ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Eye Disease and Disorders of Vision;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Patient Safety;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE African Americans and Latinos carry a disproportionate burden of glaucoma, a blinding eye disease that can lead to severely decreased quality of life. Promoting adherence with topical medications that lower intraocular pressure, the primary therapeutic target for reducing the risk of glaucoma progression, represents a critical opportunity for technology-driven interventions. The iGLAMOUR (innovations in GLaucoma Adherence and Monitoring Of Under-Represented minorities) Study aims to develop and evaluate a health information technology framework incorporating flexible sensor electronics, machine learning-based predictive models, a patient- facing mobile interface, and a clinician-facing clinical dashboard to facilitate early identification and intervention for high-risk patients in order to narrow these racial disparities and improve vision outcomes in these minority populations.

PI_NAMEs: COLEMAN, TODD P;WEINREB, ROBERT N (contact)

PROGRAM_OFFICER_NAME: PATEL, ANURADHA DIPAK

PROJECT_TERMS: Adherence;adherence rate;Affect;African American;African American population;Algorithms;Artificial Intelligence;blind;Blindness;Bluetooth;Caucasians;centralized portal;Chronic Disease;Clinical;clinical decision-making;clinical risk;Clinical Trials;Complex;Counseling;dashboard;Data;data dashboard;data visualization;design;Development;Diagnosis;digital;Disease Progression;dosage;Early identification;Early Intervention;effective intervention;Effectiveness;Electronic Health Record;electronic sensor;Electronics;Evaluation;experience;Eye;Eye diseases;Eyedrops;field study;flexibility;flexible electronics;Glaucoma;glaucoma test;Health;Health Care Costs;health care delivery;health information technology;Health Technology;high risk;human centered design;improved;Individual;innovation;interest;interoperability;Intervention;Intervention Studies;Interview;Knowledge;Label;Latino;Latino Population;Life;Machine Learning;machine learning model;machine learning prediction;Measures;medication compliance;Medication Management;medication nonadherence;Methods;mHealth;Minority;Minority Groups;mobile application;mobile computing;Modeling;Monitor;Optical Coherence Tomography;Outcome;participant interview;patient engagement;Patient Self-Report;Patients;Pattern;Performance;personalized care;Persons;Pharmaceutical Preparations;Physicians;Physiologic Intraocular Pressure;Population;predictive modeling;Prevalence;primary outcome;Process;Proliferating;prototype;Provider;Qualitative Evaluations;Quality of life;racial disparity;racial health disparity;Recommendation;Reporting;Research;retinal nerve fiber layer;risk prediction;Risk Reduction;risk stratification;Screening procedure;secondary outcome;sensor;sensor technology;Signal Transduction;social culture;social health determinants;Structure;success;support tools;Technology;Testing;therapeutic target;Thick;Topical application;transmission process;Underrepresented Minority;usability;Variant;Vision;Visual Fields;wireless

PROJECT_TITLE: iGLAMOUR Study:  Innovations in Glaucoma Adherence and monitoring Of Under-Represented minorities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-K(56)R]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Chronic Pain;Digestive Diseases;Food Allergies;Neurosciences;Nutrition;Pain Research;Prevention

ORG_CITY: NEW HAVEN

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Food allergy is a disease with no known cure, high economic burden, and increasing prevalence. Oral immunotherapy (OIT) has shown effectiveness in increasing desensitization and remission in allergic individuals; however gastrointestinal complications commonly limit clinical utility. Studying the mechanisms by which mast cells elicit gastrointestinal anaphylaxis will enable novel therapies to prevent undesirable symptoms during OIT and to alleviate suffering in patients with irritable bowel syndrome (IBS).

PI_NAMEs: BACHTEL, NATHANIEL DALE (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Abdominal Pain;Acute;Affinity;Allergens;Allergic;Allergic inflammation;Anaphylaxis;Anorexia;Antibodies;Antigens;Automobile Driving;avoidance behavior;B-Lymphocytes;Basic Science;Basophils;Behavior;behavior test;Behavioral;Behavioral Paradigm;Binding;Blocking Antibodies;Body Weight decreased;Capsaicin;career;Cell Culture System;cell mediated immune response;Cells;chemotherapy;Cisplatin;Clinical;Clinical Research;clinically relevant;Colon;colonic crypt;computer program;cytokine;Data;desensitization;Development;Diarrhea;Digestive System Disorders;Disease;Disease remission;Eating;Economic Burden;Effectiveness;Endowment;Epithelial Cells;Epithelium;Food;food allergen;food antigen;Food Hypersensitivity;gastrointestinal;Gastrointestinal tract structure;GDF15 gene;Genetic;Histamine;Human;IgE;IgG1;Immune;Immune response;Immunologic Memory;In Vitro;in vivo;Incidence;Individual;Inflammation;Inflammatory;inhibitor;Intestines;Irritable Bowel Syndrome;Knockout Mice;Knowledge;Lead;Leukotrienes;Malaise;mast cell;Mediating;Mediator;Metformin;Modeling;Molecular Biology;mouse model;Mus;Nausea;Nausea and Vomiting;Nerve;Neurons;Nociceptors;nonhuman primate;novel;novel therapeutics;Nucleus solitarius;oral immunotherapy;Pathogenesis;Pathway interactions;Patients;pharmacologic;Physicians;Play;preclinical study;Predisposition;preference;Prevalence;prevent;Production;programs;Proteins;Pruritus;receptor;Regulation;Research;response;Role;Scientist;Serum;Shrews;Signal Transduction;skills;Small Intestines;Stress;Structure of area postrema;Symptoms;T-Lymphocyte;Taste aversion;Technical Expertise;Testing;Th2 Cells;Tissues;Training;Transcript;transcriptome;transcriptomics;Transforming Growth Factor beta;Transgenic Mice;Vascular Permeabilities;Vasodilation;Vomiting;Work

PROJECT_TITLE: Mast cell regulation of food allergen induced malaise through GDF15-GFRAL signaling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07C-M(20)]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: NARRATIVE The proposed research is important because increasing evidence demonstrates that congenital heart defects are a significant public burden; however, the mechanisms by which this occurs are poorly understood. Research in this area is crucial to both prevention and treatment, and therefore this research proposal addresses an important human health problem aligned with the mission of the NHLBI at the NIH.

PI_NAMEs: FIRULLI, ANTHONY B. (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: Address;Adult;Animal Model;Applications Grants;Area;BHLH Protein;Cardiac;Cardiac conduction system;Cardiac Myocytes;cardiogenesis;Child;Chromatin;Complex;Congenital Abnormality;Congenital Heart Defects;Cues;Data;Defect;Development;Disease;DNA;DNA Binding;eHAND helix-loop-helix protein;Embryo;embryonic stem cell;Enhancers;Epigenetic Process;epigenetic regulation;Etiology;Event;Family member;Fingers;gastrulation;Gene Modified;gene regulatory network;Genes;Genetic;Genetic Transcription;Genome;Growth;Health;Heart;histone methyltransferase;histone modification;Human;human disease;human induced pluripotent stem cells;Image;insight;Intervention;Knock-out;Laboratories;Left;Left ventricular structure;Life;Link;Lysine;Mediating;Mesoderm;Methylation;Methyltransferase;migration;Mission;Modeling;Molecular;Morphogenesis;Morphology;Mus;mutant;Mutate;N-Cadherin;National Heart, Lung, and Blood Institute;novel;papillary muscle;Pathogenesis;Pathway interactions;Patients;Pattern;Phenocopy;Physiology;planar cell polarity;Population;Pregnancy;Prevalence;Prevention;Primitive Streaks;progenitor;Program Research Project Grants;programs;Proliferating;Proteins;Public Health;Publishing;Regulation;Research;Research Personnel;Research Proposals;ROCK1 gene;Role;Sarcomeres;Side;Signal Pathway;Signal Transduction;Situs Inversus;Specific qualifier value;stem cell differentiation;stem cell fate;stem cell growth;stem cells;System;Testing;transcription factor;transcriptomics;United States;United States National Institutes of Health;Variant;Ventricular;Ventricular septum;Work;Zebrafish

PROJECT_TITLE: Morphogenesis and growth of the ventricular wall in development and disease

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(MA)]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

PROJECT_TERMS: Animals;Applications Grants;Biohazardous Substance;Budgets;Clinical;clinical prognosis;Congenital Abnormality;congenital heart abnormality;Defect;Development;Disease;Ethics;Etiology;Goals;Growth;Individual;Institution;meetings;Molecular;Morphogenesis;Outcome;Output;Participant;pediatric patients;Phenotype;Program Research Project Grants;programs;Radiation;Reporting;Research Project Grants;Resource Sharing;Schedule;Services;symposium;Travel;United States National Institutes of Health;Ventricular

PROJECT_TITLE: Administrative Core

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE Arboviruses represent a serious global public health threat. The infection of arthropod vectors and humans by these viruses is an essential step in the viral life cycle and one that can be targeted to stop viral spread. Here, we delineate the mechanisms promoting arbovirus infectivity in insects and mammals, and begin to elucidate what drives the adaptation of the viral glycoproteins in the hopes of targeting this critical step to stop arbovirus disease.

PI_NAMEs: STAPLEFORD, KENNETH  (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Aedes;Alpha Virus;Anti-viral Agents;Anti-viral Therapy;antiviral drug development;arboviral disease;Arboviruses;Arthropod Vectors;Biochemical;Biology;Cells;Chikungunya virus;Cholesterol;Coupled;Culicidae;deep sequencing;Disease;driving force;emerging human pathogen;emerging virus;Environmental Risk Factor;epidemic potential;Event;Evolution;Genetic;Glycoproteins;Goals;Human;In Vitro;in vivo;Infection;Insect Vectors;Insecta;Integration Host Factors;Knowledge;Life Cycle Stages;Lipids;Mammalian Cell;Mammals;Molecular;Mus;Mutation;novel;Pathogenesis;Play;Process;protein function;Proteins;Public Health;Role;Saliva;Structural Protein;targeted treatment;Technology;Temperature;Testing;thermostability;transmission process;vaccine development;Vaccines;Variant;vector;Viral;Viral Pathogenesis;Viral Structural Proteins;viral transmission;Virion;Virulence;Virus;Work

PROJECT_TITLE: Mechanisms of alphavirus infectivity and adaptation - Resubmission - 1

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Embryonic - Non-Human;Transplantation

PI_NAMEs: YANG, LEI  (contact)

PROJECT_TERMS: Animal Experiments;Animal Model;Animals;Applications Grants;blastocyst;Breeding;Cardiac;cardiogenesis;Cell model;Cell Physiology;Cells;Cellular Structures;Clone Cells;Clustered Regularly Interspaced Short Palindromic Repeats;congenital heart abnormality;cost;Cryopreservation;design;Development;Disease;Embryo;embryo culture;embryonic stem cell;ES Cell Line;Etiology;experience;Experimental Animal Model;experimental study;Founder Generation;Gene Modified;Gene Targeting;Gene Transfer Techniques;Generations;Genes;Genetic;genetic manipulation;Genetic Models;genome editing;Genotype;Goals;Growth;Human;human embryonic stem cell;Human Resources;In Vitro;in vivo;in vivo Model;Indiana;induced pluripotent stem cell;Injections;medical schools;Modeling;Modification;Molecular;Morphogenesis;Mouse Embryonic Stem Cells;mouse genetics;mouse model;Mus;Mutate;Mycoplasma;Participant;Performance;pluripotency;Program Research Project Grants;programs;Protocols documentation;Quality Control;Reagent;recruit;Regulation;screening;Services;stem cell growth;stem cells;success;Technology;Testing;Training;Transgenic Mice;transmission process;Universities;Ventricular

PROJECT_TITLE: Embryonic stem cell/induced Pluripotent stem cell growth and gene editing core


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Genetics;Heart Disease;Stem Cell Research;Stem Cell Research - Embryonic - Human

PI_NAMEs: RUBART-VAN DER LOHE, MICHAEL  (contact)

PROJECT_TERMS: Adult;Anesthesia procedures;Biological Assay;Calcium;Cardiac;Cardiac Myocytes;cardiogenesis;Cells;Conscious;Custom;Data;Development;Disease;Doctor of Medicine;Echocardiography;Electrocardiogram;Electrodes;Electrophysiology (science);Evaluation;experience;Fluorescence Microscopy;Frequencies;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Goals;Growth;Heart;human embryonic stem cell;Image;imaging system;In Situ;In Situ Hybridization;Maps;Measurement;Membrane;Microscopy;Monitor;Morphogenesis;Mus;Mutation;Optics;Patch-Clamp Techniques;Physiology;Proliferating;Property;Resolution;RNA;S phase;Services;Shapes;Structure;Surface;System;Techniques;Telemetry;Tissues;Transmission Electron Microscopy;Ultrasonography;ultrasound;Ventricular;voltage

PROJECT_TITLE: Cardiac Physiology and Imaging Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE We use a multidiscipline approach to study the neural mechanism whereby the human genetic variant OtpQ153R/+ causes obesity and glucose intolerance. To this end, we have generated new mouse genetic tools to probe the roles of Otp in two populations of hypothalamic neurons that are critical for energy and glucose balance. The overarching goal is to develop mechanism-based therapeutics to mitigate metabolic syndrome in human OtpQ153R/+ subjects.

PI_NAMEs: LIU, CHEN  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Adopted;Adult;Agonist;Alleles;Amino Acid Sequence;Appetite Stimulants;Biology;blood glucose regulation;Brain;cell motility;Central Nervous System;ChIP-seq;Code;cohort;Congenital Abnormality;Defect;Development;Diabetes Mellitus;Discipline;energy balance;Energy Metabolism;Enterobacteria phage P1 Cre recombinase;Equilibrium;European ancestry;Functional disorder;Gene Expression Profiling;Genetic;Genetic Transcription;genetic variant;genome wide association study;genomic data;Glucose;Glucose Intolerance;glucose metabolism;Goals;Heterozygote;homeodomain;Homeostasis;Human;Human Genetics;human model;human subject;Hypothalamic structure;Impairment;Individual;insight;Knock-in Mouse;Knockout Mice;Label;Lead;LoxP-flanked allele;Maps;Melanocortin 4 Receptor;Metabolic;Metabolic syndrome;Missense Mutation;Molecular;Morbid Obesity;mouse genetics;Mus;mutant;Mutation;nerve supply;neuromechanism;Neurons;Neurosecretory Systems;Non obese;novel;Obesity;paraventricular nucleus;Patients;Perinatal mortality demographics;Phenotype;Physiological;Play;Population;postnatal;prevent;progenitor;Prosencephalon;Publishing;Receptor Signaling;Reporting;Role;severe early onset obesity;single nucleus RNA-sequencing;Site;Structure of nucleus infundibularis hypothalami;Testing;Therapeutic;tool;transcription factor;transcriptome;Variant

PROJECT_TITLE: A human genetic variant ties defective hypothalamic development to obesity and diabetes

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BURLINGTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARATIVE Local blood flow is critical to supply neurons in the brain with a continuous supply of nutrients. We now describe a novel communication network through capillaries and arterioles that signal blood vessels to relax and increase blood supply to active neurons, and provide new insights into small vessel disease of the brain.

PI_NAMEs: NELSON, MARK T (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Arteries;arteriole;Astrocytes;biophysical model;Blood capillaries;Blood flow;Blood Vessels;Brain;Brain Diseases;Calcium;Calcium Signaling;Capillary Endothelial Cell;cerebral capillary;cerebral microvasculature;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular system;Communication;Complex;Computer Models;Coupled;Data;Dinoprostone;Disease;Endothelium;Equilibrium;feeding;G alpha q Protein;Goals;Health;in silico;in vivo;insight;Internet;inward rectifier potassium channel;Kinetics;Mediating;Mediator;Membrane;Metabolic;Microvascular Dysfunction;Molecular;molecular modeling;Neurons;neurotransmission;neurovascular coupling;Nitric Oxide;novel;Nutrient;operation;Oxygen;parenchymal arterioles;Perfusion;Pericytes;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Physiological;Potassium;Receptor Signaling;Regulation;Relaxation;Research;response;Role;Sensory;Signal Transduction;Site;System;Testing;Time;Vascular blood supply

PROJECT_TITLE: Capillaries as a Sensory Web that Controls Cerebral Blood Flow in Health and Disease


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

PI_NAMEs: WARE, STEPHANIE M (contact)

PROJECT_TERMS: Abnormal Cell;Alleles;Animals;ATAC-seq;Binding;biobank;Candidate Disease Gene;Cardiac;Cardiac Myocytes;cardiogenesis;Cells;Child;Chromatin;cohort;combinatorial;Complex;Congenital Abnormality;Congenital Heart Defects;Data;Data Set;Defect;Development;Developmental Biology;Disease;DNA;Embryo;embryo tissue;Embryonic Development;embryonic stem cell;Epiblast;Epigenetic Process;epigenome;Epitopes;Exhibits;exome;exome sequencing;gastrulation;Gene Expression;gene network;gene regulatory network;Genes;Genetic;Genetic study;Genetic Transcription;genetic variant;Genetic Variation;genome sequencing;Genomics;Goals;Growth;Heart;Heart Abnormalities;Human;human embryonic stem cell;Human Genetics;improved;in vivo;in vivo Model;Indiana;insight;Investigation;Knockout Mice;Lead;Left;Link;loss of function;Mediating;Mesoderm;Molecular;Morphogenesis;mouse model;Multiomic Data;multiple omics;Mus;mutation screening;Neuroectoderm;Normal tissue morphology;novel;Outcome;Pathway interactions;Patients;Pattern;Pediatric Cardiac Genomics Consortium;Penetrance;Phenotype;Play;pluripotency;Predisposition;Prevention;Primitive Streaks;progenitor;programs;rare variant;Research;Resources;Risk Factors;risk stratification;Role;Severities;single-cell RNA sequencing;Situs Inversus;somitogenesis;Specific qualifier value;stem cells;Susceptibility Gene;Syndrome;System;Testing;Therapeutic;Tissues;transcription factor;transcriptome;United States National Institutes of Health;Variant;Ventricular;whole genome;Zinc Fingers

PROJECT_TITLE: The role of ZIC3 within cardiomyocyte precursors in cardiac morphogenesis


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Hematology;Rare Diseases;Sickle Cell Disease

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative: Cytochrome b5 reductase 3 (CYB5R3) serves as a critical redox switch for substrates such as heme and coenzyme Q that are needed for controlling of biogas molecules such as nitric oxide and oxygen. Building on our currently funded NHLBI studies and published results, we aim to 1) improve our understanding of basic redox biology through work involving other CYB5R family members, 2) gain insight into unidentified and novel redox partners and substrates of CYB5R enzymes, 3) uncover the translational impact of CYB5R enzymes in human disease and 4) discover new small molecule drugs that restore redox signaling and reverse cardiovascular disease. As such, this proposal may lend critical new insight into novel targets, better strategies, and new drugs to improve the health of people living with cardiovascular disease.

PI_NAMEs: STRAUB, ADAM CARL (contact)

PROJECT_TERMS: Binding;Biology;Cardiac Myocytes;Cardiovascular Diseases;cardiovascular health;Cardiovascular Physiology;Cardiovascular system;cell type;Cells;Chemistry;Client;Coupled;cytochrome b5 reductase;Data Set;Disease;Endothelium;Enzymes;Equilibrium;Family;Family member;Funding;Gene Modified;genetic variant;Goals;Health;Heart failure;Heme;human data;human disease;Hypertension;improved;innovation;insight;Knock-out;Knowledge;National Heart, Lung, and Blood Institute;Nitric Oxide;Nitrogen;novel;novel therapeutics;Oxidation-Reduction;Oxidoreductase;Oxygen;Participant;Peroxidases;Persons;Pharmaceutical Preparations;Physiological;programs;Proteins;Publishing;Regulation;Reporting;Research;Research Proposals;Role;Sickle Cell Anemia;Signal Pathway;Signal Transduction;small molecule;Smooth Muscle;Soybeans;Testing;Therapeutic Studies;translational impact;translational study;Ubiquinone;Variant;Work

PROJECT_TITLE: Basic and Translational Studies in Redox Regulation of Cardiovascular Physiology and Disease


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Estrogen;Genetics;Women's Health Research

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Our research focus is estrogen receptor (ER)-positive luminal breast cancer, representing the majority of primary breast cancer patients, and the highly metastatic phenotype of ESR1m tumors. We will determine whether hyper-proliferation of ESR1m breast tumors induces a DNA damage response, making them vulnerable to cell cycle checkpoint or PARP inhibitors.

PI_NAMEs: FUQUA, SUZANNE AW (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: adjuvant endocrine therapy;Adjuvant Therapy;aurora kinase A;Biological Assay;Breast Cancer cell line;Breast Cancer Patient;CDC2 gene;CDK4 gene;Cell Cycle;Cell Cycle Arrest;Cell Cycle Checkpoint;Cell Cycle Proteins;ChIP-seq;Clinical;Clinical Data;combat;Complex;CRISPR/Cas technology;Critical Pathways;Development;Diagnosis;Distant;Distant Metastasis;DNA Damage;Engineering;ESR1 gene;Estrogen receptor positive;Estrogen Receptors;Estrogens;Evaluation;Evolution;experience;Experimental Designs;Experimental Models;experimental study;Freezing;Gene Expression;Genes;Genomics;Goals;Growth;Heterogeneity;Hormonal;hormone therapy;Immune checkpoint inhibitor;in vivo;Induced Mutation;inhibitor;innovation;Intervention;Kinetics;knock-down;Knowledge;Left;Ligands;Maintenance Therapy;Malignant Breast Neoplasm;Mammary Neoplasms;Metastasis Induction;Metastatic breast cancer;Modeling;mutant;Mutation;Neoplasm Metastasis;new therapeutic target;novel;novel strategies;novel therapeutics;Oncogenes;Oncology;Organoids;Outcome;Pathway interactions;patient derived xenograft model;Patients;Phenotype;Phosphorylation;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;Pre-Clinical Model;Preclinical Testing;Primary Neoplasm;Proliferating;Proteins;Recurrence;refractory cancer;replication stress;Reporter;Repression;Research;Research Personnel;Resistance;resistance mechanism;response;Role;Signal Transduction;Small Interfering RNA;stem cells;Testing;therapeutic development;therapeutically effective;therapy resistant;Time;transcriptome sequencing;Transplantation;tumor;Tumor Bank;tumor progression;Work

PROJECT_TITLE: Replication Stress and DNA Damage Response Drives ESR1 Mutant Metastasis


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Prevention;Rare Diseases;Tuberculosis;Vaccine Related

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Mycobacterium tuberculosis (Mtb)- the causative agent of tuberculosis (TB)- kills more people than any other bacteria. Macrophages normally play the first line of defense against microbes, but in the case of Mtb, they provide a site in which the bacteria can grow. We will elucidate how a protein and a lipid from Mtb, CpsA and phthiocerol dimycocerosate, respectively, enable the bacteria to evade killing by host macrophages and establish an infection. Our studies will yield important insights into why humans fail to sterilize Mtb and advance innovative therapies and vaccines for TB.

PI_NAMEs: PHILIPS, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: 2019-nCoV;acute infection;Alleles;antimicrobial;Attenuated;Autophagocytosis;Autophagolysosome;Bacillus;Bacteria;Bacterial Infections;blocking factor;Cause of Death;cell type;Cells;chronic infection;Collaborations;conditional knockout;Data;Dose;Generations;Goals;Growth;Human;Immune;Immune Evasion;Immunity;Impairment;improved;in vivo;Infection;Infection Control;innate immune function;innate immune mechanisms;Innate Immune Response;innovation;Innovative Therapy;insight;Knockout Mice;Lipids;Lung;Lysosomes;Macrophage;Mediator;Microbe;Mitochondria;Modeling;Mus;mutant;mycobacterial;Mycobacterium tuberculosis;Myeloid Cells;NADP;NADPH Oxidase;neutrophil;novel strategies;Oxidases;pathogen;Pathway interactions;Persons;Phagocytosis;Phagolysosome;Phagosomes;Phospholipase D;Play;prevent;Production;Property;Protein Export Pathway;Protein Secretion;Proteins;Reactive Inhibition;Reactive Oxygen Species;recruit;Role;Site;System;Testing;Tetracyclines;trafficking;Tuberculosis;tuberculosis treatment;Tuberculosis Vaccines;Vaccines;Virulence;Virulence Factors;Work

PROJECT_TITLE: Mechanisms of Innate Immune Evasion by Mycobacterium Tuberculosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-D(90)]


ORG_STATE: CA

PHR: PROJECT NARRATIVE  Obstructive sleep apnea (OSA) is a common condition and is a critical risk factor for the development of cardiovascular disorders in children and adults. The current proposal investigates candidate microbial strains and metabolites that are important in OSA-induced cardiovascular disease. The knowledge obtained from this study will provide valuable information for identifying novel therapeutic targets and developing effective strategies for OSA-induced cardiovascular disorders in humans.

PI_NAMEs: HADDAD, GABRIEL G (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Acceleration;Adult;Affect;Apolipoprotein E;atherogenesis;Atherosclerosis;Bile Acids;bile salts;Bioinformatics;Blood;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular risk factor;Cardiovascular system;Cells;Child;Development;Disease;Ecology;Exposure to;Family;Foam Cells;Germ-Free;GPBAR1 gene;gut bacteria;gut microbiome;Human;Hypercapnia;Hypoxia;improved;In Vitro;in vivo;insight;Knock-out;Knockout Mice;Knowledge;Laboratories;Low-Density Lipoproteins;Lung Diseases;Macrophage;Macrophage Activation;Mediating;Metabolism;metabolome;metabolomics;Metagenomics;microbial;microbiome;microbiota;Mouse Strains;Mus;Myocardial Infarction;new therapeutic target;novel;Obesity;Obstructive Sleep Apnea;oxidized low density lipoprotein;Peritoneal Macrophages;Play;Population;prevent;Primary Cell Cultures;receptor;reverse cholesterol transport;Risk Factors;Role;Sleep Disorders;Stroke;Technology;Testing;uptake

PROJECT_TITLE: Obstructive sleep apnea, the microbiome and cardiovascular disease

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Nashville

ORG_DEPT: BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative Membrane biogenesis is an essential process for all living cells and defects in this process underlies many of the most common human diseases. Moreover, the majority of drugs in the market target membrane proteins or membrane-associated processes. This research will improve our understanding of how biological membranes are assembled and how they achieve their precise composition of lipid and protein molecules.

PI_NAMEs: GRAHAM, TODD R (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Apoptotic;ATP phosphohydrolase;Binding;Biochemical Genetics;Biological;Blood coagulation;Cardiovascular Diseases;Cell fusion;Cell membrane;Cells;Coat Protein Complex I;Cytokinesis;Defect;Endosomes;Eukaryota;Eukaryotic Cell;Excision;extracellular;Family;genetic approach;Glucosylceramides;Golgi Apparatus;hearing impairment;Homeostasis;human disease;immunodeficiency;improved;Lecithin;Life;Link;lipid transport;Lipids;Liver diseases;Lysosomes;Marketing;Mediating;Membrane;membrane assembly;membrane biogenesis;Membrane Proteins;Molecular Genetics;Morphogenesis;Nervous System Disorder;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;Obesity;Organelles;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pharmaceutical Preparations;Phosphatidylethanolamine;Phosphatidylserines;Post-Translational Protein Processing;Process;protein protein interaction;protein transport;Proteins;Pump;Research;Role;Signal Transduction;Sphingolipids;Structure;System;Ubiquitination;Vesicle;Viral

PROJECT_TITLE: Mechanisms of membrane homeostasis through protein and lipid transport

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

PROJECT_TERMS: Alleles;ATAC-seq;BHLH Protein;Blood;Cardiac;Cardiac conduction system;Cardiac Myocytes;cardiogenesis;CCCTC-binding factor;Cell Lineage;Cell Physiology;cell type;Cells;Chromatin;chromatin immunoprecipitation;chromosome conformation capture;Clinical;clinical prognosis;cofactor;Communication;Complex;conditional knockout;Congenital Abnormality;congenital heart abnormality;Data;Defect;Detection;Development;Developmental Process;Diagnosis;Disease;DNA;DNA Binding;Down-Regulation;Elements;Embryo;Embryonic Heart;embryonic stem cell;Engineering;Enhancers;Epigenetic Process;epigenetic regulation;Epitopes;Etiology;GATA4 gene;Gene Expression;Gene Expression Profile;gene regulatory network;Genes;Genetic Polymorphism;Genetic Transcription;Genome;Growth;Heart;heart function;Human;human data;human embryonic stem cell;Immunoprecipitation;Impairment;in vivo;insight;Knock-out;Left ventricular structure;loss of function;Modeling;Modification;Molecular;Morphogenesis;Morphology;Mus;Myocardial;Myocardium;myocyte-specific enhancer-binding-factor 2C;Neural Crest;Outcome;Papillary;papillary muscle;Patients;Pattern;pediatric patients;Phenotype;Play;Process;programs;Proteins;Publishing;Purkinje Cells;Regulation;Role;Single Nucleotide Polymorphism;Single ventricle congenital heart disease;Site;Specific qualifier value;Structure;System;Systems Development;Testing;Transcript;transcription factor;Transcriptional Regulation;transcriptome;transcriptomics;Ventricular;Ventricular Septal Defects

PROJECT_TITLE: Transcriptional regulation of cardiac morphogenesis


NIH_SPENDING_CATS: Biotechnology;Cancer;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Proposal Description: In this project, we will delineate functions for TRIM44 and its interacting molecules in MM stem-like cells using biochemical and molecular methods. The long-term goal is to establish TRIM44 as a new therapeutic target and ultimately develop inhibitors to eradicate MM stem-like cells in the bone marrow and improve patient survival.

PI_NAMEs: MCCARTY, NAMI  (contact)

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Address;Antibodies;Autologous Stem Cell Transplantation;Autophagocytosis;B lymphoid malignancy;B-Lymphocytes;Binding;Biochemical;Biological Assay;Blood Vessels;bone;Bone Marrow;Bone Surface;Catabolism;cell growth;Cell Separation;Cell Survival;Cells;chemotherapy;Clinical;Clinical Treatment;clinically relevant;Complex;Cytolysis;Dependence;Deubiquitination;Development;DNA Sequence Alteration;Drug resistance;Endothelium;Family;Family member;Gene Expression Profiling;Gene Silencing;Goals;Heterogeneity;High Dose Chemotherapy;Human;improved;improved outcome;in vivo;inhibitor;Link;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Methods;misfolded protein;Molecular;mouse model;multicatalytic endopeptidase complex;Multiple Myeloma;Neoplasms;Neoplastic Plasma Cell;new therapeutic target;novel;Pathogenesis;Pathology;Pathway interactions;Patients;Plasma;Play;pre-clinical;Predisposition;prevent;Process;Proliferating;Proteasome Inhibition;Proteasome Inhibitor;protein aggregation;Protein Biosynthesis;protein complex;protein degradation;Protein Family;protein function;protein protein interaction;Proteins;proteostasis;proteotoxicity;receptor;Recurrence;Recurrent tumor;Refractory;Relapse;Reporting;Resistance;Resistance development;Role;Sampling;screening;Signal Pathway;Signal Transduction;stem;stem cell survival;stem cells;stem-like cell;Stress;survival outcome;System;Testing;therapy resistant;Tracer;treatment response;TRIM Motif;Ubiquitin;ubiquitin isopeptidase;Xenograft procedure

PROJECT_TITLE: Analyzing protein homeostasis pathways in multiple myeloma stem-like cells

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Hematology;Infectious Diseases;Kidney Disease;Sepsis

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Sepsis, a dysregulated response to infection, is the leading cause of acute kidney injury impacting millions of patients every year and has no proven therapy aside from supportive care. The proposed research will investigate the role of a complex biologic system, the renin-angiotensin system, and its relationship with kidney injury in sepsis. By increasing our understanding, future therapies may be developed that help treat patients with this condition and improve meaningful short- and long-term patient outcomes.

PI_NAMEs: FLANNERY, ALEXANDER H (contact)

PROGRAM_OFFICER_NAME: GREER, RAQUEL CHARLES

PROJECT_TERMS: ACE2;Acute;Acute Renal Failure with Renal Papillary Necrosis;Angiotensin II;Angiotensinogen;Angiotensins;Anti-Inflammatory Agents;bench to bedside;biobank;Biological Assay;Biological Markers;career development;Chronic;Chronic Disease;Classification;Clinical;clinical care;Clinical Research;clinical translation;cohort;college;complex biological systems;Critical Illness;Data;Death Rate;Development;End stage renal failure;Etiology;Event;Evolution;Frequencies;Functional disorder;Future;Health;Hospitalization;improved;Infection;Inflammatory;Injury;Injury to Kidney;Kentucky;Kidney;Laboratories;Learning;Machine Learning;Mass Spectrum Analysis;Measurement;Measures;Mentorship;metabolome;metabolomics;Mission;Modeling;molecular marker;mouse model;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;Outcome;patient oriented research;patient subsets;Patient-Focused Outcomes;Patients;Peptides;Peptidyl-Dipeptidase A;Pharmacy facility;Pre-Clinical Model;professor;Program Development;Prospective cohort;Proteins;Public Health;Quality of life;receptor;receptor expression;Recovery;regenerative;renal damage;Renal Replacement Therapy;Renin;Renin-Angiotensin System;Research;Research Personnel;response;Risk;Risk Marker;Role;Sepsis;Septic Shock;skills;Statistical Data Interpretation;Supportive care;Surrogate Markers;Testing;Therapeutic;Tissues;Training;translational approach;translational model;Translational Research;translational scientist;Tubular formation;Universities;Up-Regulation;urinary;Urine

PROJECT_TITLE: Classical and Alternative Renin-Angiotensin System Dysregulation in Sepsis-Associated AKI: A Reverse Translation Approach

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: Atlanta

ORG_NAME: ASSN OF FOOD/DRUG OFFICIALS/SOUTH/STATES

ORG_STATE: GA

PHR: AFDOSS PROJECT NARRATIVE AFDOSS Annual Educational Conferences provide information on current and emerging food, drug, and medical device topics impacting health and safety and helps build consensus among the states on regulatory approaches to address them. The conference presentations give local, state, and territorial regulators an opportunity to hear both a national and international perspective on food, drug, and medical device safety. Grant funding for travel costs enables participation of individuals that otherwise might not attend due to economic constraints.

PI_NAMEs: WILLIAMS, SUMMER  (contact)

PROGRAM_OFFICER_NAME: BUTLER, JENICE

PROJECT_TITLE: AFDOSS Annual Educational Conferences 2022 - 2026


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Co-Principal Investigators/ProgramDirectors (Last, First, Middle): Shekhar, Anantha; Johnson, Philip L.  Panic disorder (PD) is a severe anxiety disorder characterized by recurrent panic attacks affecting about 2- 5% of the population and resulting in severe disability in about a third of those patients. Using our well established animal model, we identified that a specific set of brain cells called orexin (hypocretin) neurons are a key regulators of panic attacks, which are inhibited by a subset of midbrain serotonergic neurons. Therefore, we will determine how interactions between these two chemical pathways regulate normal panic and how they are impacted in PD pathology. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

PI_NAMEs: TRUITT, WILLIAM ANTHONY (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: Acute;Address;Affect;Agoraphobia;Animal Model;Animals;Anxiety Disorders;Area;behavior measurement;Biological Models;brain cell;Carbon Dioxide;Cardiovascular system;Cerebrospinal Fluid;Chemicals;Chronic;Cognitive;Cognitive Therapy;comorbidity;Data;Development;Diagnosis;disability;Disabling;disabling symptom;Disinhibition;Dorsal;effective therapy;Electrophysiology (science);Esthesia;Experimental Models;Female;Fright;gastrointestinal;Gene Silencing;Genetic;Genetic Techniques;Goals;human disease;hypocretin;Hypothalamic structure;Induced Neurons;Inhalation;innovation;Interneurons;Knowledge;Laboratories;Lateral;Learning;Lesion;Life;Literature;male;Mediating;Mediator;Mental Depression;Mental disorders;Methods;Midbrain structure;Modeling;Molecular;National Institute of Mental Health;neural circuit;neuromechanism;Neurons;news;novel;optogenetics;Panic;Panic Attack;Panic Disorder;Pathologic;Pathological anxiety;Pathology;Pathway interactions;Patients;Persons;pharmacologic;Pharmacological Treatment;Phobias;Play;Population;Post-Traumatic Stress Disorders;pre-clinical;Prefrontal Cortex;Principal Investigator;Property;Psychotherapy;Publishing;Reaction;receptor;Recurrence;Research Domain Criteria;response;Rodent;Role;Selective Serotonin Reuptake Inhibitor;Serotonergic System;Serotonin;Serotonin Receptor 5-HT1A;Severities;side effect;Strategic Planning;Structure;suicidal behavior;suicidal risk;Symptoms;System;Techniques;Testing;Time;Translational Research;Wing;Work

PROJECT_TITLE: Mechanisms of Serotonin Modulation of Panic

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Machine Learning and Artificial Intelligence;Pediatric;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Cardiac outflow tract (OFT) defects, including aortic valves and the greater arteries, are estimated to cause approximately 30% of these congenital heart diseases, and they are treated with surgical correction and/or replacement. It remains unclear what would be the consequences of reduced cardiac contractility or altered intracardiac flow dynamics on valve morphogenesis, including aortic stenosis, bicuspid or tricuspid aortic valves. To understand the mechanotransduction causation downstream of blood flow and shear stress sensing, we have assembled a multi-disciplinary team to integrate advanced laser optics, imaging computation, and genetic models to decouple intracardiac flow dynamics from myocardial contractility that modulates Notch1b-mediated endothelial-to-mesenchymal transition (EndoMT) with translational implication to aortic valve disease.

PI_NAMEs: HSIAI, TZUNG K (contact);MARSDEN, ALISON L

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: 4D Imaging;aortic valve;aortic valve disorder;Aortic Valve Stenosis;Arteries;automated segmentation;Bicuspid;Biomechanics;Blood flow;Cardiac;clinically significant;Computer Models;congenital heart abnormality;Congenital Heart Defects;Coupled;Cuspid;Custom;Data;Defect;Detection;Endocardium;Endothelium;erbB-2 Receptor;Etiology;Fluorescence Microscopy;Funding;Genes;Genetic Models;Genetic Recombination;Goals;hemodynamics;Image;imaging Segmentation;Kinetics;Lasers;lens;Light;Lighting;Liquid substance;Machine Learning;mechanotransduction;Mediating;Mesenchymal;Microscopy;Mitral Valve;Morphogenesis;multidisciplinary;Mutation;Myocardial;Myocardial Contraction;Neuregulin 1;neuregulin 2;notch protein;Operative Surgical Procedures;Optics;Proliferating;receptor;Receptor Protein-Tyrosine Kinases;Reporter;Reporting;Resolution;response;Role;shear stress;Signal Pathway;Signal Transduction;simulation;single-cell RNA sequencing;spatiotemporal;Stress;Structure;System;Testing;TG gene;Time;transcriptomics;Transgenic Model;Transgenic Organisms;transmission process;Variant;Ventricular Remodeling;Vimentin

PROJECT_TITLE: Shear stress and light-field to elucidate the initiation of cardiac outflow tract


PI_NAMEs: SHOU, WEINIAN  (contact)

PROJECT_TERMS: Ablation;Adopted;Alleles;ATAC-seq;BACH1 gene;Binding;Biological;Biological Assay;blastocyst;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiovascular system;Cell Differentiation process;Cells;Chromatin;Cleavage Under Targets and Release Using Nuclease;Complex;Congenital Heart Defects;CRISPR/Cas technology;Data;Data Analyses;Defect;Development;Disease;DNA;DNA biosynthesis;Embryo;Embryonic Development;Epigenetic Process;epigenetic regulation;Event;Exhibits;experimental study;Family member;Gastrula;gastrulation;Gene Abnormality;gene editing technology;Gene Expression Profile;gene regulatory network;gene repression;Generations;Genes;Genetic;genetic association;Genetic Transcription;genetic variant;genome-wide;Germ Lines;Growth;Heart;heart defect;Histone H3;histone modification;Histones;human embryonic stem cell;In Vitro;in vivo;Knock-in Mouse;Knockout Mice;Lysine;Mass Spectrum Analysis;member;Mesoderm;Methyltransferase;Modeling;Modification;Molecular;Morphogenesis;mutant;Mutant Strains Mice;Nature;Neuroectoderm;Pattern;Phenocopy;Phenotype;Play;Process;Protein Binding Domain;Protein Family;protein protein interaction;Proteins;Proteomics;Regulation;repaired;Resolution;Role;Series;single-cell RNA sequencing;Specific qualifier value;stem cell differentiation;Stem cell pluripotency;stem cells;Structure;Testing;Transcriptional Activation;transcriptomics;Translational Regulation;Ventricular;Zebrafish

PROJECT_TITLE: The role of Smyd4 in regulating cardioprogenitor specification.


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Immunotherapies have revolutionized the treatment of cancer by improving survival benefit for patients in a number of cancer types, however, with increasingly complex treatment strategies being deployed in a variety of combinations, the risk for developing severe side-effects in the form of immunotoxicities is heightened. Through improved preclinical models, such as generating tumors in autoimmune-prone mice, we can better study the influence of immunotherapies on both tumor immunity and autoimmunity. This will address a growing need to provide accurate safety profiling and mechanistic interrogation of both combinatorial and single-agent therapies to determine optimal therapeutic regimens to improve cancer care with mimimal immune-related adverse-events.

PI_NAMEs: YOUNG, ARABELLA  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Age;anti-CTLA4;anti-tumor immune response;Autoimmune;Autoimmune Diseases;Autoimmunity;Body System;California;cancer care;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;Circadian Rhythms;Clinical;combinatorial;Combined Modality Therapy;Complex;Data Set;design;Development;diabetic;Diet;dimensional analysis;Disease;Engineering;Environment;Environmental Impact;Environmental Risk Factor;Epigenetic Process;Etiology;Event;Exposure to;Follow-Up Studies;Fostering;Frequencies;Genetic;Genetic Predisposition to Disease;genetic profiling;Goals;Health Care Costs;high dimensionality;Homeostasis;Immune;immune activation;immune cell infiltrate;immune checkpoint;Immune Evasion;immune function;Immune response;Immune system;immune-related adverse events;Immunity;immunomodulatory therapies;Immunoprecipitation;Immunotherapy;immunotoxicity;improved;Inbred NOD Mice;insight;Insulin-Dependent Diabetes Mellitus;Malignant Neoplasms;Mediating;Mentorship;microbiome;Modality;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mouse Strains;multidimensional data;Mus;Neoplasm Transplantation;Non obese;novel therapeutics;Pathology;Pathway interactions;Patients;Phase;Positioning Attribute;pre-clinical;Pre-Clinical Model;preclinical development;preservation;prevent;programmed cell death protein 1;programs;Regimen;Reporting;Research;Resistance;resistance mechanism;response;Risk;Role;Safety;safety assessment;San Francisco;Scientist;Self Tolerance;Severities;side effect;single-cell RNA sequencing;skills;Specificity;Stress;success;survival outcome;Susceptibility Gene;T cell receptor repertoire sequencing;Therapeutic;Tissues;Training;Transplantation;Treatment Efficacy;treatment strategy;tumor;Tumor Cell Line;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;Universities

PROJECT_TITLE: Developing strategies to inhibit cancer immunotherapy-induced immune-related adverse events without impeding anti-tumor immunity


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CORAL GABLES

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: The proteins synaptobrevin, SNAP25, syntaxin, Munc18 and Munc13 play a central role in the membrane fusion process that mediates neurotransmitter release. Similar proteins mediate release of hormones, histamines and various other compounds form cells of the immune system. This project is aimed at determining the precise nanomechanicxal interactions and structural changes of these proteins associated with their function, which is widespread medical significance from neurodegenerative diseases to the function of the immune system.

PI_NAMEs: LINDAU, MANFRED  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: antimicrobial;Binding;Biological Models;Cell Physiology;cell type;Cells;Chromaffin Cells;combat;Complex;cytotoxic;Data;detector;Docking;eosinophil;Event;Exocytosis;Experimental Designs;experimental study;Goals;Heparin;Histamine;Histamine Release;Hormones;Immune system;immune system function;Innate Immune System;innovation;insight;Investigation;Laboratories;mast cell;Mediating;Mediator;Medical;Membrane;Membrane Fusion;Microscopy;Molecular;Molecular Conformation;molecular dynamics;Motion;movie;nanomechanics;Neurodegenerative Disorders;Neuroendocrine Cell;Neurons;neurotransmitter release;neutrophil;Parasites;Play;Process;programs;protein complex;protein function;Proteins;receptor;reconstitution;Regulation;Research;Resolution;Role;Secretory Vesicles;SNAP receptor;Structure;synaptotagmin;syntaxin;syntaxin 1;System;trafficking;VAMP-2;Vesicle;vesicle-associated membrane protein;Viral;Vision

PROJECT_TITLE: Molecular mechanisms of exocytotic vesicle fusion and release.

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: CAMBRIDGE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: NARRATIVE Understanding the neural circuits and mechanisms of sensorimotor adaptation and learning is essential for addressing behavioral deficits associated with sensorimotor dysfunction and for identifying effective strategies for intervention. Our research brings together electrophysiological studies in nonhuman primates with computational modeling to provide an understanding of how cortical circuits support sensorimotor learning, and help lay a foundation for developing new strategies for treatment.

PI_NAMEs: JAZAYERI, MEHRDAD  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Address;Anatomy;Animal Model;Animals;Area;Basal Ganglia;Bayesian Prediction;Behavior;Behavioral;Behavioral Paradigm;behavioral study;Brain;Cerebellum;Computer Models;Decision Theory;Dorsal;dynamic system;Electrophysiology (science);Environment;Exhibits;experience;experimental study;Foundations;frontal lobe;frontier;Functional disorder;Human;improved;Intervention;Language;Learning;Medial;Modeling;Monkeys;Motor;neural;neural circuit;Neurobiology;neuromechanism;Neurons;neurotransmission;nonhuman primate;novel;novel therapeutic intervention;Output;Performance;Physiology;Population;Population Dynamics;Primates;Probability;Process;Property;Psychophysics;Reproduction;Research;response;Role;Shapes;Signal Transduction;Specificity;statistical learning;statistics;Structure;Testing;Thalamic structure;theories;Time;time interval;Variant

PROJECT_TITLE: Sensorimotor Learning Through Adjustments of Cortical Dynamics

STUDY_SECTION: SMI

STUDY_SECTION_NAME: Sensorimotor Integration Study Section[SMI]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PI_NAMEs: DURBIN, MATTHEW D. (contact)

PROJECT_TERMS: Address;Affect;Amino Acid Substitution;Amino Acids;Anatomy;Animals;Binding;Binding Sites;Biological Assay;Candidate Disease Gene;Cardiac;Cardiac Myocytes;cardiogenesis;career;cell motility;Cell Shape;Cells;cohort;Congenital Abnormality;congenital heart abnormality;Cytoplasmic Protein;Cytoskeleton;Data;Defect;Development;Disease;disease model;Dsh protein;Embryo;Embryonic Heart;Etiology;Exhibits;Family;gene function;Genetic;Genomics;Growth;Heart;heart defect;Heart Ventricle;Heterozygote;Histologic;Immune;Immunoprecipitation;in vivo;Laboratories;Left;Left ventricular structure;loss of function;MAPK8 gene;Maps;Mass Spectrum Analysis;Mentorship;migration;Molecular;Molecular Biology;Monomeric GTP-Binding Proteins;Morphogenesis;mouse model;Mus;mutant;Mutant Strains Mice;Neural Crest Cell;novel;Pathogenesis;Pathway interactions;Patients;Pattern;Phosphorylation;planar cell polarity;progenitor;Protein Kinase;protein protein interaction;Proteins;Research;Research Personnel;rho;Role;Scientist;Series;Signal Pathway;Signal Transduction;Situs Inversus;skills;stem cell migration;Structure;Testing;TNFSF5 gene;transcriptome sequencing;Transfection;Ubiquitination;Variant;Ventricular;Ventricular Septal Defects

PROJECT_TITLE: The role of SHROOM3 in congenital heart disease


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Data Science;Dietary Supplements;Networking and Information Technology R&D (NITRD);Nutrition;Precision Medicine;Prevention

ORG_CITY: CHAPEL HILL

ORG_DEPT: NUTRITION

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative (Metabolomics and Clinical Assay Center, MCAC) The Metabolomics and Clinical Assay Center (MCAC) will perform targeted and untargeted metabolomics assays, and clinical assays in blood, urine, and stool biospecimens as part of the NIH Common Fund Nutrition for Precision Health (NPH) Consortium. Clinical Centers, funded under a companion mechanism, will conduct dietary intervention studies, and collect the biospecimens from participants in the All of Us Research Program. The MCAC will collaborate with all awarded components (Clinical Centers, Dietary Assessment Center, Microbiome and Metagenomics Center, Research Coordinating Center, Artificial Intelligence for Multimodal Data Modeling and Bioinformatics Center) to derive consensus on appropriate study designs, tools, assays, and the interpretations that will reveal how human biological systems and molecular pathways interact with or mediate the relationships among dietary patterns, environmental, social, and behavioral factors to influence health status.

PI_NAMEs: SUMNER, SUSAN J (contact)

PROGRAM_OFFICER_NAME: SRINIVAS, POTHUR R

PROJECT_TERMS: acylcarnitine;algorithm development;All of Us Research Program;Amino Acids;analysis pipeline;Artificial Intelligence;Automatic Data Processing;Award;Behavioral;Biogenic Amines;Bioinformatics;Biological;Biological Assay;biological systems;Blood;Branched-Chain Amino Acids;Cardiovascular Diseases;Catabolism;Ceramides;Chronic Disease;Classification;CLIA certified;Clinical;clinical center;clinical phenotype;Clinical Research;Cloud Computing;Collaborations;Collection;Communities;Companions;computational pipelines;Consensus;Coupled;Data;data ecosystem;data infrastructure;data interoperability;Data Management Resources;data modeling;Data Set;demographics;Deposition;design;Diabetes Mellitus;dietary;Dietary Assessment;Dietary intake;Dietary Intervention;Dietary Practices;disease phenotype;disorder risk;Elements;Endocrine;Ensure;Environment;epidemiology study;evidence base;experience;Faculty;Feces;feeding;Food;Funding;Future;Genetic;Health;Health Status;Heterogeneity;Human;Illicit Drugs;improved;Individual;Inflammatory;Informatics;Ingestion;interoperability;Intervention;Intervention Studies;Knowledge;knowledge base;Laboratories;Libraries;lifestyle factors;Link;Lipids;Malignant Neoplasms;Management Information Systems;Manuals;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Pathway;metabolic phenotype;metabolic profile;Metabolism;metabolome;metabolomics;Metagenomics;metatranscriptomics;microbial;microbiome;Molecular;multimodal data;North Carolina;Nutrient;nutrition;Nutrition Assessment;Nutritional status;Nutritional Study;Obesity;Ontology;Participant;Pathway interactions;personalized intervention;Pharmaceutical Preparations;Physiology;Phytochemical;Policies;Population;Precision Health;precision nutrition;prevent;Privacy;Procedures;Process;programs;Protocols documentation;public database;quality assurance;Quality Control;Quality of life;Reporting;Research;Research Design;Research Institute;Research Personnel;Resolution;Resources;response;Sampling;Scientist;social;Sphingomyelins;Structure;Study Subject;success;System;Technology;Time;timeline;Tobacco use;tool;transcriptomics;Translating;TRUST principles;United States National Institutes of Health;Universities;Urine;Vitamins;Work

PROJECT_TITLE: Metabolomics and Clinical Assays Center


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Prevention;Racial and Ethnic Minority Health Research;Women's Health Research

ORG_CITY: DURHAM

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE For Black cisgender women living in New Orleans, Louisiana, the rate of new HIV diagnosis is almost 7 times higher than that of White women; uptake of pre-exposure prophylaxis (PrEP) has been limited. In our previous research, we found that Black cisgender women do not know of other Black cisgender women taking PrEP, and Black women are not offered PrEP during routine medical care. Therefore, we will develop and pilot implementation strategies at the patient- and provider-levels that are designed to increase PrEP uptake and retention in PrEP care among Black cisgender women.

PI_NAMEs: CLEMENT, MEREDITH EDWARDS;CORNELI, AMY LYNN (contact)

PROGRAM_OFFICER_NAME: GORDON, CHRISTOPHER M

PROJECT_TERMS: Address;Administrative Supplement;Adoption;Advisory Committees;Awareness;Black race;black women;care outcomes;Caring;cis-female;Clinic;Communities;community organizations;design;Education;Educational Curriculum;effectiveness measure;Epidemic;Evaluation;experience;Feedback;Focus Groups;follow-up;Funding;Grant;Gynecology;Health;health disparity;Health Services Accessibility;HIV;HIV diagnosis;HIV Infections;implementation evaluation;implementation outcomes;implementation research;implementation science;implementation strategy;improved;interest;Interview;Link;Location;Louisiana;Maintenance;Measures;Media Campaign;Medical;member;Methods;Modeling;Outcome;Patients;pre-exposure prophylaxis;programs;Provider;Research;Research Personnel;Research Proposals;Residencies;Sexual Health;shared decision making;sharing platform;Site;social media;social networking website;Stress;Testing;Training;Training Programs;United States National Institutes of Health;Universities;uptake;White Women;Woman;working group

PROJECT_TITLE: Start the conversation: A multi-level PrEP initiative for Black women in NOLA

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Precision Medicine;Prevention

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity, mortality, and healthcare costs. Bacterial infections are a common cause of exacerbations, however it is not known whether individuals with frequent exacerbations have specific defects in antibody function against bacteria. Investigating antibody-mediated immune function in COPD could lead to the recognition of novel risk factors for exacerbations, newly recognized sub-populations, and targeted therapeutic interventions for individuals with immune dysfunction, with potential for broader application to other pathogen types and disease processes.

PI_NAMEs: LAFON, DAVID CARDY (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: adaptive immune response;adaptive immunity;Adult;airway inflammation;Alleles;Antibodies;Antibody Response;Bacteria;Bacterial Infections;Biological Assay;Biological Markers;Biometry;Blood specimen;Bronchiectasis;career;career development;Chronic Bronchitis;Chronic Obstructive Pulmonary Disease;Clinical;Clinical Research;cohort;Cohort Studies;congenital immunodeficiency;Data;Defect;Development;Development Plans;Diagnosis;Disease;disease phenotype;disorder control;disorder risk;disorder subtype;Down-Regulation;Encapsulated;Evaluation;Exhibits;experience;follow-up;former smoker;Fostering;Frequencies;Future;gene repression;genetic variant;Goals;Health Care Costs;High Prevalence;IgG2;Image;Immune;immune function;Immune response;Immune System Diseases;Immunoglobulin G;Immunologics;Immunology;Impairment;In Vitro;Incidence;Individual;Infection;infection risk;International;Investigation;Laboratories;Measurable;Measures;Mediating;Mentorship;Methods;Microbiology;Morbidity - disease rate;mortality;neutrophil;Neutrophilia;never smoker;novel;novel strategies;older adult;Outcome Measure;Participant;pathogen;Pathway interactions;Patient Self-Report;Patients;personalized approach;personalized medicine;personalized therapeutic;Phagocytosis;Phenotype;Pneumococcal vaccine;Population;Predisposition;primary endpoint;Process;Prognosis;prospective;Recurrence;Research;research and development;Respiratory Tract Infections;response;Risk;Risk Factors;risk prediction;Sampling;Serum;Severities;Smoker;Source;Streptococcus pneumoniae;Subgroup;Symptoms;targeted treatment;Techniques;Testing;Therapeutic Intervention;tool;Training;Translational Research;vaccine trial;Vaccines;Variant

PROJECT_TITLE: Impaired Pneumococcal Antibody Function and Exacerbations of Chronic Obstructive Pulmonary Disease

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

ORG_DEPT: DENTISTRY

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Itch is a common sensory experience that allows for the detection of noxious substances and incites their removal by scratching that can be debilitating if not properly controlled. Advances in our understanding of the itch-specific neural pathway have highlighted many G protein-coupled receptors needed to transmit itch, and new discoveries in sensory neurons have emphasized the importance of G protein-coupled receptor signaling from subcellular domains to convey sensory stimuli. This research project seeks to link these new discoveries, to determine the importance of endosomal signaling of GPCRs in itch and to characterize new targets for improved therapeutics to treat pruritus.

PI_NAMEs: JENSEN, DANE D (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Address;Afferent Neurons;Agonist;Animals;antagonist;Anxiety;Behavior;Behavioral Assay;Biology;Bioluminescence;biophysical techniques;Bombesin Receptor;Cell Line;Cell membrane;Cell model;Cell Nucleus;Cell Surface Receptors;Cells;Chemicals;chronic itch;chronic pain;Clathrin;Complex;confocal imaging;Confocal Microscopy;conventional therapy;Cytosol;desensitization;design;Detection;Dynamin;Electrophysiology (science);Encapsulated;Endocytosis;Endosomes;Energy Transfer;Event;Excision;experience;Family;FDA approved;Fluorescence Resonance Energy Transfer;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Gastrin releasing peptide;genetic approach;imaging approach;improved;inhibitor;insight;Interneurons;Irritants;knock-down;Knowledge;Ligand Binding;Link;Mediating;Mental Depression;method development;Modality;Modeling;mouse model;Multiprotein Complexes;Mus;nanoengineering;nanoparticle;nanoparticle delivery;Neural Pathways;Neurons;novel therapeutics;Pathologic;Pathologic Processes;Pathway interactions;peptide P;Peptide Receptor;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Physiological;Physiological Processes;Play;prevent;Pruritus;Publishing;Quality of life;receptor;Receptor Activation;Receptor Signaling;recruit;Reporting;Research Project Grants;Resolution;response;Role;Sensory;sensory stimulus;signal recognition particle receptor;Signal Transduction;Skin;Slice;Small Interfering RNA;spatiotemporal;Spinal;Spinal Cord;Stimulus;Stress;Substance P;Suicide;TACR1 gene;targeted treatment;Testing;Therapeutic;therapeutic target;therapy design;trafficking;transmission process

PROJECT_TITLE: Mechanisms of Endosomal Signaling of Itch

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: BOSTON

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: PROJECT NARRATIVE Tuberculosis treatment is difficult, requiring multidrug treatment for many months. To more effectively treat tuberculosis, including drug resistant disease, we must develop new combination therapies that are effective against bacteria in different types of lesions. In this project, we will develop an efficient, lesion-centric pipeline for data-driven optimization of multi-drug regimens.

PI_NAMEs: ALDRIDGE, BREE BEARDSLEY (contact);KIRSCHNER, DENISE E

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: Adverse effects;Adverse reactions;Animal Model;Antibiotics;Bacteria;Callithrix;Clinic;Clinical;clinical development;Clinical Trials;clinical trials in animals;Combined Modality Therapy;Complex;Computer Models;Computer Simulation;Data;data pipeline;design;Development;Disease;Disease Resistance;drug action;Drug Approval;Drug Combinations;drug efficacy;Drug Interactions;Drug Kinetics;Drug resistance;drug response prediction;drug standard;Drug Tolerance;Ensure;Environment;environmental stressor;Ethambutol;Experimental Models;Granuloma;Growth;Human;Immune;improved;In Vitro;in vitro Assay;in vitro Model;in vivo;in vivo Model;Individual;Infection;invention;isoniazid;Lesion;Linezolid;Link;Lung;lung lesion;Macaca;mathematical model;Mauritius;Measurement;Measures;Methodology;Methods;Modeling;Molecular;mouse model;Mus;Mycobacterium tuberculosis;Necrotic Lesion;new combination therapies;nonhuman primate;novel;novel therapeutics;Organ;Outcome;pathogen;Pathology;Penetration;Pharmaceutical Preparations;pharmacodynamic model;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Pharmacotherapy;Population;Predisposition;Process;Property;Pyrazinamide;Qualifying;Recurrent disease;Regimen;Research;Resistance;response;Rifampin;side effect;standard of care;Stress;stressor;Testing;Time;treatment duration;Tuberculosis;tuberculosis drugs;tuberculosis treatment

PROJECT_TITLE: Lesion-centric optimization of multidrug therapies for tuberculosis

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Hematology;Infectious Diseases;Patient Safety;Pediatric;Sepsis

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative Overuse of blood cultures to evaluate critically ill children for bacteremia can lead to a cascade of harm in the form of false positive results, unnecessary antibiotics, increased cost, and longer length of stay. The patient- level, clinician-level, and organizational-level determinants of overuse of diagnostic tests such as blood cultures are poorly understood, and no work has evaluated overuse reduction strategies. I will use implementation and behavioral science to define those determinants, and then develop and test strategies to safely reduce blood culture overuse in critically ill children.

PI_NAMEs: WOODS-HILL, CHARLOTTE Z (contact)

PROGRAM_OFFICER_NAME: FRANK, DANIEL J

PROJECT_TERMS: Address;Adverse drug event;Antibiotic Resistance;Antibiotics;Award;Bacteremia;Behavior;Behavioral;Behavioral Sciences;Belief;Blood;Caring;Cessation of life;Childhood;Clinical;Clinical effectiveness;Clinical Trials;Cluster randomized trial;Cognitive;Communicable Diseases;Complex;Consensus;Consolidated Framework for Implementation Research;cost;Coupling;Critical Care;Critically ill children;Data;Death Rate;Decision Making;design;Diagnosis;diagnosis standard;Diagnostic;Diagnostic tests;Effectiveness;effectiveness research;Enrollment;experience;Foundations;Fright;Funding;Goals;Guidelines;Healthcare;Heart failure;Hospitalized Child;Hybrids;implementation design;implementation framework;implementation science;implementation strategy;implementation trial;improved;Incidence;Interview;Investigation;Knowledge;Laboratories;Length of Stay;Link;Maps;Medical;Mentors;Methods;Morbidity - disease rate;mortality;Outcome;overtreatment;patient safety;Patient-Focused Outcomes;Patients;Pattern;Pediatric Hospitals;Pediatric Intensive Care Units;pediatric sepsis;Pennsylvania;Performance;Philadelphia;Pilot Projects;Population;Prevalence;Proctor framework;provider factors;Qualitative Methods;Quasi-experiment;Randomized;Research Methodology;Research Personnel;Resources;Respiratory Failure;Risk;Safety;Scientist;Self Efficacy;Sepsis;Series;Signs and Symptoms;Site;skills;Symptoms;Testing;theories;trial design;Uncertainty;United States;United States Agency for Healthcare Research and Quality;Universities;unnecessary treatment;Variant;Work

PROJECT_TITLE: Leveraging implementation and behavioral science to reduce harmful overuse of diagnostic testing in critically ill children

STUDY_SECTION: MPOR

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


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

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: Project Narrative  The neural mechanisms of reward seeking and punishment avoidance remain unclear. In the proposed research program, we will determine how the central amygdala participates in such behaviors and in the generation of anxiety state. Findings from this project will have important clinical implications, as dysfunctions in the central amygdala have been implicated in anxiety disorders, depression and drug addition.

PI_NAMEs: VAN AELST, LINDA  (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Amygdaloid structure;Anxiety;Anxiety Disorders;anxiety states;anxiety-related behavior;Appetitive Behavior;Area;Aversive Stimulus;avoidance behavior;Behavior;Behavioral;behavioral response;Brain;Cell Physiology;cell type;cholinergic;Clinical;conditioned fear;Data;Desire for food;Disease;Disinhibition;Dopamine;Drug Addiction;Dynorphins;Educational process of instructing;Environment;Fiber;Fright;Functional disorder;Generations;Genetic;Genetic Markers;Goals;Human;Impairment;improved;in vivo;in vivo imaging;insight;Knowledge;Learning;Measures;Mental Depression;Moods;motivated behavior;Motivation;Mus;neuromechanism;Neurons;Neuropeptides;neuroregulation;novel;optogenetics;Pathway interactions;Pharmaceutical Preparations;Photometry;Play;Population;Process;programs;Property;Protein Kinase C;Punishment;Regulation;Research;response;Rewards;Role;sensor;Signal Transduction;Somatostatin;Stimulus;Stress;Structure;Structure of terminal stria nuclei of preoptic region;System;Techniques;Testing

PROJECT_TITLE: The central amygdala circuits in motivated behaviors


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Pediatric

ORG_CITY: Aurora

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Pediatric sports medicine is a rapidly evolving field that contains many unique elements within clinical care and research, given that many pediatric sports injuries and conditions are unique to young athletes and do not occur in other age groups. The Pediatric Research in Sports Medicine (PRiSM) Society is dedicated to the care of pediatric and adolescent athletes, and our annual meeting provides a unique space for researchers, clinicians, and trainees from a variety of different backgrounds to gather and discuss barriers to clinical practice and ways to best address them. Through our unique approach to understanding condition-specific injuries and conditions within youth athletes and developing collaborative multi-site research projects (Research Interest Groups), the PRiSM annual meeting is a forum where interdisciplinary collaborations begin, grow, and produce meaningful advancements in the field.

PI_NAMEs: HOWELL, DAVID R. (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;Adolescent;Age;age group;Area;Athletic;Athletic Injuries;Award;Biological;biological systems;career;Caring;Child health care;Childhood;clinical care;clinical practice;Clinical Research;Collaborations;Community Medicine;Country;Dedications;design;Dimensions;Discipline;Education;Elements;Ensure;Environment;Faculty;Female;flexibility;forging;Fostering;Funding;Gender;Geographic Locations;Geography;Goals;Grant;Health;Health Professional;Hybrids;Improve Access;improved;Individual;Information Dissemination;Injury;innovation;Instruction;interdisciplinary collaboration;Interdisciplinary Study;interest;Interest Group;Journals;Knowledge;Leadership;Learning;lectures;medical specialties;meetings;member;Minority;Mission;Modeling;Musculoskeletal;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Orthopedics;Pathology;Patient Outcomes Assessments;Pediatric Research;Persons;Population;posters;Prevention;programs;Publications;Publishing;Race;Research;research data dissemination;Research Peer Review;Research Personnel;Research Project Grants;Research Support;sex;Site;Societies;sound;Spinal Fractures;Sports;Sports Medicine;Students;success;symposium;Time;Training;Travel;Underrepresented Minority;United States National Institutes of Health;virtual;Youth

PROJECT_TITLE: 2022 Pediatric Research in Sports Medicine (PRiSM) Annual Conference

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ORG_DEPT: NEUROSCIENCES

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Na+ channels are clustered at the neuromuscular junction (NMJ) and are responsible for generation of the muscle action potential. However, the mechanisms responsible for NMJ Na+ channel clustering are unknown. Here, we will determine the cytoskeletal and extracellular interactions responsible for NMJ Na+ channel clustering.

PI_NAMEs: RASBAND, MATTHEW N (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Acetylcholine;Actins;Action Potentials;Affinity Chromatography;Agrin;ANK1 gene;Ankyrins;Axon;Binding;Biotinylation;Cell Adhesion Molecules;Cells;Cholinergic Receptors;Complex;conditional knockout;Cytoskeleton;design;Development;Disease;Escherichia coli;extracellular;Extracellular Matrix;Functional disorder;gain of function;Generations;improved;insight;Intrinsic drive;Ion Channel;Knock-out;Knockout Mice;Label;Link;Location;loss of function;Maintenance;Mass Spectrum Analysis;Mediating;Membrane;Methods;Mind;Modeling;Molecular;Molecular Genetics;Motor Neurons;Mus;Muscle;Muscle Contraction;Muscle function;Myasthenic Syndrome;Myotonia;Nervous System;Neuregulins;Neuroglia;Neuromuscular Diseases;Neuromuscular Junction;Neurons;Neuropathy;Nodal;periodic paralysis;Proteins;Proteomics;Ranvier's Nodes;Receptor Activation;recruit;Role;Scaffolding Protein;Site;Skeletal Muscle;Sodium Channel;Spectrin;Streptavidin;Synapses;Toxin;voltage

PROJECT_TITLE: Mechanisms of sodium channel clustering at the neuromuscular junction

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


NIH_SPENDING_CATS: Clinical Research;Eye Disease and Disorders of Vision;Lung

ORG_CITY: NEW YORK

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Light-mediated relaxation of airway smooth muscle is a novel discovery by our laboratory but the cellular signaling mechanisms of opsin receptor activation have yet to be determined. We will identify the receptor signaling pathways by using synthetic retinal derivatives and the transfection of opsin receptors to change wavelength sensitivity of airway smooth muscle. We will also explore the mechanism of endogenous activation of opsin receptors with a naturally occurring direct agonist, β-ionone, that has the ability to activate opsin receptors in the absence of light.

PI_NAMEs: YIM, PETER D (contact)

PROJECT_TERMS: 11 cis Retinal;9-cis-retinal;Agonist;Asthma;Binding;Blood Vessels;Carotene;Cell Line;Cells;Chest;chromophore;Co-Immunoprecipitations;Coupled;Cyclic AMP;Cyclic GMP;Cytoskeleton;Disease;Evaluation;Exposure to;Eye;Family;Functional disorder;G-Protein Signaling Pathway;G-Protein-Coupled Receptors;genetic regulatory protein;Genomics;GTP-Binding Protein alpha Subunits, Gs;GTP-Binding Proteins;Human;in vivo;Intestines;Ionones;Knockout Mice;Laboratories;Ligands;Light;light intensity;Link;Lung;Measures;Mediating;Mediator;Methods;Modeling;Molecular Conformation;molecular subtypes;Mus;Muscle;Muscle relaxation phase;Mutation;Myosin Light Chains;Nebulizer;novel;novel strategies;Opsin;Organ;overexpression;Pathway interactions;Penetration;Peripheral;Phosphotransferases;photoactivation;Photons;Phytochemical;protein expression;protein protein interaction;Proteins;Pulmonary function tests;receptor;Receptor Activation;receptor binding;Receptor Signaling;Relaxation;Resistance;respiratory smooth muscle;Retina;Schiff Bases;Second Messenger Systems;Signal Pathway;Signal Transduction;Signaling Protein;Smooth Muscle;Smooth Muscle Myocytes;Specificity;Techniques;Therapeutic;Tissues;Trachea;Transfection;Uterus;Variant;Vascular Smooth Muscle;Vasodilation;Visual

PROJECT_TITLE: Mechanisms and Modulation of Opsin 3 Mediated Airway Smooth Muscle Relaxation


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: NEW ORLEANS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it utilizes a new approach to advance understanding of how the brain regulates behavioral states transitions associated with fear and panic, and will thereby provide vital information about the root cause of debilitating psychiatric illnesses, such as post-traumatic stress, panic, and specific phobia. This is directly relevant to the NIH’s mission pertaining to reducing illness and disability and of laying the foundation for ad- vances in disease treatment and prevention.

PI_NAMEs: FADOK, JONATHAN P (contact)

PROJECT_TERMS: addiction;Alprazolam;Amygdaloid structure;Anxiety;Behavior;Behavior Control;Behavioral;Behavioral Paradigm;Brain;Calcium;Carbon Dioxide;Cells;Characteristics;comorbidity;Complex;Corticotropin-Releasing Hormone;Data;delivery vehicle;design;Development;disability;Disease;Emotional;emotional behavior;extracellular;Foundations;Freezing;Fright;Glutamates;Goals;Hippocampus;Hypothalamic structure;Image;in vivo;innovation;Knowledge;Mediating;Mental disorders;midbrain central gray substance;Mission;Modeling;Monitor;Mus;neural;neural circuit;neural correlate;Neurobiology;neuromechanism;neuronal circuitry;Neurons;Neurosciences;novel;novel strategies;optogenetics;Output;Panic;Panic Disorder;Pathway interactions;Pattern;Perception;Population;Population Projection;Positioning Attribute;post-traumatic stress;Post-Traumatic Stress Disorders;Prevention;Psychological Theory;Public Health;Regulation;Research;response;Role;Source;Specific Phobia;Stimulus;Structure;Substance Use Disorder;System;Testing;theories;Therapeutic;Trauma;United States National Institutes of Health;Viral Vector;Xanax

PROJECT_TITLE: Neural circuits regulating flight and panic behavior.

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE The proposal examines how a particular type of immune cell responds to its environment during the development of human inflammatory bowel disease by using animal models and different forms of this immune cell to treat this disease in animals. The goal of our research is to understand how this immune cell, termed “regulatory T cells,” in the intestine can be optimized to better suppress the disease. Information gained from this study will help identify approaches to inhibit excessive inflammation and provide treatment strategies for stopping this debilitating condition that destroys bowel.

PI_NAMEs: BAMIDELE, ADEBOWALE O (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Activities of Daily Living;Animal Model;Animals;Anions;Anti-Inflammatory Agents;Architecture;Blood Cells;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cellular biology;Cellular Metabolic Process;Clinical;Clinical Trials;Colitis;Communication;Complex;Contact Inhibition;Crista ampullaris;Cues;cytokine;Data;design;Development;Digestive System Disorders;Disease;effector T cell;Endoplasmic Reticulum;Environment;Experimental Models;extracellular;fatty acid oxidation;Fatty Acids;flexibility;FOXP3 gene;Functional disorder;gastrointestinal;glucose metabolism;glucose-regulated proteins;Glycogen (Starch) Synthase;glycogen synthase kinase 3 beta;Goals;gut inflammation;Health;Homeostasis;Human;IL2RA gene;Immune;Impairment;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory milieu;inhibitor;innovation;inorganic phosphate;Inositol;interleukin-21;Intestines;Investigation;Knowledge;Lamina Propria;Lead;Light;Link;Mediating;Metabolic;Metabolic Control;Metabolism;Mitochondria;Molecular;Molecular Target;mouse model;murine colitis;Nature;novel;oxidation;Oxidative Phosphorylation;Pathogenesis;Pathogenicity;Patients;Peripheral;peripheral blood;pharmacologic;Phenotype;Pyruvate;receptor;recruit;Refractory;Regulation;Regulatory T-Lymphocyte;Research;Role;Self Tolerance;Shapes;Signal Transduction;Structure;T cell therapy;T-Cell Development;T-Lymphocyte;Testing;TGFB1 gene;Therapeutic;time use;tissue repair;transcription factor;treatment response;treatment strategy;Voltage-Dependent Anion Channel

PROJECT_TITLE: Gastrointestinal Cues Influence Metabolic Control of Regulatory T cell Function

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Physical Activity;Prevention

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Physical activity has numerous health benefits. Physical activity behaviors develop from very early childhood. This proposed project aims to develop an analytic tool to recognize the activity types of toddlers, such as walking/running, standing, sitting, and being carried by an adult. The analytic tool developed will be useful to accurately evaluate physical activity levels among toddlers.

PI_NAMEs: KWON, SOYANG  (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: 2 year old;3 year old;5 year old;Accelerometer;Address;Adolescence;Adult;Affect;Age;Age Months;aged;Algorithms;analytical tool;Behavior;boys;Chicago;Child;Child Care;Child Rearing;Childhood;Classification;Clinic;computerized data processing;Dancing;Data;Data Set;Development;Developmental Process;early childhood;Ensure;Epidemiology;Ethnic Origin;Female;girls;Goals;Growth;Guidelines;Habits;Health;Health Benefit;Hip region structure;Home;interest;Investigation;Knowledge;Learning;Light;Machine Learning;machine learning algorithm;male;Measurement;Mediation;Methodology;Minority;Modeling;Motor;Motor Skills;National Heart, Lung, and Blood Institute;Nursery Schools;Parents;Participant;Performance;Physical activity;physical inactivity;Pilot Projects;Population;Posture;Premature Birth;Process;Public Health;Race;Recommendation;recruit;Reporting;Research Activity;response;Running;Sampling;School-Age Population;sedentary;sex;Sex Differences;social influence;Source Code;Sum;Surveys;Testing;Time;Toddler;tool;Training;training data;United States;Walking

PROJECT_TITLE: Physical Activity Measurement in Toddlers

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


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

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Alzheimer Disease (AD) brains show severe defects in the vascular system, causing ischemia, a condition known to induce reparative angiogenesis, and neuronal dysfunction. There is also evidence that reparative angiogenesis is impaired in AD brains. We discovered that a mouse model expressing Presenilin1 Familial AD (FAD) mutant shows decreased ischemia-induced angiogenesis and angiogenic protein complexes and increased neuronal death in the brain. Furthermore, endothelial cells (ECs) of these mutant brains have decreased response to angiogenic factor EphB4. Successful completion of this project will identify novel molecular mechanisms of toxicity-induced brain angiogenesis and will test whether these mechanisms are impaired in AD. In addition, the project will test whether a novel pro-angiogenic peptide that rescues angiogenic functions of FAD ECs, promotes brain neovascularization and increases neuronal survival against toxic insults.

PI_NAMEs: GEORGAKOPOULOS, ANASTASIOS  (contact);ROBAKIS, NIKOLAOS K

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Adult;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;angiogenesis;Angiogenic Factor;Angiogenic Peptides;Angiogenic Proteins;Area;Atrophic;Attenuated;Blood capillaries;Blood flow;Blood Vessels;Brain;brain endothelial cell;Brain Ischemia;C-terminal;cadherin 5;Cell Separation;cerebral microvasculature;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Chronic;Complex;Data;Defect;density;Development;Diameter;Endoglin;Endothelial Cells;Endothelium;ENG gene;EphB4 Receptor;Ephrin B Receptor;familial Alzheimer disease;Functional disorder;gamma secretase;Generations;genome-wide;Growth;Human;human disease;Impaired cognition;Impairment;In Vitro;in vivo;Injury;Intervention;Ischemia;ischemic injury;ischemic lesion;Lesion;Life;Ligands;Link;Mediating;Metabolic;Molecular;mouse model;Mus;mutant;neovascularization;Nerve Degeneration;neuroimaging;neuron loss;Neuronal Dysfunction;neuronal survival;Neurons;neuropathology;neuroprotection;neurovascular;novel;Pathogenesis;Pathologic;Pathway interactions;Peptides;Pharmacologic Substance;Play;presenilin;Production;protein complex;protein expression;Proteins;Proteolytic Processing;raf-1 Protein;receptor;repaired;Reporting;response;restoration;Role;Signal Transduction;System;Testing;tissue repair;Tissues;Toxic effect;vascular abnormality;Vascular Diseases;Vascular System

PROJECT_TITLE: Impairment of Ischemia-induced Vascular Functions by PS1 FAD Mutants

STUDY_SECTION: CMND

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Genetics;Human Genome;Liver Disease

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Insulin resistance causes metabolic diseases such as type 2 diabetes, heart attacks, strokes and liver failure. Using genomic data from people treated for insulin resistance, this project aims to identify new human insulin resistance genes and prove through nature’s own clinical trials that they would make good targets for therapeutic development.

PI_NAMEs: MAJITHIA, AMIT  (contact)

PROGRAM_OFFICER_NAME: ZAGHLOUL, NORANN

PROJECT_TERMS: adipocyte differentiation;Adipocytes;Adipose tissue;Alleles;Biological Assay;Biological Models;Candidate Disease Gene;Cardiovascular Diseases;case control;Cell Physiology;Cellular Assay;Chronic Disease;Clinical;clinical efficacy;clinical phenotype;Clinical Research;Clinical Trials;Code;combat;Complement;Conduct Clinical Trials;Credentialing;Data;Data Set;Development;Disease;disorder risk;Dissection;DNA;Dose;drug development;Epidemic;Exhibits;exome sequencing;experimental study;Failure;Fatty Liver;fatty liver disease;gene discovery;Gene Expression;Gene Expression Profiling;gene function;gene synthesis;General Population;Genes;Genetic;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome sequencing;genome-wide;Genomic approach;genomic data;Genotype;high risk;Human;improved;In Vitro;in vivo;Individual;Insulin;Insulin Resistance;insulin sensitivity;Investigation;Laboratories;Life;Lipids;Lipodystrophy;Liver Failure;loss of function;Malignant Neoplasms;man;Measurement;Measures;Metabolic Diseases;Mining;Modernization;Mutagenesis;Myocardial Infarction;Nature;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Participant;Persons;Pharmaceutical Preparations;Phenotype;Physiological;Population;PPARG gene;prevent;Process;prospective;Proteins;PTEN gene;Reading;resistance gene;response;Role;Series;Severity of illness;side effect;Sorting;Source;Stroke;targeted treatment;Testing;theories;Therapeutic;therapeutic candidate;therapeutic development;Therapeutic Effect;therapeutic gene;therapeutic target;Thiazolidinediones;Tissue Sample;transcription factor;transcriptome;transcriptomic profiling;treatment response;Variant;Work;Writing

PROJECT_TITLE: Combining experiments of man and nature to target human insulin resistance

STUDY_SECTION: GHD

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


ORG_CITY: DENVER

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

PHR: Project Narrative In the course of development, epithelial tissues must be able to dynamically remodel their dimensions to generate adult tissue morphologies, as well as permit new cells to replace aging cells. The intention of the proposed study is to examine the processes that permit directed cell movements within an epithelial context. We are using a combination of computational and cell biological approaches to determine how membrane ratcheting mechanisms permit the processive contraction of individual cellular surfaces.

PI_NAMEs: BLANKENSHIP, JAMES TODD (contact);LOERKE, DINAH

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actomyosin;Adopted;Adult;Apical;Area;Behavior;Binding;Biochemical;Biological;Biological Assay;Cell Aging;cell cortex;Cell membrane;cell motility;Cell Physiology;Cell Shape;Cell surface;Cells;constriction;Contracts;Coupled;course development;Cues;Cytoskeleton;Data;Data Analyses;Development;Dimensions;Drosophila genome;Drosophila genus;Embryo;Epithelial Cells;Epithelium;FRAP1 gene;Frequencies;gastrulation;Generations;Goals;Image;in vivo;Individual;insight;Intention;Intercalated Cell;interfacial;Lipids;Mass Spectrum Analysis;Measurement;Measures;Membrane;Mesoderm;Mitochondria;Morphogenesis;Morphology;mTOR protein;Nature;novel;Pathway interactions;Pattern;Periodicals;Periodicity;PH Domain;Phase;phosphatidylinositol 3,4,5-triphosphate;Phosphatidylinositol Phosphates;Phosphatidylinositols;Phosphotransferases;Physiologic pulse;PIK3CG gene;Population;Process;protein function;Proteins;Proteomics;Proto-Oncogene Proteins c-akt;recruit;Reporting;Signal Pathway;Signal Transduction;Surface;System;Testing;Tissues;Tubular formation;Work;wound healing

PROJECT_TITLE: Control of cell ratcheting engagement during epithelial morphogenesis

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Hematology

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative/Relevance: Atherosclerosis is a progressive inflammatory cardiovascular disease that remains the leading cause of death in the USA and worldwide in spite of widespread use of statins, other lipid lowering strategies, and life-style modifications. Remarkably, despite decades of research, little is known about late stage lesion development and mechanisms that result in the rupture or erosion of the protective fibrous cap overlying advanced atherosclerotic lesions leading to catastrophic thrombotic events including a heart attack (i.e. myocardial infarction) or stroke. Studies in this proposal will define the cell types and mechanisms that form the fibrous cap with the goal of identifying novel therapeutic approaches for promoting formation of a thicker and mechanically more robust fibrous cap (i.e. analogous to a patch on a tire) thereby reducing the probability of lesion rupture or erosion with a possible heart attack or stroke.

PI_NAMEs: OWENS, GARY K (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Aging;Antibodies;Aorta;Apolipoprotein E;Apoptosis;Arterial Fatty Streak;Arteries;Atherosclerosis;atherothrombosis;Biological Assay;biological sex;Bone Marrow Transplantation;Cardiovascular Diseases;Carotid Endarterectomy;Cause of Death;Cd68;Cell Aging;Cell Lineage;Cell Proliferation;cell type;Cells;Clinical;Clinical Research;Clonal Expansion;conditional knockout;Coronary artery;Coronary heart disease;Deoxyuridine;Dependence;Development;Diet;DNA biosynthesis;Endothelial Cells;endothelial dysfunction;Event;Excision;Exhibits;Extracellular Matrix;Failure;feeding;Female;Functional disorder;Genetic Markers;Goals;Growth;high risk;Human;IL1R1 gene;Impairment;improved;in vivo;Incidence;indexing;Individual;Inflammation;Inflammatory;insight;Intervention;Investments;irradiation;Knock-out;Knockout Mice;Label;Lesion;Lesion by Stage;Life Style Modification;Lipids;Macrophage;Maintenance;male;Mechanics;Medicine;men;Mesenchymal;Metabolism;Modeling;Morphology;Mus;Myocardial Infarction;Myofibroblast;Nature;novel;novel therapeutic intervention;Oligonucleotides;Paper;Pathogenesis;PDGFRB gene;PECAM1 gene;Permeability;Pharmaceutical Preparations;Phenotype;Platelet-Derived Growth Factor beta Receptor;Play;Predisposition;prevent;Probability;Process;Proliferating;Property;Relaxation;Research;Resistance;Role;Rupture;Sampling;senescence;senescent cell;senolytics;sex;Signal Transduction;single-cell RNA sequencing;Smooth Muscle Myocytes;Stroke;Testing;Thick;Thinness;Thrombosis;thrombotic;Time;United States;validation studies;western diet;Woman;women versus men

PROJECT_TITLE: Endothelial Cell to Mesenchymal Cell Transitions Play a Critical Biological Sex- and Aging-Dependent Role in Formation and Maintenance of the Acta2+ Atherosclerotic Lesion Protective Fibrous Cap

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Estrogen;Precision Medicine;Women's Health Research

PHR: PROJECT NARRATIVE Triple negative breast cancer (TNBC) is an aggressive form of the disease with few treatment options, high recurrence rates and disproportionately higher mortality rates. This proposal involves elucidating the mechanisms by which estrogen receptor beta (ERβ) elicits potent anti-cancer effects in TNBC and determining the utility of specifically targeting this receptor, alone and in combination with established chemotherapy regimens, for therapeutic purposes. Results of the proposed study are expected to contribute to the development of a new class of therapies, and allow for better stratification of patients to specific forms of chemotherapy, ultimately resulting in improved outcomes for thousands of patients each year.

PI_NAMEs: HAWSE, JOHN R. (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Address;Adjuvant;Adjuvant Chemotherapy;Affect;Agonist;anti-cancer;Antibodies;Architecture;Biological;Biological Markers;Biological Models;Biology;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;cancer diagnosis;Cancer Etiology;cancer type;Cell Line;Cessation of life;Characteristics;Chemoresistance;chemotherapy;Chemotherapy-Oncologic Procedure;Chromatin;Clinical;Clinical Management;clinically significant;combat;Complex;Data;Death Rate;Development;Disease;Disease Management;DNA Binding;effective therapy;efficacy evaluation;Enhancers;Epidermal Growth Factor Receptor;Epigenetic Process;ERBB2 gene;ESR1 gene;Estradiol;Estradiol Receptors;Estrogen Receptor 2;EZH2 gene;FDA approved;Foundations;Gene Expression Profile;genetic corepressor;Genetically Engineered Mouse;genome-wide;genomic locus;Goals;Histones;improved;improved outcome;In Vitro;in vitro Model;in vivo;Individual;innovation;Invaded;Knowledge;Ligands;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;migration;Modeling;Modification;Molecular;molecular subtypes;Morbidity - disease rate;mortality;Nature;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Newly Diagnosed;NF-kappa B;novel;novel strategies;Oncogenic;Organoids;participant enrollment;Pathway interactions;patient derived xenograft model;patient stratification;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase II Clinical Trials;phase II trial;Phenotype;predicting response;prevent;Primary Neoplasm;Progesterone Receptors;Prognosis;Prognostic Marker;Proliferating;prospective;Proteins;receptor;Recurrence;Recurrent disease;Refractory;Resistance;response;Retrospective cohort;Role;Signal Pathway;Signal Transduction;Specimen;standard of care;targeted agent;targeted treatment;Testing;Therapeutic;therapy outcome;tool;Treatment Protocols;treatment response;treatment strategy;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor progression;Tumor Promotion;United States;Validation;Woman;Women's mortality;women's outcomes

PROJECT_TITLE: ERβ repurposes EZH2 to suppress oncogenic NFκB signaling in TNBC

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]