NIH_SPENDING_CATS: Atherosclerosis;Bioengineering;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Nanotechnology;Regenerative Medicine

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The goal of our research is to provide molecular insights into endothelial regulation and heart regeneration and repair with the intention of uncovering next-generation therapeutic targets to increase blood vessel growth in injured heart following myocardial infarction. We discovered that loss of the epsin 1 and 2 endocytic adaptor proteins from the endothelium resulted in restoration of blood flow and contractile function in the ischemic heart through enhanced artery formation. Here, we will study the molecular mechanisms underpinning this phenomenon, which will allow us to discover novel targets that will propel development of effective treatment for ischemic heart diseases, a primary cause of mortality worldwide.

PI_NAMEs: CHEN, HONG  (contact);CHEN, KAIFU ;WANG, DA-ZHI

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Acceleration;Acute;Acute myocardial infarction;Adaptor Signaling Protein;Adult;Alleles;Arterial Fatty Streak;Arteries;artery occlusion;Blood flow;blood pressure elevation;Blood Vessels;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cardiovascular Diseases;Cell Communication;cell regeneration;Cells;Cessation of life;clinically significant;coronary angioplasty;Coronary Arteriosclerosis;Coronary artery;CXCR4 gene;Data;Development;Diabetes Mellitus;Disease;Disease Progression;Dyslipidemias;effective therapy;Encapsulated;Endothelial Cells;Endothelium;epsin;epsin 1;Family;Fibrosis;fighting;Financial Hardship;Fortification;Genetic;Goals;Growth;Health;healthy lifestyle;Heart;heart cell;Heart Diseases;Heart failure;heart function;Heart Injuries;Heterozygote;Hypertension;improved;Infarction;injury and repair;innovation;insight;Intention;Ischemia;ischemic cardiomyopathy;ischemic injury;KDR gene;Knock-out;Knockout Mice;Knowledge;Macrophage;Mediating;Medical;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Infarction;Myocardial Ischemia;Myocardial tissue;nanomedicine;nanoparticle;nanotherapy;Neonatal;neovascularization;novel;novel therapeutics;Nutrient;Obesity;Patients;pre-clinical;Pre-Clinical Model;precursor cell;prevent;Process;Proliferating;Recovery;Recurrence;regenerative;regenerative therapy;Regulation;repaired;Reperfusion Therapy;Reporting;Repression;Research;Resolution;restoration;revascularization;Risk Factors;Role;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Small Interfering RNA;Societies;standard care;Stents;Stromal Cell-Derived Factor 1;Technology;Testing;Therapeutic;therapeutic evaluation;therapeutic target;tissue repair;Vascular Endothelial Growth Factors;Vascularization;Visualization;Work

PROJECT_TITLE: Targeting Endothelial Epsins to Ameliorate Myocardial Ischemia

STUDY_SECTION: TDPS

STUDY_SECTION_NAME: Therapeutic Development and Preclinical Studies Study Section[TDPS]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Coronary microvascular disease (CMVD), or disease of the smaller arteries in the heart, contributes to the significant burden of Ischemic Heart Disease (IHD). We will determine the role of an isoform of cardiomyocyte transcriptional co-regulator Friend of GATA 2 (FOG2) in regulating angiogenic gene expression, neighboring vascular cell interactions, and the coronary microvasculature to gain insight into mechanisms of CMVD.

PI_NAMEs: GUERRATY, MARIE A (contact)

PROGRAM_OFFICER_NAME: FLEG, JEROME L

PROJECT_TERMS: Affect;angiogenesis;Angiogenesis Inhibitors;Arteries;arteriole;Blood capillaries;Blood Vessels;Cardiac;Cardiac Myocytes;Cell Communication;Cell Proliferation;Cell Separation;Cells;Cleavage Under Targets and Release Using Nuclease;Co-Immunoprecipitations;Coculture Techniques;Code;Complex;Coronary;Coronary heart disease;Data;defined contribution;Development;Disease;Endothelial Cells;Endothelium;experimental study;Friends;Functional disorder;GATA4 gene;Gene Expression;Genes;Genetic Transcription;Genome;genome-wide;Genomics;Goals;Heart;Heart failure;HIF1A gene;Homeostasis;Human;Hypoxia;Hypoxia Inducible Factor;Image;In Vitro;in vitro Model;in vivo;insight;Ischemia;knock-down;Knock-out;Length;Link;Luciferases;Maintenance;Microcirculation;Microvascular Dysfunction;migration;Modeling;Molecular;Mus;Myocardial Infarction;Myocardial Ischemia;N-terminal;novel;Outcome;overexpression;paracrine;Pathogenesis;Patients;Pericytes;Phenotype;programs;promoter;Protein Isoforms;recruit;Regulation;response;Role;skills;Smooth Muscle Myocytes;Structure;Structure-Activity Relationship;targeted treatment;Testing;Tissues;Transcription Repressor;transcriptome sequencing;Variant;Work

PROJECT_TITLE: FOG2 isoforms in Coronary Microvascular Disease

STUDY_SECTION: BBHV

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biomedical Imaging;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Orphan Drug;Prevention;Rare Diseases;Tuberculosis;Tuberculosis Vaccine;Vaccine Related

ORG_CITY: COLLEGE STATION

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: Project Narrative Tuberculosis represents one of the most frequent causes of morbidity and mortality in humans worldwide. Tuberculosis drug resistant infections are increasing throughout the world, making it critical that rapid screening strategies are developed for therapeutics and other novel interventions. This project is geared toward improvement and validation of groundbreaking imaging technologies that can be used to replace much slower and inefficient conventional approaches to track bacterial viability, whole animal localization during disease and speed development of novel therapeutics and vaccines.

PI_NAMEs: CIRILLO, JEFFREY D. (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: Animals;antimicrobial;Bacteria;beta-Lactamase;Biology;Bioluminescence;Cessation of life;Characteristics;Colony-forming units;Consumption;cost;Dangerousness;Data;data dissemination;Detection;Development;Disadvantaged;Disease;Dose;Drug resistance in tuberculosis;efficacy evaluation;Energy Transfer;Ensure;Enzymes;Event;experimental study;Feedback;Fluorescence;fluorescence imaging;Fluorogenic Substrate;Growth;Head;Hour;Human;Image;imaging study;imaging system;Imaging technology;improved;In Vitro;in vitro Model;in vivo;in vivo imaging;in vivo imaging system;Infection;Infectious Agent;insight;Intervention;Intervention Studies;Knowledge;Lung;Lung infections;Methods;microendoscope;microendoscopy;model organism;Modification;Monitor;Morbidity - disease rate;mortality;Mus;mutant;Mycobacterium tuberculosis;Nature;novel;novel strategies;novel therapeutics;novel vaccines;Optics;Organ;pathogen;Pathogenesis;Physiological;Population;preclinical study;Proteins;Publishing;quantitative imaging;Rapid screening;Recording of previous events;Reporter;Research;respiratory pathogen;Sensitivity and Specificity;Speed;System;Therapeutic;therapeutic evaluation;therapy development;Time;Tissues;Treatment Efficacy;Tuberculosis;vaccine efficacy;vaccine evaluation;Vaccines;Validation;Virulence;Work

PROJECT_TITLE: Ultrasensitive detection of Mycobacterium tuberculosis infection

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The cohesin protein complex has been proposed to shape mammalian nuclear architecture in ways critical to genome function. The purpose of this research proposal is to investigate how cohesin, and its auxiliary proteins, couple genome structure to gene regulation in vivo during brain development. These studies are poised to reveal new molecular mechanisms and physiological implications of genome structure with direct relevance to human health and disease.

PI_NAMEs: CANZIO, DANIELE  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Architecture;Bar Codes;Behavior;Biological Models;Brain;Cell Physiology;Cell surface;Cell Surface Proteins;cell type;Cells;Central Nervous System;Chromatin;Chromatin Loop;Chromosome Structures;cohesin;cohesion;combinatorial;Complex;Coupled;Coupling;Data;demethylation;Development;Developmental Process;Discrimination;Disease;DNA;Enhancers;Epigenetic Process;gain of function;Gene Cluster;Gene Expression;Gene Expression Regulation;Gene Order;Generations;Genes;Genome;genomic locus;Health;Human;in vivo;Individual;insight;Integral Membrane Protein;Link;loss of function;Mammalian Cell;mammalian genome;Mediating;Modeling;Molecular;Mus;neural;neural circuit;neurodevelopment;neuron development;Neurons;novel;Nuclear;Olfactory Epithelium;Olfactory Pathways;olfactory sensory neurons;operation;Pattern;Physiological;Play;postmitotic;Process;promoter;protein complex;protein function;Proteins;raphe nuclei;Regulation;Regulatory Element;Research Proposals;Rest;Role;Shapes;Sister;stem cell population;Structure;System;Testing;Variant

PROJECT_TITLE: Linking the molecular operations of cohesin to its physiological activity in the mammalian brain

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infant Mortality;Infectious Diseases;Maternal Health;Maternal Morbidity and Mortality;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: BERKELEY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Maternal and neonatal mortality remains high in sub-Saharan Africa, and infections are a leading cause of death. Poor water quality and highly contaminated surfaces in health care facility maternity wards are known to increase gut colonization with bacterial pathogens, including antibiotic resistant bacteria. This study will evaluate a novel intervention consisting of passively chlorinated water supply and on-site generation of chlorine disinfectant in health facilities to reduce environmental contamination, reduce colonization of mothers and neonates with sepsis-associated bacteria and antibiotic resistant microorganisms, and improve maternal and neonatal health.

PI_NAMEs: MUSILA, LILIAN ANYANGO;OTIENO, PHELGONA ;PICKERING, AMY J. (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Africa South of the Sahara;Antibiotic Resistance;antibiotic resistant infections;Antimicrobial Resistance;Bacterial Antibiotic Resistance;Bacterial Infections;bacterial resistance;Birth;Budgets;Caring;Cause of Death;Cessation of life;Childhood;chlorination;Chlorine;Cluster randomized trial;Collection;community setting;contaminated drinking water;contaminated water;cost;cost effectiveness;Data;Death Rate;Disinfectants;Disinfection;Dose;drinking water;Economics;effective intervention;Electricity;Engineering;Enrollment;Ensure;Environmental Pollution;Epidemiology;fighting;follow-up;Generations;Goals;Government;gut colonization;Hand;Health Benefit;Health care facility;health care quality;health care settings;Health Personnel;Health Resources;Healthcare;healthcare-associated infections;Hospitals;Hygiene;improved;Income;Infection;Infection Control;Infection prevention;Intervention;intervention effect;Investments;Kenya;Life;Link;Live Birth;low and middle-income countries;Low income;Manuals;Marketing;Maternal Health;Maternal Mortality;Measures;Medical;Medicine;Methods;Microbiology;microorganism;Molecular;Monitor;Mothers;Neonatal;neonatal health;neonatal infection;Neonatal Mortality;neonatal sepsis;neonate;new technology;Newborn Infant;Nosocomial Infections;novel;Outcome;pathogen;pathogenic bacteria;Pathogenicity;Pathway interactions;Phenotype;Philanthropic Fund;Postpartum Period;Prevalence;prevent;Production;Randomized, Controlled Trials;Rectum;Research;Resistance;resistance gene;Resources;Risk;Rural;Rural Health;Sanitation;Sepsis;Site;skills;Sodium Chloride;Solar Energy;Structure;Surface;Surveys;Swab;Symptoms;Technology;Telephone;Time;tool;Touch sensation;transmission process;trial design;ward;Water;water quality;water sampling;Water Supply;water treatment

PROJECT_TITLE: Multi-component chlorination intervention to reduce neonatal infections in rural health facilities

STUDY_SECTION: PRID

STUDY_SECTION_NAME: Population based Research in Infectious Disease Study Section[PRID]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Rehabilitation

ORG_CITY: CHICAGO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative This project aims to assess RF heating of deep brain stimulation devices and cardiac electronic implants during MRI in newly approved low-field MRI scanners at 0.55 T. Results will produce data that allow determination of safe imaging parameters, and support development of standards and imaging guidelines which bring MRI accessible to these patients.

PI_NAMEs: GOLESTANI RAD, LALEH  (contact)

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: Address;Adopted;Adoption;Adult;Advocate;Age;age related;Age Years;American;Biophysics;Cardiac;cardiac device;cardiac implant;Cardiac pacemaker;Cardiovascular system;Childhood;Chronic Disease;clinical application;Coiled Bodies;Communities;Complex;Computer Models;cost;cost effective;Data;Deep Brain Stimulation;design;Development;Device Safety;Devices;diagnostic value;Disparity;electric field;Electronics;Ensure;Evaluation;evidence base;experience;experimental study;forging;Friends;Future;Gel;Geometry;Growth;Guidelines;heat injury;Heating;Image;Implant;Implantable Defibrillators;implantable device;implantation;Influentials;Injury;Intervention;Investments;Knowledge;Label;Length;magnetic field;Magnetic Resonance Imaging;Magnetism;manufacture;Manufacturer;Maps;Marketing;Mathematics;Measurement;Medical;Medical Device;medical implant;Metals;Methodology;Methods;Modeling;Monitor;Morphologic artifacts;MRI Scans;Nature;neuroregulation;Outcome;Paint;Patient Care;Patients;Physiologic pulse;Play;Population;Positioning Attribute;premature;Procedures;Publications;radio frequency;Radiology Specialty;Recommendation;Resources;response;Risk;Role;Safety;safety assessment;Scientist;Secure;Specialist;System;Temperature;Testing;Time;timeline;Tissues;tool;trend;underserved area;United States National Institutes of Health;user-friendly;Validation;Variant;Vendor;welfare

PROJECT_TITLE: Assessing RF heating of active implantable medical devices in low-field MRI systems

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Aging;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunotherapy;Lung;Lung Cancer;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_NAME: MOREHOUSE SCHOOL OF MEDICINE

ORG_STATE: GA

PHR: PROJECT NARRATIVE We will investigate racial disparities for receipt of cancer treatments, the impact of time from diagnosis to first cancer treatment, number of cycles received, and dose of drugs given on survival in elderly non-small cell lung cancer (NSCLC) patients for Blacks compared to Whites, using The Surveillance, Epidemiology, and End Result database. We will further investigate whether Black patients who are underserved and live in urban and rural areas and other geographic regions in the USA, received comparable treatments that extended their survival. We will determine causal patient and provider characteristics important in NSCLC treatment that extended patients’ survival.

PI_NAMEs: HARDY, DALE SHARON (contact)

PROGRAM_OFFICER_NAME: PADGETT, LYNNE SLAUGHTER

PROJECT_TERMS: Address;Adenocarcinoma;Advanced Malignant Neoplasm;Affect;Age;aggressive therapy;Anemia;Anti-Inflammatory Agents;Antineoplastic Agents;black patient;Black Populations;Black race;Cancer Etiology;Cancer Patient;cancer survival;cancer therapy;cancer type;Carboplatin;Cessation of life;Characteristics;chemotherapy;Combined Modality Therapy;Communication;comorbidity;Data;Databases;Diagnosis;Disparity;Dose;Early Diagnosis;Educational process of instructing;Elderly;Future;Geographic Locations;Goals;Guidelines;health equity;Histology;hormone therapy;Hormones;hospital bed;Hospitals;human old age (65+);Immunotherapy;improved;Inequity;insight;Insurance;intersectionality;Knowledge;Location;Logistics;Lung;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediation;Minority;Minority Groups;Modeling;mortality;National Comprehensive Cancer Network;Non-Small-Cell Lung Carcinoma;older patient;Ownership;Patients;Pemetrexed;Performance Status;Pharmaceutical Preparations;Placebos;Platinum;Population;Progression-Free Survivals;Provider;racial disparity;Reporting;Research Design;respiratory;Retrospective cohort study;Risk;rural area;SEER Program;sex;standard care;success;Survival Rate;Symptom Burden;systematic review;Time;Toxic effect;Translating;treatment comparison;Treatment Failure;treatment guidelines;underserved area;urban area

PROJECT_TITLE: Reducing racial disparities and achieving health equity in lung cancer treatment among the underserved

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-G (55)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Digestive Diseases;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: BLOOMINGTON

ORG_DEPT: CHEMISTRY

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Novel technology will be developed to make mass measurements for complex mixtures and heterogeneous samples much higher resolution and much faster. These technological developments will have a broad impact, applications include better characterization of gene therapies, improved understanding of the mechanism of antivirals, and the detection and monitoring of disease biomarkers.

PI_NAMEs: JARROLD, MARTIN F (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Address;adduct;Amplifiers;Anti-viral Agents;Back;Benchmarking;Binding;Biological Markers;Body Fluids;Capsid;Capsid Proteins;Cells;Charge;Complex;Complex Mixtures;Computer Simulation;Computers;Coupled;Dependovirus;design;design and construction;Detection;detector;Development;Disease;Electrodes;Electrostatics;Emerging Technologies;Frequencies;gene therapy;Gene Transduction Agent;Goals;Health;Hepatitis B Antiviral;Hepatitis B Virus;Heterogeneity;Human;implementation design;improved;integrated circuit;Ions;Lead;Mass Fragmentography;Mass Spectrum Analysis;Measurement;Measures;Methods;Monitor;Morphologic artifacts;Nature;new technology;Noise;novel;novel strategies;Performance;Post-Translational Protein Processing;Preparation;prevent;Proteins;Reporting;Resolution;Sampling;Signal Transduction;Silicon;simulation;Sodium Chloride;Speed;Techniques;technology development;temporal measurement;Time;ultra high resolution;urinary;Virus Assembly;voltage;Width;Work

PROJECT_TITLE: Advancing High-Resolution Charge Detection-Mass Spectrometry


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative: Excess thyroid hormone has been associated with the development of Alzheimer's disease and related dementias (AD/ADRD). This project aims to clarify whether thyroid hormone is associated with the progression of AD/ADRD in a dose dependent manner and to determine what other characteristics make people particularly vulnerable to the actions of excess thyroid hormone for these outcomes. Since most excess thyroid hormone is the result of over treatment with thyroid hormone therapy, this work examines an important potentially preventable risk factor for AD/ADRD, a growing public health problem world- wide.

PI_NAMEs: MAMMEN, JENNIFER SOPHIE (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acceleration;adjudication;Affect;Age;Aging;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;amino acid metabolism;Attitude;Baltimore;Biological;biological adaptation to stress;Biological Markers;candidate marker;care systems;Caregivers;case control;Ceramides;Characteristics;Clinical;Cognition Disorders;Cognitive;cognitive testing;cohort;comorbidity;Data;Data Set;Decision Making;Dementia;dementia risk;design;Development;Diabetes Mellitus;Diagnosis;Disease;Dose;effective therapy;Failure;Feedback;Future;General Population;Goals;hazard;Health;Health Benefit;Healthcare;hormone therapy;Hormone use;Hormones;Hypothyroidism;Iatrogenesis;IL6 gene;Impaired cognition;improved;Incidence;Inflammation;Internships;Intervention Studies;Label;Laboratories;Lipids;Lipolysis;Longitudinal Studies;Measurement;Mediating;Meta-Analysis;Metabolic Diseases;metabolic rate;Metabolic syndrome;Metabolism;metabolomics;Mitochondria;neuroinflammation;older adult;Outcome;overtreatment;oxidation;oxidative damage;Patients;Persons;Pituitary Gland;Population;Positioning Attribute;Prevalence;Primary Care;provider behavior;Public Health;Race;Randomized;Recommendation;Regression Analysis;Reporting;response;Risk;Risk Factors;Role;screening;sex;small molecule;Source;Sphingomyelins;Structural Models;Subgroup;Surveys;System;systemic inflammatory response;Testing;Thyroid Gland;Thyroid Hormones;Thyrotoxicosis;Thyrotropin;Time;treatment effect;Tryptophan;United States;Work

PROJECT_TITLE: Thyroid Hormone Action in Alzheimer's Disease and Related Dementias

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Contraception/Reproduction;Data Science;Infertility;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The current gold standard method for sperm retrieval is still manual microscopic examination and retrieval, which is highly subjective, time-consuming, and expensive. To the best of our knowledge, there is currently no assay in the market or the commercial development pipeline that can efficiently, reliably, and rapidly help in the retrieval of sperm cells from testicular biopsies or severe factor ejaculated semen samples, and all previously developed systems and networks for sperm localization are highly susceptible to domain bias and may not maintain efficiency when identifying sperm in clinical microTESE samples. Here, we propose to develop the first domain- adaptive, automated, high-throughput, sensitive, and inexpensive AI-assisted screening, and retrieval tool for rare sperm from minimally processed heterogenous microTESE and semen samples.

PI_NAMEs: KATHRINS, MARTIN ;SHAFIEE, HADI  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Address;Affect;aspirate;Assisted Reproductive Technology;Biological;Biological Assay;Biopsy;Biopsy Specimen;Blood specimen;Categories;Cells;Child;Clinical;Complex;Conceptions;Consumption;convolutional neural network;Couples;Data;Data Set;deep learning;deep learning algorithm;deep learning model;deep neural network;design;Detection;Development;Device Designs;Devices;diverse data;Drops;Ejaculation;Evaluation;experience;Face;Fatigue;Fertility Rates;heterogenous data;hormone therapy;Hour;Human Resources;Image Analysis;improved;Individual;Infertility;Intracytoplasmic Sperm Injections;Label;large-scale imaging data;Liquid substance;Machine Learning;man;Manuals;Marketing;Medical Imaging;Medicine;men;Methods;Microdissection;Microfabrication;Microfluidics;Microscope;Microscopic;Modeling;nano;novel;Operative Surgical Procedures;Optics;Patients;Predisposition;Process;Production;Prognosis;Reporting;reproductive;Reproductive History;Retrieval;Sampling;Science;screening;Seminal fluid;Specimen;sperm cell;Sperm Count Procedure;Subcategory;success;Suspensions;System;Techniques;Time;Tissues;tool;Training;usability;Visualization;Woman

PROJECT_TITLE: Rare sperm screening and retrieval with a domain-adaptive deep learning-enabled microwell system.

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Estrogen;Mental Health;Neurosciences;Pediatric

PHR: Transgender and gender-nonbinary (TNB) adolescents may receive gender-affirming hormone therapy (GAHT) with estradiol or testosterone to induce physical changes that align with their gender identity. This has been shown to improve symptoms of anxiety and depression, but parents and caregivers often worry that giving GAHT during adolescence, a period of rapid brain maturation, may affect their child’s brain development and function and, in turn, their child’s ability to think and learn. In this proposed project, we will use advanced neuroimaging techniques and a battery of well-established tools for cognitive assessment to study the neurocognitive effects of GAHT in TNB adolescents.

PI_NAMEs: BASKARAN, CHARU ;CHAN, YEE-MING  (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: Address;Adolescence;Adolescent;Adult;Affect;Age;age related;age related changes;aged;Amygdaloid structure;Anatomy;anxiety symptoms;Area;Behavior;Behavior Control;Birth;boys;Brain;brain health;Brain region;Caregivers;Child;cisgender;Clinical;clinical care;Cognition;Cognitive;cognitive control;cognitive development;cognitive testing;cohort;Corpus striatum structure;Counseling;Critical Thinking;Data;Decision Making;depressive symptoms;Development;Distress;Education;emotion regulation;Emotions;empowerment;Enrollment;Estradiol;Estrogens;executive function;Exhibits;Family;Feeling suicidal;flexibility;Functional Magnetic Resonance Imaging;Gender;gender affirmation;gender affirming care;gender affirming hormone therapy;gender affirming hormones;gender dysphoria;Gender Identity;General Population;Goals;Gonadal Steroid Hormones;high risk population;improved;Individual;Investigation;Knowledge;Lateral;Learning;Life;Link;Longitudinal, observational study;Measures;Mental Health;Moods;multidisciplinary;National Institute of Child Health and Human Development;Neurocognitive;neuroimaging;nonbinary;Outcome;Parents;Participant;Pathway interactions;Patients;Performance;Personal Autonomy;Phase;Play;Prefrontal Cortex;prospective;psychological outcomes;recruit;Reporting;Research Personnel;response;Rest;Role;sex;Sex Characteristics;Sex Differences;Short-Term Memory;skills;Standardization;standardize measure;Statistical Models;Structure;success;symptomatic improvement;Symptoms;Techniques;Testing;Testosterone;Thick;Time;tool;transfeminine;transgender;transmasculine;United States;United States National Institutes of Health;Well in self;Youth

PROJECT_TITLE: The effects of gender-affirming sex steroids on brain development in adolescents

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Genetics;Mental Health;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LA JOLLA

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE A fundamental question in biology is - how did humans acquire their unique characteristics from their primate ancestors? We have identified a non-coding element—a member of a class of DNA sequences called human accelerated regions (HARs)—that our evidence indicates is a strong candidate to have generated human- specific traits involving cognition during human evolution. Understanding HARs is relevant to NIH’s mission of reducing illness and disability, as HARs are linked to neuro-developmental disorders such as schizophrenia and autism.

PI_NAMEs: TAN, KUN ;WILKINSON, MILES FROME (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Acceleration;Address;autism spectrum disorder;Behavior;behavior test;Behavioral;Binding;Biological Assay;Biology;Black Box;Brain;Cells;Characteristics;Cognition;Cognitive;Conserved Sequence;Creativeness;Data;Defect;design;Development;differential expression;disability;DNA Sequence;Elements;Embryo;Enhancers;Event;Evolution;Exhibits;experimental study;Finding by Cause;flexibility;Gene Expression;Generations;Genes;Genetic;Genetic Transcription;Goals;Grant;Hi-C;hindbrain;Human;human embryonic stem cell;Human Genome;Humanities;Impairment;in vitro Assay;in vivo;Intelligence;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Language;Lead;Learning;Link;Lower Organism;Mammals;Marsupialia;member;Memory;Midbrain structure;Mission;Molecular;Molecular Analysis;Mus;nerve stem cell;neural;neurodevelopment;Neurodevelopmental Disorder;Neuroectoderm;Neurons;Neurophysiology - biologic function;nonhuman primate;Pan Genus;prevent;Primates;Property;Prosencephalon;Reporter;Research;Research Personnel;Reversal Learning;Role;Schizophrenia;single-cell RNA sequencing;success;Testing;trait;transcription factor;Transcription Repressor;Transgenic Mice;United States National Institutes of Health;Untranslated RNA

PROJECT_TITLE: An Ancient Neural Enhancer that has Rapidly Evolved in the Human Lineage

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ORG_DEPT: BIOCHEMISTRY

PHR: PROJECT NARRATIVE This work employs new tools to decipher how standing genetic variation (genetic background) impacts the biology and evolution of the most common cause of fungal meningitis, Cryptococcus neoformans. Answering this fundamental question is important for understanding how genetic heterogeneity affects the function of pathogen genes, which is critical for developing effective broad-spectrum treatments.

PI_NAMEs: MADHANI, HITEN D (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Address;Affect;Biology;Cessation of life;chemical genetics;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;Complex;congenic;CRISPR/Cas technology;Cryptococcus neoformans;Data;deletion library;Drug resistance;effective therapy;Environment;Essential Genes;Evolution;experimental study;fitness;Fungal Meningitis;Gene Deletion;Gene Library;Genes;Genetic;Genetic Epistasis;genetic evolution;Genetic Heterogeneity;Genetic Variation;Genome;genome sequencing;Genomics;Genotype;Goals;Haploidy;Human;human disease;human pathogen;In Vitro;Infection;Infectious Diseases Research;Insertional Mutagenesis;Investigation;Knowledge;Laboratories;Libraries;Lung;Maps;Measurement;Mediating;member;Modeling;Mus;novel;pathogen;pathogenic fungus;Pathogenicity;Pathway interactions;Phenotype;Phylogenetic Analysis;Population;reconstruction;response;Role;Scheme;Site;small molecule;Statistical Methods;Technology;Testing;Therapeutic;tool;trait;transcriptomics;unpublished works;Variant;Virulence;Work;Yeasts

PROJECT_TITLE: Deciphering the significance of pathogen genetic variation and evolution

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


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

ORG_DEPT: NEUROSURGERY

PHR: Project Narrative Using an in vivo CRISPR screen approach, we discovered Chek2 to be the top kinase contributing to the evasion from CD8 T cell-mediated killing. Chek2 inhibition with clinical grade drugs improved the efficacy of PD-1/PD- L1 blockade. Understanding the immunosuppressive function of Chek2 is critical for testing in GBM patients.

PI_NAMEs: DMELLO, CRISMITA CLEMENT (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Abbreviations;Address;antagonist;anti-tumor immune response;Antigen Presentation;Biological Assay;Biological Markers;Blocking Antibodies;Blood Tests;blood-brain barrier permeabilization;cancer type;CD8-Positive T-Lymphocytes;cell killing;Cells;Cellular Assay;checkpoint inhibition;CHEK2 gene;ChIP-seq;Clinical;Clinical Trials;Combined Modality Therapy;CRISPR screen;cytotoxicity;Data;DNA;DNA binding protein B;DNA Damage;experimental study;Frequencies;Future;Gene Expression;gene repression;Genes;Genetic;Genetic Transcription;Glioblastoma;Glioma;Immune;immune checkpoint blockade;Immunologic Tests;Immunoprecipitation;immunoregulation;Immunosuppression;Immunotherapy;improved;in vivo;Inflammatory;inhibitor;Interferon alpha;interferon alpha receptor;Interferon Type I;Knock-out;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Methylation;Methyltransferase;Modeling;neoplastic cell;novel therapeutic intervention;Pathway interactions;Patients;PD-1 blockade;PD-1/PD-L1;PD-L1 blockade;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Play;pre-clinical;programs;promoter;Proteins;Radiation therapy;Resistance;response;RNA-Binding Proteins;Role;Signal Transduction;small molecule inhibitor;standard of care;success;synergism;T cell response;T-Cell Proliferation;T-Lymphocyte;Testing;Therapeutic;Transcription Repressor;Transcriptional Regulation;transcriptome sequencing;treatment effect;treatment strategy;Tumor Escape;tumor microenvironment

PROJECT_TITLE: The immunosuppressive function of Checkpoint kinase 2 in gliomas

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CN-V (03)]


NIH_SPENDING_CATS: Genetics

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Not applicable for application.

PI_NAMEs: MELLO, CRAIG C (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TITLE: RNA Mediated Genetic Interference in C. elegans

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE In this application, we will probe the hypothesis that mechanistic communication and spatial interactions between myeloid-derived suppressor cells (MDSC) and cancer-associated fibroblasts (CAF) drive tumor-permissive and immune suppressive signaling in the tumor microenvironment to promote chemoimmunotherapy resistance in pancreatic cancer. Our studies will precisely deconstruct the underpinnings of this previously unrecognized MDSC-CAF communication using novel mouse modeling techniques and spatial proteomics in human pancreatic cancer samples. Moreover, by developing a highly selective pharmacologic strategy to disrupt this MDSC-CAF crosstalk in preclinical models, our proposal will lay the foundation for a neoadjuvant clinical trial in patients with operable pancreatic cancer.

PI_NAMEs: DATTA, JASHODEEP  (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Acceleration;Adoptive Transfer;Affinity;anti-PD-1;Antibodies;Attenuated;Automobile Driving;cancer cell;Cancer Etiology;Cells;cellular imaging;Cessation of life;chemotherapy;ChIP-seq;Clinical;Clinical Trials;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Communication;Cues;CXCL1 gene;Cytometry;Data;Data Set;Disabling;Ecosystem;Enrollment;Evolution;Fibroblasts;Foundations;Functional disorder;gemcitabine;Genetic;granulocyte;Habitats;Human;Immune;Immuno-Chemotherapy;Immunoprecipitation;immunoregulation;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Infiltration;Inflammation;Inflammatory;inhibitor;innovation;insight;Institution;Interleukin-6;Knock-in Mouse;Knock-out;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;MAP Kinase Gene;Mass Spectrum Analysis;MEKs;Membrane;Methodology;Mission;Mitogen-Activated Protein Kinases;Modeling;Molecular;monomer;mouse model;multiple datasets;Mus;Myelogenous;Myeloid-derived suppressor cells;Neighborhoods;Neoadjuvant Therapy;neutrophil;novel;overexpression;Paclitaxel;Pancreatic Ductal Adenocarcinoma;paracrine;participant enrollment;Pathogenicity;Pathologic;Patients;peripheral blood;permissiveness;pharmacologic;Phase I Clinical Trials;phase I trial;pre-clinical;Pre-Clinical Model;preclinical development;predictive marker;prevent;Production;programs;Proteomics;Receptors, Tumor Necrosis Factor, Type II;Refractory;Regulation;Reporting;Research Personnel;Resistance;response;restraint;Role;Sampling;Signal Transduction;Specimen;STAT3 gene;T-Lymphocyte;Techniques;Therapeutic;therapy resistant;TNF gene;TNFRSF1B gene;trafficking;transcriptome;transcriptome sequencing;Transgenic Mice;transmission process;tumor;tumor growth;Tumor Immunity;tumor microenvironment;United States

PROJECT_TITLE: Disrupting MDSC-fibroblast interactions to overcome chemoimmunotherapy resistance in pancreatic cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDPT-L (02)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Depression;Frontotemporal Dementia (FTD);Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Rare Diseases

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative This K23 application from a geriatric psychiatrist aims to explore the neurobiology of affective symptoms (AS) in behavioral variant frontotemporal dementia (bvFTD) with the goal of developing and testing targeted treatments for this devastating neurodegenerative disease. A Positron Emission Tomography (PET) study to measure glucose metabolism is proposed to measure changes in neural circuitry associated with AS in bvFTD. Treatment with a multi-modal antidepressant, Vortioxetine, is then employed to investigate changes in cerebral glucose metabolism in neural networks hypothesized to be associated with AS and cognitive changes in bvFTD (default mode network, salience network), offering insights into future neurobiologically targeted therapy for neuropsychiatric symptoms in bvFTD.

PI_NAMEs: MORROW, CHRISTOPHER B. (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Acceleration;Address;Affective Symptoms;Agitation;Alzheimer's Disease;anti-depressive agents;Anxiety;Area;Behavioral;behavioral variant frontotemporal dementia;Biological Markers;Brain;career development;Career Mobility;Caregiver Burden;Cerebrum;Cessation of life;Clinical;clinical investigation;Clinical Research;Cognition;cognitive change;Cognitive deficits;cohort;Data;Dedications;Dementia;design;Development;Development Plans;disability;Disease;Elderly;Executive Dysfunction;executive function;Family Caregiver;Frontotemporal Dementia;functional decline;Functional disorder;functional improvement;Future;glucose metabolism;Goals;Grant;High Prevalence;Image Analysis;Impaired cognition;improved;insight;Major Depressive Disorder;Measures;Mental Depression;Mental disorders;Mentored Patient-Oriented Research Career Development Award;Mentors;Metabolism;Methods;Mood Disorders;mood symptom;multimodality;Nature;Nerve Degeneration;neural circuit;neural correlate;neural network;Neurobehavioral Manifestations;Neurobiology;neurochemistry;Neurodegenerative Disorders;neuroimaging;neuropathology;neuropsychiatric symptom;neuropsychiatry;Neuropsychology;novel;Outcome;Patients;Positron-Emission Tomography;programs;psychiatric symptom;Psychiatrist;Quality of life;radiotracer;Research;Research Methodology;Research Personnel;Resources;Role;Selection for Treatments;Selective Serotonin Reuptake Inhibitor;senior faculty;Serotonergic System;Serotonin;serotonin receptor;serotonin transporter;skills;Statistical Data Interpretation;symptom cluster;Symptoms;Syndrome;targeted treatment;tau Proteins;Techniques;Testing;Time;Training;Variant;Work;Writing

PROJECT_TITLE: Serotonin Modulation of Neural Circuitry in bvFTD: Understanding the Neurobiology of Mood and Cognitive Symptoms

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


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

ORG_DEPT: PHARMACOLOGY

ORG_NAME: EMORY UNIVERSITY

PHR: Narrative Alzheimer’s disease is associated with a substantial medical and societal burden, but no small molecule therapy that alters the disease progression is currently available. Several studies including our own indicate that prostaglandin-E2 receptor EP2 is associated with exacerbation of inflammation and neurodegenerative pathology and cognitive deficits in rodent models of Alzheimer’s disease. We propose to develop an EP2 inhibitor with an overall goal to suppress neuropathology and cognitive deficits in mouse models and eventually in human patients with Alzheimer’s disease.

PI_NAMEs: GANESH, THOTA  (contact);HONORE, TAGE

PROGRAM_OFFICER_NAME: REFOLO, LORENZO

PROJECT_TERMS: Acute;Acute Brain Injuries;Age Months;age related;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapy;American;Amyloid;Amyloid beta-Protein;Animal Model;antagonist;arm;Attenuated;Biological Availability;Biological Markers;Blood;Brain;brain tissue;Bypass;Canis familiaris;Cardiovascular system;CCL2 gene;Cerebrospinal Fluid;Characteristics;Chronic;Clinical;Clinical Drug Development;Cognition;Cognitive deficits;Complex;Congo Red;cost;cyclooxygenase 2;cytokine;Data;Dementia;Development;Dinoprostone;Disease;Disease Progression;Dose;drug candidate;drug development;drug discovery;Drug Kinetics;early onset;Early Onset Alzheimer Disease;efficacy study;Elderly;Epilepsy;Event;first-in-human;Formulation;frailty;Future;Genes;Goals;Grant;Hippocampus;Human;Immune response;Impaired cognition;Impairment;indexing;Inflammation;Inflammatory;inhibitor;Interleukin-1 beta;Interleukin-6;Late Onset Alzheimer Disease;Lead;lead candidate;Light;Medical;Methods;Microglia;Modeling;Motor;mouse model;Mus;Neocortex;Nerve Degeneration;Neurodegenerative Disorders;neurofilament;neuroinflammation;neuropathology;new therapeutic target;No-Observed-Adverse-Effect Level;novel;object recognition;Oral;Parkinson Disease;Pathology;Peripheral;Permeability;Pharmaceutical Preparations;Pharmacology;Phase;Phenotype;Plasma;Play;Positron-Emission Tomography;pre-clinical;pre-Investigational New Drug meeting;Preclinical Testing;prevent;Process;programs;prophylactic;Prostaglandins;Radial;Rattus;receptor;Receptor Activation;Regimen;research clinical testing;response;Risk;Rodent;Rodent Model;Role;Safety;Sampling;Senile Plaques;Sepsis;sex;Signal Transduction;small molecule;small molecule therapeutics;Status Epilepticus;Structure-Activity Relationship;tau Proteins;Testing;Therapeutic;Therapeutic Agents;Therapeutic Index;therapeutically effective;TNF gene;Toxicology;Transgenic Organisms;uptake;Water;Work

PROJECT_TITLE: Development of EP2 Receptor Antagonist to Treat Alzheimer's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-J (M3)]


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Cerebrovascular;Clinical Research;Disability Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Stroke

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Project Narrative With endovascular stroke therapy, we now can rapidly recanalize the occluded vessel that is causing stroke; however, only about half the patients that receive this treatment have a good neurological outcome. The goal of our proposal is to better understand this population that does not benefit by organizing them into different categories based on etiology of their persistent dysfunction. We will then generate models that use machine learning to predict who those patients might be, so that we could target treatments specific to the etiology of their dysfunction.

PI_NAMEs: ORTEGA-GUTIERREZ, SANTIAGO ;SHETH, SUNIL  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;Address;Affect;Aftercare;Age;algorithm development;Algorithms;Angiography;Architecture;Area;Blood Pressure;Categories;Cerebrum;Chronic disability;Classification;Clinical;Clinical Data;clinical decision support;Clinical Trials;cohort;comorbidity;Coupled;Custom;Data;Data Set;deep learning algorithm;deep learning model;disability;Disability outcome;Early identification;effective therapy;Effectiveness;Etiology;follow-up;Foundations;Functional disorder;Future;Goals;Hemorrhage;Heterogeneity;high risk;Hospitals;Hour;Image;imaging modality;improved;Infarction;Injury;Intervention;Intracranial Hemorrhages;Ischemia;Ischemic Stroke;Learning;Left;Location;Long term disability;Machine Learning;machine learning algorithm;machine learning model;Magnetic Resonance Imaging;Measurement;Measures;Methods;Microvascular Dysfunction;Modeling;Neurological outcome;novel;Outcome;patient subsets;Patients;Performance;Perfusion;persistent symptom;Population;Population Heterogeneity;Pre-Clinical Model;predict clinical outcome;Procedures;prognostication;Race;Recording of previous events;Recovery;Reperfusion Therapy;Resolution;response;revascularization;Risk;risk prediction;Role;role model;Running;sex;standard of care;Stroke;stroke therapy;support tools;System;Techniques;Testing;Thrombectomy;thrombolysis;Time;Tissues;tool;Training;United States;Work

PROJECT_TITLE: Addressing the paradox of poor outcomes despite successful recanalization in stroke

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


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

ORG_NAME: TEXAS HEART INSTITUTE

PHR: PROJECT NARRATIVE Heart attacks result in permanent loss of cardiac muscle cells, leading to increased morbidity and mortality with limited treatment options. To regenerate cardiac muscle cells, special populations of fibroblasts and immune cells are required, yet their precise functions and contributions to cardiac renewal are not well understood. In support of the NIH mission to promote better treatment and prevention strategies, my research project will elucidate the interplay between these non- muscle cells and the cardiac muscle cells, which may lead to novel therapeutics promoting cardiac renewal.

PI_NAMEs: LI, RICH GANG  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Address;Adult;aerobic glycolysis;Affect;biological adaptation to stress;Biological Assay;Birth;Blood flow;C3AR1 gene;Cardiac;Cardiac Myocytes;cardiac repair;Cardiovascular system;career;Cause of Death;Cell Communication;Cell Cycle;Cell Cycle Progression;cell growth regulation;Cell Physiology;Cell Proliferation;cell type;Cells;Cessation of life;comparison control;Complement;Complement 3;Complement 3a;Complement Activation;complement pathway;complement system;Data;Development;Environment;Extracellular Matrix;factor C;Fibroblasts;gene complementation;Genes;Genetic Transcription;Glycolysis;Glycolysis Induction;Goals;Growth Factor;Heart;Heart failure;heart function;Heart Injuries;heart metabolism;Heart Transplantation;IGF1 gene;Immune;Impairment;improved;in vivo;in vivo Model;insight;Insulin;Knock-out;Macrophage;Mediating;Metabolic;Metabolic stress;Metabolism;Metalloproteases;Mission;Modeling;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Infarction;Myocardial Ischemia;Natural Immunity;Natural regeneration;Neonatal;novel;novel therapeutics;Operative Surgical Procedures;Organ;overexpression;Oxidative Phosphorylation;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Play;Prevention strategy;Procedures;programs;Proliferating;Property;Proteins;Proteomics;receptor;regenerative;repaired;Reporter;Research;Research Personnel;Research Project Grants;response;response to injury;Role;Sarcomeres;Signal Transduction;single-cell RNA sequencing;Special Population;Therapeutic;Time;Tissues;tool;transcription factor;transcriptomics;treatment strategy;United States National Institutes of Health;Work

PROJECT_TITLE: Complement in the cellular microenvironment during cardiac renewal

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI (MA)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Project Narrative Clostridioides difficile is a toxin producing pathogen that causes life-threatening diarrhea in hospitalized patients undergoing antibiotic therapy. Chondroitin sulfate proteoglycan 4 (CSPG4) is the most critical host receptor for these toxins and eliminating CSPG4 provides protection from C. difficile disease. Our work has connected Hippo signaling to CSPG4 expression and then used a drug targeting Hippo signaling to downregulate CSPG4 and prevent C. difficile disease in a mouse model.

PI_NAMEs: LARABEE, JASON  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: anti-toxin;Antibiotic Therapy;Bacterial Toxins;Binding;Blocking Antibodies;Cecum;Cell Surface Receptors;Cells;Chondroitin Sulfate Proteoglycan;Clinical;Clostridioides difficile vaccine;Clostridium difficile;Colon;cytotoxicity;Data;design;Diarrhea;Disease;Dose;Drug Targeting;Effectiveness;Epidemic;Exhibits;experimental study;Exposure to;Foundations;glycosylation;Hospitalization;In Vitro;in vivo;Infection;Intoxication;Laboratories;Life;Malignant Neoplasms;mouse model;Mus;Mutagens;mutant;novel strategies;pathogen;Pathogenesis;pathogenic bacteria;pathogenic microbe;Pathology;Pathway interactions;Patients;Pattern;Pericytes;Phase;Phase III Clinical Trials;Population;prevent;Publishing;receptor;receptor binding;receptor expression;Recurrence;Recurrent disease;Research;Resistance;response;Signal Pathway;Signal Repression;Signal Transduction;small molecule inhibitor;Stains;success;System;Testing;Therapeutic;therapeutic effectiveness;therapeutic target;Time;Tissues;Toxin;treatment strategy;Vaccines;Work

PROJECT_TITLE: Targeting chondroitin sulfate proteoglycan 4 (CSPG4) expression as a Clostridioides difficile therapeutic

STUDY_SECTION: BHI

STUDY_SECTION_NAME: Bacterial-Host Interactions Study Section [BHI]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Physical Injury - Accidents and Adverse Effects;Wound Healing and Care

ORG_CITY: SAINT LOUIS

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative  Ammonia exposure causes the most severe chemical burns to the ocular surface. In this proposal, we will correlate the degradation of corneal sensory fibers by ammonia exposure with the impairment of corneal wound healing, which further leads to chronic corneal erosion and ulceration. Results from the proposed studies will fill the major gaps in our knowledge about the neuro-regulatory mechanism underlying corneal injuries by ammonia, and offer a new therapeutic strategy for ocular pain and injuries by ammonia.

PI_NAMEs: HUANG, ANDREW J.W. (contact);LIU, QIN

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: afferent nerve;Afferent Neurons;Ammonia;Attenuated;Axon;Behavioral;behavioral study;Blindness;Calcium;Cells;Chemical Agents;Chemical Burns;Chemical Injury;Chemical Models;Chronic;Cornea;corneal burn;corneal epithelial wound healing;corneal epithelium;Corneal Injury;Corneal pain;Corneal Ulcer;Denervation;Epithelial Cells;experimental study;Exposure to;Eye;Eye Injuries;Fiber;Gases;Genetic;Human;Image;Impairment;Inflammation;Injury;intense pain;Ion Channel;Knowledge;Light;limbal;Link;Mediating;Monitor;mouse model;Mus;Natural regeneration;Nerve;Nerve Degeneration;neural;neuromechanism;Neurons;novel;novel therapeutic intervention;ocular pain;ocular surface;Pain;Perforation;pharmacologic;Phase;prevent;Research;response;Role;Sensory;stem cells;Testing;Therapeutic;Time;Tissues;transcriptomics;Ulcer;wound healing

PROJECT_TITLE: Neural mechanism underlying corneal injuries by ammonia

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

ORG_CITY: LAWRENCE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: PROJECT NARRATIVE The development of new chemotherapeutic approaches for the treatment of infectious disease is, by acclamation, one of the preeminent challenges of modern biomedical science. This Phase II proposal is designed to strengthen and enhance the investments and infrastructure established in Phase I for the Center for Chemical Biology of Infectious Diseases. The CBID Center will continue to address critical gaps and enable researchers at the University of Kansas (KU) and associated institutions to apply these tools to better understand and potentially prevent infectious diseases.

PI_NAMEs: HEFTY, P SCOTT (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Address;Animals;Area;base;Biological;Biological Models;Biology;Centers of Research Excellence;Chemicals;Chemistry;Chemotherapy-Oncologic Procedure;Collaborations;Communicable Diseases;Communities;Core Facility;Coupled;design;Development;drug discovery;Education and Outreach;effective therapy;expectation;experience;Faculty;high throughput screening;Infectious Agent;infectious disease treatment;Infrastructure;innovation;Institution;Intervention;Investments;Kansas;member;Mentors;Mentorship;Metabolic;Microbiology;Modernization;multidisciplinary;novel;Organism;Pathway interactions;Pharmaceutical Chemistry;Pharmacologic Substance;Pharmacology;Phase;Pilot Projects;prevent;Principal Investigator;Process;professor;programs;Proteomics;Public Health;recruit;Research;research facility;Research Personnel;Research Project Grants;Resistance;Resources;Science;Scientist;Series;success;Therapeutic;tool;United States National Institutes of Health;Universities;Validation;Work

PROJECT_TITLE: Determining the metabolic capacity of Sneathia vaginalis


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: ORLANDO

ORG_NAME: ADVENTHEALTH ORLANDO

PHR: Narrative The microbial species that reside in the colon are important for many aspects of human health, including energy balance, which is important for managing body weight. In this project, we will extend the findings from a completed randomized crossover trial, which showed that under the very controlled conditions of a domiciled controlled feeding study, the gut microbiome plays a role in how much energy (calories) from the diet people excrete via fecal energy loss. We will interrogate samples from that study to quantify how many additional calories are excreted because of growth of the gut microbiome and which microbial functions contribute to fecal energy loss and therefore energy balance.

PI_NAMEs: CORBIN, KAREN DAVIDOWITZ (contact);SMITH, STEVEN RICHARD;ZENGLER, KARSTEN B

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: absorption;Archives;Automobile Driving;Bioenergetics;Biomass;Body Weight;Body Weight decreased;Calories;Cell Count;Clinical Research;Colon;colon microbiota;Consumption;Cross-Over Trials;Data;design;Development;Diet;dietary;Dietary Component;Dietary Intervention;Disease;Domiciles;Eating;energy balance;Energy Intake;Enhancers;Excretory function;Expenditure;experimental study;Exposure to;feeding;Food;Fractionation;Future;Goals;Growth;gut microbiome;gut microbiota;Health;host-microbe interactions;Human;improved;in vivo;Individual;Inpatients;Intervention;Knowledge;Link;Literature;Measurement;Medical;Metagenomics;Microbe;microbial;microbial community;microbiome;microbiome alteration;microbiota;multiple omics;novel;Nutritional;Obesity;Obesity Epidemic;Observational Study;Outcome;Persons;Phenotype;Play;Population;precision nutrition;preference;Process;programs;Proteome;Public Health;Randomized;Regulation;Role;Route;Sampling;Sampling Studies;stool sample;targeted treatment;Testing;transcriptomics;treatment optimization;weight maintenance;Weight maintenance regimen;western diet;Work

PROJECT_TITLE: Defining the Quantitative Functional Mechanisms that Underly Gut Microbiome-Diet Interactions Contributing to Human Energy Balance

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Atherosclerosis;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Nutrition;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: HERSHEY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative The total number of people with cognitive impairment and dementia including Alzheimer’s disease (AD) is expected to rise exponentially with a fast pace of population aging, placing enormous social and economic burden worldwide. Epidemiologic and pathological studies have indicated an association between vascular diseases and cognitive dysfunction, implicating vascular contributions to cognitive impairment and dementia (VCID), but the driving pathologic mechanisms of VCID remain unclear, halting the development of effective prevention and treatments. This proposal aims to investigate the mechanisms of cognitive impairment caused by atherosclerosis, the leading cause of vascular disease worldwide, and facilitate the identification of therapeutic target and early intervention for VCID.

PI_NAMEs: BAGCHI, PROSENJIT ;HE, PINGNIAN  (contact);KIM, YONGSOO

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: 3-Dimensional;Age;aging population;Alzheimer's Disease;Animal Model;Aorta;Apolipoprotein E;Arterial Fatty Streak;Arteries;Atherosclerosis;Automobile Driving;behavior test;Blood Cells;Blood flow;blood perfusion;Blood Vessels;Brain;Brain imaging;Carotid Arteries;cerebral hemodynamics;cerebrovascular;Cerebrovascular Circulation;cerebrovascular pathology;Cerebrum;Cholesterol;chromatin immunoprecipitation;Cognitive;Cognitive deficits;cognitive function;Computer Simulation;cytokine;Dementia;Development;Diet;Disease;Early Intervention;Early treatment;Economic Burden;Endothelial Cells;Epidemiology;Erythrocytes;experimental study;Fluorescence Microscopy;Functional disorder;Goals;hemodynamics;High Fat Diet;Human;human subject;hypercholesterolemia;hypoperfusion;Image;imaging platform;Impaired cognition;Impairment;in silico;In Vitro;in vivo;Inflammation;Inflammatory;insight;interest;intracranial artery;Knowledge;lifestyle intervention;Light;Maps;Measures;Memory impairment;mouse model;Mouse Strains;multidisciplinary;multimodality;Mus;neuroinflammation;neurovascular;Pathologic;Perfusion;Peripheral;Permeability;Persons;Plasma;Play;Predisposition;Prevalence;prevent;Prevention;Research;Resolution;response;Risk Factors;Role;Same-sex;Sampling;shear stress;Signal Transduction;social;Stimulus;Testing;therapeutic target;Time;ultrasound;United States National Institutes of Health;vascular cognitive impairment and dementia;Vascular Diseases;Vascular Endothelial Cell;vascular inflammation;Vascular remodeling

PROJECT_TITLE: Mechanisms of cognitive impairment caused by atherosclerosis and red blood cell released ATP

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Tissue factor (TF) is the primary initiator of blood coagulation, so the production of TF must be carefully controlled to prevent thrombotic diseases including venous thromboembolism, heart attack, and stroke. This proposal seeks to comprehensively investigate mechanisms regulating how cells turn on or off the production of TF, and how these processes are disrupted by human genetic variation. These studies suggest that genetic variation in the gene for TF may impact blood clotting in humans and contribute to bleeding or thrombotic disease.

PI_NAMEs: SCHULMAN, SOL  (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: 3' Untranslated Regions;Age;Binding;Binding Sites;Biochemical;Biological Assay;Biological Markers;blind;Blood coagulation;Blood Coagulation Factor;Blood Coagulation Factor VII;Blood Vessels;Cell surface;cell type;Cells;ChIP-seq;Clinical;Coagulation Process;Code;cohort;Computing Methodologies;Conserved Sequence;Data;dosage;Elements;Endothelium;Ensure;Epithelial Cells;Epithelium;F3 gene;Factor VIIa;Factor X;Fibrin fragment D;Genes;Genetic;genetic architecture;Genetic Code;Genetic Polymorphism;Genetic Screening;genetic testing;Genetic Transcription;Genetic Variation;genome wide association study;Genotype;GLIS2 gene;Half-Life;Hemorrhage;Hemostatic Agents;Hemostatic function;Heterozygote;Human;human disease;Human Genetics;human tissue;Individual;Inherited;Injury;lens;Libraries;Link;loss of function;Malignant Neoplasms;Maps;Mediating;Mendelian randomization;Messenger RNA;MicroRNAs;Missense Mutation;mRNA Expression;mRNA Stability;Mus;Myelogenous;Myocardial Infarction;nonhuman primate;novel therapeutics;null mutation;Pathogenesis;Pathogenicity;Pathologic;Patients;Peripheral arterial disease;Phenotype;Plasma;Population;prevent;Process;Production;promoter;Promoter Regions;Proteins;Quantitative Trait Loci;Regulation;Resistance;Risk;Role;Single Nucleotide Polymorphism;Small Interfering RNA;Specific qualifier value;Stroke;Thrombophilia;Thromboplastin;Thrombosis;thrombotic;Tissues;Transcription Coactivator;transcription factor;Transcription Repressor;Untranslated Regions;Variant;venous thromboembolism;Zebrafish

PROJECT_TITLE: Genetic architecture of tissue factor expression

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Aphasia;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Disability Research;Neurosciences;Rehabilitation;Stroke

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: Narrative Post-stroke aphasia is a significant public health problem whose symptoms depend on the stroke lesion and on the status of the surrounding brain tissue. Stroke survivors are at risk for premature brain aging and this project will evaluate the mechanistic relationship between brain tissue aging, aphasia severity and recovery.

PI_NAMEs: BONILHA, LEONARDO F (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Acceleration;Accounting;Affect;Age;age related;age related neurodegeneration;Aging;aging brain;Anatomy;Aphasia;aphasia recovery;Area;Atrophic;Behavioral;Brain;brain based;Brain Injuries;Brain region;brain tissue;cardiovascular risk factor;cerebral atrophy;Characteristics;Chronic;chronic stroke;Chronology;Clinical;Cognition;Cognitive;cohort;Communication;Compensation;connectome;Data;Data Set;Databases;Diabetes Mellitus;Education;Educational Background;Elderly;Elements;Functional Magnetic Resonance Imaging;General Population;Habits;healthy aging;Hypertension;improved;in vivo;Individual;Injury;Injury compensation;innovation;insight;Interdisciplinary Study;Knowledge;Language;Language Disorders;language impairment;language processing;Lesion;Linguistics;Link;Longitudinal cohort;Machine Learning;Measurable;Measures;Mediation;Mental Depression;Methods;Modeling;Multilingualism;multimodal neuroimaging;multimodality;neuroimaging;Neurology;Neurosciences;non-verbal;novel;Outcome;Persons;Positioning Attribute;post stroke;post stroke cognitive impairment;Predisposition;premature;prevent;prospective;protective effect;Public Health;Publishing;Quality of life;Recovery;recruit;Research;Residual state;resilience;Risk;Severities;social;Social isolation;South Carolina;Stream;Stroke;stroke survivor;stroke-induced aphasia;Structure;Symptoms;System;Testing;Tissues;Treatment outcome;Universities

PROJECT_TITLE: Brain Age in Aphasia

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


ORG_CITY: LOUISVILLE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: The objective of this study is to validate an innovative concept that the unique dual TC14012 protects against doxorubicin-induced cardiotoxicity (DICT) by activating cardiac CXCR7 to reprogram cardiomyocyte metabolism and prevent cardiac dysfunction and by antagonizing CXCR4 to inhibit cardiac mast cell infiltration and activation in multiple mouse models. We will first optimize the doses of TC14012 for protecting against DICT in two tumor-free and tumor-bearing mouse models, and then we will determine its direct effects and mechanisms on energy reserve metabolism and mitochondrial function in cardiomyocytes and on cardiac mast cell infiltration and degranulation. This project will reveal new insight into the underlying mechanisms behind and provide fundamental evidence for TC14012 as a novel approach for the prevention of DICT in future clinical studies.

PI_NAMEs: TAN, YI  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: adenoviral mediated;Affect;Affinity;Agonist;antagonist;Binding;Cancer Survivor;Cardiac;cardiac angiogenesis;Cardiac Myocytes;cardiac regeneration;Cardiometabolic Disease;cardioprotection;Cardiotonic Agents;Cardiotoxicity;Cardiovascular Diseases;Cardiovascular system;Cell Death;cell mediated immune response;Cells;chemokine receptor;chemotherapy;clinical application;Clinical Research;clinically relevant;CXCR;CXCR4 gene;CXCR4 Receptors;Development;Dexrazoxane;Disease;Dose;Down-Regulation;Doxorubicin;Etiology;FDA approved;Fibrosis;Functional disorder;Future;Genetic Transcription;Glucans;Glycogen;Health;Heart;heart defect;Heart failure;heart function;heart metabolism;Heart Septal Defects;Heterozygote;Immune;Immune response;Immunocompetent;improved;Infarction;Infiltration;Inflammation;Inflammatory;Injury;innovation;insight;Knockout Mice;Lymphoma;Malignant Neoplasms;mast cell;Mediating;Metabolism;Mitochondria;mouse model;Mus;Myocardial;Myocardial dysfunction;Myocardial Infarction;myocardial injury;Myocarditis;Myocardium;neovascularization;novel strategies;overexpression;Pathologic;Pathway interactions;Performance;Perinatal mortality demographics;Pharmaceutical Preparations;Play;postnatal;prevent;Prevention approach;programs;protective effect;Refractory;Role;sensor;Series;side effect;Signal Transduction;single-cell RNA sequencing;Site;stem cells;Stromal Cell-Derived Factor 1;Testing;Therapeutic;treatment strategy;tumor;tumor growth;tumorigenesis;Up-Regulation

PROJECT_TITLE: Dual targeting chemokine receptors prevents chemotherapy-induced cardiotoxicity

STUDY_SECTION: MPPA

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE The first allele-specific KRAS inhibitors were recently approved in lung adenocarcinoma (LUAD), but clinical benefit is limited by intrinsic and acquired resistance. We hypothesize resistance to KRAS inhibitors is driven by cancer cell differentiation into AT1-like or squamous states, which is determined by LKB1 proficiency or deficiency, respectively. Here, we interrogate the function and molecular drivers of the AT1-like and squamous transition states, which we hope would lead to new therapeutic strategies overcoming resistance to KRAS inhibitors in LUAD patients.

PI_NAMEs: TAMMELA, TUOMAS ;WONG, KWOK KIN  (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Ablation;Address;Adenocarcinoma Cell;Adopted;Alleles;Alveolar;Automobile Driving;bioluminescence imaging;cancer cell;cancer cell differentiation;Candidate Disease Gene;Cell Differentiation process;Cells;Clinic;Clinical;Complementary DNA;CRISPR/Cas technology;Detection;Epigenetic Process;Event;Exhibits;experimental study;Flow Cytometry;gain of function;Genetic;Genetic Transcription;Genetically Engineered Mouse;Genotype;Growth;Histologic;Human;Immunocompetent;improved;In Situ;in vivo;inhibitor;K-ras mouse model;Knock-out;KRAS2 gene;KRASG12D;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Malignant Squamous Cell Neoplasm;Measures;Messenger RNA;Modeling;Molecular;mortality;Mus;mutant;Mutation;novel;novel therapeutic intervention;Organoids;Outcome;overexpression;patient derived xenograft model;Patients;Pharmaceutical Preparations;Population;programs;protein biomarkers;Relapse;Reporting;Resistance;resistance mechanism;Resolution;response;Sampling;self renewing cell;single-cell RNA sequencing;small hairpin RNA;specific biomarkers;Squamous Cell;Squamous Differentiation;stem cells;STK11 gene;suicide gene;System;targeted treatment;therapy resistant;Tissues;TP53 gene;treatment response;tumor;tumor growth;Tumor Suppressor Proteins;tumor-immune system interactions;Withholding Treatment;Work;Xenograft procedure

PROJECT_TITLE: Targeting cell state transitions driving resistance to KRAS inhibitors in lung cancer

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative We propose a class of porosity-based silicon heterojunctions for minimally invasive, multi-site, leadless, non- genetic, and optoelectronic modulation of the heart. These studies will accelerate progress in understanding and treating abnormalities in the electrical conduction systems of the heart in vivo.

PI_NAMEs: HIBINO, NARUTOSHI ;TIAN, BOZHI  (contact)

PROGRAM_OFFICER_NAME: FALCONE, JESSICA

PROJECT_TERMS: 3-Dimensional;Acceleration;Acute;Adult;Anatomy;atomic layer deposition;Behavior;bioelectricity;Biological;biomaterial compatibility;Biotechnology;Blood Vessels;Cardiac;Cardiac conduction system;Cardiac pacemaker;cardiac pacing;cardiac resynchronization therapy;Cardiovascular Diagnostic Techniques;Cardiovascular system;catalyst;Catheters;Cells;Chemistry;Chronic;Computer software;congenital heart abnormality;Cultured Cells;design;Device Removal;Devices;efficacy evaluation;Electronics;Engineering;Failure;Femur;flexibility;follow-up;Heart;Heart failure;heart rhythm;Hydrogels;Implant;improved;in vivo;in vivo Model;instrument;Investigation;Laceration;Lead;Light;light intensity;Location;Longevity;Measures;Mechanics;Membrane;metal oxide;Metals;Methods;minimally invasive;Modeling;Modification;Monitor;Myocardium;Nanoporous;non-genetic;Operative Surgical Procedures;optical fiber;Optical Methods;Optics;optogenetics;Output;Pacemakers;Patients;Perforation;Performance;Physiological;Polymers;porcine model;Porosity;Positioning Attribute;Power Sources;pre-clinical;Precision therapeutics;Procedures;Property;Publishing;Rattus;Research;Risk;Rodent Model;Scanning;Semiconductors;Signal Transduction;Silicon;Site;Structure;subcutaneous;Surface;Surgical incisions;System;Techniques;Testing;Texture;Therapeutic;Tissues;Titania;tool;Venous;Ventricular;wireless;Work

PROJECT_TITLE: Multi-site photostimulation devices using porosity-based semiconductor heterojunctions for cardiac resynchronization therapy

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Bioengineering;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Nanotechnology

ORG_CITY: MILWAUKEE

ORG_NAME: VERSITI WISCONSIN, INC.

ORG_STATE: WI

PHR: PROJECT NARRATIVE Integrins are a large family of cell surface molecules involved in the progression of many diseases, including thrombosis, inflammation, cancer, and virus infection, and thus are potential therapeutic targets. This project proposes to address issues critical to understanding the emerging functions of integrins in the formation of the cellular structure tunneling nanotubes and the inflammatory response in the diseases such as COVID-19.

PI_NAMEs: ZHU, JIEQING  (contact)

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: 2019-nCoV;Actins;Address;angiogenesis;Antibodies;Attenuated;Binding;Binding Proteins;Binding Sites;Biochemical;Biogenesis;Biological Assay;Biology;Biophysics;Blood Cells;Cell Adhesion;Cell Adhesion Molecules;Cell Communication;Cell Line;Cell membrane;Cell model;Cell Physiology;Cell Proliferation;Cell surface;Cell Surface Extensions;Cell Surface Receptors;Cell Survival;cell type;Cells;Cellular biology;Cellular Stress;Cellular Structures;Chemicals;Comparative Study;Coronavirus spike protein;COVID-19;COVID-19 pathogenesis;crosslink;cytokine;Cytoplasm;Cytoplasmic Tail;Data;design and construction;Development;Disease;Electron Microscopy;Endothelial Cells;Event;Extracellular Matrix;Family;Fibronectin Receptors;Human;Immune response;Infection;Inflammation;Inflammatory;Inflammatory Response;innovation;Integrin alpha Chains;Integrin alpha5beta1;Integrin beta Chains;Integrin Binding;Integrins;intercellular communication;intercellular connection;Interleukin-1 beta;Interleukin-6;ITGA5 gene;Knock-out;knockout gene;Label;Lead;Ligand Binding;Ligands;light scattering;Lung;Macrophage;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Membrane;migration;Mitochondria;Molecular;Molecular Conformation;Molecular Sieve Chromatography;Mutagenesis;nanobodies;Nanotubes;Neurodegenerative Disorders;neutrophil;novel;Outcome Study;pathogenic bacteria;pathogenic virus;Pathologic;Pathway interactions;Phase;phosphodiesterase 4D;Physiological;Play;Process;protein purification;Proteins;receptor binding;Receptor Signaling;Regulation;Research;Resources;RGD (sequence);Role;SARS-CoV-2 spike protein;Signal Induction;Signal Pathway;Signal Transduction;Signaling Molecule;small molecule;Solid;stem cell differentiation;structural biology;Subcellular structure;therapeutic target;Thrombosis;thrombotic;tissue regeneration;tissue repair;transmission process;Umbilical vein;Vascular Endothelial Cell;Vesicle;Virus;Virus Diseases

PROJECT_TITLE: Non-conventional signaling by α5 integrin in blood and endothelial cells


NIH_SPENDING_CATS: Biotechnology;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DREXEL UNIVERSITY

PHR: The threat of disease and death due to Plasmodium falciparum and Plasmodium vivax malaria parasites remains for nearly half of the world’s population. The emerging mRNA vaccine platform has potential to address key challenges encountered in the development of malaria vaccines. This project focuses on the evaluation of mRNA technology for delivery of a malaria vaccine designed to elicit diverse responses against multiple parasite stages.

PI_NAMEs: BURNS, JAMES MATTHEW (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Address;Adjuvant;Advanced Development;Antibodies;Antibody titer measurement;Antigens;Area;Automobile Driving;Binding;Binding Proteins;Blocking Antibodies;Blood;burden of illness;C-terminal;Carrier Proteins;CD8-Positive T-Lymphocytes;cell mediated immune response;Cells;Cessation of life;Child;circumsporozoite protein;Clinical;COVID-19 pandemic;Data;design;Development;Disease;Epitopes;Erythrocytes;Evaluation;experience;Formulation;Foundations;Germ Cells;Hepatocyte;Homologous Protein;human subject;Immune response;Immunization;immunogenic;immunogenicity;Impairment;improved;Individual;International;Invaded;Left;Liver;Malaria;Malaria prevention;Malaria Vaccines;Mammalian Cell;Mediating;merozoite surface protein;Merozoite Surface Protein 1;Messenger RNA;Modification;N-terminal;Nature;neutralizing antibody;novel;Parasites;pathogenic virus;Pharmacotherapy;Plasmodium;Plasmodium falciparum;Plasmodium yoelii;Polyvalent Vaccine;Population;Predisposition;Production;programs;protein protein interaction;rapid diagnosis;Recombinants;Reporting;Research;response;Reticulocytes;RNA vaccine;Safety;Sporozoites;Subunit Vaccines;success;T cell response;Technology;Tertiary Protein Structure;Testing;Therapeutic;Time;tool;Trefoil Motif;Vaccine Antigen;vaccine candidate;Vaccine Design;vaccine development;vaccine platform;vaccine-induced immunity;Vaccines;vector control;vector mosquito;Vivax Malaria;Work

PROJECT_TITLE: Multivalent mRNA-based malaria vaccines

STUDY_SECTION: VID

STUDY_SECTION_NAME: Vaccines Against Infectious Diseases Study Section[VID]


ORG_CITY: Chicago

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: NARRATIVE The proposed research is relevant to public health because peripheral T-cell lymphomas are diagnosed in approximately 10,000 individuals in the U.S. annually. More than 70% will relapse after initial chemotherapy, and no current standardized therapies are at the relapse stage. This proposal aims to determine the relevance of novel actionable targets in T-cell lymphomas and is relevant to the NIH’s goal to foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health.

PI_NAMEs: MURGA-ZAMALLOA, CARLOS A. (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Actins;Automobile Driving;Biological Markers;Biology;biomarker identification;Cell Line;Chemoresistance;chemotherapy;chromatin immunoprecipitation;Clinical;Clinical Data;cohort;Complex;Creativeness;Cytoskeleton;Cytotoxic agent;Data;Development;Diagnosis;Disease;Disease Progression;Disease-Free Survival;Fostering;Future;Gene Expression Profile;genetic regulatory protein;Genetic Transcription;Genetically Engineered Mouse;Geography;Goals;Growth;Growth and Development function;Health;Heterogeneity;Histologic;HMGB1 gene;Immunohistochemistry;improved;in vivo;Individual;innovation;International;Knowledge;Ligands;loss of function;Macrophage;Malignant Neoplasms;Mediating;Mission;Molecular;molecular marker;mouse model;novel;novel therapeutic intervention;novel therapeutics;Oncogenic;Outcome;patient derived xenograft model;Patients;Peripheral;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiological;Play;prognostic;prognostic algorithm;Proliferating;protein activation;Proteins;Public Health;Relapse;Research;Resistance;response;Role;Sampling;scaffold;Secondary to;sensor;Serum;Signal Transduction;Signaling Protein;Solid;Specimen;Standardization;Stress;superresolution microscopy;T-Cell Lymphoma;TANK-binding kinase 1;Testing;Therapeutic;transcription factor;treatment response;tumor growth;tumor microenvironment;United States National Institutes of Health;Up-Regulation;Wiskott-Aldrich syndrome protein

PROJECT_TITLE: WASp signaling in T-cell lymphomas

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: PROJECT NARRATIVE This project will advance our understanding of how deep crypt secretory cells, an essential component of the colonic epithelium, respond during injury and inflammation to promote intestinal health. The results from these studies may provide insight into novel therapeutic targets for diseases impacting the colonic mucosa.

PI_NAMEs: SCHUMACHER, MICHAEL ANDREW (contact)

PROGRAM_OFFICER_NAME: SENGER, STEFANIA

PROJECT_TERMS: Ablation;Acute;Agonist;Apoptosis;base;Biology;Cell Count;Cell Differentiation process;Cell Lineage;Cell Physiology;Cells;Chronic;Coculture Techniques;Colitis;Colon;colonic crypt;Colonic Diseases;Colonic inflammation;Data;Dendritic Cells;design;Diphtheria Toxin;Disease;DsRed;Elements;Epidermal Growth Factor Receptor;Epithelial Cells;Epithelium;Future;Gene Expression Profile;gut inflammation;healing;Health;Host Defense;Immune;Immune signaling;Immunity;immunoregulation;Impairment;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Injury;insight;Interleukin-13;Intestines;Intrinsic factor;Investigation;Knockout Mice;Macrophage;Mediating;Modeling;Mucous Membrane;Mus;neutrophil;new therapeutic target;novel;Organoids;Pathologic;Pathway interactions;PIK3CG gene;Population;Population Sizes;Proliferating;receptor;Receptor Signaling;Recovery;Regulation;repaired;Research;Resolution;response;Role;Secretory Cell;Shapes;Signal Transduction;single-cell RNA sequencing;stem cell niche;T-Lymphocyte;targeted treatment;Testing;therapeutic target;tissue regeneration;tissue repair;Tissues;Work;wound healing

PROJECT_TITLE: Activation of deep crypt secretory cells in colonic inflammation

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Heart Disease;Pediatric;Pediatric Cardiomyopathy;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: TUFTS MEDICAL CENTER

PHR: Narrative Analyses of humans with enlarged hearts and heart failure have identified FHOD3 as a gene that influences the age when someone develops hypertrophic cardiomyopathy. The collaborative research proposed here will determine how FHOD3 gene variants influence the heart’s response to stress leading to heart failure in humans. By defining how heart cells respond to stress, these studies will provide new insights into how the heart can fail and could lead to new strategies to prevent heart disease.

PI_NAMEs: CHEN, HOWARD H.;HUGGINS, GORDON S (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Actins;Address;Adult;adverse outcome;Affect;Age;age effect;aged;Alleles;American;Animal Model;Aorta;associated symptom;Automobile Driving;Autophagocytosis;biobank;Cardiac;cardiac muscle disease;Cardiac Myocytes;cardiogenesis;Cardiomegaly;Cardiomyopathies;Cell Physiology;Clinical;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Cytoskeleton;Data;Defect;Development;Diagnosis;Embryonic Heart;Ethnic Origin;Excretory function;experience;extracellular;extracellular vesicles;fetal;FHOD3 gene;Gene Mutation;Genes;Genetic;Genetic Risk;genetic variant;Genotype;Goals;Heart;Heart Abnormalities;heart cell;heart dimension/size;heart disease prevention;Heart failure;heart function;Heart Hypertrophy;Human;Human Genetics;human induced pluripotent stem cells;Hypertrophic Cardiomyopathy;Hypertrophy;Image;Imaging technology;Impairment;improved;induced pluripotent stem cell derived cardiomyocytes;inhibitor;innovation;insight;Left Ventricular Remodeling;Lysosomes;Mediating;member;Microfilaments;Mitochondria;mitochondrial dysfunction;Modification;Monitor;mouse model;Mus;mutant;Mutation;myosin-binding protein C;nanoparticle;Nonmuscle Myosin Type IIA;novel;Operative Surgical Procedures;Organelles;Pathway interactions;patient population;Patients;personalized medicine;Persons;Phenotype;Physiological;Plasma;Population;pressure;Prevalence;Production;programs;Protein Family;Proteins;Race;Recombinant Proteins;Regulation;Research;Resources;response;risk variant;Role;Sampling;Sarcomeres;Sirolimus;Stimulus;Stress;Symptoms;tat Protein;Testing;Therapeutic;Time;Tissues;trafficking;Transgenes;Transgenic Mice;Translating;Troponin;Variant;Vesicle

PROJECT_TITLE: FHOD3 Regulation of Autophagy Pathway in Cardiomyopathy

STUDY_SECTION: BBHV

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Nanotechnology;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

PHR: PROJECT NARRATIVE Addressing immunodominance in the humoral response has the potential to advance the development of truly universal influenza vaccines. This project is relevant to public health because it aims to elucidate the fundamental mechanisms through which prolonged and targeted stimulation a toll-like receptor, facilitated by adjuvant formulation, can overcome immunodominance and broaden the antibody response to an influenza antigen. These insights will not only pave the way for future clinical trials involving similar adjuvants but also hold promise for uncovering innovative strategies to support universal vaccine development. 1

PI_NAMEs: LUO, WEI  (contact)

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: Address;Adjuvant;Advanced Development;Affect;Agonist;aluminum sulfate;Antibodies;Antibody Response;Antigen-Presenting Cells;Antigens;Autoantibodies;Autoimmune;B-Lymphocytes;Biology;cell type;Cessation of life;Clinical Trials;Development;draining lymph node;empowerment;Environment;Epitopes;Exhibits;flu;Formulation;Future;Generations;Genetic Models;Goals;Head;Health;Hemagglutinin;improved;Influenza;Influenza Hemagglutinin;influenza virus strain;influenza virus vaccine;influenzavirus;innovation;insight;Knowledge;Link;Memory;Memory B-Lymphocyte;Mus;nanoparticle;pathogen;Pathway interactions;Persons;Plasma;Plasma Cells;Process;Public Health;rational design;recruit;Regulation;Regulatory T-Lymphocyte;Research;Research Proposals;response;seasonal influenza;Shapes;Signal Transduction;spatiotemporal;stem;Structure of germinal center of lymph node;Testing;TLR7 gene;Toll-like receptors;universal influenza vaccine;universal vaccine;Vaccination;Vaccine Adjuvant;vaccine development;vaccine effectiveness;vaccine safety;vaccine strategy;Variant;Viral;Virus;Work

PROJECT_TITLE: Overcome immunodominance to support the development of universal influenza vaccines

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Health Services;Heart Disease;Patient Safety;Physical Rehabilitation;Rehabilitation

ORG_CITY: PROVIDENCE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE Although many older adults require rehabilitation in skilled nursing facilities (SNFs) following a hospitalization for heart failure, research on how medications enhance or interfere with rehabilitation is scarce. This project will rigorously examine the effects of using individual medications for heart failure and other common conditions (e.g., pain) as well as using multiple medications together on physical function and successful discharge from SNFs to home. Findings from this project will 1) inform prescribing and deprescribing interventions to sustain optimal physical function following a hospitalization for heart failure and 2) open new frontiers in aging and heart failure research by establishing a novel data resource that can be re-used to conduct previously impossible medication-related studies in SNFs.

PI_NAMEs: GOYAL, PARAG ;ZULLO, ANDREW REIS (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Activities of Daily Living;acute care;Address;Adrenergic beta-Antagonists;Aging;Analgesics;Back;care systems;Cessation of life;Clinical;Clinical assessments;Clinical Trials;Cognition;Custodial Care;Data;data resource;Data Set;Databases;Dementia;Dose;Drug Prescriptions;Dyspnea;Elderly;Electronic Health Record;Etiology;experience;frailty;Fright;frontier;functional decline;Functional impairment;functional independence;Future;Geriatrics;Goals;Health care facility;Heart failure;Heterogeneity;Home;Home Nursing Care;hospital readmission;Hospitalization;Hypotension;Impairment;improved;Individual;inhibitor;innovation;Intervention;Knowledge;large datasets;Measures;Mediator;Medicare claim;medication administration;Medication Management;Methodology;Methods;mortality;multiple chronic conditions;National Institute on Aging;novel;Nursing Homes;Observational Study;Occupational Therapy;older adult;Outcome;Pain;Patient Discharge;Patient Participation;Patient-Focused Outcomes;Patients;Pattern;Performance;Pharmaceutical Preparations;Pharmacy facility;Physical Function;Physical therapy;Polypharmacy;Population;Publishing;Records;Recovery of Function;Rehabilitation therapy;Renin-Angiotensin System;Research;Risk;Series;Skilled Nursing Facilities;Subgroup;Testing;Time;Veterans Health Administration

PROJECT_TITLE: Post-Acute Care Medication Use and Functional Recovery in Heart Failure

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Hematology;Human Genome;Rare Diseases;Women's Health Research

ORG_CITY: DAVIS

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative  DNA repair by homologous recombination (HR) is a fundamental biological process necessary for the maintenance of chromosomal integrity. The failure to maintain genomic integrity is a major source of predisposition to cancer. The research in this proposal will focus on molecular events essential for chromosomal maintenance by homologous recombination which, when defective, is known to result in predisposition to cancers, and also to hematological malignancies, bone marrow failure, and developmental abnormalities in Fanconi’s anemia.

PI_NAMEs: KOWALCZYKOWSKI, STEPHEN CHARLES (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: Affect;Behavior;Biochemical;Biological Process;Bone marrow failure;BRCA2 gene;BRCA2 Protein;cancer predisposition;Chromosomal Instability;Chromosomes;Clinical;Defect;Development;Disease;DNA;DNA Repair;Event;Failure;Fanconi's Anemia;Filament;Genes;Genome;genome integrity;Growth;Hematologic Neoplasms;homologous recombination;Human;Individual;Maintenance;Malignant Neoplasms;Mediating;Methods;Molecular;molecular imaging;mutant;Mutation;novel;PALB2 gene;paralogous gene;patient population;Predisposition;protein function;protein purification;Proteins;RAD51C gene;Reaction;reconstitution;Research;Role;single molecule;Single-Stranded DNA;Source;Tumor Suppression;Tumor Suppressor Proteins;Visualization;XRCC2 gene;XRCC3 gene

PROJECT_TITLE: Molecular Functions of BRCA2 and RAD51 Paralogs in Homologous Recombination and Chromosome Maintenance

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

PHR: PROJECT NARRATIVE Despite the advent of combination antiretroviral therapy, people with HIV (PWH) suffer from an accelerated development of cardiovascular disease, which drastically reduces their life expectancy. Despite this knowledge, the mechanisms predisposing PWH to high blood pressure, the leading risk factor for cardiovascular disease remain ill-defined and unstudied. The proposed study will combine the use of novel genetically engineered animal models, human specimens, and cultured endothelial cells with pharmacological approaches to test whether HIV derived proteins accelerate cardiovascular aging via inducing hypertension.

PI_NAMEs: BELIN DE CHANTEMELE, ERIC J (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Acceleration;Adoptive Transfer;Affect;age acceleration;Aging;AIDS prevention;AIDS-Related Disorder;Animal Model;Antibodies;antiretroviral therapy;Aorta;arterial stiffness;Blood Pressure;blood pressure control;Blood Vessels;Bone Marrow Transplantation;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cause of Death;CD4 Positive T Lymphocytes;Cessation of life;Chronic;Circulation;Clinic;Clinical Trials;Coculture Techniques;Data;Development;Disease;early onset;Endothelial Cells;endothelial dysfunction;Endothelium;Exhibits;exposed human population;Exposure to;Female;Genetic;Genetic Engineering;Genetic Transcription;HIV;HIV tat Protein;Homologous Gene;Human;Hypertension;Impairment;improved;in vivo;Incubated;Individual;Inflammation;Infusion procedures;inhibitor;Interleukins;Knowledge;Life Expectancy;Lymphocyte Activation;male;Mediating;men;Microglia;Molecular;mouse model;Mus;NADPH Oxidase;neuroinflammation;neutralizing antibody;new therapeutic target;novel;novel therapeutics;Outcome;pathological aging;Persons;pharmacologic;Phenotype;premature;Premature aging syndrome;prevent;Production;Proteins;Relaxation;Reporting;Role;senescence;senolytics;Specimen;Sympathetic Nervous System;System;T-Lymphocyte;tat Protein;Testing;Therapeutic;Vascular Diseases;Vascular Endothelial Cell;Viral Proteins;Viral reservoir;Viremia;Wild Type Mouse;Woman

PROJECT_TITLE: Mechanisms of HIV-associated Hypertension

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


NIH_SPENDING_CATS: Genetics;Lung;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Cilia motility is essential for airway clearance and is powered by a large motor called the dynein arm. Defective dynein arm is responsible for primary ciliary dyskinesia (PCD), a genetic disease characterized by mucus impaction, recurrent sinopulmonary infections and accelerated decline of lung function. This project focuses on an early step in building dynein arms and is highly relevant to PCD.

PI_NAMEs: SUN, ZHAOXIA  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acceleration;Address;arm;Biochemical;Biogenesis;Biology;Candidate Disease Gene;Cell Culture System;cell motility;Cell Physiology;Cells;Cellular biology;Cellular Membrane;Chronic lung disease;Cilia;ciliopathy;cilium biogenesis;cilium motility;Complex;Crowding;Cytosol;Data;Defect;Developmental Process;Disease;Dynein ATPase;Environment;Epithelial Cells;Etiology;experimental study;Extracellular Fluid;Fertility;fluid flow;Foundations;Future;Genes;Genetic;Genetic Diseases;Genetic study;Goals;Health;Human;Human Genetics;Individual;Infection;insight;Intervention;Investigation;Knock-in Mouse;Knowledge;Left;Liquid substance;Lung Diseases;Membrane;Messenger RNA;Modeling;Molecular;Molecular Chaperones;Monitor;Motility;Motor;mouse genetics;mouse model;Mucous body substance;Mus;mutant;novel;Organelles;Patients;Periodicity;Phase;Physical condensation;Physiological;Play;prevent;Primary Ciliary Dyskinesias;Process;Production;protein complex;protein structure;Proteins;Publishing;pulmonary function decline;Reagent;Recurrence;Regulation;Research;Respiratory Failure;Ribosomes;RNA;Role;Shapes;Speed;symptom management;Testing;Therapeutic Intervention;Trachea;Translating;Translations;Zebrafish

PROJECT_TITLE: Function of Ruvbl1-Ruvbl2 in dynein arm assembly in motile ciliated epithelial cells

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Infectious Diseases

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Narrative Pathogenic fungi are leading causes of corneal ulcers, resulting in corneal blindness and vision loss in the USA and worldwide. Risk factors are contact lens associated corneal abrasions and ocular trauma. Once the corneal barriers are compromised, fungal spores can enter the corneal stroma where they germinate, and hyphae penetrate throughout the cornea. Immune cells called neutrophils rapidly infiltrate the cornea to kill these invasive fungi, but these cells also cause tissue damage that contribute to the clinical symptoms associated with this infection. Experiments in this proposal will characterize the molecular events leading to neutrophil mediated fungal killing in corneal infections, and will identify potential molecular targets for therapeutic intervention.

PI_NAMEs: PEARLMAN, ERIC  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Adoptive Transfer;Affect;Amphotericin B;Aspergillus;Aspergillus fumigatus;associated symptom;Blindness;Candida;Candida albicans;Caspase;Cataract;Cell Adhesion Molecules;Cell surface;Cells;Clinical;Contact Lenses;Cornea;Corneal Abrasion;Corneal Diseases;Corneal Stroma;Corneal Ulcer;cytokine;Data;Developed Countries;Developing Countries;Dichloromethylene Diphosphonate;Epithelium;Event;experimental study;extracellular;Eye Injuries;Fibrosis;Fungal Spores;fungus;Fusarium;Genetic Transcription;Germination;Growth;Human;Hyphae;Immune;Immune Targeting;immunological intervention;Impairment;India;Infection;Infiltration;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Intercellular adhesion molecule 1;Interleukin-1 beta;intravital imaging;intravital microscopy;Keratitis;Lead;Liposomes;Mediating;Mediator;Molecular;molecular targeted therapies;monocyte;mouse model;multi-photon;Mus;Myeloid Cells;neutrophil;Neutrophil Activation;Neutrophil Infiltration;novel;Operative Surgical Procedures;pathogen;Pathogenesis;pathogenic fungus;Pathway interactions;Patients;Penetration;peripheral blood;Phagocytosis;pharmacologic;Plants;Population;Production;Protons;PTPRC gene;Reactive Oxygen Species;recruit;Reporter;Reporting;Reproduction spores;response;Risk Factors;Role;selective expression;Severity of illness;single-cell RNA sequencing;Site;small molecule inhibitor;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;transcriptome sequencing;Trauma;VDAC1 gene;Work;Yeasts

PROJECT_TITLE: The role of monocytes and neutrophils in fungal keratitis

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]