NIH_SPENDING_CATS: Chronic Pain;Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Pain Research;Pediatric;Peripheral Neuropathy;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Familial dysautonomia (FD) is a rare neuropathy caused by a splicing mutation in ELP1 gene that leads to variable tissue-specific skipping of exon 20. This mutation reduces the amount of ELP1 protein which is critical for the development and maintenance of specific neurons. The goal of this proposal is to identify the cell-type- specific gene network disruption caused by ELP1 loss and use spatial transcriptomics as well as patient-derived neuronal models to characterize the molecular mechanisms underlying specific neuronal degeneration in FD.

PI_NAMEs: MORINI, ELISABETTA ;SLAUGENHAUPT, SUSAN A (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Acetyltransferase;Affect;Afferent Neurons;Area;autonomic neuropathy;Cell Physiology;cell type;Cells;Central Nervous System;Clinical;Complex;Congenital Neuropathy;Data;debilitating symptom;Development;Disease;Disease Progression;Evaluation;exon skipping;Familial Dysautonomia;Foundations;Gait Ataxia;Gene Expression;Gene Expression Regulation;gene network;Genes;Genetic;Goals;Human;human disease;human model;humanized mouse;Impairment;In Situ;induced pluripotent stem cell;innovation;Intrinsic drive;Laboratories;Link;Maintenance;Modeling;Molecular;mouse model;Mus;mutant;Mutation;Nerve Degeneration;Nervous System;Nervous System Disorder;Neurobiology;Neurologic;neuron loss;Neurons;Neuropathy;Nociceptors;Pain;Pathogenesis;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Perception;Peripheral;Peripheral Nervous System;Pharmaceutical Preparations;Phenotype;Population;Proprioception;Proprioceptor;Protein Subunits;Proteins;Regulation;Resolution;Retina;Retinal Degeneration;Retinal Ganglion Cells;RNA Splicing;Role;Sensory;sensory neuropathy;single-cell RNA sequencing;stretch reflex;Structure of trigeminal ganglion;System;Temperature;Tissues;tool;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Work

PROJECT_TITLE: Understanding neuronal cell type-specific dysregulation in familial dysautonomia

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: DC

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurosciences;Rare Diseases;Usher Syndrome

ORG_CITY: PORTLAND

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTOLARYNGOLOGY

ORG_FIPS: US

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative: Public Health Relevance Hearing loss is a major health problem that significantly affects the life quality of affected individuals. Many forms of hearing loss are genetic in origin and affect hair cells, the mechanosensors that convert sound induced vibrations into electrical signals. We propose here to show how the critical mechanosensitive structure of the hair cell is assembled, and how specific genes control that assembly; this information may eventually help guide therapeutic approaches leading to hearing restoration.

PI_NAMEs: BARR-GILLESPIE, PETER GORDON (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Abbreviations;Actins;Address;Affect;Age;Apical;Auditory;base;C57BL/6 Mouse;Cadherins;Calibration;Categories;CDH23 gene;cell type;Cells;Chick;Cochlea;Complement;Complex;conditional knockout;Coupled;Cytoskeleton;Data;Data Set;deafness;Defect;depolymerization;Development;Dimensions;Electron Microscopy;Embryo;Embryonic Development;equilibration disorder;experimental study;Filament;Freeze Substitution;Freezing;Genes;genetic approach;Goals;Growth;Hair;hair cell regeneration;Hair Cells;Health;hearing impairment;Hearing problem;hearing restoration;Height;hereditary hearing loss;Image;Individual;Inner Hair Cells;interest;Kinocilium;Knock-out;Laboratories;Length;Lighting;Link;link protein;Location;Measurement;Measures;Mechanics;mechanotransduction;Mediating;Microscopy;Modeling;Molecular Motors;Motor;mouse genetics;Mouse Protein;Mus;Mutant Strains Mice;Mutation;MYO7A gene;Outer Hair Cells;Pathway interactions;Pattern;PCDH15 gene;Persons;Phase;polymerization;Polymers;Positioning Attribute;postnatal;postnatal development;Preparation;pressure;Process;Proteins;public health relevance;Publishing;Quality of life;Regulation;Role;Sampling;Scanning Electron Microscopy;Scheme;Sensory Hair;Set protein;Shapes;Signal Transduction;sound;Structure;success;superresolution imaging;Surface;Syndrome;Therapeutic;Transmission Electron Microscopy;Vestibular Diseases;Vestibular dysfunction;vibration;Visualization;Width;Work

PROJECT_TITLE: Hair Bundle Proteins

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: AI

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Digestive Diseases;Emerging Infectious Diseases;Gene Therapy;Genetics;Hematology;Infectious Diseases;Influenza;Lung;Pneumonia;Pneumonia and Influenza;Sepsis

ORG_CITY: GREER

ORG_NAME: NUBAD, LLC

ORG_STATE: SC

PHR: The work proposed here, a multidisciplinary effort encompassing organic synthesis, oligonucleotide delivery, RNA targeted screening and antibacterial studies, describes the development of sequence-specific cell permeable binders of rRNA as antibacterial therapeutics. The success of the proposed work would be a significant addition to currently available ribosome-specific approaches in broad spectrum antibacterial antibiotic development, in particular for targeting gram negative pathogens such as carbapenem-resistant Enterobacteriaceae (CRE). We propose using a small rRNA target sequences to design conjugates that can be employed to inhibit bacterial growth, opening possibilities for developing sequence-specific RNA targeted therapeutics.

PI_NAMEs: ARYA, DEV PRIYA (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Abdominal Infection;Address;Amides;Amino Sugars;Aminoglycosides;Anti-Bacterial Agents;anti-microbial drug;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;antimicrobial;Antimicrobial Resistance;antimicrobial resistant infection;Bacillus;Bacteria;Bacterial Infections;Bacterial Pneumonia;Bacterial Proteins;bacterial resistance;base;Binding;Biodistribution;Biological Assay;Biological Availability;Biology;Books;candidate identification;carbapenem-resistant Enterobacteriaceae;Cavia;Cell Wall;Cells;Cessation of life;Chemicals;Clinical;Colistin;combat;Communicable Diseases;Congresses;Coronavirus;cost;Coupled;COVID-19;COVID-19 mortality;Creativeness;Data;design;Development;Disease;Dose;Drug Design;drug development;Drug Interactions;Drug resistance;Drug Targeting;economic impact;efficacy study;Elements;Ensure;Enterobacteriaceae;Epidemic;Escherichia coli;Eukaryota;extensive drug resistance;Face;Family;fighting;Follow-Up Studies;Gram-Negative Bacteria;Growth;Health Care Costs;improved;In Vitro;in vivo;Infection;Influenza;Influenza A Virus, H1N1 Subtype;inhibitor;innovation;Institute of Medicine (U.S.);Intervention;Intra-abdominal;Klebsiella pneumoniae;Knowledge;L Forms;Lead;Left;Length of Stay;Libraries;Link;Locales;Lung Diseases;Lung infections;Malaria;Membrane;microbial;Microbial Biofilms;Modeling;mortality;Multi-Drug Resistance;multidisciplinary;Mus;Nosocomial Infections;novel;novel antibiotic class;novel therapeutic intervention;novel therapeutics;Nucleic Acid Binding;nucleic acid delivery;Nucleic Acids;oligonucleotide delivery;Oligonucleotides;Organic Synthesis;ototoxicity;pandemic influenza;pathogen;pathogenic bacteria;Pathogenicity;Patients;Peptide Nucleic Acids;Peptides;Permeability;Pharmaceutical Preparations;Phase;Pneumonia;pre-clinical;pre-Investigational New Drug meeting;preclinical study;Predisposition;prevent;priority pathogen;Prokaryotic Cells;Proliferating;Protein Biosynthesis;Protein Synthesis Inhibitors;Rapid screening;Rattus;Reporting;Research;Resistance;Resistance profile;Ribosomal RNA;Ribosomes;Risk;RNA;RNA Binding;RNA Sequences;RNA-targeting therapy;screening;Sepsis;Severe Acute Respiratory Syndrome;Severities;Societies;Solid;Specificity;Staphylococcal Infections;Structure;success;Superbug;Surgeon;synergism;Tail;targeted agent;Technology;Therapeutic;Thigh structure;tigecycline;Time;Tobramycin;Toxic effect;Translation Initiation;Tuberculosis;United States;United States National Academy of Sciences;uptake;Urinary tract infection;Viral;Work;World Health;World Health Organization

PROJECT_TITLE: Development of peptide nucleic acid antibiotics


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: MINNEAPOLIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Tick-borne Powassan virus (POWV) is an emerging public health threat, but has been understudied to date. Therefore, through this project, we will combine field and laboratory studies to evaluate whether there are regional, local, and even hyperlocal differences in the genetic structure of tick and POWV populations that affect patterns of POWV host/vector competence, virulence, and evolution.

PI_NAMEs: ALIOTA, MATTHEW T (contact);CIOTA, ALEXANDER TIMOTHY

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Address;Affect;arboviral disease;Biology;Black-legged Tick;Brain;Canada;Case Fatality Rates;Cell Line;Child;Clinical;Competence;Connecticut;cross-species transmission;Data;Deer;Disease;disease heterogeneity;disorder risk;Emerging Communicable Diseases;Encephalitis;Entomology;Europe;Evolution;field study;fitness;Flavivirus;Frequencies;Future;future outbreak;Genetic Structures;genetic variant;Genetic Variation;Genomics;Genotype;Geography;Goals;Health;Human;Human Bites;improved;In Vitro;Infection;Infectious disease threat;Infrastructure;Ixodes;Knowledge;Laboratories;Laboratory mice;Laboratory Study;Link;Metadata;Midwestern United States;Minnesota;Mus;National Institute of Allergy and Infectious Disease;Neurologic;New England;New York;Pathogenesis;Pattern;Phenotype;Phylogenetic Analysis;Population;Positioning Attribute;Powassan virus;pressure;Prevention;Public Health;Recording of previous events;Reporting;response;Risk;Russia;Sampling;Serology test;Specimen;Surveillance Program;Survivors;System;Tail;Testing;tick population;tick-borne;Tick-Borne Diseases;Tick-Borne Encephalitis Virus;tick-borne flavivirus;Ticks;transmission process;United States;United States National Institutes of Health;Variant;vector competence;vector tick;Viral;Viral Genome;viral genomics;viral transmission;virology;Virulence;Virus;virus genetics;White-Footed Mouse;Wisconsin

PROJECT_TITLE: Powassan virus evolution, fitness, and pathogenesis in the Northeast and Midwest United States

STUDY_SECTION: VDT

STUDY_SECTION_NAME: Viral Dynamics and Transmission Study Section [VDT]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: SHREVEPORT

ORG_DEPT: PHYSIOLOGY

ORG_NAME: LOUISIANA STATE UNIV HSC SHREVEPORT

ORG_STATE: LA

PHR: Project Narrative  Understanding the molecular links that control the intricate relationship between Neisseria gonorrhoeae and the cells of the innate immune system, in this case - the macrophages, is critical for novel therapy design against this highly antibiotic-resistant pathogen. The knowledge gained will provide important insight into how Neisseria manipulates the host receptors and actin polymerization machinery to invade and form a replicative niche and ultimately will aid in the design of more effective therapeutic strategies.

PI_NAMEs: DRAGOI, ANA-MARIA  (contact)

PROGRAM_OFFICER_NAME: VINCENT, LEAH REBECCA

PROJECT_TERMS: Actins;adaptive immune response;Address;Anus;Apoptosis;Automobile Driving;Bacteria;Bacterial Adhesins;Betaproteobacteria;Binding;Cell membrane;cell type;Cells;Cholesterol;Cicatrix;Cytoskeleton;Data;design;Development;Diffusion;Disease;Disease Outcome;DNA;drug resistant pathogen;Drug-resistant Neisseria Gonorrhoeae;Etiology;Event;Exudate;Filopodia;Frequencies;Genetic;Genitalia;Gonorrhea;Half-Life;Human;human data;Immune;Immune Evasion;Immunologics;immunopathology;Immunophenotyping;In Vitro;in vivo;Infection;Innate Immune Response;Innate Immune System;insight;Integration Host Factors;Invaded;Kinetics;Knowledge;Link;Macrophage;Mammalian Oviducts;Mediating;Membrane;Microscopy;Modeling;Molecular;Morbidity - disease rate;mortality;Mucosal Immunity;Mucous Membrane;Nasopharynx;Neisseria;Neisseria gonorrhoeae;neutrophil;novel therapeutics;Outcome;pathogen;Pathogenesis;Pelvic Inflammatory Disease;Phagocytes;Phagocytosis;Phenotype;polymerization;Polymers;Production;Public Health;receptor;recruit;reproductive tract;response;Role;Route;Sampling;Sampling Studies;Sexually Transmitted Diseases;Site;Surface;symptomatology;Testing;therapeutically effective;therapy design;therapy development;uptake;vaccine development;Vaginal Douching;Woman;Work

PROJECT_TITLE: Mechanism of macrophages colonization in gonorrhea

STUDY_SECTION: BHI

STUDY_SECTION_NAME: Bacterial-Host Interactions Study Section [BHI]


ADMINISTERING_IC: EY

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL EYE INSTITUTE

ORG_CITY: ANN ARBOR

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: NARRATIVE – OVERALL (Parent Project) The University of Michigan Vision Research Center provides state-of-the-art equipment and technical expertise and service for scientists at the University of Michigan to advance research programs into understanding the visual system and to develop novel therapies to treat blinding eye disease and improve the visual health of the country.

PI_NAMEs: ANTONETTI, DAVID  (contact)

PROGRAM_OFFICER_NAME: GOVER, TONY DOUGLAS

PROJECT_TERMS: Acceleration;Animal Technicians;Animals;Basic Science;Biochemistry;Biometry;Clinical;Clinical Research;Collaborations;Complex;Core Grant;Country;data integrity;Dedications;design;design and construction;Developmental Biology;Disease;Electronics;Electrophysiology (science);Engineering;Environment;Equipment;Evaluation;eye center;Eye diseases;Fluorescence Microscopy;Fostering;Goals;Grant;Health;Human;Human Resources;Image;Image Analysis;Immunology;improved;innovation;instrument;instrumentation;interest;Laboratory Animals;Laboratory Technicians;Light;Mechanics;Michigan;Microscopy;Molecular Biology;Molecular Genetics;Morphology;Neurobiology;novel therapeutics;ocular imaging;Ophthalmology;parent project;Patients;prevent;Productivity;programs;repaired;Research;Research Personnel;Resources;Scientist;Services;skills;square foot;stem cell biology;Structure;Technical Expertise;tissue processing;Universities;Vision;vision development;Vision research;vision science;Visual;Visual System


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Cancer;Liver Disease;Rare Diseases;Substance Misuse

ORG_CITY: KANSAS CITY

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative Alcohol abuse and consumption are major causes of chronic liver disease and is a major health problem in the United States without successful treatment. Alcohol consumption induces hepatic mitochondrial morphological and metabolic changes as adaptive responses to attenuate alcohol toxicity, but mitochondria become maladaptive during the chronic course of alcohol consumption. Elucidating the molecular mechanisms of how alcohol-induced mitochondrial dynamic morphological changes on mitochondrial function and mitochondria- mediated innate immune response in the pathogenesis of alcohol-associated liver disease and cancer will help to develop novel therapeutic strategies to treat alcohol-associated liver disease.

PI_NAMEs: DING, WEN-XING  (contact)

PROGRAM_OFFICER_NAME: GAO, PETER

PROJECT_TERMS: Acute;Adenosine Monophosphate;Alcohol abuse;Alcohol consumption;Alcohol dehydrogenase;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;aldehyde dehydrogenases;Apoptosis;Apoptotic;Attenuated;BAX gene;Binding;Bioenergetics;Cell Death;Cells;Chimeric Proteins;Chronic;chronic liver disease;Cirrhosis;Clinical;Cyclic GMP;cytochrome c;Data;Development;Dynamin;Ethanol Metabolism;Ethanol toxicity;Fatty Acids;feeding;Gene Activation;Genes;Goals;Guanosine Triphosphate Phosphohydrolases;Health;Hepatic;Hepatitis;Hepatocarcinogenesis;Homeostasis;Human;Impairment;improved;Inflammation;Inflammatory Response;Innate Immune Response;Inner mitochondrial membrane;Knockout Mice;Lead;Liver;Liver diseases;Liver Fibrosis;liver inflammation;liver injury;Liver Mitochondria;Liver neoplasms;liver repair;Malignant neoplasm of liver;Mediating;Metabolic;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Molecular;Morphology;Mus;NADH;Names;Natural regeneration;Nicotinamide adenine dinucleotide;novel;novel therapeutic intervention;novel therapeutics;Optic atrophy 1;Outcome;oxidation;Oxidative Stress;Pathogenesis;Pathway interactions;Patients;Periodicity;Primary carcinoma of the liver cells;Production;Proteins;Quality Control;Rattus;Respiration;response;restraint;Role;Sterility;Stimulator of Interferon Genes;Stress;tumorigenesis;United States

PROJECT_TITLE: Mechanisms of mitochondrial dynamics, quality control and mtDNA-mediated inflammation in alcohol-associated liver disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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);Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hearing Loss;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Rehabilitation

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Our project addresses the high prevalence of Alzheimer's disease and related dementias (ADRD) in the U.S. Hispanic population, with a particular focus on the impact of low language acculturation and hearing loss. We aim to investigate how language acculturation may factors interact and affect cognitive decline among Hispanic adults, leveraging data from the HCHS/SOL study. Our findings will inform public health strategies and interventions to mitigate cognitive decline risks in this vulnerable population.

PI_NAMEs: MARTINEZ AMEZCUA, PABLO  (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Acceleration;Acculturation;Address;Adult;Affect;age group;aged;Aging;aging population;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Ancillary Study;Awareness;Brain;brain health;brain magnetic resonance imaging;cardiometabolism;Chicago;Cities;Cognition;Cognitive;cognitive function;cognitive testing;cohort;Communication Barriers;Communities;community organizations;Community Outreach;Data;dementia risk;Early Intervention;Education;effective intervention;English Language;Family;Health;health care service;Health Personnel;Hearing;Hearing Aids;hearing impairment;High Prevalence;high risk;Hispanic;hispanic community;Hispanic Community Health Study/Study of Latinos;Hispanic Populations;human old age (65+);Impaired cognition;Improve Access;Intervention;Language;late life;Linguistics;Link;loss of function;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measures;metabolic abnormality assessment;middle age;Mind;modifiable risk;Modification;MRI Scans;Neurocognitive;neuroimaging;neuroimaging marker;neuropathology;Not Hispanic or Latino;oral communication;Outcome;outreach program;Participant;Pathway interactions;Personal Satisfaction;PET/CT scan;Population;Prevalence;prevent;Proxy;Public Health;Randomized, Controlled Trials;Research;research study;Risk;Risk Factors;Role;Sampling;social communication;social engagement;Spanish;Structure;Support System;Temporal Lobe;Testing;United States;Universities;Visit;Vulnerable Populations;Work;β-amyloid burden

PROJECT_TITLE: The role of language acculturation in the hearing loss-cognition association among Hispanics in the US

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-9 (M1)]


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

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

ORG_STATE: WA

PHR: Alzheimer’s disease is the 7th leading cause of death in the United States and the most common cause of dementia; however, there are still no clinically-approved treatments that cure or reverse this disease. Aberrant tau protein causes neuronal dysfunction and neurodegeneration seen in Alzheimer’s disease and multiple other dementias but the mechanism in which it does so is not completely understood. This project aims to deepen our understanding of the mechanisms of tau-induced neurodegeneration, which is key to developing new therapeutic strategies to target dementias like Alzheimer’s disease.

PI_NAMEs: KOW, REBECCA LIANG (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease related dementia;Amino Acids;Animal Model;Behavioral;Binding;brain tissue;C-terminal;Caenorhabditis elegans;Cause of Death;Cell model;Cells;Clinical;Dementia;Development;Disease;EZH2 gene;FHA Domain;Frontotemporal Dementia;gain of function;Genes;Genetic;genetic analysis;Genetic Epistasis;Genetic Screening;Genetic Transcription;Goals;Healthcare;Homologous Gene;Human;Knowledge;loss of function;loss of function mutation;Mammals;Mediating;Mediator;Memory impairment;Messenger RNA;Modeling;Molecular;mouse model;Mus;mutant;Mutation;N-terminal;Names;Nerve Degeneration;Neurodegenerative Disorders;Neuronal Dysfunction;Neurons;novel;novel therapeutic intervention;Nuclear;Outcome;overexpression;Pathologic;Pathology;Phenotype;Phosphoric Monoester Hydrolases;Population;Prevalence;protein function;Protein Kinase;Protein phosphatase;protein phosphatase inhibitor-1;Protein Truncation;Proteins;Regulation;RNA Binding;RNA Recognition Motif;RNA Splicing;tau aggregation;tau expression;tau Proteins;Tauopathies;Tertiary Protein Structure;Therapeutic;Toxic effect;Transgenic Mice;Transgenic Organisms;Translating;translational impact;United States

PROJECT_TITLE: Investigating how SUT-6/NIPP1 regulates pathological tau

STUDY_SECTION: CMND

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


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Nutrition;Prevention;Sleep Research

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE Cancer-related fatigue affects the majority of patients with blood cancer and can persist long into survivorship, thereby preventing people from returning to work, family roles, and hobbies, and reducing quality of life. This study will evaluate the ability of a 12-week time-restricted eating program (10-hour eating window during the day, fasting 14 hours at night) to reduce persistent fatigue, as well as shed light on relationships between a person’s internal body clock, sugar metabolism, and fatigue. If effective, time-restricted eating would be a safe, low-cost, widely accessible treatment that could revolutionize management fatigue among blood cancer survivors.

PI_NAMEs: KLECKNER, AMBER SIMMONS (contact)

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: Accelerometer;Address;Adherence;Affect;Aftercare;arm;Attention;Baltimore;Beverages;Biological Clocks;Blood Glucose;blood glucose regulation;Cancer Control;Cancer Survivor;chemotherapy;Chemotherapy and/or radiation;circadian;Circadian Dysregulation;Circadian Rhythms;Clinical;Cognitive Therapy;Complement;Consumption;Continuous Glucose Monitor;cost;Counseling;curative treatments;Darkness;Data;Data Collection;Dietary Practices;Dimensions;Disabling;Eating;effective therapy;Eligibility Determination;Endocrine;Ensure;Equipment and supply inventories;ethnic diversity;Etiology;Exercise;Family;Fasting;fasting glucose;Fatigue;feeding;follow-up;Food;food consumption;Functional disorder;Glucose;glucose metabolism;group intervention;Guidelines;Hematologic Neoplasms;Hematopoietic Neoplasms;Hobbies;Home;Homeostasis;Hour;improved;innovation;insight;Insulin;interstitial;Intervention;intervention delivery;Light;Maintenance;Malignant Neoplasms;Maryland;Measures;Metabolic;Metabolism;Minority Groups;Mitochondria;molecular scale;Multi-Institutional Clinical Trial;Neurons;novel;nutrition;Nutritionist;Participant;Patients;Pattern;Persons;Phase;phase 2 study;Physiological;Placebo Effect;Population;Population Heterogeneity;Population Sciences;post intervention;prevent;programs;Quality of life;racial diversity;Radiation;Randomized;Randomized, Controlled Trials;recruit;Regulation;Reporting;response;Rest;Role;Severities;shift work;side effect;Site;Sleep;sleep pattern;smartphone application;Spanish/English;stem;sugar;Survivors;survivorship;Symptoms;System;Testing;theories;Therapeutic;Time;Time-restricted feeding;Toxic effect;Treatment-Related Cancer;trial comparing;willingness;Work;Wrist

PROJECT_TITLE: Time-restricted eating to address cancer-related fatigue among survivors of hematological malignancies

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Immunotherapy;Networking and Information Technology R&D (NITRD)

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative Comprehensive bioinformatic analysis and multi-omics data integration is an essential part of a wide variety of cancer-related studies such as biomarker discovery for cancer immunotherapy or the role of epigenetics in cancer-specific regulation. This application is aimed to support the development of state of the art bioinformatics analysis pipelines through my role as principal data scientist and bioinformatics manager of The Experimental and Computational Genomics Core in the Sidney Kimmel Comprehensive Cancer Center. The support of the R50 award will enable broader access of comprehensive bioinformatic expertise provided by the Experimental and Computational Genomics Core for diverse cancer-related studies by members of the Sidney Kimmel Comprehensive Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the Convergence Institute at Johns Hopkins.

PI_NAMEs: DANILOVA, LUDMILA  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: analysis pipeline;anti-cancer research;Area;Award;Bioinformatics;Biological Assay;biomarker discovery;Cancer Center;cancer immunotherapy;cancer type;Cells;Clinical;Collaborations;Comprehensive Cancer Center;Data;Data Analyses;data integration;Data Scientist;Development;DNA Methylation;Epigenetic Process;Future;Genomics;Immunotherapy;Informatics;innovation;Malignant Neoplasms;member;Methods;Multiomic Data;multiple omics;Outcome;Play;programs;Regulation;Research;Research Activity;Research Personnel;Role;Services;Software Tools;T cell receptor repertoire sequencing;T-Lymphocyte;Techniques;Technology;The Cancer Genome Atlas;Training;tumor;tumor microenvironment;Universities;Work

PROJECT_TITLE: Comprehensive Analysis and Multi-Omics Data Integration for Cancer-Related Studies

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M2)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Heart failure caused by dilated cardiomyopathy remains irreversible, with a mortality of up to 50% within five years, despite the best available therapies. The proposed translational study investigates the newly discovered role of Factor XIIa as a stimulator of overt heart failure in dilated cardiomyopathy. This project has high clinical relevance for developing new therapeutic strategies needed to reduce mortality from heart failure.

PI_NAMEs: GLADYSHEVA, INNA P (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Adverse effects;Aldosterone;Arrhythmia;attenuation;Biological Markers;Blinded;Blood Pressure;Blood Vessels;Body fat;Cachexia;Cardiac;Cardiac Edema;Cardiovascular system;Cause of Death;Cessation of life;Chronic;Circulation;Clinical;clinically relevant;Coagulation Process;congenic breeding;Crossbreeding;Data;Development;Dilated Cardiomyopathy;disability;Edema;Endogenous Factors;Enzymatic Biochemistry;Enzyme Precursors;experimental group;Factor XIIa;Gene Modified;Generations;Genetic;Heart;Heart failure;heart failure with reduced ejection fraction;heart function;Homeostasis;Hospitalization;Human;human disease;In Vitro;in vivo;in vivo Model;Inactive Renin;insight;Intervention;kidney dysfunction;Knockout Mice;Measures;Mediating;Modeling;Molecular;Molecular Target;mortality;mouse model;Mus;Myocardial;Myocardial dysfunction;normotensive;novel;novel strategies;novel therapeutic intervention;Observational Study;Outcome;Pathogenesis;Pathologic;Pathway interactions;Patients;Peptide Hydrolases;Physiological;Plasma;prevent;Randomized;Renin;Renin-Angiotensin-Aldosterone System;Reproducibility;Role;Serine Protease;Sodium Chloride;System;Testing;Thinness;Time;tool;translational study;Treatment Failure;Water

PROJECT_TITLE: Factor XIIa is the long-sought activator of circulating renin in heart failure.

STUDY_SECTION: TDPS

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Behavioral and Social Science;Chronic Pain;Genetics;Neurosciences;Pain Research;Prevention

ORG_DEPT: ANESTHESIOLOGY

PHR: PROJECT NARRATIVE Chronic back pain is a leading cause of disability worldwide and is frequently caused by damage to the inter- vertebral discs in the spine. The objective of this application is to determine the role of epigenetic mechanisms, which regulate tissue health without changing the genomic code, in painful disc damage. These studies may reveal new approaches for the treatment of low back pain.

PI_NAMEs: STONE, LAURA S (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;age acceleration;age related;Animal Model;Anxiety;Area;Attenuated;Automobile Driving;Behavior;Behavioral;Blood;Central Nervous System;Chronic;chronic back pain;Chronic low back pain;chronic pain;Code;Data;demethylation;Development;disability;Disease;DNA Methylation;Donor person;Epigenetic Process;Exposure to;Extracellular Matrix;functional improvement;Gene Expression;Gene Expression Profile;Genes;Genetic Models;Genetic Transcription;Genomics;Goals;Growth Factor;Health;Health Care Rationing;health care service utilization;health economics;Height;Histology;Home;Homeostasis;Human;improved;in vivo;in vivo Model;indexing;Individual;Inflammation;Inflammatory;Injury;innovation;Intervention;Intervertebral disc structure;intervertebral disk degeneration;irritation;Knowledge;knowledge base;Life Style;Link;Low Back Pain;Magnetic Resonance Imaging;Maintenance;Malignant Neoplasms;Mechanics;Medical;Mental Depression;Methylation;Modeling;Modification;mouse model;Mus;nerve supply;novel;novel therapeutic intervention;Operative Surgical Procedures;opioid misuse;Pain;Pain Attribute;pain outcome;Pathologic;Pathology;Pathway interactions;Patients;pharmacologic;Physical activity;polygenic risk score;prescription opioid;prevent;Prevention;Process;programs;protein expression;Publishing;Quality of life;Research;response;Rodent;Rodent Model;Role;Running;secondary analysis;Secondary to;Security;Services;Signal Transduction;Spinal;Spinal nerve structure;Structure;targeted treatment;Therapeutic;Tissues;Validation;Vertebral column

PROJECT_TITLE: Epigenetic Drivers of Chronic Low Back Pain

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Genetics;Human Genome;Pediatric

ORG_CITY: LOS ANGELES

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE COngenital Diarrhea and Enteropathy (CoDE) are rare monogenic disorders that are under-researched and associated with enormous management costs and adverse life-long outcomes. Our main objective is to uncover the genetic origins of congenital diarrhea in children, understand the unique characteristics of these conditions, and study the responsible genes' underlying molecular and cellular mechanisms. We will use these insights to enable tools and resources for the research community, provide information and expertise to patients and the public, and develop new strategies for treatment using patient-derived cellular systems and animal models.

PI_NAMEs: GOLDENRING, JAMES RICHARD;KAJI, IZUMI ;LENCER, WAYNE I;MARTIN, MARTIN G (contact);MUISE, ALEIXO M;THIAGARAJAH, JAY

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Address;Advanced Development;Affect;Animal Disease Models;Animal Model;Applications Grants;Architecture;biobank;Biological;Biological Assay;Biological Models;Biology;Biopsy;causal variant;Cells;Cellular biology;Characteristics;Child;Clinical;clinical database;Clinical Management;clinical phenotype;clinical translation;cohort;Communities;Complement;cost;Data;data resource;data tools;Diarrhea;Disease;Enrollment;Epithelium;Etiology;exome sequencing;experience;Family;Fluid Balance;Genes;Genetic;Genetic Diseases;genome sequencing;Goals;Image;Immunofluorescence Immunologic;improved;Infant;innovation;insight;interest;intestinal epithelium;Intestines;Investigation;Libraries;Maps;Mendelian disorder;Metadata;Methods;Modality;Modeling;Molecular;Morbidity - disease rate;mortality;multidisciplinary;multimodality;multiple omics;Mus;next generation sequencing;novel;novel strategies;novel therapeutic intervention;nutrient absorption;Outcome;Pathologic;Patients;Phenotype;Physicians;pre-clinical;Proteins;Rare Diseases;repository;Research;Research Personnel;Research Project Grants;Resources;Sampling;Scientist;screening;Symptoms;System;targeted treatment;Technology;Therapeutic;therapeutic development;therapy development;Tissues;tool;transcriptome sequencing;transcriptomics;Validation;Variant;whole genome;Zebrafish

PROJECT_TITLE: COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepository

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-9 (M3)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative  CRISPR-transposase systems show tremendous potential to be generally useful programmable DNA- insertion tools to complement the power of CRISPR-Cas9, however the mechanisms governing DNA-insertion are mysterious and subject to unknown regulatory ‘rules’ that inhibit wide-spread adoption. We propose to characterize the mechanisms that govern programmed DNA-insertion using high-resolution cryo-EM focusing on the regulatory component, TnsC, from the shCAST system. Our structures will provide a detailed understanding of how CRISPR-transposase systems function at the molecular level; this information will enable engineering of the shCAST system to become a generally useful genome-editing tool.

PI_NAMEs: KELLOGG, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Adoption;Area;ATP Hydrolysis;ATP phosphohydrolase;Base Pairing;Behavior;Binding;Binding Sites;Biological Models;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Complement;Complex;CRISPR/Cas technology;Cryoelectron Microscopy;Data;DNA;DNA Binding;DNA Integration;DNA Structure;ds-DNA;Elements;Engineering;Environment;Event;Exclusion;Exhibits;Filament;Genes;genome editing;Genome engineering;Goals;Guide RNA;Health;Human;Hydrolysis;Immunity;insight;Link;Literature;Modeling;Molecular;molecular assembly/self assembly;Molecular Conformation;mu transposase;Nucleotides;Outcome;particle;preference;Process;Proteins;reconstruction;recruit;Recruitment Activity;Resolution;RNA Binding;Role;Site;Structure;System;tool;Transposase

PROJECT_TITLE: Structural Basis of Programmable DNA-Insertion via Cryo-EM Studies of CRISPR-Associated TnsC

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases

ORG_CITY: MANHATTAN

ORG_NAME: KANSAS STATE UNIVERSITY

PHR: PROJECT NARRATIVE Despite the high mortality rate and the significant potential for a public health emergency, there are no FDA- approved vaccines or antiviral drugs for MERS-CoV. In addition, members of the Merbecovirus and Sarbecovirus subgenera within the Betacoronavirus genus pose a high risk of future spillover into humans. This project aims to develop orally available antivirals for MERS-CoV and evaluate inhibitors against merbecovirus and sarbecovirus 3C-like protease, which will have a significant impact on human coronavirus research and public health.

PI_NAMEs: CHANG, KYEONG-OK  (contact);GROUTAS, WILLIAM CONSTANTINE;KIM, YUNJEONG ;PERLMAN, STANLEY

PROGRAM_OFFICER_NAME: BASU, DIPANWITA

PROJECT_TERMS: 2019-nCoV;analog;Anti-viral Agents;betacoronavirus;Binding;Biochemical;Biological Assay;Biological Availability;Category C pathogen;Cell Culture Techniques;Cells;Cellular Assay;Characteristics;Chemicals;Chiroptera;Coronavirus;Coronavirus Infections;Crystallography;cytotoxicity;Death Rate;design;Development;Disease;Disease Outbreaks;Dose;Drug resistance;Endowment;Enzymes;Evaluation;FDA approved;Funding;Future;future pandemic;Goals;high risk;Human;human coronavirus;improved;In Vitro;in vivo;indexing;inhibitor;Lead;member;Merbecovirus;meter;Middle East;Middle East Respiratory Syndrome;Middle East Respiratory Syndrome Coronavirus;mouse model;National Institute of Allergy and Infectious Disease;novel;novel coronavirus;Oral;pandemic coronavirus;Peptide Hydrolases;Pharmaceutical Preparations;pharmacologic;Polyproteins;pre-clinical;Process;Property;Protease Inhibitor;Public Health;public health emergency;receptor;Reporter;Reporting;Research;respiratory;Sarbecovirus;SARS coronavirus;Saudi Arabia;scaffold;screening;Series;Site;small molecule;South Korea;structural determinants;Structure;Structure-Activity Relationship;synergism;therapeutic target;Vaccines;Viral;Virus;Virus Replication;World Health Organization

PROJECT_TITLE: Small Molecule Protease Inhibitors against MERS-CoV and Coronaviruses of Pandemic Potential

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-T (90)]


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

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

ORG_STATE: NY

PHR: PROJECT NARRATIVE Aggressive carcinomas of the pancreas, breast, and bladder are known to exhibit basal lineage features, which is associated with poor prognosis but for unclear reasons. Building upon progress made in the last funding cycle aimed at understanding basal identity in pancreatic cancer, the major goal of this project will be to define molecular mechanisms that define this tumor subtype. We anticipate that a detailed knowledge of lineage master regulators that drive this cellular fate may unveil novel targets for therapeutic intervention.

PI_NAMEs: VAKOC, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Address;Alleles;antagonist;Area;Attenuated;attenuation;Basal Cell;base editing;base editor;Binding;Biochemical;Biochemistry;Biologic Characteristic;Biology;Bladder Carcinoma;Breast Carcinoma;cancer subtypes;Carcinoma;Cell Line;Cell Lineage;cell motility;Cell Survival;cell type;Cells;Chemoresistance;Chromatin;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Coupled;CRISPR screen;cytokine;Disease;Duct (organ) structure;Engineering;Enhancers;epigenomics;Evaluation;Exhibits;Experimental Genetics;Fostering;Funding;gain of function;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic Enhancer Element;Genetic Screening;Genetic Transcription;genome-wide;Goals;Grant;Growth;Human;IL1A gene;in vivo;Inferior;Inflammation;insight;Interferons;Invaded;knock-down;Knowledge;Length;loss of function;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Mediating;Mediator;Modeling;Molecular;Mus;Mutation;neoplastic cell;new therapeutic target;novel;Organoids;Output;Pancreas;Pancreatic carcinoma;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;patient subsets;Patient-Focused Outcomes;Phenotype;Prognosis;programs;Proteins;Publications;Publishing;reconstitution;Reporter;Repression;Research;Resolution;response;Scanning;System;Testing;Therapeutic;Therapeutic Intervention;tissue culture;trait;Transcription Coactivator;transcription factor;Transcription Repressor;Transcriptional Activation;transcriptomics;transdifferentiation;Transplantation;tumor;tumor initiation;Tumor Subtype;Work

PROJECT_TITLE: Targeting aberrant enhancer landscapes in pancreatic cancer

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Disability Research;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: BRONX

ORG_DEPT: NEUROLOGY

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Narrative Emerging research implicates gait dysfunction as a preclinical marker of Alzheimer’s disease (AD) and related dementias (ADRD). Building on our research, we will employ a team science approach with multi-modal neuroscience and biological methods to examine mechanisms underlying gait and cognitive decline in aging. Our overall hypothesis is that the interplay between pathological and resilience mechanisms in aging results in structural, functional, and neurophysiological brain changes that lead to the emergence of gait dysfunction as a preclinical marker of dementia.

PI_NAMEs: VERGHESE, JOE  (contact)

PROJECT_TERMS: Adult;Age;Aging;aging brain;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid beta-42;Attention;Biological;biological age;Biological Assay;Biological Markers;Blood;Blood Vessels;Brain;brain health;Centenarian;Classification;Cognition;Cognitive;Complex;Dementia;dementia risk;design;disability;Early Intervention;Electroencephalography;Enrollment;Epidemiologic Factors;epigenetic clock;Gait;Gait abnormality;Gait speed;healthy aging;Impaired cognition;innovation;insight;Intervention;Link;Longevity;Measures;Medial;Memory;mental imagery;Methods;Motor;Motor Activity;multidisciplinary;multimodal neuroimaging;multimodality;multisensory;Nerve Degeneration;neural;neuroimaging;neurophysiology;Neurosciences;non-demented;novel;older adult;Participant;Pathogenesis;Pathologic;pathological aging;Pathology;Pattern;Phenotype;Pilot Projects;pre-clinical;prevent;promote resilience;recruit;Research;resilience;response;Risk;Risk Factors;Sampling;Science;secondary outcome;Sensory;sensory integration;sex;Speed;Syndrome;System;tau-1;Techniques;Testing;Thinking;Walking;β-amyloid burden

PROJECT_TITLE: Gait as a Preclinical Marker for Alzheimer’s Disease and Dementia: insights from super-movers, usual-movers, and slow-movers

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-G (M1)]


NIH_SPENDING_CATS: Hearing Loss;Neurosciences

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Hearing at birth, as well as lifelong hearing preservation, requires sensory cells in the inner ear to develop and maintain a motion-sensing compartment that detects sound-borne vibrations. This project seeks to understand how this compartment acquires its unique slanted architecture required for sensory function, and how this architecture is preserved during life despite wear and tear. Accomplishment of the proposed research will help the interpretation and design of treatments for auditory dysfunction.

PI_NAMEs: TARCHINI, BASILE ROBIN (contact)

PROJECT_TERMS: Actins;Address;Adult;apical membrane;Architecture;Auditory;Birth;Cells;Chemicals;congenital hearing loss;Cues;Data;deafness;Defect;Development;Dimensions;Etiology;Functional disorder;Genes;GPSM2 gene;GTP-Binding Proteins;Hair;Hair Cells;Hearing;hearing impairment;hearing preservation;Hearing problem;Height;Investigation;Knowledge;Label;Labyrinth;Life;Maintenance;Membrane;Molecular;Monitor;Morphogenesis;Motion;Motor;mouse model;Mus;Myosin ATPase;polarized cell;Predisposition;preservation;protein complex;protein function;Proteins;public health relevance;Reporter;Research;Role;Scaffolding Protein;Sensory;Shapes;Side;sound;Structure;Syndrome;Technology;Testing;therapy design;Time;trafficking;vibration

PROJECT_TITLE: Hair Cell Polarization and Sensory Bundle Development


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Aging;Bioengineering;Cardiovascular;Clinical Research;Heart Disease;Physical Activity

ORG_CITY: Newark

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: SUBJECT NARRATIVE Despite advances in the clinical treatment procedures, advanced heart disease remains one of the leading cause of death in the United States. One main reason for the lack of optimal healthcare performance for treating these patients is the inefficiency in predicting clinical outcomes related to frailty. In the proposed research, we will develop and validate a novel objective sensor-based approach to characterize heart behavior in response to a localized rapid upper-extremity function task, among older adults with advanced heart disease to predict therapy outcomes and reversible frailty.

PI_NAMEs: TOOSIZADEH, NIMA  (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Adverse event;adverse outcome;Age;aggressive therapy;aortic valve replacement;Aortic Valve Stenosis;Arizona;arm;Assessment tool;Beds;Behavior;Biomedical Engineering;Biometry;candidate identification;candidate selection;Cardiac;Cardiology;Cardiopulmonary;Cardiovascular system;Categories;Cause of Death;Characteristics;Chest;Clinical;clinical care;Clinical Treatment;Cognitive;common treatment;comorbidity;comparison control;cost;Data;design;Disease;Elbow;Electrocardiogram;Engineering;Environment;Exercise;Eye;Fatigue;flexibility;follow-up;frailty;Geriatrics;Goals;Healthcare;Heart;Heart Diseases;heart function;Heart Rate;heart rate monitor;Homeostasis;human old age (65+);improved;Inpatients;Lasso;Lead;Left;Legal patent;Machine Learning;Measures;Methods;Mission;Modeling;Morphologic artifacts;Motion;motion sensor;Motor;motor disorder;motor impairment;multidisciplinary;multimodality;novel;older adult;Outcome;outcome prediction;Participant;Patients;Performance;Physical activity;Physiological;predict clinical outcome;Prediction of Response to Therapy;Procedures;programs;Recovery;Replacement Therapy;Research;resilience;response;Risk;Risk Assessment;risk stratification;Sampling;sensor;sex;Side;signal processing;Speed;Stress;stressor;Symptoms;System;Testing;Therapeutic;therapy outcome;tool;Training;Treatment Cost;Treatment outcome;United States;Universities;Upper Extremity;Vascular blood supply;Walking;wearable device;wearable sensor technology

PROJECT_TITLE: Heart Rate Dynamics in Response to Upper-Extremity Function Test to Identify Irreversible Frailty After Invasive Therapy in Older Adults with Advanced Heart Disease

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Biotechnology;Infectious Diseases;Microbiome;Rare Diseases;Vector-Borne Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Leishmaniasis is a serious neglected tropical disease where destructive cutaneous lesions develop, treatment is often ineffective and there is no vaccine. These studies will define how the skin microbiome promotes increased pathology in leishmaniasis, with the goal of developing new therapies for the disease.

PI_NAMEs: GRICE, ELIZABETH ANNE;SCOTT, PHILLIP  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Affect;Antimony;Bacteria;Brazil;Candidate Disease Gene;candidate validation;Caspase Inhibitor;CCL27 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chemokine;Chronic;Clinical;Collection;Combined Modality Therapy;commensal bacteria;comparative genomics;Complement;Cutaneous;Cutaneous Leishmaniasis;Cytotoxic T-Lymphocytes;Data;Development;Disease;Disease Outcome;Experimental Models;FOXP3 gene;Funding;Genes;genome sequencing;Genomic approach;Goals;Immune;Immune response;immunopathology;immunoregulation;Impaired healing;improved outcome;In Vitro;Infection;Infectious Skin Diseases;Inflammatory;Inflammatory Response;Interferon Type II;Interleukin-1 beta;keratinocyte;Leishmania;Leishmania braziliensis;Leishmaniasis;Lesion;Mediating;microbial;microbiota;mouse model;Mus;mutant;neglected tropical diseases;neutrophil;Neutrophil Activation;novel;novel therapeutics;Organoids;Parasites;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Play;Probiotics;Production;Productivity;recruit;Regulatory T-Lymphocyte;Resolution;response;Role;Severity of illness;Skin;skin barrier;skin microbiome;Soft Tissue Infections;standard of care;Staphylococcus aureus;Staphylococcus aureus infection;Testing;Therapeutic;therapeutic target;therapy development;therapy resistant;Treatment Failure;Vaccines;Variant;Virulence;Virulence Factors;whole genome

PROJECT_TITLE: Skin microbiome contributions to the pathogenesis of cutaneous leishmaniasis

STUDY_SECTION: IMII

STUDY_SECTION_NAME: Interspecies Microbial Interactions and Infectious Study Section[IMII]


ORG_CITY: BOSTON

ORG_DEPT: MISCELLANEOUS

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Type 2 Diabetes (T2D) is complex and caused by insulin resistance, impaired beta-cell function, and many genetic and upstream exposomic factors, potentially operating differently across ancestral groups. We will deploy and evaluate data science approaches to tackle the complexity of T2D risk by deriving new ancestry- aware polygenomic and polyexposure predictors of insulin resistance and beta cell dysfunction and use machine learning approaches to identifying key `omic of the drivers of the risk across race/ancestral groups. We will disseminate new open data science resources for discovering elusive exposome factors, polygenomic predictors, and their endogenous responses in T2D risk to enhance reproducible research and add value to already precious NIH cohort data.

PI_NAMEs: MANRAI, ARJUN KUMAR;MERCADER, JOSEP MARIA;PATEL, CHIRAG J. (contact)

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Architecture;Atherosclerosis;Atlases;Awareness;Behavior;Behavioral;Beta Cell;biobank;Biological;Biological Assay;Biological Markers;Blood;Cataloging;Catalogs;Cell Physiology;circulating biomarkers;cohort;Communities;Complex;Computer software;Coronary Artery Risk Development in Young Adults Study;Data;Data Science;data science resource;Databases;Development;Diabetes Mellitus;diabetes risk;dietary;Dissection;Environment;Etiology;exposed human population;Exposure to;Framingham Heart Study;Functional disorder;Funding;gene environment interaction;Genes;Genetic;genetic approach;Genetic Determinism;Genetic Risk;Genetic study;Genome;genome wide association study;genome-wide;genome-wide analysis;Genomics;Goals;Impairment;Individual;Infection;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;Investigation;Link;Machine Learning;Maps;Measures;Medicare;Mendelian randomization;metabolome;Methods;multi-ethnic;National Health and Nutrition Examination Survey;non-genetic;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;open data;Output;Pathway interactions;Phenotype;Physical activity;Physiological;Physiology;pollutant;polygenic risk score;Population Heterogeneity;Process;Proteome;Race;Reproducibility;Research;Research Personnel;Resources;response;Risk;Risk Factors;Role;Science;success;Surveys;System;Taxonomy;Time;tool;trait;United States National Institutes of Health;Variant

PROJECT_TITLE: Cataloging multi-ancestry 'omic readouts of the environmental and genetic determinants of type 2 diabetes

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Heart Disease;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Streptococcus pneumoniae (Spn) induced community-acquired pneumonia (CAP) leads to adverse cardiac outcomes during bacterial infection and even months and years that follow. The mechanisms by which pneumonia can affect the long-term risk of CVD are poorly understood. Therefore, the proposed work has very high significance since it addresses a challenging set of cardiac problems faced by many CAP patients for which currently there are no specific treatments.

PI_NAMEs: LAL, HIND  (contact);ORIHUELA, CARLOS J

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: acute infection;Address;Admission activity;Adult;Affect;Animals;Antibiotics;antimicrobial;Attenuated;Automobile Driving;Bacterial Infections;beta-Chemokines;Binding;Biology;Biomedical Engineering;Blood specimen;Cardiac;cardiac repair;cardioprotection;Cardiovascular system;Cessation of life;chemokine receptor;Chronic;Clinical;Clinical Trials;combat;community acquired pneumonia;community burden;Convalescence;cytokine;Data;Equilibrium;Event;experience;Family;Functional disorder;Genetic Models;Gram-Positive Bacteria;healing;Heart;heart damage;Heart Diseases;Hospitalization;Human;Immune response;in vivo;Individual;Infection;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Institutional Review Boards;Interleukin-1 beta;Intervention Studies;Knock-out;Link;Macrophage;Mediating;Medical;Modeling;Monoclonal Antibodies;monocyte;mortality;mouse genetics;mouse model;Myocardial dysfunction;Myocarditis;Myocardium;Nervous System;novel;novel strategies;Organ;Outcome;Pathogenesis;Pathway interactions;Patients;pharmacologic;Pneumococcal Infections;Pneumonia;Protocols documentation;receptor;recruit;repaired;Research Personnel;Respiratory System;Risk;Role;S100A8 gene;S100A9 gene;Signal Transduction;Streptococcus pneumoniae;Testing;Time;Tissue Microarray;Tissues;translational study;Troponin;Ventricular Remodeling;Work

PROJECT_TITLE: Novel strategies to mitigate cardiac damage and dysfunction following invasive pneumococcal disease


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Colorectal Cancer;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: PROJECT NARRATIVE Black men and women currently experience the highest rates of colorectal cancer of any racial and ethnic group in the US for reasons only partly understood and their risk factors have not been well-studied to date. Our new web-based decision tools will provide accurate personalized risk assessments of developing colorectal cancer for Black adults, providing clinicians and the Black community with valuable aids to identify those at highest risk for developing colorectal cancer and to inform lifestyle prevention strategies, leading to improved uptake of screening tests and earlier detection of colorectal cancer and lower mortality.

PI_NAMEs: NELSON, KERRIE P (contact)

PROGRAM_OFFICER_NAME: BURNETT, ANDREA NICOLE

PROJECT_TERMS: Accounting;Address;Adult;Age;aged;Assessment tool;Awareness;Behavioral;Biological Factors;Black American;black men;Black Populations;Black race;black women;Calibration;cancer diagnosis;cancer risk;Cardiovascular Diseases;Characteristics;Clinical;clinical risk;cohort;Cohort Studies;Colon;Colonoscopy;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;colorectal cancer screening;Communities;Consensus;Data;Death Rate;Decision Making;Diet;dietary;Disease;Distal;early onset;early onset colorectal cancer;Ethnic Population;Excision;experience;Family;follow-up;Goals;Grant;Health;health equity;Health Personnel;Healthcare;high risk;High Risk Woman;improved;Incidence;Life Style;Life Style Modification;machine learning method;Malignant Breast Neoplasm;Malignant Neoplasms;Medical;men;Modeling;Modernization;mortality;multi-ethnic;novel;Online Systems;Participant;Performance;personalized predictions;personalized risk prediction;Physicians;Population;Precancerous Polyp;predictive tools;Prevention strategy;Prognosis;prospective;Prospective cohort;Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial;Public Health;racial disparity;racial population;Recording of previous events;Rectum;Reduce health disparities;Research Support;Risk;Risk Assessment;Risk Factors;risk prediction;risk prediction model;routine screening;screening;Site;social;social factors;statistical learning;Statistical Methods;Test Result;Testing;tool;tumor;tumor heterogeneity;United States National Institutes of Health;uptake;Validation;willingness;Woman;Women's Health;Work;young adult

PROJECT_TITLE: Addressing racial disparities in colorectal cancer risk prediction

STUDY_SECTION: CHD

STUDY_SECTION_NAME: Cancer and Hematologic Disorders Study Section[CHD]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Bioengineering;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Lung;Precision Medicine;Rare Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PUBLIC HEALTH RELEVANCE Caused by inflammatory lung injury, acute respiratory distress syndrome (ARDS) is associated with the loss of ventilated airspaces, low blood oxygen, and high mortality. Dysregulation and misdistribution of lung perfusion may play an important role in determining both the clinical trajectory of ARDS and its response to treatment; unfortunately, pulmonary circulation is poorly characterized in this condition. The proposed research will use imaging to reveal the contribution of abnormal pulmonary perfusion to the progression of lung injury as well as to develop strategies to attenuate ARDS severity by targeting pulmonary circulation.

PI_NAMEs: CEREDA, MAURIZIO FRANCO (contact)

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: acute care;Acute Respiratory Distress Syndrome;Address;Affect;Alveolar;Animals;Attenuated;Blood;Blood capillaries;Blood flow;blood perfusion;Blood Pressure;Blood Vessels;Blood Volume;body position;Carbon Dioxide;Cause of Death;Cessation of life;Characteristics;Clinical;clinical decision-making;clinical investigation;contrast enhanced;contrast enhanced computed tomography;COVID-19;COVID-19 mortality;Cross-Over Studies;Data;data integration;drug preservation;Edema;electrical impedance tomography;Endothelium;Failure;Family suidae;Functional disorder;Gases;Goals;Heterogeneity;high risk;Hour;Human;Hypoxemia;Image;image translation;imaging approach;imaging biomarker;imaging modality;Imatinib;Impairment;improved;in vivo;individual patient;individualized medicine;Inflammation;Inflammatory;inhaled nitric oxide;Injections;injured;Injury;instrument;Kinetics;Knowledge;Life;Low Dose Radiation;Lung;lung imaging;lung injury;Maps;Measures;Mechanical ventilation;Mechanics;mortality;novel strategies;Outcome;Oxygen;patient response;Patients;Perfusion;perfusion imaging;personalized management;pharmacologic;Pharmacological Treatment;Phenotype;Physiological;Play;porcine model;prevent;Prone Position;public health relevance;Publishing;pulmonary arterial pressure;Pulmonary Circulation;Pulmonary Edema;Pulmonary Inflammation;pulmonary vascular disorder;real time monitoring;regional difference;Regional Perfusion;Research;Resolution;response;Risk;Role;Severities;Stress;Structure of parenchyma of lung;Supine Position;targeted treatment;Techniques;Testing;Time;Tissues;Tracer;treatment response;treatment strategy;Vascular Diseases;vasoconstriction;Vasodilation;Vasodilator Agents;ventilation;Visualization;X-Ray Computed Tomography

PROJECT_TITLE: Imaging the Pulmonary Circulation to Aid Personalized Management of Acute Respiratory Distress Syndrome

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

PHR: Project Narrative Identifying approaches for coordinating health benefits for individuals who are dually eligible for Medicare and Medicaid is challenging. Many dual-eligible beneficiaries are enrolling in private Medicare Advantage plans, which differ from Traditional Medicare in their payment incentives, provider networks, care management, and the availability of supplemental benefits. This study will investigate enrollment patterns in Medicare Advantage versus Traditional Medicare for dual eligible beneficiaries entering Medicare and compare use, spending, and health outcomes across these groups to inform federal and state policies.

PI_NAMEs: FUNG, VICKI  (contact)

PROGRAM_OFFICER_NAME: KARACA, ZEYNAL

PROJECT_TITLE: Medicare Advantage versus Traditional Medicare for Dual Eligible Beneficiaries

STUDY_SECTION: HSVR

STUDY_SECTION_NAME: Healthcare Systems and Values Research[HSVR]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Lung

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative We will determine how IL-13 contributes to COVID-19 disease through its role in induction of an inflammatory hyaluronan-containing extracellular matrix. This work has the promise of identifying novel therapies for acute and long-term COVID-19 directed at the IL-13 - hyaluronan pathway, as well as increasing our understanding of other pulmonary diseases where IL-13 and hyaluronan are known to contribute.

PI_NAMEs: ALLEN, JUDITH ;DAY, ANTHONY JOHN;MARIE, CHELSEA S.;PETRI, WILLIAM A (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: 2019-nCoV;Acute;acute COVID-19;Acute Respiratory Distress Syndrome;Adhesions;Adhesives;Biology;CD44 Antigens;CD44 gene;Cell division;Cells;Clinical Trials;Collaborations;Complex;COVID-19;COVID-19 patient;crosslink;cytokine;Deposition;Disease;Environment;Enzymes;Extracellular Matrix;Family;Host Defense;Human;Hyaluronan;IL-13Ralpha1;Immune;immune cell infiltrate;Immunity;Immunology;improved;improved outcome;Infection;Inflammation;Inflammatory;innovation;inter-alpha-inhibitor;Interleukin-13;interleukin-13 receptor;Interleukin-4;Interleukin-6;Knock-out;Lead;Leukocytes;Long COVID;Lung;Lung Diseases;Lymphoid Cell;Macrophage;Mediating;Medicine;Messenger RNA;mortality;mouse model;Mus;novel;novel therapeutic intervention;novel therapeutics;Pathogenicity;Pathology;Pathway interactions;Physicians;Polysaccharides;primary outcome;Production;pulmonary function;Pulmonary Inflammation;Pulmonary Pathology;Randomized;receptor expression;receptor function;recruit;Regenerative Medicine;Regulation;Research Personnel;respiratory;Respiratory Failure;Role;SARS-CoV-2 infection;Scientist;severe COVID-19;Severity of illness;Signal Transduction;Source;Structure of parenchyma of lung;Testing;trend;Universities;Viral;Virginia;Walking;Work

PROJECT_TITLE: Role of Hyaluronan in IL-13-mediated COVID-19 Pathology

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Substance Misuse

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Ethanol, which is consumed by most adults in the US, increases the accumulation of toxic aldehydes in our bodies and thus contributes to many common diseases. Here, we examine the role of a number of enzymes whose impaired functions can further contribute to ethanol- and aldehyde-induced toxicity, especially in specific genetic ancestry groups.

PI_NAMEs: MOCHLY-ROSEN, DARIA  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: 4 hydroxynonenal;Abbreviations;Acetaldehyde;Acute;Adenosine Triphosphate;Adult;Affect;African ancestry;aggregation database;Alcohol consumption;Alcohol dehydrogenase;Alcohol dependence;alcohol exposure;aldehyde dehydrogenases;Aldehydes;Alleles;Alzheimer's Disease;Alzheimer's disease patient;American;Amyloid beta-Protein;Asian ancestry;Bacteria;Biological Models;Cell Death;Cells;Chronic;Chronic Disease;Clinical;Colorectal Cancer;Communities;Complement;Consumption;cytotoxicity;Data;Disease;disorder risk;Drug Metabolic Detoxication;East Asian;Education;Enzymes;Ethanol;Ethanol toxicity;Evolution;Fermentation;Fibroblasts;Functional disorder;Genetic;Genetic Polymorphism;Genome;Health;high risk;Hour;Human;Human Genetics;Human Pathology;Immunologic Cytotoxicity;Impairment;In Vitro;in vivo;Individual;induced pluripotent stem cell;Inflammation;Innate Immune Response;innovation;intraperitoneal;Iron;Knock-in;Knock-in Mouse;Knock-out;Latino Population;loss of function;Mission;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;mouse model;Mus;Neurofibrillary Tangles;neurofilament;neuroinflammation;Other Genetics;Persons;precision medicine;Reactive Oxygen Species;Risk;Role;South Asian;Testing;Toxic effect;United States National Institutes of Health;Variant;Work;World Health Organization

PROJECT_TITLE: Ethanol and aldehyde dehydrogenases in health and disease

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Aging;Cardiovascular;Genetics;Heart Disease;Human Genome;Precision Medicine;Prevention

ORG_DEPT: GENETICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Mitochondria play a key role in human health, and loss of mitochondrial function has been associated with cardiovascular disease and overall mortality. We will leverage data from ~680,000 individuals to identify genes associated with mitochondrial function, providing potential therapeutic targets for aging-related diseases exacerbated by loss of mitochondrial function.

PI_NAMEs: ARKING, DAN E (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Acceleration;aging related;aging related disease;Apoptosis;Automobile Driving;biobank;Biological Markers;Cardiovascular Diseases;cardiovascular disorder risk;causal variant;Cell Physiology;Cell Respiration;Cells;Data;density;Diabetes Mellitus;Dietary Factors;DNA;DNA copy number;Dyslipidemias;Energy Metabolism;Etiology;frailty;Free Radicals;Future;Genes;genetic testing;Genetic Variation;Genome;genome wide association study;gerotherapeutic;Health;Heart failure;heteroplasmy;Human;Hydrogen Peroxide;Hypertension;Individual;Inherited;innovation;instrument;Intervention;Link;Maps;Measurable;Measurement;Measures;Mediating;Mediation;Mendelian randomization;metabolomics;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;modifiable risk;Molecular;mortality;multiple omics;Myocardial Infarction;novel;novel marker;Nuclear;Organelles;Participant;Pharmaceutical Preparations;Phenotype;Physical activity;Plasma;Play;Population;Production;Proteins;Proteomics;rare variant;Reactive Oxygen Species;Risk;Risk Factors;Role;Sample Size;Sampling;Signal Transduction;Single Nucleotide Polymorphism;Site;Stroke;Superoxides;Systems Biology;Testing;therapeutic target;Tobacco use;Trans-Omics for Precision Medicine;Validation;Variant;whole genome

PROJECT_TITLE: Mitochondrial Function and Multiomics in Aging-related Disease: Identifying Novel Biomarkers and Causal Relationships

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Aging;Biotechnology;Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Project Narrative MicroRNAs-based therapy is a promising approach to treat chronic retinal diseases, with high selectivity towards diseased tissue. Studies of this project will examine the regulatory network of microRNAs and their target genes in specific types of retinal cells, as well as their interactions mediated by extracellular vesicles containing microRNAs.

PI_NAMEs: CAI, JIYANG  (contact);LIU, YIN

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: age related;Age related macular degeneration;Aging;Algorithms;autoimmune uveitis;Binding;Biogenesis;cell type;Cells;Central Nervous System;Chronic;cofactor;Computer Models;Conditioned Culture Media;Data;Data Set;Development;Diabetic Retinopathy;Disease;disease model;Down-Regulation;Elderly;Engineering;exosome;experimental study;extracellular;extracellular vesicles;Eye;Eye diseases;Flow Cytometry;Future;Gene Expression;gene function;gene repression;Genes;Goals;Human;Human Engineering;human induced pluripotent stem cells;Image;Immune;Immune response;Immunofluorescence Immunologic;Impairment;improved;in vivo;Inflammation;inherited retinal degeneration;Injections;Injury;insight;intercellular communication;Intervention;Knockout Mice;Ligands;lipid metabolism;Lipids;Literature;Machine Learning;Measures;Mediating;Messenger RNA;Microglia;microRNA delivery;MicroRNAs;Modeling;Modification;Mus;Neural Retina;old mice;Oligonucleotides;oxidized low density lipoprotein;Pathologic;Pathology;Population Heterogeneity;Post-Transcriptional Regulation;programs;protective effect;Proteins;Publishing;receptor;Rejuvenation;release factor;response;Retina;Retinal Diseases;retinal ischemia;RNA Degradation;Role;side effect;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Small RNA;Stress;Structure;Structure of retinal pigment epithelium;Supporting Cell;Testing;TGFBR2 gene;Therapeutic;therapeutic miRNA;Tissues;Training;transcriptome sequencing;Transforming Growth Factors;Translational Repression;Translations;Untranslated RNA;uptake;vesicular release;Wild Type Mouse

PROJECT_TITLE: Extracellular microRNA-mediated intercellular communication between retinal microglia and RPE

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


NIH_SPENDING_CATS: Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Infant Mortality;Infectious Diseases;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: NARRATIVE  Congenital syphilis rates are rising in the U.S., but current diagnostic tests lack sensitivity to confirm infection among asymptomatic, syphilis-exposed newborns. Infant immune responses to congenital syphilis infection are poorly characterized but could provide new diagnostic biomarkers to inform the probability of infection among asymptomatic, syphilis-exposed infants. We will use advanced immunologic methods to expand our understanding of innate and adaptive immunopathogenesis among an established cohort of symptomatically infected infants, followed by application of these immunologic signatures to an enrolled cohort of asymptomatic, syphilis-exposed infants in order to assess their likelihood of congenital infection.

PI_NAMEs: SHIMAMURA, MASAKO  (contact)

PROGRAM_OFFICER_NAME: GLOCK, JONATHAN A

PROJECT_TERMS: adaptive immune response;Adult;Animal Model;Antibiotics;Antigens;B-Lymphocytes;Biological Assay;Biological Markers;Birth;Blood;CD8-Positive T-Lymphocytes;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Characteristics;chemokine;Clinical;Clinical Management;cohort;congenital cytomegalovirus;congenital infection;Congenital Syphilis;Control Groups;curative treatments;cytokine;Cytomegalovirus Infections;Data;Deformity;Dendritic Cells;Diagnosis;Diagnostic;diagnostic biomarker;Diagnostic tests;differential expression;Differentiation Antigens;Enrollment;Enzyme-Linked Immunosorbent Assay;Exposure to;Female of child bearing age;fetal;Flow Cytometry;follow-up;Future;Gene Expression Profile;Genetic Transcription;Human;Immune;immune activation;Immune response;Immunoassay;Immunologics;Immunology;Immunophenotyping;Impairment;improved;in utero;Infant;infant infection;Infection;Inflammation;Inflammatory;Innate Immune Response;insight;interest;Interest Group;Leukocytes;Methods;monocyte;Mothers;Natural Killer Cells;Neonatal;neonatal infection;neonate;Neurologic;Neurological disability;Newborn Infant;novel diagnostics;Outpatients;Pathogenesis;peripheral blood;potential biomarker;Probability;receptor expression;response;Serum;Signal Transduction;Symptoms;Syphilis;T cell response;targeted treatment;Testing;transcriptomics;Whole Blood

PROJECT_TITLE: Interrogating infant immune responses for diagnosis of congenital syphilis infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 FDS-M (M1)]


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

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE The intestinal epithelium is a rapidly self-renewing tissue but at the same time is prone to injury. Many pathological conditions result in the depletion of the active stem cell pool in the intestinal crypts, which become repopulated by other cell types in a process of regeneration. The current proposal aims at understanding the mechanisms that coordinate the interplay between epithelial and stromal cells during epithelial regeneration after injury and will advance the understanding of the fundamental mechanisms required for optimal gut function and provide opportunities for better treatment.

PI_NAMEs: YANG, VINCENT W (contact)

PROJECT_TERMS: Amendment;Animal Model;Architecture;Binding;Cell Differentiation process;Cell secretion;cell type;Cells;chemotherapy;Communication;Data;design;Digestive System Disorders;Enterocytes;Epigenetic Process;Epithelial Cell Proliferation;Epithelial Cells;epithelium regeneration;gamma irradiation;Gamma Rays;Gastrointestinal Diseases;Gastrointestinal tract structure;Genetic Transcription;GLI gene;Goals;Grant;HIF1A gene;Impairment;In Vitro;in vivo;Injury;intestinal crypt;intestinal epithelium;Intestines;ionization;irradiation;Ligands;Mesenchymal;Mus;National Institute of Diabetes and Digestive and Kidney Diseases;Natural regeneration;next generation sequencing;novel;organ injury;Organoids;Pathologic;Pathway interactions;Patients;Population;Predisposition;prevent;Process;progenitor;programs;Proliferating;promoter;Radiation Injuries;Radiation therapy;radiation-induced injury;reconstitution;regeneration potential;regenerative;Regenerative capacity;Regulation;Research;Research Proposals;Reserve Stem Cell;response;restoration;Role;self-renewal;SHH gene;side effect;Signal Pathway;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;smoothened signaling pathway;spatiotemporal;Specific qualifier value;stem cell division;stem cell niche;stem cells;Stromal Cells;stromal progenitor;System;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;transcriptome;transcriptomics;Villus;WNT Signaling Pathway

PROJECT_TITLE: Regulation of Intestinal Epithelial Cell Proliferation

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Caregiving Research;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Pain Research;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE The proposed project will determine the many influences on parent presence and participation in caregiving in the neonatal intensive care unit (NICU) and the importance of parent presence and participation for clinical and developmental outcomes of preterm infants. By studying these influences and how they change during an infant’s NICU hospitalization, specific interventions can be developed to improve infant outcomes. The study will also provide information to better understand race- and socioeconomic-based disparities in parent presence and participation to increase health equity.

PI_NAMEs: NIST, MARLIESE D (contact);PICKLER, RITA H

PROGRAM_OFFICER_NAME: MITCHELL, MEGAN S

PROJECT_TERMS: Achievement;Address;Affect;Age;Area;Bathing;Behavioral;biological adaptation to stress;brain abnormalities;Buffers;caregiving;Characteristics;Clinical;Cognitive;Competence;Data;Development;Disparity;Distress;Documentation;Economics;Electronic Health Record;Enrollment;Ensure;Equity;extreme prematurity;Family;feeding;Frequencies;Gestational Age;Goals;Growth;health disparity;health equity;health equity promotion;health inequalities;Healthcare Systems;Hospitalization;improved;improved outcome;Infant;Infant Development;infant outcome;Intervention;Length;Length of Stay;longitudinal design;Longitudinal Studies;Measures;Mediation;Motor;National Institute of Child Health and Human Development;Neonatal Intensive Care Units;neurodevelopment;Neurodevelopmental Impairment;Oral;Outcome;Pain;Pain management;pain score;Parent-Child Relations;Parents;perceived discrimination;Performance;Perinatology;physical separation;Pregnancy;Premature Birth;Premature Infant;Procedures;protective factors;Race;racial disparity;Reaction;Regulation;Reporting;Research Design;Research Priority;Resources;Science;Skin;social;sociodemographic disparity;sociodemographics;socioeconomic disparity;socioeconomics;Stress;Support System;Surveys;System;Target Populations;Testing;theories;therapy development;Time;Toddler;Underrepresented Populations;Visit

PROJECT_TITLE: Equity for Parent Presence and Participation in Caregiving in the NICU

STUDY_SECTION: ICSC

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: PROJECT NARRATIVE Cognitive performance is of key concern among aging populations, but little research has been conducted on cognitive performance among aging Black and Latino sexual minority men (SMM). We will use respondent- driven sampling to recruit a cohort of aging Black and Latino SMM in Northern New Jersey and assess how their social networks are constructed, and how social and physical activities promoted within these social networks and interpersonal processes (intersectional stigma and social support) may be protective for cognitive performance. Our findings will provide valuable data for health providers, public health researchers, and policymakers to more effectively intervene across the complex pathways between marginalized social position, stigma, social networks, and cognitive performance outcomes.

PI_NAMEs: FRIEDMAN, MACKEY R;RAYMOND, HENRY FISHER;YANG, CUI  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Address;Adult;Affect;Age;Aging;behavior influence;Behavioral Mechanisms;Biological;Black race;Characteristics;Cognitive;Cognitive deficits;cognitive performance;cohort;Communities;community engagement;community partners;Complex;coping;County;Data Analyses;density;Development;Disparity;Ensure;Equipment and supply inventories;Ethnic Origin;experience;Family;follow-up;Future;Health;Health behavior;Health behavior change;health data;health disparity;Health Personnel;HIV;improved;information processing;Infrastructure;Interdisciplinary Study;Intervention;Knowledge;Latino;Latino Population;Letters;marginalization;Marriage;member;men of color;Modeling;Network-based;Neuropsychology;New Jersey;Outcome;Participant;Pathway interactions;peer;Physical activity;Policy Maker;Population;prevent;preventive intervention;Process;Public Health;Race;Recording of previous events;recruit;Reporting;Research;Research Personnel;Resources;Respondent;Role;Sampling;sexual minority men;social;Social Network;social network intervention;social space;Social status;social stigma;Social support;Socialization;Source;Structure;Surveys;therapy development;Time;trend;Vulnerable Populations

PROJECT_TITLE: Social Networks and Cognitive Health among Black and Latino sexual minority men in NJ

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-L (A1)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_DEPT: BIOLOGY

PHR: NARRATIVE Small cell lung cancer is a deadly disease with few treatment options. This research will investigate how manipulation of metabolism can trigger cell death in small cell lung cancer, potentially suggesting new treatment strategies for this disease.

PI_NAMEs: DIXON, SCOTT  (contact);SAGE, JULIEN

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: addiction;Adopted;Amino Acids;anti-cancer research;Apoptosis;Apoptotic;ASCL1 gene;BETA2 protein;Binding;Biochemical Pathway;Biological Assay;Biology;Cancer Biology;cancer cell;carcinogenesis;Cell Cycle;Cell Cycle Arrest;Cell Death;Cell Death Induction;Cell Proliferation;Cell Survival;Cells;Chimeric Proteins;Clinical;comparative;Cysteine;Cysteine Metabolism Pathway;Cystine;Data;deprivation;Development;Diagnosis;Disease;enzyme therapy;Enzymes;Epigenetic Process;Evolution;Gene Expression Profile;Genes;genetic manipulation;Genetic Transcription;Goals;Image;In Vitro;in vivo;in vivo Model;Induction of Apoptosis;insight;Link;lipidomics;Lipids;lung cancer cell;Malignant neoplasm of lung;Mass Spectrum Analysis;Metabolic;Metabolism;metabolomics;Modeling;Monitor;multidisciplinary;Mutation;neuroendocrine cancer;Neuroendocrine Cell;Neurosecretory Systems;notch protein;Notch Signaling Pathway;novel;novel therapeutic intervention;novel therapeutics;paracrine;Pathway interactions;Patients;Phospholipid Metabolism;Phospholipids;Pre-Clinical Model;Process;Proliferating;Regulation;Research;response;Role;Signal Pathway;Signal Transduction;small cell lung carcinoma;Surface;Surface Antigens;Technology;Testing;Therapeutic;Therapeutic Agents;Tobacco smoking behavior;TP53 gene;Transcript;transcription factor;transcriptome sequencing;tumor;tumor growth;tumor heterogeneity;tumor metabolism;tumor microenvironment;Tumor Suppressor Genes;Work

PROJECT_TITLE: Modulating cysteine metabolism to induce cell death in small cell lung cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-D (02)]


NIH_SPENDING_CATS: Clinical Research;Data Science;Diabetes;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Narrative A multimodal, evidence-based, quantitative method is required to deliver continuous scoring for diabetic nephropathy, the most common histopathologic manifestation of diabetic kidney disease (DKD), by engaging molecular information along with digital histology, and summarizing the contributions of each pixel of a renal tissue histopathology image using quantitative morphometry and omics. The investigator team will: 1) extend digital pathology of DKD by integrating spatial molecular features to reveal hidden digital image biomarkers, 2) provide clinicians with additional useful metrics for biopsy assessment to augment the current treatment strategy of DKD, and 3) conduct a usability study to understand the feasibility of using the resulting tools in the clinic. With these deliverables, this renewal R01 application will shift the paradigm, transforming digital and computational DKD pathology to improve prognosis, diagnosis, interpretation of molecular processes, and therapy selection in DKD, and thus lead the way to translating the developed tools into the clinic.

PI_NAMEs: EADON, MICHAEL THOMAS;ROSENBERG, AVI Z;SARDER, PINAKI  (contact)

PROGRAM_OFFICER_NAME: GOSSETT, DANIEL ROBERT

PROJECT_TERMS: Angiogenesis Pathway;Angiotensin-Converting Enzyme Inhibitors;Artificial Intelligence;Biological Markers;Biometry;Biopsy;Cell Physiology;cell type;Cells;Classification;Clinic;Clinical;clinically significant;cloud based;cloud software;Communities;comorbidity;Data;deep learning;demographics;Diabetes Mellitus;diabetic;Diabetic Nephropathy;Diagnosis;Diagnostic;digital;digital applications;digital imaging;digital pathology;disease classification;disease diagnostic;disease prognosis;Disease Progression;disorder risk;End stage renal failure;evidence base;FAIR principles;follow-up;Formalin;Foundations;Histologic;Histology;Histopathology;Hypertension;Image;imaging biomarker;improved;inhibitor;Injury;interoperability;Kidney;kidney biopsy;Label;Lead;Lesion;Machine Learning;machine learning model;Measures;Medicare;Methods;Minority;Modeling;Molecular;morphometry;multimodality;Nature;novel;optimal treatments;Outcome;Paraffin Embedding;Pathologist;Pathology;Pathway interactions;Patients;Performance;Pharmaceutical Preparations;pre-clinical;predictive modeling;Process;Prognosis;Proteinuria;Recovery;Renal Tissue;Research Personnel;Retrospective cohort study;Risk;Risk Assessment;Selection for Treatments;Societies;Software Tools;spatial integration;Structure;System;Testing;Time;Tissues;tool;Training;transcriptomics;Translating;treatment strategy;usability;vector;Visual;Work

PROJECT_TITLE: Computational Imaging of Renal Structures for Diagnosing Diabetic Nephropathy.

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: The defining pathological hallmark of Lewy body diseases (LBDs) is the accumulation of misfolded and toxic a- synuclein (aSyn) through multiple mechanisms. This proposal will investigate the significance and mechanistic basis of a novel pathway that mediates the accumulation, transmission, and toxicity of aSyn through animal and cellular models, which is expected to shed critical new insights to new ways to treat LBDs.

PI_NAMEs: WOO, JUNGA "ALEXA"  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Ablation;Age;alpha synuclein;Alzheimer's disease pathology;Animal Model;ARRB2;Arrestins;Automobile Driving;Autophagocytosis;Behavioral;behavioral impairment;beta-arrestin;Binding;Biochemical;Brain;Cell membrane;Cell model;Cells;Clathrin Adaptors;Cognitive;Complex;conditional knockout;Corpus striatum structure;Dementia;Dementia with Lewy Bodies;Dorsal;Electrophysiology (science);Endocytosis;enhancer-binding protein AP-2;Event;Exhibits;experimental study;G-Protein-Coupled Receptors;Genetic;GTP-Binding Proteins;In Situ;in vivo;insight;Integral Membrane Protein;knock-down;Knockout Mice;Lewy Body Disease;Ligands;Mediating;Membrane;Modeling;Motor;Mus;Neurons;novel;Outcome;overexpression;Parkinson Disease;Parkinson's Dementia;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Phenotype;Phosphorylation;Phosphotransferases;pre-formed fibril;Process;protein protein interaction;Proteomics;receptor;recruit;Regulation;Role;Signal Induction;Signaling Protein;Synaptic plasticity;Synaptic Vesicles;synuclein;synucleinopathy;Testing;Toxic effect;trafficking;transmission process

PROJECT_TITLE: Decoding the BETA-arrestin2-LMBRD2 cascade in ALPHA-synuclein pathogenesis.

STUDY_SECTION: CMND

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


NIH_SPENDING_CATS: Osteoporosis;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative While the phenomenon of bone coupling, i.e., the complex spatial and temporal crosstalk that occurs between osteoclast-mediated bone resorption and osteoblast-dependent bone formation, is well appreciated, the molecular mechanisms that transduce signaling between osteoclasts and osteoblasts remain poorly defined. Herein, we describe a body of preliminary evidence wherein two osteoclast-derived proteolytic enzymes, the cysteine proteinase, cathepsin K (Ctsk), and the membrane-anchored matrix metalloproteinase, Mmp14/MT1- MMP, control the TGFβ/Smad/Tspan4-dependent deposition of migrasomes, a new form of extracellular vesicle that acts as a key "braking" mechanism to negatively regulate bone formation with the result that the osteoclast- specific knockout of both enzymes decreases migrasome formation, thereby triggering massive formation of new bone in vivo. The results of this study should not only shed new mechanistic light on a novel form of proteolytic crosstalk that controls bone coupling, but also identify new targets for therapeutic intervention in osteolytic disease states.

PI_NAMEs: WEISS, STEPHEN J (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Acids;angiogenesis;Biological;blood vessel development;bone;Bone Development;bone loss;Bone Marrow;bone mass;Bone remodeling;Bone Resorption;Caspase;cathepsin K;Cell Lineage;cell motility;Cells;Collagen Type I;Complex;conditional knockout;Coupling;Deposition;Disease;embryonic stem cell;Enzymes;Erythro;Event;Exhibits;Extracellular Matrix;extracellular vesicles;Family;Family member;Gene Expression;Giant Cells;Hematopoietic stem cells;Homeostasis;improved;In Vitro;in vitro activity;in vivo;insight;Knock-out;Knockout Mice;Light;Link;Maintenance;Matrix Metalloproteinases;Mediating;member;Membrane;migration;MMP14 gene;MMP9 gene;Modeling;Molecular;mouse model;Mus;Myelogenous;new therapeutic target;novel;Organelles;Osteoblasts;Osteoclasts;Osteogenesis;osteogenic;Osteolytic;Osteoporosis;Outcome;Pathologic;Peptide Hydrolases;permissiveness;platelet-derived growth factor BB;Play;premature;prevent;Process;Production;progenitor;Receptor Signaling;recruit;Rheumatoid Arthritis;Role;Signal Transduction;Signaling Molecule;skeletal;skeletal stem cell;sphingosine 1-phosphate;stem;stem cell migration;stem cell proliferation;synergism;System;Therapeutic Intervention;therapy design;transcriptome;Transforming Growth Factor beta;transmission process;triple helix;Up-Regulation

PROJECT_TITLE: A dual proteolytic axis regulates osteoclast-mediated bone coupling activity

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


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

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative Even after surgical correction, patients with coarctation of the aorta (CoA) continue to suffer from a diminished quality of life and a reduced lifespan, often due to hypertension. We will develop new standardized tools for a personalized medicine approach that improves objectivity and diagnosis in the treatment of CoA to limit the severity and duration of mechanical consequences and reduce the likelihood of hypertension. Results from these approaches will be used clinically to propose new criteria for the treatment of CoA patients.

PI_NAMEs: LADISA, JOHN FRANK (contact)

PROGRAM_OFFICER_NAME: BURNS, KRISTIN

PROJECT_TERMS: Adolescence;Affect;Age;Algorithms;Anatomy;Aorta;aorta constriction;Aortic coarctation;arm;Arteries;Birth;Blood;Blood Pressure;Cardiovascular Diseases;Catheterization;Child;Clinical;Clinical Trials;Computer Models;Congenital Cardiovascular Abnormality;Congenital Heart Defects;Data;Data Analyses;Data Set;Decision Trees;demographics;Diagnosis;Diagnostic;diagnostic tool;Echocardiography;Elasticity;Equation;follow-up;Goals;Grant;Growth;Guidelines;Health;Heart;Hypertension;hypertensive;Image;improved;indexing;Individual;Intervention;Leg;life span;Link;Machine Learning;mechanical stimulus;Mechanics;Methods;Mission;Morbidity - disease rate;Multicenter Studies;National Heart, Lung, and Blood Institute;next generation;Operative Surgical Procedures;Outcome;Outcome Study;Pathologic;Patients;Performance;personalized approach;personalized medicine;Phase;Pre-Clinical Model;Predictive Value;pressure;prevent;Prevention;Productivity;Protocols documentation;Quality of life;Research;research clinical testing;Retrospective Studies;Risk;risk prediction;Risk Reduction;Scientist;Screening procedure;Severities;Standardization;Statistical Data Interpretation;Stenosis;Structure;Testing;Tissues;tool;Translating;Translations;Update;Work

PROJECT_TITLE: Mechanisms of morbidity after correcting aortic coarctations of varying severity


ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE This renewal proposal aims to support Dr. Minmin Liu as a Research Specialist, enabling her to cultivate a stable and thriving career critical to Dr. Peter A. Jones's research program in the field of cancer epigenetics. Dr. Liu is uniquely qualified due to her strong research background, expertise in next-generation sequencing techniques, and computational data analysis for epigenetic/epigenomic studies, as well as her track record of making significant scientific contributions. Dr. Liu's proficiency will integrate cellular, biochemical, structural, and animal studies to elucidate how abnormal DNA methylation is established and interpreted in cancer cells.

PI_NAMEs: LIU, MINMIN  (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Address;Animals;Award;Biochemical;Biochemistry;bioinformatics tool;Biological;cancer cell;carcinogenesis;career;career development;Collaborations;computerized tools;Data Analyses;Development;DNA Methylation;Epigenetic Process;epigenome;epigenomics;Foundations;Freedom;Funding;Future;Genetic;genome-wide;genomic tools;Immunology;insight;Malignant Neoplasms;Measures;Methods;Methylation;Microbiology;Molecular Biology;next generation sequencing;novel;Nucleosomes;overexpression;programs;Protein Isoforms;Publications;Qualifying;Research;Research Support;Role;Science;Security;Shapes;skills;Specialist;Stem Cell Development;structural biology;Techniques;tumorigenesis

PROJECT_TITLE: Research Specialist Support- Establishing and Interpreting Abnormal DNA Methylation in Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M2)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Physical Rehabilitation;Rehabilitation

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative We have designed a series of experiments that test a new model of speech motor learning which focuses on the role of plasticity in sensory systems in both learning and retention. These studies use a combination of brain stimulation, electrophysiological and neuroimaging techniques to test the participation of sensory and motor areas in these processes and circuit level changes that predict learning and retention. Our preliminary work supports the idea that there is plasticity in each of the primary systems which participate in speech motor learning (auditory, somatosensory, motor).

PI_NAMEs: OSTRY, DAVID J (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Adaptive Behaviors;Adult;Area;Auditory;Auditory area;auditory feedback;Brain;Child;Clinical Research;Data;design;Electroencephalography;Electromyography;Electrophysiology (science);Evoked Potentials;experimental study;Functional Magnetic Resonance Imaging;Goals;Human Development;Impairment;Individual;Learning;Measures;memory consolidation;memory retention;Modeling;Motor;Motor Cortex;Motor Evoked Potentials;motor learning;Movement;neural;neuroimaging;Neurons;novel strategies;Pattern;Play;Process;Production;Property;Rehabilitation therapy;Research;response;Rest;Role;Sensory;sensory system;Series;somatosensory;Somatosensory Cortex;Speech;System;Techniques;Testing;Time;Transcranial magnetic stimulation;Work

PROJECT_TITLE: Sensorimotor Basis of Speech Motor Learning and Retention

STUDY_SECTION: MFSR

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