ORG_CITY: Newark

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Adaptation of gene transcription is earliest fundamental response of heart to compensate for increasing stress during work overload, before it goes into irreversible state of cardiac failure. In this study, we examine the underlying mechanisms that regulate basic transcriptional machinery for expression of essential and inducible genes under hypertrophic stress conditions. The project will enhance our understanding of transcription in heart, open new avenues of basic and translational research, identify factors that control gene expression and contribute to pathophysiology of cardiac hypertrophy and failure

PI_NAMEs: SAYED, DANISH  (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Acceleration;Activities of Daily Living;Acute;Basic Science;Binding;Cardiac;Cardiac Myocytes;Chromatin;chromatin immunoprecipitation;chromatin remodeling;Compensation;Complex;Congestive Heart Failure;Data;Death Rate;Development;Disease;Dissociation;Down-Regulation;early onset;Equilibrium;Essential Genes;Failure;Fibrosis;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;genome-wide;Goals;Heart;Heart failure;Heart Hypertrophy;Hypertrophy;improved;in vitro Assay;insight;knock-down;Knockout Mice;Manuscripts;Mass Spectrum Analysis;Mechanics;Mediating;Metabolic Clearance Rate;Modeling;Molecular Conformation;Molecular Weight;Morbidity - disease rate;mortality;mRNA Precursor;Mus;mutant;Myocardial dysfunction;Names;negative elongation factor;novel;Nuclear;Output;Pathogenesis;Pathologic;Phenotype;Phosphorylation;Play;Polymerase;Positive Transcriptional Elongation Factor B;pressure;Productivity;promoter;Proteins;recruit;Regulation;Research;research and development;response;Role;Running;Single-Stranded DNA;Stress;Testing;Therapeutic;therapeutic development;Transcript;transcriptome;transcriptome sequencing;Translational Research;Untranslated RNA;Ventricular Dysfunction;Work

PROJECT_TITLE: Role of Negative Elongation Factor Complex in RNA polymerase II pausing and gene transcription in Heart

STUDY_SECTION: CCHF

STUDY_SECTION_NAME: Cardiac Contractility, Hypertrophy, and Failure Study Section[CCHF]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: GENETICS

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative: This proposal seeks funding for a PhD training program in the biomedical sciences that enables students from underrepresented backgrounds to excel in research, hone their academic and professional development skills, explore biotech shadowing experiences, and engage in educational outreach activities in the community. These activities will prepare our trainees to excel in graduate school and to transition successfully into top positions in the biotech, academic, science policy and other STEM- related career sectors. As teams with diverse perspectives outperform those with more limited perspective, our program, which seeks to diversify the scientific workforce, is essential to continue the tradition of scientific excellence in the United States.

PI_NAMEs: HERMANSTYNE, TRACEY O;SKEATH, JAMES BENJAMIN (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TITLE: MAXIMIZING STUDENT DIVERSITY IN THE BIOMEDICAL SCIENCES AT WASHINGTON UNIVERSITY

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - D[TWD-D]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: NARRATIVE Metastasis is the major cause of cancer-related death, but the metabolic adaptations that enable a cancer cels originated from one organ to grow in a distal organ remain unclear. Here, we propose to develop new mathematical models to infer the metabolic fluxes rewired in metastasis, knowledge that may open new strategies to prevent and treat metastatic cancer.

PI_NAMEs: XAVIER, JOAO  (contact)

PROGRAM_OFFICER_NAME: MILLER, DAVID J

PROJECT_TERMS: 3-Dimensional;Affect;Automobile Driving;Biological Assay;Biopsy;bone;Brain;Breast;Breast Cancer Cell;Breast Cancer Model;cancer cell;Cancer Etiology;Cancer Science;cell growth;Cell Line;Cell Lineage;Cells;Cessation of life;Clinical;Coculture Techniques;Consumption;Data;Differential Equation;Diffusion;Disseminated Malignant Neoplasm;Distal;Drops;Equation;Evolution;experimental study;Game Theory;Genetic Transcription;Glucose;Glutamine;Heterogeneity;Home;Homing;Hypoxia;Image Analysis;In Vitro;in vivo;Individual;Knowledge;Label;Link;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;mathematical analysis;mathematical model;Measurement;Measures;Metabolic;metabolic abnormality assessment;Metabolism;metabolome;metabolomics;Metastatic breast cancer;Metastatic malignant neoplasm to brain;Microscopy;mimetics;Modeling;Motility;mouse model;Neoplasm Metastasis;novel;Nutrient;Organ;Oxygen;Pancreas;particle;Pathway interactions;Patients;Population;Population Heterogeneity;predictive modeling;prevent;Prevention;Primary Neoplasm;Production;Publishing;Pyruvate;Reaction;Research;Retinal blind spot;RNA analysis;Role;Sampling;Series;simulation;Site;Soil;solute;Spatial Distribution;Structure;System;Testing;three-dimensional modeling;Time;Tissues;Transcriptional Regulation;transcriptional reprogramming;transcriptomics;Tropism;tumor;tumor heterogeneity;tumor metabolism;Validation;Waste Products

PROJECT_TITLE: Mathematical modeling of metabolism rewiring in cancer eco-evolution and metastasis tropism

STUDY_SECTION: MABS

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: NORFOLK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: EASTERN VIRGINIA MEDICAL SCHOOL

ORG_STATE: VA

PHR: Public Health Relevance Statement This proposal incorporates innovative, multi-disciplinary approaches to investigate mechanisms governing the regulation of cardiac contraction in health and disease. The ultimate goal is to markedly advance fundamental knowledge of striated muscle regulation and inform the rational design of tailored therapeutic interventions that could potentially improve cardiac muscle function in diseased hearts. Therefore, this proposal has substantial health relevance and is directly in line with the mission of the National Institutes of Health.

PI_NAMEs: CHASE, P. BRYANT;GALKIN, VITOLD  (contact);PINTO, JOSE RENATO

PROJECT_TERMS: 3-Dimensional;Actins;Affect;Algorithms;Bepridil;Binding;Binding Sites;Cardiac;Cardiac Muscle Contraction;Cardiomyopathies;Cardiovascular Diseases;Communication;Complex;Computing Methodologies;Cryoelectron Microscopy;Data;Development;Dilated Cardiomyopathy;Disease;disease-causing mutation;Distal;Distant;Electron Microscopy;Equilibrium;Filament;Genetic;genetic regulatory protein;Goals;Health;Heart Diseases;Hypertrophic Cardiomyopathy;improved;Incubated;individualized medicine;inherited cardiomyopathy;innovation;interdisciplinary approach;Knowledge;Lobe;Mission;Modeling;Molecular;Molecular Conformation;multidisciplinary;Muscle function;muscle physiology;mutant;Mutation;Myocardium;Myosin ATPase;outcome prediction;Pathogenesis;Pathogenicity;Phenotype;Phosphorylation;Physiological;public health relevance;rational design;reconstruction;Regulation;Research;Side;Site;Striated Muscles;Structure;Surface;Tail;Testing;Therapeutic Intervention;Thick;Thin Filament;Thinness;Time;tool;Tropomyosin;Troponin;Troponin C;Troponin I;Troponin T;United States National Institutes of Health;Variant

PROJECT_TITLE: The mechanisms of cardiac thin filament regulation in health and disease.

STUDY_SECTION: MPPA

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Radiation Oncology

ORG_CITY: HANOVER

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE We propose to build an innovative, first-in-clinic, easy-to-use, oxygen scanner for repeated monitoring of tumor oxygen levels in cancer patients. The scanner will be built using the advanced in vivo electron paramagnetic resonance (EPR) technology developed at Dartmouth College and in partnership with ViewRay®, a pioneer in the development of MRI image-guided linear accelerator for radiation therapy. The new oxygen scanner can provide potentially important and previously unavailable information on tumor oxygen status, which is important for accurate prognosis and development of effective treatment strategies for cancer therapy.

PI_NAMEs: KUPPUSAMY, PERIANNAN  (contact)

PROGRAM_OFFICER_NAME: RIZWAN, ASIF M

PROJECT_TERMS: achievement test;Address;Animal Model;Automation;cancer care;Cancer Patient;cancer therapy;Clinic;Clinical;clinical care;Clinical Protocols;Clinical Research;clinical research site;cohort;college;commercialization;Computer software;Coupling;Custom;Data;data acquisition;Data Analyses;Data Collection;Data Reporting;Decision Making;design;design and construction;Development;Devices;diabetic;Diagnostic;digital;Documentation;effective therapy;efficacy evaluation;Electron Spin Resonance Spectroscopy;Engineering;ergonomics;Evaluation;flexibility;Generations;Good Manufacturing Process;Guidelines;healthy volunteer;heart motion;Human;human subject;image guided;image guided radiation therapy;improved;in vivo;industry partner;innovation;innovative technologies;instrumentation;light weight;Linear Accelerator Radiotherapy Systems;Magnetic Resonance Imaging;Malignant Neoplasms;manufacture;Marketing;Measurement;Measures;Medical Device;medical schools;Medical Technology;Monitor;Morphologic artifacts;Motivation;Movement;National Cancer Institute;novel;Oncology;operation;Oxygen;Oxygen saturation measurement;Patients;Performance;Peripheral Vascular Diseases;phantom model;Physiologic pulse;Prognosis;Program Research Project Grants;prototype;Radiation Oncology;Radiation therapy;Research;Resource-limited setting;Resources;respiratory;response;Role;Safety;safety and feasibility;Site;Speed;success;System;Technology;Testing;Therapeutic;therapy outcome;Time;tissue phantom;Tissues;tool;Translating;Treatment outcome;treatment strategy;tumor;Underserved Population;usability;user-friendly;Work

PROJECT_TITLE: EPR scanner for tumor oximetry in the clinic


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics;Health Effects of Indoor Air Pollution

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: NARRATIVE This project will explore a new mechanism by which a type of chemical toxicant related to the environment and occupations alters chromatin structure and gene expression, leading to human diseases such as cancer.

PI_NAMEs: JIN, CHUNYUAN  (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Acetylation;adduct;Affect;Biological Assay;Bone Marrow;building materials;cancer type;carcinogenesis;carcinogenicity;Cell Physiology;Cells;chemical carcinogen;chemical carcinogenesis;Chemicals;ChIP-seq;Chromatin;chromatin immunoprecipitation;Chromatin Modeling;Chromatin Structure;Chromosomal Instability;Cytoplasm;Data;Defect;Deposition;DNA Adducts;DNA Damage;DNA Repair;DNA-protein crosslink;Environment;Epigenetic Process;exposed human population;Formaldehyde;Fractionation;Gene Abnormality;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;Genome Stability;Genomic Instability;genomic locus;Histone H3;Histone H4;histone modification;Histones;Household Products;human disease;Impairment;In Vitro;in vivo;inducible gene expression;Industrialization;innovation;knock-down;Link;live cell imaging;Location;Lysine;Malignant neoplasm of nasopharynx;Malignant Neoplasms;Maps;Modification;Molecular;Molecular Chaperones;Monitor;Mutagenesis;Mutate;Myeloid Leukemia;novel;Nuclear Import;Occupational;Occupations;overexpression;Peptides;Post-Translational Protein Processing;Process;Proteins;Proteomics;Rattus;Reaction;Refractory;Research;Role;Schiff Bases;Site;Structure of mucous membrane of nose;Structure of parenchyma of lung;System;Testing;Tissues;Toxic effect;toxicant;trafficking;Variant;Western Blotting

PROJECT_TITLE: Chromatin assembly and formaldehyde toxicity

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Breast Cancer;Cancer;Dementia;Estrogen;Neurodegenerative;Neurosciences;Prevention;Sleep Research;Women's Health Research

ORG_CITY: HADLEY

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: NARRATIVE Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report severe side effects, including hot flashes, cognitive impairment, insomnia and mood changes. Despite long-term use in humans, little is known about the long-term effects of AIs on brain function. This proposal uses a primate model to understand how AIs affect the brain and behavior and to test whether a drug that delivers estrogens exclusively to the brain can safely alleviate these deficits.

PI_NAMEs: LACREUSE, AGNES  (contact);MERCHENTHALER, ISTVAN JOZSEF;PROKAI, LASZLO

PROGRAM_OFFICER_NAME: GREEN, PAIGE A

PROJECT_TERMS: abeta deposition;Acceleration;Accelerometer;Adjuvant Therapy;Adverse effects;Affect;age acceleration;Age-associated memory impairment;aging brain;Alzheimer's Disease;Alzheimer's disease risk;Animal Model;Architecture;Area;Aromatase;Aromatase Inhibition;Aromatase Inhibitors;Behavior;Behavior assessment;Behavioral;behavioral outcome;Brain;Brain region;brain tissue;Breast Cancer Patient;Breast Cancer Prevention;Callithrix;Callithrix jacchus jacchus;cancer recurrence;Chronic;Cognition;cognitive ability;Cognitive deficits;cognitive function;cognitive performance;computerized;depressive symptoms;design;Development;Electrophysiology (science);emotion regulation;Emotional;enzyme activity;Estradiol;Estrogens;experience;face skin;Female;frontal lobe;Gene Expression;Gene Expression Profiling;Genes;genome-wide;Goals;Heart Rate;heart rate variability;Hippocampus;Hormonal;Hot flushes;Human;Hydrocortisone;Hypothalamic structure;Image;Impaired cognition;Impairment;improved;in vivo;Individual Differences;inhibitor therapy;interest;Knowledge;Letrozole;locus ceruleus structure;Long-Term Effects;Longitudinal Studies;male;Malignant Breast Neoplasm;Measures;middle age;Modeling;Monkeys;Moods;neural;neuronal excitability;neuropathology;nonhuman primate;novel;novel therapeutics;Patients;Pattern;Persons;Pharmaceutical Preparations;Phenotype;Physiologic Thermoregulation;Physiological;Placebos;Polysomnography;Prefrontal Cortex;prevent;Primates;Prodrugs;Quality of life;Recommendation;Recording of previous events;Recurrence;Reporting;response;Severity of illness;side effect;Skin Temperature;Sleep;sleep pattern;Sleeplessness;Source;Stress;Symptoms;Tauopathies;Testing;Testosterone;translational applications;treatment group

PROJECT_TITLE: Impact of brain estrogens on cognition and brain aging in a non-human primate


NIH_SPENDING_CATS: Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Heart Disease - Coronary Heart Disease;Mental Health;Women's Health Research

ORG_CITY: ATLANTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative This grant proposal aims to investigate sympathetic activation with mental stress in women with chest pain who have coronary microvascular dysfunction. Cardiac sympathetic imaging, autonomic and vascular reactivity assessment, as well as home monitoring for autonomic function and daily life stress are proposed. The application incorporates a multi-disciplinary team of experts and innovative methods to study a clinical problem that disproportionately impacts women.

PI_NAMEs: MEHTA, PUJA KIRAN (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Acute;Address;Adrenergic beta-Antagonists;adverse outcome;Age;American;Anxiety;Applications Grants;Autonomic Dysfunction;Autonomic nervous system;Blood Vessels;Cardiac;cardiovascular risk factor;Cardiovascular system;Cellular Phone;Chest Pain;Chronic;Chronic stress;Circulation;Clinical;Clinical Trials;comorbidity;comparison group;Control Groups;Coronary;Coronary Angiography;Coronary Arteriosclerosis;Data;Data Collection;Diagnosis;disability;Disproportionately impacts women;Emotions;Event;follow-up;Frequencies;Functional disorder;Future;Goals;Health Care Costs;health related quality of life;Heart failure;heart rate variability;high risk;Home;Hospitalization;Image;Impairment;improved;innovation;Intervention;Ischemia;Knowledge;Laboratories;Life;Life Stress;Link;Measures;Mediating;men;Mental Depression;metaiodobenzylguanidine;Methods;Microvascular Dysfunction;Monitor;mortality;multidisciplinary;Myocardial;Myocardial Infarction;Myocardial Ischemia;Nervous System Physiology;Nonpharmacologic Therapy;novel therapeutics;Pathway interactions;Patients;Peripheral;Population;Positron-Emission Tomography;Postmenopause;Prognostic Marker;Psyche structure;Psychological Factors;Psychological Stress;psychosocial;Quality of life;Recording of previous events;Recurrence;reduce symptoms;response;Rest;Risk;Role;Severities;Signs and Symptoms;Standardization;Stenosis;Stress;stress reactivity;Stress Tests;stressor;sudden cardiac death;Symptom Burden;Symptoms;Testing;Therapeutic;Time;Uncertainty;vasoconstriction;wearable sensor technology;Woman;Women's prevalence;Work

PROJECT_TITLE: Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Many chemicals that cause dopaminergic neurodegeneration and Parkinson’s disease also cause mitochondrial dysfunction. However, hundreds or thousands of chemicals in commerce cause mitochondrial dysfunction, by a plethora of different mechanisms. Therefore, to inform efforts to reduce exposures relevant to Parkinson’s Disease, we will identify which specific kinds of mitochondrial toxicity cause dopaminergic neurodegeneration.

PI_NAMEs: MEYER, JOEL NEWMAN (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: adverse outcome;Affect;Age;aging related;alpha synuclein;Caenorhabditis elegans;cell type;Cells;Chemical Actions;Chemical Exposure;Chemicals;cholinergic neuron;Citric Acid Cycle;Clinical Research;Commerce;Complement;Complex;Consumption;cost;Data;Development;disorder risk;DNA Damage;dopaminergic neuron;Electrons;Environment;Environmental Pollutants;Environmental Risk Factor;Enzyme Inhibition;Enzymes;epidemiology study;Etiology;Event;experimental study;Exposure to;Genetic;Guidelines;high throughput screening;Idiopathic Parkinson Disease;in vivo;Incidence;Individual;insight;Laboratory Study;life span;Measurement;Measures;Mediating;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;model organism;Modeling;Molecular;Multienzyme Complexes;Nature;Nerve Degeneration;neurotoxicity;novel;Outcome;Oxidation-Reduction;Oxidative Stress;Oxygen Consumption;Parkinson Disease;Pathway interactions;Persons;Pharmaceutical Preparations;pollutant;Pollution;Population;Preventive;Production;Publishing;Reactive Oxygen Species;reduce symptoms;Reporter Genes;Research;Role;Stress;Testing;Therapeutic;Time;timeline;tool;Toxic effect;Toxicology;Transgenic Organisms;Treatment Cost;Work

PROJECT_TITLE: Which mechanisms of pollutant-induced mitochondrial dysfunction cause dopaminergic neurodegeneration?

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Aging;Cystic Fibrosis;Infectious Diseases;Lung;Rare Diseases

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Cystic fibrosis (CF) and its comorbidities have a major impact on human health and socioeconomic burden, making the proposed research relevant to public health. CF-associated lung disease is associated with airway inflammation and mucociliary dysfunction. We will study Fibroblast Growth Factor receptor inhibition as a potential novel anti-inflammatory therapy option, which is relevant to the NHLBI’s mission to promote the prevention and treatment of lung diseases and enhance the health of individuals so that they can live longer and more fulfilling lives.

PI_NAMEs: KRICK, STEFANIE  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Abate;Acceleration;Address;Adult;Aging;aging biomarker;Air;airway inflammation;airway obstruction;Animal Model;anti aging;Anti-Inflammatory Agents;Atherosclerosis;Attenuated;Bacterial Infections;bronchial epithelium;Caring;Cell Culture Techniques;Cell Physiology;Chronic;comorbidity;Cystic Fibrosis;cystic fibrosis airway;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;cytokine;Data;Disease;Economic Burden;Endocrine;Epithelial Cells;Exhibits;experience;FGFR1 gene;Fibroblast Growth Factor;Fibroblast Growth Factor Receptors;Functional disorder;functional improvement;Genes;Genotype;Health;health economics;Human;Impairment;improved;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammation;Inflammatory;inhibitor;Innate Immune Response;interdisciplinary approach;interest;Laboratories;Life;Life Expectancy;Ligands;Link;Liquid substance;liver inflammation;Lung;Lung Diseases;lung injury;Mission;Modeling;Morbidity - disease rate;mortality;muco-obstructive airway diseases;Mucociliary Clearance;mucoid;mucus clearance;mucus-associated lung diseases;Multiple Bacterial Drug Resistance;Mutation;National Heart, Lung, and Blood Institute;novel;novel therapeutic intervention;Obstruction;Organ;overexpression;pathogen;Population;Predisposition;Prevention;Protein Isoforms;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Public Health;Publishing;Pulmonary Cystic Fibrosis;Pulmonary Fibrosis;pulmonary function;pulmonary function decline;Pulmonary Inflammation;Quality of life;Rattus;receptor;receptor expression;Receptor Inhibition;Receptor Signaling;Recurrence;recurrent infection;Research;Respiratory Tract Infections;Risk;Role;Sepsis;Serum;Severities;Signal Pathway;Signal Transduction;socioeconomics;Structure;Structure of parenchyma of lung;Supplementation;Testing;Therapeutic Intervention;therapeutic target;Transforming Growth Factor beta;Transforming Growth Factors

PROJECT_TITLE: Targeting fibroblast growth factor receptors in cystic fibrosis-associated airway inflammation and mucociliary dysfunction

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Gene Therapy;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE The adoptive transfer of T cells engineered to express synthetic receptors that target cancer cells for elimination has emerged as an effective modality with curative potential in some types of cancer. Limitations of current adoptive cell therapies include the ability of tumor cells to escape elimination because they express low levels of, or lack, the antigen being targeted. This project will address these problems by developing two new classes of synthetic tumor targeting receptors that have exquisite sensitivity for antigen and can recognize constellations of antigens expressed on tumor cells, making treatment more effective for achieving durable remissions.

PI_NAMEs: RIDDELL, STANLEY R. (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Address;Adoptive Cell Transfers;alpha-beta T-Cell Receptor;Antibodies;Antigen Targeting;Antigens;B lymphoid malignancy;Binding;cancer cell;cancer therapy;cancer type;CD19 gene;CD22 gene;CD28 gene;CD3 Antigens;CD8-Positive T-Lymphocytes;Cell Differentiation process;Cell Physiology;Cell Separation;Cell surface;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic Lymphocytic Leukemia;Clinic;Clinical Data;clinically relevant;Collaborations;curative treatments;cytokine;Data;density;design;Development;Disease remission;engineered T cells;exhaustion;FDA approved;Foundations;Functional disorder;Funding;gamma secretase;Gene Transfer;genomic locus;Grant;Hematopoietic Neoplasms;Heterogeneity;Hybrids;Immunoglobulin Constant Region;improved;in vitro Assay;in vivo;in vivo Model;Infiltration;inhibitor;Knock-in;Knock-out;large cell Diffuse non-Hodgkin's lymphoma;lentivirally transduced;Ligands;Light;Link;Logic;Major Histocompatibility Complex;Malignant Neoplasms;Modality;MS4A1 gene;Multiple Myeloma;neoplastic cell;next generation;Normal Cell;novel;Outcome;Patients;Peptides;Population;pre-clinical;Pre-Clinical Model;Predisposition;prevent;Progress Reports;Property;Proteins;receptor;Receptor Signaling;Refractory;Relapse;ROR1 gene;Sensitivity and Specificity;Signal Pathway;Signal Transduction;Solid Neoplasm;Specific qualifier value;Specificity;Surface;synaptogenesis;T cell infiltration;T cell therapy;T-Cell Immunologic Specificity;T-Cell Receptor;T-Lymphocyte;targeted treatment;Toxic effect;TRA@ gene cluster;TRB@ gene cluster;tumor;Tumor Antigens;Tumor Escape;tumor heterogeneity;tumor microenvironment;Universities;Washington;Work

PROJECT_TITLE: Novel synthetic receptors with improved antigen specificity and specificity for cancer therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Liver Cancer;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE The current systemic therapies for liver cancer, including sorafenib and the combination of atezolizumab (anti- PD-L1) and bevacizumab (anti-VEGF), have limited therapeutic benefits with no predictive biomarkers available. Our preliminary studies uncovered roles for a targetable LIFR−NF-κB−LCN2 pathway in regulating liver tumorigenesis, sorafenib-induced ferroptotic cell death, and tumor infiltration by cytotoxic T cells. The goal of this project is to provide new insights into the mechanisms of therapeutic targeting of an iron-sequestering pathway, which has significant clinical implications in regard to the biomarkers and therapeutic targets for liver cancer.

PI_NAMEs: MA, LI  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: anti-PD-1;anti-PD-L1;BAY 54-9085;bevacizumab;Biological Markers;Breeding;cancer cell;Cancer Etiology;cancer therapy;CD8-Positive T-Lymphocytes;Cell Death;cell growth regulation;Cell Survival;cell type;Clinical;clinical development;Combined Modality Therapy;Cystine;cytokine;Cytotoxic T-Lymphocytes;Data;derepression;Development;Down-Regulation;Drug Metabolic Detoxication;Electrons;Future;Genes;Genetic study;Genetically Engineered Mouse;Glutathione;glutathione peroxidase;Goals;Hepatocarcinogenesis;Hepatocyte;Homeostasis;Human;Hydroxyl Radical;immune cell infiltrate;immune checkpoint;Immune checkpoint inhibitor;Immunotherapy;improved;in vivo;Infiltration;insight;Iron;iron deficiency;Knock-out;Knockout Mice;LCN2 gene;leukemia inhibitory factor receptor;Link;Lipid Peroxides;Liver;liver cancer model;Liver neoplasms;Malignant neoplasm of liver;Mediating;Molecular;mortality;neoplastic cell;neutralizing antibody;novel drug combination;NR0B2 gene;Oncogenes;Organ;overexpression;Pathologic;Pathway interactions;patient derived xenograft model;patient subsets;Patients;PD-1/PD-L1;Pharmaceutical Preparations;Physiological Processes;predicting response;Prediction of Response to Therapy;predictive marker;Primary carcinoma of the liver cells;Process;Production;Proliferating;Proteins;Reaction;receptor binding;receptor expression;receptor function;Receptor Inhibition;Repression;Resistance;Role;role model;Signal Transduction;Sleeping Beauty;Systemic Therapy;T cell infiltration;T-Cell Proliferation;T-Lymphocyte;targeted cancer therapy;Therapeutic;Therapeutic Studies;therapeutic target;timeline;Toxic effect;TRAF6 gene;treatment response;tumor;tumor progression;Tumor Suppressor Proteins;Ubiquitination;Unresectable;Up-Regulation;Work

PROJECT_TITLE: Targeting the LIFR-LCN2 pathway to improve liver cancer therapy

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


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Epidemiological studies clearly show that advanced age is the most important risk factor for cardiovascular disease, but we have an incomplete understanding of how aging promotes cardiovascular disease progression. The accumulation of somatic DNA mutations over time has recently been demonstrated to be a hallmark of aging in many human cell types. The overarching goal of this proposal is to define the extent of somatic mutations in aging human cardiomyocytes, provide an understanding of the mutational processes acting on aging human cardiomyocytes, and explore the link between somatic mutational burden and cardiovascular pathologies, for developing new strategies to treat millions of adults with heart disease associated with aging.

PI_NAMEs: CHOUDHURY, SANGITA  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Adopted;Adult;Age;age related;Aging;aging mechanism;aging population;Algorithms;Alleles;Autopsy;base;Brain;cancer radiation therapy;Cardiac;cardiac aging;Cardiac Myocytes;Cardiomyopathies;Cardiovascular Diseases;Cardiovascular Pathology;cardiovascular risk factor;Cell Nucleus;Cell Respiration;cell type;Cells;Copy Number Polymorphism;Cytoprotection;Data;Development;Disease;Disease Progression;disorder risk;DNA;DNA Damage;DNA Sequence Alteration;DNA sequencing;Dropout;Elderly;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;epidemiology study;Freezing;Genetic;Genome;genome analysis;genome sequencing;genome-wide;Genomic DNA;Genomics;genotoxicity;Goals;hallmarks of aging;Heart;heart disease prevention;Heart Diseases;Heart failure;Human;human old age (65+);In Vitro;Inherited;innovation;insight;Interphase Cell;Knowledge;Link;Malignant Neoplasms;Measures;Methods;Modeling;Mutagens;Mutation;Myocardial dysfunction;Myocardium;Neurons;Newborn Infant;normal aging;novel;Older Population;Organ;Oxidative Stress;Oxidative Stress Induction;Pathologic;Patients;Pattern;Phenotype;Ploidies;Point Mutation;postmitotic;Premature aging syndrome;pro-aging;Process;Radiation;radiation during childhood;radiation effect;Radiation therapy;Research;Resolution;Risk Factors;Role;Sampling;Series;Single Nucleotide Polymorphism;Somatic Mutation;Techniques;Testing;Time;Troponin T;Variant;whole genome

PROJECT_TITLE: Single cell, whole genome analysis of the aging human cardiomyocyte

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Heart Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative In mammals, the right and left heart size and function dramatically change before/after birth, but how this process is determine remain a mystery. This proposal will study a newly discovered pathway first time implicated in this process, using sophisticated genomic and molecular tools. The outcome will fill an important gap in our current knowledge and shed light to potential causes of heart diseases.

PI_NAMEs: YOKOTA, TOMOHIRO  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: Adolescent;Adult;Affect;Apoptosis;Area;Biology;Birth;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiomyopathies;cardioprotection;cell type;Cells;Cellular Stress;congenital heart abnormality;Data;Development;endoplasmic reticulum stress;fetal;Fetal Development;Fetal Heart;Foundations;Functional disorder;Future;Genetic Transcription;Genomics;Growth;Heart;heart dimension/size;Heart Diseases;heart function;hemodynamics;Hypertrophy;In Vitro;in vivo Model;Inflammatory;Injury;interdisciplinary approach;Knowledge;Left;Light;Mammals;MAP Kinase Gene;Measures;Mediating;Mitogen-Activated Protein Kinases;Molecular;mouse model;Mus;Muscle Cells;Neonatal;neonatal mice;Neonatal Mortality;Newborn Infant;novel;Outcome;Outcome Study;p38 MAPK Signaling Pathway;p38 Mitogen Activated Protein Kinase;Pathogenicity;Pathway interactions;Pattern;Perinatal;Peripheral;pharmacologic;Physiological;Physiology;postnatal;postnatal development;Process;Proliferating;Proteome;Pulmonary Circulation;Regenerative Medicine;Regulation;Reporting;Research Personnel;Role;Signal Transduction;Specificity;stem cell biology;Stress;Stress Response Signaling;Time;Tissues;tool;Transgenic Mice;Weight;XBP1 gene

PROJECT_TITLE: Novel Signaling Mechanism in Chamber-Specific Postnatal Heart Growth


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Prevention

PHR: PROJECT NARRATIVE Ventricular arrhythmias and sudden cardiac arrest are a major cause of mortality and morbidity, carrying great economical and societal impact. Our research applies primarily to arrhythmias originating in the cardiac intercalated disc and subject to the interplay between PKP2, Cx43 and intracellular calcium. We use modern physiology, proteomics and microscopy methods to investigate the mechanisms underlying the onset of disease at the molecular level and to design novel venues for therapy.

PI_NAMEs: DELMAR, MARIO  (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Adherens Junction;Adult;Area;Arrhythmia;Atlases;Calcium;cancer therapy;Cardiac;Cell membrane;Cell Physiology;Cells;Cellular Structures;Chemical Agents;Complex;Connexin 43;design;Desmosomes;Device or Instrument Development;Diagnosis;Disease Progression;Electrons;Electrophysiology (science);Elements;Gap Junctions;genomic data;Genomics;Geometry;Grant;Heart;Heart Arrest;heart rhythm;Intercalated disc;Interdigitating Dendritic Cell;Knowledge;Life;Maps;Medical;Membrane;Methods;Microscopy;Mitochondria;Modernization;Molecular;Morbidity - disease rate;mortality;Muscle Cells;Mutate;novel;Onset of illness;Organelles;phenotypic data;Physiology;plakophilin 2;Prevention;protein complex;Proteomics;Regulation;Research;Risk Assessment;Role;Site;Structure;Ventricular;Ventricular Arrhythmia;Visual;Work

PROJECT_TITLE: Molecular Atlas of the Cardiac Intercalated Disc


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Heart Disease;Patient Safety;Precision Medicine;Prevention

ORG_CITY: GAINESVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative Swallowing impairment (dysphagia) is a common complication of cardiac surgical procedures leading to malnutrition and dehydration, aspiration pneumonia, need for reintubation, increased length of hospital stay, increased cost of care, and death. This study seeks to determine contributing risk factors, accurate bedside clinical markers, and underlying pathophysiology of dysphagia in cardiac surgical patients to support a four- pronged care framework, the Model of Swallowing Integrated Care (MOSAIC). The MOSAIC framework includes prediction, prevention, detection, and treatment considerations to provide an evidence-based guide to enhance clinical decision making, promote efficient resource utilization, and ultimately improve outcomes in cardiac surgical patients.

PI_NAMEs: JENG, ERIC  (contact);PLOWMAN, EMILY KATE

PROGRAM_OFFICER_NAME: KEHL, KAREN

PROJECT_TERMS: Acute;Adoption;Adult;American;Aspiration Pneumonia;Assessment tool;Blinded;Cardiac;cardiac intensive care unit;Cardiac Surgery procedures;Cardiovascular Diseases;care costs;Caring;Cause of Death;Cessation of life;Chronic;Clinical;clinical care;clinical decision-making;Clinical Markers;Complication;computer program;Coughing;Data;Deglutition;Deglutition Disorders;Dehydration;design;Detection;Development;Early Diagnosis;Eating;Echocardiography;Economic Burden;effective intervention;Electronics;endotracheal;Enrollment;Esophagus;Evaluation;evidence base;Fiber Optics;Functional disorder;Future;Generations;Goals;Guidelines;Health;health care model;health care service utilization;Healthcare;Heart;high risk;Hospitalization;Hour;Image;Impairment;improved;improved outcome;indexing;Individual;instrument;Intake;integrated care;Intensive Care;Intervention;Intubation;kinematics;Knowledge;Larynx;Length;Length of Stay;Logistic Regressions;Malnutrition;Modeling;modifiable risk;Monitor;Morbidity - disease rate;mortality;Motor;New York;novel;Operative Surgical Procedures;Oral;Outcome;participant enrollment;Pathway interactions;patient population;Patient Triage;Patient-Focused Outcomes;Patients;Perioperative;personalized care;personalized health care;Pharyngeal structure;Phase;Physiological;Pneumonia;Population;Postoperative Care;Postoperative Period;Practice Guidelines;prediction algorithm;predictive marker;predictive tools;pressure;Prevention;Prevention strategy;Recovery;Recovery of Function;Resources;response;Risk;Risk Factors;risk prediction;risk stratification;Safety;Screening procedure;Sensitivity and Specificity;Sensory;Services;targeted treatment;Testing;Therapeutic;Time;tool;Triage;Tube;Vestibule;Voice

PROJECT_TITLE: Mechanisms, Predictors and Clinical Markers of Dysphagia in Cardiac Surgical Patients

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Anxiety Disorders;Autoimmune Disease;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Diabetes;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Pediatric;Prevention;Telehealth

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE Anxiety symptoms occur in adolescents with T1D at 2 to 3 times the rate of the general adolescent population and are associated with out-of-range glycemic control, including severe hypoglycemia and diabetic ketoacidosis, poor quality of life, and poor self-management. There are few evidence-based interventions adapted and implemented to assist with alleviating anxiety for this high-risk population. Development of an adapted MBSR mHealth application prototype will provide accessible, cost-conscious, scalable access to a safe intervention, thus reducing cost and increasing access for this high-risk population.

PI_NAMEs: RECHENBERG, KAITLYN  (contact)

PROGRAM_OFFICER_NAME: AKUBU-ODERO, MAUREEN KALAMBU

PROJECT_TERMS: 18 year old;19 year old;acceptability and feasibility;Acute;Address;Adolescent;Adult;Affect;Anxiety;anxiety management;anxiety reduction;anxiety symptoms;associated symptom;behavior test;Behavior Therapy;brief intervention;Cardiovascular system;career;Cellular Phone;Child;Childhood;Chronic;Clinical;Clinical Investigator;clinical practice;clinically significant;Complications of Diabetes Mellitus;Conscious;Consumption;Continuous Glucose Monitor;cost;data integration;design;Development;Diabetes Mellitus;Diabetic Ketoacidosis;Disease;Disease Management;Disease Outcome;effective intervention;Endocrinologist;Endocrinology;evidence base;Evidence based intervention;Evidence based treatment;experience;feasibility testing;Funding;Future;glycemic control;Goals;Health;High Prevalence;high risk population;Hour;Hypoglycemia;improved;Incidence;innovation;Insulin-Dependent Diabetes Mellitus;International;Intervention;Interview;K-Series Research Career Programs;Kidney;Knowledge;Knowledge acquisition;Learning;Life Style;Mental Depression;Mental Health;Mentors;Methods;mHealth;mhealth interventions;mindfulness intervention;mindfulness-based stress reduction;Mobile Health Application;Nature;Neuropathy;Nurse Practitioners;Nurses;Outcome;Peer Review;Perception;Physiological;Population;prevent;Process;programs;prototype;Psychologist;psychosocial;psychosocial development;Publications;Quality of life;Randomized, Controlled Trials;Research;Risk;Risk Reduction;Science;Self Management;skills;Sleeplessness;Social Workers;sustainability framework;Symptoms;Testing;therapy development;Time;Training;Treatment Protocols;United States;Work

PROJECT_TITLE: Mindfulness-Based Stress Reduction in Adolescents with Type 1 Diabetes

STUDY_SECTION: NRRC

STUDY_SECTION_NAME: Nursing Science Review Committee[NRRC(81)]


ADMINISTERING_IC: DC

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative Electrical synapses, mediated by neuronal gap junctions, are widespread throughout the auditory pathway. However, the functional roles and properties of electrical synapses in the auditory system remain poorly understood. Changes in the strength of electrical synapses are known to dynamically reconfigure neuronal circuits in various neural structures but in contrast to chemical synapses, little is known about the molecular mechanisms that underlie changes in the strength of electrical synapses. The proposed research will lead to the identification of novel molecular mechanisms involved in the regulation of electrical synapses that could fundamentally change the way we understand the organization of circuits associated with auditory dysfunction, thus contributing to the identification of novel therapeutic targets.

PI_NAMEs: PEREDA, ALBERTO E (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Adherens Junction;Anatomy;Auditory;auditory pathway;auditory processing;Auditory system;Belief;Biological;Cells;Chemical Synapse;Chemicals;Chemosensitization;Communication;Complex;Connexins;electrical property;Electrical Synapse;Electrophysiology (science);Excision;Exposure to;Family;Fishes;gap junction channel;Gap Junctions;genetic manipulation;Glutamate Receptor;Goals;Hearing problem;Heterozygote;Image;in vivo imaging;Individual;Investigation;Knowledge;Mediating;Microscopy;Modeling;Modification;Molecular;Mutation;neural;neuronal circuitry;Neurons;new therapeutic target;novel;Perception;postsynaptic;Property;Proteins;recruit;Regulation;Research;Role;scaffold;Scaffolding Protein;Shapes;Signal Transduction;Spatial Distribution;Structural Protein;Structure;Synapses;synaptic function;Synaptic plasticity;Synaptic Transmission;Transgenic Organisms;transmission process;Zebrafish

PROJECT_TITLE: Plasticity of auditory electrical synapses

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Lung Cancer;Mental Health;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Tobacco;Tobacco Smoke and Health;Violence Research

ORG_CITY: Chicago

ORG_DEPT: ADMINISTRATION

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE This application proposes to 1) examine mechanisms of neighborhood social, economic, and environmental risks for lung cancer incidence and stage at diagnosis, 2) to identify the relationship between neighborhood risks and PRMT6-mediated epigenetic changes, and 3) to explore the relationship between neighborhood risk and hair cortisol levels among high-risk individuals. Although the link between neighborhood context and lung cancer outcomes has been documented, little is known about specific mechanisms through which neighborhood context affects biological and behavioral risks for lung cancer outcomes. This study examines neighborhood contextual factors that may contribute to understanding epigenetic changes and lung cancer risk.

PI_NAMEs: KIM, SAGE J. (contact);WINN, ROBERT A.

PROGRAM_OFFICER_NAME: JONES, NANCY LYNNE

PROJECT_TERMS: Affect;African American;African American population;Area;Arginine;Behavioral;biobank;Biological;Biophysics;black men;Black Populations;Cancer Etiology;cancer health disparity;cancer risk;Censuses;Cessation of life;Characteristics;Chicago;ChIP-seq;Chronic;Chronic stress;cigarette smoking;Cities;Clinical Trials;Code;Communities;community violence;Computerized Medical Record;contextual factors;Cotinine;Crime;Data;Data Collection;Data Set;Death Rate;Disadvantaged;Disparity;Distress;Economics;Environment;Environmental Risk Factor;Epigenetic Process;Epithelium;Exposure to;Frequencies;Gene Expression;Hair;high risk;high risk population;Hydrocortisone;Immunohistochemistry;improved;in silico;Incidence;Individual;Inflammatory Response;innovation;Link;Low Prevalence;Lung;lung cancer screening;Lung Neoplasms;Malignant neoplasm of lung;Measures;Mediating;men;Methylation;minority communities;Molecular;Morbidity - disease rate;mortality;Mus;Neighborhoods;novel;Outcome;overexpression;Patients;Physiological;Population;prospective;protein expression;Protein Overexpression;Proteins;racial disparity;racial health disparity;racial minority;Research;Risk;Risk Factors;Sampling;screening;screening guidelines;segregation;Smoking;Smoking History;social;Social Conditions;social stress;social stressor;sociodemographics;socioenvironmental factor;Source;Stage at Diagnosis;Stress;Surveys;systemic inflammatory response;Testing;The Cancer Genome Atlas;Time;Tissue Sample;transcriptome sequencing;Transferase;United States;Violence;violence exposure;violent crime

PROJECT_TITLE: Reducing racial disparities in lung cancer outcomes by decoding neighborhood contextual environment (RECODE)

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Narrative Congenital heart defects (CHDs) associated with the conduction of electrical impulses can be devastating health problems. Understanding how dysfunctions arise in the early, embryonic heart is important for discovering ways to prevent or treat these CHDs. This project will develop imaging tools to capture impulse conduction in the living, beating heart of the early avian embryo in 3D, and map the molecular response of the cells of the heart, under normal and abnormal conditions.

PI_NAMEs: ROLLINS, ANDREW MARTIN (contact)

PROJECT_TERMS: 3-Dimensional;Address;Birds;Calcium;calcium indicator;Cardiac;Cardiac conduction system;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;cardiogenesis;Collaborations;Compensation;Complex;Confocal Microscopy;Congenital Abnormality;Congenital Heart Defects;Coupled;Data;Detection;Development;developmental cardiology;Dyes;Electrophysiology (science);Embryo;Embryonic Heart;Etiology;Fetal Alcohol Exposure;fluorescence imaging;Fluorescent Dyes;Fluorescent in Situ Hybridization;Functional disorder;Gene Expression;Genes;Goals;Health;Heart;heart cell;heart motion;hemodynamics;Image;image registration;Imaging Device;in vivo;Incubated;Lead;Lighting;Longitudinal Studies;Maps;Membrane;Modeling;Molecular;Morphogenesis;Motion;Multimodal Imaging;new technology;Optics;Pathology;Pattern;Pharmaceutical Preparations;Physiological;Physiology;prevent;Productivity;Property;protein expression;Quail;Qualifying;ratiometric;Reaction;reconstruction;Reporter;response;Role;Scanning;serial imaging;Signal Transduction;Structure;success;System;Techniques;Technology;technology development;Therapeutic;Time;Tissues;tool;Transfection;Transgenic Organisms;Tubular formation;two photon microscopy;Viral;voltage

PROJECT_TITLE: 5 D impulse mapping in the embryonic heart

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Caregiving Research;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Palliative Care;Precision Medicine;Social Determinants of Health

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Millions of Americans could benefit from palliative care to address the physical, psychological, and social effects of severe and chronic illness. Artificial intelligence (AI) - computer-based algorithms that can carry out tasks typically reserved for humans – has the potential to give patients and families more detailed and more accurate information about prognosis than ever before, but whether or how to use this information ethically in support of patient- and family-centered care is unknown. To ensure AI supports high quality end-of-life and palliative care that is consistent with patients’ and families’ beliefs, values, and preferences, this project will identify the benefits and challenges of AI for palliative care and then develop practical guidance for its use.

PI_NAMEs: DECAMP, MATTHEW WAYNE (contact)

PROJECT_TERMS: Address;Advanced Malignant Neoplasm;Affect;Age;algorithmic bias;Algorithms;American;Area;Artificial Intelligence;Attitude;Awareness;Belief;Bioethics;Black Box;care providers;Caregivers;Caring;Cessation of life;Chronic Disease;Clinical;Communication;Communities;Computers;Consensus;COVID-19 pandemic;Data;Data Set;Decision Making;Dementia;Depersonalization;Disease;distrust;Electronic Health Record;Eligibility Determination;end of life;Ensure;Ethics;experience;Family;Family Caregiver;Fright;Future;Gender;General Population;Goals;Health;Health Care Costs;health care quality;health equity;health inequalities;Health Services;Healthcare;Heart failure;high risk;hospice environment;Human;improved;Individual;individualized medicine;innovation;insight;Interdisciplinary Study;Intervention;Interview;Investments;Judgment;Knowledge;Lead;Learning;learning algorithm;Life Expectancy;literacy;Malignant Neoplasms;marginalized population;Mediating;Medical;Medical Research;Medicine;member;Methods;Mission;mortality;mortality risk;Nature;neglect;Nurses;Palliative Care;patient engagement;patient prognosis;Patients;Physicians;Play;Population;preference;Probability;Process;Prognosis;prognostic;prognostic tool;prognostication;psychologic;Psychologist;Race;racial bias;Recommendation;Research;research to practice;Resource Allocation;Risk;Robot;Role;Sampling;Services;Site;social;Social Workers;sociocultural determinant;Socioeconomic Status;Source;Spiritual care;statistics;Structure;Surveys;Technology;tool;Translating;treatment planning;United States;Validation;virtual;willingness

PROJECT_TITLE: A mixed-methods study of the nature, extent and consequences of artificial intelligence (AI) for individualized treatment planning in end-of-life and palliative care (EOLPC)


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Public Health Relevance / Project Narrative Across the United States, adverse events involving law enforcement officers (LEOs) and male minority youth (MMY) and the toxic stress associated with repeated negative LEO-MMY encounters raise compelling public health concerns about racial discrimination in policing. The proposed research addresses these concerns by (a) introducing a novel human development paradigm for the study of police behavior that focuses on how and to what extent LEOs identify with MMY and (b) assessing the technological viability of using broadcast police communications (BPC) for large scale analysis of police behavior, where BPC are analyzed as pre-reflective accounts of LEO thought processes, representing both reactive and stable coping mechanisms (i.e., speech acts) for ensuring the safety of LEOs and the public at large. Accordingly, we propose (1) using this novel data source to understand how LEOs and MMYs come to perceive each other, (2) test a similarly novel survey instrument for measuring LEO identification with minority youth, in the process determining how much meaningful information can be reliably extracted from audio recordings of BPC for identifying racial discrimination in policing without the need to access highly sensitive police records or video recording data.

PI_NAMEs: GRAZIUL, CHRISTOPHER ;SPENCER, MARGARET BEALE (contact)

PROGRAM_OFFICER_NAME: GILLMAN, ARIELLE SAMANTHA

PROJECT_TERMS: acronyms;Address;Adopted;Adverse event;Affective;Archives;automated speech recognition;Behavior;Behavior assessment;Belief;Chicago;combat;Communication;Communities;Complex;coping mechanism;Coping Skills;Country;course development;Data;data quality;Data Sources;Development;Dimensions;Ecosystem;effective intervention;Ensure;Evaluation;Event;experience;Exposure to;Expressed Sequence Tags;Focus Groups;Frequencies;Genetic Transcription;Goals;Health;Hour;Human;Human Development;human subject;improved;Individual;insight;instrument;Intervention;Interview;Language;Law Enforcement;Law Enforcement Officers;lens;Life Cycle Stages;Link;Machine Learning;Measures;member;Methodology;Minority;minority children;Minority Men;Modeling;Motivation;Natural Language Processing;Neighborhoods;novel;Outcome;Perception;Personal Satisfaction;perspective taking;phenomenological models;Police;Predisposition;prevent;Process;psychosocial;Public Health;public health relevance;Race;racial discrimination;racial disparity;Records;Research;Research Activity;Research Personnel;response;Rest;Risk;Safety;Scientist;social;Source;Speech;Stress;Stressful Event;Surveys;Systems Theory;Technology;Technology Assessment;Testing;Time;Training;Trauma;Trust;United States;Variant;Video Recording;Work;Youth

PROJECT_TITLE: Primed to (re)act: Can changes in procedural language prevent adverse events between police and minority male youth?

STUDY_SECTION: CLHP

STUDY_SECTION_NAME: Community-Level Health Promotion Study Section[CLHP]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Pediatric;Rare Diseases

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB

PHR: NARRATIVE Birth defects of the heart are common, life-threatening conditions that are often caused by changes in a patient’s DNA. It is now possible to determine the complete sequence of a patient’s genome, but it remains difficult to identify those disease-causing changes that do not affect genes and instead disrupt sequences that control gene activity during embryonic development of the heart. We propose a research program that will use cutting-edge genomics techniques to identify and examine these changes, generating insights to support the diagnosis and treatment of birth defects of the heart.

PI_NAMEs: PENNACCHIO, LEN ALEXANDER;VISEL, AXEL  (contact)

PROJECT_TERMS: Affect;Alleles;Biological Assay;Cardiac;Cardiac Myocytes;cardiogenesis;cell type;Cells;Cessation of life;Child;Code;cohort;Collection;Congenital Abnormality;congenital heart abnormality;CRISPR/Cas technology;Data;de novo mutation;Diagnosis;Disease;Distant;DNA;Embryo;Embryonic Development;Engineering;Enhancers;epigenomics;Etiology;exome sequencing;falls;fetal;Fetal Heart;follow-up;functional genomics;Future;Gene Expression;gene function;Gene Transfer Techniques;Genes;Genetic;Genetic Enhancer Element;genetic testing;genetic variant;Genome;Genome engineering;genome resource;genome sequencing;genomic locus;Genomics;Heart;heart defect;heart disease risk;Heart Diseases;heart function;Histologic;Human;Human Genetics;human induced pluripotent stem cells;human model;in vivo;induced pluripotent stem cell;insight;Knock-in Mouse;Letters;Life;Link;Maps;Medical Genetics;Methods;Molecular;mouse model;Mus;Mutation;National Heart, Lung, and Blood Institute;next generation;novel;Parents;Pathogenicity;Patient Care;Patients;Phenotype;Physiological;Population;proband;programs;Proteins;Reporter;Research;Resolution;Risk;Risk Assessment;risk variant;Role;single-cell RNA sequencing;Site;Structure;Techniques;Testing;Therapeutic;Tissues;tool;Trans-Omics for Precision Medicine;transcriptomics;Transgenic Mice;Untranslated RNA;Validation;Variant;whole genome;Work

PROJECT_TITLE: In vivo Characterization of Regulatory Variant Pathogenicity in Congenital Heart Disease

STUDY_SECTION: GHD

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Maternal Health;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE A more comprehensive understanding of the underlying mechanisms associated with elevated maternal distress and caregiving deficits is necessary for early detection, care management, and effective treatment options during the immediate postpartum period. This study will explore a risk phenotype for maternal distress by analyzing neurological changes in reward responsivity, caregiving behaviors, and the maternal experience of goal pursuit and perceived daily functioning in postpartum mothers. Outcomes of this project will support future work on the bidirectional nature of the maternal-child relationship as it relates to Regulatory Focus Theory, and lead to improvements in postpartum care and intervention development.

PI_NAMEs: BERNHARDT, ELISABETH  (contact)

PROGRAM_OFFICER_NAME: YOON, SUNG SUG

PROJECT_TERMS: Activities of Daily Living;Address;Anhedonia;anxiety symptoms;associated symptom;Behavior;Behavioral;Brain;Caregivers;caregiving;Child;Child Health;Child Rearing;Childbirth;Clinical assessments;Code;Cognitive;daily functioning;Data;debilitating symptom;depressive symptoms;Developmental Disabilities;digital;Disease remission;Distress;Early Diagnosis;effective therapy;Emotional;Equipment and supply inventories;Estrogens;experience;financial incentive;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;Future;Goals;Health Professional;Hormonal;Hormones;Image;Impairment;improved;Incidence;Infant;Infant Development;Informal Social Control;innovation;Interview;Left;Link;Managed Care;maternal caregiving;Measures;Methods;Modeling;Moods;Morbidity - disease rate;Mother-Child Relations;motherhood;Mothers;Nature;neural;neural correlate;Neural Pathways;neural stimulation;Neurologic;Neurons;novel strategies;Nurses;Nursing Research;Outcome;Participant;Pathway interactions;Patient Self-Report;Pattern;Phase;Phenotype;Play;postpartum care;Postpartum Period;Prefrontal Cortex;Pregnant Women;prevent;Prevention;Prevention strategy;Process;Progesterone;programs;prospective;Research;Research Training;response;Rewards;Risk;Role;secondary analysis;Self Management;Severities;Sleep;stressor;symptom management;symptom science;Symptoms;System;theories;therapy development;Time;Variant;Ventral Striatum;Withdrawal;Woman;Work

PROJECT_TITLE: Exploring a Risk Phenotype for Maternal Distress Characterized by Regulatory Focus


NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Primary Health Care;Rural Health;Social Determinants of Health

ORG_CITY: KANSAS CITY

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative Certain populations are disproportionately affected by obesity, such as families in rural areas, and treatment options for these rural children and families are limited as they face unique barriers. The current study will assess the effectiveness of iAmHealthy Parents First (a 4-month parent-only intervention followed by a 6-month family- based program) compared to iAmHealthy alone (a parent wait-list control followed by the family based program). If effective, this intervention model could easily be disseminated to improve the lives of rural children and parents who need weight management treatment.

PI_NAMEs: BEFORT, CHRISTIE ;DAVIS, ANN M (contact)

PROGRAM_OFFICER_NAME: LONG, SYLVIA ELISABETH

PROJECT_TERMS: acceptability and feasibility;Address;Adult;Affect;Age;Area;arm;behavior change;Behavior Therapy;Behavioral;Behavioral Model;Body mass index;Body Weight Changes;Body Weight decreased;Cardiovascular Diseases;Child;Child Behavior;Childhood;Clinic;Code;Commuting;Data;Daughter;design;Development;Diabetes Mellitus;Diet;Dietary intake;dissemination strategy;Effectiveness;effectiveness evaluation;effectiveness study;elementary school;evidence base;Evidence based intervention;experience;Face;Family;Food;food environment;Fostering;fruits and vegetables;Future;Genetic;group intervention;Habits;Health and Behavior in Children;Health behavior;health care settings;Home;Home environment;Hour;implementation strategy;improved;Inherited;innovation;interest;Intervention;Interview;Leadership;lifestyle intervention;low socioeconomic status;Malignant Neoplasms;Mediator;Medical;Mentored Clinical Scientist Development Program;mHealth;Modeling;moderate-to-vigorous physical activity;Monitor;Morbidity - disease rate;mortality;Nurses;Nursing Assessment;Obesity;obesity in children;obesity treatment;Outcome;Parents;Participant;Physical activity;Play;Population;post intervention;Primary Care;programs;Quality of life;Randomized;randomized trial;recruit;remote technology;Reporting;Research;retention rate;Risk Factors;Running;Rural;rural Americans;rural area;Rural Community;rural dwellers;rural families;rural health clinic;rural healthcare;Rural Population;Schedule;Schools;secondary outcome;Side;Site;Structure;Subgroup;sugar;sweetened beverage;Testing;theories;therapy design;Time;Travel;treatment effect;treatment program;tv watching;Waiting Lists;Weight;weight loss intervention;Weight maintenance regimen;Work

PROJECT_TITLE: iAmHealthy Parents First

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


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

ORG_CITY: CAMBRIDGE

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

PHR: OTHER PROJECT INFORMATION – Project Narrative The proposed research seeks to determine how stroke center certifications have changed access, volume, care, and health outcomes over time across NIH disparity populations and communities. It is relevant to public health because it will provide local, state, and federal bodies with the empirical findings they need to create systems-level solutions to the delivery of stroke care that can both improve overall population health and narrow disparities among various segments of the population. The project directly addresses NIMHD’s mission because it seeks to “explain the causes, determinants, and influences of health and life course trajectories that result in health disparities,” by studying disparities at multiple levels: at individual-, facility- and community- levels and exploring consequences of system-level changes in the healthcare system for racial/ethnic, lower socioeconomic, and rural health disparity populations.

PI_NAMEs: HSIA, RENEE YUEN-JAN;SHEN, YU-CHU  (contact)

PROGRAM_OFFICER_NAME: PADGETT, LYNNE SLAUGHTER

PROJECT_TERMS: access disparities;Acute;acute care;acute stroke;Address;Admission activity;Adopted;Adoption;aging population;aging related disease;Alternative Therapies;Area;Black race;Caring;Censuses;Certification;Cessation of life;Communities;Community Outreach;community-centered;Data;Databases;design;Dimensions;disability;Disadvantaged;Discrimination;Disparate;Disparity;Disparity population;disparity reduction;endovascular thrombectomy;ethnic minority;Ethnic Origin;ethnic segregation;experience;Face;functional outcomes;Geography;Goals;Guidelines;Health;health disparity;health disparity populations;Health Services Accessibility;Healthcare Systems;Hispanic;Home;hospital readmission;Hospitals;improved;Income;Individual;Inequality;Intervention;Intravenous;Left;Life Cycle Stages;Long term disability;Low income;Marketing;Measures;Medicare;Medicare claim;Mission;Modeling;Morbidity - disease rate;mortality;multilevel analysis;National Institute on Minority Health and Health Disparities;neighborhood disadvantage;Outcome;Pathway interactions;Patients;Pattern;Population;population health;Probability;Public Health;Race;racial disparity;racial minority;Racial Segregation;racism;Research;Resources;Role;rural area;rural health disparities;rural patients;Rural Population;segregation;Services;social health determinants;socioeconomics;Stroke;stroke patient;stroke therapy;Structural Racism;Structure;Survival Analysis;System;Technology;telehealth;telestroke;Testing;Thrombectomy;Thrombolytic Therapy;Time;treatment disparity;United States;United States National Institutes of Health;urban area

PROJECT_TITLE: Structural Racism and Discrimination in the Expansion of Hospital Stroke Care Capacity: A Multi-Level Analysis on Access to Care, Treatment, and Outcomes


NIH_SPENDING_CATS: Asthma;Lung;Prevention

PHR: Many asthmatics do not have adequate control over air flow due to airway obstruction, and treatment options are limited to one class of bronchodilator drugs which all work the same way. The proposal seeks to determine the structure of a different class of bronchodilator drug acting at bitter taste receptors on airway smooth muscle, and then find drugs with favorable pharmacologic characteristics to activate these receptors. This will lead to increased treatment options for asthma that could decrease patient morbidity and mortality.

PI_NAMEs: LIGGETT, STEPHEN B (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Affect;Affinity;Age;Agonist;Air Movements;airway obstruction;Arrestins;Asthma;asthmatic;attenuation;Back;beta-arrestin;Binding;Binding Sites;Biochemical;Biology;Bronchial Spasm;Bronchodilation;Bronchodilator Agents;Cell model;cell type;Cells;Characteristics;Clinical;Collection;Complex;constriction;Coupling;Cytometry;Data;desensitization;Disease;disorder control;Docking;Dose;drug action;Engineering;Ethnic Origin;experience;experimental study;Functional disorder;G-Protein-Coupled Receptors;Genetic Engineering;GTP-Binding Proteins;Human;in silico;interest;Intervention;Learning;Libraries;Ligand Binding;Ligands;Lung;Magnetism;Methods;Modality;Modeling;models and simulation;Molecular Conformation;molecular modeling;Morbidity - disease rate;mortality;novel;Obstruction;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;pharmacophore;Phenotype;Physiological;Physiology;predictive modeling;prevent;Prevention;Process;Property;Public Health;receptor;recruit;Relaxation;Resistance;respiratory smooth muscle;response;Signal Transduction;simulation;Slice;Smooth Muscle Myocytes;Structure;System;Tachyphylaxis;Taste Buds;Techniques;Therapeutic;three dimensional structure;Time;Transfection;Translations;treatment optimization;virtual;virtual screening;Work

PROJECT_TITLE: Characterization of biased airway smooth muscle TAS2R agonists for treating asthma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-H(03)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Pediatric Cancer;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Rehabilitation;Social Determinants of Health

ORG_CITY: IRVINE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Roughly 70,000 adolescents and young adults (AYAs; between the ages of 15-39) are diagnosed with cancer every year, an incidence that is nearly 8 times greater than in childhood cancers. Preliminary research indicates that young cancer survivors suffer from considerable challenges due to their life stage. The goal of this study is to develop a population-based cohort (n=2,000) of young adult survivors (ages 21-39; ~42% Hispanic) of the most common types of cancers in this age group who are 3-10 years post-diagnosis. We will examine their health status, including comorbidities and late effects of their cancer treatments, achievement of adult milestones, and use of health care services. Findings will provide physicians and other health care providers with evidence to guide policies concerning young adult cancer survivorship care.

PI_NAMEs: FREYER, DAVID R;MILAM, JOEL E (contact)

PROGRAM_OFFICER_NAME: DAEE, DANIELLE L

PROJECT_TERMS: Acculturation;Achievement;Address;Adherence;Adolescent;Adolescent and Young Adult;Adolescent and young adult cancer patients;Adult;Affect;Aftercare;Age;age group;Attention;California;cancer diagnosis;Cancer Patient;Cancer Survivor;Cancer Survivorship;cancer survivorship care;cancer therapy;cancer type;Caring;Child;Childhood;childhood cancer survivor;clinical trial enrollment;cohort;comorbidity;comparative;County;Development;Diagnosis;Disparity;Education;emotional distress;Employment;ethnic difference;ethnic disparity;Ethnic Origin;experience;Face;fertility preservation;Financial Hardship;financial toxicity;follow-up;Gender;Geographic Locations;Goals;Guidelines;Health;health care service utilization;health difference;health inequalities;Health Personnel;health related quality of life;Health Status;Hispanic;Hispanic Populations;Home;improved;Incidence;Inferior;Insurance;Insurance Coverage;Interview;Late Effects;Life;Life Cycle Stages;Link;Longterm Follow-up;Los Angeles;Malignant Childhood Neoplasm;Malignant Neoplasms;Marriage;Medical;Morbidity - disease rate;National Cancer Institute;neoplasm registry;Newly Diagnosed;Not Hispanic or Latino;Outcome;Outcome Study;Participant;Patient Self-Report;Patients;Personal Satisfaction;Physicians;Policies;Population;population based;Population Heterogeneity;Population Study;programs;protective factors;psychosocial;Quality of life;racial disparity;recruit;Reduce health disparities;Regression Analysis;Reporting;Research;Risk;Risk Assessment;Risk Factors;Sample Size;Sampling;Services;social;Social isolation;Surveillance Program;Surveys;Survivors;survivorship;Treatment-related toxicity;United States;Vocation;Vulnerable Populations;young adult;young cancer survivor

PROJECT_TITLE: Project Milestones: Young Adult Cancer Survivorship

STUDY_SECTION: CMPC

STUDY_SECTION_NAME: Clinical Management of Patients in Community-based Settings Study Section[CMPC]


NIH_SPENDING_CATS: Genetics;Lung;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW HAVEN

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE This proposal aims to understand how cell types in the injured mammalian lung are generated, how they behave and the molecular pathways that control them to coordinate alveolar repair. Our findings will inform lung biology and help identify novel targets for human lung disease

PI_NAMEs: CHIOCCIOLI, MAURIZIO  (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Affect;AGTR2 gene;Alveolar;alveolar epithelium;Behavior;Biology;cell behavior;cell type;Cells;cellular targeting;Chromatin;Clinical;Code;combinatorial;Data;Data Set;Distal;Epithelial Cells;Epithelium;Exhibits;Gene Expression;gene regulatory network;Heterogeneity;Human;human disease;Image;imaging system;in vivo;in vivo evaluation;in vivo regeneration;Individual;injured;Injury;Label;Lung;Lung Diseases;lung imaging;lung injury;lung repair;Machine Learning;Mammals;Modeling;Molecular;Molecular Profiling;Molecular Target;multiple omics;Mus;novel;Nucleic Acid Regulatory Sequences;Outcome;Pathway interactions;predictive modeling;Process;progenitor;repaired;Reporting;Resolution;single cell ATAC-seq;single-cell RNA sequencing;Source;spatiotemporal;Specific qualifier value;stem;stem cell differentiation;stem cell population;stem cells;System;Techniques;Testing;Therapeutic Intervention;Time;transcription factor;Work

PROJECT_TITLE: Defining the cellular dynamics that orchestrate alveolar epithelial cell repair behaviors in live mammal

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(03)]


ORG_CITY: NEW ORLEANS

ORG_DEPT: BIOLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative The proposed research is relevant to public health because the discovery of how aging-related Th17/Treg imbalance promotes PCa is ultimately expected to help inform the identification of new targeted therapeutic interventions against aging-associated prostate cancer. The findings from this project will have significant potential to be developed into prognostic biomarkers and/or translated into the prevention and treatment of human prostate cancer in the elderly. The proposed research is relevant to the part of the NIH mission pertaining to research involving host predisposing states that investigates the role of comorbidity such as aging as an etiological factor in cancer.

PI_NAMEs: ZHANG, QIUYANG  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: activating transcription factor;Age;Age Factors;age related;aged;Aging;aging process;aging related;Antibodies;Blood;bZIP Domain;cancer initiation;Case Fatality Rates;CD4 Positive T Lymphocytes;Cell Physiology;Cell Proliferation;Cell secretion;Cell Survival;Cells;Cessation of life;Chronic;Circulation;Clinical;Clinical Trials;clinically significant;comorbidity;Data;Development;Disease;efficacy evaluation;Elderly;Elderly man;Equilibrium;Etiology;evidence base;Excision;Future;gerotherapeutic;Goals;Human;immune activation;Incidence;Inflammaging;Inflammation;Inflammatory;innovation;Invaded;Knock-out;Knockout Mice;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;migration;Mission;Molecular;mortality;mouse model;Mus;Mutate;new therapeutic target;NF-kappa B;novel;novel therapeutics;old mice;Outcome;Pathogenicity;Patients;pharmacologic;Play;Prevalence;prevent;Prevention;prognostic indicator;Prognostic Marker;Prostate;prostate cancer cell;prostate cancer prevention;prostate cancer progression;Prostate Cancer therapy;prostate carcinogenesis;Public Health;Regulatory T-Lymphocyte;Reporting;Research;Role;small molecule;Specimen;T cell response;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic target;time interval;Tissues;transcription factor;Translating;tumor;tumor growth;tumor progression;Tumor Suppressor Genes;United States National Institutes of Health

PROJECT_TITLE: The Impact of Aging on Prostate Cancer with Age-Related Disruption of Th17/Treg Axis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-K(02)M]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Disability Research;Emergency Care;Mental Health;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: PITTSBURGH

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Preventing the transition from acute pain to chronic pain would reduce individual suffering and provide huge societal savings for hundreds of thousands of injured patients across the country seeking treatment in emergency departments. Identifying the specific psychological responses to traumatic physical injury that contribute to the development of chronic pain and the specific times when these transitions are strongest will inform the design of treatment and prevention strategies. Given that psychological processes are potentially amenable to intervention during the acute and subacute injury phase and are more consistently related to pain outcomes than injury severity, research informing non-pharmacological psychological interventions has the ability to shift the paradigm of post-injury pain management strategies from a largely biomedical and pharmacological approach to a multimodal approach that may serve to reduce opioid overuse yet deliver effective pain relief.

PI_NAMEs: PACELLA, MARIA LYNN (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Accident and Emergency department;Acute;Acute Pain;Age;Agreement;Anxiety;anxiety sensitivity;Autonomic nervous system;Behavior;Behavioral;Belief;Biological Markers;biopsychosocial;biopsychosocial factor;career development;Chronic;Chronic disability;chronic pain;chronic pain management;Clinical Trials Design;Cognition;Cognitive;Cognitive Therapy;Collection;coping;Country;craving;Data;Data Collection;data management;design;Development;Devices;disability;disability-adjusted life years;Distress;Ecological momentary assessment;Electronic Mail;Emergency department visit;Emotional;emotional factor;Emotions;Environment;Evolution;fitbit;Fostering;Fright;Future;Goals;Heart Rate;High Prevalence;high risk;Hour;improved;indexing;Individual;injured;Injury;innovation;Interruption;Intervention;Intervention Trial;longitudinal, prospective study;Measures;Mediating;Mental Depression;Mental disorders;Modeling;Monitor;Motorcycles;Movement;multidisciplinary;multimodality;musculoskeletal injury;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Nonpharmacologic Therapy;novel;Numeric Rating Scale;Opioid;opioid overuse;Pain;pain chronification;Pain intensity;Pain interference;Pain management;pain outcome;pain relief;pain score;patient oriented research;Patient Self-Report;Patients;Pattern;Persons;pharmacologic;Phase;Physiological;point of injury;Population;post-traumatic stress;prevent;Prevention;Prevention strategy;Process;programs;prospective;Prospective, cohort study;psychologic;Psychological Factors;Reaction;Recording of previous events;Recovery;recruit;Reporting;Research;Research Activity;Research Personnel;Resolution;response;Rest;Risk;Risk Factors;Savings;secondary analysis;Secondary pain;sensor;Severities;sex;skills;Stress;Surveys;Symptoms;System;Techniques;Text Messaging;therapy design;Time;Training;Training Activity;Trauma;Trauma patient;treatment strategy;United States;Universities;Vehicle crash;wearable device;Work;years of life lost

PROJECT_TITLE: An in-depth Examination of the Psychological Processes involved in the Transition from Acute to Chronic Pain after a Traumatic Musculoskeletal Injury

STUDY_SECTION: AMS

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


NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE Breast cancer-related job loss is associated with increased financial hardship, including difficulty paying bills, depletion of savings, accumulation of debt, and bankruptcy. In the parent grant, we are testing the effectiveness of a mobile health application designed to support working during the treatment period by increasing access to accommodations and optimizing symptom control, with the ultimate goal of promoting long-term job retention and financial stability. The 2-year R37 extension will allow us to extend the period of follow-up of the parent grant’s aims, creating up to 4 years of data with a cohort of patients within the framework of an RCT, and providing detailed information about subjective and objective indicators of financial hardship, so that we can study the long-term impact of breast cancer treatment on work and on overall financial hardship, and how our study intervention may affect these outcomes.

PI_NAMEs: BLINDER, VICTORIA S (contact)

PROGRAM_OFFICER_NAME: BRICK, RACHELLE SOPHIA

PROJECT_TERMS: Adjuvant;Adjuvant Therapy;Affect;Aftercare;Bankruptcy;breast cancer diagnosis;Breast Cancer Patient;Breast Cancer survivor;Breast Cancer therapy;Breast Cancer Treatment;Cancer Patient;Cancer Survivor;Cellular Phone;Characteristics;Charge;chemotherapy;Chemotherapy-Oncologic Procedure;cohort;Common Terminology Criteria for Adverse Events;Communication;Communities;Data;design;Diagnosis;effectiveness evaluation;effectiveness testing;efficacy testing;Employment;empowerment;Ethnic Origin;Face;Financial Hardship;flexibility;follow-up;Funding;Goals;High Prevalence;Hour;Immigrant;improved;Income;Intervention;Intervention Studies;Interview;Job loss;Knowledge;Language;Light;Link;Longitudinal Studies;Low income;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Minority;Minority Women;mobile application;mobile computing;Mobile Health Application;mortality;mortality risk;novel;Occupations;Oncology;Outcome;Pamphlets;parent grant;Parents;Participant;Pathway interactions;Patient Outcomes Assessments;Patient Self-Report;Patients;Postoperative Period;Provider;provider communication;Race;Randomized;Randomized, Controlled Trials;Reporting;Risk;Role;Savings;Schedule;Security;Sick Leave;skills;Spanish/English;standard of care;stressor;Structure;Survivors;survivorship;Symptom Burden;Symptoms;System;Target Populations;Time;tool;treatment adherence;treatment duration;trial comparing;Wages;Woman;Work;Working Women;Workplace

PROJECT_TITLE: The Breast Cancer and the Workforce Communication App: A randomized controlled trial of an English/Spanish intervention to promote long-term job retention


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Prevention;Social Determinants of Health

PHR: Project Narrative  The proposed study is directed at increasing the fundamental understanding of the causes, mechanisms, and prevention strategies of chronic kidney disease of unknown origin (CKDu) in Latin America. The study’s inclusion of examining sugarcane worker occupational exposure to particulate matter and its nephrotoxic constituents (silica, glyphosate, and heavy metals), renal biomarkers of effect, including early biological change, will advance our ability to identify factors that put individuals at risk for the development of CKDu and also detect illness at preclinical stages. Findings will lead to future interventions designed to reduce morbidity and mortality from CKDu in vulnerable populations around the world.

PI_NAMEs: ADGATE, JOHN L. (contact);NEWMAN, LEE S;SCHAEFFER, JOSHUA WILLIAM

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;Administrative Supplement;Adverse effects;Affect;agricultural community;Agricultural Workers;Agriculture;Air;air contaminant;Air Pollutants;Air Pollution;air sampling;amorphous silicate;Biological;Biological Markers;Blood;Blood Urea Nitrogen;Burn injury;Chronic;Chronic Kidney Failure;Clinical;cohort;Collaborations;Creatinine;cytokine;Data;Dehydration;Development;Diameter;Disease;Disease Progression;Environmental Pollutants;Epidemic;experience;exposure pathway;Exposure to;fine particles;Functional disorder;Future;General Population;glyphosate;Goals;Guatemala;Guatemalan;Harvest;Health;Heat Stress;Heavy Metals;Herbicides;High Prevalence;Hour;Humidity;Hydration status;Impairment;improved;Individual;Inflammation;Inflammatory;inflammatory marker;Inhalation Exposure;Injury;Injury to Kidney;International;Intervention Trial;Investigation;Kidney;Kidney Diseases;kidney dysfunction;Latin America;LCN2 gene;Lead;Life;longitudinal design;Manuals;Measurable;Measurement;Measures;Mediating;Metals;Meteorological Factors;meter;Monitor;Morbidity - disease rate;mortality;nephrotoxicity;Occupational;Occupational Exposure;Osmolalities;Participant;Particulate;Particulate Matter;Pathogenesis;Pathway interactions;Pollution;poor health outcome;Population;post gamma-globulins;pre-clinical;prevent;Prevention strategy;prospective;Questionnaires;Recommendation;Recurrence;renal damage;Renal function;Research;Risk;Risk Factors;Role;Saccharum;Sampling;Seasons;Serum;shift work;Silicon Dioxide;Soil;Therapeutic;therapy design;Thick;Time;Urine;Vasopressins;Vulnerable Populations;Weight

PROJECT_TITLE: Particulate exposure and kidney health

STUDY_SECTION: KNOD

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Nutrition

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative Disruption of lipid metabolism has been associated with metabolic syndrome including obesity, diabetes and nonalcoholic fatty liver disease (NAFLD). VLDL secretion is critical in regulating hepatic lipid homeostasis and impaired VLDL secretion leads to NAFLD and hypolipidemia. Elucidating the molecular mechanisms of how VLDL secretion is impaired by high fat diet, and how NAFLD would progress to more severe non-alcoholic steatohepatitis (NASH), will help to develop novel therapeutic strategies for NAFLD/NASH.

PI_NAMEs: NI, HONGMIN  (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: 2019-nCoV;Area;Autophagocytosis;Autophagosome;Biogenesis;Cells;Cessation of life;Cholesterol;Cholesterol Homeostasis;Coronavirus Infections;Data;Development;Diabetes Mellitus;Diet;Disease Progression;Drosophila genus;Dyslipidemias;Endoplasmic Reticulum;Fatty Liver;Fibrosis;genome wide association study;Goals;Health;Hepatic;Hepatocyte;hepatoma cell;High Fat Diet;Homeostasis;Human Genome;hypolipidemia;Impairment;Inflammation;Integral Membrane Protein;Intestines;intrahepatic;Knock-in Mouse;Knockout Mice;Knowledge;Lecithin;lipid metabolism;Lipids;Lipoproteins;Liver;Liver diseases;Mediating;Membrane;Membrane Proteins;Metabolic Diseases;Metabolic syndrome;Mitochondria;Molecular;Mus;mutant;new therapeutic target;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutic intervention;Obesity;Organelles;Outcome;overexpression;Pathogenesis;Pathway interactions;Phosphatidylethanolamine;Phosphatidylserines;phospholipid scramblase;Phospholipids;Physiological;Play;prevent;Prevention;Protein Biosynthesis;Protein Secretion;Research;restoration;Role;Site;therapeutically effective;Vacuole;Very low density lipoprotein;Work;Zebrafish

PROJECT_TITLE: Mechanisms regulating lipoprotein secretion and lipid metabolism

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Estrogen;Genetics;Kidney Disease;Lupus;Women's Health Research

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Most autoimmune diseases have a profound sex bias, affecting females of reproductive age 3-16:1 over males, and the precise cause of this bias remains unknown. We hypothesize that a short variant of estrogen receptor alpha (ERα), akin to an endogenous ERα variant, is important for anti-inflammatory effects of estrogen in innate immune cells and is targetable. This hypothesis will be tested by varying levels of ERα variants, by selecting ERα cellular location as well as using novel anti-inflammatory selective estrogen receptor modulators (SERMs) that may prove useful as adjunctive treatment for autoimmune diseases such as lupus.

PI_NAMEs: CUNNINGHAM, MELISSA A (contact)

PROGRAM_OFFICER_NAME: MANCINI, MARIE

PROJECT_TERMS: Address;AF2;Affect;Age;Anti-Inflammatory Agents;Antigen-Antibody Complex;Antiinflammatory Effect;Autoantibodies;Autoimmune Diseases;Autoimmunity;B-Lymphocytes;Binding;Biological;Blood Vessels;Bone Marrow;Cell Line;Cell membrane;Cell Physiology;cell type;Cells;Chromatin;Data;Dendritic Cells;Deposition;Development;differential expression;digital;Disease;Disproportionately impacts women;DNA Binding;Dose;End stage renal failure;Endosomes;Environmental Exposure;Epidemiology;ESR1 gene;Estrogen Receptors;Estrogens;Event;experimental study;Female;Genes;genetic corepressor;Genetic Transcription;Genomics;Goals;Gonadal Steroid Hormones;Human;Immune;Immune response;Immune Targeting;immunoregulation;In Vitro;in vivo;Incidence;Inflammation;Inflammatory;Inflammatory Infiltrate;Inflammatory Response;Innate Immune Response;Interferon Gamma Receptor Beta Chain;Investigation;Kidney;Kidney Diseases;Length;Ligand Binding Domain;Location;Lupus;Lupus Nephritis;lupus prone mice;Macrophage;male;Mediating;Membrane;monocyte;Mus;mutant;Mutant Strains Mice;Nephritis;new therapeutic target;next generation;non-genomic;novel;novel strategies;novel therapeutics;Nuclear;overexpression;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;Predisposition;Property;protective effect;Protein Isoforms;Proteins;Proteinuria;prototype;pubertal timing;Race;receptor;Reporting;reproductive;Research;response;Risk Factors;Role;Sampling;Selective Estrogen Receptor Modulators;Serum;sex;Sex Bias;Sex Chromosomes;sex disparity;Signal Transduction;Structure;Systemic Lupus Erythematosus;Technology;Testing;Therapeutic;Tissue-Specific Gene Expression;Tissues;TLR7 gene;Toll-like receptors;tool;Transactivation;transcription factor;Variant;Woman;Work;X Inactivation

PROJECT_TITLE: The Role of Estrogen Receptor Alpha Variant Size and Localization in Modulating TLR7-Induced Inflammation

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Cardiovascular disease accounts for 1 in every 3 deaths in the US, many of which are caused by pathological cardiac hypertrophy and subsequent heart failure, for which there is no cure. Our proposed studies aim to decipher the molecular mechanisms contributing to pathological cardiac hypertrophy. We anticipate that this knowledge will help to develop new, mechanistically specific and selective treatments for pathological cardiac hypertrophy and, thus, reduce mortality from this form of heart disease.

PI_NAMEs: GLEMBOTSKI, CHRIS  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: absorption;Address;Aldosterone;Amino Acids;Binding;Binding Proteins;Calcium;cancer cell;Cancer Cell Growth;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Catalytic Domain;cell type;Cessation of life;Data;Ectopic Expression;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;Epithelial Cells;Glucocorticoids;Growth;Heart;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Human;Hypertrophy;innovation;Interruption;Kidney;knock-down;Knowledge;Left;Leucine Zippers;Link;Mediating;Membrane;Methods;misfolded protein;Molecular;mortality;multicatalytic endopeptidase complex;Mus;Muscle Cells;Neonatal;novel;overexpression;Pathologic;Pathology;Peptides;Phosphotransferases;Physiologic intraventricular pressure;Plasma;pressure;Protein Biosynthesis;protein folding;Protein Overexpression;Protein Secretion;Proteins;Proteome;proteostasis;Rattus;receptor;renal epithelium;response;Role;Serum;Serum Proteins;Sgk protein;Side;Signal Transduction;Site;Study of serum;System;Therapeutic;ubiquitin-protein ligase;Ventricular

PROJECT_TITLE: Non-canonical ERAD as a Regulator of Cardiac Hypertrophy

STUDY_SECTION: MPPA

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


ORG_DEPT: CHEMISTRY

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Narrative Ligand-dependent protein degradation has emerged as a compelling strategy to pharmacologically control the protein content of cells, which has the potential to substantially increase the number of druggable proteins in human disease such as cancer. We have identified DCAF16 – a poorly characterized E3 ubiquitin ligase – as a target of electrophilic probes that promote the nuclear-restricted degradation of proteins. The goal of this proposal is to investigate biological functions of DCAF16, identify small molecules that disrupt cancer cell growth via a DCAF16-dependent mechanism, and discover additional E3 ligases with distinct and restricted expressions in different cancer types that support ligand-induced targeted protein degradation.

PI_NAMEs: ZHANG, XIAOYU  (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Advisory Committees;Antineoplastic Agents;Binding;Binding Proteins;Biological;Biological Process;Biology;Cancer Cell Growth;Cancer cell line;cancer type;career development;Catalysis;cell growth;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Chemicals;chemoproteomics;ChIP-seq;Chromatin;Clinical Trials;Communication;CRISPR/Cas technology;Cytosol;cytotoxicity;Degradation Pathway;Development;drug action;Drug Design;Educational process of instructing;Educational workshop;Environment;Enzymes;experience;gain of function;Gene Expression;Genetic Transcription;Glues;Goals;Grant;Human;human disease;Institution;Knowledge;Laboratories;Ligands;Luciferases;Malignant Neoplasms;Maps;Marketing;Mass Spectrum Analysis;MDA MB 231;Mediating;Membrane;Mentors;Methods;Molecular;Molecular Biology;multicatalytic endopeptidase complex;new therapeutic target;next generation sequencing;Nuclear;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Process;Property;protein degradation;Protein Degradation Induction;protein expression;protein function;Proteins;Proteome;Proteomics;Receptor Signaling;Research;Research Institute;Role;Scientist;screening;Site-Directed Mutagenesis;skills;small molecule;small molecule inhibitor;small molecule libraries;stable cell line;Substrate Specificity;System;Tacrolimus Binding Protein 1A;Technology;tool;Training;Training Programs;transcriptome sequencing;Ubiquitin;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Discovery of small molecule-mediated protein degradation pathways in human cancer

STUDY_SECTION: NCI

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


ADMINISTERING_IC: HG

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

ORG_CITY: SAN DIEGO

ORG_NAME: ALIDA BIOSCIENCES, INC.

PHR: Project Narrative Alida Biosciences is a start-up company focused on reading the epitranscriptomic code, a regulatory layer of biological information controlling how the genetic code is used in cells in health and in disease progression. By creating and commercializing the first platform for reading multiple elements of this epitranscriptomic code simultaneously, we will enable new science to understand the progression of diseases such as cancer and accelerate drug development targeting epitranscriptomic pathways.

PI_NAMEs: STENGEL, GUDRUN  (contact)

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: Acceleration;Address;Aging;Alternative Splicing;analysis pipeline;analytical method;Antibodies;Architecture;assay development;Automation;Bar Codes;Benchmarking;Biological;Biological Assay;Biological Sciences;Cells;Chemicals;Clinical;clinical biomarkers;Clinical Trials;clinically relevant;Code;commercial launch;commercialization;Complementary DNA;Consumption;Coupled;Custom;Data Set;Dedications;design;Detection;detection assay;detection method;detection platform;Development;Devices;Disease;Disease Progression;DNA;drug development;Drug resistance;Drug Targeting;Elements;Environmental Risk Factor;Enzymes;epitranscriptome;epitranscriptomics;Evaluation;Feedback;Funding;Genetic Code;Health;Human;Human Cell Line;improved;Individual;Infrastructure;Inosine;interest;Kinetics;Knowledge;Location;Malignant Neoplasms;Maps;Marketing;Measures;Messenger RNA;Methods;Modification;Molecular;Monitor;Monoclonal Antibodies;multiplex assay;multiplex detection;Needle biopsy procedure;Nucleotides;Pathway interactions;Performance;Phase;Phenotype;Play;Preparation;Procedures;Process;Process Measure;programs;Property;Proteins;Protocols documentation;prototype;Publications;Publishing;Questionnaires;Reaction;Reader;Reading;Reagent;Reproducibility;Ribosomal RNA;RNA;RNA Degradation;RNA metabolism;RNA purification;Role;Running;Sampling;Science;single cell analysis;Site;Small Business Innovation Research Grant;Specificity;Standardization;Structure;Surface;symposium;System;Technology;Testing;Therapeutic;Time;trafficking;transcriptome;Transfer RNA;Translation Initiation;Translations;tumor progression;usability;user-friendly;Validation;Virus Diseases

PROJECT_TITLE: Multiplexed Analysis of the Epitranscriptome