ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE USC’s “Training for the Multiscale and Multimodal Analysis of Biomarkers in Alzheimer’s Disease” (AD) will focus on preparing postdoctoral investigators for independent research careers by integrating four areas of methodologies to illuminate various aspects of biomarkers in AD at differing scales: molecular and cellular methods, imaging tools and informatics, quantitative methods for clinical trials research, and large-scale population analyses. Trainees will complete coursework and career development activities such as lab rotations, seminars, instruction for problem solving, communication, time management, and leadership skills, as well as career guidance, including instruction and training in grant writing, in order to apply successfully for future fellowships and career development and independent research support.

PI_NAMEs: TOGA, ARTHUR W (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TITLE: Training in the Multiscale and Multimodal Analysis of Biomarkers in Alzheimer’s Disease


ADMINISTERING_IC: AA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Aging;Alcoholism, Alcohol Use and Health;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Hypertension;Physical Activity;Prevention;Substance Misuse

ORG_CITY: ARLINGTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TEXAS ARLINGTON

ORG_STATE: TX

PHR: Project Narrative Repeated binge drinking is associated with elevated systolic blood pressure, which confronts more than half of mid-life adults in the United States. This K99/R00 application proposes training and research to develop a research strategy that integrates vascular physiology, physical therapies, and alcohol-related health. This will address the gaps in knowledge of mechanisms underlying alcohol-attributable contribution to elevated blood pressure and help identify/develop therapeutic approaches to decrease the burden of hypertension in mid-life adults.

PI_NAMEs: HWANG, CHUEH-LUNG  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Address;Adult;Aerobic Exercise;Age;age group;age related changes;Aging;alcohol abstinence;alcohol research;Alcohols;Area;Arteries;Attention;binge drinker;binge drinking;Biopsy;Blood Pressure;blood pressure elevation;blood pressure reduction;Blood Vessels;Cardiovascular Diseases;Cardiovascular Physiology;cardiovascular risk factor;career;career development;Clinical;Data;Development;Development Plans;early onset;effective intervention;Effectiveness;Environment;Event;exercise intervention;exercise training;Fatty acid glycerol esters;fitness;Foundations;Goals;Health;Hour;Human;Hypertension;improved;Interval training;Intervention;Knowledge;longitudinal design;Measures;Microvascular Dysfunction;middle age;Mission;National Institute on Alcohol Abuse and Alcoholism;Nerve;Norepinephrine;normal aging;Phase;Physical therapy;Physiology;Population;prevent;Prevention Research;Public Health;randomized controlled design;receptor;Recording of previous events;Reporting;Research;Research Personnel;Research Training;Resistance;response;Rest;Role;Site;skills;Therapeutic;therapeutic target;Training;United States;United States National Institutes of Health;urinary;Urine;vascular injury;vasoconstriction;Vasoconstrictor Agents;Vasodilation;young adult

PROJECT_TITLE: Reducing blood pressure in mid-life adult binge drinkers: the role of microvascular function and sympathetic activity

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Pain Research;Rare Diseases;Wound Healing and Care

ORG_CITY: IRVINE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative The major objectives of this renewal research application are: 1) identify the underlying mechanisms leading to adverse outcomes following corneal collagen crosslinking (CXL) using ultraviolet light (UVA) and riboflavin (Rf), and 2) develop alternative strategies that provide safer and more effective CXL for the treatment of corneal ectasia and refractive errors.

PI_NAMEs: JESTER, JAMES V (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: adverse outcome;Area;Bacterial Infections;Cell Death;cell injury;Cell Survival;Clinical Research;Collagen;Cornea;corneal epithelium;corneal scar;Coupled;crosslink;Data;Debridement;density;Devices;Diameter;Diffusion;Epithelial Cells;Epithelium;Excipients;Excision;experience;Eye;Funding;Gene Expression;Goals;Hour;individual patient;Inflammation;Inflammatory;intraepithelial;ionization;Keratoconus;Lasers;lens;Light;Measures;Minor;Modeling;Nerve;novel;Optics;Oryctolagus cuniculus;Pain;Pathological Dilatation;Patients;Penetration;photoactivation;Photons;Physiologic pulse;Plasma;Postoperative Pain;Procedures;Publications;Recovery;Refractive Errors;repaired;Research;Research Project Grants;Riboflavin;Risk;Safety;side effect;Stromal Cells;Testing;Therapeutic;two-photon;Ultraviolet Rays;Visual;wound healing

PROJECT_TITLE: Non-linear Optical Collagen Cross-linking (NLO CXL) for Treatment of Keratoconus


ADMINISTERING_IC: AG

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Frontotemporal dementia (FTD) is a heterogeneous group of similar clinical syndromes often presenting with impairments in social cognition, executive function, or language that is caused by either tauopathies or TDP-43 proteinopathies part of the frontotemporal lobar degeneration spectrum. To determine whether tau and TDP-43 pathology cause distinct patterns of neurodegeneration currently elusive to studies of clinically similar FTD patients, this project proposes to use new quantitative techniques to determine the relative loss of neural microcircuits within a comparative cortical layer framework of FTD patients. The innovative study of laminar microcircuits will not only advance our understanding of disease-specific patterns of selective vulnerability, mechanisms of progression, and the neural substrates of cognitive impairment in FTD, the cellular changes to laminar architecture will aid the discovery of anatomically-grounded diagnostic markers and therapeutic targets urgently needed in the FTD spectrum.

PI_NAMEs: OHM, DANIEL TIMOTHY (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Address;Anatomy;Antibodies;Architecture;Area;Autopsy;Axon;Bioinformatics;Biological;Biological Markers;Brain;brain behavior;Brain region;Cessation of life;Classification;Clinical;clinically relevant;Cluster Analysis;Cognition;Cognitive;cohort;comparative;Comparative Study;connectome;Data;Dementia;demographics;Development;Diagnosis;Diagnostic;diagnostic biomarker;digital;Disease;Disinhibition;Disparate;Distant;executive function;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;Genetic;Goals;Heterogeneity;high dimensionality;Human;Impaired cognition;Impairment;improved;in vivo;innovation;Interneurons;Knowledge;Language;Life;Link;Machine Learning;Measures;Mediating;Mentors;Methods;Microscopic;Modeling;Myelin;Neocortex;Nerve Degeneration;neural;Neural Pathways;Neurocognitive;Neurodegenerative Disorders;neuroimaging;neuron loss;neuronal cell body;Neurons;neuroprotection;novel;Pathologic;Pathology;Pathway interactions;Patients;Pattern;Population;preservation;Property;prospective;protein TDP-43;Proteins;Regional Anatomy;Research;Resolution;Resources;segmentation algorithm;social cognition;Stains;Stratum Granulosum;Subgroup;Symptoms;Synaptic Transmission;Syndrome;tau Proteins;Tauopathies;Techniques;Testing;Therapeutic;Therapeutic Studies;therapeutic target;Training;translational impact;Translational Research;Visualization;white matter

PROJECT_TITLE: Histopathologic interrogation of laminar microcircuits underlying cognition in frontotemporal dementia

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: AI

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: LOS ANGELES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The UCLA Microbial Pathogenesis Training Program provides essential support that unites students, postdoctoral fellows and faculty conducting research on pathogens that cause immense morbidity and mortality, and the host immune responses to these agents. Trainees are broadly educated in an array of biochemical and cellular mechanisms critical for establishing and maintaining microbial infections, as well as approaches used to combat diseases. Developing and achieving research career objectives are also integral components of our training program.

PI_NAMEs: JOHNSON, PATRICIA JEAN (contact)

PROGRAM_OFFICER_NAME: BROWN, LILIANA L

PROJECT_TITLE: Multidisciplinary Training in Microbial Pathogenesis

STUDY_SECTION: MID

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


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Hepatitis;Infectious Diseases;Liver Disease;Prevention

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: PROJECT NARRATIVE Hepatitis E virus is a leading cause of acute hepatitis worldwide and infection often persists in immunocompro- mised patients resulting in increased risk of severe liver diseases. The project will investigate the role of the antibodies in HEV infection and determine if antibodies can be used to prevent or cure chronic HEV infection.

PI_NAMEs: FENG, ZONGDI  (contact);GRAKOUI, ARASH

PROGRAM_OFFICER_NAME: DYALL, JULIE

PROJECT_TERMS: Acute Hepatitis;Affect;Antibodies;Antibody titer measurement;Binding;Blood Circulation;C-terminal;Capsid;Capsid Proteins;Cell Culture Techniques;Cells;Chronic Hepatitis;Complex;Cryoelectron Microscopy;Data;Effectiveness;Endosomes;Enteral;Feces;Glycoengineering;Goals;Hepatitis E virus;Hepatocyte;humanized mouse;Immune system;Immunocompromised Host;Immunoglobulin G;Individual;Infection;insight;Knowledge;Left;Life Cycle Stages;Liver Cirrhosis;Liver diseases;liver injury;Lysosomes;Macaca;Mediating;Membrane;Monoclonal Antibodies;neutralizing antibody;neutralizing monoclonal antibodies;novel;novel strategies;organ transplant recipient;particle;Patients;prevent;Process;Publishing;receptor;Research;Resistance;Risk;RNA Viruses;Role;Serum;Solid;Structural Models;Structure;Surface;Testing;Therapeutic;Therapeutic Effect;transmission process;uptake;Vaccinated;Vaccination;vaccine-induced antibodies;Vaccines;Viral;Viral Antigens;viral transmission;Virion;Virus;Virus Diseases;Work

PROJECT_TITLE: Role of antibodies in hepatitis E virus infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDA-S(90)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: DALLAS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Therapeutic use of CRISPR/Cas is currently limited by the lack of safe and effective delivery carriers that can mediate gene editing in vivo to targeted tissues and cells. In this grant, we study recently developed Selective ORgan Targeting (SORT) lipid nanoparticles (LNPs) that can mediate tissue-specific gene editing in the liver, lung, and spleen. Outcomes of this work will include elucidating the fundamental mechanisms how and why SORT LNPs target extrahepatic tissues, determining how SORT molecules control efficacy and tolerability for improved gene editing, quantifying cell-type gene editing specificity to expand targeted gene editing, and ultimately opening new avenues for CRISPR/Cas-based correction of genetic diseases by developing efficacious, safe, and translatable nanoparticle carriers.

PI_NAMEs: SIEGWART, DANIEL JOHN (contact)

PROGRAM_OFFICER_NAME: CHEN, JERMONT

PROJECT_TERMS: Acceleration;Adsorption;Affect;Applications Grants;Binding;Biodistribution;biophysical properties;Brain;cell type;Cells;cellular engineering;Charge;Chemical Structure;Chemicals;clinical translation;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Coupled;COVID-19;CRISPR/Cas technology;Dangerousness;Data;Development;Disease;Dose;Dreams;Drug or chemical Tissue Distribution;efficacy validation;Encapsulated;Endosomes;Endothelium;Epithelium;Event;Extrahepatic;Formulation;Funding;Gene Delivery;gene-editing approach;Genes;Genetic Diseases;Genetically Engineered Mouse;genome editing;Genomic medicine;Grant;Hepatic Tissue;Hepatocyte;Human;immunogenicity;improved;In Vitro;in vivo;insight;Intramuscular;Intravenous;intravenous injection;Knowledge;Learning;lipid nanoparticle;Lipids;Liver;Lung;Measures;Mediating;Messenger RNA;mRNA lipid nano particle vaccine;Muscle;Mutate;nanoparticle;nanoparticle delivery;National Institute of Biomedical Imaging and Bioengineering;novel;novel therapeutics;nucleic acid delivery;Nucleic Acids;Organ;Outcome;promoter;Property;Proteins;Ribonucleoproteins;RNA;Skin;Specificity;Spleen;Structure;Structure-Activity Relationship;success;therapeutic genome editing;Therapeutic Uses;Tissues;tool;Tropism;United States National Institutes of Health;Vaccines;Viral Vector;Work

PROJECT_TITLE: Defining the molecular interactions within nanoparticles that enable delivery of long nucleic acids

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: CHICAGO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Chemical probes and technology platforms that enable direct measurement of protein activity in complex biological samples would promote more detailed molecular characterization of cells, tissues and organisms. This information would be useful in order to understand, diagnose and treat human diseases like cancer. This proposal aims to create of suite of multiplexed, ultrasensitive proteomic platforms that enable direct quantitation of endogenous active proteins in single cells from human tumor samples.

PI_NAMEs: MOELLERING, RAYMOND E (contact)

PROGRAM_OFFICER_NAME: COUCH, JENNIFER A

PROJECT_TERMS: Address;Advanced Development;anti-cancer research;Atlas of Cancer Mortality in the United States;Benchmarking;Biological;Biological Markers;Biopsy;Breast;Breast Cancer Cell;Breast Cancer Patient;cancer cell;Cancer cell line;Cell Line;Cells;Chemicals;chemoproteomics;Clinic;Clinical;clinical application;Complex;Data;design;detection platform;Development;Diagnosis;Disease;Early Intervention;Elements;enzyme activity;Enzymes;Family;Future;Goals;Grant;Human;human disease;Image;improved;In Situ;Individual;innovation;Knowledge;Ligation;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Maps;Measurement;Measures;Messenger RNA;Methods;Microfluidics;Molecular;molecular phenotype;Molecular Probes;Molecular Profiling;Neoplasm Circulating Cells;Neoplasm Metastasis;novel;Operative Surgical Procedures;Organism;Outcome;Patient Care;Patients;Phosphotransferases;Positioning Attribute;Primary Neoplasm;protein biomarkers;Protein Family;Proteins;Proteome;Proteomics;Publishing;Punch Biopsy;Reagent;Reporting;Research;Resolution;Sampling;Services;Severity of illness;Signal Transduction;single cell proteins;Specimen;Technology;technology platform;technology validation;Testing;Therapeutic;Tissue Sample;Tissues;translational applications;treatment response;tumor;Tumor Tissue;Validation;Visualization

PROJECT_TITLE: Single-Cell Protein Activity Profiling in Breast Cancer Cells and Tissues


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Bioengineering;Hearing Loss;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: PORTLAND

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Patients with hearing impairment and central neurological disorders have difficulty understanding speech and processing other complex sounds in dynamic, noisy environments. This study seeks to understand how the auditory cortex represents important sensory information as individuals move through the world, changing the location and overlap of sounds arriving at their ears. These experiments will provide insight into basic function of the healthy brain that can inform treatment of hearing disorders.

PI_NAMEs: DAVID, STEPHEN V (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acoustics;Address;Affect;Algorithms;Anatomy;Animal Model;Animals;Architecture;Arousal;artificial neural network;Attention;Auditory;Auditory area;auditory processing;Auditory Prosthesis;Auditory system;Behavior;Behavioral;Brain;Calibration;Chronic;Code;Compensation;Complex;Computational Technique;computer framework;Computer Models;convolutional neural network;Cues;Data;deaf;discrimination task;Ear;Engineering;Environment;Equipment;experimental study;Feedback;Ferrets;hard of hearing;Head;Hearing;hearing impairment;Hearing problem;Implant;improved;Individual;insight;Location;Loudness;Machine Learning;Measurement;Measures;Methods;Microelectrodes;Modeling;Motion;Motor;Motor Activity;Movement;Nervous System Disorder;neural;Neurons;neurophysiology;normal hearing;Patients;Population;Positioning Attribute;Posture;Process;Property;receptive field;Research;response;Role;Rotation;Sensory;sensory input;Shapes;signal processing;Signal Transduction;sound;Source;Specificity;Speech;Stimulus;Study models;System;Technology;Testing;tool;Update;vestibular system;Visualization;Visualization software;Work

PROJECT_TITLE: Dynamic neural coding of spectro-temporal sound features during free movement

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Pregnancy;Prevention;Serious Mental Illness;Sleep Research;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE This research will provide definitive evidence about whether treating prenatal insomnia with digital cognitive behavior therapy for insomnia prevents depression during the perinatal period (i.e., pregnancy and the postpartum period). Currently, there are few intervention options for preventing perinatal depression, none focus on women with prenatal insomnia, and the accessibility of existing interventions is limited. Several attributes of our approach will facilitate its broad dissemination, including focusing on the low stigma target of insomnia and using a scalable intervention, with significant public health impact for reducing the burden of perinatal depression for mothers, children, families, and society.

PI_NAMEs: FELDER, JENNIFER NICOLE (contact)

PROGRAM_OFFICER_NAME: CHU, SERENA PO-LAN

PROJECT_TERMS: Address;animation;antepartum depression;Arousal;Belief;Blinded;Child;Child Rearing;Childbirth;Clinical Trials Design;clinically relevant;Cognitive;Cognitive Therapy;comparison group;Complication;confirmatory trial;Data;depression prevention;depressive symptoms;design;digital;Education;Educational Intervention;efficacy evaluation;efficacy testing;emotion regulation;Enrollment;experience;Family;flexibility;follow-up;Frequencies;Health Expenditures;Impairment;improved;Incidence;interest;Intervention;Knowledge;Major Depressive Disorder;Mediating;Mediator;Medicaid services;Mental Depression;Mothers;Outcome;Participant;Perinatal;perinatal depressive symptom;perinatal period;peripartum depression;Population;Postpartum Depression;Postpartum Period;preference;Pregnancy;Pregnant Women;prenatal;prenatal experience;prevent;Prevention;preventive intervention;primary outcome;productivity loss;programs;Public Health;Randomized;Randomized, Controlled Trials;Recording of previous events;Research;Research Personnel;Risk Factors;Schedule;Severities;Sleep;sleep health;Sleeplessness;social stigma;societal costs;Societies;standard care;suicidal risk;symptomatic improvement;Symptoms;Testing;Therapeutic;Therapeutic Intervention;Thinking;Training;Travel;Wait Time;web site;welfare;Woman

PROJECT_TITLE: Efficacy of digital cognitive behavior therapy for insomnia for the prevention of perinatal depression


NIH_SPENDING_CATS: Aging;Biotechnology;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention

PHR: PROJECT NARRATIVE Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Understanding of the genetic basis of this debilitating disease is essential for its control and management, as they will guide us to therapeutic targets. We will integrate the use of human genetics, genomics and anima models to gain mechanistic insight into biological processes underlying elevated IOP and glaucoma.

PI_NAMEs: NAIR, KAYARAT SAIDAS  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Affect;Alleles;Aqueous Humor;Binding Sites;Biological Assay;Biological Process;Biology;Blindness;Cell Adhesion;Cell Culture Techniques;Cells;ChIP-seq;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Consensus;Cytoskeletal Modeling;Defect;Development;Dexamethasone;Disease;Disease Progression;DNA Binding;Drainage procedure;Enhancers;Exhibits;Extracellular Matrix;Extracellular Matrix Proteins;FOXC1 gene;Functional disorder;functional genomics;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic approach;Genetic Transcription;Genomic approach;Genomics;Glaucoma;Goals;Heterozygote;high intraocular pressure;Homeostasis;Human;Human Genetics;Impairment;in vitro Assay;insight;Introns;lentiviral-mediated;Maintenance;Mediating;Modeling;Molecular;mouse model;Mus;Nucleic Acid Regulatory Sequences;optic nerve disorder;overexpression;Pathogenesis;Pathway interactions;Persons;Physiologic Intraocular Pressure;Play;Prevalence;prevent;Primary Open Angle Glaucoma;programs;Promoter Regions;Public Health;Regulation;Reporter;Resistance;Risk Factors;Role;Structure of sinus venosus of sclera;Study models;Susceptibility Gene;System;targeted treatment;Testing;therapeutic target;Tissues;Trabecular meshwork structure;transcription factor;transcription regulatory network;transcriptome sequencing;Transforming Growth Factor beta;Untranslated RNA;Variant

PROJECT_TITLE: Determining Molecular Mechanisms of Human Glaucoma Genes

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


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

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The complex biology of aging, characterized by a progressive loss of cellular and physiological function, is particularly evident in hematopoietic stem cells (HSCs) where aging results in a reduced capacity to self-renew and differentiate into lymphoid lineages. We propose a two-pronged approach for reversing HSC aging via cellular reprogramming, involving 1) profiling molecular signatures of aging in HSCs at single cell resolution to both develop metrics for aging and nominate transcription factors (TFs) involved in aging and self-renewal and 2) screening of TFs nominated by single-cell RNA-sequencing for restoration of HSC quiescence, self-renewal, lymphoid/myeloid balance, and systemic effects in an in vivo mouse aging model. Novel TFs will be characterized for their mechanism in renewing HSCs and restoring other downstream lineages in the bone marrow, and the framework presented will provide a generalizable approach for understanding stem cell aging and discovering new therapeutic interventions.

PI_NAMEs: ABUDAYYEH, OMAR O (contact);GOOTENBERG, JONATHAN SAMUEL

PROGRAM_OFFICER_NAME: COGLIATI, TIZIANA PAOLA

PROJECT_TERMS: Affect;Age;age effect;age related;age related changes;age-related disease;aged;Aging;aging biomarker;aging clocks;aging process;aging related;aging related disease;aging reversal;Animals;Area;Bar Codes;Biological Assay;Biology;Biology of Aging;Blood;Blood Cells;bone aging;Bone Marrow;Bone Marrow Cells;c-myc Genes;Cell Aging;Cell Cycle;Cell Lineage;cell regeneration;Cell Reprogramming;cell type;Cells;cellular engineering;cellular transduction;Chronology;Complex;Computer Models;Coupling;Data;Data Set;Degenerative Disorder;Deterioration;Development;Disease;Engineering;Engraftment;Equilibrium;Evaluation;Eye;Foundations;Gene Expression Profile;Genes;Genetic Transcription;Health;hematopoietic stem cell aging;Hematopoietic Stem Cell heterogeneity;hematopoietic stem cell niche;hematopoietic stem cell quiescence;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Heterogeneity;high throughput screening;Human;immune function;improved;In Situ;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Injury;injury and repair;insight;Intervention;irradiation;Libraries;Lymphoid;Measurement;Methods;Modeling;Modification;Molecular;Molecular Profiling;Mus;Muscle;muscle repair;Myelogenous;novel;novel therapeutic intervention;novel therapeutics;old mice;Outcome;Output;overexpression;Phenotype;Physiological;Physiology;Population;post-transplant;predictive modeling;programs;Recovery;regeneration potential;Rejuvenation;Resolution;response to injury;restoration;RNA;screening;self-renewal;senescent cell;sex;single cell sequencing;single-cell RNA sequencing;Skin;small molecule;stem cell aging;stem cell niche;stem cell population;stem cells;Testing;therapeutic candidate;Tissues;tool;tool development;Training;transcription factor;transcriptome;transcriptomics;Transplantation;Validation;Viral;Whole Organism

PROJECT_TITLE: Discovery and manipulation of transcription factors to restore long term stem cell repopulation in aged bone-marrow

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Measuring stress reactivity in addition to stress exposure will help provide important insights into the mechanisms underlying the persistent Black-White inequities seen in adverse pregnancy outcomes. Given the growing evidence that APOs serve as an early warning sign for future CVD risk, our findings have important implications for inequities in cardiovascular disease risk as well.

PI_NAMEs: GROBMAN, WILLIAM ADAM;KERSHAW, KIARRI N (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: adverse outcome;adverse pregnancy outcome;Affective;biological adaptation to stress;Black race;black women;black/white disparity;Blood Pressure;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;Cells;Child;Chronic;coping;Decidua Basalis;Disparity;Ecological momentary assessment;Education;Environment;Event;experience;Exposure to;Face;Frequencies;Future;Goals;Health;Health behavior;health inequalities;heart rate variability;Histologic;Histology;Hydrocortisone;Hypertension;Hypothalamic structure;immune function;Immune system;Income;Individual;Inequity;Inflammation;insight;Laboratories;Lesion;Life;Life Cycle Stages;maternal stress;Measurement;Measures;Mediating;mortality;Mothers;negative affect;Neighborhoods;neonatal morbidity;Neurosecretory Systems;Not Hispanic or Latino;Nulliparity;Outcome;Participant;Physiological;Pituitary Gland;Placenta;Play;Population;Pregnancy;pregnancy disorder;Pregnancy Outcome;Pregnant Women;Premature Birth;prenatal exposure;prenatal stress;psychologic;Psychological Stress;racial difference;racial discrimination;racial disparity;Reaction;Reporting;Research;Resources;response;Risk;Salivary;Severities;Sex Discrimination;Small for Gestational Age Infant;social stressor;Socioeconomic Status;Stress;Stress and Coping;stress reactivity;Stressful Event;stressor;Testing;Time;White Women;Woman

PROJECT_TITLE: Understanding the contributions of stress reactivity to racial disparities in adverse placental and pregnancy outcomes

STUDY_SECTION: MESH

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


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

ORG_DEPT: GENETICS

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Narrative We have identified a novel regulator of brain aging, neural network and microglial function that may protect against memory loss and the pathology of Alzheimer's disease. This proposal explores the role of REST in the dysfunction of neurons and microglia in Alzheimer's disease using precisely targeted gene knockout mice and new REST-activating drugs. Using these approaches, we will attempt to define basic mechanisms that underlie memory loss in Alzheimer's disease with potentially important therapeutic implications.

PI_NAMEs: YANKNER, BRUCE A (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Abeta clearance;Affect;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid;Brain;Cell Culture Techniques;ChIP-seq;Chronic;Development;druggable target;entorhinal cortex;extend lifespan;Failure;Functional impairment;gene network;Genes;Goals;Hippocampus;Human;Immune;Impaired cognition;improved;Inflammatory;insight;interdisciplinary approach;Intervention;Knock-out;knockout gene;Knockout Mice;life span;Mediating;Memory;Memory Loss;Microglia;mild cognitive impairment;mouse model;Mus;neural circuit;neural network;neuroinflammation;Neuronal Dysfunction;Neurons;neuroprotection;neurotoxic;novel;novel therapeutic intervention;Pathology;Peripheral;Phagocytosis;Pharmaceutical Preparations;prevent;Proteins;prototype;Regulation;response;Role;Signal Pathway;Site;Specificity;Stress;Synaptic plasticity;tau Proteins;Therapeutic;tool;Toxic effect;transcription factor REST;transcriptome sequencing;Transgenic Organisms;Translations

PROJECT_TITLE: Targeting REST in Alzheimer's Disease


ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

ORG_STATE: MI

PHR: PROJECT NARRATIVE  Aging is a complex process involving many physiological, anatomic, metabolic, cellular, and molecular changes. We have identified a molecular change that appears to track the number of times that a cell lineage has divided. We propose to explore the mechanistic underpinnings of this process, and to develop this finding into a molecular clock.

PI_NAMEs: LAIRD, PETER W (contact)

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: Acceleration;age acceleration;Aging;aging related;Anatomy;Attention;Attenuated;Automobile Driving;Behavior;Biological Clocks;Biology;Calibration;Cell Aging;Cell Culture Techniques;Cell Cycle;Cell Cycle Inhibition;Cell division;Cell Line;Cell Lineage;cell type;Cells;Chromatin;Chromosome Mapping;Chronology;Circadian Rhythms;Complex;Contact Inhibition;CpG dinucleotide;CpG Islands;Cues;Cytosine;Data;Degenerative Disorder;Dependence;deprivation;design;Development;Disease;DNA;DNA Maintenance;DNA Methylation;DNA methyltransferase inhibition;DNA Modification Methylases;DNMT3a;DNMT3B gene;Elasticity;epigenetic clock;Epigenetic Process;Fibroblasts;Gene Expression;Genome;genomic locus;Genomics;Health;Histones;Human;human disease;human tissue;Individual;inhibitor;Intervention;life span;Link;Maintenance;Malignant Neoplasms;malignant phenotype;Measures;Metabolic;Methylation;Mitosis;Mitotic;Modeling;Molecular;molecular clock;Outcome;overexpression;Phenotype;Physiological;premalignant;premature;prevent;Process;Recording of previous events;Reporting;Research;Resistance;Role;senescence;Serum;Techniques;Telomerase;Testing;Time;Tissues;tool;ubiquitin-protein ligase

PROJECT_TITLE: Progressive DNA Hypomethylation as a Measure of Mitotic History and Potential Contributor to Replicative Senescence.


ADMINISTERING_IC: HG

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: SANTA CRUZ

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: PROJECT NARRATIVE The UCSC Genome Browser (https://genome.ucsc.edu) brings together many sources of information to help researchers and doctors understand the function of genes and other regions of the human genome. The Browser helps researchers intelligently design therapies for a broad range of diseases. For diseases caused by genetic variation, it helps doctors understand which variations cause which diseases.

PI_NAMEs: HAEUSSLER, MAXIMILIAN  (contact)

PROGRAM_OFFICER_NAME: WELLINGTON, CHRISTOPHER

PROJECT_TERMS: Address;Algorithms;Alleles;Animals;annotation  system;Archives;base;Biochemical;Biological Assay;biomedical resource;Cells;Chromosomes;Clinical;Code;Collaborations;Complex;Computer Analysis;Computer software;Custom;Data;data access;data integration;Data Reporting;Data Set;Data Sources;Databases;design;Designer Drugs;Diploidy;Disease;Disease Progression;diverse data;DNA;DNA sequencing;Documentation;Drug Design;drug-sensitive;Ecosystem;empowerment;Engineering;Ensure;Equity;ethnic diversity;European;experience;Eye;Gene Family;gene function;Generations;Genes;Genetic Diseases;Genetic study;Genetic Variation;Genome;genome annotation;genome browser;genome resource;genomic data;Genomics;Haploidy;Human;Human Genome;human pangenome;Humanities;improved;Individual;Infrastructure;Internet;Investments;Maps;Medical;member;Mitochondria;model organism;Modernization;Molecular;Mus;National Human Genome Research Institute;new technology;Noise;outreach;pan-genome;Patient Care;Performance;Personally Identifiable Information;Persons;Physiology;Population;programs;Proteins;Publications;Publishing;reference genome;repository;Reproducibility;Research;Research Personnel;Resources;Sampling;Science;Scientist;Sequence Analysis;Series;side effect;single cell technology;single molecule;single-cell RNA sequencing;software development;Source;System;Technology;Testing;Text;therapy design;Tissues;tool;Transcript;Underrepresented Minority;Underserved Population;Untranslated RNA;Update;Variant;Visualization;Visualization software;web based software;web site;web-based tool;Work

PROJECT_TITLE: The UCSC Genome Browser

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Contraception/Reproduction;Endometriosis;Genetics;Pain Research;Women's Health Research

ORG_CITY: HOUSTON

ORG_DEPT: PATHOLOGY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PUBLIC HEALTH RELEVANCE With the decline in pharmaceutical company interest in common and morbid women’s health indications, our current proposal to identify drugs that block the functions of kinases (a druggable class of proteins in our genomes), as novel treatments for endometriosis will address an NICHD mandate of the Gynecologic Health and Disease Branch to identify and develop novel non-hormonal therapeutic agents for treatment of gynecologic pain syndromes. Our collective genetic validation, cell biology, and drug discovery experiences will bring novel drug-like inhibitors to targeted patient populations of women seeking new alternatives to control endometriosis as stand-alone therapies or as sequential treatment during the required hiatus following hormone antagonists. Our multidisciplinary team of reproductive biologists, medicinal chemists, pharmacologists, immunologists, entrepreneurs, and clinicians will work together to identify new classes of therapeutics to target unique endometriosis-relevant kinase pathways.

PI_NAMEs: MATZUK, MARTIN M. (contact)

PROGRAM_OFFICER_NAME: ALLEN, CATHERINE LEIGH

PROJECT_TERMS: Address;Affect;Affinity;AMHR2 gene;Bar Codes;Binding;BMPR2 gene;Cell Line;Cells;Cellular biology;Chemicals;Chemistry;Clinical;Collection;college;comparison control;CSF1R gene;Data;Data Set;Disease;DNA;DNA biosynthesis;drug discovery;drug-like compound;Dysmenorrhea;Dyspareunia;efficacious treatment;Endocrine;endometrial organoid;endometriosis;Endometrium;EPHA2 gene;experience;Family;FDA approved;Foundations;Gene Combinations;Gene Expression;Genetic;Genome;Grant;Growth;Gynecologic;Health;Hormone Antagonists;Hormones;Human Genome;Immunologist;In Vitro;in vivo;in vivo Model;Incidence;Induction of Apoptosis;Infertility;Infiltration;Inflammation;Inflammatory;inhibitor;interest;IRAK3 gene;kinase inhibitor;knock-down;Lead;Lesion;Libraries;MAP3K8 gene;Mediating;Medicine;Menorrhagia;Metabolic;Methods;Molecular;mouse model;multidisciplinary;MYLK gene;National Institute of Child Health and Human Development;new chemical entity;new therapeutic target;novel;novel therapeutics;NTRK2 gene;NUAK1 gene;Organoids;Ovarian Clear Cell Tumor;Ovarian Endometriosis;overexpression;Pain;Paper;Pathogenesis;Pathologic;Pathway interactions;patient population;Patients;Peritoneal;Pharmaceutical Preparations;Pharmacologic Substance;Phosphotransferases;Physiological;pre-clinical;Proliferating;Promega;Protein Kinase;Proteins;public health relevance;Publishing;receptor;Recombinants;reproductive;Role;screening;Sequential Treatment;Small Interfering RNA;small molecule;small molecule inhibitor;Stromal Cells;Syndrome;System;Technology;technology platform;Testing;TGFBR2 gene;Therapeutic;Therapeutic Agents;therapeutic target;Tissues;Transforming Growth Factor beta;Validation;web portal;Woman;Women's Health;Work

PROJECT_TITLE: Kinases as Therapeutic Targets for Endometriosis

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: PROJECT NARRATIVE Despite great advancement in immunotherapy for melanoma, such as adoptive cell transfer therapy and checkpoint blockade, the clinical outcomes remain less satisfactory due to a variety of factors that lessen antitumor efficacy. By investigating the role and mechanism of a safe attenuated Brucella melitensis mutant producing a tryptophan metabolite in modulating the suppressive tumor microenvironment and immunotherapy resistance, the proposed research will define and establish this microbe as a novel immunomodulatory agent that can be exploited to significantly improve current melanoma immunotherapy.

PI_NAMEs: SONG, JIANXUN JIM (contact)

PROGRAM_OFFICER_NAME: RASOOLY, AVRAHAM

PROJECT_TERMS: adaptive immunity;Adoptive Cell Transfers;Animals;antigen-specific T cells;Attenuated;Brucella melitensis;cancer immunotherapy;cancer therapy;Cell-Mediated Cytolysis;Cells;Clinical;Combined Modality Therapy;cytokine;cytotoxic;Data;Development;Effectiveness;Engineering;Evaluation;Goals;Goat;Granzyme;humanized mouse;hydroxyindole;Immune;immune checkpoint blockade;immune modulating agents;Immunocompetent;immunodeficiency;immunomodulatory strategy;immunoregulation;Immunotherapy;improved;Inflammatory;innovation;Knowledge;Laboratories;Macaca mulatta;Macrophage;Major Histocompatibility Complex;Mediating;Melanoma;Memory;Microbe;microbial;microbiota;Modeling;Molecular;Mus;mutant;Natural Immunity;neoplasm immunotherapy;neoplastic cell;nonhuman primate;novel;novel therapeutic intervention;Outcome;Pathogenesis;PD-1/PD-L1;PD-L1 blockade;permissiveness;Phenotype;Production;Proteins;Publishing;recruit;Regulation;Research;Resistance;Role;Safety;Sheep;Signal Transduction;System;T cell therapy;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic candidate;tissue culture;Tissues;Tryptophan;tumor;Tumor Antigens;tumor growth;Tumor Immunity;tumor immunology;tumor microenvironment;Tumor Suppression;Tumor Tissue;tumor-immune system interactions;vaccine discovery;Vaccines;Work

PROJECT_TITLE: Combating melanoma with an attenuated bacterial therapeutic

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIO-D(01)Q]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Contraception/Reproduction;Emerging Infectious Diseases;Health Services;Infectious Diseases;Infertility;Pelvic Inflammatory Disease;Prevention;Sexually Transmitted Infections;Urologic Diseases;Women's Health Research

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Defining the lifetime risk of Chlamydia trachomatis in men and characteristics associated with infection in the US population will provide critical information to either support or change current chlamydia screening guidelines. Determining the lifetime risk of Mycoplasma genitalium in the US, whether it is associated with pelvic inflammatory disease, and the extent of antimicrobial resistance in the population will guide nascent national testing and treatment recommendations for M. genitalium.

PI_NAMEs: MANHART, LISA E (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Address;Age;aged;Agreement;Antibiotics;Antibodies;Antimicrobial Resistance;Bacteria;Characteristics;Chlamydia;Chlamydia trachomatis;chronic pelvic pain;Clinic;Clinic Visits;Consensus;cost effectiveness;Data;Detection;Diagnosis;Distant;Ectopic Pregnancy;Effectiveness;emerging pathogen;Epidemiology;experience;Female infertility;female reproductive tract;female reproductive tract infection;General Population;Genitourinary system;Guidelines;Health Care Costs;high risk;high risk population;High Risk Woman;IgG3;Immunoglobulin G;improved;Incidence;Individual;Infection;infection risk;Infertility;lifetime risk;Macrolide-resistance;male;mathematical model;men;Modeling;Morbidity - disease rate;Mycoplasma genitalium;National Health and Nutrition Examination Survey;national surveillance;novel;Output;Patient Self-Report;Pelvic Inflammatory Disease;Persons;Population;population based;pressure;Prevalence;Prevention;prevention effectiveness;Prevention program;programs;Public Health;quinolone resistance;Recommendation;Recording of previous events;Reporting;Reproductive Health;Role;routine screening;screening;screening guidelines;Seroepidemiologic Studies;Serology test;seropositive;Seroprevalences;Serum;sex;sexually active;Sexually Transmitted Diseases;Specimen;Syndrome;Testing;Time;transmission process;Treatment outcome;Urethritis;Urine;Woman;women's treatment;Work;young man

PROJECT_TITLE: Cumulative burden of Chlamydia trachomatis and Mycoplasma genitalium in the US: implications for screening guidelines and antimicrobial resistance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-Z(02)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Epilepsy;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: FORT WORTH

ORG_NAME: COOK CHILDREN'S MEDICAL CENTER

PHR: Narrative To lessen the negative impact of medically refractory epilepsy in children, a new pre-surgical noninvasive biomarker that identifies reliably the area of the brain that generates the epileptic seizures is essential. The proposed experiments are relevant to public health because they may lead to a significant improvement of the presurgical evaluation procedure and postsurgical outcome of pediatric patients with refractory epilepsy. The project is relevant to NINDS’s mission because the resulting findings could significantly improve the quality of life in children with epilepsy, one of the most common pediatric neurological disorders, which has a major impact on children’s development and may significantly affect their adult life.

PI_NAMEs: PAPADELIS, CHRISTOS  (contact)

PROGRAM_OFFICER_NAME: HARTMAN, ADAM L

PROJECT_TERMS: 18 year old;3D Print;Address;Adult;Affect;Area;Biological Markers;blind;Brain;Categories;Child;Child Development;Childhood;Clinical;Data;density;Development;Electrodes;Electroencephalography;Epilepsy;Evaluation;Excision;experience;experimental study;Freedom;Head;High Frequency Oscillation;improved;improved outcome;innovation;instrument;Intractable Epilepsy;Life;Link;Literature;Location;Magnetoencephalography;Measures;Medical;Methods;Mission;Monitor;Morbidity - disease rate;Motor;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neuroimaging;Neurology;neurosurgery;novel;Operative Surgical Procedures;Outcome;Pathologic;Patient-Focused Outcomes;Patients;pediatric patients;Pharmaceutical Preparations;Physiological;Predictive Value;Procedures;Public Health;Publishing;Quality of life;Research;Resected;Sampling;Seizures;signal processing;Spatial Distribution;Specificity;success;surgery outcome;Techniques;Technology;Test Result;Testing;Time;Tissues;tool;unsupervised clustering;unsupervised learning;Visual

PROJECT_TITLE: Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Social Determinants of Health

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative The goal of the proposed predoctoral training program is to prepare the next generation of HIV researchers to improve health equity and HIV prevention, treatment and care outcomes by: (1) developing theoretical competency in social-structural, intersectional and critical health equity approaches to HIV; (2) using these theoretical approaches to design and conduct rigorous research; (3) formulating strategic interventions grounded in social-structural and intersectional approaches; and (4) engaging equitably with the intersectionally diverse communities disproportionately affected by HIV, throughout all stages of research and intervention.

PI_NAMEs: BOWLEG, INGRID ALISA;KERRIGAN, DEANNA L (contact)

PROGRAM_OFFICER_NAME: KAMATH, SUSANNAH M A

PROJECT_TERMS: Address;HIV;social structure;structural determinants;Training Programs

PROJECT_TITLE: Training Program in Approaches to Address Social-Structural Factors Related to HIV Intersectionally (TASHI)


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: MILWAUKEE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE Identification of mtDNA alterations prognostic of MDS after HCT will improve our understanding of the etiology of MDS, help developing individualized risk stratification and improving the outcomes for patients with poor HCT prognostic features.

PI_NAMEs: DONG, JING  (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acute;Acute leukemia;Acute Myelocytic Leukemia;Address;Affect;Allogenic;Bioinformatics;biological heterogeneity;Biological Markers;bisulfite sequencing;Bone Marrow;Bone marrow failure;Cancer Center;Candidate Disease Gene;career;Cells;chronic graft versus host disease;Chronic Leukemia;Clinical;Clinical Data;clinical heterogeneity;Clonal Hematopoietic Stem Cell;curative treatments;Cytogenetics;cytopenia;Data;Decision Making;design;Disease;Disease-Free Survival;DNA Methylation;DNA Sequence Alteration;Dysmyelopoietic Syndromes;Enrollment;Epidemiologic Methods;Epidemiology;Epigenetic Process;epigenomics;Etiology;Exhibits;experience;Future;Genes;Genetic;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome sciences;genome sequencing;genomic data;Genomics;Goals;Haplogroup;Hematological Disease;Hematology;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;heme biosynthesis;high risk;HLA Antigens;Homeostasis;Impairment;improved;improved outcome;individual response;Ineffective Hematopoiesis;Inferior;innovation;insertion/deletion mutation;Iron;K-Series Research Career Programs;Knowledge;Medical;Medicine;Mentors;Methodology;Methylation;Mitochondria;Mitochondrial DNA;mitochondrial DNA alteration;mitochondrial genome;Mitochondrial Inheritance;modifiable risk;Modification;Molecular;Molecular Epidemiology;Morbidity - disease rate;Morphology;mortality;Mutation;new therapeutic target;non-genetic;novel;novel marker;Nuclear;Outcome;outcome prediction;Pathogenesis;patient subsets;Patient-Focused Outcomes;Patients;personalized risk prediction;Play;Ploidies;population based;post-transplant;precision medicine;predictive marker;professor;prognostic;Prognostic Marker;prognostic model;prognostic signature;prognostic value;programs;Recommendation;Recurrent disease;Relapse;relapse risk;Research;Research Personnel;Risk;Risk Factors;risk stratification;Risk-Benefit Assessment;risk/benefit ratio;Role;Single Nucleotide Polymorphism;statistics;stem cell homeostasis;Stem cell transplant;Stratification;Subgroup;System;Technology;Therapeutic;Time;Training;Transplantation;treatment response;Variant;whole genome

PROJECT_TITLE: Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(JA)]


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Machine Learning and Artificial Intelligence;Precision Medicine;Prevention;Substance Misuse

ORG_CITY: ALBUQUERQUE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF NEW MEXICO

ORG_STATE: NM

PHR: Project Narrative This study is designed to improve the effectiveness of treatments for alcohol use disorder by providing predictions about which drug will work best to reduce heavy drinking and which behavioral treatment will work best to prevent relapse.

PI_NAMEs: VAN HORN, M LEE (contact)

PROGRAM_OFFICER_NAME: FALK, DANIEL EVAN

PROJECT_TERMS: acamprosate;alcohol abuse therapy;Alcohol consumption;alcohol intervention;alcohol response;alcohol use disorder;Algorithms;Area;behavior test;Behavior Therapy;Behavioral;Biological Markers;Caring;Characteristics;Client;Clinical;Clinical Data;clinical decision-making;clinical practice;Clinical Trials;Clinical Trials Cooperative Group;Communication;Complex;Data;design;Disease;Ensure;experience;Goals;Heavy Drinking;Heterogeneity;improved;improved outcome;Individual;Individual Differences;individual response;individualized medicine;Intervention;Literature;machine learning algorithm;Methods;mindfulness intervention;Naltrexone;novel strategies;Outcome;Patients;personalized approach;personalized medicine;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;predicting response;prediction algorithm;Prediction of Response to Therapy;predictive modeling;Prevention program;Provider;Psychosocial Factor;Public Health;Publishing;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;Reaction;Relapse;relapse prevention;Research;Research Personnel;response;Sampling;Selection for Treatments;simulation;Specific qualifier value;Symptoms;Telephone;Testing;theories;topiramate;treatment effect;Treatment Effectiveness;Treatment Efficacy;Treatment outcome;treatment response;usability;Validation;Work

PROJECT_TITLE: Predicting individual responses to treatment for alcohol use disorder.

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: The proposed research to develop the Functional and Fine-Mapping Approach to Improve Responsible Risk-modeling of Polygenic Risk Scores (‘FFAIRR-PRS’) approach will address key gaps in the current ability to deliver polygenic scores – new tools for genetic risk assessment – accurately to diverse populations, and reflects deep commitment to the overall goals of the NHGRI consortium. First, we propose to harmonize and aggregate individual-level data from >50,000 individuals of South Asian ancestry – prioritized on the basis of marked under-representation in studies to date – within the ANVIL data ecosystem, developing and sharing analytic workflows and new statistical genetics approaches. Second, using a ‘diversity-first’ approach, we propose to validate the FFAIR-PRS approach for enhanced polygenic score development, and build integrated and calibrated absolute risk estimators to facilitate ultimate clinical adoption via other ongoing research efforts.

PI_NAMEs: NATARAJAN, PRADEEP  (contact)

PROGRAM_OFFICER_NAME: MINEAR, MOLLIE A

PROJECT_TERMS: Accounting;Address;Adherence;Adoption;Asian ancestry;Asian population;Atrial Fibrillation;Automobile Driving;Awareness;Benchmarking;biobank;Calibration;Cholesterol;Classification;Clinical;Clinical Data;clinical implementation;Clinical Informatics;Clinical Medicine;clinical risk;Complex;Coronary Arteriosclerosis;Data;data ecosystem;Data Set;data sharing;Development;Disease;Disparity;DNA;Environmental Exposure;Equity;European;Family;functional genomics;gene environment interaction;Gene Frequency;Genes;Genetic;genetic approach;genetic architecture;genetic risk assessment;genome sequencing;genome wide association study;Genomic medicine;Genotype;Goals;Health;healthy lifestyle;Heritability;improved;indexing;Individual;Inherited;interest;Life Style;Link;Linkage Disequilibrium;London;Malignant Breast Neoplasm;Maps;Modeling;Mutation;National Human Genome Research Institute;non-genetic;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Output;Pattern;Performance;personalized approach;Pharmaceutical Preparations;Phase;Phenotype;phenotypic data;polygenic risk score;Population;Population Heterogeneity;portability;Prevalence;Probability;Public Health;Recommendation;Recording of previous events;Records;recruit;Research;Risk;Risk Factors;risk stratification;risk variant;Signal Transduction;Site;South Asian;statistics;tool;trait;United Kingdom;Variant;whole genome;working group

PROJECT_TITLE: Enabling improved applicability and transferability of polygenic scores across diverse populations- a focus on South Asians


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics;Nanotechnology

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: PROJECT NARRATIVE The proposed research takes novel approaches to elucidating the fundamental behaviors and roles of chromosomes, which are the repositories of our genetic material. We study meiosis, aberrancies of which confer infertility and birth defects; we study mammalian chromosome organization and segregation, defects in which underlie cancer; and we study E.coli, including L-forms, a lifestyle that bacteria use to evade antibiotics. Our research will therefore have a broad impact on many fundamental issues that directly impact human health.

PI_NAMEs: KLECKNER, NANCY E (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: 4D Imaging;Algorithms;Antibiotic Resistance;Antibiotics;Bacteria;Behavior;Breathing;Caenorhabditis elegans;Cell division;Cells;cellular imaging;Chromosome Segregation;Chromosome Structures;Chromosomes;Congenital Abnormality;Cytogenetics;Defect;Detection;Diffuse;DNA;Escherichia coli;Evolution;fungus;Genetic;Genetic Materials;Genetic Recombination;Health;Homologous Gene;Human;In Vitro;in vivo;Infertility;L Forms;Life Style;live cell imaging;Malignant Neoplasms;Mammalian Chromosomes;Mechanics;Meiosis;Membrane;Metaphase;Microscopy;Mitosis;Mitotic;Mitotic Chromosome;Modeling;Movement;nanocrystal;novel;novel strategies;Pattern;Process;reconstitution;repository;Research;Role;Saccharomycetales;segregation;sensor;Sepharose;Sexual Reproduction;Side;Sister;Sister Chromatid;Site;Spottings;Stress;Structure;Time;tool;Untranslated RNA;Visualization

PROJECT_TITLE: Chromosome organization and function in time and space:  meiosis, mitosis and E.coli

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

PHR: RELEVANCE (See instructions): Opioids are a class of drugs that act on neuromodulatory receptors throughout the brain and the highly addictive nature of opioids has continued to drive the ongoing opioid epidemic in the U.S. Using computational modeling and biological models, we test the concept that the order of neuromodulation impacts the net effect of opposing neuromodulators. Our findings may be relevant when considering the neurobiological basis of several behavioral phenomena related to opioid use disorder.

PI_NAMEs: WANG, YANGYANG  (contact)

PROGRAM_OFFICER_NAME: MOLLICK, JESSICA ANN

PROJECT_TERMS: Affect;Behavior;Behavioral;Biological Models;Blood gas;Brain;Breathing;Central Nervous System;Cessation of life;Collaborations;computational neuroscience;Computer Models;Data;Diffusion;drug action;dynamic system;Electrophysiology (science);evidence base;Excitatory Postsynaptic Potentials;Experimental Models;Glutamate Receptor;Glutamates;Homeostasis;Individual;Instruction;Knowledge;Measures;Modeling;mortality;mu opioid receptors;Nature;Neurobiology;Neuromodulator;Neurons;neurophysiology;neuroregulation;Norepinephrine;Opioid;opioid epidemic;opioid mortality;opioid use disorder;Organism;Persons;Population;postsynaptic;preBotzinger complex;presynaptic;Property;receptor;Receptor Activation;Research Personnel;Respiration;respiratory;response;Scientist;Synapses;Systems Theory;Testing;transmission process;United States;Ventilatory Depression;Work

PROJECT_TITLE: CRCNS: Evidence-based modeling of neuromodulatory action on network properties


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Nutrition;Obesity;Prevention

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative Caloric restriction – a behavioral intervention that prolongs lifespan in model organisms – has beneficial metabolic effects in humans including weight loss and improvement in blood pressure and lipid levels. Intermittent fasting has emerged as a popular alternative to caloric restriction as it does not require daily adherence to a dietary protocol, but whether the benefits of fasting protocols are dependent on weight loss is not known. In this study we will investigate the metabolic effects of fasting and evaluate whether these effects, including negative effects on bone metabolism, are independent of weight loss.

PI_NAMEs: FAZELI, POUNEH KHADEJEH (contact);STEINHAUSER, MATTHEW

PROGRAM_OFFICER_NAME: SILVA, CORINNE M

PROJECT_TERMS: Adherence;Adipose tissue;Aging;arm;Behavior Therapy;Biochemical;Blood;blood glucose regulation;blood lipid;Blood Pressure;Body Composition;Body Weight;Body Weight Changes;Body Weight decreased;bone;Bone Density;bone loss;bone metabolism;bone turnover;Caloric Restriction;Calories;Carbon;Cardiometabolic Disease;cardiometabolism;Clinical;clinical phenotype;Clinical Research;Control Groups;Coupling;Data;design;Diabetes Mellitus;diabetes risk;Diet;dietary;Dose;Dual-Energy X-Ray Absorptiometry;Energy Intake;epidemiology study;Event;Fasting;Fatty acid glycerol esters;feeding;Foundations;frailty;Future;Glucose Clamp;glucose metabolism;Goals;Health;high risk;Hour;Human;Hyperinsulinism;improved;Inflammation;insulin sensitivity;Interdisciplinary Study;Intermittent fasting;Intervention;Life;life span;lipid metabolism;lipidomics;Lipids;Longevity;Low-Density Lipoproteins;Measures;Mediating;Metabolic;metabolomics;Methods;model organism;Modeling;Molecular;multidisciplinary;multiple omics;novel;Overweight;Pathway interactions;Patients;Peripheral;pharmacologic;Physiological;pi bond;programs;Protocols documentation;Randomized;randomized, clinical trials;randomized, controlled study;Religion;Research Design;Resolution;response;Risk;Sampling;secondary analysis;serial imaging;subcutaneous;Surrogate Endpoint;Testing;Time-restricted feeding;Triglycerides;volunteer;weight maintenance

PROJECT_TITLE: Beneficial reprogramming of lipid metabolism with intermittent fasting

STUDY_SECTION: HSDO

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


NIH_SPENDING_CATS: Breast Cancer;Breastfeeding, Lactation and Breast Milk;Cancer;Clinical Research;Maternal Health;Prevention;Women's Health Research

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: A delayed first childbirth, which is common in American women, is associated with increased breast cancer risk, but it is unclear whether this increased risk is caused by pregnancy or lactation or both. We hypothesize that lactation in women with a delayed childbirth instigates cancer formation from preexistent precancerous lesions, more common in older women than in younger women. This hypothesis, if proven, has important implications for women with a delayed childbirth and may help them make an informed decision regarding whether they choose to breastfeed or not, or just for a short amount of time.

PI_NAMEs: LI, YI  (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: 20 year old;Age;age related;Age Years;Alveolar;Alveolar Cell;American;Atypia;Automobile Driving;Biological Markers;Breast;Breast Cancer Risk Factor;Breast Feeding;breast lesion;breast tumorigenesis;cancer risk;carcinogenesis;Cells;child bearing;Childbirth;Clinical Trials;Complement;Correlative Study;Data;Diagnosis;digital;Epidemiology;epidemiology study;ERBB2 gene;Estrogen receptor positive;Estrogens;First Births;Genomics;Glycine decarboxylase;Human;Hyperplasia;Infant;inhibitor;insight;Intraductal Hyperplasia;Knock-out;Knowledge;Lactation;Length;Lesion;Lobular;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary gland;Mammary Neoplasms;Mediating;Mediator;Methods;Modeling;Molecular;Mothers;mouse model;Mus;new therapeutic target;novel;Nulliparity;older women;Oncogenes;overexpression;parity;Pathway interactions;PIK3CA gene;Population;Pregnancy;premalignant;Premalignant Cell;progenitor;Property;Proteins;Proteomics;Rattus;Reporting;Reproduction;reproductive;reproductive hormone;Research;Risk;Rodent Model;Role;Specific qualifier value;Specimen;Stat5 protein;Study models;Testing;Time;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;tumorigenesis;Virus;Woman;Work;young woman

PROJECT_TITLE: Lactation on Breast Tumorigenesis

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Precision Medicine

PHR: Health, digital and research literacy focus on ensuring that individuals have the knowledge, resources and skills necessary to make informed decisions about their health, how they can contribute to research, and how to engage with health information and research in a digital environment. By developing and distributing community-based programs and services around these topics and helping communities understand Precision Medicine, the work of the NAPC will improve public health and increase awareness of the All of Us Research Program, which will in turn increase public interest and participation, and support the program’s goals to diversify biomedical research data and advance individualized healthcare.

PI_NAMEs: BARGER, RENAE E (contact);WALTON, LINDA J

PROGRAM_OFFICER_NAME: YOON, SUNG SUG

PROJECT_TERMS: Address;All of Us Research Program;Area;Award;Awareness;Biomedical Research;Clinical Research;Collaborations;Communities;community based participatory approach;community based participatory research;community engagement;Community Health;community organizations;community partners;Comprehension;Country;Data;Decision Making;design;Development;digital;digital health;E-learning;Ecosystem;Education;effectiveness evaluation;Ensure;Environment;equity, diversity, and inclusion;Evaluation;experience;Foundations;Funding;Goals;Health;health literacy;Healthcare;human centered design;Human Resources;improved;Individual;innovation;Institution;interest;Iowa;Knowledge;Language;Learning;learning strategy;Libraries;Linguistics;literacy;Maintenance;Medicine;member;Methods;Monitor;novel;Population;precision medicine;Productivity;Program Development;Program Effectiveness;programs;Public Health;Publications;Recording of previous events;Reproduction;Research;Resources;Role;Science;Secure;Services;skills;Specialist;Technology;tool;Training;Training and Education;Training Support;Underrepresented Populations;United States National Institutes of Health;United States National Library of Medicine;Universities;Work

PROJECT_TITLE: NNLM All of Us Program Center


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome

ORG_NAME: BENAROYA RESEARCH INST AT VIRGINIA MASON

PHR: Project Narrative The proposed research is relevant to the mission of the NIH because a better understanding of the mechanisms by which immune responses to self-associated commensal microbes will contribute to treatment of inflammatory, immune-mediated and autoimmune disorders. The proposed work is of particular relevance to host defense against infections and parasites, and to immune-mediated diseases such as inflammatory bowel disease.

PI_NAMEs: HARRISON, OLIVER JAMES;LACY-HULBERT, ADAM  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: adaptive immune response;Adaptive Immune System;Affect;Antibodies;Antibody Formation;Antibody Repertoire;Antibody Response;Antibody titer measurement;Antigens;Autoimmune Diseases;Autoimmunity;Autophagocytosis;autoreactivity;B-Lymphocytes;Bacteria;CD19 gene;Cell Surface Receptors;Cells;Colitis;commensal bacteria;commensal microbes;Complex;Data;Development;dextran sulfate sodium induced colitis;Disease;Epithelium;Equilibrium;experimental study;Exploratory/Developmental Grant;Failure;Generations;Grant;Growth;gut inflammation;Homeostasis;Host Defense;Immune;Immune response;Immune signaling;Immune System Diseases;immune system function;Immunity;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin G;Infection;Infection prevention;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;Innate Immune System;insight;Integrin alphaVbeta3;Integrins;intestinal homeostasis;Intestines;Invaded;Knock-out;Knockout Mice;Lead;Ligands;Link;Location;Measures;Mediating;Methods;microbial;microbial colonization;microorganism;Mission;Mucositis;Mucous Membrane;Mus;novel;Parasites;pathogen;Pathology;Pathway interactions;Patients;Peyer's Patches;Predisposition;prevent;Production;Reagent;Receptor Signaling;Regulation;Research;response;Role;Signal Transduction;Structure of germinal center of lymph node;Surface;systemic inflammatory response;Testing;Toll-like receptors;United States National Institutes of Health;Virus;Work

PROJECT_TITLE: Regulation of TLR signaling in anti-commensal B cell responses and mucosal inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-K(57)]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: NEUROSCIENCES

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: This proposal aims to understand how the properties of microtubules are locally regulated in neurons, and how this regulation influences the transport and delivery of cargo to synapses. It does so by investigating the function of an immobile kinesin, VAB-8/KIF26, which we recently identified as a local cytoskeletal regulator in C.elegans. The results are expected to increase our fundamental understanding of neuronal microtubules and axonal transport, which is important given their critical roles in neuronal health and disease.

PI_NAMEs: YOGEV, SHAUL  (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Affect;Animals;Architecture;Axon;Axonal Transport;Binding;Biochemical;Biological;Caenorhabditis elegans;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Cytoskeleton;Data;Defect;Dendrites;Disease;Equilibrium;Event;extracellular;Failure;Functional disorder;Genetic;genetic analysis;Genome engineering;Health;Image;Immobilization;In Vitro;in vivo;in vivo imaging;insight;Kinesin;Knowledge;Length;Link;Maintenance;Mediating;Microtubule Polymerization;Microtubules;Molecular;Molecular Motors;Motility;Motor;mutant;neuron development;Neurons;Outcome;Pathway interactions;Pattern;pharmacologic;Pharmacology;Polymers;Positioning Attribute;Post-Translational Protein Processing;presynaptic;Probability;Property;Publishing;receptor;reconstruction;Regulation;Role;Signal Transduction;Site;Synapses;Synaptic Vesicles;synaptogenesis;Testing;ubiquitin-protein ligase;WNT Signaling Pathway;Work

PROJECT_TITLE: Local regulation of neuronal microtubules and synaptic cargo

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


NIH_SPENDING_CATS: Aging;Burden of Illness;Clinical Research;Health Services;Kidney Disease

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE For the past several decades, dialysis has been the prevailing treatment paradigm among advanced chronic kidney disease (CKD) patients who are ineligible for or unlikely to receive kidney transplantation. As dialysis may not offer survival benefit nor improved quality of life among certain dialysis subgroups including elderly and multi-morbid patients, there has been growing interest in conservative dialysis-free management as an alternative patient-centered treatment strategy. In this proposal, we will compare hard outcomes and patient- centered endpoints among patients receiving conservative management vs. dialysis transition, and we will develop clinical prediction models that will identify which patients will most benefit from conservative dialysis- free treatment.

PI_NAMEs: KALANTAR-ZADEH, KAMYAR ;RHEE, CONNIE MEEYOUNG (contact)

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: Address;Admission activity;alternative treatment;American;associated symptom;Attenuated;Biochemical;California;Caring;Characteristics;Chronic Kidney Failure;Clinic;Clinical;clinical practice;clinical predictive model;clinical predictors;clinical prognostic;cohort;comorbidity;comparative;comparative effectiveness;Data;Data Collection;Data Sources;Databases;Dialysis patients;Dialysis procedure;disorder subtype;Elderly;End stage renal failure;functional decline;Guidelines;Health;Health Care Costs;health related quality of life;Healthcare;Hospitalization;Human Activities;improved;indexing;Individual;Inflammation;Information Systems;innovation;instrument;Integrated Health Care Systems;Intensive Care;Intensive Care Units;interest;Kidney;Kidney Diseases;Kidney Failure;Kidney Transplantation;Knowledge;Link;Malnutrition;Medicare;Modeling;mortality;National Institute of Diabetes and Digestive and Kidney Diseases;nutrition;Nutritional;Nutritional status;Outcome;Pathway interactions;Patient Care;patient oriented;Patient-Focused Outcomes;Patients;Physical activity;Physical Performance;Policies;Population;predictive modeling;predictive tools;Preparation;preservation;primary outcome;Professional Organizations;programs;prospective;Prospective cohort;Quality of life;recruit;Renal function;Research;Residual state;Resources;secondary analysis;secondary outcome;shared decision making;Skilled Nursing Facilities;Subgroup;Surveys;Survival Rate;Symptoms;Time;tool;Transplantation;treatment center;Treatment Cost;treatment strategy;Uncertainty;United States;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;Uremia;Withdrawal

PROJECT_TITLE: Defining Optimal Transitions of Care in Advanced Kidney Disease: Conservative Management vs. Dialysis Approaches

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Lung;Lung Cancer

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative Integrins, the principal extracellular matrix (ECM) receptor of the cell, have been implicated in every step of tumor development including tumor initiation, progression, and metastasis. Integrin-targeted drugs have classically focused on antagonizing the integrin extracellular domain, thus preventing ECM:integrin binding. Based on our preliminary data, our central hypothesis posits that these ectodomain-targeted drugs neglect constitutive signaling from the integrin cytoplasmic tail and thus future drug development strategies should focus on this ligand-independent signaling.

PI_NAMEs: HAAKE, SCOTT  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Adenocarcinoma Cell;Agar;Binding;cancer clinical trial;CD29 Antigen;Cell Adhesion;Cell Line;cell motility;Cell Proliferation;Cells;Complex;Cytoplasmic Tail;Data;Development;Dimerization;drug development;Drug Targeting;ECM receptor;epithelial to mesenchymal transition;Epithelium;Extracellular Domain;Extracellular Matrix;Funding;Future;Gene Expression Profile;Gene Expression Profiling;Genes;Growth;Histological Techniques;Human;human data;in vitro Model;in vivo;Integral Membrane Protein;Integrin Binding;Integrins;Knock-out;Ligands;Lung;Lung Adenocarcinoma;lung cancer cell;Lysine;Malignant Epithelial Cell;Malignant neoplasm of lung;Malignant Neoplasms;mechanotransduction;Mediating;Membrane;Mentors;mouse model;Mutate;neglect;Neoplasm Metastasis;Nude Mice;Oncology;Pathway Analysis;Phosphorylation;Physicians;PIK3CG gene;Polyubiquitination;prevent;Proteins;Proto-Oncogene Proteins c-akt;receptor;Receptor Cell;Receptor Signaling;response;Role;Scientist;Signal Transduction;single-cell RNA sequencing;skills;Tail;Testing;The Cancer Genome Atlas;Therapeutic;Tissue-Specific Gene Expression;TRAF6 gene;Training;transcriptome sequencing;tumor;tumor growth;tumor initiation;Tumor Promotion;tumorigenesis;Ubiquitin

PROJECT_TITLE: Constitutive Integrin Beta1 Signaling in Lung Cancer

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


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;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Narrative Normal aging is associated with deficits in cognition that correlate with myelin damage and inflammation and ADRD-like pathology, such as accumulation of pathological Tau and A-Beta. Our recent work with our monkey models of aging and cortical injury demonstrated the mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are highly efficacious in facilitating recovery and reducing inflammation, myelin damage and tau and A-Beta. In the current study, we will test whether administration of MSC-EVs in aged monkeys will enhance cognitive performance and reduce age-related markers of inflammation, myelin damage and ADRD-like pathology in blood and CSF and post-mortem brain tissue. !

PI_NAMEs: MOORE, TARA L (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: abeta accumulation;abeta deposition;Affect;Age;age related;age related biomarkers;age related changes;Age-associated memory impairment;aged;Aging;aging related;Alzheimer's disease model;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;APP-PS1;Atrophic;Attention;Autopsy;Axon;axon growth;beta amyloid pathology;Biological;Biological Markers;Biophysics;Blood;Brain;brain tissue;Brain-Derived Neurotrophic Factor;Categories;Cell Respiration;Cells;Chronic;Cognition;Cognitive deficits;cognitive enhancement;cognitive function;cognitive performance;cognitive testing;cytokine;Data;Dendrites;Deposition;Diabetes Mellitus;diabetic rat;Diffuse;efficacy testing;Electron Microscopy;Electrophysiology (science);Enzyme-Linked Immunosorbent Assay;Equilibrium;executive function;experience;extracellular vesicles;Female;Functional disorder;Gene Expression;hippocampal pyramidal neuron;Human;hyperphosphorylated tau;Immunohistochemistry;Impaired cognition;Impairment;improved;In Vitro;Inflammation;Inflammatory;inflammatory marker;Injury;Intervention;Label;life span;light microscopy;Macaca mulatta;Mediating;Memory;Mesenchymal Stem Cells;Microglia;Modeling;Molecular;Monkeys;Morphology;motor function recovery;MRI Scans;multidisciplinary;Mus;Myelin;Myelin Basic Proteins;myelination;Nature;neural;neuroinflammation;neuron loss;Neurons;neuropathology;neurotrophic factor;nonhuman primate;normal aging;Oligodendroglia;patch clamp;Pathologic;Pathology;Pathway interactions;Performance;Peripheral;Primates;programs;Property;protein expression;Proteins;Proteomics;Recovery;Recovery of Function;remyelination;Rodent;Rodent Model;Sampling;Slice;stem cells;Structure;Synapses;synaptic function;Synaptic Transmission;tau Proteins;Testing;tissue repair;Training;Treatment Efficacy;Umbilicus;United States National Institutes of Health;white matter;Work

PROJECT_TITLE: Extracellular Vesicle treatment and age-related neuropathology in non-human primates

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Glioblastoma multiforme (GB) is the most common and deadly form of adult primary brain cancer with a current median survival of just over one year. This research focuses on the study and evaluation of the potential pathologic role of circulating glioma cells (CGCs) and the characteristics and signaling mechanism(s) which generate and sustain this subpopulation. Results of these studies will ultimately benefit public health by potentially improving our understanding of glioma tumor biology, mechanisms of recurrence, and evaluating novel therapeutic approaches against these brain tumors and cancers in general.

PI_NAMEs: DORSEY, JAY FITZGERALD (contact);FAN, YI

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Address;Adult;Beds;Biological;Biology;Blood;Brain Neoplasms;cancer stem cell;Cell Separation;Cell Survival;Cells;Characteristics;chemotherapy;Circulation;cytotoxic;Data;Detection;Development;Evaluation;Excision;Foundations;Generations;Genetic;genetic approach;Genetic Transcription;genotoxicity;Glioblastoma;Glioma;Growth;Homing;Human;improved;Individual;Infrastructure;inhibitor;innovation;Intravenous;Invaded;Investigation;Kinetics;knock-down;lentivirally transduced;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Methodology;Methods;Micrometastasis;Modeling;Molecular;Molecular Target;mouse model;Mus;neoplastic cell;neuro-oncology;Neurosphere;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Pathogenesis;Pathologic;Pathway interactions;Patients;Pattern;pharmacologic;Phenotype;Population;Positioning Attribute;pre-clinical;Primary Brain Neoplasms;Primary Neoplasm;Property;Public Health;Radiation therapy;Radio;Recurrence;Recurrent tumor;Relapse;Reporting;Research;Resistance;RNA;Role;Signal Transduction;single-cell RNA sequencing;Site;Solid Neoplasm;Specimen;standard of care;stem cell niche;stem cells;stemness;System;targeted treatment;temozolomide;Testing;Therapeutic;therapeutic evaluation;Transgenic Mice;Transgenic Organisms;Treatment Efficacy;tumor;Tumor Biology;tumor growth;tumor initiation;tumor progression;tumorigenesis;Tumorigenicity;Virus;WNT Signaling Pathway

PROJECT_TITLE: Dissecting the biology and consequence of circulating glioma cells

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_DEPT: BIOLOGY

PHR: Experience-dependent refinement and efficient memory storage in CNS circuits is thought to require homeostatic forms of plasticity, such as synaptic scaling and intrinsic plasticity, that stabilize overall neuronal activity by endowing individual neurons with a 'firing rate set point'. Here we will investigate the mechanisms and function of these set points, and ask how their loss impacts critical features of circuit function including memory stability. These studies will enhance our understanding of neurological disorders that arise from aberrant circuit excitability, and will provide a new avenue of investigation into disorders (such as PTSD) that arise from excessive generalization during aversive learning.

PI_NAMEs: TURRIGIANO, GINA G (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Animals;autism spectrum disorder;Back;Central Nervous System;Development;Disease;Endowment;Epilepsy;experience;Feedback;Goals;hippocampal pyramidal neuron;Homeostasis;in vivo;Individual;Investigation;Learning;Memory;memory encoding;Molecular;Nature;neocortical;Nervous System Disorder;Neurons;Post-Traumatic Stress Disorders;prevent;Process;programs;Property;Research Support;Role;Sensory;Synapses;Testing;tool;Work

PROJECT_TITLE: Mechanisms and Function of Firing Rate Homeostasis in Cortical Circuits


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: TALLAHASSEE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Narrative: The current project proposes a transformative approach to improving health equity by engaging communities to develop a systems map of racism in integrated primary care and establishing a process for developing, simulating, and measuring effects of new antiracism interventions in health care.

PI_NAMEs: NAAR, SYLVIE  (contact);PETTUS, CARRIE

PROGRAM_OFFICER_NAME: MUJURU, PRISCAH

PROJECT_TERMS: Address;Adoption;African American population;anti-racism;Attention;Attitude;Awareness;Behavior;behavioral and social science;Black American;Black race;care systems;combat;Communication;Communities;community based participatory research;community engagement;community engagement process;comorbidity;Complex;computerized;COVID-19;design;Diagnosis;Diffuse;Diffusion;Diffusion of Innovation;Discrimination;Ensure;evidence base;Evidence based intervention;experience;Foundations;Future;Health;health care delivery;health care service;health disparity;health equity;Health equity research;health inequalities;Health system;Healthcare;Healthcare Systems;Imprisonment;improved;Individual;Inequity;innovation;insight;Institutional Racism;Institutionalization;Integrated Health Care Systems;Intervention;Intervention Studies;Jail;Light;Low income;Maps;marginalized population;Mathematics;Measurement;Measures;Mental Health;Mental Health Services;Methods;Minority Groups;model building;Modeling;Monitor;Organizational Culture;Outcome;Pathway interactions;patient centered medical home;Patients;Phase;physical conditioning;Policies;Prevalence;Primary Care;primary care setting;Prisons;Process;Provider;Race;racial health disparity;racism;response;Science;screening;simulation;social health determinants;Specific qualifier value;Sterile coverings;System;Testing;theories;therapy development;tool;Training Activity;Translating;Translational Research;Treatment Efficacy;United States;Violence

PROJECT_TITLE: Transforming Health Equity Research in Integrated Primary Care: Antiracism as a Disruptive Innovation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-J(70)R]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Patient Safety;Rehabilitation;Social Determinants of Health

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: This work will develop an electronic health record-embedded discharge planning system to prevent undesired and unnecessary discharges to skilled nursing facilities; the initial step on a common pathway that often ends in long-term placement for patients with Alzheimer’s Disease and related dementias.

PI_NAMEs: CHEVILLE, ANDREA LYNNE (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Acceleration;acceptability and feasibility;acute care;Address;Advance Care Planning;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Area;Attention;Binding;care systems;Caregivers;Caring;Clinical;clinical decision support;Cognition;Cognitive;cognitive rehabilitation;computerized;Computers;cost;Data;Decision Making;Detection;Dimensions;Disadvantaged;Discharge Plannings;Early identification;Electronic Health Record;Elements;Eligibility Determination;Expenditure;experience;functional loss;Future;Goals;Health care facility;health data;Healthcare;Home;Home Health Care Agencies;Hospitalization;Hospitals;Impaired cognition;improved;Institution;Institutionalization;inter-institutional;Length of Stay;machine learning algorithm;mortality;Multi-Institutional Clinical Trial;novel;nursing skill;Outcome;Outcome Measure;Pathway interactions;Patient Outcomes Assessments;patient portal;patient-level barriers;Patients;pragmatic trial;preference;premature;pressure;prevent;Probability;Process;prototype;Provider;rehabilitation service;Rehabilitation therapy;Reporting;Risk;Savings;service delivery;Services;Site;Skilled Nursing Facilities;social factors;social health determinants;Social isolation;Standardization;statistics;System;Testing;Time;usability;user centered design;Work

PROJECT_TITLE: Project HoPe: Achieving Home Discharge for institutionally-bound Patients with PROMs, AI, and the EHR

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-K(90)]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: NARRATIVE Inherited retinal degenerative diseases and age-related macular degeneration are debilitating visual disorders for which there are currently no curative treatments. Thyroid hormone signaling regulates cell proliferation, differentiation, and metabolism, and has been associated with cone photoreceptor viability. This study will investigate thyroid hormone signaling activity in degenerating cones/retinas as well as the mechanism(s) underlying thyroid hormone signaling-induced cone death, and determine whether suppressing thyroid hormone signaling locally in the retina represents a strategy for cone protection.

PI_NAMEs: DING, XI-QIN  (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Acceleration;Age related macular degeneration;Antioxidants;Blindness;Cell Death;Cell Proliferation;Cessation of life;Cleavage Under Targets and Release Using Nuclease;Cone;curative treatments;cytotoxic;defined contribution;Deterioration;Development;disease heterogeneity;Enzymes;Evaluation;Eye;Future;Gene Expression;Genes;Genetic;Genetic Transcription;Goals;hormonal signals;Human;Incidence;Inherited;insight;Iodothyronine Deiodinase;Knowledge;Leber's amaurosis;macula;Metabolic;Metabolism;mitochondrial metabolism;Molecular;mouse model;Mus;Necrosis;Opsin;Optical Coherence Tomography;Outcome;oxidative damage;Oxidative Stress;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;photoreceptor degeneration;Physiological;Population;preservation;Process;Production;protein kinase inhibitor;Protein-Serine-Threonine Kinases;receptor;Regulation;response;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;Retinitis Pigmentosa;Role;Signal Induction;Signal Transduction;sodium iodate;Technology;Testing;therapeutic target;Thinness;thyroid associated ophthalmopathies;Thyroid Gland;Thyroid Hormone Receptor;Thyroid Hormones;Thyrotropin;transcriptome sequencing;Triiodothyronine;Vision Disorders;Visual impairment

PROJECT_TITLE: Thyroid Hormone Signaling and Cone Photoreceptor Degeneration

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


NIH_SPENDING_CATS: Aging;Cardiovascular;Osteoporosis

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Patients with a rare premature aging disease accumulate a protein called prelamin A that is only transiently expressed in non-affected people. In this project, we will use a unique mouse model that accumulates prelamin A to determine how it contributes to osteoporosis and blood vessel defects, conditions that frequently occur in older individuals. We will determine the molecular mechanisms by which prelamin A alters cells and if it actually accumulates in tissues during normal aging, which would provide a new insight into the aging process.

PI_NAMEs: MICHAELIS, SUSAN D. (contact);WORMAN, HOWARD J

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: Acceleration;Affect;Age;age related;Age related pathologies;Aging;aging population;aging process;aging related disease;Animal Model;Antibodies;Arterial Fatty Streak;Atherosclerosis;Biological;Blood Vessels;bone;bone cell;Bone Development;bone loss;Bone Resorption;Bone Tissue;C-terminal;Cardiovascular Diseases;Cell Aging;Cells;Chronic;Chronology;Clinical;Cultured Cells;Data;Defect;Deposition;Development;Dietary Intervention;Disease;disease phenotype;DNA;DNA Sequence Alteration;Dysplasia;Event;Exhibits;experimental study;Failure to Thrive;farnesylation;Fibroblasts;Fracture;Genetic;Genetic Transcription;Grant;Growth;High Fat Diet;Human;human subject;human tissue;In Vitro;in vivo;Inflammation;Inflammatory Response;insight;Intervention;Lamin Type A;Length;Life;life span;Lipids;Low Density Lipoprotein Receptor;Membrane Proteins;Metalloproteases;Modeling;Modification;Molecular;mouse model;Mouse Strains;Mus;Mutation;normal aging;novel;Nuclear Envelope;Nuclear Matrix-Associated Proteins;old mice;Older Population;Organism;Osteoblasts;Osteoclasts;Osteoporosis;Patients;Persons;Phenotype;Physiological;Point Mutation;prelamin A;premature;Premature aging syndrome;Progeria;programs;Protein Secretion;Proteins;Reporting;response;Role;Rupture;senescence;sensor;Signal Transduction;Site;Smooth Muscle Myocytes;Stimulator of Interferon Genes;Syndrome;Testing;therapeutic target;Tissue Microarray;Tissues;transcriptome;transcriptomics;Variant;Vascular Diseases;Vascular Smooth Muscle;Viral;Zinc

PROJECT_TITLE: Role for prelamin A in premature and physiological aging

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Narrative Numerous recent studies have consistently shown that likely no two cells in the human body have the exact same genomes, a phenomenon called somatic mosaicism. Mosaicism can be studied using various approaches, but the study of mutations directly in the cell promises a comprehensive characterization of mosaicism in any tissue. However, all existing methods have significant limitations for studying the genome in a cell. Here we propose to benchmark and test new approaches for comprehensive, accurate, and high-throughput analyses of the genomes of single cells.

PI_NAMEs: URBAN, ALEXANDER ECKEHART (contact);VACCARINO, FLORA M

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Autopsy;Benchmarking;Blood;Blood Cells;Blood Vessels;Bone Marrow;Brain;Cell Line;cell type;Cells;Characteristics;Clonal Expansion;Clone Cells;Cloning;comparative;Data;Detection;Disadvantaged;DNA;DNA amplification;DNA Insertion Elements;Endothelial Cells;Epithelial Cells;Failure;Fibroblasts;Freezing;Frequencies;Genes;Genome;genome analysis;genome-wide;Genomic DNA;Genomic Segment;genomic variation;Haplotypes;high throughput analysis;Human;Human body;Human Genome;improved;In Vitro;Individual;induced pluripotent stem cell;insertion/deletion mutation;Length;method development;Methods;Microglia;mosaic variant;Mosaicism;Mutation;Mutation Detection;Neuroglia;Neurons;Noise;Normal tissue morphology;novel;novel strategies;Nucleosomes;Organism;Phase;Phenotype;Production;Resolution;Resources;Sampling;single cell analysis;Skin;Somatic Mutation;stem;Techniques;Technology;telomere;Testing;Tissue Procurements;Tissues;tool;transcriptome;Urine;Variant;variant detection;whole genome

PROJECT_TITLE: Establishing and benchmarking advanced methods to comprehensively characterize somatic genome variation in single human cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CDB-K(70)R]


PHR: PUBLIC HEALTH RELEVANCE/NARRATIVE Type 2 diabetes mellitus (T2DM) is one of the major health problems facing today’s society and projected to afflict nearly 1 in 3 people by year 2050. It is therefore critical to improve our understanding of the molecular mechanisms driving the increasing prevalence of T2DM which can lead to the development of novel therapeutic and preventative approaches. Thus the underlying goals of this proposal are to uncover novel molecular mechanisms responsible for the regulation of pancreatic β-cell function in people exposed to enviromental stressors associated with increased risk of T2DM such as circadian rhythms disruptions and diet induced obesity.

PI_NAMEs: MATVEYENKO, ALEKSEY V (contact)

PROJECT_TERMS: Address;ARNTL gene;Automobile Driving;Beta Cell;Binding;Binding Sites;cell dedifferentiation;Cell Physiology;Cells;Characteristics;ChIP-seq;Chronic;circadian;Circadian desynchrony;Circadian Dysregulation;circadian pacemaker;circadian regulation;Circadian Rhythms;Complement Factor D;Complex;Cues;Data;design;Development;diet-induced obesity;DNA;DNA Binding;Endoplasmic Reticulum;Enhancers;environmental stressor;Epigenetic Process;Etiology;Exposure to;Failure;Fasting;Feedback;feeding;Food;FOXO1A gene;functional decline;Functional disorder;Funding;gain of function;Genes;Genetic;Genetic Predisposition to Disease;Genetic Transcription;Glucose Intolerance;Goals;Health;Homeostasis;Hour;Human;human stem cell-derived;Hyperglycemia;Hyperinsulinism;Hypothalamic structure;Immunodeficient Mouse;Impairment;improved;in vivo;insight;Insulin;insulin secretion;islet;Laboratories;Lead;Light;light entrainment;loss of function;Luciferases;Mediating;Molecular;mouse model;multiple omics;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;novel therapeutics;Nutritive Value;Obesity;Periodicity;Peripheral;Persons;Physiological;Physiology;preservation;Prevalence;prevent;Prevention;Prevention strategy;Process;programs;Proteins;proteostasis;proteostasis loss;public health relevance;Regulation;Reporter;response;Risk;Role;Secretory Cell;Signal Transduction;single cell ATAC-seq;Societies;Stress;stressor;Structure of beta Cell of islet;suprachiasmatic nucleus;System;Systems Biology;Techniques;Testing;therapeutic target;Tissues;Transcript;transcription factor;Transcriptional Regulation;transcriptome sequencing;Transplantation;treatment strategy;Viral;Work

PROJECT_TITLE: Role of Circadian Misalignment in Beta-cell Failure in Type 2 Diabetes

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