NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Cost Effectiveness Research;Emerging Infectious Diseases;Health Services;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Respiratory viral surge events, in which hospitals face capacity strain from an influx of infected patients, range from annual respiratory viral seasons dominated by seasonal influenza to rarer and more severe epidemics and pandemics such as due to COVID-19. It is unknown what enables hospitals to display adaptation and resiliency, thereby threatening care quality for both infected patients and uninfected patients during viral surges. The proposed work aims to understand how care delivery and outcomes change over the course of a respiratory viral surge event and what organizational factors may account for observed differences in hospital adaptation and resiliency.

PI_NAMEs: ANESI, GEORGE L (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Accounting;Acute;Acute respiratory failure;Adherence;Administrator;Admission activity;Adoption;Affect;Applications Grants;Bioethics;biomedical referral center;care delivery;care outcomes;career;Career Choice;career development;career preparation;Caring;Characteristics;Chronic Obstructive Pulmonary Disease;Clinical;clinical epidemiology;combat;Congestive Heart Failure;Coronavirus;cost;Cost Effectiveness Analysis;COVID-19;COVID-19 pandemic;COVID-19 patient;Critical Care;Critical Illness;Data;Diagnosis;discrete data;Electronic Health Record;Epidemic;Event;evidence base;experience;Face;falls;Family Caregiver;Future;Goals;Grant;Healthcare;Hospitalization;Hospitals;Hypersensitivity;implementation science;improved;indexing;Individual;Infection;Influenza;Influenza A Virus, H1N1 Subtype;innovation;instructor;interest;Intervention;Interview;Knowledge;Leadership;Lung;Master of Science;Measures;Medical;medical schools;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methodology;Middle East Respiratory Syndrome;novel;operation;Outcome;Outcome Measure;pandemic disease;Patient Admission;Patient-Centered Care;Patient-Focused Outcomes;Patients;Pennsylvania;Perception;Plants;Pneumonia;Positioning Attribute;preservation;Process;process improvement;Public Health;Publications;Qualitative Research;Quality of Care;Readiness;Research;Research Methodology;Research Personnel;Research Training;resilience;respiratory;response;Retrospective cohort study;Risk;seasonal influenza;Seasons;Sepsis;Services;Severe Acute Respiratory Syndrome;Statistical Models;Structure;supplemental oxygen;symposium;Testing;Time;Training;Universities;Viral;Virus;Work

PROJECT_TITLE: Hospital adaptation and resiliency for infected and uninfected patients during respiratory viral surge events: from seasonal influenza to COVID-19

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: BRONX

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Narrative The current drought of novel antibiotics and the rapid emergence of antibiotic resistance in Mycobacterium tuberculosis is threatening to make one of humankind’s deadliest infectious diseases incurable. This threat calls for new and innovative drug discovery paradigms. By leveraging CRISPRi technology and non-targeted metabolomics, we will use a combined computational/experimental strategy, that is based on the comparison of genetic and drug induced metabolic effects, to perform high-throughput de novo functional annotations of large libraries of anti-tubercular compounds with unknown mode of action.

PI_NAMEs: BERNEY, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TERMS: Algorithms;Anti-Bacterial Agents;Antibiotics;antimicrobial;Antineoplastic Agents;Antitubercular Agents;Atlases;Biochemical;Biological;Biological Assay;Biology;Cancer cell line;Categories;Cells;Chemicals;Communicable Diseases;comparative;Computer Models;computerized tools;Consumption;CRISPR interference;CRISPR/Cas technology;Custom;Data;Databases;Dimensions;Droughts;drug action;drug candidate;drug discovery;Drug Kinetics;Drug Screening;Drug Targeting;emerging antibiotic resistance;Ensure;Environment;Escherichia coli;Essential Genes;Event;Expression Library;Fingerprint;follow-up;gene function;Genes;Genetic;Goals;Growth;Growth Inhibitors;in vivo;inhibitor;innovation;insight;knock-down;Lead;Libraries;lung cancer cell;Mass Spectrum Analysis;Measures;Metabolic;metabolic profile;metabolome;metabolomics;meter;Methodology;Methods;Molecular;Multidrug-Resistant Tuberculosis;Mycobacterium smegmatis;Mycobacterium tuberculosis;Nature;novel;novel strategies;overexpression;Pharmaceutical Preparations;Phenotype;Property;Proteolysis;Regulator Genes;Reproducibility;response;Safety;small molecule;small molecule libraries;Switzerland;System;Techniques;Technology;Time;transcription factor;tuberculosis drugs;Validation;Work

PROJECT_TITLE: Identification of new inhibitors of essential functions in M. tuberculosis by high-throughput metabolic profiling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DDR-C(01)]


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Biotechnology;Genetics;Infectious Diseases;Lyme Disease;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: RICHMOND

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project narrative: Lyme disease remains an important public health issue. This work will identify the functional determinants and stage-specific effector mechanisms of the c-di-GMP binding protein, PlzA. These analyses will enhance our understanding of the molecular mechanisms of pathogenesis of the Lyme disease spirochetes and provide information that can be exploited in a broader sense to better understand the structure and function of c-di-GMP regulated RNA chaperones and the xPilZ domain proteins.

PI_NAMEs: DAVIES, CHRISTOPHER ;MARCONI, RICHARD T (contact);SAMUELS, D. SCOTT

PROGRAM_OFFICER_NAME: BOWDEN, NADINE

PROJECT_TERMS: Alleles;Amino Acids;Bacteria;Binding;Binding Proteins;Binding Sites;Biological;Biological Assay;Biological Process;Biopsy;Borrelia burgdorferi;Cell Physiology;Chemotaxis;CISH gene;Co-Immunoprecipitations;comparative;Data;diguanylate cyclase;DNA;Electrophoretic Mobility Shift Assay;Environment;environmental change;enzootic;Gene Expression;gene replacement;Genes;Genome;Growth;Hand;In Vitro;Incidence;Infection;Ixodes;Ligand Binding;Ligands;Lyme Disease;lyme pathogenesis;Mammals;Mediating;Midgut;Molecular;Molecular Chaperones;Morphology;Motility;Mus;mutant;Mutate;Mutation;Mutation Analysis;Nature;Northern Blotting;Organ;Outcome;Outcome Study;overexpression;Periodicity;Plasmids;posttranscriptional;Process;Property;protein protein interaction;Proteins;Public Health;Regulation;Regulator Genes;RNA;RNA annealing;RNA Binding;RNA immunoprecipitation sequencing;Sequence Analysis;Series;seroconversion;Site;Site-Directed Mutagenesis;Structure;Structure-Activity Relationship;Surface;Surface Plasmon Resonance;Tertiary Protein Structure;Testing;Tick-Borne Diseases;Ticks;Tissues;Transgenic Organisms;Translations;transmission process;Validation;Work

PROJECT_TITLE: PlzA, cyclic-di-GMP and the enzootic cycle for Lyme disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-Y(80)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: CHARLESTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE While there are some indications that socio-economic forces play a role in minority health disparities, there have been over a dozen publications in the past three years that strongly indicate a genetic component to the increased cancer risk and poorer prognosis for African Americans with many cancers, including colorectal cancer. This proposal focuses on two coding region variants in the p53 tumor suppressor gene (Pro47Ser and Tyr107His) that my research shows are “hypomorphs”; I will use genetically engineered mouse models to ascertain the impact of these variants on cancer risk and progression, with a focus on colorectal cancer.

PI_NAMEs: BARNOUD, THIBAUT  (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: adenoma;African;African American population;African American Women;African ancestry;Alleles;Amino Acids;Apoptosis;Binding;Biochemical;Biological Assay;Cancer Etiology;cancer health disparity;Cancer Prognosis;cancer risk;cancer therapy;career;career development;Cell Death;Cells;Cessation of life;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Colitis;Collaborations;Colon;colon cancer cell line;Colorectal Cancer;colorectal cancer progression;colorectal cancer risk;CRISPR/Cas technology;Data;Death Rate;Development;dextran sulfate sodium induced colitis;Diet;Disparity;DNA Binding Domain;Engineering;Ethnic Origin;Ethnic Population;Etiology;Event;Faculty;Family;Fluorescence Polarization;Foundations;Fox Chase Cancer Center;Gatekeeping;Gene Targeting;Genes;Genetic;Genetic Polymorphism;Genetic Transcription;genetic variant;Genetic Variation;Genetically Engineered Mouse;Genotype;Glutathione;Goals;Impairment;Incidence;Individual;Induction of Apoptosis;interest;Investigational Therapies;Iron;Iron Chelating Agents;Iron Chelation;Knock-in Mouse;Knowledge;KRAS2 gene;Learning;Li-Fraumeni Syndrome;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mentors;minority health disparity;Modeling;mouse model;Mus;Mutation;novel;novel therapeutic intervention;Pathway interactions;Persons;Phosphorylation;Population;Population Sciences;Positioning Attribute;Postdoctoral Fellow;pre-doctoral;Premenopause;Prognosis;Proteins;Publications;Reagent;Research;Research Personnel;Resources;Response Elements;Risk;Role;Single Nucleotide Polymorphism;skills;socioeconomics;Structure;Susceptibility Gene;targeted treatment;Techniques;Testing;The Wistar Institute;Tissues;tool;TP53 gene;Training;Transactivation;Transgenic Model;tumor;tumor progression;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;United States;Universities;Variant

PROJECT_TITLE: Genetics of Tumor Suppression by p53

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Dental, Oral, and Craniofacial Disease;Neurosciences;Nutrition;Obesity

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Obesity and diabetes, now among the leading causes of preventable death in the United States, are associated with chronic overconsumption of high sugar foods and beverages, reinforced in large part by their palatable taste. The research proposed here seeks to more fully understand how these essential nutrients are detected and drive ingestion via a novel glucoreceptor on the frontline of the gustatory system, with the long term goal of identifying pharmacological and dietary interventions that more effectively curb sugar appetite.

PI_NAMEs: SCHIER, LINDSEY A (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: afferent nerve;Amino Acids;Artificial Sweeteners;Behavior;Behavioral;Beverages;Brain;Cells;chorda tympani;Chronic;CNS processing;Consummatory Behavior;Consumption;Desire for food;detection of nutrient;Diabetes Mellitus;Diet;dietary;Dietary Intervention;Dietary Sugars;discrimination task;Electrophysiology (science);Enzyme Activation;Enzymes;Esthesia;experience;experimental study;Food;Fructose;G-Protein-Coupled Receptors;Genetic;Glossopharyngeal nerve structure;Glucokinase;Glucose;glucose receptor;Goals;Human;Ingestion;interdisciplinary approach;Laboratories;Learning;Ligands;Link;Liquid substance;Measures;Metabolic;Modeling;Molecular;Motivation;Mus;Nerve;neural;neurophysiology;neurotransmission;novel;Nutrient;nutrition;Obesity;Oral;Oral cavity;Outcome;Output;Pathway interactions;Peripheral;pharmacologic;Phosphorylation;Play;preventable death;Property;Psychophysics;Publishing;receptor;Research;response;Rewards;Rodent;Role;Sensory;sensory input;sensory mechanism;Series;Signal Transduction;Site;sugar;sweet receptor;sweet taste perception;Synaptic Transmission;Taste Buds;Taste Perception;taste system;Testing;Tissues;Tongue;transmission process;United States;Water;Western Blotting;Work

PROJECT_TITLE: Roles for Glucosensors in Taste Function

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Narrative Proper ion channel folding is critical for normal cardiac cell function, and mutations in these channels can lead to potentially life-threatening arrhythmias such as long-QT syndrome, short-QT syndrome, Brugada syndrome, Lev-Lenegre syndrome, and Idiopathic ventricular fibrillation. This research will elucidate the structural mechanism and biophysical determinants of potassium channel folding and evaluate a proposed mechanism by which mutations in the pore helix of hERG may cause misfolding and lead to long-QT syndrome.

PI_NAMEs: MOLINA, ANDREW VINCENT (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Affect;Agreement;Arrhythmia;Behavior;Biochemical;Biogenesis;Biological;Biological Models;biophysical techniques;Biophysics;Brugada syndrome;Cardiac;Cardiac health;Cardiac Myocytes;Cell Physiology;Cells;Disease;disease-causing mutation;disulfide bond;Engineering;Event;Fluorescence;Fluorescence Resonance Energy Transfer;Future;Grain;heart function;heart rhythm;Human;Hydrogen;Image;In Vitro;in vivo;innovation;insight;Ion Channel;Ion Transport;Ions;Kinetics;Label;Lead;Life;Light;Lipid Bilayers;Long QT Syndrome;Mass Spectrum Analysis;Membrane;Membrane Lipids;Membrane Proteins;membrane reconstitution;Methods;Missense Mutation;Modeling;Molecular;monomer;Mutation;Nature;novel;Pathogenesis;Pathologic;Pathway interactions;physical property;Physiologic pulse;Potassium Channel;potassium ion;prevent;Process;protein folding;Proteins;Publishing;Rationalization;reconstitution;Regulation;Research;Role;Scanning Probe Microscopy;Short QT syndrome;simulation;Spectrum Analysis;Speed;superresolution imaging;superresolution microscopy;Syndrome;Techniques;Temperature;ultra high resolution;Variant;Ventricular Fibrillation;Vesicle;Water;Work

PROJECT_TITLE: Uncovering the Mechanism of Potassium Channel Folding and Assembly with Implications for the Molecular Basis of Cardiac Arrhythmia


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Protein polymers called microtubules are a critical part of the dynamic internal scaffolding of eukaryotic cells. They have the remarkable ability to change their configuration to allow cells to accomplish such different tasks as division, migration, transport of internal material and shape acquisition. Our research seeks to identify and characterize the mechanisms underlying microtubule dynamics and spatial organization, which will contribute to improving human health because defects in these mechanisms are linked to neurodegenerative diseases, cancer, and developmental disorders.

PI_NAMEs: DIXIT, RAMANAND  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Address;Animals;Cells;Cellular biology;Complex;Cytoskeleton;Defect;Development;developmental disease;Disease;Eukaryotic Cell;Evolution;Filament;genetic regulatory protein;Goals;Growth;Health;Human;improved;insight;interdisciplinary approach;internal control;katanin;Link;Maintenance;Malignant Neoplasms;Microfluidic Microchips;Microtubule Stabilization;Microtubules;migration;Minus End of the Microtubule;Molecular;Mouse-ear Cress;Neurodegenerative Disorders;Organism;Pattern;Physiology;Plants;Plus End of the Microtubule;Polymers;programs;protein crosslink;Proteins;Reagent;Research;response;Rest;scaffold;Shapes;Signal Transduction;Structure;System;Time;tool

PROJECT_TITLE: Mechanisms for building and remodeling microtubule arrays

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-J(55)R]


NIH_SPENDING_CATS: Genetics

ORG_CITY: KANSAS CITY

ORG_NAME: STOWERS INSTITUTE FOR MEDICAL RESEARCH

PHR: Project Narrative  Non-traditional gene expression regulatory mechanisms continue to emerge that challenge the dogmatic understanding of how genes are transcribed and translated into functional proteins. The results of the studies detailed herein will be a critical contribution to our understanding of how translation of small coding regions in the 3’ untranslated region (3’UTR) enhance translation of the canonical coding region in higher organisms. This is a novel, widespread and potent post-transcriptional regulatory mechanism. Understanding the regulatory functions of small ORFs in the 3’UTR will provide an entry point and perhaps even a diagnostic tool to associate mutations with human diseases.

PI_NAMEs: BAZZINI, ARIEL  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: 3' Untranslated Regions;5' Untranslated Regions;Affect;Amino Acid Sequence;Automobile Driving;biochemical tools;Biological;Biological Assay;Biological Process;Biology;Candidate Disease Gene;Cell division;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Codon Nucleotides;CRISPR/Cas technology;Cytometry;Data;Development;Diagnostic;diagnostic tool;Disease;Embryo;enhancing factor;experimental study;Flow Cytometry;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;genomic profiles;Goals;Half-Life;Health;High Prevalence;Homologous Gene;Human;human disease;innovation;insight;knock-down;Laboratories;Location;Malignant Neoplasms;Mediating;Messenger RNA;MicroRNAs;Molecular;Mutation;Mutation Detection;novel;Open Reading Frames;Organism;Outcome;Output;overexpression;Pathologic;Pathway interactions;Peptides;Phenotype;Post-Transcriptional Regulation;posttranscriptional;prevent;Process;Proteins;Proteomics;recruit;Regulation;Reporter;Research;ribosome profiling;Ribosomes;RNA;Role;Shapes;Stress;targeted treatment;Terminator Codon;Therapeutic Intervention;tool;transcriptome sequencing;Translating;translational engagement;Translational Regulation;Translations;Untranslated Regions;Untranslated RNA;Vertebrates;Work;Zebrafish

PROJECT_TITLE: Small translated ORFs in the 3'UTR enhance translation in vertebrates

STUDY_SECTION: MGB

STUDY_SECTION_NAME: Molecular Genetics B Study Section[MGB]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Many Black communities in Metro-Atlanta face high levels of environmental exposures that can negatively impact the health of Black children. The proposed Center for Children's Health Assessment, Research Translation, and Combating Environmental Racism (CHARTER), will develop effective strategies to translate research findings of importance to children's environmental health to relevant stakeholders in the community, academia, and healthcare. The CHARTER center will work with community partners to develop communication products that can be used to improve children's health.

PI_NAMEs: AHN, SUN JOO JOO;MCCAULEY, LINDA A. (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: Academia;Achievement;Affect;Behavioral Sciences;Black race;catalyst;Center for Translational Science Activities;Child;Child Health;Clinical;clinical practice;college;Communication;Communities;community engagement;Community Health;Community Outreach;community partners;Dedications;Development;Dissemination and Implementation;Environment;Environmental Exposure;Environmental Health;Environmental Impact;experience;Face;Faculty;Family;Fostering;Goals;Health;health assessment;health communication;health disparity;health literacy;Health Personnel;Health Status;Healthcare;Historically Black Colleges and Universities;improved;Individual;innovation;Interdisciplinary Study;International;Investigation;Journalism;Knowledge;Mentors;Modeling;next generation;Play;Populations at Risk;Pregnant Women;programs;Psychology;Public Health;Public Health Practice;racism;rapid growth;Research;Research Personnel;Risk;Role;Science;Scientist;social;Translating;Translational Research;Translations;Universities;Work

PROJECT_TITLE: Center for Children’s Health Assessment, Research Translation, and Combating Environmental Racism (CHARTER)


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: COLLEGE PARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: NARRATIVE Adolescence is a vulnerable period for the development of loneliness, particularly for individuals with autism spectrum disorder (ASD), and these feelings of loneliness predict significant negative mental and physical health outcomes. underpinning the need to understand risk and protective mechanisms for the development of loneliness in high-risk populations such as ASD. Using a prospective, longitudinal design and cutting-edge, ecologically valid measures, the current proposal will provide critical missing information about the cognitive, neural, and social mechanisms that predict the development of loneliness in adolescents with typical development and ASD. A better understanding of these risk and protective mechanisms will allow for more targeted interventions to reduce the experience of loneliness and associated negative outcomes.

PI_NAMEs: REDCAY, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: 14 year old;Address;Adolescence;Adolescent;adolescent with autism spectrum disorder;Adult;adverse outcome;Affect;Affective;Age;autism spectrum disorder;Behavior assessment;Behavioral;biopsychosocial;Brain;Chronic Disease;Cognitive;cognitive system;Complex;Data;Development;Ecological momentary assessment;effective intervention;emotional distress;experience;Feeling;Friendships;Functional Magnetic Resonance Imaging;functional MRI scan;Goals;high risk population;high-risk adolescents;imaging approach;Individual;individuals with autism spectrum disorder;informant;innovation;Intervention;Investigation;Knowledge;laboratory experiment;Link;Loneliness;longitudinal design;Measures;Mediating;Mental Depression;Mental Health;Methods;Mission;model development;Modeling;Moods;mortality;movie;National Institute of Mental Health;neural;neuromechanism;novel;Outcome;Participant;Patient Self-Report;Patients;peer;peer influence;Perception;physical conditioning;Play;Population;Process;prospective;protective factors;Public Health;Questionnaires;Reporting;Research;response;Rewards;Risk;Risk Factors;Role;Sampling;Self-Injurious Behavior;Silk;social;Social Interaction;Social Processes;Stimulus;Suicide;Surveys;System;Teenagers;Testing;Time;translational impact;Work

PROJECT_TITLE: A Prospective-Longitudinal Investigation of the Biopsychosocial Predictors of Loneliness Across Adolescence in Autism and Typical Development


NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: MCCAULEY, LINDA A. (contact)

PROJECT_TERMS: Academia;Advisory Committees;African American;Area;Black race;Child;Child Health;Collaborations;Communication;Communities;community collaboration;community engagement;Community Outreach;Development;Educational workshop;Environment;Environmental Exposure;Environmental Health;Environmental Impact;Evaluation;Foundations;Funding;Goals;Health;health assessment;Health Personnel;Individual;innovation;Institution;Investigation;Knowledge;knowledge translation;Lead;Leadership;meetings;Mentorship;Monitor;National Institute of Environmental Health Sciences;Outcome;Output;outreach;racism;recruit;Research;Research Personnel;Resource Allocation;Role;Scholarship;Science;Services;synergism;Translating;Translational Research;Translations;Underrepresented Populations;Universities;University adminstration;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health;Women's Health Research

PI_NAMEs: MARSIT, CARMEN JOSEPH (contact)

PROJECT_TERMS: Address;Advocacy;Affect;Area;Black Populations;black women;Black, Indigenous, People of Color;career;career development;Career Mobility;Child;Child Health;Clinical Sciences;college;Communities;community engagement;Coupled;Data;Development;Disparity;education research;Educational process of instructing;Educational workshop;Environment;Environmental Health;environmental health disparity;experience;Faculty;Feedback;Fellowship;Fortification;Funding;Generations;Goals;Health;health assessment;health care delivery;health care disparity;health disparity;Health Promotion;Health Services Accessibility;Historically Black Colleges and Universities;Improve Access;Inequality;Inequity;innovation;Interdisciplinary Study;Knowledge;marginalization;Maternal and Child Health;Mentors;metabolomics;microbiome;Mission;multidisciplinary;National Institute of Environmental Health Sciences;Organization and Administration;Pilot Projects;Prevention;Process;Program Development;programs;racism;Research;Research Personnel;Resources;Role;Science;Scientist;Services;skills;Structure;Study Section;success;synergism;Teacher Professional Development;Time;Toxic Environmental Substances;Toxicant exposure;Toxicology;Training;Training Programs;Translational Research;Translations;Underrepresented Minority;United States Health Resources and Services Administration;United States National Institutes of Health;Universities;Women's Health

PROJECT_TITLE: Development Core


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness;Tobacco

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE This study will examine the effect of transdermal nicotine on cognitive control network function and depression symptoms in older adults with late-life depression. This will advance our understanding of whether or not modulation of cognitive control network function leads to clinical improvement in depression. If our hypotheses are correct, nicotinic receptor agonists may develop into an important antidepressant augmentation strategy.

PI_NAMEs: TAYLOR, WARREN D (contact)

PROGRAM_OFFICER_NAME: EVANS, JOVIER D

PROJECT_TERMS: acetylcholine receptor agonist;Affect;affective disturbance;Agonist;Anterior;anti-depressive agents;Attention;Blinded;Blood;blood oxygenation level dependent response;Brain region;Clinical;clinical effect;cognitive benefits;cognitive control;Cognitive deficits;cognitive enhancement;cognitive performance;cognitive testing;Conflict (Psychology);Data;Depressed mood;depressive symptoms;Detection;disability;Dose;Elderly;emotion dysregulation;emotion regulation;Emotional;Episodic memory;Executive Dysfunction;Exhibits;Functional disorder;Functional Magnetic Resonance Imaging;geriatric depression;Goals;Image;improved;Individual;innovation;Left;Magnetic Resonance Imaging;Major Depressive Disorder;Measures;Mediating;Mental Depression;Mental disorders;mood symptom;Moods;Negative Finding;network dysfunction;neural;Neurobehavioral Manifestations;Neuropsychological Tests;Nicotine;nicotine exposure;nicotine patch;Nicotinic Receptors;older adult;open label;Outcome;Patient Self-Report;Performance;Pharmacotherapy;Phase;pilot trial;Placebo Control;Placebos;Process;Randomized;Randomized, Controlled Trials;Reaction Time;Research;response;rumination;secondary outcome;Selective Serotonin Reuptake Inhibitor;Severities;Short-Term Memory;Specificity;Stimulus;Symptoms;System;targeted imaging;Task Performances;Testing;Therapeutic;Thinking;trait;Validation;Work

PROJECT_TITLE: Nicotinic Modulation of the Cognitive Control System in Late-Life Depression


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Networking and Information Technology R&D (NITRD);Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: AHN, SUN JOO JOO (contact)

PROJECT_TERMS: Acceleration;Address;Area;Awareness;Black race;career;Child;Child Health;child services;Childhood;clinical practice;Collaborations;Communication;Communities;community engagement;Consultations;Coupled;design;Education;Educational workshop;Environmental Health;Equity;Family;gaming environment;Generation Gaps;Grant;Guidelines;health assessment;Health behavior;Health Campaign;health literacy;Health Personnel;Health Promotion;improved;Individual;inner city;innovation;innovative technologies;interest;Knowledge;Lead;learning materials;medical specialties;member;Methods;Mind;Organization and Administration;Persons;Policies;Policy Maker;programs;Public Health;Public Health Practice;racism;Research;Research Personnel;Resources;Risk;risk mitigation;Science;Scientist;Services;social;Social Distance;Testing;Time;Training;Translating;Translational Research;Translations;underserved community;Universities;Urban Community;virtual environment;virtual reality;virtual reality simulation;Work;Youth

PROJECT_TITLE: Translation Core


NIH_SPENDING_CATS: Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: OBOT WITHERSPOON, NSEDU   (contact)

PROJECT_TERMS: Area;Automobile Driving;care providers;Center for Translational Science Activities;Child;Child Care;Child Health;Childhood;Communities;Data;Databases;digital;digital health;digital platform;Disease;Educational Curriculum;Educational Materials;Effectiveness;Electronic Mail;Ensure;Environmental Exposure;Environmental Health;Environmental Impact;experience;Face;Family;Funding;Goals;Grant;Health;health assessment;health communication;health knowledge;Home;implementation efforts;implementation science;Infrastructure;insight;International;Internet;Knowledge;Malignant Childhood Neoplasm;Marketing;medical specialties;meetings;member;National Institute of Environmental Health Sciences;Neighborhoods;neurodevelopment;Nursing Faculty;Outcome;Persons;Policy Maker;Positioning Attribute;Privatization;Program Evaluation;programs;Public Health;racism;Recommendation;Recording of previous events;Research;Resources;Science;Scientific Advances and Accomplishments;social;Stress;success;symposium;Training;Translating;Translational Research;Translations;Trust;Work

PROJECT_TITLE: Coordinating Center


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Genetic mutations as well as gene duplication events affecting AT-1/SLC33A1, SLC25A1 and SLC13A5 are all associated with similar neurodegenerative and neurodevelopmental defects. Here, we report the successful generation of mouse models that reproduce the above human diseases. We also report novel mechanistic discoveries underlying the disease phenotypes. The long-term objective of this proposal is to dissect the molecular and biochemical mechanisms associated with the above diseases and explore therapeutic strategies to prevent or rescue them.

PI_NAMEs: PUGLIELLI, LUIGI  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Acetyl Coenzyme A;Acetylation;Acetyltransferase;Affect;Animals;Area;autism spectrum disorder;Autophagocytosis;Biochemical;Biochemical Pathway;Biochemistry;Biological;Biological Process;Biology;Biomedical Research;Brain;Cell membrane;citrate carrier;Citrates;Complement;Cytosol;Databases;Defect;Developmental Delay Disorders;Disease;disease phenotype;DNA Sequence Alteration;Embryo;Encephalopathies;Endoplasmic Reticulum;epileptic encephalopathies;Equilibrium;Event;Funding;Gene Duplication;Generations;Genetic;Glutamate-ammonia-ligase adenylyltransferase;Hereditary Sensory and Autonomic Neuropathies;Heterozygote;HSPB1 gene;human disease;Individual;Inherited;Intellectual functioning disability;Laboratories;life span;loss of function;Lysine;Mass Spectrum Analysis;Membrane Transport Proteins;Metabolic;Metabolic Pathway;mitochondrial membrane;Modeling;Molecular;mouse model;Mus;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurodevelopmental Disorder;Neurons;Nonsense Codon;novel;Outcome;overexpression;Paper;Pathway interactions;Phenotype;Play;prevent;Progeria;Proteins;Proteome;proteostasis;Publishing;Quality Control;Reporting;Research;Role;Spastic Paraplegia;Testing;Therapeutic;Transgenic Mice

PROJECT_TITLE: Spastic paraplegia, neurodegeneration and autism: possible role for AT- 1/SLC33A1?

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: AUSTIN

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE A phenomenological model of post-infarct myocardial remodeling will be developed examining the impacts of polymer injection therapy on left ventricle wall structure. We will incorporate heart-speciﬁc image data both to tai- lor predictions and treatment to individual hearts, and to validate tissue and organ-level predictions. We envision that this model will in the future be used clinically to guide patient-speciﬁc polymer injection therapy.

PI_NAMEs: GOODBRAKE, CHRISTIAN  (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Aftercare;American;Anatomy;Animals;Cardiac;Cardiovascular system;chemokine;Cicatrix;Clinical;Collagen;Combined Modality Therapy;Complex;Computer Models;Congestive Heart Failure;Connective Tissue;Consumption;cost;cytokine;Data;density;Deposition;Development;Diffusion Magnetic Resonance Imaging;Evolution;Fiber;Fibroblasts;Future;Geometry;Goals;Growth;Guidelines;Health;Heart;Heart failure;heart function;Heart Ventricle;Image;Imaging technology;Impairment;Individual;individual patient;individualized medicine;Infarction;Injection of therapeutic agent;Injections;Investigation;Ischemia;Left;Left Ventricular Remodeling;Left ventricular structure;Leukocytes;Link;Measures;Mechanics;Mitral Valve;Mitral Valve Insufficiency;Modality;Modeling;Muscle Cells;Myocardial;Myocardial Infarction;Myocardium;Nature;Necrosis;Nodule;optimal treatments;Organ;Patients;phenomenological models;Polymers;preclinical study;predictive modeling;pressure;Process;Research;Resolution;response;Shapes;Sheep;simulation;Site;Specimen;Stress;Structure;therapy development;Time;Tissues;Translations;Treatment Protocols;Validation;Ventricular Remodeling

PROJECT_TITLE: A predictive model of left ventricle remodeling in the presence of injected polymer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F15-Y(20)L]


NIH_SPENDING_CATS: Clinical Research;Lung;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Epithelial cells (EpCs) play an important role in host defense, providing a barrier to the outside world and activating the immune system in response to outside insults. We have found that a unique epithelial cell called a tuft cell is activated by allergens and promotes allergic inflammation. The goals of this grant are to understand how tuft cells remodel the airway barrier in durable ways that promote chronic inflammation.

PI_NAMEs: BARRETT, NORA AMANDA (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Acetylcholine;airborne allergen;airway epithelium;airway inflammation;airway remodeling;airway repair;Allergens;Allergic inflammation;Automobile Driving;Basal Cell;Biological Assay;Bleomycin;Cell Differentiation process;Cells;Chronic;chronic inflammatory disease;chronic rhinosinusitis;cysteinyl-leukotriene;cytokine;Data;designer receptors exclusively activated by designer drugs;Development;Distal;Elements;Epithelial Cells;Epithelium;epithelium regeneration;Fluorescent in Situ Hybridization;Generations;Gland;Goals;Goblet Cells;Grant;Helminths;Histologic;Host Defense;Human;Immune;Immune system;Inflammation;Inflammatory;Influenza;injured airway;Interleukin-13;Intestines;Label;Leukotriene E4;lipid mediator;Local Therapy;Lung;lung injury;lung repair;Lymphoid Cell;Mesenchymal;Metaplasia;microbiota;Molds;Molecular;mouse model;Mucous Membrane;Mus;Nose;novel;pathogen;Pathologic;Pathway interactions;Patients;Pattern;pharmacologic;Play;polyposis;Population;progenitor;programs;pulmonary function;Pyroglyphidae;receptor;regenerative;Regenerative pathway;Reporter;Reporting;response;Role;Sensory;Sentinel;Shapes;single-cell RNA sequencing;Specialized Epithelial Cell;stem cell population;Submucosa;Surface;Taste Buds;Testing;Tissues;Trachea;Tracheal Epithelium;transcription factor;transcriptome sequencing;wound healing

PROJECT_TITLE: Type 2 Inflammation and Remodeling Elicited Through an LTE4/OXGR1-dependent pathway

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-B (03)]


NIH_SPENDING_CATS: Chronic Pain;Estrogen;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury;Women's Health Research

ORG_CITY: WASHINGTON

ORG_DEPT: NEUROLOGY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Narrative Chronic neuropathic pain is a significant health care problem in the United States and Worldwide. Studies in this application will investigate divergent mechanism through which TNFR1 and TNFR2 signaling governs the development and recovery from chronic pain, respectively. Furthermore, we will interrogate the development of novel therapies that are effective in both women and men with chronic pain.

PI_NAMEs: BETHEA, JOHN ROLAND (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Age;Agonist;Anterior;Attenuated;Brain region;Cell Communication;Cells;chronic neuropathic pain;chronic pain;chronic pain management;cingulate cortex;Combined Modality Therapy;Data;design;Development;Disease;effective therapy;Elderly;Estrogen Receptor 2;Estrogen Receptors;Estrogen Replacements;Estrogens;Female;Fulvestrant;Genetic;genetic approach;Genetic study;Goals;Healthcare;Hippocampus;Immune;Individual;Inflammation;inhibitor;injury and repair;male;Mediator;men;Modeling;Mus;neuroinflammation;Neurons;neuropathology;novel therapeutics;NR1 gene;Ovariectomy;Pain;Pathologic;Pathologic Processes;Peripheral nerve injury;pharmacologic;prevent;Process;Publishing;receptor;Receptor Signaling;Receptors, Tumor Necrosis Factor, Type II;Recovery;Resolution;Role;Series;sex;Sex Differences;Signal Transduction;somatosensory;Somatosensory Cortex;Spinal cord injury;Synapses;Testing;Therapeutic;therapy development;TNF gene;TNFRSF1A gene;TNFRSF1B gene;Tumor Necrosis Factor Receptor;United States;Woman

PROJECT_TITLE: TNF in Injury and Repair Processes Following Traumatic SCI

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Alcohol use and IPV are serious problems in the Veteran population, and since these two problems are closely linked, interventions that address both problems may have considerable promise. The proposed study may prove important in advancing this area of research and practice through providing data demonstrating the benefits of a brief pre-group alcohol intervention. There is some evidence that alcohol-related problems represent a barrier for group IPV intervention program compliance and effectiveness, and thus a brief pre-group alcohol intervention may be particularly impactful. The study team is currently implementing an evidence-based IPV intervention nationally in VA, and thus possible enhancement of the program through inclusion of alcohol intervention may have substantial positive benefits for a large number of Veterans, their intimate partners, and other family members.

PI_NAMEs: TAFT, CASEY T (contact)

PROJECT_TERMS: Address;Aftercare;Alcohol abuse;alcohol consequences;Alcohol consumption;alcohol intervention;alcohol involvement;alcohol misuse;alcohol related problem;alcohol seeking behavior;Alcoholics Anonymous;Alcohols;Area;Awareness;Clergy;clinically relevant;Communities;Data;Development;Education;Educational Intervention;Effectiveness;Ensure;evidence base;Family;Family member;follow-up;Friends;Group Homes;group intervention;Healthcare Systems;help-seeking behavior;Home;Intervention;intervention program;Interview;intimate partner violence;Link;Location;male;Marriage and Family;Measures;Medical center;military veteran;Modeling;Monitor;Motivation;motivational enhancement therapy;Outcome;Participant;Personal Satisfaction;prevent;programs;psychologic;Randomized;Readiness;Reporting;Research;Risk;Safety;Schedule;screening;Source;standard care;substance use treatment;System;Telephone;Testing;Therapeutic Intervention;trauma exposure;treatment as usual;treatment group;Veterans;violence perpetration

PROJECT_TITLE: Adjunctive Motivational Alcohol Intervention to Prevent Intimate Partner Violence


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Human Genome;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Genetic disease risk often manifests through complex feedback between molecular abnormalities and changes in tissue structure, but rigorously quantifying these tissue changes to map their genetic risk factors remains a significant challenge. In this project, we will develop and validate a deep learning analytical framework to integrate histological traits into systems genetics analysis of complex diseases. Our analytical framework will enable the routine inclusion of histological evaluation into systems genetics and will facilitate a more comprehensive and accurate determination modifier genes and pathways, providing greater opportunities for therapeutic intervention.

PI_NAMEs: MAHONEY, JOHN MATTHEW (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Adopted;Affect;Age;age related;aged;Alleles;Automobile Driving;Biological Models;Biomedical Research;Categories;Cell Death;Chromosome Mapping;Clinical;cohort;Communities;Complex;Computer Vision Systems;Data;Data Set;deep learning;deep neural network;design;Development;Disease;disorder risk;Dissection;Etiology;Evaluation;Feedback;Fibrosis;fitness;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic analysis;genetic approach;Genetic Diseases;Genetic Models;Genetic Risk;genetic risk factor;Genetic study;Genetic Variation;Genome;Genotype;Heritability;Histologic;histological image;Histology;Histopathology;Human;human model;Image;image processing;improved;Inflammation;Kidney;Kidney Diseases;Maps;Measures;Mediating;Mediation;Mediator;Methodology;Methods;Modeling;Molecular;Molecular Abnormality;Molecular Disease;Molecular Profiling;multi-scale modeling;Mus;Network-based;novel;novel strategies;Oranges;Organ;Organism;Outcome;Outcome Study;Pathologist;Pathway Analysis;Pathway interactions;Patients;Pattern;Phenotype;Physiological;Physiology;poor health outcome;Population Heterogeneity;Pre-Clinical Model;Proteome;Proteomics;Public Health;Quantitative Genetics;Quantitative Trait Loci;Renal function;risk variant;Statistical Models;Structure;System;Testing;therapeutic development;Therapeutic Intervention;Time;Tissue-Specific Gene Expression;Tissues;tool;Training;trait;transcriptome;transcriptomics;Variant

PROJECT_TITLE: Integrating high-throughput histology with systems genetics through causal graphical models

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


PHR: PROJECT NARRATIVE Antibody Fc-dependent effector functions are central to the mechanism of action of numerous therapeutic antibodies for the treatment infectious diseases and cancer. Fc effector functions are triggered by the crosslinking of multiple Fc receptors by multivalent antibody coated pathogenic cells. The work described here will seek to delineate, in unprecedented detail, the cytotoxic mechanisms and signaling events triggered by each receptor on myeloid cells and thus provide a rational framework for the engineering of therapeutic antibodies having more potent effector functions and improved clinical efficacy.

PI_NAMEs: GEORGIOU, GEORGE GEORGIOU (contact);VARADARAJAN, NAVIN

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Affinity;Anti-Infective Agents;Antibodies;antibody-dependent cell cytotoxicity;Antigen-Antibody Complex;Antigens;Area;Binding;Biological Assay;Biological Products;Cell Cycle Kinetics;cell killing;Cell surface;Cells;clinical development;clinical efficacy;Coupled;crosslink;cytokine;Cytometry;cytotoxic;cytotoxicity;Data;density;Development;Effector Cell;Engineering;Event;Fc domain;Fc Receptor;Glean;Human;IgG1;Immune checkpoint inhibitor;immunological synapse formation;improved;Individual;infectious disease treatment;inhibiting antibody;Kinetics;Leukocytes;Ligation;Macrophage;Malignant Neoplasms;Maps;Measurement;Mediating;microscopic imaging;Molecular;monocyte;Myelogenous;Myeloid Cells;nano;Natural Killer Cells;neutrophil;novel;Outcome;pathogen;Pathogenicity;Phagocytosis;Phenotype;Phosphopeptides;phosphoproteomics;Phosphorylated Peptide;Play;Process;Property;receptor;receptor binding;receptor expression;Role;Signal Transduction;sound;Surface;Synapses;Testing;Therapeutic antibodies;Therapeutic Monoclonal Antibodies;Work

PROJECT_TITLE: Systematic, molecular level analysis of the Fc receptor ligation on antibody effector functions


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Lung;Rare Diseases

ORG_CITY: DENVER

ORG_NAME: NATIONAL JEWISH HEALTH

ORG_STATE: CO

PHR: PROJECT NARRATIVE Through our published and preliminary data, we have identified a novel process by which expression of matrix metalloproteinase (MMP)-3 in acute lung injury/ARDS drives disease pathology. Our work will answer critical questions about why some patients resolve ARDS while others progress to life-threatening disease and by developing a therapeutic inhibitor of disease progression, as well as essential information about which patients and at what stages of disease progression therapeutic intervention will be most beneficial. Successful completion of these studies will advance our understanding of ARDS and provide a novel therapeutic approach for this devastating disorder.

PI_NAMEs: DOWNEY, GREGORY PAUL (contact);RADISKY, DEREK C;RADISKY, EVETTE S

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: Acceleration;Acids;Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Adhesions;Affect;Affinity;Alveolar;alveolar epithelium;Animal Model;Area;aspirate;Basal Cell;Basement membrane;Binding;biobank;Biological Markers;Blood;Blood capillaries;Cell Culture Techniques;Cell secretion;Cells;Characteristics;Clinical;Clinical Data;Clinical Research;Clinical/Radiologic;clinically relevant;conditional knockout;Data;design;Directed Molecular Evolution;Disease;Disease Progression;Distal;Epithelial Cells;epithelial injury;epithelial repair;Epithelium;Event;experimental study;Extracellular Matrix;Failure;Fibroblasts;Gases;Health Care Costs;healthcare burden;high risk;Human;human disease;Immunohistochemistry;Impairment;improved outcome;In Vitro;in vivo Model;indexing;Inflammation;influenza infection;influenzavirus;inhibitor;inhibitor therapy;Injury;injury and repair;Intercellular Junctions;Interdisciplinary Study;Kinetics;Knowledge;Laboratories;Life;Link;Liquid substance;Lung;Lung Diseases;lung injury;lung repair;Macrophage;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Mediating;Membrane;MMP3 gene;mortality;mouse model;Mus;neutrophil;novel;novel therapeutic intervention;Organ Donor;overexpression;Pathogenesis;Pathology;Pathology processes;Pathway interactions;patient subsets;Patients;Peptide Hydrolases;Permeability;personalized strategies;Persons;Physiological;Play;pleiotropism;Population;pre-clinical;Pre-Clinical Model;predictive marker;preservation;prevent;Process;Production;Proteolysis;Publishing;Pulmonary Edema;Recovery;repaired;Research;Research Proposals;Resistance;Resolution;response;restoration;Role;Sampling;single cell analysis;single-cell RNA sequencing;Slice;specific biomarkers;Stimulus;Stromelysin 1;Structure of parenchyma of lung;Supportive care;Testing;Therapeutic;Therapeutic Agents;therapeutic evaluation;Therapeutic Intervention;Time;Tissue Inhibitor of Metalloproteinase-1;Tissue Inhibitor of Metalloproteinases;Tissues;transcriptomics;Transgenic Mice;translational applications;United States National Institutes of Health;Variant;ventilation;Work

PROJECT_TITLE: Proteolysis in the Pathogenesis of ARDS

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(05)]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Lung;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PUBLIC HEALTH RELEVANCE Over 700,000 Americans receive invasive mechanical ventilation in an ICU each year. Many of these patients do not receive evidence-based therapies proven to save lives, leading to preventable morbidity and mortality. Innovative strategies to overcome the barriers to evidence-based practice and speed knowledge translation in the ICU are urgently needed. By developing novel approaches for knowledge translation in acute respiratory failure, this research program will help new treatments reach the bedside more quickly, leading to improved outcomes for critically ill patients.

PI_NAMEs: KAHN, JEREMY M (contact)

PROGRAM_OFFICER_NAME: STEFAN, MIHAELA STEFANIA

PROJECT_TERMS: Acute respiratory failure;Address;American;Behavior;biomedical informatics;Clinical Trials;Collaborations;Critical Care;Critical Illness;Electronics;evidence base;Evidence based practice;Evidence based treatment;experience;Goals;Health system;Hospitals;improved;improved outcome;innovation;Intelligence;Intensive Care;knowledge translation;Link;Measures;Mechanical ventilation;Mediator;member;Memory;Morbidity - disease rate;mortality;novel;novel strategies;Patient Care;Patient-Focused Outcomes;Patients;Performance;Physicians;Principal Investigator;programs;Psychology;public health relevance;Research;Role;Science;Scientist;Sociology;Speed;support tools;tool;Translations;uptake

PROJECT_TITLE: Organizational strategies for improving evidence-uptake in intensive care


ORG_CITY: PHILADELPHIA

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE  When you inhale harmful bacteria, they can stimulate bitter or sweet taste receptors found in epithelial cells or immune cells to activate immune defenses. We need new ways to test which taste receptors are activated by specific bacteria, as well as better ways to screen for activation of specific taste receptors for food and nutrition research. The research described here will develop and validate a new cell-based method to screen for taste receptor activation and will reveal new insights into cellular signaling pathways activated by taste receptors.

PI_NAMEs: LEE, ROBERT J. (contact)

PROJECT_TERMS: Address;Adrenergic Receptor;Agonist;airway epithelium;Amino Acids;arm;Arrestins;Aspergillus flavus;Aspergillus fumigatus;Bacteria;Binding;Binding Proteins;Biological Assay;Biology;Calcium;Calcium Channel;calcium indicator;Calcium Signaling;Cells;Clinical;clinically relevant;Complex Mixtures;Couples;Cultured Cells;Cyclic AMP;Data;Development;Epithelial Cells;Epithelium;Exhibits;expression vector;Family;Fluo 4;Fluorescence;Food;fungus;Future;G-Protein-Coupled Receptors;Genetic Transcription;Glutaminase;Glutamine;GTP-Binding Proteins;Heterotrimeric GTP-Binding Proteins;High Pressure Liquid Chromatography;high throughput screening;Immune;Immunologic Receptors;improved;Inhalation;Innate Immune Response;insight;instrumentation;Ligands;Mediating;Methicillin;Methicillin Resistance;Methods;Molecular;Natural Immunity;novel;nutrition;Nutritional Study;Optical Methods;Optics;Orphan;pathogen;pathogenic bacteria;pathogenic fungus;Pathway interactions;Peptide Hydrolases;Phospholipase C;Phospholipases A;Phosphotransferases;Plant Extracts;Play;Potassium Channel;preservation;prevent;Protein Isoforms;Pseudomonas aeruginosa;Publications;Publishing;Quinine;rat Gnat3 protein;Reader;receptor;Receptor Activation;Reporting;Research;respiratory smooth muscle;response;Role;screening;Sensory;Signal Pathway;Signal Transduction;Signaling Protein;Staphylococcus aureus;sweet receptor;sweet taste perception;Taste Buds;Taste Perception;taste transduction;Testing;Tissues;Tongue;tool;Validation;Vegetables;Visualization;voltage;Work

PROJECT_TITLE: Development and validation of novel optical methods for direct screening of taste receptor activation

STUDY_SECTION: NIC

STUDY_SECTION_NAME: Neuroscience of Interoception and Chemosensation Study Section[NIC]


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Regenerative Medicine;Wound Healing and Care

ORG_CITY: CINCINNATI

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Engineered skin substitute (ESS) has been successfully used for wound closure in burns, burn scars, chronic wounds, and giant nevi. However, ESS only fulfills basic skin functions and fails to match the structural and biophysical characteristics of the human skin. The proposed research will apply a three-pronged strategy to bioengineer hair follicles in ESS: fabricating the hair follicle niche environment at the tissue level, stimulating with BMP6 at the molecular level, and reprogramming the DP phenotype at the genetic level The knowledge gained is of great importance to engineer fully functional skin constructs and promote regenerative medicine.

PI_NAMEs: ZHANG, YUHANG  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: 3-Dimensional;Ablation;Acceleration;Address;base;Biological;Biology;Biomedical Engineering;biophysical properties;BMP6 gene;Burn injury;burn scars;burn wound;Cell Physiology;cell type;Cells;chronic wound;Complex;CRISPR-mediated transcriptional activation;Cutaneous;Dermal;design;Engineered skin;Engineering;Environment;Epithelium;experimental study;Failure;Fibroblasts;Genetic;Goals;Growth;Hair;Hair bulb structure;Hair follicle structure;hair papilla;Hair shaft structure;Health Benefit;Human;Human Characteristics;improved;In Vitro;in vivo;innovation;keratinocyte;Knowledge;Lasers;Mechanics;Mediating;Mesenchymal;Microanatomy;micropore;Modeling;Molecular;mouse model;multi-scale modeling;Nevus;novel;Outcome;Pattern;Phenotype;Population;programs;Proliferating;Property;Regenerative Medicine;Research;Role;self assembly;Signal Transduction;Skin;Skin Substitutes;Skin Tissue;Societies;SOX18 gene;spheroids;Sweat Glands;System;Testing;Tissue Engineering;Tissues;tongue papilla;tool;transcription factor;Work;wound closure

PROJECT_TITLE: Multiscale modeling of an inductive hair follicle microenvironment in engineered skin substitute

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: ROCHESTER

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: PROJECT NARRATIVE Multiple common forms of hereditary, age-related, and noise-induced hearing loss are ascribed to disturbance of the lymphatic fluids in the inner ear. This project has Relevance to Public Health because it holds promise to improve quality of life in these individuals by establishing a new method for drug or gene delivery into the inner ear. Our results can guide potential treatments for disorders related to the cochlear-fluids.

PI_NAMEs: NAM, JONG-HOON  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Acoustic Stimulation;Acoustics;Adult;age related;Agitation;Animals;Apical;Area;base;Biophysics;Blood;Body Fluids;cell motility;Characteristics;Cochlea;Cochlear duct;Cochlear nucleus;Computer Models;Custom;Data;design;Diffusion;Disease;Distant;Drug Delivery Systems;Drug Targeting;Electric Stimulation;Electrodes;Experimental Designs;experimental study;Fluid Balance;Frequencies;Gene Delivery;gene therapy;Geometry;Gerbils;Goals;Health;Hearing;hearing impairment;Hour;Image;Implant;improved;in silico;In Vitro;in vivo;Individual;Inherited;Injections;inner ear diseases;innovation;insight;Kainic Acid;Labyrinth;Learning;Length;Liquid substance;Location;Lymph;Measures;Mechanical Stimulation;Mechanics;mechanotransduction;Methods;Microfluidics;minimally invasive;Modeling;models and simulation;Molecular;Motility;Motion;neural;Neurotoxins;Noise;Noise-Induced Hearing Loss;novel;Operative Surgical Procedures;Optical Coherence Tomography;Outer Hair Cells;Pattern;Perforation;Pharmaceutical Preparations;Phase;physiologic model;Physiological;prevent hearing loss;Public Health;Pump;Quality of life;Radial;Resolution;response;Rest;round window;Salicylic Acids;Sensorineural Hearing Loss;Series;Site;sound;sound frequency;Source;Stimulus;Structure;surgical risk;Temporal bone structure;Testing;theories;Time;Tissues;United States;vibration;virtual

PROJECT_TITLE: Mass transport in the inner-ear fluid


NIH_SPENDING_CATS: Asthma;Clinical Research;Clinical Trials and Supportive Activities;Emergency Care;Health Services;Infectious Diseases;Lung;Pediatric

ORG_CITY: TUCSON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative The proposed project is a multicenter clinical trial that seeks to determine the efficacy of Azithromycin for the treatment of severe wheezing in preschoolers who present to the Emergency Department. The trial will also determine the prevalence of bacteria and viruses associated with these events and any correlation with responsiveness to Azithromycin. The trial will be conducted at six clinical sites from the Pediatric Emergency Care Applied Research Network (PECARN).

PI_NAMEs: DENNINGHOFF, KURT R;MARTINEZ, FERNANDO D (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 17q;5 year old;6 year old;Accident and Emergency department;Acute;Admission activity;age group;aged;airway obstruction;Ambulatory Care Facilities;Anti-Bacterial Agents;Antibiotics;Antiinflammatory Effect;Applied Research;Asthma;Azithromycin;Bacteria;Bacterial Infections;bacterial resistance;Biological;Cephalosporins;Child;clinical research site;Clinical Trials;Clinical Trials Design;Diagnosis;disability;Dose;efficacy evaluation;Emergency Care;Emergency department visit;Event;experience;Future;Gene Cluster;Genes;Genetic;Genetic Carriers;Genetic Polymorphism;Genomics;Guidelines;Haemophilus influenzae;Health Care Costs;health care service utilization;high risk;Hospitalization;hospitalization rates;IL8 gene;improved;Life;Longitudinal Studies;Lower respiratory tract structure;Macrolides;Microbe;microbial;microbial community;microbiota;Modernization;Moraxella catarrhalis;Multi-Institutional Clinical Trial;Nasopharynx;novel therapeutics;Nursery Schools;Outcome;pathogenic bacteria;Pathogenicity;pediatric emergency;Penicillins;Pharyngeal structure;Placebos;Play;Population;predicting response;Preschool Child;Prevalence;Property;psychologic;Randomized;Recommendation;Reporting;Resistance;respiratory;respiratory microbiome;response;Risk;Risk Factors;Role;Sampling;Schedule;School-Age Population;Severities;Severity of illness;social;Source;Streptococcus pneumoniae;symptomatic improvement;Symptoms;Technology;Testing;treatment guidelines;United States;Variant;Virus;Wheezing

PROJECT_TITLE: 1/2: AZithromycin Therapy in Preschoolers with a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Serious Mental Illness;Suicide;Suicide Prevention

PHR: PROJECT NARRATIVE This application aims to examine the role of flexible emotion regulation in the context of interpersonal stress at the behavioural and physiological level as a proximal indicator of risk for suicidal ideation and behavior in a high-risk adolescent sample. This proposal has both scientific and clinical significance because there are few studies clarifying the contribution of regulatory processes as they contribute to short-term risk for adolescent suicide. This research has the potential to identify factors that inform when adolescents are at greatest risk for suicidal outcomes in periods of transition and to identify targets for intervention during these periods.

PI_NAMEs: BETTIS, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Address;Adolescent;Adolescent and Young Adult;Adolescent Risk Behavior;adolescent suicide;Affect;Affective;Age;Arousal;Autonomic nervous system;Behavior assessment;Behavioral;Biological;biological adaptation to stress;Cause of Death;Clinical;Clinical Research;clinical translation;clinically significant;cognitive function;Collaborations;Cues;Data;data acquisition;Data Analyses;Data Collection;Development;Disease;Ecological momentary assessment;effective intervention;emotion dysregulation;emotion regulation;Emotional;emotional functioning;Emotions;Event;evidence base;experience;Feeling suicidal;flexibility;follow up assessment;follow-up;Fostering;Frequencies;Future;Goals;Grant;high risk;high-risk adolescents;hospital services;Hospitals;improved;in vivo;indexing;Individual;innovation;inpatient psychiatric treatment;Intervention;Investigation;Laboratories;Life;Mentorship;Methodology;Methods;mobile application;Monitor;multilevel analysis;National Institute of Mental Health;Nature;Outcome;Parasympathetic Nervous System;Participant;Patient Self-Report;Physiological;post intervention;Process;programs;promote resilience;prospective;Protocols documentation;Psychophysiology;Public Health;Questionnaires;Recording of previous events;recruit;Regulation;Research;research study;respiratory;response;Risk;Risk Factors;Role;Sampling;Series;Services;Severities;Shapes;Sinus Arrhythmia;skills;social media;Stress;stressor;suicidal adolescent;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;suicide rate;Sympathetic Nervous System;Testing;theories;Time;Training;Translational Research;vulnerable adolescent;Writing;Youth

PROJECT_TITLE: Emotion Regulation Flexibility and Suicide Risk

STUDY_SECTION: PDRP

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Narrative The studies will lead to a deeper understanding of how synapses and circuits perform computations. These studies are directly relevant to numerous neurological disorders that involve proteins implicated in short-term plasticity, such as Parkinson's disease, epilepsy and schizophrenia.

PI_NAMEs: REGEHR, WADE G (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Adult;Behavior;Behavior Control;Behavioral;Brain;Calcium;Calcium Signaling;cell type;Cerebellar Cortex;Cerebellar Diseases;Chemosensitization;Elements;Epilepsy;Feedback;Frequencies;Functional disorder;Future;Goals;Grant;in vivo;insight;Kinetics;knockout animal;Knockout Mice;Mediating;millisecond;Molecular Genetics;motor learning;Nervous System Disorder;Neurons;neurotransmitter release;Output;Parkinson Disease;Play;presynaptic;presynaptic neurons;Probability;Protein Isoforms;protein kinase C beta;Proteins;Purkinje Cells;Role;Schizophrenia;sensor;Social Behavior;Synapses;synaptic function;Synaptic plasticity;synaptotagmin VII;Testing;Time;transmission process;Viral

PROJECT_TITLE: Mechanisms and Functions of Synapses and Circuits


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

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: Triple negative breast cancer (TNBC, characterized by lack of expression of ER, PR, and Her2) is one of the most aggressive and deadliest types of cancer, with high incidence of metastatic progression. Despite significant progress, the molecular mechanisms that lead to the acquisition of metastatic ability in cancer cells are not fully elucidated. The aim of our proposed research is to identify novel metabolic vulnerabilities that can be leveraged therapeutically to suppress TNBC invasiveness and metastasis.

PI_NAMEs: BIANCHI-SMIRAGLIA, ANNA  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Affect;Area;Aryl Hydrocarbon Receptor;Automobile Driving;Biology;breast cancer progression;cancer cell;cancer invasiveness;cancer type;Cell membrane;cell motility;Cells;Data;design;Detection;Distant;Elements;Enzymes;experimental study;ezrin;Family;Focal Adhesion Kinase 1;Focal Adhesions;G-Protein-Coupled Receptors;gain of function;Genetic;Genetic Transcription;Goals;GTP-Binding Proteins;Guanosine;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;improved;in vivo;Incidence;Inositol;insight;Invaded;Kruppel-like transcription factors;Lesion;loss of function;Malignant Breast Neoplasm;Malignant Neoplasms;MDA MB 231;Mediating;Mediator;Membrane;Metabolic;Metabolic Pathway;Metabolism;Metastatic breast cancer;Molecular;Monitor;Monomeric GTP-Binding Proteins;mortality;Motility;Mutation;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;novel therapeutic intervention;Oncogenic;Organ;Oxidoreductase;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Pharmacological Treatment;Physiological;Play;prevent;Prevention;Process;Production;protein activation;Proteins;Regulation;Reporter;Reporting;Research;rho GTP-Binding Proteins;Role;sensor;Signal Transduction;Site;small hairpin RNA;Stains;Structure;Supplementation;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;transcription factor;Transcriptional Regulation;triple-negative invasive breast carcinoma;tumor;Tumor Cell Invasion;tumor growth;tumor progression;tumorigenesis;virtual;Work

PROJECT_TITLE: Leveraging the GTP Biosynthetic Pathway for Anti-Tumor Therapies

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Aging;Cardiovascular;Contraception/Reproduction;Estrogen;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Hypertension;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research;Women's Health Research

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

PHR: PROJECT NARRATIVE Although women are commonly viewed as protected from cardiovascular disease until menopause, recent clinical evidence indicates that excess salt consumption and obesity abrogate the cardioprotective effects of female sex hormones. However, the mechanisms whereby salt and obesity induce vascular disorders and blood pressure elevation in premenopausal women remain poorly defined and unstudied. The proposed study will combine the use of novel genetically engineered animal models with discarded human samples, cultured endothelial cells and pharmacological approaches to investigate the potential contribution of both leptin and progesterone.

PI_NAMEs: BELIN DE CHANTEMELE, ERIC J (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: adipokines;Adrenal Glands;Affect;African American population;Age;Aldosterone;Animal Model;Animals;Arteries;Blood Pressure;blood pressure elevation;Blood Vessels;cardioprotection;Cardiovascular Diseases;Cardiovascular system;Caucasians;Cessation of life;Clinical;Consumption;Coronary Arteriosclerosis;CYP11B2 gene;Data;Development;Diet;diet-induced obesity;dietary;disability;Endothelial Cells;endothelial dysfunction;Endothelium;Excess Dietary Salt;Exhibits;Female;female sex hormone;Genetic;genetic approach;Genetic Engineering;high salt diet;Human;human tissue;Hypertension;Impairment;Inbred BALB C Mice;Knowledge;Leptin;Leptin deficiency;leptin receptor;male;Mediating;men;Menopause;Mineralocorticoid Receptor;mortality;mouse model;Mus;novel;nutrition;Obesity;Obesity associated cardiovascular disease;Obesity Related Hypertension;Outcome;overexpression;Persons;pharmacologic;Phenotype;Premenopause;Prevention;Production;Progesterone;Progesterone Receptors;protective effect;racial difference;Receptor Activation;receptor expression;Receptor Inhibition;reproductive;Resistance;restoration;Risk;Risk Factors;salt sensitive;Sampling;sex;Sex Differences;sociodemographics;Sodium Chloride;steroid hormone;Stroke;Testing;Time;Vascular Diseases;Widespread Disease;Woman;women patients

PROJECT_TITLE: Mechanism of cardiovascular disease in premenopausal women

STUDY_SECTION: HM

STUDY_SECTION_NAME: Hypertension and Microcirculation Study Section[HM]


NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT NARRATIVE  Group 1 metabotropic glutamate receptors (Gp1 mGluR)-mediated synaptic plasticity requires rapid activation of protein translation but the precise mechanisms are still not fully understood. The proposed study aims to investigate a promising yet underdeveloped molecule, murine double minute-2 (Mdm2), in Gp1 mGluR- dependent protein translation and synaptic plasticity. Completion of this proposal will significantly expand our understanding of Gp1 mGluR-mediated synaptic plasticity and may introduce novel therapeutic targets into treating mGluR-associated neurological disorders.

PI_NAMEs: TSAI, NIEN-PEI  (contact);ZHANG, KAI

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Animal Behavior;Animal Model;autism spectrum disorder;Brain;Cancer Biology;Cell Cycle;Cell Nucleus;Clinical Trials;Cognition;Cytoplasm;Data;derepression;Development;Disease;Double Minutes;Environment;experience;FMR1 gene;Fragile X Syndrome;Genes;Genets;Hippocampus;Human;Impairment;in vivo;Inherited;Intention;knock-down;Knockout Mice;Knowledge;Lead;Long-Term Depression;loss of function mutation;Mediating;Mental disorders;metabotropic glutamate receptor 5;metabotropic glutamate receptor type 1;Microfluidic Microchips;Molecular;mouse model;Mus;Nervous System;Nervous System Disorder;Neuronal Differentiation;Neuronal Plasticity;Neurons;new therapeutic target;novel;optogenetics;Organism;Outcome;Patients;pharmacologic;Phenotype;Physiological;Polyribosomes;Process;protein activation;Proteins;Publishing;Receptor Activation;Receptor Signaling;Research;Ribosomal Proteins;Ribosomes;Role;Study models;Synapses;synaptic depression;Synaptic plasticity;Synaptic Transmission;Translational Activation;Translational Repression;Translations;ubiquitin-protein ligase

PROJECT_TITLE: Mechanism of Gp1 mGluR-dependent translation and plasticity


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Depression;Genetic Testing;Genetics;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention;Serious Mental Illness;Suicide;Suicide Prevention

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Project Narrative  Suicide is one of the top 10 leading causes of death in the United States and 10-25 times the number that die contemplate suicide every year. Large gaps remain in our understanding of genetic risk factors of suicidal ideation and attempt as well as genetic and clinical risk factors that contribute to transition from ideation to attempt. This investigation will use natural language processing, machine learning, electronic health records for over 1 million people, and two major biobanks from the United States and the United Kingdom to study the clinical and genetic risk factors necessary to improve identification of patients at highest risk of suicidal behaviors.

PI_NAMEs: RUDERFER, DOUGLAS ;WALSH, COLIN GEORGE (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Affect;Algorithms;American;Behavior;biobank;Cause of Death;Cessation of life;Clinical;Clinical Informatics;clinical phenotype;clinical predictive model;clinical risk;Code;Country;Data;depressive symptoms;design;Diagnostic;Electronic Health Record;epidemiology study;Family Study;Feeling suicidal;Genetic;genetic analysis;genetic architecture;genetic association;Genetic Risk;genetic risk factor;Genetic study;Genetic Variation;Genomics;Genotype;Goals;Healthcare Systems;Heritability;high risk;Hospitals;ideation;improved;Individual;Investigation;Life Expectancy;Literature;Machine Learning;member;Mental Depression;Mental disorders;Methods;Modeling;Natural Language Processing;Neurotic Disorders;open source;outcome prediction;Patients;Performance;Persons;Phenotype;phenotyping algorithm;Population;portability;Predictive Factor;predictive modeling;Prevalence;Prevention;Preventive;Provider;Psyche structure;psychiatric comorbidity;Public Health;Publishing;Recording of previous events;Reporting;Research;Research Personnel;Resources;Risk;Risk Factors;risk stratification;Role;Running;Sampling;Schizophrenia;Signal Transduction;Structure;structured data;suicidal;suicidal behavior;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;Symptoms;Testing;Thinking;Time;trait;United Kingdom;United States;Work

PROJECT_TITLE: Distinguishing Clinical and Genetic Risk of Suicidal Ideation from Attempts to Inform Prevention

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: NARRATIVE Mutations in telomerase and telomere dysfunction are implicated in the pathogenesis of a growing number of human disorders, including end-stage liver disease and cancer. In this proposal, we will determine the molecular mechanisms behind hepatic cell failure and transformation in settings of impaired telomerase, and elucidate new pathways involved in the progression of this response after telomere damage. We will use a unique combination of molecular and cellular models to significantly increase current knowledge on hepatocyte function and transformation in settings of short telomeres, DNA damage, and mutant telomerase.

PI_NAMEs: BATISTA, LUIS FRANCISCO ZIRNBERGER (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Address;Biochemical;cell growth regulation;cell injury;Cell Lineage;Cell model;Cells;Cicatrix;Complex;connective tissue growth factor;Copy Number Polymorphism;Data;Development;Disease;Distal;DNA Damage;DNA Repair;Elements;end stage liver disease;Etiology;Event;Failure;Fibrosis;Functional disorder;Genomic Instability;Goals;Hepatic Stellate Cell;Hepatic Tissue;Hepatocyte;hepatocyte nuclear factor;Human;human embryonic stem cell;human pluripotent stem cell;Impairment;In Vitro;in vivo;Induced Hepatocytes;Knockout Mice;Knowledge;Length;Link;Liver;Liver Failure;Liver Fibrosis;liver function;loss of function mutation;Malignant neoplasm of liver;Methylation;Modeling;Molecular;molecular modeling;mutant;Mutation;novel;paracrine;Pathogenesis;Pathway interactions;Patient-Focused Outcomes;Patients;Physiological;Positioning Attribute;prevent;Primary carcinoma of the liver cells;Process;promoter;Promoter Regions;Protocols documentation;response;Risk Factors;RNA-Directed DNA Polymerase;Role;Signal Pathway;Somatic Mutation;stellate cell;stem cell biology;stem cell differentiation;System;targeted treatment;Telomerase;telomere;telomere damage;Telomere Maintenance;Telomere Shortening;Time;tool;TP53 gene;transcription factor

PROJECT_TITLE: Telomere dysfunction and telomerase reactivation in the etiology and progression of liver cancer

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Clinical Research;Infectious Diseases;Lung;Microbiome;Pulmonary Fibrosis;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Dr. Moore's laboratory has provided seminal studies related to the immunobiology of lung injury, repair and fibrosis both in the context of stem cell transplantation as well as idiopathic forms of disease for over 20 years. This award will support on-going studies to understand how herpesvirus infections promote pneumonitis and fibrosis post-stem cell transplant, to understand how the lung microbiome changes during fibrosis and signals via innate immune receptors, to understand how heparin-binding EGF-like (HB-EGF) growth factor production by myeloid cells drives lung fibrosis and will seek to understand how innate immune signaling can impact lung injury in the setting of influenza and bacterial co-infections.

PI_NAMEs: MOORE, BETHANY B. (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: angiogenesis;Animal Model;Animals;Area;Award;Bacterial Infections;Biological Markers;chemokine;Clinic;co-infection;Complication;Data;Disease;Eicosanoids;Etiology;Fibrosis;Growth Factor;Hematopoietic Stem Cell Transplantation;Heparin Binding;heparin-binding EGF-like growth factor;Herpesviridae Infections;Human;Immune response;Immune signaling;Immunobiology;Immunologic Receptors;Influenza;interest;Laboratories;Lung;Lung Diseases;lung injury;lung microbiome;Malignant Neoplasms;Mediating;microbiome;Myelogenous;Myeloid Cells;Natural Immunity;novel;novel marker;novel therapeutics;Pathogenesis;Pathologic;Pathway interactions;Patients;pneumonitis and fibrosis;Process;Production;programs;Proteins;Proteomics;Publishing;Pulmonary Fibrosis;Pulmonary Inflammation;Receptor Signaling;Regulation;repaired;Research;Research Personnel;Role;Seminal;Shapes;Signal Transduction;Stem cell transplant;therapeutic target;validation studies;Viral;Virus Diseases;Work

PROJECT_TITLE: Immunobiology of Lung Injury and Fibrosis


ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: RELEVANCE (See instructions): Concerns over the potential effects of industry funding and COI have been a recurrent feature in the study of the biomedical research enterprise and related clinical practice. Empowering researchers and policymakers with evidence-based approaches for the management of COIs in networks of research is essential for safeguarding the study of health and medicine and reducing the risk of negative effects on the practice of science and patients who rely on that science.

PI_NAMEs: BARBOUR, JOSHUA BEN;GRAHAM, SAMUEL  (contact);MAJDIK, ZOLTAN ;ROUSSEAU, JUSTIN FREDERICK

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Adverse event;Biomedical Research;Circulation;Classification;clinical practice;Communication;Conflict (Psychology);Conflict of Interest;Data;design;Development;Disclosure;Drug Prescriptions;empowerment;Evaluation;evidence base;evidence based guidelines;Foundations;Funding;Health;High Performance Computing;improved;Individual;Industry;innovation;Instruction;Machine Learning;medication safety;Medicine;novel;Outcome;Patients;Pharmaceutical Preparations;Policies;Policy Maker;Publishing;Recommendation;Recurrence;Reporting;Research;Research Personnel;Risk;Risk Reduction;Science;Severities;stem;System;Testing;United States Food and Drug Administration

PROJECT_TITLE: A Network Science Approach to Conflicts of Interest: Metrics, Policies, and Communication Design


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative A diagnosis of pancreatic cancer is nearly always a death sentence, and this disease is projected to become the second-leading cause of cancer deaths in the western world over the next decade. This is because most patients develop widespread metastatic disease that progresses rapidly and is treatment-resistant. Here we propose to solve key mechanisms that drive this aggressive disease, by investigating how human pancreatic cancers learned to harness sugar (glucose) in unique ways to fuel metastatic tumor growth in patients who died from widespread metastasis.

PI_NAMEs: MCDONALD, OLIVER GENE (contact)

PROJECT_TERMS: 3-Dimensional;Acceleration;Acetyl Coenzyme A;addiction;Back;Bypass;cancer cell;Cancer Etiology;Catalysis;Cell Physiology;Cells;Cessation of life;Chemicals;Chromatin;Circulation;cofactor;Consumption;Conversion disorder;Coupled;Data;Dependence;design;Diagnosis;Disease;Disease Progression;Disseminated Malignant Neoplasm;Distant Metastasis;DNA Sequence;effective therapy;Enzymes;Epigenetic Process;epigenome;epigenomics;Evolution;experimental study;FASN gene;fatty acid biosynthesis;fatty acid metabolism;Fatty Acids;fitness;G6PD gene;Gene Expression;Genes;genetic selection;Genetic Transcription;Glucose;Growth;histone acetyltransferase;Human;Hypoglycemia;individual patient;inorganic phosphate;insight;Knowledge;Learning;Left;Link;Liver;Lung;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;manufacture;Metabolic;Metabolic Pathway;Metabolism;Modification;Mutate;NADP;Names;Natural Selections;Neoplasm Metastasis;non-genetic;overexpression;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Pathway interactions;Patients;Pentosephosphate Pathway;Phosphogluconate Dehydrogenase;Preclinical Testing;Primary Neoplasm;Production;programs;Reaction;Recurrence;Recycling;Repression;Research Design;Research Methodology;Resistance;Route;Series;small molecule inhibitor;Specificity;sugar;Testing;therapeutic target;therapy resistant;Tissues;transcriptome;treatment strategy;tumor growth;Tumor Promotion;tumorigenesis;TXNIP gene;Western World;Work

PROJECT_TITLE: THE EVOLUTION OF PGD ADDICTION IN HUMAN PANCREATIC CANCER

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: PROJECT NARRATIVE With the increased use of immuno-modulatory drugs for such diseases as multiple sclerosis, rheumatoid arthritis, and Crohn's disease, and the now common practice of renal transplantation, human polyomaviruses have emerged as significant human pathogens. These viruses currently have no effective therapy. Characterizing the sites of polyomavirus replication in the cell nucleus, the objective of this proposal, is critically important for the identification of possible therapeutic anti-viral drug targets.

PI_NAMEs: GARCEA, ROBERT L (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: 3-Dimensional;Affect;Anti-viral Agents;Architecture;Binding Proteins;Capsid Proteins;Cell Line;Cell Nucleus;Cell Physiology;Cells;Chromatin;Collaborations;Complement;Complex;Coupled;Crohn's disease;Cytoplasm;Disease;DNA biosynthesis;DNA Repair;DNA Viruses;Drug Targeting;effective therapy;Electron Microscopy;Family;Genetic;genetic approach;Genetic Transcription;Genome;Goals;high resolution imaging;Human;human pathogen;Image;imaging facilities;immune modulating agents;immunomodulatory therapies;Infection;inhibitor;insight;Kidney Transplantation;Label;light microscopy;Link;Location;Mass Spectrum Analysis;Methods;Microscopy;Modeling;Molecular;Molecular Machines;Morphology;mouse polyomavirus;Multiple Sclerosis;Mus;mutant;Mutation;nanometer resolution;new therapeutic target;Nuclear;Nuclear Structure;Pathway interactions;Physiologic pulse;Polyomavirus;Process;Production;Productivity;Protein Analysis;protein expression;Proteins;Quality Control;recruit;Resolution;Rheumatoid Arthritis;RNA;Site;spatial relationship;Structure;Viral;viral DNA;Viral Genome;Viral Proteins;Virion;virology;Virus;Virus Assembly;Virus Replication;Visualization

PROJECT_TITLE: Mechanisms in Polyomavirus Assembly

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-W(02)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN ANTONIO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Narrative Bromodomain-containing protein 4 (BRD4) is upregulated in solid cancers and hematological malignancies, including acute myeloid leukemia. Despite the clinical significance of BRD4 in cancers, the role of BRD4 in normal hematopoiesis and hematopoietic stem cell biology remains largely unknown. The major goal of this project is to uncover the hidden role of BRD4 in normal and malignant hematopoiesis with specific emphasis on the molecular mechanisms by which BRD4 regulates hematopoietic stem/progenitor cell functions.

PI_NAMEs: YANG, FENG-CHUN  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Acetylation;Active Sites;Acute Myelocytic Leukemia;Affect;Apoptosis;Behavior;Binding;Biology;BRD2 gene;Bromodomain;Bromodomains and extra-terminal domain inhibitor;C-terminal;CD34 gene;Cell Cycle Progression;Cell Lineage;Cell Physiology;Cell Survival;Cells;Chromatin;Chromatin Structure;Cleavage Under Targets and Release Using Nuclease;Clinical Trials;clinically significant;Complex;cyclin T1;Data;Development;Disease;Exhibits;Fibrosis;Frequencies;Gene Expression;Gene Targeting;Genes;Genetic Crosses;Genetic Transcription;genome-wide;Genomics;Goals;Hematologic Neoplasms;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;Hematopoietic stem cells;Hematopoietic System;Heterozygote;Histone Acetylation;histone acetyltransferase;histone modification;Histones;Human;Impairment;In Vitro;in vivo;Induction of Apoptosis;Inflammatory;Injections;knock-down;Knock-out;Knockout Mice;Knowledge;leukemic transformation;Lysine;Malignant - descriptor;Malignant Neoplasms;Maps;Mediating;member;Mitotic Cell Cycle;Molecular;mouse model;Mus;MYC gene;Myeloproliferative disease;Output;overexpression;Pathogenesis;Population;Positive Transcriptional Elongation Factor B;Protein Family;Proteins;recruit;Regulation;RNA Polymerase II;Role;single-cell RNA sequencing;small molecule;small molecule inhibitor;Solid;Solid Neoplasm;stem cell biology;stem cell function;Tail;Testing;Thrombocytopenia;Toxic effect;Transcription Elongation;transcriptome;transgene expression;Transgenic Mice;Transgenic Organisms;tumor

PROJECT_TITLE: Role of BRD4 in Normal Hematopoiesis and Hematopoietic Stem Cell Biology

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative for R01 application by Hayakawa and Lo Meningeal stem cell signals for improving sensorimotor and cognitive outcomes after stroke The meninges are primarily known as brain protective membranes, but it is now increasingly recognized that these membranes may surprisingly contain multipotent stem cells. Is it possible that this meningeal compartment may represent a novel stem cell niche to promote neurovascular unit recovery after stroke? Here, we propose that the meninges is a novel source of stem cell signals that can be leveraged to repair the blood-brain barrier, rescue the vasculome and boost neurogenesis. Altogether, these mechanisms should augment sensorimotor recovery as well as ameliorate post-stroke dementia after focal cerebral ischemia.

PI_NAMEs: HAYAKAWA, KAZUHIDE  (contact);LO, ENG H.

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Accounting;activin A;AMD3100;Animal Model;Astrocytes;Behavior assessment;behavior test;Blood - brain barrier anatomy;blood damage;Blood Vessels;BMP2 gene;Brain;brain endothelial cell;Brain Injuries;Brain-Derived Neurotrophic Factor;CD 200;Cell Communication;Cell Culture Techniques;Cell Death;Cells;Cerebral cortex;Cerebral endothelium;Cerebral Ischemia;Coculture Techniques;Cognitive;cognitive recovery;Collaborations;Cre lox recombination system;CRISPR/Cas technology;CXCR;CXCR4 gene;Data;Defect;Development;endothelial repair;Endothelium;experimental study;Female;functional outcomes;gain of function;Genes;Goals;Growth Factor;HDAC3 gene;Human;improved;in vivo;in vivo imaging;in vivo Model;Infarction;inhibitor;Injury;Ischemia;Label;Literature;Location;loss of function;Macrophage;male;Maps;Mediating;Mediator;Membrane;Meningeal;Meninges;Methods;migration;Modeling;Modification;Molecular;mortality;mouse model;Multipotent Stem Cells;Mus;neural;neurogenesis;Neuroglia;neurological recovery;Neuronal Injury;Neurons;neurovascular;neurovascular unit;neutralizing antibody;new therapeutic target;novel;novel strategies;optical imaging;Outcome;Pathway interactions;Patients;Pericytes;pharmacologic;post stroke;post stroke dementia;Process;Publishing;Radial;Rattus;receptor;Recovery;repaired;response;restoration;Signal Transduction;Source;spatiotemporal;stem cell migration;stem cell niche;stem cell proliferation;stem cells;Stroke;stroke cognitive outcome;stroke recovery;Stromal Cell-Derived Factor 1;Testing;Therapeutic;therapeutic target;tool;Transforming Growth Factor beta;Up-Regulation;Western Blotting

PROJECT_TITLE: Meningeal Stem Cell Signals for Improving Sensorimotor and Cognitive Outcomes After Stroke

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Cardiovascular;Complementary and Integrative Health;Genetics;Heart Disease;Human Genome;Nutrition

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Our goal is to investigate the impact of diet, metabolic enzymes, and pressure overload on the histone code, and how this influences changes in gene expression in the healthy and hypertrophied/failing hearts and, in turn, how it impacts progression of the disease. Deciphering the histone code and how diet can modify it, gives us the means to exploit it to our advantage, especially during pathological conditions. We are proposing that histone H3K9-butyryl, H3K9- crotonyl, and H3K9-b-hydroxybutyryl, are products of the b-oxidation intermediates, butyryl-CoA, crotonyl-CoA, and b-hydroxybutyryl-CoA, or the ketone body, b-hydroxybutyrate, that are produced in the nucleus. The genomic distribution of these modified histones, how they are modified by diet in the presence or absence of stress, and their functional relevance, particularly in the heart, have not been investigated. Our results show that a high-fat diet exacerbates pressure overload-induced gene expression in the heart, worsening the prognosis of the disease, as a result of modifying the histone code. We hypothesize that we can temper these effects and improve disease outcome by modulating the histone marks by diet, including low-fat and ketogenic diets.

PI_NAMEs: ABDELLATIF, MAHA  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Acceleration;Acetylation;acyl group;Aging;beta-Hydroxybutyrate;Butyryl-CoA dehydrogenase;Carbohydrates;CDK9 Protein Kinase;Cell Nucleus;Cells;ChIP-seq;Coenzyme A;Data;Diet;dietary;Dietary Fats;Disease Outcome;disease prognosis;Disease Progression;Enzymes;Fat-Free Diets;Fatty acid glycerol esters;Fatty Acids;Gene Expression;Genes;Genetic Transcription;genome-wide;Genomics;Glucose;Goals;Health;Heart;Heart failure;Heart Hypertrophy;High Fat Diet;Histone Code;histone methylation;histone modification;Histones;Human;Hypertrophy;improved;improved outcome;ketogenic diet;ketogentic;Ketone Bodies;knock-down;Ligase;Lysine;Mediating;Metabolic;Metabolism;Molecular;Mus;Nonesterified Fatty Acids;Nuclear;Outcome;oxidation;Oxidoreductase;Pathologic;pressure;promoter;recruit;Regulation;Reporting;Role;Source;Stress;Transcriptional Regulation;transcriptome sequencing

PROJECT_TITLE: The regulation of the histone code during cardiac hypertrophy

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Wound Healing and Care

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: NARRATIVE Skin wounds are acute stresses that can be life-threatening unless efficiently repaired. Wounding of barrier epithelia such as the epidermis causes loss of bodily fluids and can result in opportunistic infections at the wound site. Biomedically important pathologies of wound healing range from excessive wound healing (hypertrophic scarring and keloid) to non-healing chronic wounds and diabetic ulcers. This project uses a simple model of skin wound healing in the nematode C. elegans to understand how epidermal tissues detect and repair damage.

PI_NAMEs: CHISHOLM, ANDREW D (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: acute stress;Address;Adult;Animals;Apical;Basement membrane;Biogenesis;Biology;Body Fluids;Caenorhabditis elegans;chronic wound;Communication;diabetic ulcer;Environment;Epidermis;Epithelium;Extracellular Matrix;Future;Genes;Genetic;Goals;Health;Human;Hypertrophic Cicatrix;injury and repair;insight;Keloid;Knowledge;Life;Lipids;loss of function;Maintenance;Modeling;Molecular;Nematoda;Opportunistic Infections;Organism;Pathology;Permeability;programs;repaired;Research;Role;Site;Skin;skin fibrosis;skin organogenesis;Skin repair;skin wound;Skin wound healing;System;Tissues;Work;wound;wound healing

PROJECT_TITLE: Maintenance and Repair of the C. elegans Skin

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-J(55)R]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Relevance The relevance of this application is rooted in the fundamental translational biology of how mitochondrial calcium impacts myocyte death and metabolism, both of which are dramatically altered in heart failure or immediately after myocardial infarctino injury. The proposal will investigate the mechanisms and genes that alter intra-mitochondrial calcium levels. A better understanding of how we might reduce or inhibit dramatic increases in mitochondrial calcium after ischemic injury would lead to novel protective strategies, such that myocytes could be prevented from necrotic death.

PI_NAMEs: BERS, DONALD M;MOLKENTIN, JEFFERY D (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Ablation;Acute;Acute myocardial infarction;Adenylate Cyclase;Adrenergic Agents;Adult;Affect;Apoptotic;Binding;Biology;Biophysics;Calcium;Cardiac;Cardiac Myocytes;cardioprotection;Cell Death;Cellular biology;Cessation of life;Complex;Cyclic AMP-Dependent Protein Kinases;cyclophilin D;Data;Disease;Drug Design;Electron Transport;Energy Supply;fighting;Functional disorder;gain of function;Gene Deletion;Genes;genetic analysis;genetic selection;Genome;Goals;Grant;Heart;Heart failure;heart function;heart metabolism;in vivo;infancy;Injury;Inner mitochondrial membrane;innovation;ischemic injury;Joints;Knock-in;Knockout Mice;Laboratories;Life;loss of function;Mediating;Membrane;Metabolic;Metabolism;Mitochondria;Mitochondrial Matrix;Mitochondrial Membrane Protein;mitochondrial metabolism;mitochondrial permeability transition pore;Molecular;Molecular Genetics;mouse genetics;mouse model;Mus;Muscle Cells;Mutation;Myocardial;Myocardial Infarction;NADH;Necrosis;new therapeutic target;novel;Output;overexpression;Oxidoreductase;Paper;paralogous gene;Pathologic;Pathway interactions;PDE2 phosphodiesterase;Performance;Permeability;phosphoric diester hydrolase;Phosphorylation;Physiological;Physiological Adaptation;Physiology;prevent;Production;Proteins;Publications;Publishing;Regulation;Reperfusion Injury;response;Role;Signal Transduction;Site;skills;Stress;System;Testing;Time;Tissues;translational potential;uptake

PROJECT_TITLE: Molecular examination of mitochondrial calcium control

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]