ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

PHR: PROJECT NARRATIVE Acute lung injury (ALI) is a frequent and often lethal secondary organ complication of acute kidney injury (AKI) that has no therapies. The combination of AKI with ALI carries a 60-80% mortality risk with no specific therapies. The proposed research is relevant to the mission of the VA as it may lead to the development of novel therapeutic options for secondary organ complications of AKI, in particular ALI. The expected outcomes of our studies are thus relevant to the mission of the VA to reduce morbidity and mortality in kidney patients and could significantly impact suffering and health care expenditure.

PI_NAMEs: HERRLICH, ANDREAS  (contact)

PROJECT_TERMS: Acute Lung Injury;Acute myocardial infarction;Acute Renal Failure with Renal Papillary Necrosis;Alveolar Macrophages;Bilateral;Bone Marrow;Brain;CCL2 gene;Cell surface;cell type;Cells;Circulation;Complication;Creatinine;cytokine;Cytometry;Data;Development;Gene Expression Profile;Genetic;Goals;Health Expenditures;Heart;Heterogeneity;Human;Immune;Immune response;in vivo;Inflammation;Inflammatory;injured;Injury;Injury to Kidney;innovation;Interleukin-6;interstitial;Kidney;kidney cell;Knock-out;knockout gene;Knockout Mice;Lung;lung injury;Macrophage;Maps;Measurement;Mediating;Mediator;Membrane;Metalloproteases;Mission;Molecular;monocyte;Morbidity - disease rate;mortality;mortality risk;Mus;Necrosis;Nephrectomy;neutrophil;novel;novel strategies;novel therapeutics;Organ;Outcome;Patients;Phenotype;Proliferating;promote resilience;Publishing;rat KIM-1 protein;Recovery;recruit;Reporting;Research;Respiratory Acidosis;response;response to injury;Role;Secondary to;Sepsis;Serum;Signal Transduction;single-cell RNA sequencing;Site;Source;Stains;Stroke;systemic intervention;T-Lymphocyte;targeted treatment;Testing;therapy development;Time;time use;tissue injury;Tissues;TNF gene;TNFRSF1A gene;translational impact;Tubular formation;tumor;Tumor Cell Necrosis;Up-Regulation;Urine;Work

PROJECT_TITLE: Remote injury responses after AKI


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: CHICAGO

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: PROJECT NARRATIVE To date, there is no proven effective cure for alcoholic liver disease. The work proposed in this application will dissect the pathogenic role of a protein complex of liver origin as a central upstream regulator of a proinflammatory program that besides being detrimental to the liver, drives intestinal injury; hence, creating an amplifying feedback loop in alcoholic liver disease. The results from this project will benefit the design of new therapies for preventing or treating this devastating disease that affects many US Veterans and is currently on the rise.

PI_NAMEs: NIETO, NATALIA  (contact)

PROJECT_TERMS: Ablation;Acute Alcoholic Hepatitis;Affect;Affinity;Alcoholic Liver Diseases;Antibodies;Binding;Biological Assay;Biological Markers;CCL2 gene;Clinical;Clinical Trials;Complex;CX3CL1 gene;cytokine;Data;design;Disease;Epithelial Cells;Ethanol;Feedback;feeding;Functional disorder;Goals;Hepatic;Hepatocyte;HMGB1 gene;in vitro testing;in vivo;Infiltration;Inflammation;Inflammatory;Injury;Interleukin-1 beta;intestinal barrier;intestinal epithelium;intestinal injury;Intestinal permeability;Kupffer Cells;Ligands;Liver;liver injury;Macrophage;Measures;Molecular;Mus;Myeloid Cells;novel;novel therapeutics;oxidation;Pathogenesis;Pathogenicity;Pathologic;Patients;Pattern;Phosphoproteins;Prediction of Response to Therapy;prevent;problem drinker;Production;programs;progression risk;protein complex;protein expression;receptor;receptor binding;receptor for advanced glycation endproducts;response;Role;Sampling;Serum;Signal Transduction;Source;Sterility;Testing;Therapeutic;Tight Junctions;TNF gene;Treatment outcome;Veterans;Work

PROJECT_TITLE: Pathogenic role of a protein complex of liver origin as regulator of a proinflammatory program that drives hepatic and intestinal injury in alcoholic liver disease


ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

ORG_STATE: IA

PHR: The outcomes of septic patients in the VA are known to vary depending on facility and region of treatment. Typically, the care of septic patients at high risk of death is provided in the ICU. While there are known treatment modalities that improve the outcomes of sepsis patients, it is unclear what these modalities are and if these modalities are used in the VA consistently. This proposal will use advanced datasets, previously not available, and qualitative measures to examine the care delivered in septic patients in the VA. In this proposal, we describe using data from the TeleICU and other VA sources to develop a better understanding of the care delivered in VA ICUs to look for variation in practice and modalities that are associated with improved outcomes in sepsis.

PI_NAMEs: BLUM, JAMES MARLOW (contact);REISINGER, HEATHER SCHACHT

PROJECT_TERMS: Acute Physiology and Chronic Health Evaluation;Acute Respiratory Distress Syndrome;Address;Administrator;Admission activity;Affect;Antibiotic Therapy;Antibiotics;Area;Beds;care costs;Care given by nurses;Caring;Characteristics;Clinical;Clinical Data;clinical decision support;Computerized Medical Record;Coronary;Critical Care;Data;Data Analyses;Data Collection;Data Set;Data Sources;data warehouse;Death Rate;design;Diagnosis;Drops;Early Intervention;effective therapy;efficacy evaluation;Elements;Ethnography;Evaluation;Event;Geography;health care service;Healthcare;Healthcare Systems;hemodynamics;high risk;Hospital Mortality;Hospitals;Hypotension;improved;improved outcome;Incidence;Infection;Informatics;Information Systems;innovation;Inpatients;insight;Intensive Care;Intervention;Investigation;Learning;Liquid substance;Lung;Managed Care;Measures;Mechanical ventilation;Methodology;Methods;Modality;Modeling;Monitor;mortality;mortality risk;multidisciplinary;novel;Nurses;Outcome;patient population;Patients;Physicians;Physiological;Physiology;Population;Positioning Attribute;primary outcome;Private Sector;Process;Process Measure;programs;Prophylactic treatment;Protocols documentation;Provider;Reporting;response;Risk Adjustment;Risk Factors;Safety;Sepsis;septic patients;Site;Source;Specificity;Standardization;Statistical Models;survival prediction;System;Telemedicine;Testing;therapy resistant;Time;United States;Update;Variant;Vasoconstrictor Agents;ventilation;Ventilator;Veterans;virtual healthcare;Work

PROJECT_TITLE: Building a Learning Healthcare System to Understand and Improve Sepsis Outcomes in the VA TeleICU Network

STUDY_SECTION_NAME: HSR-5 Health Care System Organization and Delivery and Women's Health[HSR5]


ORG_CITY: LONG BEACH

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: CA

PHR: PROJECT NARRATIVE  Vitamin B1 is indispensable for normal human health due to the essential roles it plays in oxidative energy metabolism, ATP generation, reduction of oxidative stress, and mitochondrial function. Humans cannot synthesize vitamin B1, and thus, must obtain it from exogenous sources ( i. e, diet and the gut microbiota) via absorption along the intestinal tract. Deficiency of vitamin B1 occurs in conditions like inflammatory bowel diseases, sepsis and chronic alcoholism, which affect significant number of our Veterans and the general population. It is therefore of physiological, nutritional and pathophysiological importance to understand how the different forms of vitamin B1 are absorbed in the gut and how conditions/factors that the intestine is exposed to under certain disease states affect these absorptive processes. This is our objective in this proposal. Results should provide novel information regarding vitamin B1 absorption in health and disease, which should assist in the designing of effective strategies to optimize its homeostasis/nutrition, and thus, improve human health.

PI_NAMEs: SAID, HAMID M (contact)

PROJECT_TERMS: absorption;Affect;Affinity;Alcoholism;Apical;apical membrane;C-terminal;Cell Physiology;Cells;Cellular biology;Chronic;Colon;cytokine;Cytoplasm;Cytoplasmic Tail;design;Diet;dietary;Diphosphates;Diphosphotransferases;Disease;Energy Metabolism;Enzymes;Epithelial Cells;Epithelium;Exposure to;Flagellin;Functional disorder;gastrointestinal system;General Population;Generations;Genes;Genomics;gut microbiota;Gut Mucosa;Health;Homeostasis;Human;Hypoxia;Impairment;improved;Inflammatory;Inflammatory Bowel Diseases;Intestinal Absorption;intestinal epithelium;Intestines;Investigation;Knockout Mice;Laboratories;Large Intestine;Lipopolysaccharides;Mammals;Mediating;microbiota;Mitochondria;Molecular;mouse model;Normal Cell;novel;nutrition;Nutritional;Organ;Oxidative Stress;Phenotype;Phosphorylation;Physiological;Physiology;Play;Process;Production;Proteins;Regulation;Research;Role;Sepsis;Small Intestines;Source;Susceptibility Gene;System;Testing;Thiamine;Transport Process;Ulcerative Colitis;uptake;Veterans;Vitamin Deficiency;Vitamins;Water-Soluble Vitamin

PROJECT_TITLE: Effect of Pathophysiological Conditions on Intestinal Absorption of Free Thiamin


ORG_CITY: MINNEAPOLIS

ORG_NAME: MINNEAPOLIS VA  MEDICAL CENTER

ORG_STATE: MN

PHR: Obesity and its associated comorbidities reduces healthspan and quality of life, including that of Veterans. Easy access to obesogenic diets drives weight gain, metabolic disorders and sleep disturbances. Orexin is a brain compound that increases calorie burning while stabilizing sleep/wake states, and it prevents weight gain during overfeeding in rodents. We would like to develop orexin-based anti-obesity therapies for humans, but orexin itself does not cross the blood-brain barrier, which is needed to achieve the anti-obesity affects. To this end, we have developed two novel compounds (orexin agonists) that mimic the effects of orexin, but which can cross the blood-brain barrier, making them promising candidates for use in human obesity. In this application we will test these two novel small molecular weight orexin agonists in mice, to determine their effectiveness as anti-obesity agents and in improving sleep/wake patterns. The overall goal is to provide preclinical data on these agents for use in future studies, to help address obesity in the Veteran population.

PI_NAMEs: KOTZ, CATHERINE M (contact)

PROJECT_TERMS: Address;Adult;Affect;Affinity;Age;Agonist;Anti-Obesity Agents;Automobile Driving;Behavior;Behavioral;Biological Availability;blood-brain barrier crossing;blood-brain barrier permeabilization;Body Weight;Body Weight decreased;Brain;Calories;Caring;Chronic Disease;Cognition;comorbidity;Data;Desire for food;Development;Diet;diet-induced obesity;Eating;effective therapy;Effectiveness;efficacy testing;Energy Metabolism;Environment;Evaluation;Exercise;exercise program;Expenditure;Exposure to;feeding;Feeding behaviors;Future;General Population;Goals;good diet;Health;Health Care Costs;Healthcare Systems;healthspan;High Fat Diet;Home;Homeostasis;Human;hypocretin;Hypothalamic structure;improved;improvement on sleep;in vivo;Indirect Calorimetry;Individual;interest;Lateral;Measures;Medical;Metabolic;Metabolic Diseases;Methods;military veteran;Modeling;Moderate Exercise;Molecular Weight;Morbidity - disease rate;Movement;Mus;Narcolepsy;Neurodegenerative Disorders;Neurons;Neuropeptides;novel;Obese Mice;obese person;Obesity;obesity development;obesity prevention;obesity treatment;obesogenic;orexin A;Outcome;Overweight;Pattern;Peptide Hydrolases;Peptides;Peripheral;Pharmaceutical Preparations;Pharmacotherapy;Physical activity;Physical Exercise;Physiological;Population;pre-clinical;Predisposition;prevent;Prevention;Property;Quality of life;receptor;Receptor Activation;reduced food intake;Research;research and development;Rodent;scale up;side effect;Sleep;Sleep Disorders;Sleep disturbances;Sleep Wake Cycle;small molecule;Structure;Subconscious;success;System;Testing;Therapeutic;therapeutic target;Thermogenesis;tool;total energy expenditure;Treatment outcome;Vertebral column;Veterans;Veterans Health Administration;Weight Gain;weight maintenance;wireless

PROJECT_TITLE: Orexin agonists as novel obesity therapeutics


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: Plasmodium vivax (Pv) malaria is the most widespread malaria infection, with an estimated 2.85 billion at risk and >10 million clinical cases annually. Of the approximately 170,000 active duty soldiers deployed overseas today, at least 10% are in countries endemic for Pv, and malaria is the second most common chronic infectious disease of active personnel. Pv is a concern for veterans because following initial exposure and illness, the parasite develops latent stages in the liver, and relapse can occur up to 5 years after leaving endemic areas. The Military Infectious Disease Research Program has prioritized the development of a Pv vaccine. Results of this research will enable progress toward a multi-component vaccine and novel therapeutics against Pv, thus aiding attempts at elimination, and will also advance the potential of antibody therapies for severely ill individuals and those in need of sustained prophylaxis during seasonal transmission and tours of duty.

PI_NAMEs: KING, CHRISTOPHER L (contact)

PROJECT_TERMS: acquired immunity;active duty;Affinity Chromatography;Animals;Antibodies;Antibody Therapy;Antigen Receptors;Antigens;Aotus primate;Area;asexual;Australia;B-Lymphocytes;Beds;Binding;Binding Proteins;Blocking Antibodies;Blood;Cambodia;chemokine receptor;Chronic;Chronic Disease;Clinical;clinical risk;Collaborations;Communicable Diseases;Country;Crystallization;Culicidae;Data;Development;Disease;Drug resistance;Epitopes;Erythrocytes;Erythroid Cells;experience;experimental study;Exposure to;Generations;Geographic Locations;Geography;global health;Goals;Health Policy;Human;human monoclonal antibodies;Human Resources;Immune response;Immunity;Immunoglobulin G;In Vitro;in vivo;Individual;Infection;Infectious Diseases Research;inhibiting antibody;Invaded;Life Cycle Stages;Ligands;Liver;Malaria;malaria infection;Mediating;Medical center;Military Personnel;Modeling;Monitor;Monkeys;Monoclonal Antibodies;Morbidity - disease rate;mortality;mosquito-borne;nanobodies;Nature;nonhuman primate;novel;novel therapeutics;Outcome;Parasitemia;Parasites;Peru;Phase;Plasmodium falciparum;Plasmodium vivax;Plasmodium vivax vaccine;Population;Primates;Production;programs;Prophylactic treatment;Protein Sortings;Proteins;Public Health;receptor;Recombinant Proteins;Relapse;Research;Residual state;Reticulocytes;Risk;Risk Reduction;Scientist;Seasons;Serum;Soldier;Sporozoites;standard measure;Syndrome;Testing;TFRC gene;Transcend;transmission process;United States Department of Veterans Affairs;Universities;vaccine candidate;vaccine development;vaccine strategy;Vaccines;Veterans;Vivax Malaria

PROJECT_TITLE: Defining targets of protective immunity in Plasmodium vivax using human monoclonal antibodies


ORG_CITY: Decatur

ORG_STATE: GA

PHR: Diabetes (DM) complications are the major cause of DM morbidity, mortality, and costs. As current care does not take advantage of progress in genetics, we will incorporate genetics. Since Veterans thought to have type 2 DM may also have genes for type 1 DM, we will assess the contributions of these genetic loads to the patterns of disease. To account for a wide range of risk, we will assess the combined contributions of genetic and nongenetic risk factors to the DM complications of eye and kidney disease, hypoglycemia, and heart failure, including development and testing of predictive models. Since changes to our DNA can alter what our genes do, we will identify “epigenomic” markers and molecular systems underlying DM complications. Our study of the genetics of diagnosis, gene-environment interactions, epigenomics, and predictive models should both aid translation – to identify risk in individuals, and help personalize treatment to reduce DM complications and hypoglycemia – and support discovery of new therapies to mitigate the underlying processes.

PI_NAMEs: PHILLIPS, LAWRENCE S (contact);SUN, YAN

PROJECT_TERMS: Adolescent;Adult;Age;Blood Pressure;Body mass index;Caring;Characteristics;Clinical;clinical risk;clinical translation;comorbidity;Complications of Diabetes Mellitus;Consensus;cost;Data;demographics;Development;Diabetes Mellitus;diabetic;Diabetic Ketoacidosis;Diagnosis;Disease;DNA;EFRAC;Emergency Situation;Epigenetic Process;epigenome-wide association studies;epigenomics;Ethnic Origin;Exclusion;Eye diseases;gene environment interaction;Gene Expression;Genes;Genetic;genetic disorder diagnosis;Genetic Load;Genetic Risk;Genetic study;genetic variant;Genome;genome wide association study;genome-wide;genomic locus;Glycosylated hemoglobin A;Goals;Health;Heart failure;Hypoglycemia;improved;Individual;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Kidney Diseases;Libraries;Life Style;Literature;macrovascular disease;Mediating;Mediation;Mendelian randomization;Methods;Methylation;military service;Modeling;Modification;Molecular;Morbidity - disease rate;mortality;multi-ethnic;multiple omics;Mutation;Natural History;non-genetic;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutics;Outcome;Outpatients;Participant;Pathway interactions;Pattern;personalized care;personalized medicine;Persons;phenomics;Phenotype;Physiological;polygenic risk score;precision medicine;predictive modeling;preservation;Process;Prognosis;programs;Proteinuria;Race;Reporting;Retinal Diseases;Risk;Risk Factors;Site;statistics;System;Testing;Time;trait;Translations;Veterans;Visit

PROJECT_TITLE: Diabetic Complications and Genetic Variants in the Million Veterans Program


FUNDING_MECHANISM: OTHERS

PHR: PROJECT NARRATIVE Sudden cardiac arrest is highly prevalent in the United States, affecting over 380,000 Americans every year and occurring in 4 out of every 1000 Veterans Administration hospitalizations. The mortality for sudden cardiac arrest exceeds 70%. Despite the high prevalence and mortality, there are no pharmacologic therapies that have been shown to improve survival outcomes in these patients. This project aims to better understand the molecular mechanisms of sudden cardiac arrest by evaluating mitochondrial DNA changes and related cardiac inflammation in mouse and cellular models, which may lead to novel targets to improve outcomes following sudden cardiac arrest.

PI_NAMEs: RUTLEDGE, CODY ANDREW (contact)

PROJECT_TERMS: Admission activity;Adult;Affect;American;Anti-Inflammatory Agents;Bacterial DNA;Cardiac;Cardiac Myocytes;Cardiac Volume;Cardiogenic Shock;Cardiovascular Diseases;career;career development;Cell Death;Cell model;Cells;Characteristics;Chemicals;circulating DNA;Clinical;Clinical Research;clinically relevant;Cyclic GMP;cytokine;Cytokine Signaling;Cytoplasm;Data;Development;disease model;experimental study;extracellular;factor A;Flow Cytometry;Functional disorder;Future;Gene Proteins;Genes;genetic manipulation;Goals;Grant;Heart;Heart Arrest;Heart Diseases;heart function;High Prevalence;Hospital Administration;Hospitalization;Hospitals;Human;Hypoxia;immune activation;Immune response;Immune signaling;improved;improved outcome;In Vitro;in vivo Model;Induced Heart Arrest;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Injury;Innate Immune Response;Innate Immune System;Intensive Care;Ischemia;Knock-out;Knockout Mice;LoxP-flanked allele;Mediating;Mentorship;Microscopy;military veteran;Mitochondria;Mitochondrial DNA;Molecular;mortality;mouse model;mtTF1 transcription factor;Multiple Organ Failure;Mus;Myocardial dysfunction;Myocarditis;Myocardium;novel;Nuclear;Operative Surgical Procedures;Organ;Outcome;overexpression;Pathologic;Patients;Pattern;Peripheral;Permeability;Pharmaceutical Preparations;pharmacologic;Physicians;preservation;prevent;Recovery;Reperfusion Injury;Research;research and development;response;Resuscitation;Role;Scientist;Septic Shock;Serum;Signal Pathway;Signal Transduction;Stimulator of Interferon Genes;Structure;sudden cardiac death;survival outcome;Survivors;Syndrome;System;Testing;Therapeutic Intervention;therapeutic target;Time;Tissues;Training;transcription factor;transcriptome sequencing;Transgenic Mice;Translational trial;United States;United States Department of Veterans Affairs;Universities;Veterans;Visualization;Work

PROJECT_TITLE: The Role of Mitochondrial DNA in Innate Immune Activation after Sudden CardiacArrest


ORG_CITY: ANN ARBOR

ORG_STATE: MI

PHR: Excess steroid hormone production from the adrenal cortex increases with age and contributes to hypertension, heart failure, obesity, glucose intolerance, and low bone mass. Veterans are vulnerable to these diseases and the associated morbidity due to their prior exposures and complex medical histories. Surgery is the preferred treatment, but many Veterans are not surgical candidates, and current medical treatments are limited to receptor antagonists that all have narrow therapeutic indices and significant side effects. The two different enzymes that catalyze the last steps of cortisol and aldosterone synthesis are ideal drug targets, but these enzymes are very similar. Drugs that inhibit specific steps in aldosterone and cortisol synthesis would be better treatments, but we do not know enough about the differences of these highly related enzymes to rationally design drugs to block only one of these reactions. To pave the way for better treatments of aldosterone and cortisol excess, we propose to systematically dissect the biochemistry of these two enzymes.

PI_NAMEs: AUCHUS, RICHARD J. (contact)

PROJECT_TERMS: Acceleration;Active Sites;Adrenal Cortex;Adrenal Glands;Adverse effects;Affinity;Age;Aldosterone;Anabolism;Androgens;antagonist;Binding;Biochemical;Biochemistry;bone mass;carbohydrate metabolism;Cell Line;Cells;Cessation of life;chemical property;Chromosome 8;comorbidity;Complex;Consumption;Corticosterone;Cortodoxone;Coupling;CYP11B2 gene;Cytochrome P450;Data;Deoxycorticosterone;Diabetes Mellitus;Disease;Dissociation;Drug Design;Drug Targeting;Dyslipidemias;Enabling Factors;Environment;enzyme activity;enzyme structure;enzyme substrate;Enzymes;Equilibrium;experimental study;Genes;Geometry;Glucocorticoids;Glucose Intolerance;Goals;Heart failure;Homeostasis;Human;human disease;Hydrocortisone;Hydroxylation;Hypertension;hypertension treatment;Hypotension;Impairment;in vivo;inhibitor therapy;insight;instrumentation;Intrinsic factor;Kinetics;Laboratories;Lipids;Medical;Medical History;Membrane;Membrane Lipids;Metabolism;Michigan;Microscopic;Mineralocorticoids;Mitochondria;Mixed Function Oxygenases;Molecular Conformation;Morbidity - disease rate;Mutagenesis;Mutation;NADP;nanodisk;Nature;novel;Obesity;Operative Surgical Procedures;Organ;Oxidases;oxidation;Oxidation-Reduction;Pathway interactions;Pharmaceutical Preparations;physical property;Physiological;Point Mutation;Positioning Attribute;Production;Property;rational design;Reaction;receptor;Regulation;Reproducibility;Research;response;Series;side effect;single molecule;small molecule;Sodium Chloride;steroid hormone;Steroids;Stress;surgical risk;System;tandem mass spectrometry;Testing;Therapeutic Index;tool;Transfection;Universities;Veterans;Water;Work;Zona Fasciculata;Zona Glomerulosa;Zona Reticularis

PROJECT_TITLE: The terminal steps of cortisol and aldosterone biosynthesis


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurological disease characterized by progressive paralysis due to motor neuron (MN) degeneration. We propose a multicenter, translational study using both post- mortem tissue from ALS patients and transgenic ALS mice to test the hypothesis that in ALS, an altered sphingosine-1-phosphate (S1P) system drives the proinflammatory activation of astrocytes and microglia and that treatment with S1P modulators will interfere with the proinflammatory process to slow down (or recover) the degeneration of MN. To evaluate pathology, we will use a combination of biochemical, immunohistochemical, spectroscopy, and imaging techniques. The study will provide valuable data towards understanding the pathological process of ALS and finding new therapeutic approaches to prevent, slow, or cure the disease.

PI_NAMEs: DEDEOGLU, ALPASLAN  (contact)

PROJECT_TERMS: Activated Lymphocyte;Affect;Age;ALS patients;Alzheimer's disease model;Amyloid beta-Protein;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;analog;Anatomy;Animal Model;Anti-Inflammatory Agents;Antiinflammatory Effect;Apoptosis;Area;Astrocytes;Atrophic;Autopsy;biobank;Biochemical;blood-brain barrier crossing;Body Weight;Brain;Cell Physiology;Central Nervous System;Ceramides;Cerebral cortex;Cessation of life;Clinical;Clinical assessments;Complex;Cortical Cord;cytokine;Data;Diagnosis;Diffusion;Disease;Disease Progression;Dose;effective therapy;Etiology;FOXP3 gene;Functional disorder;Gene Mutation;Generations;Genes;glial activation;Goals;gray matter;Human;Imaging Techniques;immune cell infiltrate;Immune system;Immunosuppressive Agents;improved;Infiltration;Inflammation;Inflammatory;lipid metabolism;Lipids;Longevity;Lumbar spinal cord structure;Lymphocyte;Lymphocyte Activation;Lymphocyte Depletion;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Memory;Metabolism;Microglia;migration;Monitor;Motor;Motor Cortex;motor neuron degeneration;Motor Neurons;mouse model;Multiple Sclerosis;multiple sclerosis treatment;Mus;Muscle Weakness;Natural Immunity;Nature;Nervous System Disorder;neurochemistry;Neuroglia;neuroinflammation;neuropathology;neuroprotection;neurotoxic;neurotrophic factor;novel strategies;novel therapeutic intervention;novel therapeutics;oligodendrocyte progenitor;Onset of illness;optimal treatments;Oral;Paralysed;Pathogenesis;Pathogenicity;Pathologic;Pathologic Processes;Pathology;Pathway interactions;Pharmaceutical Preparations;Pharmacology;Phase;Phenotype;Phosphotransferases;preclinical study;prevent;Process;protein TDP-43;receptor;Recovery;Regulatory T-Lymphocyte;remyelination;research clinical testing;response;Role;Sampling;side effect;Signal Transduction;spasticity;Specificity;Spectrum Analysis;Sphingolipids;Sphingosine;sphingosine 1-phosphate;sphingosine-1-phosphate lyase;sphingosine-1-phosphate phosphatase;Sphingosine-1-Phosphate Receptor;Spinal Cord;stem cells;superoxide dismutase 1;Survival Rate;Symptoms;System;T-Lymphocyte;Techniques;Testing;Therapeutic;therapeutic target;Tissues;Transgenic Organisms;Translating;translational study;treatment effect;white matter

PROJECT_TITLE: Sphingosine-1-phosphate system as a therapeutic target for amyotrophic lateral sclerosis


ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI VA MEDICAL CENTER RESEARCH

PHR: Post-traumatic stress disorder is a major problem for the VA. According to the VA, 14% of individuals that served in OIF or OEF develop PTSD, a rate that is substantially higher than the general population (7-8%). Women veterans appear to be more a risk for PTSD than men. Frontline treatment options (e.g., SSRIs) can improve symptoms but do not currently offer a cure. To develop further strategies to this end, it is critical to understand the foundations of the disease process as it develops. This proposal examines the role prefrontal cortex stress hormone (glucocorticoid) receptors in driving development of PTSD behavioral pathologies, ranging from anxiety symptoms, exaggerated fear responses and cognitive dysfunction. These studies employ pharmacological, genetic and cell physiological approaches to test the role of abnormal glucocorticoid signaling in generation of behavioral disturbances in rodent models. Our results will inform future strategies to target abnormal stress hormone signals in behavioral pathologies.

PI_NAMEs: HERMAN, JAMES P (contact)

PROJECT_TERMS: Ablation;Address;Affect;Amygdaloid structure;Animal Model;antagonist;Anterior;Anxiety;anxiety symptoms;anxiety-related behavior;Automobile Driving;Behavior;Behavioral;Binding;Brain;Cells;cellular pathology;cingulate cortex;conditioned fear;Data;Decision Making;design;Development;Disease;Electrophysiology (science);Emotional;Emotions;Endocrine;Experimental Designs;Exposure to;Extinction;fear memory;Foundations;Fright;Functional disorder;Future;Gene Deletion;General Population;Generations;Genetic;genetic variant;Glucocorticoid Receptor;Glucocorticoids;Hormonal;hormonal signals;Hormones;Human;Hydrocortisone;hypothalamic-pituitary-adrenal axis;Impaired cognition;Impairment;Impulsivity;inattention;Incidence;Individual;Infusion procedures;insight;Link;Machine Learning;Mediating;Memory;men;military service;Modeling;Modification;Nature;Neurons;novel;patch clamp;Pathologic;Pathology;pharmacologic;Physiological;Pituitary Gland;Population;post-trauma;Post-Traumatic Stress Disorders;Predisposing Factor;Predisposition;Prefrontal Cortex;Prevention;Process;Pyramidal Cells;Rattus;receptor;receptor binding;receptor expression;receptor sensitivity;Receptor Signaling;Regulation;Reproducibility;Research;response;Risk;Rodent;Rodent Model;Role;Selective Serotonin Reuptake Inhibitor;Severities;sexual assault;Signal Transduction;social;Stress;symptomatic improvement;Symptoms;Testing;Time;trait;Trauma;trauma exposure;traumatic stress;Veterans;Viral Vector;Withdrawal;Woman

PROJECT_TITLE: Glucocorticoid Receptor Mechanisms of Traumatic Stress Pathology


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Traumatic brain injury (TBI) results in cellular structural damage followed by widespread dysfunctions including maladaptive dysregulation of injury-response mechanisms and ultimately neurological. We aim to characterize the molecular mechanisms that modulate progressive brain neurodegeneration and associated neurological impairments after TBI. Veterans are a distinct group of brain trauma patients because military TBI features specific conditions, before and after trauma that impact the developing neuropathology. Recent studies have shown that stress results in significant and wide-ranging negative effects on the brain that may be mediated by pro-inflammatory systemic and central (brain) mechanisms. These processes that may underpin the development of post-traumatic stress disorder (PTSD) become even more significant in association with TBI. We hypothesize that exposure to pre- and/or post-TBI stress changes the trajectory of neuroinflammation and neurodegeneration progression in TBI, accelerating and extending the neuropathological processes.

PI_NAMEs: STOICA, BOGDAN ADRIAN (contact)

PROJECT_TERMS: Acceleration;Address;Affective;Attenuated;Brain;Brain Injuries;cell type;Cells;Chronic;Clinical Data;Cognitive;Complex;Data;design;Development;Disease;Exposure to;Flow Cytometry;Functional disorder;Gene Expression;Genes;glial activation;Goals;Immune;Impaired cognition;Impairment;improved;Inflammation;Inflammatory;Injury;Lead;Mediating;Microglia;MicroRNAs;Military Personnel;Modeling;Molecular;Motor;nano-string;Nerve Degeneration;Nervous System Physiology;neurobehavioral;neuroinflammation;Neurologic;Neurologic Deficit;Neurologic Dysfunctions;neuron loss;Neurons;neuropathology;neurorestoration;neurotoxic;neurotoxicity;novel;Organ;Pathway interactions;Patients;Phenotype;Population;Post-Traumatic Stress Disorders;posttranscriptional;pre-clinical;Process;programs;progressive neurodegeneration;repaired;response;response to injury;restoration;Stress;System;Testing;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissues;Trauma;Trauma patient;Traumatic Brain Injury;traumatic stress;United States Department of Veterans Affairs;Untranslated RNA;Up-Regulation;Veterans

PROJECT_TITLE: MicroRNA-regulated Pathways Control Chronic-Progressive Neuroinflammation and Neurodegeneration Following TBI


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: The kidney provides fluid balance and toxin removal essential to human health. The filtering units (glomeruli) and the permeable drains (tubules) that carry and remove fluid from the body can be easily damaged, and such damage (called 'acute kidney injury', or AKI) often leads to prolonged hospitalization and permanent kidney damage among Veterans. However, physicians are currently only able to measure the function of the glomeruli. I plan to study measures of tubular function in the kidney. My goal is to provide an understanding of how AKI happens and to develop clinical tests that can predict risk of AKI. Based on the data generated from the CDA2 award, I intend to apply for an independent research grant from the VA. I envision testing the markers in a variety of clinical settings, for instance, in cancer patients exposed to life-saving but potentially kidney-damaging medications.

PI_NAMEs: BULLEN, ALEXANDER LIONEL (contact)

PROJECT_TERMS: Acute;Acute Lung Injury;Acute Renal Failure with Renal Papillary Necrosis;Admission activity;Albuminuria;arm;Atrophic;Award;Biological Markers;Blood Pressure;blood pressure intervention;blood pressure reduction;Body Fluids;Cancer Patient;career;cell injury;Cell Physiology;Cells;Clinical;clinical biomarkers;Clinical Investigator;Clinical Research;clinical trial implementation;cohort;community living;comorbidity;Complex;Data;Dehydration;demographics;design;Development;Diagnosis;Distal;Doctor of Philosophy;endothelial dysfunction;Event;Excision;experience;Exposure to;Fellowship;Fibrosis;Filtration;Fluid Balance;Functional disorder;Funding;Future;Generations;Goals;Health;hemodynamics;high risk;Hospitalization;Host Defense;Human;Hypotension;improved;Individual;Infection;Inflammatory Infiltrate;Injury;injury recovery;insight;Intervention Trial;Investigation;Kidney;Kidney Diseases;LCN2 gene;Life;Measurement;Measures;Medical;Medical center;Mentors;Mentorship;Methodology;multidisciplinary;Necrosis;novel marker;Obstruction;Operative Surgical Procedures;Outpatients;Participant;Patient Admission;patient oriented research;Patients;Permeability;Pharmaceutical Preparations;Physicians;Play;predictive marker;Predisposition;Process;programs;Proteins;Proteinuria;Randomized;Recording of previous events;Recovery;renal damage;Renal function;Renal tubule structure;Research;Research Design;Research Personnel;Research Project Grants;Risk;Risk Assessment;Risk Factors;risk prediction;Role;Secondary to;Statistical Methods;Testing;Thrombosis;Time;Toxin;Training;Translating;Translations;Tubular formation;Veterans;Visit;Work

PROJECT_TITLE: Kidney Tubule Cell Function and Future Risk of Acute Kidney Injury


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: Alcohol use disorders is highly co-morbid with depression and chronic pain, and especially high in veterans, but there is limited research on the impact of these co-morbidities on brain neurobiology. The goal of the proposed training and research is to delineate the overlapping and co-occurring patterns from neuroimaging and clinical symptomologies that form a brain signature of depression and chronic pain within the alcohol use disorder brain signature through the use of advanced computational modeling algorithms to better inform individualized precision medicine treatment approaches for veterans.

PI_NAMEs: MURRAY, DONNA  (contact)

PROJECT_TERMS: 21 year old;Adult;alcohol use disorder;Alcohols;Algorithms;Behavior;behavior measurement;Behavioral;biosignature;Brain;Brain Diseases;career;Cause of Death;chronic depression;chronic pain;Clinical;clinical practice;Cognition;Communication;comorbid depression;comorbidity;Computer Analysis;Computer Models;Computing Methodologies;Data;depressive symptoms;Disease;dual diagnosis;effective therapy;evidence base;Exclusion;Functional Magnetic Resonance Imaging;Glutamates;Goals;Individual;individualized medicine;Interdisciplinary Study;Knowledge;Machine Learning;machine learning algorithm;machine learning method;magnetic resonance spectroscopic imaging;Measures;Mental Depression;Mentors;Methods;military veteran;Modeling;multidimensional data;Multimodal Imaging;multimodal neuroimaging;N-acetylaspartate;neural;neural circuit;neural patterning;neurobiological mechanism;Neurobiology;neurochemistry;neuroimaging;neuromechanism;Neurons;Outcome;Pain;pain symptom;Participant;Patient Self-Report;Patients;Pattern;Persons;precision medicine;predictive modeling;programs;Psychiatry;Questionnaires;recruit;Relapse;relapse risk;Reporting;Research;Research Personnel;Rest;Sampling;Scientist;Severities;Substance Addiction;Substance Use Disorder;symptomatology;Symptoms;Synaptic plasticity;Techniques;Testing;Training;treatment response;United States;unsupervised learning;Veterans;Work

PROJECT_TITLE: The neurobiological mechanisms of untreated pain and depression to relapse risk in substance dependence


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Liver damage leads to scaring of the liver in a pathologic process known as cirrhosis. This leads to many different complications that lead to a poor quality of life, including severe intestinal bleeding, fluid buildup in the abdomen, and others. This proposal aims to understand the cause of this scarring in the liver, and ultimately to provide insights that lead to new therapies to treat this problem.

PI_NAMEs: ROCKEY, DON C. (contact)

PROJECT_TERMS: Abdomen;Actins;alpha Actin;Architecture;Biological;Biology;Body System;Cardiovascular system;Cell Physiology;cell transformation;Cells;Cellular biology;Characteristics;Chronic;chronic liver disease;chronic liver injury;Cicatrix;Cirrhosis;Complex;Cytoskeleton;Data;Effector Cell;Elements;Exhibits;Extracellular Matrix;Extracellular Matrix Proteins;factor A;Family;fibrogenesis;Fibrosis;Generations;Genes;Genetic Transcription;Goals;Hemorrhage;Hepatic;Hepatic Fibrogenesis;Hepatic Stellate Cell;In Vitro;in vivo;Injury;innovation;insight;Interruption;Intestines;Knockout Mice;Laboratories;Life;Liquid substance;Liver;Liver Cirrhosis;Liver Fibrosis;liver injury;Mediating;MicroRNAs;Molecular;Muscle Proteins;myocardin;Myofibroblast;Myosin Heavy Chains;Normal tissue morphology;novel;novel therapeutics;Organ;Pathogenesis;Pathologic Processes;Pathway interactions;Phenotype;Population;prevent;Process;Production;programs;Protein Isoforms;Proteins;Quality of life;Regulation;Regulatory Element;response;response to injury;Role;Serum Response Factor;Smooth Muscle;Smooth Muscle Myocytes;stellate cell;Structure;Tissues;transcription factor;Up-Regulation;Vascular System;Veterans;Work;wound healing

PROJECT_TITLE: Pathobiology of hepatic fibrosis and cirrhosis


PHR: Narrative The commensal gut microbiota is a robust modulator of innate immune signaling and skeletal growth and maturation, but there is a limited understanding of commensal gut microbiota actions impacting skeletal maturation and deterioration. While innate immune complement signaling has been shown to regulate pathogenic microbes and promote osteoblast-osteoclast differentiation and signaling, the role of complement in the maturing and aging skeleton in health and disease remains to be elucidated. Mechanisms underlying how the commensal gut microbiota regulates the skeleton across the lifespan are unclear, thus lies a critical need to advance our understanding of commensal gut microbiota mechanisms impacting bone mass accrual in our young service members and Nation’s Veterans.

PI_NAMEs: HATHAWAY-SCHRADER, JESSICA DIANN (contact)

PROJECT_TERMS: Adult;Age;age related;age related changes;aged;Aging;Anaphylatoxins;Animals;Area;bone;bone cell;Bone Density;bone fracture repair;bone health;bone loss;Bone Marrow;bone mass;Bone Resorption;C3AR1 gene;career;career development;Cells;commensal microbes;Complement;Complement 3a;Complement Receptor;Data;deprivation;Deterioration;Development;dextran sulfate sodium induced colitis;Disease;experience;fracture risk;Funding Mechanisms;germ free condition;Germ-Free;Goals;Gonadal Steroid Hormones;Growth;gut microbiota;Health;host microbiota;Immune;Immune response;Immune signaling;Immunity;Immunologic Stimulation;immunoregulation;Impairment;improved;In Vitro;in vivo;Infection;Inflammatory;Inflammatory Bowel Diseases;innovation;Intervention;Intestines;knock-down;Knowledge;Lactobacillus plantarum;life span;Mediating;Mediator;Mentors;microbiota;Modeling;Mus;Osteoblasts;osteoclastogenesis;Osteoclasts;osteoimmunology;Osteopenia;Osteoporosis;Pathogenesis;pathogenic microbe;Phase;postdoctoral investigator;Probiotics;Process;Puberty;receptor;recruit;Reporting;Research;Research Personnel;Resources;Risk;Role;service member;Services;Signal Transduction;skeletal;Skeletal Development;skeletal maturation;Skeleton;Solid;substantia spongiosa;System;Testing;Therapeutic Intervention;tool;Training;Transgenic Mice;Up-Regulation;Veterans;Work;young adult

PROJECT_TITLE: Role of Complement in Commensal Microbiota Actions Regulating Sketal Maturation


PHR: Tinnitus and hearing loss have been the #1 and #2 disabilities at the VA for more than a decade. These auditory disorders are associated with depression, isolation, anxiety disorders, PTSD, sleep deprivation, cognition, loss of employability, and increased industrial and motor vehicle accidents. Yet there is no effective treatment for either disorder and genetic distinction between the two disorders is as yet uncharacterized.  Our plan is to use the rich data in the Million Veteran Program to perform and analyze genome-wide association studies in order to identify relevant genes. In our current work, we have established a pipeline and for the first time, identified genetic variants associated with tinnitus. We will computationally separate and examine the genetic architecture of these two auditory disorders using military- and Veteran-relevant etiologies, i.e., age-related, chronic noise secondary to military exposures, blast, and traumatic brain injury. Identifying genes and their relevant pathways will direct pharmaceutical approaches towards treatment and ultimate cure.

PI_NAMEs: NIEVERGELT, CAROLINE M (contact)

PROJECT_TERMS: Acoustic Trauma;Acoustics;Address;Age;age related;Anatomy;Anxiety Disorders;Auditory;biobank;Biological;Biology;Brain;brain tissue;causal variant;Chronic;Clinical;clinical development;clinical diagnosis;clinical phenotype;clinically relevant;Cochlea;Cognition;Cognitive Therapy;cohort;comorbidity;cost;Counseling;Data;Data Collection;disability;disability payment;Disease;Dissection;effective therapy;Ensure;Etiology;European ancestry;Exposure to;Foundations;Future;gene discovery;Genes;Genetic;genetic architecture;Genetic Risk;genetic variant;genome wide association study;genome-wide;Genomics;Goals;Health Care Visit;Hearing;Hearing Aids;hearing impairment;Hearing problem;Hearing Tests;Heritability;Heterogeneity;improved;indexing;Industrialization;Injury;Knowledge;Measures;Medial;Mental Depression;Meta-Analysis;Military Personnel;military veteran;Modeling;Monitor;Neurobiology;Noise;noise exposure;novel;Pathway interactions;patient population;Patient Self-Report;Pharmacologic Substance;phenomenological models;Phenotype;polygenic risk score;Population Heterogeneity;Population Programs;Post-Traumatic Stress Disorders;Predisposition;Preparation;Productivity;programs;protein protein interaction;Publishing;Quality of life;Research;Risk Factors;risk prediction;risk variant;Secondary to;Signal Transduction;Sleep Deprivation;sleep difficulty;Speech Intelligibility;Subjective Tinnitus;Symptoms;Time;Tinnitus;Tissues;tool;trait;transcriptomics;Traumatic Brain Injury;Twin Studies;United Kingdom;Untranslated RNA;Validation;Variant;vehicular accident;Veterans;Vulnerable Populations;Work

PROJECT_TITLE: Genetic Architecture of Tinnitus and its Relationship to Hearing Loss


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Liver Cancer;Liver Disease;Prevention;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: NARRATIVE The current “one-size-fits-all” strategy for hepatocellular carcinoma (HCC) early detection using abdominal ultrasound +/- a serum biomarker, alpha fetoprotein (AFP), in all patients with cirrhosis ignores the heterogeneity in HCC risk among patients with cirrhosis and the suboptimal accuracy of current screening tests, highlighting a need for risk stratification and early detection biomarkers. Our Clinical Validation Center for HCC (CVC-HCC) will leverage existing infrastructure across five health systems to create two novel resources not offered by the current sample sets including (1) a biorepository with both blood and imaging data from patients, with and without HCC, representing contemporary etiologies of liver disease for Phase I-II biomarker studies and (2) a prospective cohort of patients with indeterminate liver nodules to evaluate HCC risk stratification and early detection biomarkers to conduct Phase III biomarker studies using a prospective- specimen-collection, retrospective-blinded-evaluation (PRoBE) design. Overall, our CVC-HCC will lead to significant advances in phase I-III validation of novel biomarkers for HCC risk stratification and early detection, areas of need that will facilitate development of well-designed phase IV clinical utility trials.

PI_NAMEs: KANWAL, FASIHA ;MARRERO, JORGE A;PARIKH, NEEHAR DILIP;SINGAL, AMIT  (contact)

PROGRAM_OFFICER_NAME: KOHAAR, INDU

PROJECT_TERMS: Abdomen;Area;biobank;Biological Markers;biomarker discovery;biomarker panel;biomarker validation;Blinded;Blood;blood-based biomarker;Cancer Etiology;Cessation of life;Cirrhosis;Clinical;clinical practice;clinical risk;cohort;curative treatments;Data;design;Detection;Development;Diagnostic;early detection biomarkers;Early Detection Research Network;Early Diagnosis;Effectiveness;ethnic minority;Etiology;Evaluation;Funding;Future;Goals;Guidelines;Health system;Heterogeneity;high risk;Image;imaging biomarker;imaging study;improved;Infrastructure;Liver;Liver diseases;Magnetic Resonance Imaging;Malignant neoplasm of liver;Malignant Neoplasms;Modeling;Molecular Profiling;Nodule;novel;novel marker;patient population;patient stratification;Patients;Performance;Phase;phase 2 study;phase 3 study;Policies;Population;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;prospective;Prospective cohort;racial minority;radiological imaging;Radiology Specialty;radiomics;Recommendation;Resources;Risk;Risk Factors;risk stratification;sample collection;Sampling;screening;Serum;Testing;Texas;Translations;tumor;ultrasound;Validation;validation studies;Viral hepatitis;Work;α-Fetoproteins

PROJECT_TITLE: Clinical Validation Center for Hepatocellular Carcinoma


PHR: Lung cancer represents a considerable disease burden within the Veteran population. It is diagnosed at a rate of 18.8%, second only to prostate cancer in highest incidence. However, even after definitive treatment, lung cancer patients remain at risk for recurrent disease and developing second primary lung cancers for which imaging surveillance guidelines exist. By examining the patterns of care, guideline concordance, and clinical outcomes associated with post-treatment surveillance following definitive treatment for lung cancer, the VA may better define the elements of quality care for lung cancer patients and enhance the ability of the healthcare system to respond to the anticipated increased imaging demands associated with the adoption of CT screening within the VA population.

PI_NAMEs: BACKHUS, LEAH M (contact)

PROJECT_TERMS: Address;Adherence;adherence rate;Adoption;Affect;Aftercare;American;burden of illness;Cancer Patient;cancer recurrence;cancer therapy;cancer type;care providers;Caring;Categories;chest computed tomography;Clinical;Clinical Cancer Center;Clinical Data;Clinical Practice Guideline;Code;cohort;comorbidity;compare effectiveness;Comprehensive Cancer Center;computed tomography screening;Conflict (Psychology);Curative Surgery;Data;Data Collection;Data Files;Data Set;data warehouse;demographics;Detection;Development;Diagnosis;Diagnostic;Disease;Early Diagnosis;Effectiveness;effectiveness evaluation;Electronic Health Record;Electronics;Elements;Environment;Excision;Face;feeding;follow-up;Frequencies;Goals;Guideline Adherence;Guidelines;Healthcare Systems;high risk;high risk population;ICD-9;Image;Incidence;innovation;Inpatients;Institution;Intervention;Light;Link;Literature;lung cancer screening;Lung CAT Scan;Lung nodule;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Manuals;Mediator;Medical;Medicare;Methods;military veteran;Modeling;mortality;multiple data sources;National Comprehensive Cancer Network;neoplasm registry;novel;Operative Surgical Procedures;Outcome;Patient imaging;Patients;Pattern;Patterns of Care;Population;Process;prospective;Provider;Publishing;Quality of Care;radiologist;Radiology Specialty;Randomized;randomized trial;Recommendation;Records;Recurrence;Recurrent disease;Regimen;Reporting;Risk;routine imaging;screening;screening guidelines;secondary analysis;Series;Smoker;structured data;Subgroup;surveillance imaging;surveillance strategy;Surveys;survival outcome;Testing;Text;Thoracic Surgeon;Time;time interval;tool;trend;Variant;Veterans;Vital Status;X-Ray Computed Tomography

PROJECT_TITLE: Imaging Surveillance After Lung Cancer Treatment

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


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Cancer

ORG_CITY: LA JOLLA

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE This application seeks funding to continue a training program in developmental therapeutics focused on cancer drugs at the Moores Cancer Center at the University of California, San Diego. Our vision is that cancer can be controlled with novel drug, immunologic and viral therapeutics directed at molecular targets that allow individualization of treatment. The mission of the program is to provide training to postdoctoral PhD and MD- physician-scientists in each of the major steps in the development of novel cancer therapeutics so as to position these individuals to play leading roles in translating laboratory-based discoveries into safe and effective therapeutic agents.

PI_NAMEs: BOUVET, MICHAEL  (contact);STUPACK, DWAYNE G.

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Cancer Center;drug development;Training Programs

PROJECT_TITLE: UCSD Cancer Center Training Program in Drug Development

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE Mutations in KCNMA1 BK potassium channels produce a wide range of neurological disorders which include epilepsy and autism. Most studies that seek to understand the biophysical basis of these disorders have not studied the major forms of the mutant channels. We plan to do so using single channel recording and analysis.

PI_NAMEs: MAGLEBY, KARL L;SALKOFF, LAWRENCE B (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Alleles;arterial tortuosity;Ataxia;Atrophic;autism spectrum disorder;Biophysics;bone;Categories;Cell membrane;Cells;Cerebrum;clinical phenotype;Complication;Congenital Abnormality;Coupling;Developmental Delay Disorders;Disease;Dominant-Negative Mutation;Electrophysiology (science);Epilepsy;expectation;Fragile X Syndrome;Frequencies;gain of function;Genes;Genetic Diseases;Genetic Predisposition to Disease;genetic variant;Genetic Variation;Heterozygote;Hybrids;Individual;Intellectual functioning disability;Laboratories;large-conductance calcium-activated potassium channels;loss of function;malformation;Modeling;Molecular;Muscle hypotonia;mutant;Mutation;Nervous System Disorder;novel strategies;Patients;Phenotype;Physiological;Population;Potassium Channel;prevent;Property;Reporting;Severities;stoichiometry;Syndrome;System;Techniques;Testing;Variant;voltage

PROJECT_TITLE: New approaches to understanding BK channelopathies at the molecular level of single channels

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


ORG_CITY: SYDNEY

ORG_COUNTRY: AUSTRALIA

ORG_FIPS: AS

ORG_NAME: UNIVERSITY OF NEW SOUTH WALES

PHR: PROJECT NARRATIVE Malignant melanoma is the most dangerous skin cancer, with a very poor survival rate once metastasis has occurred. Current treatments target the primary tumor and not the process of metastasis, and once the cancer has disseminated, chemotherapy has limited value. This project aims to integrate novel tissue engineered tumor mimics with patient derived tumor xenografts to explore progression towards patient-specific models for therapeutic development.

PI_NAMEs: COPLAND, JOHN A.;KILIAN, KRISTOPHER ALAN (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Biology;Biomedical Engineering;Biomimetics;Biopsy;BRAF gene;Cell Fraction;Cell Line;cell type;Cells;Cessation of life;Characteristics;chemotherapy;Clinical Trials;Combinatorics;Combined Modality Therapy;Cues;Cutaneous Melanoma;Dangerousness;Data;design;Development;Disease;Disease Progression;drug development;Drug resistance;drug sensitivity;Engineering;Epigenetic Process;epigenetic regulation;Excision;Extracellular Matrix;geometric structure;Geometry;Growth;Harvest;Heterogeneity;high throughput analysis;Human;Implant;In Vitro;in vivo;individualized medicine;inhibitor;International;intravital imaging;Invaded;knock-down;Laboratories;Lead;Malignant Neoplasms;Mechanics;mechanotransduction;MEK inhibition;MEKs;melanocyte;Melanoma;Melanoma Cell;Metastatic Melanoma;Modeling;Monitor;mouse model;Mus;mutant;Mutation;Neoplasm Metastasis;novel;novel therapeutic intervention;novel therapeutics;Nude Mice;Operative Surgical Procedures;patient derived xenograft model;patient response;Patient-Focused Outcomes;Patients;Phenotype;Pigments;Pilot Projects;pluripotency;Pre-Clinical Model;Primary Neoplasm;Process;Prognosis;programs;prospective;Proteins;Reproducibility;Resistance;response;RNA Interference;Role;screening;Signal Transduction;Skin Cancer;Somatic Mutation;standard of care;stemness;Structure-Activity Relationship;success;Survival Rate;Suspensions;System;targeted treatment;Techniques;Therapeutic;therapeutic development;three-dimensional modeling;Tissue Engineering;Tissues;tool;Translating;treatment response;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Tissue;tumor xenograft;tumorigenesis;tumorigenic;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Engineered microtumor arrays for development of combination therapies

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Digestive Diseases;Emerging Infectious Diseases;Genetics;Immunization;Immunotherapy;Infectious Diseases;Kidney Disease;Liver Disease;Organ Transplantation;Precision Medicine;Prevention;Transplantation;Vaccine Related

ORG_NAME: PALO ALTO VETERANS INSTIT FOR RESEARCH

PHR: PROJECT NARRATIVE This project seeks to identify intrinsic differences in immune phenotype and function, irrespective of the degree of immunosuppression, between liver and kidney transplant recipients who did or did not respond to SARS-CoV- 2 vaccination. The studies will employ state-of-the-art technologies to decipher phenotypic, transcriptional, and epigenetic features of responders versus non-responders at the single cell level. The proposed high-risk mechanistic experiments on ex vivo human cells, have the potential to deepen our understanding of the immune responses against SARS-CoV2 vaccine in organ transplant recipients (high reward) and will provide the basis for larger studies to test the generated hypotheses.

PI_NAMEs: CRAVEDI, PAOLO ;MALTZMAN, JONATHAN S (contact)

PROGRAM_OFFICER_NAME: ROBIEN, MARK ANDREW

PROJECT_TERMS: 2019-nCoV;adaptive immune response;Address;Affect;Antibody Response;ATAC-seq;B-Lymphocytes;booster vaccine;Cells;Chromatin;cohort;Collaborations;COVID-19;COVID-19 vaccination;COVID-19 vaccine;Cryopreservation;Data;Development;Dose;Epigenetic Process;Evaluation;experimental study;Gene Expression;General Population;Genetic Transcription;Goals;high reward;high risk;Human;Immune;immune function;Immune response;Immunosuppression;improved;Individual;Infection;Innate Immune Response;Kidney;Kidney Transplantation;Laboratories;Link;Liver;liver transplantation;Measures;Molecular;Morbidity - disease rate;mortality;Organ;organ transplant recipient;Organ Transplantation;Outcome;Patients;Peripheral Blood Mononuclear Cell;Phenotype;Population;post SARS-CoV-2 infection;Productivity;Publishing;Recording of previous events;Regimen;responders and non-responders;response;response biomarker;RNA vaccination;RNA vaccine;Sampling;SARS-CoV-2 spike protein;seroconversion;Serology;single nucleus RNA-sequencing;Solid;success;T cell clonality;T cell response;T-Cell Activation;T-Lymphocyte;Technology;Testing;Transplant Recipients;Vaccination;Vaccines;Viral;Virus;Work

PROJECT_TITLE: Deciphering the Molecular Mechanisms of Response to COVID Vaccine in Kidney Transplant Recipients


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prostate Cancer;Rural Health;Urologic Diseases;Women's Health Research

ORG_CITY: SALT LAKE CITY

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE Fear of recurrence or cancer coming back is an important issue for the estimated 17 million cancer survivors who are alive in the US today, but cancer recurrence information is currently not available for research in the national cancer registry data due to difficulties in capturing this information. At the Utah Cancer Registry, we have multiple statewide linkages to health records data that other registries do not have, that could facilitate obtaining cancer recurrence data. We propose to develop methods to identify recurrence and validate the methods with the Cancer Registry in Seattle-Puget Sound, so that other researchers can apply the methods to data in the cancer registries and with additional data linkages that are rapidly increasing across cancer registries in various states.

PI_NAMEs: DOHERTY, JENNIFER A. (contact);HASHIBE, MIA

PROGRAM_OFFICER_NAME: MARIOTTO, ANGELA B

PROJECT_TERMS: Accident and Emergency department;Accreditation;Age;Algorithms;Ambulatory Surgical Procedures;American College of Surgeons;Back;Biochemical;Breast;breast cancer registry;Cancer Patient;cancer recurrence;cancer site;Cancer Survivor;cancer type;Caring;Cause of Death;Characteristics;clinical practice;Clinical Trials;Code;Collection;Computerized Medical Record;cost;Data;Data Collection;Data Linkages;data registry;Data Sources;data streams;Databases;Death Certificates;Denmark;Diagnosis;Disease-Free Survival;Electronics;ethnic diversity;Ethnic Origin;Evaluation;Event;Fright;Generations;Health;Health care facility;Health Maintenance Organizations;health record;Hispanic Populations;Hospitals;improved;Incidence;Individual;Inpatients;learning algorithm;Link;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;Medical Records;Medicare;Medicare claim;men;Methods;multiple data sources;National Cancer Institute;National Cancer Program;neoplasm registry;novel;Pathology Report;patient registry;Patients;Performance;Population;population based;Population Database;Population Study;Positioning Attribute;prediction algorithm;Predictive Value;primary endpoint;Procedures;Prostate;Protocols documentation;public database;Race;racial diversity;Recurrence;Registries;Reporting;Research;Research Personnel;Risk;Rural;Rural Population;Sampling;SEER Program;sound;Source;Stress;Structure;survivorship;training data;Treatment Effectiveness;Treatment Efficacy;Utah;Validation;Woman;Work

PROJECT_TITLE: Identifying Cancer Recurrence with Novel Data Linkages with a Cancer Registry

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Eating Disorders;Mental Health;Neurosciences;Nutrition;Obesity

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project narrative The proposed research is relevant to public health because obesity rates are steadily increasing and there are significant health and financial costs associated with this increase. Understanding the neural mechanisms that underlie feeding, and specifically those underlying non-homeostatic feeding and responses to food-associated cues, which can drive feeding the absence of homeostatic need, is necessary to identify new targets and approaches to treat obesity and other eating disorders. Thus, this proposal is relevant to the part of NIH’s mission that pertains to fostering fundamental basic science discoveries, using innovative approaches, with the goal of ultimately improving health.

PI_NAMEs: BURGESS, CHRISTIAN RICHARD (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Adaptive Behaviors;Advertisements;Amygdaloid structure;Anatomy;Anorexia;Area;Arousal;Attention;Automobile Driving;Basic Science;Behavior;Behavioral;behavioral response;billboard;Brain;Brain region;Candy;Cognitive;Consummatory Behavior;Consumption;craving;Cues;Eating;Eating Disorders;Environment;feeding;Feeding behaviors;Fiber;Financial cost;Food;food consumption;Food Processing;Fostering;Future;Genetic;Goals;Health;Health Care Costs;hormonal signals;Human;Hunger;Hyperphagia;Hypothalamic structure;imaging approach;improved;in vivo;in vivo calcium imaging;Injections;innovation;Investigation;Knockout Mice;Lateral;Learning;Maps;Mediating;melanin-concentrating hormone;melanin-concentrating hormone receptor;Metabolic;Metabolism;Mission;Modeling;Modernization;neural;neuromechanism;Neurons;Nucleus Accumbens;Obesity;Obesity Epidemic;optogenetics;Pathway interactions;peptide hormone;Phenotype;Photometry;Population;Prevalence;Process;Public Health;rabies viral tracing;Research;response;reward processing;Rewards;Role;Sensory;sensory stimulus;Signal Transduction;Site;Sleep;sleep behavior;Societies;Stimulus;Structure;Structure of nucleus infundibularis hypothalami;System;tool;United States National Institutes of Health;Visual;Work;zona incerta

PROJECT_TITLE: Elucidating the role for MCH neurons in feeding behavior and responses to sensory food cues

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Project Narrative  Acute kidney injury (AKI) is a common and serious complication in hospitalized Veterans. Patients with AKI are at significant risk for the subsequent development of chronic kidney disease (CKD). This proposal will focus on the lymphatic system, which is crucial for maintaining fluid balance, transporting lipids, and aiding in immune function, within the kidney particularly during AKI and the AKI to CKD transition. Successful completion of the aims of this project will help better understand the pathogenesis of AKI during both injury and repair and could provide new avenues targeting the lymphatic system for therapeutic interventions in AKI.

PI_NAMEs: AGARWAL, ANUPAM ;LEE, TIMMY C (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Acute Renal Failure with Renal Papillary Necrosis;Bilateral;Cell Lineage;Cell Separation;Cells;Chronic;Chronic Kidney Failure;Cisplatin;Clinical;Clinical Trials;Collaborations;Complication;COVID-19 patient;Critical Illness;Cytometry;Data Reporting;Development;Dialysis procedure;Diphtheria Toxin;diphtheria toxin receptor;Disease;Drainage procedure;Excision;Exclusion;Exhibits;Exposure to;FLT4 gene;Fluid Balance;Funding;Goals;Health;Heart;Hospitalization;Human;Hypoxia;Image;immune function;Impairment;In Vitro;in vitro Assay;in vivo;Indiana;Inflammation;Inflammatory;Injury;injury and repair;injury recovery;Injury to Kidney;insight;Intensive Care Units;Intervention;Kidney;Knowledge;Ligands;lipid transport;Liquid substance;Lymphangiogenesis;Lymphatic;Lymphatic Endothelial Cells;Lymphatic function;Lymphatic Research;Lymphatic System;lymphatic vessel;Macrophage;Maps;Mediating;medical complication;Modality;Modeling;monocyte;Morbidity - disease rate;mortality;Mus;Myelogenous;Myeloid Cells;nephrotoxicity;NF-kappa B;novel;Operative Surgical Procedures;Pathogenesis;Pathologic;Patients;Phase;preservation;Publishing;receptor;Recovery;Renal function;Renal tubule structure;Reperfusion Injury;Reporter;Risk;Role;Signal Transduction;Source;Structure;Supportive care;Techniques;Testing;Therapeutic Intervention;Time;tissue repair;Tissues;transcriptomics;Transgenic Mice;translational therapeutics;Tube;Universities;Up-Regulation;Vascular Endothelial Growth Factor C;Vascular Endothelial Growth Factor D;Vascular Endothelial Growth Factor Receptor-3;Vascular Endothelial Growth Factors;Veterans;Work

PROJECT_TITLE: Lymphangiogenesis in the pathogenesis of acute kidney injury


ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Bacterial pneumonia and influenza are a leading cause of death worldwide. Our veteran patient populations are at particular risk for these infections due to advanced age, chronic medical conditions, and other factors. Neutrophils are a type of white blood cell that is critically important to fighting bacterial and other infections. Unfortunately, how to properly regulate neutrophil functions is not well understood, because up until relatively recently, the field of immunology has not appreciated the considerable diversity of neutrophil subtypes that can develop during infections. Our research will investigate whether neutrophils that develop during flu infections possess different characteristics and functional capabilities than neutrophils generated to fight bacterial infections. A new powerful technology called mass cytometry will be used to detect over 30 markers on individual neutrophils, to identify neutrophil subsets. Ultimately, these results be used to create new treatments to regulate neutrophil functions more appropriately.

PI_NAMEs: DENG, JANE C (contact)

PROJECT_TERMS: Adopted;Animals;Anti-Bacterial Agents;Antibiotics;antimicrobial;Bacteria;Bacterial Infections;Bacterial Pneumonia;bactericide;Biological Response Modifiers;Bone Marrow;Cause of Death;Cell Count;Cell Surface Receptors;cell type;Cells;Characteristics;Chronic;Circulation;Clinical Management;cytokine;Cytometry;Data;demographics;Development;Effector Cell;Elderly;Equilibrium;extracellular;fighting;flu;Focal Infection;Gene Expression Profile;Gene Expression Profiling;Generations;Heterogeneity;high risk;Histology;Host Defense;Human;Immune;Immunologic Receptors;Immunology;immunomodulatory therapies;immunoregulation;Impairment;improved;in vivo;Individual;Infection;infection risk;Inflammatory;Inflammatory Response;Influenza;influenza infection;influenza pneumonia;Ingestion;Interferon Type I;Investigation;Lead;Leukocytes;Literature;Lung;Lung infections;Malignant Neoplasms;Mediating;Mediator;Medical;military veteran;Molecular;mouse model;Mus;Myelogenous;Nature;neutrophil;novel;pandemic influenza;pathogen;Pathway interactions;patient population;Patients;Pattern;Performance;Phagocytosis;Phenotype;Pneumococcal Infections;Pneumonia;Population;Predisposition;Production;Reactive Oxygen Species;receptor expression;recruit;Regulation;Reporting;Research;Resistance;response;Role;Secondary to;Site;Spleen;Stimulus;Streptococcus pneumoniae;Techniques;Technology;Testing;Time;transcriptome;transcriptome sequencing;Veterans;Viral;Viral Pathogenesis;Viral Respiratory Tract Infection;Virus Diseases

PROJECT_TITLE: Neutrophil heterogeneity and function in host defense during pulmonary infection


PHR: Veterans who get much of their healthcare in the VA system are often hospitalized or seen emergently at non- VA community hospitals or clinics. While this is often necessary and wanted, some research says that getting care at multiple places can result in problems like higher risk for getting re-admitted to the hospital or having medical complications. In order to make cross-system healthcare safer, the VA Office of Community Care is designing programs to coordinate Veterans’ medical care during and after visits in community hospitals. Our research team plans to study these new programs when VA facilities across the country start using them in 2018. We plan to measure whether or not Veterans are more likely to get readmitted to the hospital or seen in emergency departments once the programs start, and we’ll ask Veterans, doctors, and nurses what they think about the programs. Our goal is to figure out if the programs are helpful and successful, and to improve them for the future.

PI_NAMEs: GEBREGZIABHER, MULUGETA GEBRESELASSIE (contact)

PROJECT_TERMS: Accident and Emergency department;Acute;acute care;Address;Adoption;Back;Budgets;care coordination;care systems;Caring;Case Study;Collaborations;Communities;community clinic;Community Healthcare;Community Hospitals;community partners;cost;Cost Savings;Cost-Benefit Analysis;Costs and Benefits;Country;Data;Data Reporting;Data Sources;Databases;design;Eligibility Determination;Emergency department visit;Evaluation;Event;evidence base;Evidence based practice;experience;Failure;Future;Goals;Health;health care service utilization;Healthcare;Healthcare Systems;Heart failure;high risk;hospital care;hospital readmission;Hospitalization;Hospitals;implementation evaluation;implementation fidelity;Improve Access;improved;improved outcome;Intervention;Interview;Knowledge;Length of Stay;Maintenance;Measures;Medical;medical complication;Methods;model design;Modeling;mortality;mortality risk;Needs Assessment;Notification;Nurses;operation;Outcome;Patient Discharge;Patients;Perception;program costs;program dissemination;Program Effectiveness;Program Evaluation;programs;prospective;Provider;Questionnaires;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Reporting;Research;response;risk stratification;Rural;Rural Health;satisfaction;Savings;Services;success;System;Telephone Interviews;Time;Veterans;Visit;Voice;Work

PROJECT_TITLE: Evaluating Care Coordination for Community Hospitalized Veterans to Improve Outcomes in Dual Use (ECHOeD)


ORG_CITY: COLUMBIA

ORG_NAME: HARRY S. TRUMAN MEMORIAL VA HOSPITAL

PHR: The mechanisms of heart failure are complex, and include hemodynamic overload and local and systemic neurohormonal changes. Although pharmacologic treatment of heart failure has made significant advances, the associated mortality and morbidity remains high with significant cost to the Veterans Healthcare System. RECK (Reversion Inducing Cysteine Rich Protein with Kazal Motifs) expression is significantly reduced in human heart failure. Since RECK targets multiple mediators known to contribute to adverse cardiac remodeling and heart failure development, we believe that strategies that induce RECK expression in the heart will ameliorate the structural and compositional changes within the heart, and vastly improve outcomes for cardiac patients.

PI_NAMEs: BYSANI, CHANDRASEKAR  (contact)

PROJECT_TERMS: Age Years;Angiotensin II;Angiotensins;aorta constriction;Aortic Valve Stenosis;Biochemical;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;cardioprotection;Caring;Cessation of life;Characteristics;Chronic;Complex;Congestive Heart Failure;coronary fibrosis;cost;Coupled;cysteine rich protein;Data;Dependovirus;Development;Disease;Disintegrins;Epidermal Growth Factor Receptor;experience;Fibroblasts;Fibrosis;Functional disorder;Gene Deletion;Genetic;glycoprotein 130;Goals;GPI Membrane Anchors;Healthcare Systems;Heart;Heart failure;Heart Hypertrophy;hemodynamics;Histologic;hospital readmission;Hospitalization;Human;human old age (65+);Hypertension;Hypertrophy;improved;improved outcome;In Vitro;in vivo;Inflammation Mediators;Inflammatory;Infusion procedures;Intervention;Left Ventricular Hypertrophy;lifetime risk;Maps;Matrix Metalloproteinases;Mediator;Medicare;Membrane;Metalloproteases;migration;Molecular;Morbidity - disease rate;mortality;Mus;Myocardial;new therapeutic target;novel;novel therapeutic intervention;older patient;overexpression;Pathogenesis;Patients;pharmacologic;Pharmacological Treatment;Play;pressure;prevent;Prevention;Prevention strategy;Process;Profibrotic signal;promoter;protective effect;Proteins;Public Health;Publishing;Reporting;Repression;Role;Satellite Viruses;Secondary to;Serotyping;Signal Transduction;Structure;Testing;therapeutic gene;Transgenic Organisms;treatment strategy;United States Department of Veterans Affairs;Veterans;Wild Type Mouse

PROJECT_TITLE: RECK in Adverse Cardiac Remodeling and Heart Failure


ORG_CITY: HUNTINGTON

ORG_NAME: HUNTINGTON VETERANS AFFAIRS MED CTR

ORG_STATE: WV

PHR: Diarrhea is one of the most common causes of disability of U.S. Veterans while they serve overseas. The most common chronic diarrheal disease in this country and in Veterans is inflammatory bowel disease (IBD; e.g. Crohn’s disease). Diarrhea is the most common and disabling morbidity of IBD. The prevalence of IBD has increased 2 to 3-fold among VA users and its prevalence is also known to increase with each decade of life in Veterans. Malabsorption of electrolytes and fluid by intestinal epithelial cells is a critical determinant of diarrhea in IBD, in which immune inflammatory mediators are known to play pivotal role. Thus, the overall goal of this project is to understand how NaCl absorption is regulated in the IBD intestine so that this novel information may form the foundation for designing new, superior, and specific immune-based therapies for diarrhea in IBD.

PI_NAMEs: SUNDARAM, UMA  (contact)

PROJECT_TERMS: absorption;Affect;Affinity;Animal Model;Anions;APPBP2 gene;Arachidonic Acids;Bicarbonates;brush border membrane;Brush Cell;Cells;Chronic;Chronic diarrhea;clinically relevant;Colon;common symptom;Complication;Country;Coupled;Crohn's disease;crypt cell;Data;design;Diarrhea;diarrheal disease;Dinoprostone;disability;Disabling;disabling symptom;disease model;Electrolytes;Enteritis;Epithelial Cells;Epithelium;Foundations;Funding;Genetic Transcription;Glucose;Goals;gut inflammation;Homeostasis;Human;Immune;immunoregulation;Immunotherapy;Impairment;in vivo;Inflammation Mediators;Inflammatory;Inflammatory Bowel Diseases;inhaled nitric oxide;insight;Intestinal Diseases;intestinal epithelium;Intestinal Mucosa;intestinal villi;Intestines;Life;Link;Liquid substance;Malabsorption Syndromes;Malnutrition;mast cell;Mediating;Modality;Modeling;Molecular;monolayer;Morbidity - disease rate;mouse model;Mucous Membrane;Mus;novel;Nutrient;operation;Oral Rehydration Therapy;Organoids;Oryctolagus cuniculus;Outcome;Pathway interactions;Phosphorylation;Physiological;Play;Prevalence;Process;Prostaglandin-Endoperoxide Synthase;Prostaglandins;putative anion transporter 1;Regulation;Role;Secondary to;side effect;SLC26A3 gene;Small Intestines;therapeutically effective;trafficking;Ulcerative Colitis;Veterans;Villus

PROJECT_TITLE: Regulation of intestinal NaCl absorption


ORG_CITY: INDIANAPOLIS

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: Deterioration of kidney function, or acute kidney failure is an important contributing factor to the morbidity and mortality of hospitalized veterans. Unfortunately, there is no established treatment to date for this disease except supportive care with dialysis. Our proposed research will study the role of a protein, Tamm-Horsfall Protein (THP), that may protect the kidneys in the setting of injury. Therefore, this project has improtant direct relevance to veterans health. A better understanding of the role of THP holds promise for future therapeutic stategies that improve outcomes of kidney failure by enhancing the protective role of this protein.

PI_NAMEs: ASHKAR, TAREK MAURICE (contact)

PROJECT_TERMS: Acute;Acute Kidney Failure;Acute Renal Failure with Renal Papillary Necrosis;Animal Model;Apical;Area;Binding;Cells;Chronic Kidney Failure;Circulation;Closure by clamp;Cytometry;Data;Deterioration;Dialysis procedure;Disease;Dose;Epithelium;Excretory function;experimental study;Flow Cytometry;Functional disorder;Funding;Future;gene therapy;General Population;Goals;healing;Health;Homeostasis;Homing;Hospitalization;Human;Immune;Immunofluorescence Immunologic;immunoregulation;Impairment;improved outcome;Inflammation;Inflammatory;Injury;Injury to Kidney;innovation;interstitial;Investigation;Ischemia;Kidney;kidney cell;Kidney Diseases;Kidney Failure;Knockout Mice;Knowledge;Limb structure;Macrophage;Mediating;monomer;Mononuclear;Morbidity - disease rate;mortality;Mortality Determinants;multiplexed imaging;Myeloid Cells;Neutrophil Infiltration;novel;novel therapeutic intervention;Outcome;Pathogenesis;Phagocytes;pharmacologic;Phase;Phenotype;Population;Production;Proliferating;Protein Deficiency;protein purification;Proteins;Publishing;Qualifying;Recovery;Renal function;renal ischemia;Reperfusion Injury;Reperfusion Therapy;Research;response;Role;Shapes;Signal Pathway;Signal Transduction;Source;Spatial Distribution;Structure of ascending limb of Henle's loop;sulfated glycoprotein 2;Supportive care;Techniques;Testing;Therapeutic;Therapeutic Uses;therapy development;Thick;Three-Dimensional Imaging;Time;Tissues;transcriptomics;translational potential;Tubular formation;UMOD gene;urinary;Urine;Veterans;Western Blotting;Wild Type Mouse;Work

PROJECT_TITLE: The immunomodulatory function of Tamm-Horsfall protein in acute kidney injury


ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

PHR: The U.S. Veterans are under risk to develop lethal blood cancers due to exposure to carcinogens, such as agent orange, during their active military service. Many of these cancers are treated with hematopoietic cell transplantation (HCT) or bone marrow transplantation (BMT), where the successful outcome of transplant procedure is curtailed by the devastating and lethal graft-versus-host disease (GVHD). The US Veterans are likewise under risk to develop end-stage organ failure (such as kidney failure), where successful treatment with organ transplantation is curtailed by rejection. GVHD or rejection of a solid organ can be prevented without the use of toxic immune suppressive medications by inducing a condition called mixed chimerism, which is characterized by the presence of recipient and donor blood cells after transplantation. Our studies are expected to lead to the identification of novel, safe and potent therapeutic approaches to treat Veterans against GVHD or organ rejection by stimulating mixed chimerism, while preventing the relapse of the cancer.

PI_NAMEs: INCE, MIRAC NEDIM (contact)

PROJECT_TERMS: Achievement;agent orange;Antigen-Presenting Cells;Antigens;B-Cell Neoplasm;Blood Cells;Blood donor;Bone Marrow Cell Transplantation;Bone Marrow Cells;Bone Marrow Purging;Bone Marrow Transplantation;cancer recurrence;Cancer Relapse;cancer risk;Carcinogens;Cell Survival;Cells;chemotherapy;Chemotherapy and/or radiation;Chimerism;Clinical;clinical practice;Clinical Protocols;Complication;conditional knockout;conditioning;Critical Pathways;Development;Disease;Dose;Elements;end-stage organ failure;environmental agent;Exposure to;Generations;Genetic;Goals;Graft Rejection;graft vs host disease;Graft-Versus-Tumor Induction;gut colonization;Helminths;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;High Dose Chemotherapy;high risk;Hygiene;Immune;Immune system;Immune System Diseases;Immune Tolerance;Immunomodulators;immunoregulation;Intestines;irradiation;Kidney Failure;Knockout Mice;Knowledge;leukemia/lymphoma;Lymphocyte;Malignant Neoplasms;Mediating;member;microorganism;Military Personnel;military service;Modeling;Mus;neoplastic cell;novel;novel strategies;novel therapeutic intervention;Organ;Organ failure;organ transplant rejection;Organ Transplantation;Outcome;Pathway interactions;Patients;Peptides;Peripheral;Pharmaceutical Preparations;Population;Preparation;preservation;prevent;Procedures;Property;Protocols documentation;recurrent infection;Regimen;Regulation;Regulatory Pathway;Relapse;relapse prevention;Research;response;Risk;Role;Signal Pathway;Signal Transduction;small molecule;Soldier;Solid;T-Lymphocyte;Therapeutic;Thymectomy;Thymus Gland;Tissues;tool;Transforming Growth Factor beta;transplant model;Transplant Recipients;Transplantation;Transplantation Tolerance;Treatment Protocols;treatment strategy;tumor;Veterans

PROJECT_TITLE: Mixed Chimerism-Dependent Tolerance After Myeloablative Bone Marrow Transplantation


ORG_CITY: SAN ANTONIO

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

PHR: Parkinson’s disease (PD) is a major cause of morbidity and mortality in the Veteran population, comprising an increasingly prevalent neurodegenerative disease with profound motor, cognitive, and behavioral dysfunction. More than a million Americans suffer from PD, of whom more than 80,000 are Veterans, and about 50,000 new cases are diagnosed annually. The burden of PD is especially heavy in the Veteran population, due in part to the aging demographic – age is the best documented risk factor – as well as the risks of traumatic brain injury and exposure to environmental neurotoxins in military settings. The total US economic burden of PD – currently $52B annually – is expected to skyrocket as almost eight million baby boomers, including many Vietnam era Veterans, have recently turned 60, the age at which PD prevalence begins to increase sharply. Identification of early diagnostic biomarkers, as we propose to do in this application, will provide the best opportunity for effective early intervention to treat the disease before disabling symptoms appear.

PI_NAMEs: CLARK, ROBERT A (contact)

PROJECT_TERMS: Acceleration;Age;age group;Age Months;aging demography;American;Animal Model;Anosmia;antagonist;Anti-Hypertensive Agents;Appetite Stimulants;arterial spin labeling;baby boomer;Behavior assessment;Behavioral;Biochemical;Biochemistry;Biological Markers;biomarker identification;Brain;Brain region;Cerebral cortex;Cerebrovascular Circulation;Clinic;Clinical;clinical diagnosis;Cognitive;Dependence;Detection;Development;Diagnosis;diagnostic biomarker;Diffusion Magnetic Resonance Imaging;Disabling;disabling symptom;Disease;Disease Progression;Dopamine;early detection biomarkers;Early Diagnosis;Early identification;Early Intervention;Economic Burden;Event;Exhibits;Exposure to;functional decline;Functional disorder;Functional Magnetic Resonance Imaging;High Fat Diet;Homeostasis;Hormones;Human;Imaging technology;Immunohistochemistry;Impairment;improved outcome;Inflammation;innovation;insight;interest;Journals;Lead;Learning;Letters;Link;Magnetic Resonance Imaging;Measurable;Mediator;Metabolic;Metabolism;Military Personnel;military veteran;mitochondrial dysfunction;Modality;Morbidity - disease rate;mortality;Motor;mouse model;multimodality;Mus;Nerve Degeneration;Neuroanatomy;neurobehavioral test;Neurodegenerative Disorders;neuroimaging;neuroinflammation;Neurons;Neurosciences;Neurotoxins;Non-Insulin-Dependent Diabetes Mellitus;novel;olfactory bulb;Olfactory dysfunction;Olfactory Pathways;Onset of illness;overexpression;Oxidative Stress;Oxidative Stress Induction;Parkinson Disease;Pathogenesis;Pathology;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;pre-clinical;Prevalence;prevent;Printing;Process;Publications;receptor;Renin-Angiotensin System;Reporting;Research;Resolution;response;Risk;Risk Factors;Role;Signaling Molecule;Smell Perception;Symptoms;synuclein;synucleinopathy;Testing;Toxic effect;Transgenic Mice;Translating;Traumatic Brain Injury;Up-Regulation;Veterans;Vietnam;Work

PROJECT_TITLE: Analysis of Olfactory Dysfunction for Early Diagnosis of Parkinson's Disease


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health

ORG_CITY: BOSTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling condition. The goal of the proposed training program is to provide advanced training and professional development experiences to postdoctoral fellows who will comprise the next generation of expert clinical scientists in this important public health area.

PI_NAMEs: KEANE, TERENCE M;SLOAN, DENISE M. (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TITLE: Postdoctoral Training Program in Stress and Trauma


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;HIV/AIDS;Infectious Diseases;Urologic Diseases

PHR: NARRATIVE This project will determine the importance of different mechanisms that allow HIV persistence in gastrointestinal, genitourinary, and adipose tissues. Duplication of HIV DNA by cell division, transmission of HIV RNA between cells within tissues, and trafficking of virus between these tissues may all contribute to HIV persistence. This study will analyze and compare these processes, so that HIV cure research can focus on the critical obstacles to eradication of the virus from these under-studied organ systems.

PI_NAMEs: RIVERA-NIEVES, JESUS ;SMITH, DAVID MITCHELL (contact)

PROGRAM_OFFICER_NAME: NGUYEN, KHOA DINH DANG

PROJECT_TERMS: Address;Adipose tissue;Aftercare;Age;Aging;Altruism;Anti-Retroviral Agents;antiretroviral therapy;assault;Automobile Driving;Autopsy;Bayesian Method;Binding;biomarker panel;Blood;Blood specimen;Body System;CD4 Positive T Lymphocytes;Cell division;cell motility;Cell Proliferation;Cells;Cessation of life;Clonal Expansion;Clonality;cohort;Collecting Cell;Cytometry;Data;Data Set;defined contribution;density;Development;digital;DNA;DNA Sequence;Enrollment;Environment;Event;Gastroenterology;gastrointestinal;Gastrointestinal tract structure;Genetic Transcription;Genitourinary system;genome sequencing;Gifts;Health;HIV;HIV Genome;Human;ileum;Immune;Immunologic Markers;Immunologics;Immunology;improved;Individual;Inflammation;innovation;insight;integration site;interest;Interruption;Intra-abdominal;Length;Linear Models;Macrophage;Maps;Mass Spectrum Analysis;Measures;migration;Modernization;Mucous Membrane;National Institute of Diabetes and Digestive and Kidney Diseases;novel;Participant;Pathogenesis;Pathway interactions;Penetration;peripheral blood;Persons;Pharmaceutical Preparations;Phenotype;Plasma;Predisposition;Process;Prostate;Proviruses;reproductive tract;Research;response;RNA;Role;Site;Source;subcutaneous;Time;Tissue Sample;Tissues;trafficking;trait;transmission process;urogenital tract;Viral;viral rebound;Viremia;virology;Virus;Work

PROJECT_TITLE: HIV Persistence and Renewal in the Gastrointestinal, Genitourinary and Adipose Tissues

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-J(50)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Palliative Care;Prevention

ORG_CITY: LITTLE ROCK

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Cancer is the second leading cause of death in the US. The Partnership in Cancer Research program provides hands-on experiences in cancer research coupled with knowledge of cancer biology and clinical care to ignite the imagination of future physicians to solve difficult problems and improve cancer outcomes.

PI_NAMEs: KENDRICK, SAMANTHA  (contact)

PROGRAM_OFFICER_NAME: ZAHIR, NASTARAN

PROJECT_TERMS: Active Learning;Address;Affect;anti-cancer research;Antineoplastic Protocols;Arkansas;Basic Science;Behavioral Research;Biomedical Research;Cancer Biology;cancer rehabilitation;Cancer Research Project;cancer therapy;career;Career Choice;Caring;Cause of Death;Cellular biology;Clinic;Clinical;clinical care;clinical practice;Clinical Research;Clinical Trials;cohort;Communities;community engaged research;community setting;Coupled;Course Content;design;Diagnosis;education planning;education research;Educational Activities;Educational Grants;Entrepreneurship;Evaluation;experience;Faculty;Future;Goals;health care availability;Health Policy;Health Services Accessibility;Heart;Hour;Imagination;Improve Access;improved;Individual;innovation;insight;interest;Knowledge;Laboratories;Learning;Malignant neoplasm of cervix uteri;Malignant neoplasm of lung;Malignant Neoplasms;Medical;Medical Students;Medicine;member;Mentors;Molecular and Cellular Biology;Molecular Biology;Obesity;Outcome;outcome disparities;palliation;Palliative Care;Participant;Patients;Persons;Physicians;Population;Poverty;Prevention;programs;Public Health;Quality of life;recruit;Reporting;Research;Research Personnel;Research Project Grants;Science;Screening for cancer;Secure;simulation;social media;Specialist;student participation;Students;Support Groups;Surveys;Testing;Time;Training;Underrepresented Minority;Universities;Vision;Visit

PROJECT_TITLE: Partnership in Cancer Research (PCAR)


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Pulmonary hypertension (PH), despite new therapeutic advances, continues to be associated with significant morbidity and mortality. It is increasingly clear that inflammation plays a critical role in the disease, yet at present, there are no therapies that effectively ameliorate this component of the disease process. This proposal seeks to uncover novel pathogenic processes linking pulmonary vascular inflammation and vascular remodeling. In this proposal we test the hypothesis that early and persistent pulmonary vascular specific activation of complement leads to persistent inflammation and vascular remodeling. We propose to uncover new biomarkers and new targets for intervention in this devasting disease.

PI_NAMEs: STENMARK, KURT R. (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: adaptive immunity;Address;Age;Animal Model;Animals;antibody detection;Automobile Driving;Biological Markers;Biological Models;biomarker identification;Blood Platelets;Blood Vessels;Cattle;Cells;Cessation of life;Chimeric Proteins;Chronic;circulating biomarkers;Clinical;Complement;Complement Activation;complement pathway;Development;Diagnosis;Disease;disease heterogeneity;Disease Progression;Endothelium;Environment;Experimental Animal Model;extracellular;Extracellular Matrix;Gene Modified;Genetic Heterogeneity;Genetic Processes;Genetic Transcription;Goals;Heterogeneity;Human;Hypoxia;hypoxia-induced pulmonary hypertension;Image;Immunity;Immunoglobulins;in vivo;Individual;individualized medicine;Inflammation;Inflammatory;inhibitor;Intervention;Investigation;Lesion;Link;Lung;lung vascular inflammation;Macrophage;Mass Spectrum Analysis;Mediating;Methodology;Modeling;Molecular;Molecular Profiling;Monoclonal Antibodies;monocyte;Morbidity - disease rate;mortality;Mouse Protein;Mus;Natural Immunity;neoantigens;novel;novel therapeutics;Pathogenesis;Pathogenicity;Pathologic;Patients;Peptide Initiation Factors;Phenotype;Platelet Activation;Play;Positioning Attribute;Process;Proteome;Proteomics;pulmonary arterial hypertension;Pulmonary arterial remodeling;Pulmonary Hypertension;pulmonary vascular disorder;Rattus;recruit;Research Personnel;Resolution;Role;Schistosoma;Schistosomiasis;sex;Shapes;Signal Transduction;Site;SU 5416;T-Lymphocyte;Techniques;Testing;Thrombospondin 1;Tissues;translational goal;Transplantation;treatment response;United States Food and Drug Administration;vascular inflammation;Vascular remodeling

PROJECT_TITLE: Complement Mediated Remodeling in Pulmonary Vascular Disease


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Alzheimer’s disease (AD) is a progressive brain disorder characterized by the death of the nerve cells that control memory and thinking skills, leading to the inability of the person to carry out daily activities. AD is linked to inflammation and metabolism defects. This proposal will investigate if altered expression of a protein that binds fatty acids, and regulates inflammation and metabolism, plays a role in the progression of the disease in AD patients and mouse models.

PI_NAMEs: PEHAR, MARIANA ATINA (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: Abeta clearance;adeno-associated viral vector;Affect;aged;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-Protein;Anti-Inflammatory Agents;APP-PS1;Appearance;Arachidonic Acids;association cortex;Astrocytes;behavior test;Biological Markers;Biology;Brain Diseases;Cell Culture Techniques;Cell Physiology;Cellular Metabolic Process;Central Nervous System;Cerebrospinal Fluid;Clinical;Cognitive;cyclooxygenase 2;cytokine;Cytoplasmic Granules;Data;Defect;Dementia;Development;Disease Progression;Docosahexaenoic Acids;Down-Regulation;Elderly;Endoplasmic Reticulum;Energy-Generating Resources;enzyme substrate;extracellular;fatty acid metabolism;fatty acid-binding proteins;Fatty Acids;Functional disorder;Gene Expression;gene therapy;Genetic Transcription;Gliosis;Goals;Growth;Human;human induced pluripotent stem cells;human subject;immunoregulation;Impaired cognition;Impairment;in vivo;Individual;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Innate Immune Response;innovation;Intracellular Transport;Ligands;Link;lipid metabolism;lipid transport;Lipids;Longitudinal Studies;Mediating;Memory;Metabolic;Metabolism;metabolomics;Mitochondria;mitochondrial dysfunction;Molecular;Monitor;mouse model;Mus;Nerve Degeneration;Neurites;Neurofibrillary Tangles;neuroinflammation;neuron loss;neurotoxicity;novel;novel marker;Outcome Measure;Oxidative Stress;Participant;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peroxisome Proliferator-Activated Receptors;Persons;Phenotype;Positron-Emission Tomography;postnatal;PPAR gamma;preclinical study;Process;Production;Proteomics;Receptor Signaling;Regulation;Research;Resolution;response;Risk;Role;Sampling;Senile Plaques;Signal Transduction;Signaling Molecule;skills;Symptoms;System;tau aggregation;Testing;Therapeutic;therapeutic target;Thinking;transcription factor;transcriptomics;translational study;Treatment Efficacy;Up-Regulation;uptake;Wisconsin

PROJECT_TITLE: A link between lipid-mediated signaling and inflammation during neurodegeneration

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-Z(55)]


NIH_SPENDING_CATS: Lung;Pulmonary Hypertension

PHR: The core will provide administrative support and the overall leadership for the scientific integration of all projects in the PPG. It is responsible for financial oversight of all projects and for direct communication with the University’s involved and with the NIH. The PI, Dr. Stenmark has significant experience in directing large multidisciplinary programs.

PROJECT_TERMS: Advisory Committees;Animals;Bioinformatics;Biology;Biometry;Blood Vessels;Budgets;California;Clinic;clinical database;clinical translation;Collaborations;Colorado;Communication;Community Outreach;Complement;Complex;Contracts;Documentation;Education;Effectiveness;Ensure;Equipment;Expenditure;experience;Fostering;Grant;Health;Hospitals;human tissue;Hypoxia;IACUC;Image;Individual;Institutional Review Boards;Leadership;Link;Lung;mathematical model;Mediating;meetings;Monitor;multidisciplinary;National Center for Research Resources;Phenotype;Plasma;Productivity;Program Research Project Grants;programs;Progress Reports;Pulmonary Hypertension;pulmonary vascular disorder;Recommendation;repaired;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Rest;Safety;Sampling;San Francisco;Service delivery model;Site;statistical service;Suggestion;tool;Training;Translational Research;United States National Institutes of Health;Universities;Washington;web site

PROJECT_TITLE: Administrative Core


PHR: The animal core will act as repository and center for distribution of the mice rats and bovine animals proposed in the program. It provides a unique infrastructure that allows for successful and reproducible generation of the animal models used and provides state of the art hemodynamic assessments.

PI_NAMEs: IRWIN, DAVID CHARLES (contact)

PROJECT_TERMS: Animal Euthanasia;Animal Husbandry;Animal Model;animal tissue;Animals;Blood gas;Blood Gas Analysis;Blood Pressure;Blood Pressure Monitors;Blood specimen;Breeding;Cardiac Output;Catheters;Cattle;Chronic;Clinical;clinical application;Collection;Complement;Data;data acquisition;Data Analyses;Data Collection;data integrity;Dyes;Echocardiography;Ensure;Equipment;Euthanasia;Experimental Designs;Flow Cytometry;Generations;Goals;heart function;hemodynamics;Human;Human Resources;Hypoxia;IACUC;Image;Inbred Mouse;Infrastructure;Institution;instrumentation;Insurance;Leadership;Liquid substance;Maintenance;Mediating;Methodology;Methods;Mission;Modeling;Molecular;Monitor;mouse model;Mus;non-invasive monitor;Organ;Organ Harvestings;Pathology;Play;Postdoctoral Fellow;Process;Program Research Project Grants;programs;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vasoconstriction;Rattus;repository;Reproducibility;Research Personnel;Role;Sampling;Schedule;Severities;Signal Transduction;solid state;Standardization;synergism;System;Tail;Technical Expertise;Technology;Tissue and Organ Harvesting;Tissue Banks;Tissue Fixation;Tissue Sample;Tissues;tool;Training;Transducers;Transgenic Mice;Transgenic Model;Vascular remodeling

PROJECT_TITLE: Animal Core