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

PHR: PROJECT NARRATIVE: Per the program announcement, the Cumulative Project Narrative has been included in the Overall Component, Other Project Information section.

PI_NAMEs: STRITTMATTER, STEPHEN M (contact)

PROJECT_TERMS: Advisory Committees;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease related dementia;Biological;career;career development;catalyst;Cells;Cellular biology;Clinical Data;cohesion;Communication;Communities;Data;Development;Discipline;Disease;education research;effective therapy;Ensure;Environment;Fostering;Goals;Grant;Health Insurance Portability and Accountability Act;Heterogeneity;IACUC;Image;Individual;innovation;Knowledge;Leadership;Logistics;meetings;member;Mentors;Methodology;Monitor;Neurosciences;NIH Program Announcements;Procedures;programs;Regulation;Research;Research Personnel;Research Project Grants;Research Support;Resources;Specimen;Tissues;Translating;Translational Research;United States National Institutes of Health;Work

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: LA JOLLA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The proposed study will investigate the role of LZK and DLK, a pair of MAP kinase kinase kinases, in the multicellular responses to spinal cord injury, which will provide novel insight on the neuron intrinsic and extrinsic regulation of axonal repair after spinal cord injury. If manipulating LZK and/or DLK is found to enhance tissue and axonal repair after spinal cord injury, this would pave the way to develop therapeutic intervention targeting LZK and/or DLK. The ultimate goal is to improve the quality of life for people with spinal cord injury or related neurological conditions.

PI_NAMEs: ZHENG, BINHAI  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Adopted;Animal Model;Area;Astrocytes;astrogliosis;Axon;axon growth;axon injury;axon regeneration;axonal degeneration;axonal sprouting;Brain Injuries;Caenorhabditis elegans;Cell Death;cell type;Central Nervous System;central nervous system injury;Cicatrix;Complex;Contusions;Corticospinal Tracts;Coupled;Data;Drosophila genus;Explosion;Fibroblasts;functional restoration;Future;gain of function;Gene Deletion;Genetic;genetic approach;Goals;Homologous Gene;IGF1 gene;improved;inhibitor;Injury;injury and repair;insight;Invertebrates;Knowledge;Leucine Zippers;Literature;loss of function;Macrophage;MAP Kinase Kinase Kinase;Mediating;Microglia;Modeling;Molecular;mouse genetics;Mus;Natural regeneration;Neurodegenerative Disorders;Neurologic;Neuronal Injury;Neurons;novel;Optic Nerve Injuries;osteopontin;Outcome;overexpression;Paralysed;Pathway interactions;Pericytes;Peripheral nerve injury;Persons;Phenotype;Phosphotransferases;Play;Positioning Attribute;preservation;Process;PTEN gene;Publications;Publishing;Quality of life;Recovery;Recovery of Function;regenerative;Regulation;repaired;Research;response;response to injury;RiboTag;Role;seal;Signal Pathway;Signal Transduction;Site;Spinal Cord;Spinal cord injury;spinal cord repair;STAT3 gene;Stroke;synergism;Testing;therapeutic development;Therapeutic Intervention;tissue repair;Tissues;transcriptomics;Viral

PROJECT_TITLE: The Role of a Pair of MAP3Ks in the Multicellular Response to Spinal Cord Injury

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: NEW HAVEN

ORG_DEPT: DERMATOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Effective methods to regenerate hair follicles in adult humans are limited, largely because the events that lead to hair follicle formation are poorly mapped. In this grant, we leverage state-of-the art single-cell genomic methods, live imaging, and in vivo models to build a high-resolution roadmap of the key steps that lead to hair follicle induction. The ultimate goal of this project is to develop faithful methods to restore these events in adult skin in an effort to promote hair follicle regeneration, while also providing an experimental framework that can be used to study the formation of other skin appendages.

PI_NAMEs: MYUNG, PEGGY S (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Ablation;Acceleration;Address;Adult;Affect;appendage;CDKN1B gene;Cell Cycle;Cell Differentiation process;Cell Lineage;Cells;Collaborations;Computing Methodologies;Coupled;Cues;Cutaneous;Data;Dermal;Development;Diffusion;Embryo;Engineering;Epithelium;Event;Fibroblasts;Fluorescent in Situ Hybridization;Genetic;Genetic Transcription;Goals;Grant;Growth;Hair follicle structure;hair regeneration;Human;Image;In Vitro;in vivo;in vivo Model;innovation;Kinetics;Label;Location;Maps;Mathematics;Mesenchymal;Methods;Modeling;Molecular;Morphogenesis;Morphology;mouse model;Mus;mutant;Natural regeneration;Pathway interactions;Phase;Physical condensation;Population;Process;progenitor;programs;Proliferating;Protocols documentation;regenerative;Resolution;RNA;Role;Signal Pathway;Signal Transduction;single cell genomics;single molecule;single-cell RNA sequencing;Skin;spatiotemporal;Specific qualifier value;Techniques;Time;tongue papilla;two-photon;Undifferentiated

PROJECT_TITLE: Delineating spatiotemporal dynamics of hair follicle dermal niche specification at the single-cell level

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

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

PI_NAMEs: VAN DYCK, CHRISTOPHER H (contact)

PROJECT_TERMS: abeta deposition;Acceleration;Action Research;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Autopsy;Biological;Biological Markers;biomarker validation;Categories;Cessation of life;Classification;Clinical;Clinical Research;Cognitive;Collaborations;Collection;Consent;data management;Data Set;Dementia;Development;Diagnostic;Diagnostics Research;Disease;disease phenotype;Early Diagnosis;education research;Enrollment;Evaluation;Exclusion Criteria;First Degree Relative;follow up assessment;Future;Goals;Image;imaging study;improved;inclusion criteria;interest;Liquid substance;Longitudinal Studies;Measures;Methods;middle age;mild cognitive impairment;Nerve Degeneration;neuroimaging;neuropathology;Neurosciences;NIH Program Announcements;nonalzheimer dementia;outreach;Participant;participant enrollment;Pathogenesis;Pathologic;Patients;Plasma;Population;pre-clinical;prevent;programs;Protocols documentation;recruit;repository;Research;Research Personnel;Research Project Grants;research study;Research Support;Resources;Serum;Specimen;study population;Synapses;System;Target Populations;tau Proteins;Testing;Therapeutic;therapeutic development;therapy development;Time;Training;translational scientist;validation studies;Whole Blood;Work

PROJECT_TITLE: Clinical Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Data Science;Dementia;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

PI_NAMEs: ALLORE, HEATHER GWYNN (contact)

PROJECT_TERMS: Aging;Alzheimer's Disease;Bioinformatics;Biological Markers;Biological Specimen Banks;Biomedical Computing;biomedical informatics;Biometry;Clinical;Clinical Research;Collaborations;computational neuroscience;Computer software;Data;Data Analyses;data exchange;data infrastructure;data integration;data management;data sharing;data standards;data tools;Databases;design;Development;Education;education research;Educational workshop;Enrollment;Ensure;Evaluation;Faculty;falls;follow-up;graduate student;Guidelines;Image;Individual;Infrastructure;innovation;interest;Medical Students;meetings;Mentors;method development;Methodology;neuroimaging;neuropathology;neuroproteomics;Neurosciences;Neurosciences Research;NIH Program Announcements;novel;Ontology;outreach;Participant;Postdoctoral Fellow;Procedures;Progress Reports;Quality Control;recruit;Research;Research Design;Research Personnel;Resolution;Sampling;Series;Software Tools;Statistical Data Interpretation;Statistical Methods;statistics;System;Tissues;United States National Institutes of Health;Vocabulary;webinar;Work

PROJECT_TITLE: Data Management Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Data Science;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Precision Medicine;Prevention

PI_NAMEs: NAIRN, ANGUS C. (contact)

PROJECT_TERMS: aging biomarker;Alzheimer's Disease;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;assay development;biobank;Bioinformatics;Biological Assay;Biological Markers;Biological Specimen Banks;biomarker selection;brain tissue;Cell Extracts;cell free DNA;Clinical;Cognitive;Computational Biology;Data;data integration;data management;Databases;design;Development;disease heterogeneity;Disease susceptibility;DNA Integration;DNA Methylation;Education;Education and Outreach;Enzyme-Linked Immunosorbent Assay;Epigenetic age;Epigenetic Process;experience;Future;Gene Expression;Genetic;Health and Retirement Study;high dimensionality;Human;Image;Immune;improved;Intervention;Knowledge Portal;Mass Spectrum Analysis;Measures;member;Methodology;Methods;Modeling;Molecular;mortality;Multiomic Data;neuropathology;NIH Program Announcements;novel;novel marker;outreach;Pathway Analysis;Play;Predisposition;Protein Analysis;protein biomarkers;Proteomics;Research;Research Personnel;Research Project Grants;risk prediction;Sampling;Scientist;Standardization;Statistical Models;statistics;System;Systems Biology;tau Proteins;tau-1;Tissue Banks;tissue biomarkers;Training;transcriptomics;Validation;Validity and Reliability;Work

PROJECT_TITLE: Biomarker Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Influenza;Pneumonia and Influenza;Rare Diseases

ORG_CITY: Chicago

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative This is highly significant project for the public health because it will elucidate a broad antiviral mechanism, which will be likely translated into a novel antiviral countermeasure for HIV-1 and other highly pathogenic human viruses including SARS-CoV2, Ebola viruses, and influenza viruses.

PI_NAMEs: ZHENG, YONG-HUI  (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: 2019-nCoV;Ablation;Acetylgalactosamine;Adopted;alpha helix;Bioinformatics;CCL7 gene;CD4 Positive T Lymphocytes;Cell Line;Cell membrane;Cells;Cellular Membrane;Chikungunya virus;Chimeric Proteins;Complex;Coronavirus;CRISPR/Cas technology;Defect;Ebola virus;Endoplasmic Reticulum;Eukaryotic Cell;experimental study;Family;Glycoproteins;Glycoside Hydrolases;glycosylation;glycosyltransferase;Goals;Golgi Apparatus;gp160;Hemagglutinin;HIV;HIV-1;Human;Human immunodeficiency virus test;Hybrids;Infection;Influenza A virus;influenzavirus;Investigation;Knock-out;Laboratories;Lymphocytic choriomeningitis virus;Lysosomes;Macrophage;Mannose;Mediating;member;Membrane;Membrane Fusion;Middle East Respiratory Syndrome;Middle East Respiratory Syndrome Coronavirus;Molecular;monocyte;Mouse Mammary Tumor Virus;novel;Nucleocapsid;Oligosaccharides;Organelles;particle;Pathogenicity;Play;polypeptide;Polysaccharides;Polyubiquitination;porcine epidemic diarrhea virus;Process;Protein Biosynthesis;protein degradation;protein folding;Protein Glycosylation;protein oligomer;protein transport;Proteins;Public Health;receptor;receptor binding;Reporting;RNA Interference;Rod;Role;SARS coronavirus;SARS-CoV-2 spike protein;SIV;SNAP receptor;Structure;Surface;T-Lymphocyte;Testing;trans-Golgi Network;Translating;Translational Research;ubiquitin-protein ligase;Vesicular stomatitis Indiana virus;Viral;Viral Fusion Proteins;Viral Physiology;Viral Proteins;Virion;virology;Virus;Virus Diseases;Virus Replication;Zika Virus

PROJECT_TITLE: HIV-1 Env gp160 maturation in the Golgi apparatus

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: HUTTNER, ANITA JULIANE (contact)

PROJECT_TERMS: age related neurodegeneration;aged;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Autopsy;B-Lymphocytes;biobank;Biological Markers;Biopsy Specimen;Brain;brain control;brain tissue;candidate validation;cell bank;Cell Culture Techniques;Cell Line;Cerebrovascular Disorders;Characteristics;Clinical;Collaborations;Collection;Communities;comorbidity;Data;Data Analyses;Data Collection;data management;data standards;demented;design;Diagnosis;Disease;Dura Mater;Fibroblasts;Freezing;Frontotemporal Lobar Degenerations;Genetic;Goals;hippocampal sclerosis;Home;Human;Image;Individual;induced pluripotent stem cell;Investigation;Lewy Body Disease;Link;Macaca mulatta;Methodology;Modeling;Nerve Degeneration;Neurodegenerative Disorders;neuroimaging;neuropathology;Neurosciences;NIH Program Announcements;nonhuman primate;novel;Participant;Pathogenicity;Pathologic;Patients;Process;Qualifying;Research;Research Personnel;Resolution;Resources;Rhesus;Sampling;Skin;Spinal Cord;statistics;stem cell technology;success;Tissue Sample;Tissues;Work

PROJECT_TITLE: Neuropathology Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research

PI_NAMEs: MAROTTOLI, RICHARD  (contact)

PROJECT_TERMS: abeta deposition;Acceleration;Action Research;Advocate;Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;apolipoprotein E-4;Biological;Biological Markers;Caring;Categories;Classification;Clinical;clinical center;clinical investigation;Cognitive;cognitive testing;Collaborations;Collection;Communication;Communities;community advisory board;community organizations;community partners;Connecticut;Dementia;Diagnosis;Diagnostic;Early Diagnosis;Education;Elderly;Enrollment;Ensure;Ethnic Population;Evaluation;Family;Family member;Federally Qualified Health Center;First Degree Relative;Fostering;Funding;Future;General Population;Goals;Group Practice;Health Personnel;Health Professional;Health system;improved;Individual;Infrastructure;interest;Liquid substance;Longitudinal Studies;Medical;middle age;mild cognitive impairment;Minority;Minority Groups;Minority Health Research;Minority Recruitment;Modeling;Needs Assessment;Nerve Degeneration;neuroimaging;neuroimaging marker;Neurosciences;New York;NIH Program Announcements;nonalzheimer dementia;outreach;Participant;participant retention;Pathogenesis;Pathologic;Patient Participation;Patient Recruitments;Patients;Population;pre-clinical;prevent;primary care clinician;programs;Protocols documentation;racial difference;racial minority;racial population;recruit;Research;research study;Resources;Rhode Island;service providers;Services;Source;study population;tau Proteins;therapeutic development;therapy development;Underrepresented Populations;Work

PROJECT_TITLE: Outreach Recruitment and Education (ORE) Core


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics;Neurosciences

ORG_CITY: MINNEAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Inward Rectifier K+ channels (KIR) play key roles in the operation of cells in neuromuscular and other tissue. We will provide the first comprehensive assessment of missense and topological mutations’ effects on KIR trafficking and function. Acquisition of these data is the required first step to build quantitative biophysical model of the sequence, structure, and function relationship in KIR, to understand the mechanistic basis for KIR mutation phenotypes in disease etiology, to identify new treatment strategies for KIR-linked disorders, and to rational engineering of KIR as chemogenetic reagents.

PI_NAMEs: SCHMIDT, DANIEL  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: addiction;Amino Acids;Benchmarking;Benign;Biological Assay;biophysical model;Cardiology;Cardiovascular Diseases;Cell Line;Cell surface;Cells;Clinical;Coupled;Data;data acquisition;Data Set;Defect;Diabetes Mellitus;Disease;Drug Modulation;Engineering;Etiology;Flow Cytometry;Genetic;Genotype;GIRK1 subunit, G protein-coupled inwardly-rectifying potassium channel;human disease;inward rectifier potassium channel;Ion Channel;Ions;Libraries;Ligands;Link;Machine Learning;Maps;Membrane Potentials;Metabolic Diseases;Missense Mutation;Modeling;Molecular;Molecular Chaperones;Mutagenesis;Mutation;Nervous System Disorder;neuromuscular;Neurons;next generation sequencing;novel therapeutic intervention;novel therapeutics;operation;Pathogenicity;Peptides;Pharmaceutical Preparations;Phenotype;phenotypic data;Play;Potassium Channel;Property;Proteins;Reagent;Regulation;Resources;Rest;Role;Sirolimus;structural determinants;Structure;Surface;technological innovation;Tertiary Protein Structure;Tissues;tool;trafficking;Trimethoprim;Variant

PROJECT_TITLE: Comprehensive mapping of trafficking and functional robustness in Inward Rectifier K+ channels for variant pathogenicity prediction and model-guided engineering of chemogenetic reagents

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Compelling evidence exists that vulnerable populations such as people of color, persons of lower socioeconomic status, or individuals with limited health literacy continue to have significant health problems. We are proposing to train nurse scientists who can address these problems in new and effective ways which in turn will promote health equity.

PI_NAMEs: HAN, HAE-RA  (contact)

PROGRAM_OFFICER_NAME: KEHL, KAREN

PROJECT_TERMS: health equity;Life Cycle Stages

PROJECT_TITLE: Strength-Based Health Equity Across the Life Course


ADMINISTERING_IC: AA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: PROJECT NARRATIVE Microglia have been recently implicated in the development and maintenance of alcohol use disorder (AUD). Although research on this cell type has bloomed in recent years, little is understood about the role of microglia in the development of AUD following early life stress. The present study proposes to investigate the effects of early life stress and alcohol exposure on microglia function in a holistic and unbiased manner.

PI_NAMEs: GIRONDA, STEPHEN CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: 3-Dimensional;Affect;Affinity Chromatography;Alcohol consumption;alcohol exposure;alcohol use disorder;Alcohols;Behavior;Brain;Brain region;cell type;Cessation of life;comorbidity;Darkness;Data;deter alcohol use;Development;Disease;drinking;drinking behavior;Early identification;early life stress;Early treatment;Environmental Exposure;Epidemiology;Ethanol;Event;Exhibits;experimental study;Exposure to;Functional disorder;Future;Gene Expression;Genetic Transcription;Goals;Grant;Hippocampus;Homeostasis;insight;Investigation;Knock-in Mouse;Label;Lead;Lifestyle-related condition;Light;Limbic System;Link;Literature;Maintenance;Medial;Microglia;Microscopy;Modeling;Morphology;mRNA sequencing;Mus;Nervous System Disorder;neuropsychiatric disorder;novel;Outcome;periadolescent;Persons;Phenotype;pre-clinical;Prefrontal Cortex;prevent;Preventive care;Protocols documentation;reconstruction;Regulation;Research;Resolution;Rest;Ribosomes;Risk Factors;RNA;Rodent Model;Role;Running;Sampling;social stress;Societies;Sorting;Stains;Stimulus;Stress;Structure;Synapses;synaptogenesis;Techniques;Transgenic Mice;Translating;United States;Work

PROJECT_TITLE: Alterations in Microglial function moderate the development of maladaptive drinking behaviors following early life stress and are exacerbated by ethanol consumption


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences

PI_NAMEs: CARSON, RICHARD E. (contact)

PROJECT_TERMS: aged;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer’s disease biomarker;Amyloid;analytical method;Atlases;Autopsy;Behavior;Behavioral Model;Binding;Biological Markers;Brain;Clinical;Clinical Research;Clinical Trials;Cognitive;connectome;connectome based predictive modeling;Data;Data Analyses;data management;Data Set;deep learning;density;Development;Dimensions;Disease Pathway;Disease Progression;experience;fluorodeoxyglucose;Functional disorder;Functional Magnetic Resonance Imaging;Future;glucose metabolism;Goals;Hippocampus;Human;human data;human imaging;human subject;Image;Image Analysis;imaging biomarker;Imaging Device;imaging study;Imaging technology;in vivo;in vivo imaging;Individual;Infrastructure;innovation;Link;Magnetic Resonance;Magnetic Resonance Imaging;Measurable;Measures;Methodology;Methods;mild cognitive impairment;Modeling;multimodal data;Multimodal Imaging;multimodality;Nerve Degeneration;neuroimaging;neuropathology;next generation;NIH Program Announcements;Noise;nonhuman primate;novel;novel strategies;Paper;Participant;Patients;Pattern;Phenotype;Positron-Emission Tomography;pre-clinical;Principal Investigator;programs;Radiation Dose Unit;Research;Research Personnel;research study;Resolution;Resources;Scanning;Statistical Data Interpretation;Statistical Models;Structure;Study Subject;success;Synapses;System;tau Proteins;Techniques;Tracer;Training;Work

PROJECT_TITLE: Imaging Core


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Mental Health;Prevention;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: NARRATIVE Evidence shows transgender women (TW) will only use biomedical HIV prevention strategies that have been rigorously assessed for safety, tolerability, and efficacy in this population, however, TW's participation in HIV vaccine trials is exceedingly low (<2% of trials participants), which will likely preclude their uptake of future vaccines. In response, the proposed R21 will develop and test a tailored digital health communication tool titled “VaxCom” to increase recruitment and enrollment of TW in Phase 1 vaccine trials by cuing discussions on TW's unique HIV vaccine questions/concerns, Phase 1 trials participation, and by presenting the associated information on these topics in a way that is targeted and meaningful to TW. Increasing TW's participation in Phase 1 HIV vaccine trials has the potential to generate meaningful TW-specific safety data, which can be leveraged to improve their participation in subsequent HIV vaccine trials phases.

PI_NAMEs: RAEL, CHRISTINE TAGLIAFERRI (contact);SOLER, JORGE ;STONBRAKER, SAMANTHA

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: Address;Adherence;Agreement;AIDS prevention;Anti-Retroviral Agents;Blood;Clinical;Collaborations;Communication;Communication Tools;Communities;Companions;Comprehension;Data;data quality;Databases;design;Development;digital communication;digital health;digital tool;Discrimination;Enrollment;Ensure;Evaluation;experience;Face;FDA approved;flexibility;Funding;Future;handheld mobile device;health care availability;health information technology;HIV;HIV vaccine;HIV Vaccine Trials Network;Human immunodeficiency virus test;Image;Immunity;improved;Incidence;Information Specialists;Injections;Institution;Intervention;Interview;Investments;Knowledge;Literature;medication compliance;mobile computing;Modeling;Names;New York;Nucleic Acids;operation;Oral;Participant;Persons;Pharmaceutical Preparations;Phase;phase 1 study;phase I trial;pilot test;Population;pre-exposure prophylaxis;preference;Prevalence;Prevention strategy;Process;prototype;Reaction;recruit;Registries;Reporting;Research;response;Safety;safety assessment;safety testing;Signal Transduction;Site;social;social culture;social stigma;Specialist;success;System;Testing;tool;transgender;transgender women;transphobia;United States;Universities;uptake;usability;vaccine candidate;vaccine trial;Vaccines;Viral Vector;virtual;Visit;willingness;Work

PROJECT_TITLE: Formative work to develop differentiated communication tools to facilitate transgender women's recruitment, enrollment, and retention in HIV vaccine trials


PI_NAMEs: GRUTZENDLER, JAIME  (contact)

PROJECT_TERMS: Address;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;American;Applications Grants;Area;Award;Basic Science;biological research;Biometry;Capsicum;career;career development;Categories;Clinical;clinical center;clinical investigation;Clinical Research;Clinical Sciences;cohort;Collaborations;Community Outreach;Cultural Backgrounds;demented;Dementia;design;Development;Disease;diversity and inclusion;Education;education research;Educational Activities;Educational Curriculum;Educational process of instructing;Elderly;Ensure;Ethics;experience;Faculty;Fertilization;Financial Support;Funding;Funding Opportunities;Future;Goals;graduate student;Grant;Growth;Heterogeneity;improved;Individual;Infrastructure;innovation;Institution;Interdisciplinary Education;interest;Knowledge;Leadership;Learning;Letters;Link;Manuscripts;meetings;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Monitor;multidisciplinary;Nerve Degeneration;Neurology;Neurosciences;New York;NIH Program Announcements;Outcome;Pattern;Periodicals;Preparation;Professional Competence;Program Effectiveness;programs;Psychiatry;Quality of life;Radiology Specialty;recruit;Research;research and development;Research Design;Research Personnel;Research Project Grants;Resources;responsible research conduct;satisfaction;Services;skills;success;Time;Training;Translational Research;translational research program;Underrepresented Populations;Universities;Update;Work;Writing

PROJECT_TITLE: Research Education Core


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Rehabilitation

ORG_CITY: GAINESVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it comprehensively investigates nervous system mechanism of rotator cuff tears-induced pain, a common shoulder injury that affects approximately 4.5 million Americans every year. Understanding these mechanisms will identify targets for interventions and move us toward developing patient-specific treatments for individuals with rotator cuff tears. The proposed project is relevant to the NIAMS’ mission to investigate the cause, treatment, and prevention of musculoskeletal diseases.

PI_NAMEs: POZZI, FEDERICO  (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Acute;Address;Affect;Affective;American;Area;Biomechanics;Brain;Brain imaging;Brain region;Caring;Chronic;chronic musculoskeletal pain;chronic pain;Clinical;clinical pain;clinically relevant;Cognitive;cognitive modulation of pain;Data;design;Disease;Dissociation;Etiology;experimental study;follow-up;Foundations;Goals;Impairment;improved;Individual;individualized medicine;Injury;innovation;Intervention;Investigation;Isometric Exercise;Kinesiology;Knowledge;Measures;Medical;Medicine;Mission;Motor;Movement;muscular structure;Musculoskeletal Diseases;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Nervous System;neuroimaging;Neurosciences;novel;Operative Surgical Procedures;Outcome;Pain;pain processing;Pain Research;pain sensitivity;pain symptom;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Pattern;Phenotype;physical therapist;Play;Positioning Attribute;Prevention;Public Health;Reaction;Recovery;Recovery of Function;recruit;repaired;Research;Research Project Grants;response;Rest;Role;Rotator Cuff;rotator cuff tear;Sensory;Severities;Shoulder;shoulder injury;Stimulus;Strategic Planning;Symptoms;Tendon structure;Testing;trait;treatment optimization;treatment response

PROJECT_TITLE: Nervous system influences on recovery from painful rotator cuff tears

STUDY_SECTION: NPI

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


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: NARRATIVE Human cells can mount multi-pronged defensive responses to viral infection. The protein TRIM5 is positioned to initiate and organize these responses to retroviral infection and can directly interfere with the viral life cycle, transmit immune activating signals, and marshal cellular degradative pathways. The purpose of this project is to use cellular and proteomic approaches to determine how TRIM5 coordinates its myriad antiviral activities upon recognition of retroviral capsids with the long term goal of enabling our understanding and potential therapeutic manipulation of protective or pathogenic cellular responses to retroviruses including HIV-1.

PI_NAMEs: MANDELL, MICHAEL AARON (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Address;Alleles;Anti-Inflammatory Agents;Anti-Retroviral Agents;Anti-viral Response;Anti-viral Therapy;Autophagocytosis;Autophagosome;Binding;Biochemical;Biogenesis;Biological;Capsid;Cell Survival;Cells;Complex;cytokine;Cytoplasm;Cytoprotection;Data;Degradation Pathway;Detection;Development;Disease;DNA;Evolution;Family;Flavivirus;Foundations;Genes;Genetic;Goals;HIV;HIV Infections;HIV-1;Homeostasis;Host Defense;Human;human disease;Immune;immune activation;Immune signaling;Immunologics;Individual;Infection;Inflammation;Inflammatory;innovation;insight;Interferon alpha;Interferons;Knowledge;Life Cycle Stages;Ligation;Link;Malignant Neoplasms;Mediating;Membrane;Methodology;Modeling;Molecular;Natural Immunity;novel;Outcome;Pathogenicity;Pathway interactions;Pattern Recognition;Pattern recognition receptor;Persons;Phosphotransferases;Play;Positioning Attribute;Predisposition;Primate Retrovirus;Process;Production;Protein Family;Protein Isoforms;Proteins;Proteomics;Publishing;Quality Control;Regulation;Reporting;response;Retroviridae;Risk;Role;scaffold;Schizophrenia;Shapes;Signal Pathway;Signal Transduction;Signaling Protein;System;TBK1 gene;Testing;Therapeutic;transmission process;TRIM Family;TRIM5 gene;Viral;Viral Physiology;Viral Proteins;Virus;Virus Diseases;Work

PROJECT_TITLE: Cellular responses to retroviral capsid recognition

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Hematology;Kidney Disease;Neurodegenerative;Prevention

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE The current application seeks to identify and understand the role of DNA changes in blood cells in the development of new onset mild cognitive impairment, dementia and kidney disease progression. Strong epidemiologic evidence indicates that chronic kidney disease (CKD), an age-related clinical disorder is associated with accelerated cognitive function decline. Knowledge gained from this work may contribute to the discovery of new ways to reduce the burden of cognitive function decline and kidney disease progression associated with aging.

PI_NAMEs: CHONCHOL, MICHEL BENJAMIN (contact);SHLUSH, LIRAN

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Acceleration;Adipocytes;Adult;age related;age-related disease;aged;Aging;aging related;Automobile Driving;Biological;Blood;Blood Cells;blood pressure intervention;Bone Marrow;Cardiovascular Diseases;Cardiovascular system;Cells;Cessation of life;Chronic;Chronic Kidney Failure;Clinical;clinical risk;Clonal Evolution;Clonal Expansion;Cognitive;cognitive function;cohort;Data;Dementia;Development;Disease;Disease Progression;DNA;Elderly;environmental stressor;Epidemiology;Event;Fatty acid glycerol esters;Femur;functional decline;Genes;Genetic;genomic data;global health;Goals;Growth;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;high risk;Human;Impaired cognition;Impairment;Incidence;Individual;Inflammatory;inflammatory marker;insight;Interleukin-6;Intervention Trial;Kidney;Kidney Diseases;Knowledge;leukemia;Link;Magnetic Resonance Imaging;Malignant Neoplasms;metabolomics;mild cognitive impairment;Modeling;mortality;mutant;Mutation;novel;Participant;Pathogenesis;Pathologic;Patient Recruitments;Patients;Play;Prevalence;Prognosis;prospective;Quality of life;recruit;Renal function;Resources;Risk Factors;Role;Shapes;Somatic Mutation;systemic inflammatory response;targeted sequencing;Testing;Vascular Diseases;Vertebral column;Work

PROJECT_TITLE: Clonal hematopoiesis, mild cognitive impairment and kidney function decline


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: LINCOLN

ORG_NAME: UNIVERSITY OF NEBRASKA LINCOLN

ORG_STATE: NE

PHR: PROJECT NARRATIVE Neuropeptides and peptide hormones act as messengers to facilitate communication between cells in the central nervous system and endocrine system. Because many human diseases are caused by a dysregulation of normal cellular communication, it is critically important for human health to fully understand and selectively modulate these signaling pathways. This research develops chemical probes and approaches to interrogate the molecular mechanisms of peptide transmitters in disease, which will reveal new targets for therapeutic intervention.

PI_NAMEs: CHECCO, JAMES WILLIAM (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Agonist;antagonist;Area;Biomedical Research;Cells;Central Nervous System;Chemicals;Communication;Complement;design;Diabetes Mellitus;Disease;Endocrine system;Event;Goals;Health;hormonal signals;Hormones;Human;human disease;intercellular communication;interdisciplinary approach;Malignant Neoplasms;Mass Spectrum Analysis;Methods;Molecular;Neurodegenerative Disorders;Neuropeptides;new therapeutic target;novel;novel therapeutics;Obesity;Osteoporosis;peptide hormone;Peptide Receptor;Peptide Signal Sequences;Peptides;peptidomimetics;Physiology;Post-Translational Protein Processing;programs;Proteins;receptor;Research;Role;Route;Signal Pathway;Signal Transduction;Signaling Molecule;System;Therapeutic;Therapeutic Agents;Therapeutic Intervention;therapeutic target;tool;Work

PROJECT_TITLE: Chemical approaches to interrogate neuropeptide and peptide hormone signaling in disease

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


ORG_CITY: MADISON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative The goal of Graduate Training in Molecular and Cellular Pharmacology (GTMCP) at the University of Wisconsin- Madison is to train a diverse group of students in the discipline of Pharmacology to prepare them for careers that focus on the development of new therapeutics to treat disease. This application highlights a redesigned curriculum that strongly emphasizes the importance of rigor and reproducibility and mentor-mentee relationships, the necessity for professional development opportunities throughout graduate training to expose students to a wide variety of career options in the Pharmacological Sciences, and inclusive research training focused on the development of operational and technical skills in quantitative and systems Pharmacology to provide trainees with a mechanistic understanding of drug action, how it relates to normal human physiology, and how to exploit this knowledge to ameliorate pathophysiological conditions.

PI_NAMEs: AUDHYA, ANJON  (contact);LEBEAU, AARON MATTHEW

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Molecular;Pharmacology;Training

STUDY_SECTION: TWD

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: LOS ANGELES

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Public Health Narrative The UCLA Chemistry Biology Interface (CBI) Training Program trains a diverse set of scientists working towards a PhD to apply state-of-the-art tools of chemical research to biological problems. The graduates of this program will become leading researchers in rigorous and ethical biomedical research and will develop the understanding and skills that will advance medical research and health in the United States.

PI_NAMEs: HARRAN, PATRICK G. (contact)

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TERMS: Biology;Chemistry;Training Programs

PROJECT_TITLE: Chemistry Biology Interface Training Program

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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

ORG_CITY: BOSTON

ORG_DEPT: BIOLOGY

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

ORG_STATE: MA

PHR: Project Narrative Investigating the neural basis of social behavior such as mating and aggression provides a strong framework to reveal general principles of how the nervous system supports behavior. This proposal seeks to define the manner by which sensory input relating to social partners is processed and transmitted throughout the brain to guide appropriate behavior. The results of these experiments will determine broad principles of how the brain parses out and acts on social information—the comprehension of which will greatly inform our understanding of maladaptive social behaviors in humans.

PI_NAMEs: MONK, KEVIN JAMES (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TERMS: Accessory Olfactory Bulbs;Address;Affect;Afferent Neurons;Age;Aggressive behavior;Amygdaloid structure;Anatomy;Animals;Area;awake;Behavior;behavior change;Behavioral;Brain;Complex;Comprehension;Coupled;Detection;Electrophysiology (science);Environment;Event;experience;experimental study;feature detection;Female;flexibility;genetic manipulation;Head;Human;Image;Individual;information processing;innovation;Investigation;Label;Life;Limbic System;male;Medial;Memory;Microscope;mitral cell;Mus;nerve supply;Nervous System;network architecture;neural;neuromechanism;Neurons;olfactory bulb glomeruli;Output;Partner in relationship;Pathway interactions;Pattern;Peripheral;Pheromone;Physiological;Population;Process;Recording of previous events;response;Sampling;Sensory;sensory input;sensory mechanism;sex;Sexual Partners;Shapes;Signal Transduction;Site;social;Social Behavior;Social Controls;Social Interaction;social learning;stimulus processing;Structure;Structure of terminal stria nuclei of preoptic region;Support System;System;Technology;Training;transmission process;Viral;Vomeronasal Systems

PROJECT_TITLE: Social Information Processing in the Vomeronasal System during Active Behavior


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

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: NARRATIVE While the prevalence of autism continues to rise (currently 1 in 44 children), the brain bases of the communication challenges observed in autistic individuals remain unclear. It is hypothesized that motor differences may underlie many of the speech, language, and communication difficulties observed in autistic individuals. This project will precisely characterize the motor regions in the brain related to speech production in autistic and neurotypical adults, thoroughly assess the speech, language, and motor profiles of these adults, and examine the relationship between the speech production motor brain activation and behavioral profiles of these individuals, with the goal of better understanding the role of the motor system in communication for autistic adults.

PI_NAMEs: O'BRIEN, AMANDA  (contact)

PROJECT_TERMS: Academia;Address;Adult;adult with autism spectrum disorder;Age;American Psychiatric Association;Articulation;autism spectrum disorder;autistic;autistic children;base;Behavior;Behavioral;behavioral phenotyping;behavioral study;Brain;brain based;Brain region;career;Child;Clinical;Communication;Communication difficulty;design;Development;Diagnosis;Functional Magnetic Resonance Imaging;Goals;Heterogeneity;improved;Individual;individuals with autism spectrum disorder;insight;interest;Knowledge;Language;Literature;Measures;Mentors;Motor;Motor Skills;Movement;neuroimaging;novel;Oral;Participant;Phenotype;Play;Population;Prevalence;Process;Production;recruit;repetitive behavior;Research;Role;Scanning;skills;social communication;social skills;Speech;Symptoms;syntax;System;Testing;Training;Validation;Variant;Vocabulary;Work;Writing

PROJECT_TITLE: The Role of the Motor System in Speech and Language in Autism


ORG_CITY: SEATTLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative BK channels are potassium channels involved in multiple physiological functions. Mutations in the BK channel underlie a group of human channelopathies characterized by neurodevelopmental delay, seizures, and movement disorders. Proximity of BK channels to calcium channels is crucial for their function; however, little is known about the mechanisms governing this channel-to-channel proximity. Our long-term goal is to identify the mechanisms controlling the spatial organization of BK channels and its co-clustering with calcium channels.

PI_NAMEs: VIVAS, OSCAR  (contact)

PROJECT_TERMS: Area;Biophysics;C-terminal;Calcium;Calcium Binding;Calcium Channel;Cardiovascular system;Cell membrane;Cholesterol;Cytoplasm;design;Disease;Electrophysiology (science);Endocrine system;Epilepsy;Fluorometry;gastrointestinal system;Goals;Health;Human;insight;Ion Channel;large-conductance calcium-activated potassium channels;lipid metabolism;Lipids;Lymphatic System;Maintenance;Mediating;Membrane Lipids;Molecular;Movement Disorders;muscular system;Mutation;Names;Nervous System Physiology;Organ;Pharmacology;Phosphatidylinositols;Physiological;Potassium;Potassium Channel;programs;Reproductive system;Research;Role;Signal Transduction;Skeletal system;Source;superresolution microscopy;Urinary system;Visual System;voltage;Work

PROJECT_TITLE: Mechanisms behind the clustering of BK and calcium channels

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-G(07)R]


NIH_SPENDING_CATS: Genetics;Immunotherapy

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Regulatory T (Treg) cells play an essential role in controlling autoimmune diseases and chronic inflammation and understanding the mechanisms that control the function of Treg cells would be important in devising novel treatments of autoimmune and inflammatory disease. We have uncovered a key molecular pathway by which Treg cells lose their immune suppressive function due to their loss of a master protein called Foxp3 and identified novel approaches to re-establish the function of Treg cells under such conditions, relevant to chronic human inflammatory diseases such as asthma, autoimmune diseases and others in which Treg cells are unable to control the immune response. The proposed studies aim to understand how this pathway leads to inflammation and autoimmunity and may lead to novel therapies for inflammatory and autoimmune diseases by boosting Treg cell activity to promote immunological tolerance.

PI_NAMEs: CHARBONNIER, LOUIS-MARIE  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: aerobic glycolysis;Agreement;airborne allergen;Allergic;Antigens;Asthma;Attenuated;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmunity;Cell Differentiation process;Cell Physiology;Cells;Cellular biology;Cellular Metabolic Process;Chronic;combinatorial;commensal microbes;Coupled;Cues;cytokine;Development;Disease;disease model;effector T cell;Elements;Environment;Environmental Exposure;Epigenetic Process;Equilibrium;Evolution;Exhibits;Failure;fatty acid oxidation;Female;Food;FOXP1 gene;FOXP3 gene;Gene Expression Profile;Genes;genetic approach;Genetic Transcription;Glucose;graft vs host disease;Heterogeneity;Heterozygote;Human;human subject;IL2RA gene;Immune;Immune response;Immune System Diseases;Immune Tolerance;immunoregulation;Immunosuppression;imprint;improved;Inflammation;Inflammatory;inflammatory milieu;insight;Interleukin-2;Intervention;loss of function mutation;Lymphoproliferative Disorders;Maintenance;Mendelian disorder;Metabolic;Molecular;Mus;novel;novel strategies;novel therapeutics;Oxidative Phosphorylation;Pathway interactions;Peripheral;personalized intervention;pharmacologic;Phenotype;Play;Population;Precision therapeutics;prevent;Process;programs;Proteins;Regulation;Regulatory T-Lymphocyte;respiratory;restoration;Role;Severities;Severity of illness;Signal Transduction;single-cell RNA sequencing;targeted treatment;Time;transcription factor;transcriptome

PROJECT_TITLE: Reprogramming of Regulatory T cells to Promote Immune Tolerance

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Breast Cancer;Cancer;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Precision Medicine;Prevention;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: This grant would help develop a new approach to studying the progression of brain metastasis in vitro. This is the most lethal complication of breast cancer. The ability to uncover mechanisms of tumor progression during extravasation and colonization will help prevent and treat brain metastasis thus saving lives and improving the quality of life for thousands of patients every year.

PI_NAMEs: FU, JIANPING ;MERAJVER, SOFIA DIANA (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Address;advanced breast cancer;Advanced Development;Animals;Artificial Intelligence;Astrocytes;Behavior;Biological Assay;Blood;Blood - brain barrier anatomy;Brain;brain endothelial cell;cancer cell;Cells;Cellular Morphology;Classification;classification algorithm;Communities;Complication;Computer software;confocal imaging;Cultured Cells;design;Development;Devices;Disseminated Malignant Neoplasm;Event;experience;experimental study;Extracellular Matrix;Extravasation;flexibility;Future;Generations;genomic signature;Genomics;Goals;Grant;Human;hydrodynamic flow;Image;improved;In Vitro;in vitro Model;in vivo;indexing;Individual;Investigation;Length;Lesion;Libraries;live cell imaging;machine learning classifier;Malignant Breast Neoplasm;Malignant Neoplasms;matrigel;Measures;Membrane;Metastatic malignant neoplasm to brain;meter;Microfluidics;Microglia;Micrometastasis;Modeling;Molecular;Molecular Profiling;mouse model;multiple omics;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel strategies;organ on a chip;Pathway interactions;Patients;Pericytes;personalized medicine;Phenotype;Physiological;Plug-in;Porosity;predictive marker;preservation;prevent;Prevention;Primary Neoplasm;Process;Proteomics;Pump;Quality of life;Recovery;Reproducibility;Research;self organization;Site;Software Validation;Standardization;success;Syringes;System;targeted treatment;Technology;technology platform;Therapeutic;therapeutic evaluation;Three-dimensional analysis;Three-Dimensional Image;tool;tumor;tumor microenvironment;tumor progression;Validation;Work

PROJECT_TITLE: Advanced development and validation of an in vitro platform to phenotype brain metastatic tumor cells using artificial intelligence


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Cancer;Liver Disease;Prevention;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have reached epidemic proportions, and remain without FDA-approved therapy. Numerous candidate therapies have been thwarted by inefficacy or side effects, underscoring the need to identify new therapeutic targets that coordinately prevent steatosis, without untoward side effects. We have uncovered here a novel mechanism, the inhibition of which provides uniquely coordinated protection from NAFLD and NASH, and we propose experiments to understand the process in molecular and physiological detail, in order to determine if targeting this pathway may have therapeutic potential.

PI_NAMEs: ARANY, ZOLTAN P (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: ADD-1 protein;arm;Biogenesis;cell type;Characteristics;Cirrhosis;Complex;Confusion;Data;detection of nutrient;Diet;Disease;EIF4EBP1 gene;Epidemic;experimental study;fatty acid oxidation;FDA approved;Feedback;FRAP1 gene;Grant;GTP-Binding Proteins;GTPase-Activating Proteins;Hepatic;Hepatocyte;Homeostasis;Human;In Vitro;in vivo;Knock-out;Knockout Mice;Lead;lipid biosynthesis;Lipids;Literature;Liver;liver cancer model;Liver Fibrosis;liver injury;Malignant Neoplasms;Mediating;Metabolic;Mitochondria;Molecular;Mus;Mutagenesis;new therapeutic target;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;Pathway interactions;Persons;phosphoproteomics;Phosphorylation;Physiological;prevent;Prevention;Primary carcinoma of the liver cells;Process;Proteins;Reporting;response;Role;side effect;Signal Transduction;small hairpin RNA;Small Interfering RNA;Steatohepatitis;stem;Technology;Testing;TFE3 gene;Therapeutic;therapeutic siRNA;therapeutic target;transcription factor;translational potential;TSC1 gene;Tumor Suppressor Proteins

PROJECT_TITLE: Selective mTORC1 inhibition to prevent and treat NAFLD and NASH

STUDY_SECTION: NMHD

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Neurosciences;Substance Misuse

ORG_DEPT: PHARMACOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Project Narrative The purpose of the Drugs of Abuse Training Program at Temple University is to provide comprehensive training for doctoral students and post-doctoral fellows in the areas of the neurobiology of addiction, pharmacology of drugs of abuse, and their intersection with HIV/AIDS. There is a need at the national level for well-trained innovative basic science researchers in areas related to substance abuse, in order to discover new treatment and prevention stategies to combat addictive diseases and their consequences including HIV/AIDS.

PI_NAMEs: UNTERWALD, ELLEN M (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: drug of abuse;Neuropeptides;Training Programs

PROJECT_TITLE: Training Program: Drugs of Abuse & Related Neuropeptides


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Brain Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Social Determinants of Health

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

PHR: NARRATIVE Physician-scientists have a critical role to play in the development, refinement, and application of novel strategies for the diagnosis, treatment, prevention, and cure of mental illness, but the number of highly trained physician-scientists entering psychiatry remains inadequate. The Integrated Mentored Patient-Oriented Research Training (IMPORT) Program has a 15-year history of supporting and accelerating the careers of physician-scientist trainees at psychiatry at Yale; our graduates have gone on to do important work across the country. Here we continue and enhance this program, keeping the core structure that has worked so well while enhancing focus on key areas required for success of the next generation.

PI_NAMEs: PITTENGER, CHRISTOPHER JOHN (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Acceleration;Address;Affect;Area;career;career development;Clinic;Clinical;clinical training;Collaborations;Communication;Communities;community engagement;cost;Country;COVID-19 pandemic;design;Development;Diagnosis;Disparity population;Distress;Educational Curriculum;Exclusion;experience;Faculty;Feedback;flexibility;Functional disorder;Funding;Genomics;Grant;Human;improved;innovation;insight;Institution;interdisciplinary collaboration;Investments;Laboratories;Leadership;Learning;medical schools;Mental disorders;Mental Health;Mentors;Mentorship;Modeling;Morbidity - disease rate;neurodevelopment;Neuroimmune;Neurosciences;next generation;novel strategies;novel therapeutic intervention;novel therapeutics;patient engagement;patient oriented research;Patients;peer;Phase;Philosophy;Physicians;Play;Population;Populations at Risk;Positioning Attribute;Prevention;Principal Investigator;programs;Provider;Psychiatry;Psychology;racial minority;Recording of previous events;recruit;Reporting;Research;Research Project Grants;Research Training;Residencies;response;Role;Science;Scientist;sexual minority;skills;social health determinants;Societies;Structure;success;support network;Talents;Therapeutic;Time;Training;Training Programs;Training Support;United States National Institutes of Health;Work;Writing

PROJECT_TITLE: Integrated Mentored Patient-Oriented Research Training (IMPORT) in Psychiatry


ADMINISTERING_IC: HL

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Hematology;Rare Diseases;Sickle Cell Disease

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Using novel microscopic imaging and microfluidic manipulation methods, a subpopulation of “unfit” cells is identified in the blood of sickle cell disease patients that may be responsible for vaso-occlusive crises. The proposal seeks to bring further innovations in imaging and microfluidic techniques that may allow us to better understand the mechanistic origins of these unfit cells and the consequences on their sickling propensity. The planned work will provide the foundation to explore how pharmaceutical interventions may affect this population of “unfit” cells and related patient outcome.

PI_NAMEs: DAO, MING ;HIGGINS, JOHN MATTHEW;SO, PETER T. (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Affect;Affinity;bioimaging;Biological Assay;Biological Markers;biomechanical test;Biomechanics;Biophysics;Blood;Blood Cells;Cell Cycle;Cell Fraction;Cell Nucleus;Cells;Cellular Assay;cellular imaging;Circulation;Clinical;Color;Complication;Defect;design;Detection;Development;Dose;Extinction;Fatigue;Fetal Hemoglobin;fitness;Foundations;Functional disorder;Hemoglobin;hemoglobin polymer;hydroxyurea;Image;In Vitro;in vivo;indexing;inhibitor;innovation;Intervention;Joints;Kinetics;Measurement;Measures;mechanical load;Mechanical Stress;Mechanics;Membrane;Methods;Microfluidics;microscopic imaging;Microscopy;Morbidity - disease rate;Morphology;mortality;next generation;novel;Outcome;Oxygen;oxygen transport;Patient Monitoring;patient response;Patient-Focused Outcomes;Patients;Periodicity;Permeability;Pharmacologic Substance;Phase;polymerization;Polymers;Population;Property;Publications;Research Personnel;Residual state;Resolution;Rheology;Risk;risk stratification;Role;Severity of illness;Shapes;Sickle Cell;Sickle Cell Anemia;Sickle Hemoglobin;sickling;small molecule;Specimen;Speed;Stress;Techniques;technological innovation;Testing;treatment response;Validation;vaso-occlusive crisis;Viscosity;Water;Work

PROJECT_TITLE: Single-cell measurement of cyclic stress on sickle blood cells by imaging-microfluidics

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


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

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Significant research efforts are currently underway to understand and prevent the pathogeneses of Alzheimer’s disease and related dementias, both of which are associated with memory loss and cognitive decline. The hallmark of Alzheimer’s disease pathogenesis is characterized by the accumulation of amyloid-  peptide plaques and tau-containing neurofibrillary tangles in the brain, and the cause of this is not fully understood. This proposal will uncover the key route of brain-derived A or tau clearance that could contribute to the better understanding of the etiopathogenesis of Alzheimer’s disease and related dementias.

PI_NAMEs: KIM, YOUNG-BUM  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Abeta clearance;abeta deposition;Acceleration;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Behavior;Binding;Biochemical;Biological Process;Blood;Blood Circulation;Brain;Cell membrane;cerebrospinal fluid clearance;Cessation of life;Circulation;Clinical;Complex;Coupled;Data;Dementia;Deposition;Development;Diet;dimer;disability;effective therapy;Endocytosis;Endothelial Cells;Epithelial Cells;Fatty acid glycerol esters;feeding;Functional disorder;Genetic Engineering;Goals;High Fat Diet;hyperphosphorylated tau;Image;Impaired cognition;Impairment;In Vitro;in vivo;inducible Cre;Injections;innovation;insight;interest;LDL-Receptor Related Protein 1;leptin receptor;Lipoprotein Receptor;loss of function;Memory impairment;Memory Loss;Metabolic;Molecular;mouse model;Mus;neurodegenerative dementia;Neurodegenerative Disorders;Neurofibrillary Tangles;neuropathology;new therapeutic target;novel;novel strategies;Obesity;overexpression;Overnutrition;Pathogenesis;Pathologic;Peptides;Physiological;prevent;Proteins;Public Health;Regulation;Research;response;Role;Route;Senile Plaques;Short-Term Memory;Structure of choroid plexus;System;tau aggregation;tau Proteins;Techniques;Testing;Tissue Engineering;transcytosis;Transgenic Mice;two-photon;uptake;vesicle transport

PROJECT_TITLE: Role of LRP1 in Alzheimer’s disease

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Human

PHR: NARRATIVE RNA damage is created by endonuclease cleavage and often leads to RNA ligation, degradation, or stabilization. Several RNA repair enzymes have important roles in RNA metabolism, host-pathogen conflicts, and tissue development, but we do not understand how the dysregulation RNA damage and repair causes disease.

PI_NAMEs: HESSELBERTH, JAY R (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Biology;Coupled;Development;Disease;DNA Damage;DNA Repair;endonuclease;Exonuclease;Genetic Code;Genome;Human;Hydroxyl Radical;inorganic phosphate;Lesion;Ligation;Mediating;Modification;pathogen;Periodicity;Phosphotransferases;Physiological;preservation;repair enzyme;repaired;response;Ribose;RNA;RNA Decay;RNA metabolism;RNA Processing;Role;System;Tissues

PROJECT_TITLE: Biology of RNA damage and repair

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


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Pediatric;Prevention

PHR: NARRATIVE This study will critically advance the understanding of early emotional predictors of later psychopathology in infants at familial risk for ASD, improving diagnostic precision and hastening access to empirically-validated preventative and early interventions in this vulnerable group. Consistent with the Research Domain Criteria research framework recommendations, the project (1) employs multiple levels of analysis, (2) investigates negative and positive valence systems as well as arousal systems, (3) examines a spectrum of ASD risk with long-term goals of improving diagnostic precision in ASD and enabling discovery of novel treatment targets and interventions both during prodromal and early syndromal stages of the disorder.

PI_NAMEs: CHAWARSKA, KATARZYNA  (contact);MACARI, SUZANNE

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: Affective;Age Months;Aggressive behavior;Anger;Anxiety;Area;Arousal;Attention;Attenuated;autism spectrum disorder;autism symptoms;autistic children;behavior measurement;Behavioral;Biological Markers;Characteristics;Clinical;clinical care;cohort;comorbidity;Data;depressive symptoms;Development;Diagnosis;Diagnostic;Disease;disorder risk;early childhood;Early Diagnosis;Early identification;Early Intervention;Emotional;emotional reaction;Emotions;Exhibits;Face;Family;Feeling suicidal;Foundations;Fright;Future;General Population;Genetic;Goals;Health Services Accessibility;high risk;high risk infant;Impairment;improved;Impulsivity;indexing;individuals with autism spectrum disorder;infancy;Infant;innovation;inpatient psychiatric treatment;Intervention;Investigation;Knowledge;Life;Link;longitudinal design;Measurement;Measures;Methods;Modality;Moods;multimodality;Nature;Negative Valence;novel;Outcome;Parents;Pattern;personalized diagnostics;Phenotype;Physiological;Population;Positive Valence;predictive marker;preventive intervention;prospective;Psychopathology;Recommendation;repetitive behavior;Reporting;Research;Research Domain Criteria;response;Risk;Risk Factors;Severities;showing emotion;Siblings;social;social deficits;Social Environment;social vulnerability;Standardization;Statistical Models;Stress;Symptoms;System;Temperament;TFF1 gene;Toddler;treatment services;two-dimensional;Vulnerable Populations

PROJECT_TITLE: Multimodal investigation of emotional reactivity as a predictor of later psychopathology in infants at risk for ASD

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: ITHACA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE To combat the epidemics of obesity and metabolic disease, a growing number of pharmacological strategies have emerged that leverage key hormonal signaling pathways regulated by enteroendocrine cells (EECs), a rare secretory lineage of the intestinal epithelium essential for metabolic health. Despite these advancements, the molecular regulators of EEC homeostasis, especially in the contexts of diet-induced obesity and bariatric surgery, remain incompletely understood. This proposal aims to address this knowledge gap by examining the context- specific roles of an EEC lineage-enriched microRNA molecule (microRNA-375) in the regulation of EEC biology, which may ultimately reveal novel therapeutic targets for the treatment of obesity and its comorbidities.

PI_NAMEs: KOCH-LASKOWSKI, KIERAN LOUISE (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: Address;Adult;Affect;Animal Feed;Animal Model;Animals;bariatric surgery;Bariatrics;Behavior Therapy;Bioinformatics;Biological;Biological Assay;blood glucose regulation;Body Weight;Body Weight decreased;candidate identification;Cell Lineage;Cell Maintenance;cell type;Cells;Cellular biology;Child;Chronic;Circulation;combat;comorbidity;Complex;Data;Data Set;Desire for food;detection of nutrient;Development;Diet;diet-induced obesity;dietary;Dietary Intervention;Disease;effective therapy;Endocrine;energy balance;Enteroendocrine Cell;environmental change;Epidemic;feeding;Gastrectomy;gastrointestinal epithelium;Gene Expression;Genes;Genomics;global health;glucose tolerance;Greater curvature of stomach;Health;High Fat Diet;Homeostasis;Hormonal;hormonal signals;Hormone secretion;Hormones;Human;Immunohistochemistry;improved;in vivo;in vivo Model;interdisciplinary approach;interest;intestinal crypt;intestinal epithelium;intestinal villi;Intestines;Islets of Langerhans;knockout animal;Knockout Mice;Knowledge;Measurement;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;MicroRNAs;Molecular;Mus;new therapeutic target;Obesity;Obesity Epidemic;obesity treatment;obesogenic;Operative Surgical Procedures;Pathogenesis;Pathway interactions;Patients;pharmacologic;Pharmacotherapy;Phenotype;Physiological;Physiology;Play;posttranscriptional;Prevalence;preventable death;Procedures;Regulation;Resolution;restoration;Role;Sampling;Satiation;Secretory Cell;Shapes;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Small Intestines;Small RNA;stem cells;Stimulus;Stomach;Techniques;Testing;therapeutic target;transcriptome sequencing;transcriptomics;Untranslated RNA;Villus;Weight maintenance regimen;Work

PROJECT_TITLE: MicroRNA-375 regulation of enteroendocrine cell biology in diet-induced obesity and bariatric surgery


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: STANFORD

ORG_DEPT: BIOPHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: NARRATIVE As the most prevalent cause of dementia, Alzheimer's disease affects millions of Americans and imposes a major burden on our society, but the cause of Alzheimer's disease remains unclear and therapeutic avenues to stop Alzheimer's disease progression have not been identified. Recent progress described major risk genes for Alzheimer's disease that point to changes in lipid metabolism in neurons and in microglia and that suggest synaptic impairments as a cause of the disease, consistent with direct measurements on patient samples that also described synaptic impairments, microglial dysfunction, and changes in cholesterol metabolism as a common feature of the disease. Based on these findings, the present application aims to test in human neurons and in mouse brain whether genetic changes associated with Alzheimer's disease predispose to the disease by impairing synaptic function via a lipid-dependent mechanism, thereby providing insight into potential new pathogenetic pathways in Alzheimer's disease that may be amenable to future therapeutic interventions.

PI_NAMEs: SUDHOF, THOMAS C. (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: abeta accumulation;Abeta synthesis;Adopted;Adult;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;American;Amyloid;Amyloid Beta A4 Precursor Protein;Amyloid beta-Protein;amyloid formation;Apolipoprotein E;apolipoprotein E-4;Behavior;Brain;Cells;Cellular biology;Cholesterol;Cholesterol Homeostasis;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;Cytoplasmic Protein;Dementia;Disease;Disease Progression;drug development;Early Onset Familial Alzheimer's Disease;electrical property;Electrophysiology (science);experimental study;familial Alzheimer disease;Functional disorder;Future;gamma secretase;Genes;Genetic;Genetic study;Genetic Transcription;genetic variant;Human;Impaired cognition;Impairment;in vivo;Induced Mutation;induced pluripotent stem cell;Inflammatory Response;insight;interdisciplinary approach;Knockout Mice;Link;lipid metabolism;lipid transport;Lipids;Measurement;Mediating;Membrane Proteins;Microglia;mouse model;Mus;Mutation;Nature;neural circuit;Neurodegenerative Disorders;Neuroglia;neuron loss;Neurons;notch protein;novel;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Peptide Hydrolases;pharmacologic;Phenotype;Preparation;presenilin;presenilin-1;prevent;Property;Protein Fragment;rare variant;Regulation;risk variant;Role;Sampling;secretase;Signal Transduction;Societies;Synapses;synaptic failure;synaptic function;Synaptic Transmission;Techniques;Testing;Therapeutic;Therapeutic Intervention;transcriptome sequencing;transcriptomics;TREM2 gene;United States;Up-Regulation;Variant

PROJECT_TITLE: Regulation of cholesterol by y-secretase and ApoE: Implications for AD pathogenesis and synaptic function

STUDY_SECTION: CMND

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


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Our goal here is to elucidate the mechanistic regulation of neuro-glio-vascular (NGV) restoration underlying acute coma recovery and to test a targeted pharmacological therapy that promotes NGV restoration in our novel, recently developed rodent model of brainstem coma. We hope that the first glimpse of thalamic regulation of astrocyte function and pharmacological modulation of glutamate- astrocytic signaling will help refine the therapeutic paradigm to target astrocytes to promote acute coma recovery.

PI_NAMEs: YU, XIN  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Acute;Animals;antagonist;Arousal;Astrocytes;Behavior assessment;Behavioral;blood oxygen level dependent;Blood Vessels;Brain;Brain Stem;Calcium;Cerebral cortex;cingulate cortex;Coma;Conscious;Coupled;Coupling;Data;Death Rate;Deep Brain Stimulation;drug development;Electrophysiology (science);Ensure;experience;experimental study;extracellular;Fiber;Frequencies;Functional Magnetic Resonance Imaging;Future;gliovascular;Glutamate Transporter;Glutamates;Goals;hemodynamics;Homeostasis;Hour;Human;Imaging technology;inhibitor;Injury;insight;interest;Label;Lesion;Measures;Mediating;Modeling;Multimodal Imaging;multimodality;Neurons;neuroregulation;neurovascular;nonhuman primate;noradrenergic;novel;novel therapeutic intervention;optogenetics;Outcome;Pathway interactions;Patients;Permanent Vegetative States;Persons;pharmacologic;Pharmacological Treatment;Photometry;Protocols documentation;Publishing;Rattus;Recovery;Regulation;Rest;restoration;Rodent;Rodent Model;Role;Signal Transduction;Specificity;System;Testing;Thalamic structure;Therapeutic;Time;tool;Wakefulness;Work

PROJECT_TITLE: Investigating the Thalamic Regulation of Neuro-Glio-Vascular Restoration Underlying Acute Coma Recovery with Multi-Modal fMRI in a Brainstem Coma Rodent Model

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

PHR: 8. Project Narrative  Our proposed studies will test the hypotheses the chromatin loop extrusion and RAG scanning contributes to the different mechanistic strategies used by the Igh and Igk loci for long-range V(D)J recombination and that the loop extrusion mechanism can be harnessed for discovery of therapeutic antibodies. To carry out these studies we have developed a host of powerful new technologies. The proposed work should reveal new paradigms for understanding V(D)J recombination in vivo, illuminate the range of mechanisms employed for long-range V(D)J recombination in antigen receptor loci.

PI_NAMEs: ALT, FREDERICK W. (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: abl Oncogene;Address;Antibody Repertoire;Antigen Receptors;Architecture;Area;B-Lymphocytes;Binding;Biological Assay;cell population study;Cells;Chromatin;Chromatin Loop;Chromosomes;cohesin;Complex;Data;Development;Diffusion;Distal;Elements;Endonuclease V;Event;Exons;experimental study;Funding;G1 Arrest;Generation of Antibody Diversity;Genes;Genetic Recombination;Genetic Transcription;genome-wide;Goals;high throughput analysis;Human;IgK;Immunology;in vivo;insight;Intercistronic Region;interstitial;Light;Lymphocyte;Malignant Neoplasms;Maps;Mediating;Modification;Mus;new technology;Pattern;Play;Population;Process;progenitor;protein complex;Proteins;Publishing;Reaction;Resolution;Role;Scanning;T-Lymphocyte;Technology;Testing;Therapeutic antibodies;Trans-Activators;transcription factor;V(D)J Recombination;Work

PROJECT_TITLE: Mechanisms That Control Antigen Receptor Variable Region Exon Assembly

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Infectious Diseases;Kidney Disease;Prevention;Transplantation

ORG_CITY: BIRMINGHAM

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PUBLIC HEALTH RELEVANCE STATEMENT More than 1.1 million people in the United States (US) are living with human immunodeficiency virus (HIV) infection, and an estimated 30% of people living with HIV (PLWH) have evidence of chronic kidney disease (CKD). Compared to the general population, the rate of end-stage renal disease among PLWH is tenfold greater and mortality on dialysis is 19-fold higher. With the observed high rates of mortality on dialysis, the ability to risk stratify PLWH by risk for future development of CKD is critical for identifying those at highest risk who would benefit from early referral for nephrology care and transplant evaluation and lowest risk who could be eligible living kidney donors for PLWH in need of transplant.

PI_NAMEs: LOCKE, JAYME ELIZABETH (contact);SAWINSKI, DEIRDRE

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;antiretroviral therapy;Biological;care outcomes;Caring;Categories;CD4 Lymphocyte Count;Characteristics;Chronic Kidney Failure;Clinical;clinical decision-making;cohort;comorbidity;Complication;Data;Death Rate;Development;Dialysis procedure;Disease;Disease Progression;disorder risk;DNA;Donor person;Donor Selection;Eligibility Determination;End stage renal failure;Enrollment;Evaluation;Failure;follow-up;Future;gene environment interaction;General Population;Genes;Genetic;Genetic Risk;genetic variant;Genetic Variation;Genotype;hazard;high risk;Histologic;Histology;HIV;HIV Infections;HIV risk;improved;Incidence;Individual Differences;insight;Intervention;Kidney;kidney biopsy;Kidney Diseases;Knowledge;Light;Living Donors;living kidney donor;Measures;Mendelian randomization;Methods;Modification;mortality;Natural History;Nephrology;novel;Outcome;Participant;Patient-Focused Outcomes;Pennsylvania;Persons;Phenotype;Population;predictive tools;Predictive Value;Process;prognostic;prospective;public health relevance;Regimen;Research;response;Risk;risk prediction;risk stratification;Specimen;Structural Models;System;Time;tool;Transplantation;United States;Universities;Update;Validation;Variant;Viral;Virus Diseases

PROJECT_TITLE: Genetic, Environmental & Histologic Basis for Kidney Disease Risk among Persons Living with HIV

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Genetics;Immunization;Immunotherapy;Liver Cancer;Liver Disease;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Vaccine Related

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Fibrolamellar hepatocellular carcinoma (FLC) is a rare cancer of children and adults that has no standard or effective treatment options. The overall goal of our project is to study a novel cancer treatment vaccine developed for FLC, in combination with other drugs that work on the human immune system. Using samples from the clinical trial and samples from other patients with this rare cancer, we will study mechanisms of response and resistance to immunotherapy in this cancer.

PI_NAMEs: THOMAS, PAUL G.;YARCHOAN, MARK  (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Active Sites;Adolescent and Young Adult;Adoptive Cell Transfers;Adult;Affect;Amino Acid Sequence;anti-tumor immune response;antigen-specific T cells;Area;arm;biobank;Biochemical;Biopsy;Biopsy Specimen;Blood;Cancer Center;cancer therapy;Catalytic Domain;Cell Therapy;Cells;cellular transduction;Child;Chimera organism;Chimeric Proteins;Cirrhosis;Clinical;Clinical Research;Clinical Trials;Code;Collection;Combined Modality Therapy;Cyclic AMP-Dependent Protein Kinases;cytokine;Cytometry;Cytotoxic T-Lymphocytes;Data;effective therapy;Effectiveness;Environment;enzyme linked immunospot assay;Epitopes;Event;exhaustion;Exons;Fibrolamellar Hepatocellular Carcinoma;Foundations;Frequencies;fusion gene;Gene Fusion;Genes;genomic signature;Goals;Human;humanized mouse;Immune;Immune checkpoint inhibitor;immune modulating agents;immune resistance;Immune response;Immune system;Immune Targeting;immunogenicity;Immunohistochemistry;Immunotherapy;in vivo;inhibitor;innovation;Institution;ipilimumab;Laboratory Study;Liver;Liver neoplasms;Malignant neoplasm of liver;Malignant Neoplasms;Maps;Modeling;mouse model;multiplexed imaging;neoantigens;next generation;Nivolumab;novel;novel therapeutic intervention;Pathway interactions;Patients;Pediatric Oncology;Peptide Vaccines;Peptide/MHC Complex;Peptides;peripheral blood;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Pilot Projects;Population;Pre-Clinical Model;preservation;prevent;Primary Malignant Neoplasm of Liver;PRKACA gene;rare cancer;Recurrence;Refractory;Resistance;Resolution;response;Safety;safety testing;Saint Jude Children's Research Hospital;Sampling;single-cell RNA sequencing;small molecule inhibitor;Specificity;Specimen;Stains;standard care;synergism;Systemic Therapy;T cell response;T-Cell Activation;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;T-Lymphocyte Epitopes;Tissues;Toxic effect;Transcript;transcriptome;tumor;tumor microenvironment;Universities;Unresectable;vaccine development;Vaccines;Work;young adult

PROJECT_TITLE: Neoantigen-specific T cell responses for Fibrolamellar Hepatocellular Carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-D(08)F]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Breast Cancer;Cancer;Immunotherapy;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

PHR: Project Narrative The oncogenic EGFR variant, EGFRvIII, and the GTP-binding/protein crosslinking enzyme Transglutaminase-2, have been implicated in aggressive brain cancer. Recently, we have gained important new insights into how these signaling proteins are highly expressed in aggressive glioma stem cells and their functional consequences for the development of high-grade brain cancer. The hope is that this information will also highlight new therapeutic strategies.

PI_NAMEs: CERIONE, RICHARD A. (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Adopted;Affect;aggressive breast cancer;angiogenesis;Binding;Breast Cancer Cell;cancer cell;Cancer Cell Growth;Cancer Etiology;Cell Death;Cell secretion;Cell Survival;Cells;Cessation of life;Coupled;cytotoxic;cytotoxicity;Deacetylase;Dependence;design;Development;Disease;Down-Regulation;endogenous stem cells;Endosomes;Enzymes;Epidermal Growth Factor Receptor;epidermal growth factor receptor VIII;Exhibits;exosome;extracellular vesicles;Funding;Glioma;Glutaminase;Glutamine;Goals;Growth;GTP Binding;immune checkpoint;Immune Evasion;Immune response;inhibitor;insight;interest;Laboratories;Ligands;Location;Malignant neoplasm of brain;Malignant Neoplasms;Metabolic;Metabolism;Methods;microvesicles;Molecular Conformation;neoplastic cell;new therapeutic target;novel strategies;novel therapeutic intervention;Oncogenic;Play;Production;programmed cell death ligand 1;protective effect;protein crosslink;Proteins;Reagent;Receptor Signaling;Role;Signal Pathway;Signal Transduction;Signaling Protein;SIRT1 gene;small molecule;stem;stem cells;survivin;Therapeutic;trafficking;transglutaminase 2;translational study;Tumor Angiogenesis;tumor initiators;tumor microenvironment;tumor progression;Tumor Promotion;Up-Regulation;Variant

PROJECT_TITLE: The unique roles of the GTP-binding/protein crosslinking enzyme transglutaminase-2 and signaling partners in aggressive cancers

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Clinical Research;Eye Disease and Disorders of Vision;Lupus

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: Project Narrative  Autoimmune diseases cause a large social burden on both the patients afflicted with the disease and their support systems. The Accelerated Medicine Partnerships in Autoimmune and Immune-Mediated Diseases (AMP AIM) is a consortium of Governmental, University, Biotech, and Non-profit institutions that will work to assemble an unparalleled repository of samples and data from biopsy tissues using advanced technologies and analysis approaches of samples from four autoimmune diseases: System Lupus Erythematosus (or “Lupus”), Rheumatoid Arthritis (RA), Sjogren’s Syndrome (SjD), and Psoriatic Spectrum of Disease (Psoriasis, PsD). The Oklahoma Medical Research Foundation’s Tissue Research Core (OMRF TRC) proposes to provide the Network with 1) standard methods, 2) centralized sample storage/management, 3) centralized testing, 4) collection of tissue pathology data, and 5) data systems to organize all data through its existing staff and infrastructure.

PI_NAMEs: GUTHRIDGE, JOEL MARVIN (contact);JAMES, JUDITH A

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: Acceleration;adjudication;Attention;Autoimmune;Autoimmune Diseases;Awareness;biobank;Biological Markers;Biopsy;Biotechnology;Caring;Cells;Certification;Characteristics;Cladribine;Clinical;clinical application;clinically actionable;cohort;Collection;cost effective;Country;Data;Data Protection;Data Set;Database Management Systems;Dedications;design;digital imaging;digital pathology;Disease;distributed data;Emerging Technologies;Ensure;Equipment and supply inventories;experience;Foundations;Genetic;high dimensionality;Histology;Image;Immune;Immune System Diseases;improved;Industry Standard;Information Systems;Infrastructure;innovation;Institution;Institutional Review Boards;interest;International;Investments;Knowledge;Leadership;Location;Logistics;Lupus;Lupus Erythematosus;Manuals;Measurement;Mediating;Medical Research;Medicine;Methods;migration;Mission;Modality;Molecular;Molecular Profiling;Monitor;Multiomic Data;multiple omics;Oklahoma;Pathology;Patients;Phenotype;phenotypic biomarker;Play;Positioning Attribute;Procedures;Process;programs;Protocols documentation;Psoriasis;Quality Control;Recording of previous events;repository;Research;Rheumatoid Arthritis;Sampling;Science;Secure;Services;Shipping;single cell analysis;Site;Sjogren's Syndrome;social;Solid;Space Perception;Staff Development;Standardization;success;Support System;System;Systemic Lupus Erythematosus;Technology;Testing;Tissue Banks;Tissue imaging;Tissue Sample;Tissues;Training;transcriptomics;Universities;Work

PROJECT_TITLE: Accelerating Medicines Partnership-Autoimmune and Immunologic Disease Tissue Research Core


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome;Machine Learning and Artificial Intelligence

PHR: NARRATIVE This research proposal aims to develop an improved computational framework to discover non- coding functional variants in the human genome and evaluate their contribution to human diseases in a tissue- and cell-type-resolved manner. We will build machine-learning ensemble models to predict regulatory variants using existing and emerging epigenomic data and validate our prediction experimentally. The new method developed in this study will help us to uncover underlying genetic and molecular mechanisms of human diseases.

PI_NAMEs: LEE, DONGWON  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Albumins;Allelic Imbalance;Base Sequence;Benchmarking;Binding;Biological Assay;Biological Process;Brain;Cell Line;Cell Nucleus;cell type;Cells;Chromatin;Chromosome Mapping;Classification;computer framework;Creatinine;CRISPR/Cas technology;Data;Data Set;deep learning;Disease;DNA Sequence;Enhancers;epigenomics;Etiology;Exhibits;experimental study;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;genome wide association study;genomic data;Glomerular Filtration Rate;Heart;Heritability;Human;human disease;Human Genome;Immune;improved;in silico;Kidney;kidney cell;Learning;Libraries;Luciferases;Lung;Machine Learning;machine learning method;Maps;Methodology;Methods;model building;Modeling;Molecular;Muscle;Phenotype;Placenta;Play;pre-trained model;Proliferating;promoter;public database;Quantitative Trait Loci;Regulatory Element;Reporter;Research Proposals;Risk;Role;statistics;Step training;support vector machine;Techniques;Tissues;Training;trait;transcription factor;Untranslated RNA;Urine;Validation;Variant

PROJECT_TITLE: An ensemble framework for regulatory variant prediction.


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: New World Arenaviruses (NWA) are single-stranded RNA viruses that cause viral hemorrhagic fevers in humans with high mortality and a better understanding of how host factors influence infection is important to our ability to prevent and treat infection. We recently discovered a new host factor, TRIM2 that in concert with SIRPA, a protein known to block phagocytosis, inhibits virus infection by restricting entry of viruses into cells. This proposal will build upon this finding and use mouse and cell culture models to determine how TRIM2 and SIRPA work to inhibit infection, with the ultimate goal of finding anti-viral therapies

PI_NAMEs: ROSS, SUSAN R (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: 2019-nCoV;Actins;Aerosols;Amino Acid Motifs;Anti-viral Response;Anti-viral Therapy;Apoptosis;Arenavirus;Arenavirus Infections;Argentina;Binding;Biological Process;Blood Platelets;C-terminal;Cell Culture Techniques;Cell Extracts;Cell Proliferation;Cell surface;Cell Surface Proteins;cell type;Cells;cellular targeting;Complex;Cultured Cells;cytokine;Cytoskeleton;Data;Disease;Ebola;Endocytosis;Endothelium;Erythrocytes;experimental study;Family;Functional disorder;Genes;Glycoproteins;Goals;Human;Human Pathology;Image;Immune response;Immune system;In Vitro;in vivo;Incidence;Infection;Infection Control;insight;Integration Host Factors;Junin virus;knock-down;Knockout Mice;Link;Lymphocytic choriomeningitis virus;Macrophage;Mediating;member;Modeling;mortality;Mus;Mutation;neoplastic cell;Nervous System Disorder;novel;novel strategies;novel therapeutic intervention;Old World Arenaviruses;pathogenic virus;Pathogenicity;Pathway interactions;Patients;Phagocytosis;Phagocytosis Inhibition;Phosphoric Monoester Hydrolases;Phosphorylation;prevent;Primates;Process;Protein Family;Proteins;PTPN6 gene;PTPNS1 gene;receptor;RNA interference screen;RNA Viruses;Rodent;Role;Sentinel;Signal Transduction;Signal Transduction Pathway;Small Interfering RNA;Specificity;Survivors;Tacaribe Complex Viruses;Tacaribe virus;Testing;TFRC gene;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissue Extracts;trafficking;transmission process;TRIM Motif;tumor;ubiquitin ligase;Ubiquitination;Vaccines;Vesicular stomatitis Indiana virus;Viral;Viral Hemorrhagic Fevers;viral transmission;Virus;Virus Diseases;Visualization;Work;Zika Virus;Zoonoses

PROJECT_TITLE: The role of TRIM2 and SIRPA in New World Arenavirus entry

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Digestive Diseases;Genetics;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: RELEVANCE STATEMENT A major focus of the project is DNA replication, a fundamental event that is required in all life forms, and its disruption can lead to several forms of disease, including cancer. The central engine of the replication machinery is the hexameric MCM complex, which represents a logical, promising target for anti-cancer therapies. A second focus of the project is the human RNA helicase DDX3X, which is associated with several human diseases, including HIV, HCV, and the brain cancer medulloblastoma.

PI_NAMEs: ENEMARK, ERIC  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: ATP Hydrolysis;ATP phosphohydrolase;Base Pairing;Binding;cancer therapy;Cell division;Complex;Cryoelectron Microscopy;Data;Disease;DNA;DNA biosynthesis;Enzymes;Eukaryotic Cell;Event;Genetic Materials;helicase;Hepatitis C virus;HIV;Human;human disease;In Vitro;Knowledge;Life;Malignant neoplasm of brain;Malignant Neoplasms;MCM Protein;Medulloblastoma;Methods;Molecular;Nucleic Acids;Organism;Polymerase;Process;Proteins;Research;RNA;RNA Helicase;RNA Processing;Structure;X-Ray Crystallography

PROJECT_TITLE: Molecular mechanisms of nucleic acid machines

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Despite long-standing racial disparities in lung cancer treatment and outcomes, the underlying reasons remain inadequately understood. We will comprehensively and simultaneously assess the contributions of affordability, accommodation, acceptability, accessibility, and availability barriers to lung cancer disparities in a nationally representative cohort of lung cancer patients. The results will advance our understanding of the potentially modifiable barriers to lung cancer care in African American patients, and thus will help inform multilevel intervention strategies to improve lung cancer care and reduce the burden of lung cancer in this vulnerable population.

PI_NAMEs: LIAN, MIN ;LIU, YING  (contact)

PROGRAM_OFFICER_NAME: MUJURU, PRISCAH

PROJECT_TERMS: Address;Affect;African American;African American population;American;beneficiary;Cancer Burden;cancer care;Cancer Etiology;cancer health disparity;Cancer Patient;cancer therapy;Cessation of life;Characteristics;chemotherapy;Classification;cohort;Continuity of Patient Care;Data;Databases;density;Diagnosis;differences in access;Dimensions;Disease;Disparity;Disparity population;disparity reduction;Early Diagnosis;Education;effective intervention;Ethnic Population;European;experience;genetic testing;geographic barrier;Guidelines;health care availability;Health Insurance;Healthcare Systems;Hospitals;improved;Incidence;Inferior;insight;Insurance Coverage;Intervention;long-standing disparities;longitudinal database;lung cancer screening;Malignant neoplasm of lung;Measures;Mediastinal;Medicare;Modality;Modeling;mortality;multimodality;Neighborhoods;Non-Small-Cell Lung Carcinoma;Not Hispanic or Latino;novel;Operative Surgical Procedures;Outcome;outcome disparities;Palliative Care;patient expectation;Patients;population based;Population Study;population survey;Provider;racial difference;racial disparity;racial population;Radiation therapy;Risk;Role;rural dwellers;Sampling;screening;SEER Program;service organization;Services;social disparities;sociodemographics;Stage at Diagnosis;Staging;Statistical Models;surveillance data;Surveys;System;targeted treatment;Testing;treatment and outcome;treatment disparity;United States;Vulnerable Populations

PROJECT_TITLE: Healthcare Access Dimensions and Racial Disparities in Lung Cancer

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Diabetes;Genetics;Infectious Diseases;Microbiome;Wound Healing and Care

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: Project Narrative Diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) are common chronic wounds and are very serious diseases frequently complicated by infection. The focus of this project is to identify response mechanisms of patients’ skin regulated by the microbiome that are common for both types of ulcers, DFUs and VLUs. The results from this project will characterize mechanisms important for chronic wound healing, provide important new knowledge regarding chronic wound infection, and be used for the development of novel targeted therapeutics to fight wound infection and promote wound healing.

PI_NAMEs: BURGESS, JAMIE LEE (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Affect;Amputation;angiogenesis;Animal Model;antimicrobial;Apoptosis;Aryl Hydrocarbon Receptor;Bacterial Infections;Benign;Bioinformatics;Biological Assay;Cell Cycle Progression;cell motility;Cells;Characteristics;chronic wound;Clinical;commensal bacteria;Complex;Complications of Diabetes Mellitus;Coupled;Data;Development;Diabetic Foot;Diabetic Foot Ulcer;Diagnostic;Disease;Economic Burden;effective therapy;Epidermis;Etiology;Fibroblast Growth Factor Receptor 2;Fibrosis;fighting;Flow Cytometry;Foundations;genetic signature;Genetic Transcription;Goals;healing;Health Care Costs;Healthcare Systems;Histopathology;host microbiome;Human;human tissue;Immune response;Impaired healing;Impairment;Infection;Inflammatory Response;inhibitor;innovation;insight;Knowledge;Laboratories;Leg;Leg Ulcer;Maps;Mediating;methicillin resistant Staphylococcus aureus;Microbial Biofilms;microbiome;MicroRNAs;migration;Modeling;Molecular;Morbidity - disease rate;mortality;National Institute of Diabetes and Digestive and Kidney Diseases;new therapeutic target;novel;Organ;Outcome;pathogen;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Persons;Phenotype;Population;Prevention;Proliferating;Quality of life;receptor;Receptor Signaling;recurrent infection;Regulatory Pathway;repaired;response;Role;Sampling;Side;Signal Pathway;Signal Transduction;Skin;skin microbiome;Staphylococcus aureus;Staphylococcus epidermidis;STAT1 protein;Stat3 protein;targeted treatment;Testing;therapeutic target;therapy development;Tissue Sample;Tissues;transcriptome;transcriptome sequencing;transcriptomics;treatment strategy;Ulcer;Venous;wound;wound closure;wound environment;wound healing;Wound Infection;Wound models;wound treatment

PROJECT_TITLE: Core mechanisms that contribute to inhibition of wound healing in diabetic foot and venous leg ulcers


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: We propose to characterize how HIV-1 Gag and envelope proteins interact to facilitate the assembly of envelope proteins into virus particles, and to regulate the functions of envelope proteins in virus particles. These investigations will help clarify how HIV Gag and envelope proteins cooperate, and will foster the development of novel approaches to interfere with HIV-1 replication.

PI_NAMEs: BARKLIS, ERIC W (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;AIDS diagnosis;Binding;Binding Sites;Biochemical;C-terminal;Cell membrane;cell type;Ceramides;Cholesterol;Collaborations;Cytoplasmic Tail;Defect;Detergents;Development;env Gene Products;Epidemic;Fostering;Foundations;Funding;gag Gene Products;Glycoproteins;Goals;HIV;HIV-1;Impairment;insight;Intracellular Membranes;Investigation;Ligands;Lipids;Membrane;Membrane Microdomains;Methods;Modeling;Molecular Chaperones;Molecular Conformation;Monitor;mutant;Mutation;myristoylation;N-terminal;nanobodies;novel;novel strategies;Phosphatidylinositol 4,5-Diphosphate;Phospholipids;Protein Precursors;Proteins;RNA;RNA Binding;Role;Signal Transduction;Site;Sphingomyelins;Structure;therapy design;trafficking;Variant;Viral;Virion;Virus;Virus Assembly

PROJECT_TITLE: HIV-1 Gag Precursor Protein Interactions

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]