Single Nucleotide Polymorphism;social;Societies;STK11 gene;Supporting Cell;Symptoms;Syndrome;System;T-Lymphocyte;Testing;therapy development;Time;Toxic effect;transcriptome;Variant;Veterans;Warfarin;Woman;Work;β-amyloid burden


ORG_CITY: NASHVILLE

ORG_STATE: TN

PHR: Esophageal Squamous Cell Cancer (ESCC) accounts for approximately 90% of the incident 456,000 esophageal cancers worldwide. Data from the VA Central Cancer Registry (VACCR) between 1995-2005 revealed 3,493 new cases of ESCC (44% of all esophageal cancers). Patients often present with advanced disease, as 60-91% of patients presented with at least Stage II disease, and 26% present with metastatic disease. Current therapies include a combination of chemotherapy, radiation, and surgical intervention, which are not specific and in many cases not effective. Median survival time after diagnosis is 14.2-15.3 months. As such, new, more specific therapies are necessary. The advent of immune checkpoint inhibitors to reactivate antitumor immunosurvelliance and clearance represents a new treatment avenue for difficult to manage cancers. Our overarching hypothesis is that eosinophils could be cellular targets for immunotherapy in difficult to manage patients with ESCC.

PI_NAMEs: CHOKSI, YASH  (contact)

PROJECT_TERMS: 3-Dimensional;Adoptive Cell Transfers;advanced disease;Aftercare;Alcohol consumption;antioxidant enzyme;Apoptosis;Area;Biology;Blood Vessels;Bone Marrow;Carcinoma;CCL11 gene;Cells;Cellular Structures;cellular targeting;Chemotactic Factors;clinically relevant;Coculture Techniques;Combination Drug Therapy;cytokine;cytotoxic;Data;Deglutition;Diagnosis;Disease;Dysplasia;Electrons;eosinophil;eosinophil peroxidase;Eosinophilic Infiltrate;Eotaxin;Epithelial Cells;Epithelium;Equilibrium;Esophageal carcinoma;Esophageal Intraepithelial Neoplasia;Esophageal Neoplasms;esophageal squamous cell cancer;Esophageal Squamous Cell Carcinoma;Esophagectomy;Esophagus;glutathione peroxidase;health related quality of life;High Prevalence;Homeostasis;Human;human disease;Hydrogen Peroxide;IL8 gene;Immune;Immune checkpoint inhibitor;Immunotherapy;improved;Infiltration;Inflammatory Response;insight;Interleukin-10;Interleukin-2;Interleukin-5;Invaded;Light;Lipids;Malignant Epithelial Cell;Malignant neoplasm of esophagus;Malignant Neoplasms;Mediating;Metastatic Neoplasm to Lymph Nodes;Methods;Modeling;Modification;mouse model;Mus;neoplasm registry;neoplastic cell;Operative Surgical Procedures;Organoids;Oxidants;oxidation;Oxidative Stress;Oxides;Pathway interactions;Patients;Peroxidases;Play;Population;Production;Radiation;Reactive Oxygen Species;recruit;Reduced Glutathione;Regulation;Role;Signal Transduction;smoking prevalence;Squamous cell carcinoma;Stage at Diagnosis;Testing;Therapeutic Intervention;Thiocyanates;Time;Tissues;TNF gene;tumor;Tumor Biology;Tumor Immunity;tumor initiation;tumor microenvironment;tumor progression;tumorigenesis;tumorigenic;Water

PROJECT_TITLE: The role of eosinophils and oxidative stress in esophageal malignancy


ORG_CITY: ANN ARBOR

ORG_STATE: MI

PHR: Infections with methicillin-resistant S. aureus or MRSA constitute a public health imperative. These studies will focus on the development of a uniquely efficacious nanoparticle vaccine against critical virulence factors that will be efficacious in preventing MRSA in the Veteran population, in members of the armed services, and in the public-at-large.

PI_NAMEs: OSCHERWITZ, JON  (contact)

PROJECT_TERMS: Adjuvant;Aerosols;alpha Toxin;Amino Acids;Antibodies;Antigens;Bacillus anthracis;Bacteria;Bacterial Endocarditis;Biological Assay;Chickenpox;Clinical Trials;Communicable Diseases;Communities;cross reactivity;Cytolysins;cytotoxicity;Cytotoxin;Data;design;Development;Disease;economic impact;efficacy evaluation;Enabling Factors;Epitopes;Evaluation;Gram-Positive Bacteria;Growth;Hemolysin;Hepatitis;HIV-1;Hospitals;Host Defense;Human;human disease;Humoral Immunities;Immune Sera;Immunity;Immunization;immunogenic;In Vitro;Infection;Infectious Skin Diseases;leukotoxin;lung injury;Malaria;Mediating;Medical;member;Methicillin Resistance;methicillin resistant Staphylococcus aureus;military veteran;Modeling;Molecular;Monoclonal Antibodies;Morbidity - disease rate;mortality;mouse model;Mus;nanoparticle;neutralizing antibody;Oryctolagus cuniculus;Panton-Valentine leukocidin;pathogen;Performance;Pertussis;Phase;Pneumonia;Poliomyelitis;prevent;Production;protective efficacy;prototype;Public Health;Reproduction spores;resistant strain;response;Sepsis;Services;Skin injury;Specificity;Staphylococcal Vaccines;Staphylococcus aureus;Staphylococcus aureus infection;success;Superantigens;tissue injury;Toxin;United States;Vaccination;vaccine failure;vaccine trial;Vaccines;Validation;Vancomycin;Virulence;Virulence Factors;Virulent;Virus-like particle;Vulnerable Populations;Work

PROJECT_TITLE: A multivalent vaccine for Staphylococcus aureus