ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Understanding the molecular basis of HIV infection is critical to the development of new preventative, therapeutic, and curative treatments. This project focuses on understanding the role of CPSF6 in the virus lifecycle, a host protein recruited to the incoming virus core for yet unknown reasons. We hypothesize that recruitment of CPSF6 disrupts its normal function in the host cell, contributing to a permissive state for virus replication.

PI_NAMEs: HULTQUIST, JUDD F (contact)

PROJECT_TERMS: 3' Untranslated Regions;Agonist;Binding;Capsid;CD4 Positive T Lymphocytes;Cell Line;Cell Survival;cell type;Cells;Chemicals;Cleavage And Polyadenylation Specificity Factor;cleavage factor;Code;Complex;CRISPR/Cas technology;curative treatments;Cyclophilin A;Cytoplasm;Data;Defect;Dependence;design;Detection;Development;Distal;Enhancers;gene editing technology;Genes;Genetic;Genetic Epistasis;Genetic Transcription;Heterochromatin;HIV;HIV Infections;HIV-1;Hour;Immune;Immune response;in vivo;Infection;Infection Control;innate immune function;Innate Immune Response;Integration Host Factors;integration site;Interferons;knock-down;Knock-out;Laboratory Finding;lead candidate;Life Cycle Stages;Link;Mammalian Cell;Mediating;member;Messenger RNA;Molecular;mutant;Mutation;Nuclear;Nuclear Translocation;overexpression;permissiveness;Phase;Phenocopy;Phenotype;Play;Polyadenylation;Polyadenylation Pathway;Post-Transcriptional Regulation;Post-Translational Protein Processing;preference;prevent;Proteins;recruit;Regulation;Regulatory Pathway;Reporting;response;Role;Route;Saquinavir;Site;small molecule;T-Lymphocyte;Testing;Therapeutic;Time;trafficking;transcriptome;Viral;Virus;virus core;Virus Replication;Work

PROJECT_TITLE: Deciphering the Role of CPSF6 in HIV Infection

STUDY_SECTION: HVCD

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


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Human Genome;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Women's Health Research

ORG_CITY: ATLANTA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_FIPS: US

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE We propose to adapt Gegoria’s existing statewide family history screening program for BRCA-associated cancers with the goal to increase the number and diversity of women who receive family history assessment and the opportunity to access risk-stratified cancer prevention in rural public health clinics. Study findings will further inform program dissemination and sustainability across all 187 Georgia public health clinics, and yield insights enabling improved implementation of other genomic applications at the population level and among other rural, underserved communities.

PI_NAMEs: GUAN, YUE  (contact)

PROGRAM_OFFICER_NAME: SARMA, ELIZABETH ANNE

PROJECT_TERMS: Address;Adopted;Age;aggressive breast cancer;Awareness;Black race;black women;BRCA mutations;Breast Cancer Risk Factor;breast imaging;cancer genetics;cancer genomics;cancer prevention;Caring;Clinic;Clinic Visits;Communication;Consultations;cost;Disparity;Education;Effectiveness;effectiveness evaluation;Eligibility Determination;ethnic minority population;Ethnic Population;Evaluation Research;evidence base;Exploration, Preparation, Implementation, and Sustainment;Family;Family history of;federal poverty level;follow-up;Genetic;Genetic Risk;Genetic Screening;Genetic Services;genetic testing;Genomics;Goals;Guidelines;health disparity;health organization;Health Services Research;high risk;High Risk Woman;implementation framework;implementation research;improved;Infrastructure;insight;Left;Life;Malignant Neoplasms;Measures;Minority Groups;mutation carrier;Oncology;Phase;Population;population based;Population Heterogeneity;Poverty;Preparation;Prevention;Process;program dissemination;Program Sustainability;programs;psychosocial;Public Health;racial diversity;racial population;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recording of previous events;Research;Risk;risk stratification;Rural;rural area;Rural Community;rural dwellers;screening;Screening for cancer;screening program;Screening Result;secondary outcome;service uptake;Services;Site;success;Testing;Time;underserved community;Uninsured;United States Preventative Services Task Force;uptake;Visit;White Women;Woman

PROJECT_TITLE: Evaluating an evidence-based family history screening program adapted to increase reach and uptake of screening for BRCA-associated cancers in rural public health clinics

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Ion channels are a major protein class important for human health and disease. Although many ion channels are linked to Mendelian disorders, a major challenge is to understand which mutations in these genes disrupt the function of the protein and cause disease. This work will study large patient cohorts and generate large in vitro functional datasets to better understand ion channel biology and decipher which mutations in ion channel genes are linked to disease.

PI_NAMEs: GLAZER, ANDREW M. (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: 3-Dimensional;Affect;American;biobank;Biology;Body System;Cell surface;Cells;Charge;Classification;Clinical;cohort;Data;Data Set;Disease;disease phenotype;Effectiveness;Environment;Epilepsy;experimental study;gamma-Aminobutyric Acid;Genes;genetic analysis;genetic testing;genetic variant;genome sequencing;Genomic medicine;Health;High-Throughput Nucleotide Sequencing;Homeostasis;Homologous Gene;Human;In Vitro;Ion Channel;Ion Channel Gating;Ions;Learning;Libraries;Ligands;Link;Measures;Medical Genetics;medical schools;Membrane Lipids;Mendelian disorder;Mutagenesis;Mutation;Mutation Analysis;mutation screening;novel;patch clamp;Pathogenicity;Patients;Phenotype;phenotypic data;Play;protein function;protein structure;Proteins;Reaction;receptor;Role;Tissues;trafficking;Variant;variant of unknown significance;Work

PROJECT_TITLE: High-throughput discovery of disease-associated ion channel variants

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-J(55)R]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Hearing Loss;Human Genome

ORG_CITY: CORAL GABLES

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: NARRATIVE We will expand our comprehensive genomic and phenotypic deafness database for clinical care of deaf individuals and will identify and characterize variants of novel and known genes involved in hearing loss using state-of-the-art genome sequencing and structured bioinformatic analyses including established multi-tier genomic profiling approach as well as a customized local pipeline platform and functional and multi-omics analysis. This will enhance our understanding of biology of the normal hearing and the genetic aberrations that result in hearing impairments.

PI_NAMEs: LIU, XUE Z (contact)

PROGRAM_OFFICER_NAME: WATSON, BRACIE

PROJECT_TERMS: Address;Adult;Affect;American;analysis pipeline;Animal Model;Auditory;bead chip;Bioinformatics;Biological;Biological Assay;Biological Models;Biology;Biopsy;Birth;Candidate Disease Gene;causal variant;Cells;Clinical;clinical care;Clinical Data;clinical database;clinically significant;Code;cohort;CRISPR/Cas technology;Data;Data Analyses;Data Set;Databases;deaf;deafness;Derivation procedure;Development;diagnostic algorithm;Disease;Ear;Elderly;Exclusion;exome;experimental study;Family;follow-up;Foundations;Functional disorder;gene discovery;gene panel;gene therapy;gene-targeted therapy;Generations;Genes;Genetic;genetic analysis;genetic epidemiology;Genetic Heterogeneity;genetic testing;genome analysis;genome editing;genome sequencing;genomic profiling;Genomics;Goals;hard of hearing;Hearing;hearing impairment;Hearing Tests;hereditary hearing loss;Human;Human Genetics;improved;in silico;Inbreeding;Individual;induced pluripotent stem cell;Infant;Inherited;insight;Investigation;Knowledge;Labyrinth;Machine Learning;Methylation;Minority;Molecular;Molecular Diagnosis;Molecular Genetics;mouse model;multiple omics;Mus;mutant;Mutation;Neurological disability;normal hearing;novel;novel therapeutics;Nucleic Acid Regulatory Sequences;Octogenarian;Organoids;Pathogenicity;Pathway interactions;Patients;Persons;Pharmacotherapy;Phenotype;Physiology;Population;precision medicine;proband;Procedures;Productivity;programs;Proteins;Protocols documentation;Publications;repository;Research;Role;Sampling;segregation;Sensory Disorders;single-cell RNA sequencing;Structure;System;targeted treatment;Technology;therapeutic evaluation;Tissues;tool;transcriptome sequencing;Untranslated RNA;Variant;Zebrafish

PROJECT_TITLE: Molecular Genetics on Non Syndromic Hearing Loss (NSHL)

STUDY_SECTION: GHD

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


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BURLINGTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: NARRATIVE Cardiovascular disease and stroke are the leading causes of death and disability in the United States, and are intimately related to cognitive impairment and dementia. Cardiovascular disease is not simply a disease of the heart or blood vessels, but rather it impacts every organ. We propose a Center of Biomedical Research Excellence (COBRE), the “Vermont Center on Cardiovascular and Brain Health” (VCCBH) that will nucleate the University of Vermont's considerable research expertise in cardiovascular and neurovascular research to address these issues from diverse, mutually reinforcing basic science, clinical science and epidemiology perspectives. While advancing science, the Center will support the transition of early career faculty to independent scientists.

PI_NAMEs: CUSHMAN, MARY  (contact);NELSON, MARK T

PROGRAM_OFFICER_NAME: KOVBASNJUK, OLGA NIKOLAEVNA

PROJECT_TERMS: Address;American;American Heart Association;Area;Basic Science;Brain Diseases;brain health;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;career;Cause of Death;Centers of Research Excellence;Cessation of life;Clinical;clinical epidemiology;Clinical Research;Clinical Sciences;cognitive function;Collaborations;college;Communication;Communities;Core Facility;cost;Dementia;Development;Dimensions;disability;Discipline;Disease;Disparate;early-career faculty;Education;Electrophysiology (science);Epidemiology;Ethnic Origin;Evaluation;Evolution;experience;Faculty;Fostering;Funding;Future;Gender;Goals;Grant;Heart Diseases;Hematological Disease;Image;Impaired cognition;improved;Infrastructure;innovation;Institution;instrumentation;Interdisciplinary Study;meetings;member;Mentors;Mentorship;Microvascular Dysfunction;Molecular Epidemiology;mortality;multidisciplinary;Myocardial Infarction;neurovascular;next generation;novel;optimal treatments;Organ;peer coaching;Persons;Phase;Physiology;Process;Program Development;programs;Race;recruit;Research;Research Design;Research Institute;Research Personnel;Research Support;Resources;Role;Science;Scientist;skills;Stroke;success;supportive environment;symposium;synergism;Teacher Professional Development;Training;United States;United States National Institutes of Health;Universities;vascular cognitive impairment and dementia;Vermont;Whole Organism;Work

PROJECT_TITLE: Vermont Center for Cardiovascular and Brain Health


NIH_SPENDING_CATS: Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Neurosciences

PI_NAMEs: CUSHMAN, MARY  (contact)

PROJECT_TERMS: Accountability;Advisory Committees;American;Annual Reports;Attention;Award;Basic Science;Brain Diseases;brain health;Budgets;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;career;career development;Cause of Death;Centers of Research Excellence;Clinical;Clinical Investigator;Clinical Sciences;cohort;Collaborations;college;Communication;Communities;Core Facility;cost;Data;Databases;Dementia;Development;Dimensions;disability;Discipline;Disease;Education;Ensure;Equity;experience;Faculty;faculty mentor;Fostering;Foundations;Funding;Future;General Population;Goals;Grant;Heart;Image;Impaired cognition;improved;Infrastructure;innovation;Institution;interest;Leadership;man;Medicine;member;Mentors;Mentorship;Microvascular Dysfunction;Molecular Epidemiology;multidisciplinary;neurovascular;next generation;operation;Outcome;Pathogenesis;peer coaching;Persons;Phase;Physiology;Positioning Attribute;Program Development;programs;prospective;Protocols documentation;recruit;Research;research and development;Research Design;Research Institute;Research Personnel;Resources;Science;Scientist;Services;Specimen;Strategic Planning;Stroke;success;symposium;Teacher Professional Development;Techniques;Underrepresented Minority;Universities;Vermont;Woman;Work

PROJECT_TITLE: Core A: Administrative Core


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: The Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT) at the University of Pittsburgh (NEXT- UP) will continue to leverage the regional dominance of UPMC in healthcare, the CTSI, existing clinical research networks at the University of Pittsburgh, and other institutional resources for its successful clinical trials structure. NEXT-UP will continue to engage in practices that have led to successful enrollment into studies and will work to further increase capacity for entering patients into trials, as well as contribute to the educational, collaborative, and administrative functions of the overall network. NEXT-UP will actively support career development for early stage academic clinician researchers in neuroscience.

PI_NAMEs: CLEMENS, PAULA R (contact)

PROGRAM_OFFICER_NAME: OHAYON, JOAN M

PROJECT_TERMS: Adult;Advisory Committees;Agreement;base;Benchmarking;career;career development;Childhood;Clinical;clinical care;Clinical Investigator;clinical practice;Clinical Research;clinical research site;Clinical Sciences;clinical training;Clinical Trials;Clinical Trials Network;Collaborations;Communities;community clinic;community collaboration;Community Outreach;Community Physician;Data Coordinating Center;Education;Enrollment;experience;follow-up;Fostering;gene therapy;Goals;Group Therapy;Healthcare;Infrastructure;innovation;Institution;Institutional Review Boards;Intervention;Leadership;Maryland;Medical center;meetings;member;Mentors;Mission;Modeling;Monitor;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;Neurologic;Neurosciences;Ohio;outreach;outreach program;Participant;Patient Care;patient registry;Patients;Pediatric Neurology;Pennsylvania;Performance;performance site;Physicians;pre-clinical;Program Development;programs;Provider;recruit;Reporting;Research;Research Personnel;Research Training;Resources;Rotation;Running;Site;Standardization;Structure;success;Support Groups;therapeutic development;timeline;Training;Training Programs;Translating;Translational Research;Translations;Universities;West Virginia;Work;working group

PROJECT_TITLE: Network of Excellence in Neuroscience Clinical Trials (University of Pittsburgh CRS)


NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Clinical Research;Heart Disease;Neurosciences;Prevention

PI_NAMEs: ZAKAI, NEIL ADRIAN (contact)

PROJECT_TERMS: Address;Adult;American Heart Association;Area;assay development;Atherosclerosis;Award;Back;biobank;Biochemistry;Biological;Biological Assay;Biological Markers;Biology;Biometry;Biostatistical Methods;brain health;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;career;Cause of Death;Centers of Research Excellence;Cessation of life;Chronic Disease;Clinical;Clinical Research;Clinical Trials;Cohort Studies;Collaborations;Collection;Communities;complex data;Consultations;Coronary heart disease;cost estimate;Dementia;design;disability;Discipline;Disease;Educational workshop;Elements;Ensure;Epidemiologist;Epidemiology;Evolution;experience;Experimental Designs;Faculty;Fee-for-Service Plans;flipped classroom;Funding;Future;genome sequencing;Genomics;Grant;Health;Heart Diseases;Hematologist;Home;Impaired cognition;Individual;innovation;Institution;investigator training;Jackson Heart Study;Journals;Knowledge;Laboratories;laboratory experience;Leadership;Mediator;Mentors;metabolomics;Methods;modifiable behavior;modifiable risk;Molecular;Molecular Epidemiology;Multi-Ethnic Study of Atherosclerosis;multidisciplinary;National Heart, Lung, and Blood Institute;neurovascular;novel;observational cohort study;operation;Participant;Performance;Philosophy;Population;Population Research;Program Development;Proteomics;Public Health;Publications;Quality Control;Reasons for Geographic And Racial Differences in Stroke;Reporting;Research;Research Design;Research Personnel;Resources;Risk Factors;Role;Sampling;Scientist;Service delivery model;Services;skills;South Asian;Specific qualifier value;Statistical Data Interpretation;Stroke;success;Testing;Time;Trans-Omics for Precision Medicine;Translating;Universities;Vermont;whole genome;Work

PROJECT_TITLE: Core B:  Study Design and Molecular Epidemiology Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Neurosciences

PI_NAMEs: HENNIG, GRANT  (contact)

PROJECT_TERMS: 3-Dimensional;3D Print;4D Imaging;Active Learning;Address;Amyloid beta-Protein;Animals;arteriole;awake;Basic Science;Blood capillaries;brain health;Calcium;cardiovascular health;cell preparation;Cells;Centers of Research Excellence;Clinical;Complex;Computer software;Confocal Microscopy;Coupled;design;Development;Dimensions;Doctor of Philosophy;educational atmosphere;Electrophysiology (science);Environment;Equipment;experimental study;fabrication;Faculty;Faculty Recruitment;Fee-for-Service Plans;flexibility;Future;Goals;graduate student;Grant;heart function;Human Resources;Hyperemia;Hypertension;Image;Image Analysis;imaging capabilities;imaging modality;imaging system;in vivo imaging;Individual;Infrastructure;instrument;instrumentation;Investigation;investigator training;Laboratories;Learning;Microscope;Microscopy;millisecond;Modeling;mouse model;multi-photon;neuron loss;Neurosciences;neurovascular;Nevada;Nomads;operation;Optics;Pericytes;Pharmacology;Physiology;professor;programs;recruit;replicator;Research;Research Personnel;Resolution;restoration;Running;Sampling;Signal Transduction;skill acquisition;skills;System;Techniques;Technology;temporal measurement;Testing;Three-Dimensional Image;Time;tissue preparation;Training;Universities;Vermont;Work;Writing

PROJECT_TITLE: Core C:  Customized Physiology and Imaging Core


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Diabetes;Heart Disease;Heart Disease - Coronary Heart Disease;Obesity

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative/Relevance: Atherosclerosis is a progressive cardiovascular disease that remains the leading cause of death in the USA and worldwide in spite of widespread use of statins, other lipid lowering therapies, and life-style modifications. Of major concern, the incidence of symptomatic atherosclerosis in younger individuals is rising at an alarming rate primarily due to the global epidemic of obesity and early onset type 2 (insulin resistant) diabetes (T2D) and the associated metabolic disease (MetD) characterized by insulin resistance and increases in blood glucose, insulin, triglycerides, and cholesterol levels. Indeed, numerous high quality studies provide evidence that each of these factors may contribute to accelerated atherosclerosis development, progression, and end stage disease pathogenesis including rupture of the protective fibrous cap overlying advanced atherosclerotic lesions resulting in a heart attack or stroke. However, a major unresolved question is which if any of the T2D/MetD associated changes impair the ability of smooth muscle cells (SMC) or other cell types to form and maintain the protective fibrous cap. The goals of studies in this proposal are to address this question, and to identify novel therapeutic approaches to enhance the ability of these cells to form and maintain a thick and mechanically robust fibrous cap (i.e. analogous to a stronger patch on a tire) even in the context of T2D/MetD.

PI_NAMEs: OWENS, GARY K (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Acceleration;Address;aerobic glycolysis;Antibodies;Aorta;Arterial Fatty Streak;Atherosclerosis;Black race;Blood Glucose;Cardiovascular Diseases;Cardiovascular system;Carotid Endarterectomy;Cause of Death;Cd68;Cell Differentiation process;Cell Lineage;cell type;Cells;Characteristics;Cholesterol;Collagen;cytokine;Development;Diabetes Mellitus;diabetic;diabetic patient;Dose;Down-Regulation;early onset;end stage disease;Endothelial Cells;Event;Female;femoral artery;Foam Cells;Genes;Genomics;Glucose;glucose uptake;Goals;Grant;Hemorrhage;High Prevalence;Histologic;Human;human female;Hyperglycemia;Hyperlipidemia;Immune;Impairment;Incidence;indexing;Individual;Inflammatory;Injury;Insulin;Insulin Receptor;insulin receptor substrate 1 protein;Insulin Resistance;insulin secretion;Insulin-Like Growth Factor I;Insulin-Like-Growth Factor I Receptor;interest;Interleukin-1 beta;Investments;IRS2 gene;Knock-out;Knockout Mice;LDL Cholesterol Lipoproteins;Lesion;Lesion by Stage;Life Style Modification;Lipids;Macrophage;Maintenance;Mechanics;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;mortality;multiplexed imaging;Mus;Myocardial Infarction;Myofibroblast;Nature;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Obesity Epidemic;Pathogenesis;Pathway interactions;Patients;Phenotype;Proteins;PTPN6 gene;Receptor Signaling;Resistance;Role;Rupture;Sampling;Scaffolding Protein;sex;Signal Transduction;single-cell RNA sequencing;Smooth Muscle Myocytes;Stains;Streptozocin;Stroke;Sudan;Testing;Thick;Thinness;Triglycerides;validation studies;women versus men

PROJECT_TITLE: Role of Smooth Muscle Cell Insulin Resistance and Systemic Metabolic Dysfunction in Atherosclerosis Development and Late Stage Lesion Pathogenesis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE – OVERALL Alzheimer's disease and related dementias (ADRD) represent one of the greatest health problems in the United States and the state of Michigan. Building on longstanding strengths in dementia research, outreach and training at three universities working as a consortium, the Michigan ADRC will lead a regional effort to identify, understand and modulate the many factors beyond β-amyloid that contribute to brain dysfunction and degeneration in ADRD.

PI_NAMEs: PAULSON, HENRY L (contact)

PROGRAM_OFFICER_NAME: ELLIOTT, CERISE

PROJECT_TERMS: Acceleration;Address;Affect;African American;Aging;aging demography;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease therapy;American;Amyloid;Amyloid beta-Protein;Award;Biological Markers;Black American;Black race;brain dysfunction;Capsicum;Centers of Research Excellence;Clinical;Cognition;Collaborations;Communities;contextual factors;Dementia;Development;Diagnosis;Diagnostic;Disclosure;Disease;disorder risk;Education;Education and Outreach;education research;Elderly;Ensure;Environment;experience;Foundations;frontotemporal lobar dementia amyotrophic lateral sclerosis;Funding;gene environment interaction;Health;Health Disparities Research;health disparity;Health Professional;Heterogeneity;Hispanic;improved;innovation;Institution;Knowledge;Latino;Lead;Lewy Body Dementia;Link;Longitudinal cohort;Mentors;Michigan;Modification;molecular imaging;Molecular Profiling;Multi-Institutional Clinical Trial;Nerve Degeneration;neuroimaging;next generation;Nonpharmacologic Therapy;novel;novel diagnostics;novel marker;novel therapeutic intervention;outreach;Parkinson Disease;patient engagement;Peripheral;Population Research;programs;Protein-Folding Disease;racial diversity;recruit;Research;Research Subjects;Research Support;Resources;Risk;Rotation;Scientist;Site;Students;symposium;Therapeutic;Training;training opportunity;translational neuroscience;United States;Universities;Vascular Dementia;Work

PROJECT_TITLE: Michigan Alzheimer's Disease Research Center


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

PROJECT_TERMS: Address;Advocacy;Age;age related;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Awareness;Biological Markers;Black race;brain dysfunction;Brain imaging;Clinical;clinical care;cognitive change;cohesion;Collaborations;Communication;Communities;Counseling;data exchange;Dementia;Development;Disclosure;Education and Outreach;education research;Educational Activities;Ensure;ethnic disparity;Funding;Goals;Health Professional;Human Resources;human subject;innovation;Leadership;Link;Manuscripts;Medical;meetings;Michigan;Mission;Nerve Degeneration;Neurologic;Neuropsychology;next generation;Ohio;outreach;Patient Recruitments;Positioning Attribute;Productivity;programs;racial disparity;Reproducibility;Research;Research Personnel;research study;Resources;Risk Factors;Sampling;skills;sound;Strategic Planning;success;supportive environment;synergism;Talents;Training;training opportunity;United States National Institutes of Health;Universities;Work


NIH_SPENDING_CATS: Bioengineering;Data Science;Immunotherapy;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: STANFORD

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Recent technological advances have enabled the production of large immune monitoring datasets, providing an opportunity for systems-level efforts to harness the power of the immune system in developing immune therapies and diagnostic tests. In this project, we will develop machine learning algorithms for analysis of the immune system at a single-cell level, in a multiomics setting integrated with various other biological measurements, and subject to adjustments based on population-level factors. This work will provide a strong quantitative bridge between large-scale epidemiologic trends and deep biological profiling to investigate the complex mechanisms that govern the immune system in clinical settings.

PI_NAMEs: AGHAEEPOUR, NIMA  (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Address;Algorithmic Analysis;Algorithms;Area;biobank;Biological;Biological Assay;biological systems;Cells;Characteristics;Clinical;cohort;Cohort Studies;Collaborations;Complex;Computer software;curse of dimensionality;Data;Data Set;Development;Diagnostic tests;Disease;Elasticity;Ensure;Epidemiological trend;flexibility;Foundations;genome analysis;Immune;Immune response;Immune system;Immunity;Immunodiagnostics;Immunologic Monitoring;Immunological Models;Immunologics;Immunotherapy;Knowledge;Laboratories;learning strategy;Machine Learning;machine learning algorithm;Measurement;Measures;Medical History;metabolome;microbiome;Modality;Modeling;Multiomic Data;multiple omics;Nature;open source;patient population;patient subsets;Patients;Population;predict clinical outcome;Production;programs;Proteome;Reproducibility;Research;response;Series;Socioeconomic Factors;System;Technology;Visualization;Work

PROJECT_TITLE: Machine Learning for Integrative Modeling of the Immune System in Clinical Settings

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Kidney Disease

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: NARRATIVE More than 400 million people suffer from diabetes in the world and one third of them may eventually develop diabetic kidney disease (DKD). The loss of podocytes, an integral part of the filtration system in the kidney, is a major contributor to the DKD progression. In this research proposal, we aim to investigate the mechanisms mediating the podocyte loss in diabetic kidney disease, so that future therapeutic approaches may be developed to mitigate the podocyte loss in DKD.

PI_NAMEs: HE, JOHN CIJIANG;LEE, KYUNG  (contact)

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Adriamycin PFS;Alanine;Albuminuria;Amino Acids;Apoptosis;Apoptotic;Attenuated;biobank;Cell Cycle Arrest;Cell Death;cell injury;Cell model;Cells;Cessation of life;cohort;Cytoprotection;Data;Data Set;Detection;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Nephropathy;Disease;Disease Progression;End stage renal failure;Endothelial Cells;Enzymes;Epithelial Cells;Event;Experimental Models;Extracellular Domain;Filtration;Focal and Segmental Glomerulosclerosis;Future;Gene Expression;Genes;glomerular endothelium;Glomerular Filtration Rate;Homeostasis;Human;In Vitro;in vivo;Incidence;Induction of Apoptosis;Injury;Integral Membrane Protein;Kidney;kidney cell;Kidney Diseases;knock-down;Knowledge;Maps;Matrix Metalloproteinases;Mediating;Membrane;Messenger RNA;Modeling;Molecular;mouse model;mRNA Expression;Mus;mutant;Nephrotic Syndrome;novel;Oncogenic;Outcome;overexpression;paracrine;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Peptide Hydrolases;Persons;Phosphotransferases;Plasma;podocyte;Point Mutation;Prognostic Marker;Protein Kinase;Proteins;Publishing;Regulation;Renal glomerular disease;Reporting;Research Proposals;response;Retinoic Acid Binding;Retinoic Acid Receptor;risk variant;Role;Signal Induction;Signal Pathway;Signal Transduction;Site;Site-Directed Mutagenesis;System;Therapeutic;TNF gene;TP53 gene;transcriptomics;Translating;Tretinoin;Tubular formation;Tumor Suppressor Proteins;uptake;urinary;Urine;Work

PROJECT_TITLE: Role of RARRES1 in diabetic kidney disease

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


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

PI_NAMEs: HAMPSTEAD, BENJAMIN MICHAEL (contact)

PROJECT_TERMS: Address;African American;Age;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Back;Biological Markers;Black American;Blood;Blood specimen;Blood Vessels;blood-based biomarker;brain dysfunction;career;Classification;Clinic;Clinical;clinical care;clinical practice;Clinical Research;Clinical Trials;cohort;Collaborations;Collection;Communities;cost;Data;data management;Data Reporting;Dementia;Detection;Disclosure;Disease;Early Diagnosis;education research;Enrollment;Ensure;Ethics;Evaluation;Event;experience;Feedback;Funding;Future;Goals;Hispanic;Impaired cognition;implementation facilitation;Individual;Infrastructure;Institution;Interdisciplinary Study;interest;Latino;Learning;Link;Location;Longitudinal cohort;Magnetic Resonance Imaging;metabolic imaging;Michigan;Minority Recruitment;Modeling;Monitor;MRI Scans;Nerve Degeneration;neuroimaging;neuropathology;next generation;novel marker;Observational Study;operation;outreach;Participant;Patients;pharmacologic;Population Control;Positioning Attribute;Positron-Emission Tomography;recruit;Registries;repository;Research;Research Personnel;Resource Sharing;Resources;Risk;saliva sample;Scanning;Secure;Specimen;structural imaging;success;tau Proteins;Therapeutic Intervention;Training;training opportunity;transmission process;treatment response;Universities

PROJECT_TITLE: Core B: Clinical Core


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE The proposed research represents a new and alternative strategy for characterizing important structural parameters of disordered proteins, proteins with intrinsically disordered regions, and mixtures of disordered proteins, all of which are critical for cellular function and are implicated in many degenerative disorders and epigenetic diseases. Disorder makes these proteins difficult to characterize structurally, and existing methods for analyzing them are unable to separately analyze mixtures of disordered proteins often found in cells. Thus, the proposed research is relevant to the NIH mission as it contributes to the fundamental knowledge of human molecular biology and is relevant for its application in reducing illness in patients with neurodegenerative disorders and epigenetic diseases.

PI_NAMEs: WEBB, IAN  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Affect;Binding;Biological;biophysical tools;Cell Physiology;Cells;Cellular biology;crosslink;Degenerative Disorder;Disease;DNA;Epigenetic Process;experimental study;Gases;Goals;Histones;Human;Individual;insight;ion mobility;Knowledge;Label;Laboratories;Ligand Binding;Link;Mass Spectrum Analysis;Measures;Methods;Mission;Molecular Biology;Molecular Conformation;molecular dynamics;Neurodegenerative Disorders;Nucleosomes;Patients;Phase;Post-Translational Protein Processing;Protein Conformation;protein folding;protein structure;Proteins;Proteome;Reader;Research;Role;small molecule;Specificity;Structure;Tail;Time;tool;United States National Institutes of Health;Work

PROJECT_TITLE: Intrinsically Disordered Protein Structural Dynamics from Combined Solution and Gas-Phase Approaches


NIH_SPENDING_CATS: Clinical Research;Genetics;Neurodegenerative;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative TBCK-encephalopathy is a recently described genetic disorder that causes intellectual disability, seizures and weakness in children across the world. Most of the children affected to date are Puerto Rican, presenting with severe loss of neurologic function, while other children have milder symptoms. Elucidating how loss of the TBCK protein leads to neurologic disease, particularly by examining the role mitochondria in relevant disease models, may provide insight into the mechanisms that lead to neurodegeneration and may help develop new therapies for this devastating disease.

PI_NAMEs: ORTIZ-GONZALEZ, XILMA R (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Address;Affect;Age;Alleles;Atrophic;Autism Diagnosis;autism symptoms;Automobile Driving;Autophagocytosis;autosome;Biogenesis;Biological;Biological Assay;Biology;Brain;Branched-Chain Amino Acids;Child;Childhood;Clinical;clinical diagnosis;Co-Immunoprecipitations;Complex;CRISPR/Cas technology;Data;Disease;disease model;Down-Regulation;Encephalopathies;Environment;Epilepsy;experimental study;Face;Fibroblasts;Fishes;fluorescence lifetime imaging;Frameshift Mutation;FRAP1 gene;Frequencies;Functional disorder;Future;gene replacement;Genes;Genetic Diseases;Genotype;Glycoprotein Degradation Pathway;Goals;Homidium Bromide;Human;Impairment;In Situ;in vivo;Independent Scientist Award;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;insight;Institution;Intellectual functioning disability;Label;Learning;Leucine;loss of function;Measures;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;Motor Neurons;Mutation;NADH;Names;Nerve Degeneration;Nervous System Disorder;Nervous System Physiology;Neurodegenerative Disorders;neurodegenerative phenotype;Neurodevelopmental Disorder;neurogenetics;Neurologic;Neurologic Symptoms;neuromuscular;Neurons;Neurosciences;new therapeutic target;novel;novel therapeutics;null mutation;overexpression;Pathway interactions;Patients;Phenotype;Phosphotransferases;Physicians;Physiological;Play;Positioning Attribute;programs;protein expression;Protein Glycosylation;Protein Kinase;protein protein interaction;Proteomics;Puerto Rican;Quality Control;Reporting;Research;Respiration;Respiratory Chain;Role;Scientist;Seizures;Severities;Signal Transduction;Spinal Muscular Atrophy;Symptoms;Syndrome;Techniques;Testing;Therapeutic;tool;Training;Treatment Efficacy;vector;Work;Zebrafish

PROJECT_TITLE: TBCK Encephaloneuronopathy: establishing the role of mitochondrial dysfunction in promoting neurodegeneration

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


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;Data Science;Dementia;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention

PI_NAMEs: BAKULSKI, KELLY  (contact)

PROJECT_TERMS: Alzheimer's Disease;Alzheimer's disease related dementia;Applications Grants;Area;Big Data;Bioinformatics;Biological Markers;Characteristics;Clinical;cohort;Collaborations;Communication;Communities;Complex;complex data;Consultations;Data;Data Analyses;Data Collection;Data Coordinating Center;data integration;data integrity;data management;Data Security;data sharing;data visualization;Database Management Systems;Databases;design;Development;Discipline;education research;educational atmosphere;electronic data;environmental enrichment for laboratory animals;Epidemiology;experience;Exposure to;Faculty;flexibility;Funding;Generations;Genetic;Genomics;Goals;Grant;Health Insurance Portability and Accountability Act;Image;improved;innovation;Institution;Institutional Review Boards;International;investigator training;Knowledge;Link;machine learning prediction;Magnetic Resonance Imaging;Measures;meetings;member;Methods;Michigan;multiple data sources;multiple omics;neuroimaging;neuropathology;Neuropsychology;next generation;Operations Research;outreach;Participant;Pathologic;Patient Recruitments;Phenotype;polygenic risk score;Prevention;Procedures;Process;Proteomics;query tools;Reproducibility;Research;Research Personnel;Risk Factors;Scientist;Secure;Seminal;skills;Statistical Data Interpretation;Statistical Models;statistics;Techniques;Technology;Telemedicine;Time;Training;training opportunity;user-friendly;Visit;Work

PROJECT_TITLE: Core C: Data Management and Statistical Core


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Skin Cancer

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

PHR: Project narrative Treatment of melanoma with drugs leads to the emergence of new cell lineages that are drug resistant. In this proposal we will explore whether the new cell states that convey resistance in melanoma are dependent upon an epigenetic enzyme called histone deacetylase HDAC8. We will determine how activation of HDAC8 allows melanoma cells to survive in the presence of drug and to evade immune attack, and will develop new therapeutic strategies that limit HDAC8-mediated drug resistance.

PI_NAMEs: LICHT, JONATHAN D.;SMALLEY, KEIRAN  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: 3-Dimensional;Acetylation;Address;Affect;Antigen Presentation;Antigens;ATAC-seq;BRAF gene;cancer type;CD8-Positive T-Lymphocytes;Cell Line;Cell Lineage;Cells;checkpoint therapy;Chromatin;Chromatin Loop;Clinical;Clinical Trials;cofactor;cohesin;Complex;CRISPR screen;Data;Deacetylation;Development;drug maintenance;Drug resistance;drug withdrawal;Environment;Enzymes;EP300 gene;Epidermal Growth Factor Receptor;Epigenetic Process;Excision;Exclusion;Future;Gene Expression;Genes;Genetic Transcription;Grant;HDAC8 gene;Hi-C;Histocompatibility Antigens Class I;Histone Deacetylase;Histone Deacetylase Inhibitor;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune Evasion;Immune system;immunoregulation;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo;inhibitor;inhibitor therapy;insight;Interferons;Interleukin-11;jun Oncogene;loss of function;Mediating;MEKs;Melanoma;Melanoma Cell;Mesenchymal;Modeling;mouse model;multiple omics;Mus;Mutation;Myelogenous;novel;novel therapeutic intervention;novel therapeutics;overexpression;Pathway interactions;Pharmaceutical Preparations;Phenotype;prevent;Prevention;programs;Proteins;Proteomics;PTEN gene;recruit;Resistance;response;Role;sample fixation;Signal Transduction;Signaling Protein;single-cell RNA sequencing;small molecule inhibitor;Specimen;T cell infiltration;T-Lymphocyte;targeted treatment;Testing;therapy resistant;transcription factor;Transcription Factor AP-1;treatment response;tumor;tumor eradication;tumor-immune system interactions;Work

PROJECT_TITLE: Defining and targeting epigenetic plasticity-driven drug resistance and immune escape in melanoma

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Gene Therapy;Genetics;Infectious Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The virus that causes COVID-19 has a large RNA genome that often folds into structures at important sites. We will attack its genome using a new type of nucleic acid drug that recognizes not only the sequence but also the structure of the viral RNA. Using this innovative technology, we have identified promising drug candidates and will optimize them and discover new drugs for effectively treating the disease.

PI_NAMEs: GUO, FENG  (contact)

PROGRAM_OFFICER_NAME: BASU, DIPANWITA

PROJECT_TERMS: 2019-nCoV;3-Dimensional;Academia;Address;Affect;Affinity;Algorithms;Animal Model;Anti-viral Agents;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;base;Base Pairing;Binding;Biochemical;Biological;Cells;Cessation of life;Chemicals;clinical candidate;Clinical Trials;Communicable Diseases;Complex;COVID-19;COVID-19 pandemic;COVID-19 treatment;Cytomegalovirus;Data;design;Development;Disease;drug candidate;drug development;drug resistant virus;Elements;Emergency Situation;Emerging Communicable Diseases;Feedback;fighting;Formulation;Foundations;Free Energy;Genetic Transcription;Genome;Goals;health care availability;high risk;Human;Hydrogen Bonding;improved;in vivo;Industry;innovation;innovative technologies;intravenous injection;Lead;lead optimization;Life;Literature;Methods;Modification;Molecular Biology;Monitor;mouse model;Mus;Mutation;Nose;novel drug class;novel therapeutics;Nucleic Acids;Oligonucleotides;pandemic disease;Pathogenicity;Pattern;Persons;Pharmaceutical Preparations;Phylogenetic Analysis;Predisposition;prevent;Prevention;Production;Program Development;Property;Proteins;remdesivir;Reporting;Research;RNA;RNA Viruses;SARS-CoV-2 inhibitor;Shapes;Site;Specificity;Structure;Symptoms;synthetic nucleic acid;Technology;technology platform;Testing;Therapeutic Effect;three dimensional structure;United States Food and Drug Administration;Vaccines;Vertebral column;Viral;viral RNA;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Developing three-dimensional antisense oligonucleotide drugs against COVID-19


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: LITTLE ROCK

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE  Mechanical signals promote osteoblast differentiation and bone formation, but the molecular mechanisms remain unclear. The aim of proposed studies is to uncover the underlying mechanisms and this will be accomplished by studying a mechanosensitive ion channel Piezo1 and its downstream effectors in osteocytes. The successful completion of this work may provide new strategies to modulate regenerative responses and develop therapies to treat the bone loss related to disuse or advanced age.

PI_NAMEs: XIONG, JINHU  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Adult;Aging;Agonist;Alleles;Area;bone;Bone Formation Stimulation;Bone Growth;bone loss;bone mass;Bone Matrix;Bone Regeneration;Bone remodeling;Bone Resorption;bone strength;Calcium;Calcium Channel;Calcium Channel Inhibition;Calcium Signaling;Cell model;Cell Surface Proteins;Cells;Chemicals;Cilia;Complement;conditional knockout;cortical bone;dentin matrix protein 1;Development;Elderly;Enterobacteria phage P1 Cre recombinase;Exhibits;fluid flow;Focal Adhesions;fracture risk;Generations;Genes;genetic approach;Hindlimb Suspension;Homeostasis;human old age (65+);Immobilization;In Vitro;in vivo;Individual;inhibitor;Integrins;Ion Channel;Knockout Mice;Knowledge;Ligands;Liquid substance;mechanical force;mechanical load;mechanical signal;Mechanical Stimulation;mechanical stimulus;Mechanics;mechanotransduction;Mediating;Modeling;Molecular;mouse genetics;Mus;old mice;osteoblast differentiation;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;overexpression;pharmacologic;Phenotype;Piezo 1 ion channel;Play;postnatal;prevent;Rattus;Regenerative response;response;Role;shear stress;Signal Pathway;skeletal;Skeleton;Stimulus;Structure;substantia spongiosa;Tail;Tail Suspension;Testing;therapy development;tibia;Transgenes;Transgenic Mice;ulna;Wild Type Mouse;WNT Signaling Pathway;Work

PROJECT_TITLE: The role of Piezo1 in bone homeostasis and mechanotransduction

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: HG

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_DEPT: SOCIAL SCIENCES

PHR: This application is for continued T32 support of a research training program at Stanford University to create independent scholars who can conduct rigorous research on ethical, legal and social implications of genetics and genomics (ELSI). Since 2016, with support of a T32 award, we have appointed 7 postdoctoral scholars into the program, all women, one Latina and one African-American. The goal of this renewal is to train 7 more postdoctoral fellows and to continue our successful contribution to the diversity and excellence of the ELSI research communities.

PI_NAMEs: CHO, MILDRED K. (contact);TABOR, HOLLY K

PROGRAM_OFFICER_NAME: STERLING, RENE

PROJECT_TERMS: ethical, legal, and social implication;Research;Training Programs

PROJECT_TITLE: The Stanford Training Program in ELSI Research


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

PI_NAMEs: LIEBERMAN, ANDREW P (contact)

PROJECT_TERMS: Advisory Committees;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Area;Autopsy;Basic Science;Biological;Biological Markers;Black race;Brain;brain dysfunction;brain tissue;Caregivers;Clinical;Clinical Data;Clinical Research;cohort;Collaborations;Collection;Communication;Communities;Country;Data;data analysis pipeline;data management;Databases;demented;Dementia;diagnostic criteria;Diagnostic Services;Disease;DNA;education research;Educational Activities;Educational process of instructing;Evaluation;Family;Freezing;Future;Goals;Health Professional;Hispanic;innovation;innovative technologies;Institution;Investigation;Latino;Michigan;Microscopy;Nerve Degeneration;neuropathology;next generation;outreach services;Participant;Pathogenesis;Patients;Physicians;Plasma;Practice Guidelines;Procedures;profession allied to medicine;Reagent;Recruitment Activity;Research;Research Activity;Research Personnel;Research Project Grants;Resource Sharing;Resources;Sampling;Serum;Standardization;Technology;Therapeutic;Tissue Banks;tissue fixing;Tissues;Training;translational study;Universities;Whole Blood;Work

PROJECT_TITLE: Core D: Neuropathology Core


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: As the human lifespan increases, a critical challenge is to simultaneously improve healthspan. Studying individuals that are predisposed to exceptional longevity will help us achieve that goal. Biobehavioral factors can extend healthspan, by improving well-being and driving healthier outcomes. We will develop a monkey model of familial exceptional longevity and identify the unique biobehavioral phenotypes of these individuals to stimulate new research that will help people live longer, healthier lives.

PI_NAMEs: KINNALLY, ERIN LORAINE (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Adult;Age;age acceleration;aged;Aging;Animals;Assessment tool;Attention;Automobile Driving;Behavior;Benchmarking;biobehavior;Biological Aging;Biological Markers;biopsychosocial;Blood Chemical Analysis;California;Characteristics;Chronology;Cognition;Cognitive;cognitive reserve;Data;Deceleration;Decision Making;disorder risk;Elderly;emotion regulation;Emotional;Exhibits;Expectancy;Experimental Animal Model;extend lifespan;Family;flexibility;Funding;Future;genetic pedigree;Geriatrics;Goals;Health;Health Promotion;healthspan;healthy aging;Human;human model;Impaired cognition;improved;In Situ;Individual;Individual Differences;individual variation;Infant;innovation;Intervention;Length;Life;Life Expectancy;Link;Longevity;Macaca;Macaca mulatta;Maps;Mental Depression;Methods;middle age;Modeling;Molecular;Monkeys;Motivation;National Institute on Aging;neural;new technology;nonhuman primate;novel;Outcome;Personal Satisfaction;Persons;Phenotype;positive emotional state;Primates;Problem Solving;programs;promote resilience;prospective;Quality of life;Recording of previous events;Research;resilience;Resources;Sensory;Short-Term Memory;social;social attention;Standardization;Stress and Coping;stress resilience;Surveys;Technology;Time;tool;trait;translational research program;Withdrawal;Work

PROJECT_TITLE: Exceptional Longevity and Biobehavioral Aging in Rhesus Macaques

STUDY_SECTION: BRLE

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Women's Health Research

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE The proposed project will develop a fluid mechanics approach to studying tracer transport through tissue for perfusion quantification in magnetic resonance imaging, which is termed as quantitative transport mapping (QTM). Thesuccessful outcome of this project will establish the fluid mechanics based QTM for perfusion quantification as a more effective alternative to Kety's method with preservation of local mass conservation and without the problem of arterial input function.

PI_NAMEs: WANG, YI  (contact)

PROGRAM_OFFICER_NAME: DUAN, QI

PROJECT_TERMS: Address;Anatomy;Angiography;arterial spin labeling;Arteries;Biophysics;Black Box;Blood flow;Blood Vessels;Brain;Breast;breast imaging;clinical practice;Clinical Trials;Collection;Complex;Computing Methodologies;contrast enhanced;Data;Data Set;deep learning;deep neural network;Defect;Equation;Feasibility Studies;Fingerprint;Goals;Image;improved;interest;Ischemic Stroke;Kidney;kidney imaging;Kidney Transplantation;Knowledge;large datasets;Laws;Liquid substance;Magnetic Resonance Imaging;Malignant Neoplasms;Mammary Neoplasms;Maps;Mechanics;Medical Imaging;Methods;millisecond;Organ;Outcome;Output;Patients;Perfusion;Permeability;Positron-Emission Tomography;Predisposition;preservation;Process;Property;Quantitative Microscopy;Research Project Grants;Resolution;simulation;Specific qualifier value;Stroke;Structure;Technology;Time;Tissues;Tracer;Training;tumor

PROJECT_TITLE: Fluid mechanics approach to tissue perfusion quantification in MRI

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


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 Services;Neurodegenerative;Neurosciences

PI_NAMEs: ROBERTS, SCOTT  (contact)

PROJECT_TERMS: Achievement;Address;advanced dementia;Affect;African American;Aging;Ally;Alzheimer's Disease;Alzheimer's disease related dementia;amyloid imaging;Area;Awareness;Biological Markers;Black American;Black race;Caregivers;Clinical;clinically significant;Collaborations;Communication;Communities;community based participatory research;community engagement;Community Outreach;community partnership;Community Physician;Consensus;contextual factors;COVID-19 pandemic;data management;Dementia;dementia care;Development;Diagnosis;Disclosure;Education;Education and Outreach;education research;Educational Materials;Elderly;Evaluation;Event;experience;Faculty;Family;Family member;Funding;Genetic;Gerontology;Goals;graduate student;health communication;Health education;Health Personnel;Health Professional;Individual;innovation;interest;Knowledge;Lead;lectures;Lewy Body Dementia;Longitudinal cohort;Longitudinal cohort study;Memory;Memory Loss;Mentors;Methods;Michigan;Mission;multidisciplinary;neuroimaging;neuropathology;Neuropsychological Tests;Newsletter;Ohio;Online Systems;outreach;Participant;Patients;Personal Satisfaction;Persons;Policy Maker;Population Heterogeneity;Postdoctoral Fellow;Process;Program Evaluation;programs;Protocols documentation;Provider;recruit;Research;Research Personnel;research study;Research Training;Resources;Risk;Schools;skill acquisition;skills;Test Result;Training;Training Activity;Training and Education;United States National Institutes of Health;Universities;virtual;volunteer;web site

PROJECT_TITLE: Core E: Outreach, Recruitment, and Engagement Core


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurosciences;Prevention;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE  This proposal focuses on the fungal pathogenic Mucor species complex, which includes zygomycete pathogens that cause devastating infections in humans that are difficult to treat, with limited drug treatment options, and requiring surgical debridement in some patients. In this proposal, we aim to elucidate the molecular mechanisms and targets of epimutation, a novel mechanism of antimicrobial drug resistance in which RNAi silences drug target genes, and define the impact of host-pathogen interactions on epimutation. Results from these studies will inform treatment and prevention strategies for patients afflicted with Mucor infections by providing insights into novel mechanisms of pathogenesis and resistance to antifungal drugs as well as by stimulating development of novel antifungal drugs.

PI_NAMEs: HEITMAN, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Animal Model;Animals;anti-fungal agents;Anti-sense RNA;Azoles;Blood - brain barrier anatomy;Brain;calcineurin phosphatase;Categories;Cells;Central Nervous System Infections;Class Zygomycetes;Clinical;Coculture Techniques;Complex;Debridement;Development;Distant;DNA Transposable Elements;drug action;Drug resistance;Drug resistance pathway;drug sensitivity;Drug Targeting;drug-sensitive;Engineering;Evolution;Exhibits;FK506;Foundations;Frequencies;Fungal Drug Resistance;Gene Silencing;Genes;Genetic;Genetic Models;Genome Stability;genome-wide;Genomics;Germination;Helicase Gene;host-microbe interactions;Human;human pathogen;Hyphae;Immune;Immunocompetent;Immunocompromised Host;In Vitro;in vitro Model;Infection;infectious disease evolution;insight;Link;Macrophage;Mating Types;Mediating;Messenger RNA;Microbe;microbial;Microbial Drug Resistance;Modeling;Molecular;Morbidity - disease rate;mortality;Mucor;Mucormycosis;novel;Operative Surgical Procedures;Organ;Organoids;Outcome Study;pathogen;Pathogenesis;pathogenic fungus;pathogenic microbe;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phylogenetic Analysis;Polyenes;Positioning Attribute;Prevention;Prevention strategy;Process;Protein phosphatase;Publishing;Resistance;response;Rhizopus;RNA Helicase;RNA Interference;Role;Series;Sexual Reproduction;Small RNA;Stress;Testing;transcriptome;transcriptome sequencing;treatment strategy;Yeasts

PROJECT_TITLE: RNAi-dependent epimutation roles in antimicrobial drug resistance and pathogenesis

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE Cytochrome b5 reductase 3 (Cyb5R3) regulates soluble guanylyl cyclase heme iron redox state, a key enzyme controlling cerebral artery vascular tone. In this application, we will investigate whether a high frequency genetic variant (T117S) in Cyb5R3, which exists with 23% minor allele frequency in African Americans compared to less than 1% in Euro-Americans, contributes to cerebral vascular dysfunction and ischemic stroke. The proposed studies will fill a major void in our understanding of the role of CYB5R3 T117S in the pathogenesis of ischemic stroke, with the potential for the development of new strategies and therapeutics to treat a large proportion of AA who suffer from ischemic stroke.

PI_NAMEs: STRAUB, ADAM CARL (contact);SUN, DANDAN ;WOOD, KATHERINE C

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acetylcholine;Adult;African American;African American population;African American Women;African ancestry;African race;Age;American;Amino Acids;Attenuated;Binding;Biology;Blood Vessels;Brain Infarction;Brain Injuries;Cardiovascular system;Caucasians;cerebral artery;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Cerebrum;Clinical;Cyclic GMP;Cyclic GMP-Dependent Protein Kinases;cytochrome b5 reductase;Data;desensitization;Development;disability;Disparity;efficacy evaluation;Endothelial Cells;Enzymes;Etiology;Frequencies;Gene Frequency;Genetic;genetic variant;Genotype;Guanosine Triphosphate;Heme;Heme Iron;Image;Impairment;improved;Incidence;Individual;Infarction;innovation;iron (III) reductase;Ischemic Stroke;Knock-in;Knock-out;Knockout Mice;Knowledge;Magnetic Resonance Imaging;male;Mediating;Medical;middle age;Middle Cerebral Artery Occlusion;Minor;Morbidity - disease rate;mortality;mouse model;Mus;Myography;Nervous System Physiology;Nitric Oxide;Nitric Oxide Donors;Not Hispanic or Latino;novel;Oral Administration;Oxidants;oxidation;Oxidation-Reduction;oxidative damage;Oxidative Stress;Pathogenesis;Pathway interactions;personalized medicine;Pharmaceutical Preparations;Phenocopy;Phenotype;Pilot Projects;post stroke;pre-clinical;precision medicine;preservation;Prevalence;racial health disparity;Recovery;Recovery of Function;Regulation;Relaxation;Resolution;Role;Serine;Sex Differences;Signal Transduction;Smooth Muscle Myocytes;Soluble Guanylate Cyclase;Stroke;stroke outcome;Testing;Therapeutic;Threonine;tool;two-photon;Variant;Vascular Smooth Muscle;vasoconstriction;Vasodilation;White Women;Wood material

PROJECT_TITLE: Cerebral Vascular Redox Regulation in Stroke

STUDY_SECTION: ANIE

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


PI_NAMEs: KANAAN, NICHOLAS M (contact)

PROJECT_TERMS: Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Antibodies;Automobile Driving;Biological Assay;Biological Markers;Blood;blood-based biomarker;Brain;cardiovascular risk factor;Clinical;clinical center;Clinical Management;clinical practice;Clinical Research;Clinical Trials;Collaborations;Collection;cost;Coupled;Data;data management;Databases;Dementia;Development;Diagnosis;Diagnostic;diagnostic accuracy;Disease;disease heterogeneity;Disease Progression;education research;Educational Activities;Enzyme-Linked Immunosorbent Assay;Ethnic Population;Evaluation;Faculty;Future;genomic data;Goals;Health Professional;health training;improved;innovation;Interleukin-10;Interleukin-6;Light;Longitudinal cohort;Magnetic Resonance Imaging;Mass Spectrum Analysis;Measurement;Measures;Michigan;Modality;Molecular Profiling;neurofilament;neuroimaging;neuropathology;Neuropsychology;novel;novel marker;Onset of illness;patient population;Patient Recruitments;Patients;Peripheral;Physicians;Plasma;Positron-Emission Tomography;precision medicine;Proteomics;racial population;Reagent;Research;Research Personnel;Research Support;Resources;Sampling;Scientist;Shapes;single molecule;Students;System;targeted biomarker;tau Proteins;Technology;Time;TNF gene;Translational Research;Universities

PROJECT_TITLE: Core F: Biomarker Core


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: Huntington

ORG_NAME: MARSHALL UNIVERSITY

ORG_STATE: WV

PHR: Mishandling of salt balance by our body contributes to the development and progression of many common diseases, including hypertension and organ damage due to failure to remove excess amount of salt. We propose to demonstrate a new major regulatory mechanism of salt handling by the kidney, and that malfunction of this mechanism by the protein Na/K-ATPase compromises our body's ability to remove salt from the body. Therefore, the proposed investigation has profound basic and clinical implications, and may also provide new targets for developing better therapeutics.

PI_NAMEs: PIERRE, SANDRINE V (contact)

PROGRAM_OFFICER_NAME: KETCHUM, CHRISTIAN J

PROJECT_TERMS: Abbreviations;absorption;animal tissue;Apical;ATP phosphohydrolase;ATP1A1 gene;Attention;Bicarbonates;Binding;Binding Sites;Biochemical;blood pressure control;Blood Pressure Monitors;Cardiac Glycosides;Cardiac Myocytes;Cardiovascular system;Cell Culture Techniques;Cell Line;Cells;Chronic;Clinical;Communities;Complex;Cytoskeleton;Development;Disease;electrical potential;Epidermal Growth Factor Receptor;Epithelial Cells;epithelial Na+ channel;Failure;Fluid Balance;Foundations;Generations;Genetic;Glomerular Filtration Rate;Homeostasis;Hypertension;hypertensive;in vivo;Investigation;Ion Pumps;Ion Transport;Kidney;knock-down;Knock-out;Laboratories;Ligands;Lipids;Mediating;Membrane;Membrane Proteins;Modeling;Molecular;Molecular Conformation;mouse model;Mus;Muscle Contraction;mutant;Mutation;Natriuresis;neurotransmission;Organ;Ouabain;Patients;Peptides;pharmacologic;Phenotype;Phosphotransferases;Physiological;Physiology;Protein Isoforms;Proteins;Protocols documentation;Proximal Kidney Tubules;Reactive Oxygen Species;receptor;receptor function;Receptor Signaling;Regulation;renal epithelium;Reporting;Role;salt balance;salt intake;saluretic;Scaffolding Protein;Second Messenger Systems;Signal Transduction;Signaling Protein;Sodium;Sodium Chloride;src-Family Kinases;symporter;Technology;Telemetry;Testing;Textbooks;Therapeutic;tool;Transactivation;uptake;virtual;Work

PROJECT_TITLE: ATP1A1-dependent Regulation of Sodium Handling by the Renal Proximal Tubule: Mechanism and Implications in Salt-Sensitivity

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: MORGANTOWN

ORG_NAME: WEST VIRGINIA UNIVERSITY

PHR: PROJECT NARRATIVE Nanotechnology has provided important advancements in the area of engineering innovation, however, introduction of engineered nanomaterials in these technologies is not without hazard, and the negative effects on human health, at present, can only be speculated without detailed evaluation of their toxic nature. The proposed experiments are relevant to public health because they will enhance our understanding of the pathogenesis of engineered nanomaterial exposure and aid in the development of biomarkers and prophylactic interventions designed to lessen complications that are associated with engineered nanomaterial exposure. Thus, the proposed research is relevant to the NIH's mission that pertains to the pursuit of fundamental knowledge to extend healthy life and reduce the burden of illness.

PI_NAMEs: HOLLANDER, JOHN M (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acute;Address;Adenosine;Adult;Adult Children;Affect;Antioxidants;Applications Grants;Area;Automobile Driving;Bioenergetics;biomarker development;Biomedical Research;burden of illness;Cardiac;Cardiovascular system;clinical diagnostics;consumer product;Cytosine;Data;design;Development;developmental plasticity;Diet;Disease;Engineering;Environmental Impact;Epigenetic Process;epigenetic regulation;Equilibrium;Evaluation;Exhibits;experimental study;Exposure to;fetal;Fetal Development;Fetal Heart;Functional disorder;Future;Genome;Goals;hazard;Health;Human;Industrialization;Inhalation Exposure;innovation;insight;Knowledge;Laboratories;Life;Link;manufacturing process;Maternal Exposure;Messenger RNA;Metabolic syndrome;Methylation;Mission;Mitochondria;mitochondrial dysfunction;mitochondrial messenger RNA;Mitochondrial Proteins;Modeling;mouse model;Myocardial dysfunction;nano;nanoengineering;nanomaterials;Nanotechnology;Nature;novel;Nuclear;Organ;Organelles;Outcome;Oxidants;Oxidation-Reduction;particle exposure;Particulate Matter;Pathogenesis;Pathologic;Pathology;Play;Predisposition;Production;programs;prophylactic;Proteins;Proteomics;Public Health;Reporting;Research;Risk;Role;Signal Transduction;Structure;Supplementation;Technology;Testing;therapy design;titanium dioxide;Transgenic Mice;ultrafine particle;United States National Institutes of Health;Xenobiotics

PROJECT_TITLE: Influence of Particulate Matter on Fetal Mitochondrial Programming

STUDY_SECTION: EDD

STUDY_SECTION_NAME: Environmental Determinants of Disease Study Section [EDD]


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;Clinical Research;Dementia;Neurodegenerative;Neurosciences

PI_NAMEs: NOLL, DOUGLAS C (contact)

PROJECT_TERMS: Agreement;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Amyloid beta-Protein;arterial spin labeling;Autopsy;Basic Science;Biological Markers;biomarker validation;Blood Vessels;Clinical;Clinical Markers;Clinical Research;Collaborations;Consult;Consultations;Data;data management;Dedications;Deposition;design;Diagnosis;Diffusion;Diffusion Magnetic Resonance Imaging;Disease Progression;Early Diagnosis;Education;education research;Educational workshop;Eligibility Determination;eligible participant;Ensure;flexibility;Functional Magnetic Resonance Imaging;Gold;Health;Hippocampus;Image;image archival system;image processing;imaging biomarker;Imaging Device;Instruction;Iron;Laboratories;Lead;Lesion;Link;longitudinal analysis;Longitudinal cohort;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maps;Measures;meetings;Methods;Michigan;Modality;Modeling;Monitor;morphometry;multimodality;Myelin;Nerve Degeneration;neuroimaging;neuropathology;next generation;novel;novel marker;Participant;Pathology;Peripheral;Physics;Positron-Emission Tomography;Predisposition;Protocols documentation;rapid growth;recruit;Research;Research Personnel;Schedule;Scientist;Site;Source;Staging;Standardization;Structural Models;Structure;tau Proteins;Testing;Tissues;tool;Tracer;Training;Universities;Validation;Water;Work

PROJECT_TITLE: Core G: Neuroimaging Core


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Prevention

ORG_CITY: Newark

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative This project is relevant to the mission of the NIH because Cryptococcus neoformans is an important human pathogen that is difficult to treat with limited drug options, and this project aims to understand a novel mechanism of antifungal drug resistance. Characterizing how lipid translocation contributes to antifungal drug resistance will identify new drug targets and will guide efforts to develop antibody-based new disease prevention and control strategies.

PI_NAMEs: XUE, CHAOYANG  (contact)

PROJECT_TERMS: 3-Dimensional;Acquired Immunodeficiency Syndrome;Animal Model;anti-fungal agents;Antibodies;Antifungal Therapy;ATP phosphohydrolase;Bacteria;Binding;Biological;Calcium;Calcium Channel;Calcium Signaling;Caspofungin;Cell Death;cell growth regulation;Cell membrane;Cell Membrane Structures;Cell Physiology;Cell surface;Cells;Cellular Membrane;Cessation of life;Chelating Agents;Combined Modality Therapy;Cryo-electron tomography;Cryptococcosis;Cryptococcus;Cryptococcus gattii;Cryptococcus neoformans;D Cells;Data;Development;Disease;disorder control;disorder prevention;drug development;drug distribution;Drug resistance;Drug resistance pathway;drug sensitivity;Drug Targeting;echinocandin resistance;efficacious treatment;Electron Microscope;Enzymes;Epitopes;Exhibits;exportin 1 protein;Fab Immunoglobulins;forward genetics;Fungal Drug Resistance;fungicide;fungus;Future;Generations;Genetic study;glucan synthase;Goals;HIV/AIDS;Homeostasis;Human;human pathogen;Immunoglobulin Fragments;Immunoprecipitation;Impairment;In Vitro;in vivo;Infection;inhibitor;Ions;Knowledge;Lipid Bilayers;Lipids;Liposomes;Macrophage;Mass Spectrum Analysis;Mediating;Membrane;Membrane Proteins;Methods;Mission;Modeling;Molecular;Molecular Weight;Monoclonal Antibodies;mouse model;Mus;mutant;Mycoses;new therapeutic target;novel;novel therapeutics;Outcome;overexpression;pathogenic fungus;Peptides;Phagocytosis;Pharmaceutical Preparations;Phosphatidylserines;Phospholipids;polyclonal antibody;Polyenes;pre-clinical;Proteins;research and development;Resistance;resistance mechanism;Role;Scanning;Sequence Homology;Siblings;Structure;success;Surface;Testing;Therapeutic;Toxic effect;trafficking;Treatment Protocols;treatment strategy;Triazoles;United States National Institutes of Health;uptake;Vesicle;Virulence;yeast two hybrid system

PROJECT_TITLE: Role of phospholipids in antifungal drug resistance in Cryptococcus neoformans


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Immunotherapy;Neurosciences;Rare Diseases

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: Low-grade gliomas (LGG) predominantly affect adolescent and young adult (AYA) patients and two thirds of these patients experience malignant progression and lethal outcomes given we have no effective strategies or treatments to predict or prevent malignant progression. We discovered that current treatment failures are associated with the accumulation of immunosuppressive myeloid cells from the bone marrow, which evolve to impair the function of anti-tumor immunity. With this study, our goal is to develop novel immune surveillance approaches for AYA patients with LGGs at risk for malignant progression.

PI_NAMEs: RAJAPPA, PRAJWAL  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Adolescent and Young Adult;Affect;angiogenesis;Automobile Driving;Blood;Bone Marrow;Bone Marrow Cells;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Differentiation process;Cell Separation;Cells;Central Nervous System Neoplasms;Circulation;clinically significant;Cytometry;Data;Dependence;differential expression;digital;experience;Flow Cytometry;Genes;Glioma;Goals;Human;ID2 gene;immune checkpoint;Immunologic Surveillance;Immunosuppression;immunosuppressive macrophages;Impairment;in vivo;Infiltration;insight;interest;knock-down;Knock-out;Macrophage;Malignant - descriptor;Malignant Glioma;Methods;Migration Inhibitory Factor;Modeling;mouse model;Mus;mutant;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Natural Killer Cells;novel;Outcome;overexpression;Pathway interactions;Patients;Peripheral;peripheral blood;Pharmacological Treatment;Phenotype;Phosphotransferases;Population;prevent;Process;Prognosis;receptor;Risk;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;Spatial Distribution;Spleen;T-Lymphocyte;Testing;transcriptome sequencing;transcriptomics;Translating;Transplantation;Treatment Failure;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;Up-Regulation

PROJECT_TITLE: Bone marrow-derived myeloid cell dysregulation in malignant progression of glioma

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


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

PI_NAMEs: ALBIN, ROGER L (contact)

PROJECT_TERMS: African American;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;American;Applications Grants;Area;Award;Basic Science;Biometry;Capsicum;career;career development;Clinical;Collaborations;Communication;Communities;Complement;contextual factors;Development;Discipline;early-career faculty;education research;Educational Activities;Educational Curriculum;Educational process of instructing;effective therapy;Eligibility Determination;experience;Fostering;Funding;Generations;Goals;Grant;implementation research;Institution;inter-institutional;Interdisciplinary Study;Joints;Knowledge;knowledge integration;Manuscripts;massive open online courses;Mentors;Michigan;Modeling;multidisciplinary;Nature;next generation;online course;Postdoctoral Fellow;Preparation;Prevention strategy;Professional Competence;programs;recruit;Research;Research Personnel;Resource Development;Resources;Scientist;skills;symposium;Talents;Training;training opportunity;translational pipeline;Travel;Underrepresented Minority;Universities;Woman;Work

PROJECT_TITLE: Research Education Component


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Mental Health;Neurosciences

ORG_CITY: SEATTLE

ORG_NAME: ALLEN INSTITUTE

ORG_STATE: WA

PHR: This project seeks to elucidate the concept of the brain cell type and its relation to the brain architecture and function, by establishing links between molecular and anatomical cell types, circuit connectivity, and functional neural activity in the mouse primary visual cortex (V1). We will record activity of neurons, use multiplexed fluorescence in-situ hybridization (mFISH) to identify their cell types as defined by gene expression, analyze neuronal morphologies and connectivity using Electron Microscopy (EM) reconstruction of the V1 circuit, and release the resulting data and knowledge as a free atlas for the community. The findings and data from this project will serve as foundational resources for future scientific studies and biomedical applications aiming to leverage the relations between brain cell types, circuit structure, and its function.

PI_NAMEs: ARKHIPOV, ANTON  (contact);GARRETT, MARINA E.

PROGRAM_OFFICER_NAME: YAO, YONG

PROJECT_TERMS: Anatomy;Animals;Architecture;Area;area striata;area V1;Arousal;Atlases;awake;Brain;brain cell;Calcium;cell type;Cells;Characteristics;Code;Communities;Complement;Computer software;connectome data;Data;Data Analyses;data modalities;Data Set;data sharing;Disease;electrical property;Electron Microscopy;Electrophysiology (science);Evolution;excitatory neuron;experimental study;Fluorescent in Situ Hybridization;Future;Gene Expression;Gene Expression Profile;Grain;Image;In Situ Hybridization;in vivo;in vivo calcium imaging;in vivo imaging;Individual;Infrastructure;inhibitory neuron;Knowledge;Learning;lens;Link;Location;Locomotion;Maps;Measures;Methods;microscopic imaging;Mission;Molecular;Monitor;Morphology;Motion;Motor Activity;Movement;movie;Mus;Nature;neural;neuroimaging;Neurons;Neurosciences;Noise;online resource;patch sequencing;Pathology;Pathway interactions;Pattern;preference;Process;Property;reconstruction;Research;Resources;response;Role;segregation;Stimulus;Stream;Structure;Subcellular Anatomy;Taxonomy;Time;Tissue imaging;Tissues;tool;transcriptomics;Visual;Visual Cortex;visual information;visual processing;visual stimulus

PROJECT_TITLE: Bridging Function, Connectivity, and Transcriptomics of Mouse Cortical Neurons


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Urologic Diseases

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Little is known about what host-microbe interactions mediate urinary tract infections (UTI) by Acinetobacter baumannii, a bacterial pathogen whose alarming rates of multi-drug resistance (MDR) poses a global health threat. Given the waning effectiveness of antibiotic therapies, we must investigate the host and microbial determinants of MDR A. baumannii UTI in order to develop novel, antibiotic-sparing therapies and identify patients at risk of these infections. We propose a multidisciplinary approach that will not only address fundamental questions on A. baumannii uropathogenesis, but can also be readily applied to address similar questions in other forms of MDR A. baumannii disease.

PI_NAMEs: CALIX, JUAN JOSE (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acinetobacter;Acinetobacter baumannii;Address;Affect;analysis pipeline;Animals;Antibiotic Therapy;Antibiotics;Biologic Characteristic;Biological;Biological Assay;Bladder;career;Centers for Disease Control and Prevention (U.S.);Characteristics;Clinical;Clinical Data;clinical predictors;clinically relevant;cohort;Communities;comparative;Comparative Genomic Analysis;comparative genomics;Competence;Development;Disease;disorder risk;Effectiveness;Elements;Enterobacteriaceae;Environment;Epidemic;Epidemiology;epidemiology study;Escherichia coli;Etiology;Exhibits;fitness;Future;genetic element;genome sequencing;global health;Growth;Healthcare Systems;Hospitals;host-microbe interactions;Human;In Vitro;Infection;infection risk;Integration Host Factors;interdisciplinary approach;Intervention;Intestinal Diseases;Investigation;Link;Mediating;Mentors;Metabolic;microbial;Modeling;Molecular;Molecular Analysis;Multi-Drug Resistance;multidisciplinary;Multidrug-resistant Acinetobacter;Mus;Mutagenesis;Names;neglect;Nosocomial pneumonia;novel;pathogen;Pathogenesis;pathogenic bacteria;patient population;Patients;Pattern;Phylogenetic Analysis;Play;Population;Populations at Risk;Predisposing Factor;Prevalence;prospective;Pseudomonas;Pseudomonas aeruginosa;Publishing;Research;respiratory;Respiratory System;Respiratory Tract Infections;Retrospective cohort;Risk Factors;Role;Septicemia;Site;Source;Techniques;therapeutic target;tool;Training;trait;translational scientist;urinary;Urinary tract;Urinary tract infection;Urine;Uropathogen;Uropathogenic E. coli;urovirulent isolates;Virulence;whole genome;Work;World Health Organization

PROJECT_TITLE: Defining microbial and host determinants of Acinetobacter survival in the urinary tract

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Clinical Research;Patient Safety;Precision Medicine

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE  Antibiotics are often prescribed using a “one-size-fits-all” approach in critically ill patients, despite the multiple physiologic changes that occur during critical illness and can affect antibiotic concentrations and exposure (pharmacokinetics) and their ability to reach targets (pharmacodynamics). This proposal seeks to develop and prospectively validate population models describing antibiotic concentrations and their variability in critical illness for use in model-informed precision dosing (MIPD), an approach in which dosing regimens can be tailored to individual patient and clinical factors, and to evaluate the association between antibiotic target attainment and outcomes. This research is highly relevant to public health as it will optimize the use of antibiotics in critically ill patients, maximizing their efficacy and limiting their toxicity to improve clinical outcomes.

PI_NAMEs: TANG GIRDWOOD, SONYA C (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Address;Adult;Affect;Anti-Bacterial Agents;Antibiotics;bactericide;beta-Lactams;Clinical;cost;Critical Illness;Dangerousness;Data;Disease;Dose;Drug Kinetics;Electronic Health Record;Ensure;Foundations;Frequencies;improved;improved outcome;Individual;individual patient;innovation;Intensive Care Units;Knowledge;model building;Modeling;models and simulation;Morbidity - disease rate;mortality;nephrotoxicity;neurotoxicity;Odds Ratio;Outcome;Patient Admission;patient population;Patients;personalized approach;Pharmaceutical Preparations;Pharmacodynamics;Physiological;Population;precision medicine;programs;prospective;Public Health;Publishing;Regimen;Research;Resources;Risk;support tools;Therapeutic Intervention;Time;tool;Toxic effect

PROJECT_TITLE: Antibiotic Model-Informed Precision Dosing in Critical Illness

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


PHR: PROJECT NARRATIVE Mechanosensitive channels participate in an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. Our proposed structural and functional studies of mechanosensitive channels will provide critical information that will ultimately lead to development of new antimicrobial reagents and new treatment strategies for diseases associated with altered mechanical force sensation.

PI_NAMEs: YUAN, PENG  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Address;Adopted;Algae;Animals;antimicrobial;Architecture;Atherosclerosis;Bacteria;Biochemical;biophysical analysis;Biophysics;Bypass;C-terminal;Cells;chronic pain;Collection;Complex;Consensus;deafness;Development;Disease;Electrophysiology (science);Escherichia coli;Esthesia;Family member;fungus;gain of function;Hearing;Homologous Gene;innovation;insight;Ion Channel;Ions;Lead;Ligand Binding;Ligands;Lipids;Literature;Malignant Neoplasms;mechanical force;Mechanics;mechanotransduction;Mediating;Membrane;Membrane Proteins;microorganism;Modeling;Molecular Conformation;Morphogenesis;mutant;novel therapeutic intervention;novel therapeutics;Organism;Osmoregulation;Osmosis;Osmotic Pressure;Pathogenicity;Pathology;periplasm;Physiological Processes;Piezo ion channels;Plants;Positioning Attribute;potassium ion;Production;Proprioception;Proteins;Reagent;reconstitution;Resolution;response;Rest;Rupture;Sampling;Shapes;Signal Transduction;Spheroplasts;stem;structural biology;Structure;System;Testing;Touch sensation;Transmembrane Domain;treatment strategy;Work;Xenopus oocyte

PROJECT_TITLE: Structural Mechanism for Gating of Mechanosensitive Channels

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Prevention;Substance Misuse

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE The PSRTP is unique in its multi-disciplinary focus on prevention science as it relates to alcohol misuse, dependence, and related problems. The program provides the broad, yet intense, training experiences necessary to give early career researchers the depth and breadth of conceptual understanding, theoretical and methodological sophistication, and practical knowledge and skills necessary to advance the field.

PI_NAMEs: GRUBE, JOEL WILLIAM (contact);PASCHALL, MALLIE J

PROGRAM_OFFICER_NAME: CASTLE, I-JEN

PROJECT_TITLE: Prevention Science Research Training Program


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Neurosciences

ORG_CITY: Los Angeles

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE This research will identify brain and biobehavioral mechanisms that explain why individuals with depression show diverse patterns of success or failure with regulating their affect and their parasympathetic nervous system. We will identify subgroups based on their patterns of success with regulation in everyday life, examine brain mechanisms that underlie these groupings, and will test a real-world intervention to improve regulation success. This knowledge will be critical for understanding the heterogeneity in depression and for developing real-world interventions to prevent or improve the course of depression, toward the goal of precision medicine.

PI_NAMEs: STANGE, JONATHAN P (contact)

PROGRAM_OFFICER_NAME: TALKOVSKY, ALEXANDER MAXWELL

PROJECT_TERMS: active control;Affect;Behavior;Behavioral;biobehavior;Biofeedback;Biofeedback Training;Brain;brain circuitry;Characteristics;Classification;Clinical;cognitive control;Confidence Intervals;Data;Depressed mood;design;Dimensions;disability;Disease remission;Entropy;experience;Failure;Goals;Grouping;heart rate variability;Heterogeneity;improved;indexing;Individual;individualized medicine;Intervention;Knowledge;Laboratories;Life;Major Depressive Disorder;Measures;Mental Depression;Mental Health;Methodology;National Institute of Mental Health;neural;neuroimaging;neuromechanism;neurophysiology;Outcome;Parasympathetic Nervous System;Participant;Pattern;Phase;Phenotype;Physiological;Physiology;precision medicine;prevent;Process;Psychopathology;Psychophysiology;Randomized;Recovery;Regulation;remediation;Research;response;Rest;Risk;Sampling;screening;Screening procedure;Selection for Treatments;skills;Strategic Planning;Subgroup;success;Testing;Time;treatment response;young adult

PROJECT_TITLE: Ambulatory phenotyping with real-time indices of discordant affect regulation: Exploring opportunities for targeted intervention in depression

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CHICAGO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Numerous conditions that cause learning/memory impairments (e.g., Alzheimer’s, epilepsy, traumatic brain injury, post-traumatic stress disorder, schizophrenia, and stroke) affect the hippocampus, and the dentate gyrus specifically. Mossy cells, a commonly overlooked hippocampal cell type, regulate activity in the dentate gyrus and are particularly vulnerable to damage in many of these disorders. The proposed research will determine how mossy cells regulate the formation and retrieval of memories, offering new targets to treat memory impairments commonly observed in neurological disorders.

PI_NAMEs: GOODSMITH, DOUGLAS  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Affect;Alzheimer's Disease;Animals;Area;awake;Back;Behavior;Calcium;cell type;Cells;Cognition Disorders;Communication;Computer Models;Data;dentate gyrus;Disease;Dorsal;Ensure;Environment;Epilepsy;Episodic memory;Equilibrium;Event;experience;Fire - disasters;flexibility;Future;Goals;granule cell;Hippocampus;Image;in vivo;Individual;insight;Interneurons;Learning;Location;Mediating;Memory;memory encoding;Memory impairment;memory process;memory recall;memory retrieval;Modeling;Mus;Nervous System Disorder;neural;Neurologic;neuroregulation;novel;novel strategies;optogenetics;Output;Pattern;Population;Population Dynamics;Post-Traumatic Stress Disorders;prevent;Process;Property;Pyramidal Cells;Reporting;Research;Retrieval;Role;Schizophrenia;spatial memory;Stroke;theories;Traumatic Brain Injury;two-photon;virtual;virtual environment

PROJECT_TITLE: The role of dentate gyrus mossy cells in coordinating episodic memory formation and retrieval

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Clinical Research;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Amyotrophic lateral sclerosis is a progressive neurodegenerative disease whose pathologic hallmark is cytoplasmic mislocalization of the nuclear protein TDP-43 in motor neurons, where it is bound up in cytoplasmic stress granules. Both cytoplasmic toxicity and loss of nuclear function of TDP-43 contribute to neuronal death. The goal of this proposal is to determine the effects of reversing TDP-43 mislocalization, by sustainably knocking down Ataxin 2, a key stress granule component, and by enhancing nuclear import, both alone and in combination with Ataxin 2 knockdown.

PI_NAMEs: AMADO, DEFNE AUDREY (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Address;adeno-associated viral vector;adenovirus mediated delivery;Adult;Advisory Committees;Affect;aggregation factor;ALS pathology;Amyotrophic Lateral Sclerosis;Antisense Oligonucleotides;Area;Arsenites;Behavioral;Binding;biological adaptation to stress;Brain;Brain Stem;burden of illness;C9ORF72;career;Cell Death;Cell Line;Cell Nucleus;Cell Survival;Cells;Cervical spinal cord structure;Cessation of life;Clinical;Clinical Trials;Cortical Cord;Cytopathology;Cytoplasm;Data;Dedications;Dipeptides;Disease;DNA-Binding Proteins;Ensure;Exhibits;experience;extend lifespan;Fluoroscopy;Funding;gain of function;Gait;gene therapy;Genetic Models;Genetic Transcription;Goals;Grant;high risk;Histopathology;Human;improved;In Vitro;in vivo;Institution;Investigation;Karyopherins;knock-down;Knowledge;Longevity;loss of function;Lumbar spinal cord structure;Measures;Mediating;Mentors;Mentorship;Mission;Modeling;Molecular Biology;Motor Cortex;motor function improvement;Motor Neuron Disease;Motor Neurons;mouse model;Mus;National Institute of Neurological Disorders and Stroke;Neonatal;Nervous System;Neurodegenerative Disorders;Neurologist;Neurology;neuron loss;neuronal survival;Neurons;neuroprotection;Neurosciences;neurotropic;novel;novel therapeutics;Nuclear;Nuclear Import;Nuclear Protein;nucleocytoplasmic transport;overexpression;Pathologic;Patients;Pennsylvania;Physicians;preference;prevent;protein TDP-43;Proteins;Qualifying;Reporter;Repression;Resources;RNA Interference;RNA Splicing;SCA2 protein;Scientist;skills;Spinal Cord;sporadic amyotrophic lateral sclerosis;Stress;stress granule;stress reduction;success;synergism;Tars;Testing;Therapeutic;Toxic effect;Training;translation factor;Translations;Universities;vector;Viral;Viral Vector;Work

PROJECT_TITLE: Viral-based Therapeutic Approaches for Reversal of ALS Pathology


NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: SCN3A-related neurodevelopmental disorder (SCN3A-NDD) is a recently identified condition caused by pathogenic variants in the gene SCN3A encoding the voltage-gated sodium channel subunit Nav1 .3; this syndrome is defined by treatment resistant epilepsy, severe to profound intellectual disability, and, unexpectedly, malformation of cortical development, yet how sodium channel function might regulate brain development and channel dysfunction lead to brain malformation is entirely unknown. The objective of this proposal is to investigate how variants in SCN3A lead to these complex neurological phenotypes including epilepsy and structural brain malformation. The work proposed here will link across levels of analysis from human genetics, to ion channel and neuronal dysfunction, to clinical phenotype, in order to inform therapeutic discovery or preventative measures for this devastating disorder which is currently without treatment or cure.

PI_NAMEs: MERCHANT, JULIE PRIYA (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Acceleration;Anatomy;Axon;Bathing;Benign;Biological Models;Biology;biophysical properties;Biophysics;blind;Brain;brain malformation;career;Cell Line;Cells;Cerebral cortex;channel blockers;Clinical;clinical phenotype;Closure by clamp;cohort;Complex;Cortical Malformation;CRISPR/Cas technology;Cultured Cells;Data;Defect;Development;Disease;disease model;Electrophysiology (science);Embryo;Epilepsy;Exhibits;experimental group;experimental study;fluorescence imaging;Foundations;Functional disorder;Generations;Genes;genetic variant;Genetic Variation;Genotype;Growth;Heterozygote;Human;Human Genetics;Image;imaging system;immunocytochemistry;In Vitro;Individual;Induced Neurons;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;infancy;Inherited;innovation;insight;Intellectual functioning disability;Ion Channel;Lead;Link;malformation in cortical development;Mentors;Microfluidics;migration;Modeling;Morphogenesis;Morphology;Neuroanatomy;Neurodevelopmental Disorder;Neurologic;neuron development;Neuronal Dysfunction;neuronal excitability;Neurons;novel;Parents;Pathogenicity;Pathologic;Patients;Perfusion;pharmacologic;Phenotype;Physiological;Physiology;prevent;Preventive measure;Property;Prosencephalon;Recurrence;Resistance;Role;Sodium;Sodium Channel;stem cell model;Structural defect;Syndrome;System;targeted treatment;Techniques;Testing;Tetrodotoxin;Therapeutic;Training;Transfection;translational neuroscience;Variant;variant of unknown significance;voltage;voltage clamp;Work

PROJECT_TITLE: Models and mechanisms of SCN3A neurodevelopmental disorder