NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Digestive Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Stomach Cancer

PHR: PROTEOMICS AND METABOLOMICS CORE B NARRATIVE The use of state-of-the-art proteomics, metabolomics, and imaging mass spectrometry technologies in the three Projects will identify protein, lipid, and metabolite changes in gastric cells and bacterial cells that play important roles in gastric cancer.

PI_NAMEs: SCHEY, KEVIN L (contact)

PROJECT_TERMS: Algorithms;Animal Model;Area;Bile Acids;biological systems;Biopsy;cancer biomarkers;carcinogenesis;Cells;Collaborations;Complex;Consultations;Core Facility;Data;Data Analyses;Databases;Dedications;Deoxycholic Acid;Development;Dietary Factors;Dimensions;Elements;Ensure;Environment;Experimental Designs;experimental study;flexibility;gastric carcinogenesis;gastric organoids;Gastric Tissue;Genome;Gerbils;Goals;Helicobacter Infections;Helicobacter pylori;Histopathology;Homeostasis;Human Resources;human tissue;Image;imaging modality;Immunohistochemistry;In Vitro;Individual;Inductively Coupled Plasma Mass Spectrometry;Inflammation;informatics tool;inhibitor;Institution;instrumentation;Iron;Label;Lesion;lipidomics;Lipids;Location;malignant stomach neoplasm;mass spectrometer;mass spectrometric imaging;Mass Spectrum Analysis;Measurement;Measures;Metabolic;metabolome;metabolomics;Methodology;Methods;Modeling;Modification;Molecular;Molecular Analysis;molecular imaging;molecular marker;multiple reaction monitoring;Mus;new technology;new therapeutic target;novel strategies;Organoids;Pathogenicity;Patients;Peptides;Performance;Play;Post-Translational Protein Processing;Predisposing Factor;premalignant;Preparation;Protein Analysis;protein expression;protein metabolite;Proteins;Proteome;Proteomics;Research;Research Personnel;Resolution;response;Rodent;Role;Running;Sampling;Services;Sodium Chloride;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Speed;stable isotope;Stomach;synergism;Technology;therapeutic target;Tissue imaging;Tissue Microarray;Tissue Sample;Tissues;tool;Training;treatment response;uptake;Validation

PROJECT_TITLE: Proteomics and Metabolomics


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Neurosciences;Pediatric

ORG_CITY: CHAPEL HILL

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROLOGY

ORG_FIPS: US

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that affects over 6.1 million children in the United States and approximately 5-10% of children worldwide. Individuals with and without clinical ADHD diagnoses can experience a wide range of ADHD symptoms; therefore, understanding the neural substrates that underlie the heterogeneous ADHD phenotype will allow for better transdiagnostic identification of individuals who may benefit from treatment for ADHD-related symptoms. Thus, the proposed studies will implement a dynamic functional connectivity approach and assess behavioral variability associated with ADHD symptom burden within and across diagnostic categories to better understand the neurobiology of the ADHD phenotype.

PI_NAMEs: CASCONE, ARIANNA DAME (contact)

PROGRAM_OFFICER_NAME: CORNELL, ASHLEY ROSE

PROJECT_TERMS: Adult;Affect;Age;Algorithms;Attention deficit hyperactivity disorder;Behavior;Behavior assessment;Behavioral;Behavioral Symptoms;Brain;Categories;Child;Childhood;Classification Scheme;Clinical;clinical diagnosis;clinically relevant;cognitive control;Communities;comparison control;Data;Detection;Development;Diagnosis;Diagnostic;Dimensions;Disease;emotional symptom;Exhibits;experience;Functional Magnetic Resonance Imaging;Future;Goals;Heterogeneity;Hyperactivity;Impairment;improved;Impulsivity;inattention;Individual;Intervention;Investigation;Link;Literature;Measures;Methods;National Research Service Awards;neural;Neurobiology;Neurodevelopmental Disorder;Neuronal Dysfunction;novel;Outcome;Participant;Pattern;Performance;Phenotype;Population;pre-doctoral;Process;Reaction Time;Research;Research Personnel;response;Rest;Risk;Sampling;Social outcome;Subgroup;Symptom Burden;Symptoms;Techniques;Thinking;Training;Transcend;United States;Variant

PROJECT_TITLE: Categorical and dimensional investigations of dynamic functional connectivity and behavior during response inhibition in children with and without ADHD


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: LEXINGTON

ORG_NAME: VA MEDICAL CENTER - LEXINGTON, KY

ORG_STATE: KY

PHR: Many Veterans experience low-level blast (LLB) exposure during tour of duty and training operations. The extent of chronic post-traumatic stress disorder (PTSD) traits after cumulative LLB exposure is unknown. Additionally, there is no clear understanding of which pathological mechanisms drive impairment after LLB exposure. The overall objective of this application is to determine the timing of acute neurovascular dysfunction after LLB and how repeating LLB contributes to chronic neurovascular impairment and neuropsychological deficits. We will examine the behavioral profile and neurovascular outcomes after LLB, coupled with pathologically relevant biomarkers. This research will improve our understanding of the effects of LLB and identify biomarkers for neurological injury. The proposed mentored research plan will increase understanding of the chronic effects of occupational blast exposure to identify therapies which will improve Veteran health while providing a foundation for the applicant’s independent VA research program.

PI_NAMEs: HUBBARD, WILLIAM BRAD (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Address;Affect;Aggressive behavior;Aging;Amygdaloid structure;Animal Model;Animals;Anxiety;arterial spin labeling;Behavior;Behavior assessment;behavior test;Behavioral;behavioral impairment;Bioenergetics;Biological Assay;Biological Markers;biomarker identification;blast exposure;Blast Injuries;Blood - brain barrier anatomy;Blood Platelets;Blood Vessels;blood-based biomarker;blood-brain barrier disruption;Brain;Brain region;career development;cerebrovascular;Cerebrovascular Circulation;cerebrovascular reactivity;Chronic;Chronic Post Traumatic Stress Disorder;Clinical;clinically relevant;cohort;Coupled;Data;depressive symptoms;Development;Development Plans;Euthanasia;exosome;experience;Exposure to;Foundations;Functional disorder;Grant;Health;Image;Immunohistochemistry;Impairment;improved;inhibitor;Investigation;Kentucky;Knowledge;Life;Literature;Matrix Metalloproteinases;Measures;Mentors;MicroRNAs;Military Personnel;military veteran;Modeling;multimodality;Nervous System Trauma;Neurocognitive;neuroimaging;Neurologic Deficit;Neurologic Dysfunctions;Neurological outcome;Neurons;neuropathology;Neuropsychology;neurovascular;neurovascular unit;novel;Occupational;Occupational Exposure;operation;Outcome;Pathologic;Peripheral;Phenotype;phosphodiesterase V;Post-Traumatic Stress Disorders;pre-clinical;Predisposition;pressure;primary outcome;programs;Proteins;psychologic;psychological outcomes;Publishing;Rattus;Recording of previous events;Recovery;Reporting;Research;Research Personnel;restoration;Risk;Rodent;Rodent Model;Role;Serum;sildenafil;skills;Social Interaction;Soldier;Stains;stress related disorder;student mentoring;Symptoms;Techniques;Testing;Therapeutic;therapeutic target;Time;time interval;Tissues;Training;Training Programs;trait;Universities;Vascular Diseases;Veterans;Writing

PROJECT_TITLE: Psychological deficits after low level blast exposure: role of neurovascular disruption


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: Military personnel deployed to Afghanistan and Southwest Asia were exposed to high levels of fine particulate matter. Although there is concern about adverse respiratory health effects, objective evidence of exposure- related disease is limited. We will conduct respiratory health assessments in 280 participants in VA Cooperative Study #595 “Service and Health Among Deployed Veterans (SHADE)” at four sites (Boston, Minneapolis, Seattle, Houston). CT imaging will be used assess whether these Veterans have structural lung disease and will be combined with health assessments from the other sites. This information will be use to define exposure related pulmonary disease that will have clinical utility for the recognition of Veterans with deployment-related lung disease and the development of future treatment strategies.

PI_NAMEs: GARSHICK, ERIC  (contact)

PROJECT_TERMS: Address;Afghanistan;airway inflammation;airway obstruction;Alveolus;Asia;attenuation;base;Biochemical;Biological Markers;Boston;burn pit;Chronic Obstructive Pulmonary Disease;chronic respiratory disease;Clinical;clinical application;Clinical Research;Cluster Analysis;Complement;cooperative study;Coughing;Country;Deposition;design;Development;Diameter;Diffusion;Disease;disorder subtype;Dose;dust storms;Dyspnea;Enrollment;Eosinophilia;eosinophilic inflammation;Epidemiology;Exhalation;experience;Exposure to;fine particles;Forced expiratory volume function;former smoker;Future;Gases;Health;health assessment;Human Resources;Hypersensitivity;IgE;immune activation;Immune response;Impairment;Industrialization;injured airway;Iraq;Lead;Location;Lung;Lung Diseases;Medical center;meter;Military Personnel;never smoker;Nitric Oxide;Obstructive Lung Diseases;Participant;particle;Particulate Matter;Patients;Phenotype;Physiological;Prevalence;programs;Pulmonary Emphysema;pulmonary function;Questionnaires;Records;recruit;Reporting;respiratory health;Respiratory Signs and Symptoms;Scanning;Services;Shortness of Breath;Site;small airways disease;Smoke;Smoking History;sound;Source;Spirometry;Structural defect;Symptoms;Testing;Time;treatment strategy;United States National Aeronautics and Space Administration;Veterans;Vital capacity;wasting;Wheezing;X-Ray Computed Tomography

PROJECT_TITLE: CMA: Pulmonary and Systemic Effects of Deployment Related Particulate Matter Exposures


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Chronic Pain;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Prolonged use of opioid agonists such as fentanyl, resulting from chronic pain management and from illicit use, induce physical dependence and withdrawal, and a paradoxical decrease in pain tolerance (opioid-induced hyperalgesia, OIH). Opioid withdrawal and OIH are associated with enhanced neural excitability in the central amygdala, but the specific circuits affected, and the behavioral implications of hyperexcitability in those cell types, are not completely understood. This proposal will investigate the impact of fentanyl dependence on neural activity characterized cell type-specific ascending pain pathway between the parabrachial nucleus and the central amygdala and examine how its activity drives withdrawal and OIH.

PI_NAMEs: WOOLDRIDGE, LISA  (contact)

PROGRAM_OFFICER_NAME: BABECKI, BETH

PROJECT_TERMS: Address;Affect;Amygdaloid structure;Analgesics;Animals;antagonist;Anterior;associated symptom;Attenuated;Automobile Driving;Aversive Stimulus;Behavior;Behavior Control;Behavioral;behavioral pharmacology;Biological Assay;Brain;Calcium;career;cell type;Cells;Chronic;chronic pain management;Clinical;Coupled;Dependence;drinking water;endogenous opioids;Experimental Designs;Fentanyl;fentanyl exposure;Fiber;FOS gene;Foundations;Functional disorder;Future;Genetic;genetic manipulation;Glutamates;Goals;GTP-Binding Proteins;Hyperactivity;Hyperalgesia;Image;Immediate-Early Genes;in vivo;in vivo calcium imaging;Investigation;Knowledge;Lateral;Life;Mediating;Mediator;Modeling;Molecular Target;mouse model;Mus;neural;neural circuit;Neurons;neuroregulation;Neurosciences;Neurosciences Research;Nociception;novel therapeutics;Opiate Addiction;Opioid;Opioid agonist;opioid exposure;opioid misuse;Opioid Receptor;opioid use;opioid use disorder;opioid withdrawal;Pain;Pain management;Pain Threshold;parabrachial nucleus;Pathway interactions;Patients;Photometry;Physical Dependence;Pontine structure;Population;Predisposition;prescription opioid;Process;protein kinase C-delta;Public Health;Recreation;Repression;Research Personnel;response;Rewards;Rodent;Role;side effect;Signal Transduction;statistics;Stimulus;Substance Withdrawal Syndrome;synthetic opioid;Techniques;Training;Viral;Viral Vector;Withdrawal;Work

PROJECT_TITLE: Impact of fentanyl dependence on a parabrachio-amygdalar opioid circuit


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Military personnel deployed to Afghanistan and Southwest Asia were exposed to high levels of fine particulate matter. Although there is concern about adverse respiratory health effects, objective evidence of exposure- related disease is limited. As a participating center in VA Cooperative Studies Program #595, Service and Health Among Deployed Veterans (SHADE), we have the unique opportunity to further define exposure related pulmonary findings. We will conduct additional in-depth respiratory health assessments in a subset of 280 participants in SHADE at four sites (Seattle, Boston, Minneapolis, and Houston). In this proposal, three additional clinical physiologic tests will be performed (diffusing capacity, impulse oscillometry, and nitrogen multiple breath washout) that will be combined with health assessments from the other sites. This information will be used to define early air-pollution related pulmonary disease that has the potential to help in the recognition and treatment of Veterans with deployment-related lung disease.

PI_NAMEs: FAN, VINCENT S (contact)

PROJECT_TERMS: Address;Afghanistan;Air;Air Pollution;airway obstruction;Airway Resistance;Alveolus;Asia;associated symptom;Biochemical;Biological Markers;Blood;Boston;Breath Tests;Bronchiolitis;burn pit;Carbon Monoxide;Case Series;chronic respiratory disease;Clinical;Clinical Research;Cluster Analysis;Complement;cooperative study;Coughing;Country;Data;Deposition;Development;Diameter;Diffusion;Disease;disorder subtype;dust storms;Dyspnea;Enrollment;eosinophilic inflammation;Epidemiology;epidemiology study;experience;Exposure to;fine particles;former smoker;Functional Residual Capacity;Funding;Future;Gases;Goals;Health;health assessment;Healthcare Systems;Heterogeneity;Human Resources;IgE;immune activation;Immune response;Impairment;indexing;Industrialization;injured airway;interstitial;Iraq;Location;Lung;Lung CAT Scan;Lung Diseases;lung injury;lung volume;Measurement;Measures;Mechanics;meter;Military Personnel;never smoker;Nitrogen;Obstructive Lung Diseases;Oscillometry;Oxygen;Parents;Participant;particle;Particulate Matter;Peripheral;Physiological;Physiology;Population;programs;Pulmonary Emphysema;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Questionnaires;Records;recruit;Reporting;Research;Respiratory Disease;respiratory health;Respiratory Signs and Symptoms;Services;Shortness of Breath;Site;small airways disease;Smoke;Smoker;Smoking History;Solid;sound;Source;Spirometry;Structural defect;Symptoms;Testing;Thick;Time;ventilation;Veterans;wasting;Wheezing;X-Ray Computed Tomography


ORG_CITY: MINNEAPOLIS

ORG_NAME: MINNEAPOLIS VA  MEDICAL CENTER

ORG_STATE: MN

PHR: Relevance: Military personnel deployed to Southeast Asia (SA) report increased respiratory symptoms relative to non-deployed. Unique to SA deployment is a history of exposure to high levels of airborne particulate matter ≤ 2.5 µm in diameter (PM2.5) consisting of seasonal dust storms, burn-pit smoke, and unregulated industrial and vehicular pollutants. Objective findings among returning Veterans are limited and specific pulmonary conditions attributed to symptoms and PM2.5 exposure remain unknown. As a participating center for the VA Cooperative Study #595 Service and Health Among Deployed Veterans (SHADE) we have the unique opportunity to define exposure related pulmonary findings. The resultant exposure-related disease types identified have potential clinical utility in the recognition and development of future treatment and management strategies for Veterans with deployment-related lung disease.

PI_NAMEs: KHERADMAND, FARRAH ;WENDT, CHRIS H (contact)

PROJECT_TERMS: Adaptive Immune System;Airborne Particulate Matter;airway inflammation;airway obstruction;Asia;Asthma;Autoantigens;Biochemical;Bioinformatics;Biological Markers;biomarker discovery;Biometry;Biophysics;Boston;burn pit;Cells;Chronic;Clinical;clinical application;Cluster Analysis;cohort;Complement;cooperative study;Coughing;cytokine;Data;design;Desmosine;Development;Diameter;Diffusion;Disease;disorder subtype;dust storms;Dyspnea;Early identification;Eosinophilia;eosinophilic inflammation;Exhalation;Exposure to;Fibrinogen;former smoker;Funding;Future;Gases;Goals;Health;Hypersensitivity;IgE;Immune;immune activation;Immune response;Immunity;Immunologic Markers;Immunology;Industrialization;Inflammasome;Inflammatory;injured airway;Innate Immune System;Lung;Lung Diseases;lung injury;Measurement;Measures;metabolomics;meter;Military Personnel;monocyte;multiple omics;Nitric Oxide;parent project;Participant;Particulate Matter;Patients;Phenotype;Physiological;pollutant;Predisposition;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary function tests;Pulmonary Inflammation;Quantitative Evaluations;Recording of previous events;recruit;Reporting;respiratory;Respiratory Signs and Symptoms;response;Risk;Seasons;Secretory Cell;secretory protein;Services;Site;Smoke;Smoking History;soluble RAGE;sound;Southeastern Asia;Sphingolipids;Spirometry;Structure;Structure of parenchyma of lung;Symptoms;systemic inflammatory response;Technology;Testing;treatment strategy;Veterans;Wheezing;X-Ray Computed Tomography

PROJECT_TITLE: CMA:Pulmonary and Systemic Effects of Deployment Related Particulate Matter Exposures


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: PROJECT NARRATIVE – RELEVANCE FOR PUBLIC HEALTH This research application addresses a fundamental gap in our understanding of mucosal HIV-1 transmission: How is HIV-1 infection established in the female genital tract mucosa? Fundamental questions remain unanswered regarding the significance of mucosal macrophages as early targets of HIV-1 infection, mechanisms and pathways by which cervical macrophages become infected, their role in early virus amplification and spread, and virologic and cellular determinants that affect their susceptibility to HIV-1 infection. The research proposed in this grant application will elucidate the role of tissue macrophages in establishing HIV-1 infection of cervical explant tissue, and thereby will inform the development of interventions modalities aimed at preventing mucosal HIV-1 transmission.

PI_NAMEs: KAPPES, JOHN CHRISTOPHER (contact)

PROJECT_TERMS: Address;Affect;AIDS prevention;analytical method;Applications Grants;Biology;CD4 Positive T Lymphocytes;Cells;Cervical;Characteristics;Color;Communicable Diseases;Confocal Microscopy;Data;Dose;Exhibits;Exposure to;Female;female reproductive tract;Frequencies;Heterosexuals;HIV;HIV-1;HIV/AIDS;Human;Human Resources;In Situ;Incidence;Individual;Infection;innovation;Investigation;Macrophage;men;military service;Modality;Modeling;monocyte;mucosal HIV infection;Mucous Membrane;multiparametric imaging;nonhuman primate;pandemic disease;Pathway interactions;Pharmaceutical Preparations;Physiological;Population;Predisposition;prevent;Prevention;Prevention strategy;Process;Public Health Applications Research;public health relevance;Publishing;Readiness;Recording of previous events;Reporter;reproductive tract;Research;Risk;Role;Services;SIV;spatial relationship;spatiotemporal;T-Lymphocyte;therapy development;Time;Tissues;transmission process;Tropism;Validation;Veterans;viral transmission;Virus;virus host interaction;Virus Replication;Woman;Work

PROJECT_TITLE: Elucidating mechanisms of HIV-1 mucosal transmission


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: Despite advances in treatment, lung cancer is the leading cause of cancer-related death in the U.S. Therefore, there is an urgent need to develop a new strategy for treatment to lower the lung cancer mortality. Dr. Park is investigating a new therapeutic strategy for lung cancer by creating a hostile microenvironment for immune cells. Tumor cells secrete mediators to transform immune cells to help tumor cells grow. As a result, the transformed immune cells aid tumor growth as opposed to stopping the expansion. Through this project, Dr. Park will examine the cellular and biochemical mechanisms of how the tumor cell-secreted mediator increases the number of tumor-favoring immune cells. Furthermore, he will develop new approaches to intervening the tumor-favoring immune cells to get therapeutic benefits for lung cancer treatment.

PI_NAMEs: PARK, GYE YOUNG  (contact)

PROJECT_TERMS: Adopted;Anabolism;anti-cancer;arm;Attenuated;Basic Science;Binding;Biochemical;Biopsy;Body Fluids;Cancer Biology;Cancer Etiology;cancer immunotherapy;Cancer Model;cancer therapy;Cell Lineage;Cell Proliferation;Cell secretion;Cells;Cellular biology;Cessation of life;chemokine;Chemotaxis;Clinical;clinical material;Clinical Trials;Colony-Stimulating Factors;conditional knockout;CSF1R gene;cytokine;Cytometry;Data;Dendritic Cells;Development;Encapsulated;exoenzyme;extracellular;Genes;genetic analysis;Human;Immune;immune function;Immune system;immunogenic;Immunologics;Immunologist;Infiltration;Inhalation;inhibitor;innovation;Knockout Mice;Lung;Lung Adenocarcinoma;lysophosphatidic acid;Lysophospholipase;Macrophage;Macrophage Colony-Stimulating Factor;Macrophage Colony-Stimulating Factor Receptor;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Mediator;migration;mortality;mouse model;Mouse Strains;Mus;Mutation;Myelogenous;Myeloid Cells;Nanodelivery;neoplastic cell;novel;novel strategies;novel therapeutic intervention;Oncologist;Outcome;paracrine;Pathway interactions;Patient Recruitments;Patients;Phenotype;Phospholipids;Play;Population;Progression-Free Survivals;Prospective Studies;receptor;Receptor Activation;Receptor Cell;Receptor Inhibition;Reporting;Research;Research Personnel;Role;Sampling;Stimulus;System;Tamoxifen;targeted agent;Techniques;Testing;Therapeutic;Therapeutic Effect;Therapeutic Intervention;Tissues;transcriptome sequencing;Transgenic Mice;tumor;Tumor Biology;Tumor Cell Biology;tumor growth;tumor microenvironment;tumor progression;tumor-immune system interactions;Tumor-infiltrating immune cells;ultrasound

PROJECT_TITLE: CSF1 Receptor-Mediated Tumor Microenvironment in Lung Cancer


PHR: U.S. Veterans have higher than usual rates of certain illnesses including insomnia, sleep apnea, post-traumatic stress disorder and traumatic brain injury, these all involve sleep disturbance. Because of this, many Veterans are given prescription sleep medicines, and the number of these cases has increased rapidly in recent years. Brain waves of various speeds correspond to behaviors and/or brain function. Deep and restorative Non- Rapid-Eye-Movement sleep is characterized by so called delta waves, these are slow, and they are good for mental health, memory and clear thinking. Unfortunately, modern sleep medicines reduce these healthy waves. This could be a contributing factor in why today's sleep medicines are often linked to suicide risk and mental problems. Using a cutting-edge genetic engineering tool called CRISPR-Cas9, I will examine neurocircuitry governing therapeutic effects vs side effects of sleep medicines. This pre-clinical work will lay the foundation for developing next-generation medicines, that will provide better care for our Veterans.

PI_NAMEs: UYGUN, DAVID SAMUEL (contact)

PROJECT_TERMS: Ablation;Accounting;Address;adeno-associated viral vector;Arousal;Attenuated;attenuation;Award;basal forebrain;Basic Science;Behavior;Binding;Brain;Brain region;Calcium-Binding Proteins;Caring;Cell Nucleus;Cerebral cortex;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;Cognitive deficits;cognitive performance;CRISPR/Cas technology;Data;Dependovirus;Development;Dissection;Dose;Electroencephalography;Electrophysiology (science);Eszopiclone;Excision;Foundations;GABA-A Receptor;gamma-Aminobutyric Acid;gene editing technology;gene-editing approach;General Population;Genetic;genetic approach;Genetic Engineering;genetic manipulation;Glutamates;Homeostasis;Hypothalamic structure;improved;In Vitro;in vivo;Injections;Intervention;intraperitoneal;knock-down;Lateral;Light;Link;Mediating;Medicine;Memory;men;Mental Health;Microdialysis;Modeling;Modernization;Molecular;mood regulation;Moods;mouse genetics;Mus;Neocortex;neural circuit;Neurons;neuropsychiatry;Neurotransmitters;next generation;non rapid eye movement;overexpression;Pacemakers;Parvalbumins;patch clamp;Patient Care;Patients;Periodicity;Pharmaceutical Preparations;Population;positive allosteric modulator;Post-Traumatic Stress Disorders;postsynaptic;pre-clinical;Prevalence;Proteins;Psyche structure;receptor;Regulation;Reporting;Reproducibility;Research;Research Proposals;response;Rest;Risk Reduction;Role;Sensory Receptors;side effect;Sleep;Sleep Apnea Syndromes;Sleep Disorders;Sleep disturbances;Sleeplessness;Slow-Wave Sleep;Speed;Stress;Structure;Structure of paraventricular nucleus of thalamus;suicidal risk;Synapses;Techniques;Testing;Thalamic structure;Therapeutic;Therapeutic Effect;Thinking;Time;tool;Training;Transgenic Mice;transmission process;Traumatic Brain Injury;United States;vector;vesicular glutamate transporter 2;Veterans;Woman;Work;zolpidem

PROJECT_TITLE: Using CRISPR-Cas9 genetic abscission in vivo to study the role of GABA-A receptors of the thalamic reticular nucleus in regulating non-rapid-eye-movement sleep and drug induced sleep


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Extra-articular ligaments such as the medial collateral ligament (MCL) often heal without surgery, while intra- articular ligaments such as the anterior cruciate ligament (ACL) do not. We hypothesize that the major difference between the two is access to vascular supply, specifically perivascular stem cells (PSCs). PSCs are an adult stem cell population that are associated with blood vessels throughout the body, and have been shown to differentiate into all mesenchymal lineages, including collagen-producing fibroblasts. We propose to establish that perivascular stem cells are indeed the cells responsible for extra-articular ligament repair by performing lineage tracing of PSCs in a model of MCL injury, and examining healing MCL with partial PSC ablation. Additionally, we plan to characterize the effects of PSCs on MCL healing and a scaffold-based model of ACL reconstruction. Collectively, these studies would establish the foundation for new PSC-based clinical therapies to treat ligament injury.

PI_NAMEs: LEONG, NATALIE L (contact)

PROJECT_TERMS: Ablation;Address;adult stem cell;Anterior Cruciate Ligament;anterior cruciate ligament reconstruction;anterior cruciate ligament rupture;Articular ligaments;Basic Science;Biomimetics;Blood Vessels;Cells;Clinical;clinically relevant;Collagen;collateral ligament;directed differentiation;efficacy evaluation;Event;experimental study;Fibroblasts;Foundations;Genetic;Goals;healing;health goals;Histologic;Human;improved;In Vitro;in vivo;Incidence;Infiltration;Injection of therapeutic agent;Injections;Injury;Intervention;Knee;Label;ligament injury;Ligaments;Medial;Mediating;Mesenchymal;Mesenchymal Stem Cells;Methods;military veteran;Modeling;mouse model;Mus;Natural regeneration;Occupational;Operative Surgical Procedures;Pericytes;Platelet-Derived Growth Factor beta Receptor;Play;polycaprolactone;Process;Quality of life;Rattus;reconstruction;Reconstructive Surgical Procedures;Recreation;repaired;Reporting;Role;rotator cuff injury;rotator cuff tear;scaffold;service member;Shoulder;Site;Source;Sprain;stem cell population;stem cell therapy;stem cells;Tamoxifen;Techniques;Tendon Injuries;Tendon structure;Therapeutic;Tissue Engineering;Tissues;Vascular blood supply;Vascularization;Veterans;Wild Type Mouse

PROJECT_TITLE: Role of Perivascular Stem Cells in Ligament Healing and Regeneration


ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: Toxoplasma gondii is a proliﬁc eukaryotic parasite that is widely distributed throughout the world. Infection with T. gondii can cause severe and potentially fatal brain and eye disease, especially in immunocompromised individuals. Worldwide, T. gondii is also a leading infectious cause of blindness in otherwise healthy individuals. The current ﬁrst-line therapy for T. gondii is a combination of the drugs pyrimethamine and sulfadiazine, but this regimen suffers from a number of shortcomings. These drugs must be taken for weeks to months, frequently cause toxic side effects, and are incapable of eradicating chronic infection. We need new medicines for T. gondii that are safer, better tolerated, more effective, and can be given for shorter durations.  To this end, Dr. Alday and his colleagues have screened the 68,689 compounds in the Global Health Chemical Diversity Library (GHCDL) to ﬁnd those that inhibit the growth of T. gondii. In doing so, 359 hit compounds were found that strongly inhibit the growth of this parasite. The potency of each of these has been measured and a subset of 73 highly potent and selective compounds selected for further study. All compounds in the GHCDL were chosen for their drug-like physicochemical properties that predict good absorption and distribution when taken orally. Therefore it seems reasonable to hypothesize that within the 359 compounds that strongly inhibit T. gondii growth are those that will be effective against toxoplasmosis when given orally and thus excellent starting points from which to develop new drugs. Dr. Alday's research will systematically evaluate this hypothesis in three parts. First, the potency of all 73 compounds will be veriﬁed. An initial study of the structure-activity relationships of the three most promising will be done. Secondly, Dr. Alday will determine the mechanism of action for the top 10 most promising compounds by creating resistant mutants and identifying relevant mutations using whole-genome sequencing. Finally, the effectiveness of the top 10 compounds will be tested in mouse models of infection.  Dr. Alday is a physician-scientist at Oregon Health & Science University and the Portland VA Medical Center. Clinically, he is trained in internal medicine and infectious disease (ID), rotates on the inpatient ID consult service, and has an outpatient ID clinic. His PhD is in biochemistry, with a focus on the physical chemistry of protein-protein and protein-small molecule interactions. This unusual background gives him a strong background from which to pursue the work described in this CDA application. He has worked in the Portland VAMC Experimental Chemotherapy Lab with Dr. Michael Riscoe and Dr. Stone Doggett over the past three years, developing proﬁciency in the molecular and biochemical methods needed to evaluate drugs and their mechanism of action in protozoan parasites. The work proposed in this CDA will provide Dr. Alday with further training in drug design, evaluation of drug mechanisms, and in vivo efﬁcacy studies he needs to become an independent VA investigator. As part of this training grant, he has assembled a team of senior scientists and physician-scientists with expertise in molecular parasitology and drug development. Collectively, they have mentored dozens of trainees towards independence. This panel will meet formally every six months to review Dr. Alday's progress. Additionally, this panel will provide input regarding experimental approaches, review manuscripts prior to publication, and give advise about career development. Dr. Alday will take graduate-level classes in pharmacokinetics and genome sequencing and present his work at scientiﬁc meetings. Prior to the end of this CDA, Dr. Alday will have identiﬁed promising lead compounds ready for advancement down the drug development pathway as well as new targets for future drug development efforts. Moving these leads forward will form the basis for VA Merit Review and NIH R01 grant applications that will establish him as an independent clinician-scientist devoted to caring for veterans afﬂicted by infectious diseases through service and research.

PI_NAMEs: ALDAY, PHIL HOLLAND (contact)

PROJECT_TERMS: absorption;acute infection;Anti-Infective Agents;Antibiotics;Applications Grants;Biochemical;Biochemistry;Biology;Blindness;Brain;Brain Diseases;career development;Caring;Cells;Cessation of life;Chemicals;chemotherapy;chronic infection;Clinic;Clinical;Communicable Diseases;Consult;CRISPR/Cas technology;Cyst;Data;Development;disability;Diversity Library;Doctor of Philosophy;Dose;Drug Combinations;Drug Design;drug development;Drug Evaluation;Drug Kinetics;drug mechanism;Drug resistance;drug testing;Effectiveness;effectiveness testing;efficacy study;Essential Genes;Evaluation;experimental study;Eye diseases;forward genetics;Future;Genetic;genetic approach;Genome;genome sequencing;global health;Grant;Growth;Health;Health Benefit;Healthcare Systems;HIV;Human;Immunocompromised Host;immunosuppressed;Immunosuppression;improved;in vivo;in vivo imaging system;Individual;Infection;infection burden;Inpatients;insight;Internal Medicine;K-Series Research Career Programs;Knock-out;latent infection;Lead;Libraries;Manuscripts;Measures;Medical;Medical center;Medicine;meetings;member;Mentors;Methods;Molecular;Monitor;mouse model;Mutagenesis;mutant;Mutation;new therapeutic target;novel;novel therapeutics;Open Reading Frames;Oral;Oral Administration;Oregon;Organ;Outpatients;Parasites;Parasitic infection;Parasitology;Pathway interactions;Pharmaceutical Chemistry;Pharmaceutical Preparations;Physical Chemistry;Physicians;Population;Positioning Attribute;pressure;prevent;Property;prophylactic;Protein Chemistry;Proteins;Protozoa;Publications;Pyrimethamine;reactivation from latency;Regimen;Research;Research Personnel;Resistance;resistant strain;Resources;Risk;Rotation;Savings;Science;Scientist;Senior Scientist;Serum;Services;side effect;Single Nucleotide Polymorphism;Site-Directed Mutagenesis;small molecule;Solid;Source;Stem cell transplant;Structure-Activity Relationship;Sulfadiazine;System;Testing;Time;Tissues;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Training;Transplantation;United States National Institutes of Health;Universities;Veterans;whole genome;Work

PROJECT_TITLE: Development of new drugs for Toxoplasma by advancing hits from the Global Health Chemical Diversity Library


PHR: Our military personnel and Veterans are disproportionately affected by neuropsychiatric conditions influenced adversely by stress such as depression and post-traumatic stress disorder, which are extremely debilitating and difficult to treat. While it is well known that estrogen signaling mediates stress susceptibility in females, we recently discovered that estrogen signaling—via conversion from testosterone—also mediates stress susceptibility in males. To translate this discovery into improved care for stress-related disorders we will further examine the role of estrogen signaling in animal models of stress-induced neuropsychiatric disorders. This will position us to then identify a pharmacological approach to target estrogen receptors selectively in the brain, thus conferring efficacy for stress-related disorders in both men and women without peripheral side effects. The knowledge generated from these studies will directly support the development of new treatments, offering substantial benefit to military personnel and Veterans who urgently need improved care.

PI_NAMEs: GOULD, TODD D (contact)

PROJECT_TERMS: acute stress;Affect;Age;age related;Amygdaloid structure;Animal Model;Animals;anti-depressive agents;Anxiety;Aromatase;Basic Science;Behavior;Behavioral;biological adaptation to stress;Biological Availability;Biological Markers;Brain;Caring;Data;depressive symptoms;deprivation;Development;Disease;disease model;Effectiveness;Erectile dysfunction;Estradiol;Estrogen Receptor 2;Estrogen Receptors;Estrogens;Exhibits;experimental study;Exposure to;Extinction;Female;Fright;Funding;Future;Galanin;Goals;Gynecomastia;Hormones;Human;human male;Hypogonadism;improved;in vivo evaluation;Individual;intravenous administration;Investigational Drugs;Knowledge;maladaptive behavior;male;Measures;Mediating;Mediator;men;Mental Depression;mental development;Mental disorders;Military Personnel;military veteran;Modeling;Mus;NADP;neural circuit;neuropsychiatric disorder;neuropsychiatry;novel;novel therapeutics;Nucleus Accumbens;old mice;Oral;Oral Administration;Oxidoreductase;Pathologic;Pathway interactions;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;Pharmacology and Toxicology;Phenotype;Pituitary Gland;Population;Positioning Attribute;Post-Traumatic Stress Disorders;pre-clinical;Predisposition;Prodrugs;Production;Progesterone Receptors;Property;Rattus;receptor expression;response;Risk Factors;Rodent;Rodent Model;Role;sex;side effect;Signal Transduction;Startle Reaction;Stress;stress related disorder;stress resilience;stressor;Structure;Testing;Testosterone;testosterone replacement therapy;Therapeutic;Translating;Treatment Effectiveness;Treatment Efficacy;Uterus;Veterans;Woman

PROJECT_TITLE: Estradiol treatment of stress-related psychiatric disorders in Veterans


ORG_CITY: AUGUSTA

ORG_NAME: CHARLIE NORWOOD VA MEDICAL CENTER

ORG_STATE: GA

PHR: Project Narrative The suicide rate in the United States has increased 33% from 1999 to 2017. Further, United States military veterans have an increased risk of suicide compared with the general population, and approximately 18 to 22 veterans die from suicide each day. It has been reported that up to 90% of individuals who complete suicide have an underlying psychiatric disorder, mainly PTSD or depression. Recent evidence indicate that inflammation, as manifested by increased levels of pro‐inflammatory cytokines contributes to the pathophysiology of suicidality. However, there is a critical need for studies that are designed to determine the role of specific components of the immune system in suicidal behavior in order to identify novel therapeutic targets. This application will explore the role of complement immune system in suicidal behavior using human postmortem brain tissues from suicide subjects and animal models. The findings of this study may provide avenues to develop newer therapeutic agents for suicidal behavior.

PI_NAMEs: PILLAI, ANILKUMAR  (contact)

PROJECT_TERMS: Accidents;adaptive immune response;Address;Animal Model;anti-depressive agents;Area;arm;Attenuated;Autopsy;Behavior;Behavioral Paradigm;Bone Marrow;Brain;brain behavior;brain tissue;Cessation of life;Chimera organism;Chronic;Chronic stress;Classical Complement Pathway;Complement;Complement 3;Complement Activation;Complement Factor H;Complement Inactivators;complement pathway;complement system;completed suicide;Confounding Factors (Epidemiology);cytokine;Data;Depressed mood;depressive symptoms;design;Diagnosis;Disease;experimental study;Exposure to;Feeling suicidal;Functional disorder;General Population;Goals;Human;Immune;Immune system;Immunity;Impulsivity;Individual;Infiltration;Inflammation;Inflammatory;knockout gene;Knockout Mice;Learned Helplessness;Lectin;Measures;Mediating;Mental Depression;Mental disorders;Messenger RNA;Microglia;military veteran;Modeling;monocyte;mouse model;Mus;Myeloid Cells;new therapeutic target;novel;novel therapeutics;Pathway interactions;Peripheral;Persons;Pharmaceutical Preparations;Pre-Clinical Model;Prefrontal Cortex;prevent;Proteins;Publishing;Recording of previous events;recruit;Regulation;Reporting;Risk Factors;Role;Stress;Substance of Abuse;suicidal;suicidal behavior;suicidal risk;Suicide;suicide brain;suicide rate;Therapeutic;Therapeutic Agents;trauma exposure;United States;Veterans;War

PROJECT_TITLE: Complement system and suicidal behavior


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: Inflammatory Bowel Disease is a growing problem among veterans and new approaches to repair injured epithelium are needed. We have demonstrated that enteroendocrine cells, a rare and overlooked lineage in the intestinal epithelium, are dynamically altered during injury to promote the secretion of wound repairing hormones. We have developed a novel long-term culture system of primary intestinal enteroendocrine cells that recreates key features of normal development and in vivo injury. We propose to use this system, along with animal models and cutting-edge techniques of developmental biology and computational genomics, to dissect the mechanisms by which enteroendocrine cells are dynamically regulated during injury and identify secreted factors that promote wound healing. Successful completion of the proposed aims and training plan will prepare the candidate to become an independent physician scientist identifying translational therapies derived from enteroendocrine cells for veterans suffering from intestinal and metabolic disease.

PI_NAMEs: MUEGGE, BRIAN DAVID (contact)

PROJECT_TERMS: Academic skills;Achievement;Address;Adopted;Advisory Committees;Air;Animal Model;Animals;Applications Grants;Area;Award;Biology;career;career development;Cell Culture System;Cell Culture Techniques;Cell Line;Cell Lineage;Cell Physiology;Cell Reprogramming;Cell secretion;Cells;Cellular Stress;Colon;Computational Biology;Computer Analysis;Computing Methodologies;cytokine;Data;Development;Developmental Biology;Disease;Doctor of Medicine;Doctor of Philosophy;Endocrine;Endocrine system;Endocrinology;endoplasmic reticulum stress;Ensure;Enteroendocrine Cell;epithelial injury;Epithelium;experience;experimental study;Fellowship;Foundations;Future;Genetic Transcription;Genomics;GLP-2;glucagon-like peptide 1;Goals;Goblet Cells;Grant;Growth;Growth Factor;healing;Health Priorities;Healthcare Systems;Homeostasis;Hormone secretion;Hormones;In Vitro;in vitro Model;in vivo;Inflammatory Bowel Diseases;Injury;injury and repair;insight;intercellular communication;Internal Medicine;Intestinal Diseases;intestinal epithelium;intestinal injury;Intestines;Knock-out;Knowledge;Laboratories;Liquid substance;Medical center;Mentors;Metabolic Diseases;Metabolism;Methods;microbial products;Modeling;Molecular;Monitor;monolayer;Mucous Membrane;new therapeutic target;novel;novel strategies;Outcome;Paracrine Communication;Pathway interactions;Patients;Pattern;Phenotype;Physicians;Population;Prevalence;Production;progenitor;programs;Publishing;receptor;Regulation;repaired;Research;Residencies;Resistance;Resolution;response;response to injury;Sampling;Scientist;Serotonin;Signal Transduction;single nucleus RNA-sequencing;single-cell RNA sequencing;skills;Somatostatin;Source;stem cells;Structure;symposium;System;Techniques;Technology;Testing;Training;transcriptomics;translational therapeutics;Universities;Veterans;Washington;Work;wound healing;Writing

PROJECT_TITLE: Enteroendocrine cell reprogramming during intestinal injury


PHR: Peripheral artery bypass and coronary artery bypass grafting using saphenous veins are limb and life- saving operations for Veterans, who are disproportionately affected because of high rates of tobacco use, diabetes, and obesity. Unfortunately, up to one-third of these bypass grafts fail within one to two years after placement, and there are no known therapies that decrease this failure rate, making it a highly significant clinical problem. This proposal seeks to take a new therapeutic approach to treating saphenous vein bypass grafts to prevent mid-term failure, with the goal of translating these findings to the many Veterans undergoing these procedures yearly.

PI_NAMEs: TANG, GALE LYNN (contact)

PROJECT_TERMS: Affect;Angioplasty;Animal Model;Animals;Aorta;Area;Arterial Injury;Arteries;Bypass;cell growth;cell motility;Cell Proliferation;cell type;Cells;Clinical;Clinical Trials;clinically relevant;Coronary;Coronary Arteriosclerosis;Coronary Artery Bypass;cyclin-dependent kinase inhibitor 1B;Data;Dependovirus;Diabetes Mellitus;Engraftment;Extracellular Matrix;Failure;Foundations;Future;Genotype;Goals;graft failure;Green Fluorescent Proteins;Growth;Heart failure;high risk;Human;Hyperplasia;immunodeficiency;Implant;improved;in vivo evaluation;Infection;injured;Intervention;Iron;Ischemia;Knowledge;Label;Legal patent;Life;limb loss;Limb structure;Link;Magnetic Resonance Imaging;Medial;Methods;migration;military veteran;Modeling;Myocardial Infarction;non-smoking;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Nude Rats;Obesity;operation;particle;Pathologic;Patients;Pericytes;Peripheral;Peripheral arterial disease;Phase I/II Trial;Play;prevent;Procedures;Process;Rattus;Reaction;Regulation;Reporting;Risk Factors;Role;Saphenous Vein;Secondary to;Single Nucleotide Polymorphism;Smoker;Smoking;Smooth Muscle Myocytes;SNP genotyping;success;Surface;Testing;Therapeutic;Therapeutic Agents;therapeutic target;Therapeutic Uses;Thick;Tissues;Tobacco use;Translating;Tunica Adventitia;ultrasound;Vein graft;Veins;Veterans;Work

PROJECT_TITLE: The effect of adventitial vein cells on vein graft neointimal hyperplasia


ORG_CITY: EAST ORANGE

ORG_NAME: VA NEW JERSEY HEALTH CARE SYSTEM

ORG_STATE: NJ

PHR: Traumatic brain injury remains a prevalent problem among the Veteran population. Information about the influence of genetics has proven to be very useful for other disorders, however the genetic factors affecting the response to traumatic brain injury are largely unknown. We will take advantage of a set of model strains of mice that provide a high degree of genetic variation and examine the effects of blast-induced injury and the subsequent recovery. By comparing the course of behavioral deficits between the different strains, we will be able to determine the genes that are involved in the injury induced neurodegeneration and repair. The results of this project will provide a foundation for future work optimizing injury models and identifying therapeutic approaches that can be tailored to individuals based on genetic information.

PI_NAMEs: CITRON, BRUCE A. (contact)

PROJECT_TERMS: Address;Affect;Anxiety;Behavior;behavior test;Behavioral;behavioral outcome;Biochemistry;blast exposure;Blast Injuries;Blood;Blood - brain barrier anatomy;Brain;brain dysfunction;Brain Injuries;Cells;cognitive performance;coping;design;Disease;effective therapy;experience;experimental study;Exposure to;Eye;Foundations;Functional impairment;functional outcomes;Future;Gastrointestinal tract structure;Gene Expression;Genes;Genetic;Genetic Drift;genetic information;Genetic Predisposition to Disease;Genetic Variation;Genomics;Genotype;Health;health assessment;Histologic;Human Resources;improved;Individual;Inflammatory;Injury;injury recovery;instrument;instrumentation;International;Investigation;Kidney;Laboratories;Lead;Liver;Long-Term Effects;Lung;Memory;Messenger RNA;Military Personnel;military veteran;Modeling;Molecular;Motor;mouse model;Mouse Strains;Mus;Nerve Degeneration;Neuroglia;Neurons;neuropathology;neuroprotection;Organ;Outcome;Pattern;Performance;Play;Positioning Attribute;Predisposition;pressure;Quantitative Reverse Transcriptase PCR;Recording of previous events;Recovery;Recovery of Function;repaired;Reporting;Research;Research Personnel;resilience;Resistance;resistant strain;response;response to injury;Role;Services;sex;Sex Differences;Source;Spleen;System;TBI treatment;Testing;Therapeutic;therapeutic target;Tissue-Specific Gene Expression;Tissues;transcriptome sequencing;Traumatic Brain Injury;Traumatic Brain Injury recovery;traumatic event;Tube;Veterans;Western Blotting;Work

PROJECT_TITLE: SDR: Genomic analysis of blast tube induced TBI in mice


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

ORG_STATE: MI

PHR: This project is highly relevant to the health of Gulf War Veterans because it will establish a humanized mouse model of Gulf War Veteran's Illness. This will be achieved by fecal microbiota transplantation from stool samples donated by Gulf War Veterans with this condition into mice. This approach will incorporate the exact toxicant exposure conditions to which gulf War Veterans were exposed because they are imprinted into at least the gut microbiome. This innovative model will more closely portray the symptoms of Gulf War Veteran's Illness and fill gaps in our understanding of how altered communication along the gut–brain axis contributes to this chronic health condition.

PI_NAMEs: ANGOA-PEREZ, MARIANA  (contact);KUHN, DONALD M

PROJECT_TERMS: Animal Model;Anxiety;anxiety-like behavior;associated symptom;Award;blast exposure;Bromides;burn pit;Chronic;cohort;Communicable Diseases;Communication;comorbidity;Complex;Development;diagnostic criteria;Disease;disease mechanisms study;Dose;dysbiosis;Dyspepsia;Equation;Fatigue;fecal transplantation;Frequencies;Functional disorder;Gulf War;Gulf War veteran;gut microbiome;gut-brain axis;Health;Heterogeneity;Human;humanized mouse;imprint;Individual;innovation;Insecticides;Institute of Medicine (U.S.);Knowledge;learning outcome;Link;Literature;microbiota transplantation;Minor;Modeling;mouse model;Mus;Outcome;Pathologic;Patient Self-Report;Permethrin;Persian Gulf Syndrome;Phenotype;Pilot Projects;Post-Traumatic Stress Disorders;Psychophysiologic Disorders;pyridostigmine;Reporting;Sarin;Sex Differences;stool sample;stressor;Stretching;Study models;Symptoms;Testing;toxicant;Toxicant exposure;Transplant Recipients;Uranium;Vaccines;War

PROJECT_TITLE: Humanized Mouse Model of Gulf War Veterans' Illness


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Rehabilitation;Social Determinants of Health

PHR: Project Narrative The purpose of this research is to improve quality of life for historically marginalized cancer survivors by increasing physical activity. A culturally targeted intervention that is feasible to implement in the cancer care system will be co-developed and tested with African American cancer survivors. The project will serve as a foundation for intervening with other historically marginalized cancer survivors.

PI_NAMEs: HIRSCHEY, RACHEL  (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, ANGELA R

PROJECT_TERMS: Accelerometer;Address;Adoption;Advanced Development;African American;African American population;Award;Biological Markers;cancer care;cancer health disparity;Cancer Survivor;cancer therapy;cancer type;care systems;Cause of Death;Characteristics;chemotherapy;Clinic;Clinical;Colorectal Cancer;colorectal cancer treatment;Control Groups;cost;Data;Death Rate;Development;Diagnosis;Discrimination;effectiveness testing;efficacy testing;Environment;Ethnic Population;exercise intervention;expectation;experience;Fatigue;Feedback;fitbit;Foundations;Functional disorder;Future;Goals;group intervention;Habits;Health;Health Promotion;Healthcare Systems;high risk;implementation design;implementation intervention;improved;Individual;Inflammation;interest;Intervention;Interview;Intestines;Knowledge;Lived experience;Low income;Malignant Breast Neoplasm;Malignant Neoplasms;marginalization;Measures;Mental Depression;Meta-Analysis;multi-component intervention;National Institute on Minority Health and Health Disparities;Neighborhoods;novel strategies;Oncology;Outcome;Outcome Measure;Pain;Participant;Pathway interactions;Persons;Physical activity;Pilot Projects;pilot test;Population;post intervention;Poverty;Predictive Factor;programs;Provider;Psychological reinforcement;psychosocial;Publishing;Quality of life;Race;racial population;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;recruit;Reporting;Research;Research Personnel;Resources;response;Sampling;Scientist;Self Efficacy;side effect;skills;social culture;standard care;Stress;Surveys;Survivors;Symptoms;Tablets;Technology;Testing;Text Messaging;Therapeutic Intervention;Time;Training;Treatment Protocols;Treatment Side Effects;Variant;vigorous intensity;Walking;wearable device

PROJECT_TITLE: Physical activity intervention co-created and pilot tested with African American Colorectal Cancer Survivors


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Duchenne/ Becker Muscular Dystrophy;Gene Therapy;Genetics;Heart Disease;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

ORG_STATE: CA

PHR: Project Narrative Duchenne Muscular Dystrophy is a devastating fatal genetic disease that causes muscle degeneration with no known cure. This project aims to leverage a novel strategy to engineer a full-length gene-replacement therapy and validate its efficacy in model mice. Our work will lay the foundation for future trials in higher mammals with the goal of eventual treatment and cure in patients.

PI_NAMEs: HSU, RYAN HON HEAN (contact)

PROGRAM_OFFICER_NAME: SURPRIS, MARIPIERRE PAYEN

PROJECT_TERMS: Affect;Age;Base Pairing;Behavioral;Binding;Biochemical;Bioinformatics;Biological Assay;Biological Markers;Birth;Capsid;Cardiac;Catalytic RNA;Cells;Cessation of life;Clinical Treatment;Clinical Trials;cohort;combinatorial;CRISPR/Cas technology;Data;Dependovirus;design;design and construction;Development;Disease;Disease Progression;DNA;Dose;Duchenne muscular dystrophy;Dystrophin;Electrophysiology (science);Elements;Emerging Technologies;Engineering;Enzymes;Exons;experimental study;Foundations;functional restoration;Future;Gene Delivery;gene replacement;gene replacement therapy;gene therapy;Generations;Genes;Genetic Diseases;Genetic Engineering;Genetic Transcription;Goals;Immune response;immunogenicity;improved;In Vitro;in vivo;insertion/deletion mutation;Introns;Length;Libraries;Limb structure;liver function;male;Mammals;mdx mouse;Measures;Mechanics;Mediating;micro-dystrophin;mini-dystrophin;Molecular;Monitor;Morphology;mouse model;mRNA Expression;mRNA Translation;Mus;Muscle;muscle degeneration;Muscle function;muscular dystrophy mouse model;Mutation;Myocardial Degeneration;Myocardium;new technology;Nonsense Mutation;novel;novel strategies;Paralysed;Patients;Physiological;preclinical trial;promoter;protein complex;protein expression;Protein Fragment;Proteins;Quality of life;Reaction;reconstitution;Reporter;Research;research clinical testing;Respiratory Diaphragm;RNA;RNA Splicing;Sequence Analysis;Serum;Site;skeletal;Spliceosomes;Split Genes;System;systemic toxicity;targeted delivery;Technology;technology validation;Testing;Therapeutic;Therapeutic Effect;Tissues;Toxic effect;Transcript;transcriptome;transcriptome sequencing;Translations;Variant;Western Blotting;Work

PROJECT_TITLE: A Novel Technology for Full-Length Gene Replacement Therapy of Duchenne Muscular Dystrophy

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Mental Health;Mental Illness;Neurosciences

ORG_CITY: DALLAS

ORG_DEPT: PSYCHIATRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE: The proposed research is relevant to public health because Major Depressive Disorder represents a major national cost measured by both patient suffering and economic burden; and despite significant advances in care, a third of patients remain treatment-resistant. Upon conclusion, we will understand the role for changes in lateral habenula activity in reduced reward responsivity after stress. This discovery will stimulate new therapeutic avenues directed at targeting these changes to restore reward responsivity in depression.

PI_NAMEs: SHABEL, STEVEN  (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TERMS: Acute;acute stress;Adult;Affect;Anhedonia;Animals;Behavior;Behavioral;Brain;Brain imaging;Brain region;Caring;Chronic;Chronic stress;Consumption;Cost Measures;Data;Decision Making;design;disability;Disease;Economic Burden;effective therapy;Effectiveness;Electrophysiology (science);Fiber;Future;Grant;Habenula;Hyperactivity;Image;improved;in vivo;Investigation;Lateral;Major Depressive Disorder;Measures;Mental Depression;Modeling;Molecular;Mus;Neurons;neurotransmission;novel therapeutics;Output;Pathology;Patients;Pharmaceutical Preparations;Phase;Photometry;preference;Process;Protocols documentation;Public Health;Punishment;Research;Resistance;response;reward processing;Rewards;Risk Factors;Role;Shock;side effect;Signal Transduction;Slice;social defeat;social stress;Specific qualifier value;Stress;Sucrose;Tail;Testing;two-photon;Validation

PROJECT_TITLE: Neuronal signaling mechanisms of stress-induced anhedonia in the lateral habenula

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Pre-exposure prophylaxis (PrEP) may be a viable option for African American women at-risk for HIV infection, but few studies have identified optimal strategies to reach African American women in need of PrEP nor examined effective strategies to scale-up PrEP among African American women in the South. African American women in the South experience high rates of intimate partner violence (IPV) which could force women to choose between HIV prevention or IPV prevention. The proposed research study seeks to develop, pilot-test, and evaluate a PrEP Implementation Toolkit within two community healthcare clinics located in Jackson, Mississippi to increase PrEP uptake among African American, address IPV as a barrier to PrEP uptake, and ultimately combat racial disparities in women’s HIV diagnoses.

PI_NAMEs: WILLIE, TIARA C. (contact)

PROGRAM_OFFICER_NAME: DAGHER, RADA K

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adoption;Affect;African American;African American Women;Age;AIDS prevention;Award;care seeking;career;Caring;Clinic;Clinical;combat;Community Healthcare;condoms;Counseling;Data;design;Development;disparities in women;Disproportionately impacts women;Doctor of Philosophy;Educational workshop;Effectiveness;Eligibility Determination;Epidemic;epidemic preparedness;Epidemiologist;Evaluation;experience;Face;Focus Groups;Forcible intercourse;Funding;Future;Goals;Grant;High Risk Woman;HIV;HIV diagnosis;HIV Infections;HIV risk;HIV Seropositivity;implementation framework;implementation science;implementation study;Incidence;Infection;informant;innovation;interest;Interruption;Interview;intimate partner violence;Knowledge;Manuscripts;Mentored Research Scientist Development Award;Mentorship;Mississippi;Neighborhood Health Center;novel;Outcome;Patients;pilot test;pre-exposure prophylaxis;Prevalence;prevent;Prevention program;Prevention Research;Prevention strategy;preventive intervention;Primary Care;Principal Investigator;Productivity;programs;racial disparity;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Readiness;Recommendation;reproductive;Research;research study;Risk;Safety;scale up;screening;service delivery;Services;skills;symposium;Testing;therapy development;Time Series Analysis;Training;United States Health Resources and Services Administration;Unsafe Sex;uptake;violence exposure;violence prevention;Waiting Lists;Woman;women patients;women's diagnosis;Work;Writing

PROJECT_TITLE: Using Implementation Science to Increase PrEP Uptake among African American Women in the South


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Neurosciences;Obesity;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

ORG_CITY: IRVINE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative Asian Americans have more sleep deficiencies compared to Whites or Hispanics. The proposed longitudinal study will test if immigrant stressors, including stress from COVID-19, have an impact on sleep, and how sleep is associated with cardiometabolic health outcomes in a community-based sample of Chinese, Korean, and Vietnamese Americans. This innovative study will elucidate health issues of the understudied group and identify modifiable factors that will serve as targets for intervention to reduce sleep disparities in Asian Americans.

PI_NAMEs: LEE, SUNMIN  (contact)

PROGRAM_OFFICER_NAME: MARTIN, IMAN

PROJECT_TERMS: Adult;Affect;African American population;American;anti-Asian;Asian;Asian Americans;Asian population;biological adaptation to stress;Blood;Body mass index;Buffers;cardiometabolic risk;cardiometabolism;Chinese;Chinese American;Cholesterol;Chronic Disease;Communities;Conflict (Psychology);COVID-19;COVID-19 impact;COVID-19 stress;Data;Data Reporting;Development;Diabetes Mellitus;Diagnosis;Dimensions;Disparity;Drowsiness;Dryness;Emotional;Environment;Ethnic Origin;Ethnic Population;experience;follow-up;Future;Glycosylated hemoglobin A;Goals;Hate;Health;health disparity;high body mass index;High Prevalence;Hispanic Populations;Hypertension;Immigrant;Immigration;Individual;inflammatory marker;innovation;Interleukin-6;Intervention;Japanese American;Koreans;Light;Limited English Proficiency;Link;Longitudinal Studies;Low Prevalence;Measures;Mediating;Metabolic syndrome;Minority Groups;multi-ethnic;neighborhood disadvantage;Neighborhoods;novel;Obesity;Outcome;Patient Self-Report;perceived stress;Perception;Politics;poor health outcome;poor sleep;Population;protective factors;Psyche structure;Psychological Impact;Psychological Stress;psychosocial stressors;racial population;racism;rapid growth;Religion;Reporting;Research;Research Personnel;Risk;Role;Sampling;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep Disorders;Sleep disturbances;sleep health;Sleeplessness;social cohesion;Social support;sociodemographics;Speech;Spottings;Stress;stressor;study population;Subgroup;Testing;TNF gene;Vietnamese;Waist-Hip Ratio;War

PROJECT_TITLE: Sleep and health disparities among Asian Americans: roles of stressors and protective factors

STUDY_SECTION: HDEP

STUDY_SECTION_NAME: Health Disparities and Equity Promotion Study Section[HDEP]


NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human;Women's Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Proper interaction of placental cells with the maternal immune system is required for induction of tolerance and establishment of pregnancy. The study of such interactions is currently limited to model systems which do not adequately represent these processes in an ongoing pregnancy in vivo. This project will apply findings from primary decidual and placental cells to human pluripotent stem cells in order to establish in vitro models, for the study of these important cell-cell interactions at the maternal-placental interface.

PI_NAMEs: BUI, JACK D;PARAST, MANA M (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: adaptive immune response;Alloantigen;amnion;Animal Model;Apoptosis;Biological Assay;Biological Models;Blood;Blood flow;Cell Communication;Cell Differentiation process;Cell Physiology;cell type;Cells;Coculture Techniques;cytokine;cytotoxic;cytotoxicity;Data;Decidua;Decidua Basalis;Decidual Cell;Endometrium;Environment;Epithelial Cells;experience;Face;fetal;Fetus;First Pregnancy Trimester;Flow Cytometry;Functional disorder;Galactose Binding Lectin;Gene Expression;Generations;Goals;Growth and Development function;Human;human model;human pluripotent stem cell;Hypoxia;Immune;Immune Evasion;Immune response;Immunofluorescence Immunologic;in vitro Model;in vivo;induced pluripotent stem cell;Inflammatory;Innate Immune Response;insight;Interleukin-15;Invaded;Knowledge;Leukocytes;male;maternal immune system;Maternal-Fetal Exchange;Mesenchymal Stem Cells;Methods;Modeling;Natural Killer Cells;pathogen;Patients;peripheral blood;Peripheral Blood Mononuclear Cell;Phenotype;Placenta;placental trophoblasts;Placentation;pluripotent stem cell differentiation;Population;Pregnancy;Pregnant Uterus;Premature Birth;Premature Labor;Process;programs;Protocols documentation;Publishing;Regenerative Medicine;Reproducibility;Research Personnel;Resolution;Resources;response;Risk;Sendai virus;Series;single-cell RNA sequencing;Staging;Stromal Cell-Derived Factor 1;Study models;Surface;Technology;Tissues;transcriptomics;trophoblast;Umbilical cord structure;Uterus;vascular abnormality;Vascular remodeling;Villous;Work

PROJECT_TITLE: Modeling human trophoblast-NK cell interactions in term and preterm birth

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PROVIDENCE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: NARRATIVE Mutations in ASH1L are a major cause of autism spectrum disorder (ASD) when these genetic changes impair protein function. The ASH1L transcription factor is a protein that regulates large groups of genes simultaneously, including other autism genes. Our goals in this proposal are 1) identify cellular defects in human neurons with patient mutations in ASH1L using iPSC-derived experimental systems, 2) study the functional and circuit defects associated with ASH1L deficiency, and 3) identify the epigenetic and transcriptional signatures associated with ASH1L using mouse and human experimental systems. For all of these Aims, we will rescue the phenotypes identified using a mechanistic approach.

PI_NAMEs: LIU, JUDY SHIH-HWA;LIZARRAGA, SOFIA BEATRIZ (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: Affect;ASH1L gene;ATAC-seq;autism spectrum disorder;Bioinformatics;Biology;Brain;cell type;Cells;ChIP-seq;Chromatin;Chromatin Remodeling Factor;confocal imaging;Corpus Callosum;Data;Defect;density;derepression;Development;Developmental Gene;Disease;Electrocorticogram;Electrophysiology (science);Epigenetic Process;FOXP1 gene;Functional disorder;Gene Expression Profile;gene network;gene repression;Genes;Genetic Predisposition to Disease;Genetic Research;genetic risk factor;Genetic Transcription;genome editing;Goals;high risk;histone methyltransferase;Histones;Human;human stem cells;imaging approach;Impairment;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;innovation;interdisciplinary approach;Intervention;Link;Mediating;Molecular;Morphogenesis;multi-electrode arrays;Mus;Mutant Strains Mice;Mutation;neural;Neuroanatomy;neurodevelopment;Neurodevelopmental Disorder;neuron development;Neuronal Dysfunction;neuronal excitability;Neurons;Neurosciences;novel;novel therapeutic intervention;patch clamp;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phenotype;Polycomb;Positioning Attribute;pre-clinical;programs;protein expression;protein function;Proteins;Repressor Proteins;Research;Risk Factors;risk variant;Rodent;Role;single-cell RNA sequencing;Slice;Structure;Synapses;synaptic function;System;Testing;Therapeutic;therapeutic target;transcription factor;Transferase;translational approach;treatment strategy;Work

PROJECT_TITLE: ASH1L mediated transcription networks in autism spectrum disorders


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Prevention;Social Determinants of Health

PHR: NARRATIVE This project is designed to test whether epigenetic changes play a role in the impact of social environmental stress exposure on respiratory and quality of life health outcomes in chronic obstructive pulmonary disease (COPD), which disproportionately affects low income individuals. We will combine data from the CURE and MOVE COPD studies, including one low-income health disparities population, with rigorous measures of personal exposure to social stress and COPD respiratory and quality of life outcomes as well as matched blood and airway biospecimens. Our results may provide new modifiable candidate loci/pathways that are important regulators of COPD health outcomes, and could lead to new detection, intervention, and/or treatment strategies.

PI_NAMEs: LADD-ACOSTA, CHRISTINE  (contact)

PROJECT_TERMS: accelerated epigenetic aging;Address;adverse childhood events;Adverse effects;Affect;Age;age acceleration;age related;aging mechanism;Algorithms;Behavior Therapy;Behavioral;Biological;biological adaptation to stress;biological age;Biological Markers;biomarker performance;Blood;Body mass index;burden of illness;Cause of Death;Cell Physiology;Chronic Obstructive Pulmonary Disease;Chronology;community violence;Critical Care;Data;Data Collection;design;Detection;Discrimination;Disease;Disease Outcome;Disparity;DNA;DNA Methylation;Education;effectiveness evaluation;Effectiveness of Interventions;environmental stressor;Epidemiology;epigenetic aging;Epigenetic Process;epigenomics;Exposure to;Frequencies;Gene Expression;genome-wide;Goals;Health;health disparity;health disparity populations;Hospitalization;improved;Income;indexing;Individual;insight;inter-individual variation;Intervention;Knowledge;life span;Low income;Low Income Population;low socioeconomic status;Lung;Measures;Mediation;Medicine;methylation pattern;Molecular Target;Morbidity - disease rate;mortality;Outcome;Pathogenesis;Pathway interactions;perceived stress;Pharmaceutical Preparations;Pharmacologic Substance;poor health outcome;Population;Prevalence;Prevention;Productivity;Protocols documentation;Quality of life;Research Personnel;respiratory;Respiratory Disease;Respiratory Signs and Symptoms;response;Risk Factors;RNA;Role;Sampling;Severities;Smoking History;social;Social Environment;Social Sciences;social stress;social stressor;Socioeconomic Status;Specimen;Sputum;stem;Stress;stressor;success;Testing;treatment strategy;United States;Violence

PROJECT_TITLE: The role of epigenetics in the adverse effects of social environmental stressors on COPD outcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(55)R]


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Esophageal Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Racial and Ethnic Minority Health Research;Rare Diseases;Rural Health;Social Determinants of Health

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

PHR: This project is relevant to public health because, while surgery is one crucial step to achieve curative intent for patients with gastrointestinal cancers, disparities in access and quality of surgery care exist for African American patients. To address these disparities in two states of the Deep South, we propose to identify gaps in surgical care, examine potential mechanisms that contribute to these gaps, and develop a surgery-focused lay navigation model in combination with Enhanced Recovery After Surgery (ERAS) processes to support African American GI cancer patients from the pre to post surgery. The product of this project, i.e., a plan to eliminate surgical disparities in this region, is relevant to the National Institute on Minority Health and Health Disparities (NIMHD) and the National Cancer Institute (NCI) as reported in PAR- 18-288 on Surgical Disparities Research.

PI_NAMEs: CHU, DANIEL I;PISU, MARIA  (contact)

PROGRAM_OFFICER_NAME: SOLIS SANABRIA, CAROLINA VANESSA

PROJECT_TERMS: access disparities;Address;Adopted;Adoption;Affect;African American;African American population;Alabama;American;Area;Automobile Driving;cancer care;Cancer Patient;cancer surgery;cancer therapy;care providers;Caring;Clinical;Colorectal Cancer;County;Data;Deep South;design;Development;Diagnosis;Disparity;disparity elimination;disparity reduction;Economics;effective intervention;ethnic disparity;Ethnic Origin;Exposure to;Future;Gastrointestinal Surgical Procedures;Goals;health disparity;Health Services Accessibility;Hospital Records;Improve Access;improved outcome;Incidence;Individual;Individual Adjustment;Institution;Intervention;Interview;Knowledge;Length of Stay;Malignant neoplasm of esophagus;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of pancreas;Medical;Methods;Minority;Mississippi;Modeling;mortality;multidisciplinary;multimodality;National Cancer Institute;National Institute on Minority Health and Health Disparities;Operative Surgical Procedures;Outcome;Pathway interactions;Patient Self-Report;Patients;Perioperative;Persons;Phase;Physiological;pilot test;Population;Postoperative Period;postoperative recovery;Process;programs;prototype;Provider;Public Health;Quality of Care;Race;racial disparity;Recovery;Reporting;Research;Research Methodology;Research Personnel;Resources;Scientific Advances and Accomplishments;Social Environment;sociodemographics;Standardization;Stress;surgery outcome;surgical disparities;Surveys;System;Testing;Time;Universities;uptake;US State

PROJECT_TITLE: Designing a Plan of Action for Better Access and Quality of Surgery for African-Americans with Gastrointestinal Cancers in the Deep South


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Infant Mortality;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: SAN DIEGO

ORG_NAME: RADY PEDIATRIC GENOMICS & SYSTEMS MEDICINE INSTITUTE

PHR: Project Narrative Infant mortality is one of the leading indicators of a nation's health. Knowledge of causes of infant mortality shapes public health policy and prioritizes diseases for investments in surveillance, intervention and medical research. The proposed multidisciplinary research team will build on our pioneering work in genomic medicine to identify as yet unknown genetic causes of infant mortality in 1,000 consecutive infant deaths in San Diego County, and will explore environmental contributors to those same deaths to inform future strategies for prevention and intervention.

PI_NAMEs: CHAMBERS, CHRISTINA ;KINGSMORE, STEPHEN FRANCIS (contact)

PROJECT_TERMS: 1 year old;Archives;Back to Sleep;Birth Records;Black Populations;Blood;Cause of Death;Cessation of life;Child;Classification;Clinical;Collection;Communities;County;Data;Death Certificates;Death Records;Diagnosis;Disease;disease diagnosis;Dryness;Early Diagnosis;effective therapy;Electronic Health Record;Environmental Risk Factor;Evidence based treatment;Foundations;Future;Genetic;Genetic Diseases;genetic disorder diagnosis;genome sequencing;Genomic medicine;Genomics;Health;health disparity;Health Policy;Health Priorities;high risk;high risk infant;Hospitals;Hour;Infant;infant morbidity;infant morbidity/mortality;Infant Mortality;Interdisciplinary Study;Intervention;Intervention Studies;Investments;Knowledge;knowledge base;Latino Population;Length of Stay;Life;Literature;Measures;Medical Research;Methods;Modeling;Molecular;mortality;Mothers;Newborn Infant;Not Hispanic or Latino;Outcome;Outcome Study;Palliative Care;Pediatric Hospitals;Policy Maker;Population Study;Prevention strategy;programs;Public Health;Publishing;Research;Research Personnel;Scientist;Shapes;Sleep;sociodemographics;Spottings;Testing;Work

PROJECT_TITLE: Genomic and Environmental Determinants of Infant Deaths in San Diego County in 2015-2022

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: ADMINISTRATION

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on equitable access to emergency care, an important public health metric, by examining racial disparities in emergency department transfers, including how long patients wait before they are transferred and what hospitals they are transferred to. Once conducted, the proposed study can inform policymakers on specific ways to improve health equity, such as by promulgating regulations to promote non-disparate emergency department transfers, or expanding protocolization of emergency department transfers. The proposed research is relevant to NIMHD’s mission to conduct and support research in health disparities, and their specific interest in examining the “impact of structural racism and discrimination in health care settings on access to and quality of care and health outcomes.”

PI_NAMEs: HSUAN, CHARLEEN  (contact)

PROJECT_TERMS: Accident and Emergency department;Acquired Immunodeficiency Syndrome;Address;Admission activity;Behavior;Black race;Burn Units;California;Caring;Data;Discrimination;Disparity;Doctor of Philosophy;Emergency Care;Emergency Department patient;Employment;Equity;Ethnic Origin;experience;Goals;Grant;Health;health care settings;health disparity;health equity;Hispanic;hospital readmission;Hospitals;improved;Inequity;innovation;inpatient service;insight;Insurance;Insurance Coverage;interest;Laws;Length of Stay;marginalization;marginalized population;Measures;Medicaid;Medical emergency;Medicare;Mental disorders;Minority;minority patient;Mission;mortality;National Institute on Minority Health and Health Disparities;New York;non-compliance;Not Hispanic or Latino;Outcome;Ownership;Patient Admission;Patient Transfer;Patient-Focused Outcomes;Patients;payment;Physicians;Policies;Policy Maker;preservation;Public Health;Public Hospitals;Qualifying;Quality of Care;Race;racial difference;racial disparity;Regulation;Research;Research Personnel;Research Support;safety net;socioeconomic diversity;Structural Racism;System;trauma units;Variant;Visit;Work

PROJECT_TITLE: Structural Racism and Discrimination in Emergency Department Transfers: Unintended Consequences of the Emergency Medical Treatment and Labor Act (EMTALA)


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health;Stroke

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Delayed arrival to the hospital, which occurs more often in racial minority and socioeconomically disadvantaged patients, is the single most important reason for not receiving curable treatments for stroke. We aim to understand the social network mechanisms that drive this health disparity by measuring and modeling social networks of patients and persons in their networks during stroke. This study will re-frame the perspective of stroke delay and lead to network-based interventions to improve equitable access to therapies.

PI_NAMEs: DHAND, AMAR  (contact);SHETH, KEVIN NAVIN

PROGRAM_OFFICER_NAME: PATEL, ANURADHA DIPAK

PROJECT_TERMS: Acute;acute stroke;Address;Affect;African American;Age;Attenuated;Black race;Characteristics;Data;Databases;Decision Making;density;design;Dimensions;disability;Disparity;disparity reduction;Ensure;Equity;Frequencies;Future;Goals;health disparity;Health Services Accessibility;high risk;Hospitalization;Hospitals;Hour;improved;improved outcome;Individual;Intervention;Knowledge;low socioeconomic status;Measures;Modeling;Morbidity - disease rate;multidisciplinary;Network-based;Outcome;patient population;Patients;Persons;Population;Population Heterogeneity;Populations at Risk;post stroke;Public Health;Race;racial disparity;racial minority;recruit;Research;Risk;Risk Factors;simulation;social;social contact;Social Environment;Social Network;social network intervention;social structure;socioeconomic disadvantage;socioeconomic disparity;Socioeconomic Status;socioeconomics;Stroke;stroke clinical trials;stroke model;stroke outcome;stroke patient;stroke symptom;stroke therapy;Stroke Volume;Structure;Symptoms;Testing;Time;Translations;Work

PROJECT_TITLE: Social networks and risk of delayed arrival to the hospital during stroke


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Autism;Brain Disorders;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention

ORG_CITY: RICHMOND

ORG_DEPT: PHARMACOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Although, there has been ample progress in identifying genetic risk factors for autism spectrum disorder (ASD), a substantial fraction of ASD status cannot be explained by genetic sequence variation. DNA methylation (DNAm) may account for part of this unexplained variation and, therefore, we proposed to perform methylome- wide investigations using sequencing-based DNAm data and novel statistical approaches. The successful completion of this project means that we have identified ASD associated methylation marks that will enhance our understanding of the ASD etiology and may be used for risk prediction and early diagnosis of ASD.

PI_NAMEs: ABERG, KAROLINA ANNA (contact);VAN DEN OORD, EDWIN

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Affect;Age;Algorithms;autism spectrum disorder;Autopsy;Binding;biobank;Bioconductor;Biological Assay;Birth;Blood;Blood specimen;Brain;Brain Diseases;Case/Control Studies;cell type;chromatin modification;Data;Development;Diagnosis;disorder risk;DNA analysis;DNA Integration;DNA Methylation;DNA Methylation Regulation;DNA Sequence;Early Diagnosis;Early Intervention;Environment;Environmental Risk Factor;Epidemiology;Epigenetic Process;Equation;Etiology;exome sequencing;experience;factor A;follow-up;Genes;Genetic;genetic information;genetic risk factor;genome wide association study;genome-wide;Genomics;Genotype;Goals;Human Genome;improved;in utero;Individual;Investigation;Machine Learning;Mediating;Methylation;methylation biomarker;methylome;methylomics;Modeling;multidimensional data;Neonatal;Neurodevelopmental Disorder;novel;Participant;Phenotype;phenotypic data;Population;population based;prenatal;Process;Protocols documentation;Psychiatry;Risk;Risk Factors;risk prediction;Role;sample collection;Sampling;screening;Sequence Analysis;Sex Bias;Site;Statistical Data Interpretation;Time;transcriptome sequencing;Universities;Variant;Virginia;Whole Blood;X Chromosome;young adult

PROJECT_TITLE: Developmental methylomics of autism spectrum disorder

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Palliative Care;Patient Safety;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Identifying and elucidating sources of potential disparities in outcomes after major surgery in older Americans is needed to ensure that all persons aged 65 years or older receive high-quality care before, during, and after geriatric surgery, regardless of race, ethnicity, socioeconomic status, or geographic location. By taking a comprehensive, multifactorial, and multilevel approach that emphasizes the importance of social contextual factors, the proposed research will build the evidence that is essential to understanding the sources and mechanisms of potential disparities in outcomes after major surgery. These actionable results will inform novel interventions, collaborations, and policies designed to improve these outcomes and reduce surgical inequities in older Americans.

PI_NAMEs: BECHER, ROBERT DAVID;GILL, THOMAS MICHAEL (contact)

PROJECT_TERMS: Accounting;Address;Admission activity;Age;age group;Aging;American;Black Populations;Caring;Characteristics;Clinical;clinical risk;cohort;Collaborations;community living;complement system;contextual factors;Data;Data Set;Death Rate;design;Disadvantaged;Disparity;Disparity population;Elderly;ethnic minority;Ethnic Origin;Event;frailty;functional decline;Geographic Locations;Geography;Health;Home;Hospice Care;hospice environment;hospice utilization;hospital readmission;Hospitalization;human old age (65+);Impaired cognition;improved outcome;Incidence;Individual;Inequity;Injury;innovation;Intervention;Knowledge;longitudinal analysis;Longitudinal Studies;Measures;Medicare;Musculoskeletal;novel;Nursing Homes;Older Population;Operative Surgical Procedures;Outcome;Palliative Care;patient oriented;Patients;Persons;phenotypic data;Policies;Population;Public Health;Quality of Care;Race;racial minority;Rehabilitation therapy;Research;Resources;Risk;Risk Factors;Sampling;Series;Social Environment;Societies;Socioeconomic Status;Source;Testing;trend;United States;Work

PROJECT_TITLE: A Multifactorial Approach to Evaluating Disparities in Outcomes after Major Surgery in Disadvantaged Older Persons

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: LOS ANGELES

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PUBLIC HEALTH RELEVANCE: The last stages of neuronal development involve specialization into  specific cell “fates”, and a current goal in neuroscience is to understand what leads to cell diversity.  This proposal will examine the role of DNA methylation in sexual differentiation of neurochemical  phenotype providing a potential mechanism by which cell identity is determined in the male and female  brain. This work will contribute to understanding brain development in both sexes, an important  endeavor given that many developmental and neuropsychiatric disorders are sex-biased.

PI_NAMEs: CORTES, LAURA  (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Area;Atmosphere;Birth;Brain;career development;Cells;Cognition;Development;developmental disease;Disease;DNA;DNA Methylation;DNA Methylation Inhibition;DNA Modification Methylases;Ensure;Environment;Epigenetic Process;epigenome;epigenomics;ESR1 gene;Female;Fluorescent in Situ Hybridization;Goals;Hypothalamic structure;Immunoprecipitation;Incidence;Institution;inter-institutional;male;Methylation;Moods;Mus;Neonatal;neonatal brain development;Nervous System Disorder;neurochemistry;Neurodevelopmental Disorder;neuron development;Neurons;neuropsychiatric disorder;neuroregulation;Neurosciences;Newborn Infant;Phase;Phenotype;Population;postnatal development;Pregnancy;Preoptic Areas;Process;professor;promoter;public health relevance;Reporting;Research;Research Personnel;Role;Scientist;Severities;sex;Sex Bias;Sex Differences;Sex Differentiation;single molecule;Techniques;tenure track;Testing;tool;Training;translocase;Universities;Weaning;Work

PROJECT_TITLE: The neural control of thermoregulatory changes accompanying pregnancy


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Neurosciences;Sleep Research;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the elucidation of new mechanisms (i.e., chronobiology) will increase the understanding of the negative consequences of common drugs on brain and behavior. This mechanistic neuroscience cannot be done in humans. Thus, the proposed research is relevant to part of NCI/NIH’s mission that pertains to reducing cancer-related comorbidities, which in turn, improves health and quality of life.

PI_NAMEs: PYTER, LEAH M (contact)

PROGRAM_OFFICER_NAME: GOOD, MARGE

PROJECT_TERMS: Address;Adjuvant Chemotherapy;Affect;Alcohols;Anti-Inflammatory Agents;Basic Science;Behavior;Behavior assessment;behavior change;Behavioral;Biological;Biological Clocks;Biometry;Brain;Breast Cancer Patient;Breast Cancer survivor;Cancer Patient;cancer therapy;Cells;chemotherapy;Chemotherapy-Oncologic Procedure;Chronobiology;circadian;circadian biology;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Clinical Data;clinical practice;Cognitive;comorbidity;Cues;Data;design;Diabetes Mellitus;disorder risk;Etiology;Eukaryota;experimental study;Fatigue;Foundations;Genes;Genetic;glial activation;Goals;hazard;Health;Health Benefit;Hospital Costs;Human;Hypothalamic structure;improved;in vivo;Inflammation;innovation;Intervention;Jet Lag Syndrome;Knowledge;Light;loved ones;Lupus;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Medical Oncology;Mental Health;Methods;Mission;Molecular;mortality;Motivation;mouse model;neuroinflammation;Neurosciences;Nonpharmacologic Therapy;novel;Oncology;Operative Surgical Procedures;Outcome;Pacemakers;Paclitaxel;Pathway interactions;Patients;Periodicity;Pharmaceutical Preparations;pharmacologic;Phase;Phase response curves;Phototherapy;Physical assessment;Physiological;Physiology;Planning Techniques;Population;Predisposition;prevent;Psychoneuroimmunology;Public Health;Quality of life;Research;Research Project Grants;Resolution;Rest;Role;Running;Scientist;shift work;Signal Transduction;Stem cell transplant;suprachiasmatic nucleus;Survival Rate;Survivors;Symptoms;System;Systems Biology;Testing;translational model;United States National Institutes of Health;virtual;Work

PROJECT_TITLE: Chemotherapy-induced circadian master clock disruptions and fatigue

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Hematology;Infant Mortality;Patient Safety;Pediatric;Rare Diseases

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative This research proposes to develop an automated workflow that combines computational fluid dynamics, shape optimization, and blood coagulation biochemistry to deliver a computational tool that can virtually optimize a given patient's planned anatomy to help surgeons achieve the desired hemodynamics and offer comprehensive predictability. In this project, we will focus our tool's application to improve patient-specific Fontan pathways (that post-operatively creates a non-natural venous return of blood to lungs in patients with single ventricle defects) to 1) improve venous return of blood from liver and overall flow balance to lungs, 2) minimize energy loss and clotting risk, that are all paramount to short- and long-term success of Fontan surgery. Once clinical applicability is determined, we can extend our tool to other surgeries in pediatric and adult cardiothoracic care where achieving an efficient blood flow and minimizing/predicting thrombosis are important.

PI_NAMEs: GOVINDARAJAN, VIJAY  (contact)

PROGRAM_OFFICER_NAME: EGERSON, D'ANDREA R

PROJECT_TERMS: Adult;Affect;Algorithms;Anatomy;Aneurysm;aortic arch;Arteriovenous malformation;Assessment tool;biochemical model;Biochemistry;Blood;Blood coagulation;Blood flow;Blood Platelets;blood pump;Cardiac;Cardiac Surgery procedures;Caring;Childhood;Circulation;Clinical;clinical application;Coagulation Process;cohort;Collection;comparative;Complex;computerized tools;congenital heart abnormality;Consumption;Coupled;Custom;Data;Deposition;design;Diameter;Distal;Engineering;Environment;Equilibrium;Evaluation;Failure;Family suidae;Fibrin;Flare;Fontan Procedure;Gases;Geometry;Heart;Hematologist;hemodynamics;Hepatic;Image;improved;in silico;In Vitro;in vitro Model;insight;Intervention;kidney dysfunction;Life;Liquid substance;Liver;Lung;Magnetic Resonance Imaging;Manuals;Methodology;Methods;Modeling;Monitor;Morbidity - disease rate;mortality;multidisciplinary;novel;Operative Surgical Procedures;Organ;Outcome;palliative;Palliative Care;Pathway interactions;Patients;Physiology;Play;Polytetrafluoroethylene;Postoperative Period;pressure;prevent;prospective;Proteins;Protocols documentation;pulmonary arteriovenous malformation;reconstruction;repaired;Research;Risk;Role;Route;Shapes;Single ventricle congenital heart disease;success;Surgeon;surgery outcome;Techniques;Thrombin;Thrombosis;thrombotic;Thrombus;Time;tool;Validation;Variant;Venous;Ventricular;virtual;virtual surgery;Work

PROJECT_TITLE: A Novel computational approach to optimize Fontan and improve surgical predictability

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Biotechnology;Cardiovascular;Gene Therapy;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Nanotechnology

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: Project Narrative: Cardiovascular disease is the leading cause of death globally. We propose to design a novel cell-selective nanotherapy and test its efficacy to reduce restenosis and atherosclerotic in mouse models and in human coronary arteries. Successful completion of these studies will advance the field of cardiovascular disease treatment.

PI_NAMEs: TOTARY-JAIN, HANA  (contact)

PROGRAM_OFFICER_NAME: FLEG, JEROME L

PROJECT_TERMS: Adenovirus Vector;Affect;Animal Model;Apolipoprotein E;Arterial Fatty Streak;Atherosclerosis;Biological;Blood Vessels;Cannulations;Cardiovascular Diseases;Cardiovascular system;Carotid Arteries;Categories;Cause of Death;Cell Physiology;Cells;Cessation of life;Clinical;Clinical Research;Coronary Arteriosclerosis;Coronary artery;Cyclin-Dependent Kinase Inhibitor;cyclin-dependent kinase inhibitor 1B;design;Development;disability;efficacy evaluation;endonuclease;Endothelial Cells;Endothelium;Epidemic;Event;ex vivo perfusion;Exhibits;femoral artery;Foundations;Functional disorder;Goals;healing;Heart;Human;human tissue;Hyperplasia;Incidence;Infection;Inflammation;Inflammatory Infiltrate;Injury;Interleukin-1 beta;Intervention;Knock-out;Lipids;Messenger RNA;MicroRNAs;Modeling;mouse model;Mus;nanoparticle;nanoswitch;nanotherapeutic;nanotherapy;novel;novel strategies;Oryctolagus cuniculus;overexpression;Penetration;Peptides;personalized medicine;Pharmaceutical Preparations;pharmacologic;Physiology;preclinical study;protein expression;Proteins;Rattus;recombinant virus;Recurrence;Regional Perfusion;Resistance;response;restenosis;Safety;self assembly;siRNA delivery;Site;Small Interfering RNA;Smooth Muscle Myocytes;Technology;Testing;Therapeutic;Thrombophilia;Thrombosis;Time;tool;Toxic effect;Translating;translational potential;treatment strategy;Untranslated Regions;uptake;Vascular Endothelial Cell;Vascular Smooth Muscle;vascular smooth muscle cell proliferation;Venous

PROJECT_TITLE: Cell-Selective Therapies for Coronary Artery Disease

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: Project Narrative The Genome Aggregation Database (gnomAD) will provide public access to the largest and most diverse genome sequencing resource in the field. gnomAD is critical to help doctors and scientists interpret the genomes of the human population and understand which changes in an individual’s DNA may lead to disease or have no effect.

PI_NAMEs: DALY, MARK JOSEPH;REHM, HEIDI L (contact)

PROGRAM_OFFICER_NAME: MORALES, JOANNELLA

PROJECT_TERMS: aggregation database;All of Us Research Program;Architecture;Basic Science;biobank;Biological;Clinical;ClinVar;cloud based;cohort;Collection;Communities;Computer software;cost efficient;Data;data access;Data Aggregation;Data Set;data sharing;Databases;Diagnostic;Disease;DNA;empowerment;Ensure;Equity;exome;Frequencies;functional genomics;Funding;Genes;genetic variant;Genetic Variation;Genome;Genome Mappings;genome resource;genome sequencing;genome-wide;genomic data;Genomic medicine;Genotype;Health;health care settings;Human;Human Genetics;improved;Individual;Infrastructure;insertion/deletion mutation;Intuition;Joints;large datasets;Link;Maintenance;Maps;Medical Genetics;Methods;Mutation;Natural Selections;novel;Pathogenicity;Phenotype;phenotypic data;Population;pressure;Production;Proteins;Publications;Quality Control;rare variant;Resolution;Resources;Sample Size;Sampling;Scientist;Single Nucleotide Polymorphism;Statistical Data Interpretation;tool;Training;Untranslated RNA;Variant;virtual;web site;Work