ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROSURGERY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The goal of the NRCDP is to recruit, identify, and supporting promising neurosurgeons at the beginning of their careers, when they are most vulnerable, so that they can successfully transition into independent neurosurgeon scientists. The first 10 years of the program were tremendously successful. During the next five years, we aim to build on this success by fostering greater diversity, equity, and inclusion at all program levels, creating a “Pipeline Program” for recruiting the most talented and diverse group of K12 applicants, expanding the “Training Program” to accelerate timing to first independent NIH award, and establishing an NRCDP leadership structure that embraces continuous renewal and evolution.

PI_NAMEs: AMIN-HANJANI, SEPIDEH ;ESKANDAR, EMAD N;HOLLY, LANGSTON TYLER;ZIPFEL, GREGORY J (contact)

PROGRAM_OFFICER_NAME: WEIGAND, LETITIA ALEXIS

PROJECT_TERMS: Academy;Acceleration;Achievement;Address;Advisory Committees;Affect;Award;career development;Development;Disabling;Disease;Eligibility Determination;equity, diversity, and inclusion;Ethics;Evolution;Faculty;Fellowship;Fostering;Funding;Goals;Grant;Individual;innovation;Institution;Interview;Leadership;member;Mentored Clinical Scientist Development Program;Mentors;Nervous System;Neurosurgeon;neurosurgery;Pathogenesis;Preparation;Program Development;programs;Qualifying;recruit;Reproducibility;Research;Research Personnel;Residencies;Review Committee;Scientist;Secure;Structure;Study Section;success;symposium;System;Talents;Time;Training;Training Programs;United States National Institutes of Health

PROJECT_TITLE: Neurosurgeon Research Career Development Program (NRCDP)


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NEW HAVEN

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Parkinson’s disease (PD) is a devastating disease with no cure, and patients rely on a combination of drugs to reduce symptoms and maintain quality of life. One class of drugs used in PD therapy, catechol-O-methyltransferase inhibitors (COMT-I), exhibit interindividual differences in drug efficacy, adverse side effects, and microbiome disruption. This project will dissect how metabolism of COMT-I drugs by the gut microbiome impacts drug efficacy, toxicity, and microbiome disruption.

PI_NAMEs: VERDEGAAL, ANDREW ALBERT (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: 16S ribosomal RNA sequencing;Adverse event;Affect;American;Analytical Chemistry;Anti-Bacterial Agents;Antibiotics;Area;Bacteria;bacterial community;bacterial metabolism;Bacteroides thetaiotaomicron;Biochemistry;Biological Assay;Biological Availability;Brain;Catechol O-Methyltransferase;Communities;Complex;Data;Disease;Dopamine;dopaminergic neuron;Drug Combinations;drug efficacy;drug metabolism;Drug Side Effects;Drug toxicity;Drug usage;Educational process of instructing;entacapone;Enzymes;Exhibits;experimental study;Exposure to;Family;gastrointestinal;Genetic;Genetic Transcription;Gnotobiotic;gut microbes;gut microbiome;gut microbiota;Hepatotoxicity;Human;Human Microbiome;improved;In Vitro;in vivo;Individual Differences;inhibitor;inhibitor therapy;insight;Intervention;Levodopa;Link;liquid chromatography mass spectrometry;Mass Spectrum Analysis;Mediating;Mentorship;Metabolic;Metabolism;Metagenomics;microbial;Microbiology;microbiome;microbiome composition;model organism;Motor Manifestations;Mus;Nervous System;Neurologic;Neurologic Symptoms;neurotransmission;Neurotransmitters;Nitroreductases;Oral;Parkinson Disease;Patients;Peripheral;Pharmaceutical Preparations;Pharmacology;Pharmacotherapy;Production;Quality of life;reduce symptoms;Reporting;Research;Research Personnel;Research Training;side effect;skills;Structure;Testing;Tissues;tolcapone;Toxic effect;Training;training opportunity;Variant;Writing

PROJECT_TITLE: Bacterial metabolism of catechol-O-methyltransferase inhibitors alters drug efficacy and toxicity


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Genetics;Liver Disease;Nutrition

ORG_CITY: SAN ANTONIO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: NARRATIVE  Liver metabolic dysfunction leads to disturbances in lipid and glucose metabolism, and directly contributes to the development of type 2 diabetes (T2D and nonalcoholic fatty liver disease (NAFLD). The increased prevalence of these metabolic diseases presents a significant threat to public health, and treatment strategies that address the underlying pathological processes are urgently needed. Our proposed studies will reveal novel mechanisms linking the diabetes candidate gene transcription factor 7-like 2 (TCF7L2) to key metabolic pathways in liver that may have significant implications for the treatment of T2D and NAFLD.

PI_NAMEs: NORTON, LUKE  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Address;Adult;amino acid metabolism;Ammonia;Architecture;ATAC-seq;beta catenin;Candidate Disease Gene;Catabolism;Cell Nucleus;Central Vein;Cirrhosis;Clinical;Couples;Data;Defect;design;Development;Diabetes Mellitus;dietary;Disease;Drug Metabolic Detoxication;Enzymes;Equilibrium;experimental study;fibrogenesis;Fibrosis;Genes;Genetic Polymorphism;Genetic Transcription;Genomics;Glucose;glucose metabolism;Glutamate-Ammonia Ligase;Glutamates;Glutamine;Hepatic;Hepatocyte;HMG-Box Domains;Homeostasis;hormone regulation;Human;human model;in vivo;Link;lipid metabolism;Lipids;Liver;Liver diseases;Liver Fibrosis;Lobular;Lobule;Maintenance;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic Pathway;Metabolism;Modeling;Molecular;mouse model;multiple omics;Mus;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Pathologic Processes;Pathway interactions;Peripheral;Physiological;Play;Population;Portal triad;Prevalence;Primary carcinoma of the liver cells;Proteins;Public Health;Publishing;Regulation;Rodent;Rodent Model;Role;Signal Pathway;single nucleus RNA-sequencing;spatiotemporal;TCF7L2 gene;Techniques;Testing;Tissues;tool;transcription factor;Transcriptional Regulation;transcriptome;treatment strategy

PROJECT_TITLE: The Regulation of Hepatic Metabolic Zonation by the Diabetes Gene TCF7L2

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SEATTLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Epigenetic mechanisms, involving chemical modifications to the proteins that help package our genomes, help cells turn on the right genes at the right time to drive cell differentiation; yet, how they work to control gene activation remains unclear and widely debated. We seek to understand an epigenetic mechanism we recently discovered, that helps blood stem cells turn into a specialized cell type. Because mutations in these epigenetic mechanisms are major drivers of malignancy, these studies will yield broad insights into tumorigenesis across different cancer types.

PI_NAMEs: KUEH, HAO YUAN  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acceleration;Alleles;Binding;Biological Assay;Biology;Blood;cancer type;Cell Differentiation process;Cell Lineage;cell type;Cells;cellular development;Chemicals;Chromatin;Collaborations;Color;derepression;Development;Developmental Gene;Developmental Process;Disease;Enhancers;Environment;Enzymes;Epigenetic Process;Etiology;Event;Excision;gain of function mutation;Gene Activation;Gene Expression;Genes;Genome;genomic locus;Goals;Hematopoietic stem cells;Histone H3;histone modification;Homeostasis;In Vitro;insight;leukemia;Lysine;Malignant - descriptor;Malignant Neoplasms;Measures;Methods;Methylation;Modeling;Modification;mouse model;Mus;Mutation;notch protein;Nucleic Acid Regulatory Sequences;Oncogenic;Peptide Initiation Factors;Polycomb;Process;progenitor;Proteins;recruit;Regulation;Reporter;Repression;response;Role;Signal Transduction;Specific qualifier value;stem;stem cells;System;T-Cell Development;T-Lymphocyte;TCF Transcription Factor;Testing;Thymus Gland;Time;tool;transcription factor;tumorigenesis;Untranslated RNA;Visualization;Work

PROJECT_TITLE: A chromatin-based timer controlling T-cell development

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ADMINISTERING_IC: HS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: CLEVELAND

ORG_NAME: UNIVERSITY HOSPITALS OF CLEVELAND

ORG_STATE: OH

PHR: The EMPOWER study is an integrated, multilevel (patient, provide, and system) approach that addresses key barriers to diagnosing and managing UI in the primary care setting. Implementation strategies include large- scale screening, empowering patients to discuss UI with their providers, provider education and training, practice facilitation through nurse navigation, and a novel mobile platform “chatbot” to engage patients in self- management of their UI. The implementation plan is fully aligned with AHRQ's EvidenceNow framework: practice facilitation, expert consultation, shared learning collaborative, data feedback and benchmarking, and health-information technology support.

PI_NAMEs: HIJAZ, ADONIS K (contact);RAO, GOUTHAM

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Empowering Women and Providers for Improved Care of Urinary Incontinence : EMPOWER Study


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Many environmental chemicals linked to Parkinson’s disease have been proposed to exert their effects via disruption of vesicular storage of dopamine. This project will focus on the role of SV2C, which has recently been identified in a genome-wide study of Parkinson’s disease, in maintaining vesicular dopamine homeostasis and protecting neurons from toxicity.

PI_NAMEs: MILLER, GARY W (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: alpha synuclein;Behavioral;Biological;Biological Assay;brain tissue;Caenorhabditis elegans;cell injury;Cell Membrane Permeability;Cells;Characteristics;Chemicals;Coupled;Cytosol;Data;Development;Diffusion;Disease;Dopamine;dopamine quinone;dopaminergic neuron;Electron Microscopy;environmental chemical;Environmental Exposure;Exposure to;Extravasation;Funding;genome wide association study;genome-wide analysis;Glycoproteins;Health;Herbicides;Homeostasis;Human;Idiopathic Parkinson Disease;Image;Impairment;Induced Neurons;Insecticides;Knockout Mice;Laboratories;Link;Measures;Mediating;model organism;Morphology;Motivation;motor behavior;mouse model;Mus;mutant;Nature;Nerve Degeneration;neurochemistry;Neuromodulator;Neurons;neurotoxicity;Neurotransmitters;Parkinson Disease;Pathogenesis;Pathologic;Periodicity;pH gradient;Polychlorinated Biphenyls;Positioning Attribute;prevent;Process;Production;Property;Proteins;Reader;Research;Resistance;response;Rewards;Risk Factors;Role;Scanning;Sex Differences;Source;Synapses;synaptic function;Synaptic Vesicles;synuclein;targeted treatment;Techniques;Testing;Therapeutic Intervention;Time;Toxic effect;toxicant;Transfection;transgene expression;uptake;Vesicle;vesicular monoamine transporter

PROJECT_TITLE: Vesicular modulation of dopamine neuron toxicity

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

PHR: Diabetic foot ulcers are common, debilitating, and costly complications of diabetes, disproportionately impacting Black and rural Veterans. Forty percent of individuals have an ulcer recurrence within a year of ulcer healing and 65% within 5 years. Monitoring plantar foot temperatures is one of the few interventions that reduces the risk of ulcer recurrence. Despite the evidence, adoption has been poor because the original procedures, including the use of handheld thermometers, were burdensome and time-consuming. Podimetrics, a private company, has developed a temperature monitoring system involving a “smart” mat that can wirelessly transmit data and a remote monitoring team that works with VA providers to assist with triage and monitoring. This care model has incredible promise, but has been untested in VA. We propose to conduct a randomized trial to evaluate effectiveness of remote temperature monitoring as well as costs. Additionally, we will evaluate the implementation process, including barriers and facilitators to use among key stakeholders.

PI_NAMEs: LITTMAN, ALYSON  (contact)

PROJECT_TERMS: Address;Adoption;Affect;Amputation;Behavior;Biometry;Black race;budget impact;care costs;Caregivers;Caring;Case Manager;Complications of Diabetes Mellitus;Consolidated Framework for Implementation Research;Consumption;Contralateral;cost;Cost Analysis;Cost Savings;Data;Data Analyses;Data Collection;Data Sources;design;Diabetes Mellitus;diabetic;Diabetic Foot Ulcer;Dissemination and Implementation;Early Diagnosis;Early treatment;Ecosystem;Effectiveness;effectiveness evaluation;Emergency department visit;Enrollment;Equity;Exclusion Criteria;experience;foot;Future;healing;Health;health equity;Healthcare;Healthcare Systems;high risk;Home;Hospitalization;Hot Spot;implementation barriers;implementation evaluation;implementation facilitators;implementation framework;implementation process;Improve Access;Individual;Inflammation;innovation;Inpatients;Intervention;Interview;Knowledge;limb loss;Measures;Methodology;Modeling;Monitor;Netherlands;new technology;Observational Study;Outcome;Outpatients;participant enrollment;Patient Outcomes Assessments;Patient Selection;Patients;Personal Satisfaction;Persons;Play;primary outcome;Privatization;Procedures;Process;programs;Protocols documentation;Provider;public-private partnership;Quality of life;Race;Randomized;randomized trial;randomized, controlled study;Randomized, Controlled Trials;Recording of previous events;Recurrence;remote assessment;remote monitoring;Reporting;Research;Resources;Risk;Risk Reduction;Role;Rural;rurality;satisfaction;Scanning;secondary outcome;Seminal;Services;Severities;Site;Skin;Subgroup;System;Technology;Temperature;Thermometers;Time;treatment as usual;Triage;Ulcer;Uncertainty;Veterans;wireless data transmission;wireless transmission;Work

PROJECT_TITLE: Home foot-temperature monitoring through smart mat technology to improve access, equity, and outcomes in high-risk patients with diabetes

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative G protein-mediated signaling pathways regulate numerous physiological responses, including neuron development, neurotransmitter responses, cardiovascular function, cell differentiation, cell migration, immune cell function, and smell, taste, and vision. Dysregulation of G protein-mediated signaling pathways contribute to numerous disease states, including neurological diseases, heart disease, hypertension, cancer, metastasis, endocrine disorders, and blindness. Understanding novel cellular mechanisms that regulate disease causing, mutationally activated G proteins will provide new knowledge and opportunities to therapeutically target unwanted G protein responses.

PI_NAMEs: WEDEGAERTNER, PHILIP B (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Address;Adult;Binding;Biochemical;Biological Assay;Biosensor;Blindness;Blood capillaries;Cardiovascular Physiology;Cell Differentiation process;cell growth regulation;Cell membrane;Cell model;cell motility;Cell Physiology;Cells;Codon Nucleotides;Congenital Hemangioma;Cultured Cells;Cyclodepsipeptides;Cytoplasm;Data;Disease;Endocrine System Diseases;experience;extracellular;Fluorescence Microscopy;G-Protein-Coupled Receptors;Genes;genetic regulatory protein;Glutamine;GNAQ gene;GTP Binding;GTP-Binding Proteins;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate;Heart Diseases;Heterotrimeric GTP-Binding Proteins;human disease;Hydrolysis;Hypertension;Immune;Immunofluorescence Microscopy;inhibitor;Knowledge;Link;live cell microscopy;Location;malformation;malignant neoplasm of eye;Malignant Neoplasms;Mediating;Membrane;Mitogen-Activated Protein Kinases;Modeling;Molecular;mutant;Mutation;Mutation Analysis;Natural Products;Neoplasm Metastasis;Neoplasms in Vascular Tissue;Nervous System Disorder;neuron development;Neurotransmitters;new therapeutic target;novel;Oncogenic;palmitoylation;Pathway interactions;Patients;pharmacologic;Phospholipase C;Physiological;Physiological Processes;Plasma Cells;Play;protein function;Protein Subunits;Proteins;receptor-mediated signaling;reconstitution;Refractory;Regulation;Research Project Grants;Research Proposals;Resistance;resistance mechanism;response;rho;Role;Signal Pathway;Signal Transduction;Smell Perception;Somatic Mutation;Sturge-Weber Syndrome;Surface;Taste Perception;Testing;therapeutic target;trafficking;transmission process;Uveal Melanoma;Vision;Work

PROJECT_TITLE: Regulation of Mutationally Activated Gq/11

STUDY_SECTION: MIST

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


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome

ORG_CITY: SALT LAKE CITY

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE This project aims to determine the influence of previously identified gene defects on the development of superficial fibrosing disorders, including Peyronie’s and Dupuytren’s diseases, as well as to identify associated and comorbid conditions in familial cases of these diseases. A deeper understanding of the genetic factors that underpin these conditions will facilitate patient risk stratification and permit development of targeted, effective therapies for these conditions.

PI_NAMEs: PASTUSZAK, ALEXANDER WOJCIECH (contact)

PROGRAM_OFFICER_NAME: KIRKALI, ZIYA

PROJECT_TERMS: Address;Affect;animal data;Animal Model;autosome;Basic Science;Benign;Biological Assay;Candidate Disease Gene;Cells;clinical diagnosis;clinical risk;Coitus;Collagen;comorbidity;Contracture;CRISPR/Cas technology;Data;Databases;Defect;Deformity;Deposition;Development;Diagnosis;differential expression;Disease;Disease susceptibility;DNA Sequence Alteration;effective therapy;Epidermal Growth Factor;erection;Etiology;Extended Family;Family member;Fibroblasts;Fibrosis;Functional disorder;Gene Dosage;Gene Expression Profile;gene function;Genealogy;Genes;Genetic;Genetic Diseases;genetic pedigree;Genetic Polymorphism;Genetic Screening;Genetic Transcription;genetic variant;genome sequencing;Goals;Hand;Health;Heritability;High Prevalence;high risk;Human;human data;Hydroxyproline;Immunohistochemistry;improved;In Vitro;in vitro Assay;Individual;Inflammation;Inflammatory;inflammatory marker;interest;Investigation;Link;Major Depressive Disorder;male;Malignant Neoplasms;Medical Records;men;microdeletion;Molecular;molecular targeted therapies;mouse model;Mus;Mutation;neural;Neurophysiology - biologic function;Nodule;Organ;Other Genetics;Pathogenesis;Pathogenicity;Pathway interactions;Patient risk;patient stratification;Patients;penis;Peyronie Disease;Phosphoric Monoester Hydrolases;physical impairment;Population;Population Database;Predisposition;Proteins;psychologic;recruit;risk stratification;Role;Science;Sexual Dysfunction;Signal Pathway;targeted treatment;Testing;transcriptome sequencing;Transforming Growth Factor beta;translational model;translational study;Trichrome stain method;Tunica Albuginea;United States;Utah;Validation;Variant;whole genome;Work;Zinc Fingers

PROJECT_TITLE: Validation and Identification of Genetic Variants in Peyronie's and Dupuytren's Disease that Predispose to Fibrosis and Inflammation

STUDY_SECTION: KUFD

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


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Narrative Proton-coupled electron transfer (PCET) lies at the heart of radical enzymology, and a vast number of enzymes are now known to derive their function from radicals generated by PCET. Of the enzymes that operate by PCET, ribonucleotide reductase (RNR) is exceptional in its biological function and is paramount to health owing to the enzyme’s function in nucleic acid metabolism and consequently in its central role in cancer. Discovery of new therapeutics therefore relies on an understanding of the PCET pathway of RNR, as disruption of the PCET pathway is a critical target for drug design in the treatment of cancer.

PI_NAMEs: NOCERA, DANIEL G. (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Active Sites;Address;Affinity;Amino Acids;Anabolism;Anti-Bacterial Agents;Anti-Inflammatory Agents;Anti-Retroviral Agents;Biochemical;Biochemistry;Biological;Biological Assay;Biological Process;Biology;biophysical techniques;Biophysics;cancer therapy;Chemicals;Chemistry;chemotherapy;Clinical;cofactor;Complex;Coupled;Coupling;Cryoelectron Microscopy;Cysteine;Data;Deoxyribonucleotides;design;Development;Disease;DNA;DNA biosynthesis;Drug Design;Drug Targeting;Electrochemistry;Electron Transport;Electrons;Enzymatic Biochemistry;Enzymes;Equipment and supply inventories;Event;Experimental Designs;Face;Funding;Future;Generations;Goals;Health;Heart;holistic approach;Human;Individual;inhibitor;innovation;insight;interdisciplinary approach;Kinetics;Knowledge;Life;Link;Malignant Neoplasms;Mediating;Methodology;Methods;Modality;Modeling;Molecular Biology;Molecular Conformation;monomer;Nature;novel therapeutics;nucleic acid metabolism;Nucleotides;Outcome;Oxidation-Reduction;Oxidoreductase;Pathway interactions;Pharmaceutical Preparations;Phase;Play;Positioning Attribute;Prevalence;Process;protein structure;Protons;Reaction;Regulation;repaired;Resolution;Ribonucleotide Reductase;Ribonucleotides;Role;Selenocysteine;Site;small molecule therapeutics;Specificity;Spectrum Analysis;Structure;System;Techniques;therapeutic target;Therapeutic Uses;tool;Tryptophan;Tyrosine;unnatural amino acids;Variant;Visualization;Work

PROJECT_TITLE: Structure-Function Studies of Ribonucleotide Reductase

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Cardiovascular;Clinical Research;Endocannabinoid System Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Mental Health;Neurosciences;Physical Activity;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Narrative Endocannabinoids, lipid messengers, are a principal modulator of stress, regulate emotions and cardiovascular function, and have diurnal rhythmicity. In order to determine how the large daily fluctuation in endocannabinoid signaling at rest impacts emotional and cardiovascular reactivity in response to an abrupt stressor, we will use a circadian protocol that allows us to equally distribute all behaviors such as stress exposure, meals, and sleep, across the circadian cycle. Our hypothesized differential endocannabinoid and associated cardiovascular response to a stress across the circadian system provides a plausible pathway that could underlie risks for development of cardiovascular disease in night and rotating shift workers.

PI_NAMEs: BOWLES, NICOLE P (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: Acute;acute stress;Adult;Affect;Age;aged;Area;Arithmetic;Arousal;Attenuated;awake;Behavior;Biological;biological adaptation to stress;Black American;Black Populations;Black race;Blood Platelets;Cardiac;cardiometabolism;cardioprotection;Cardiovascular Diseases;cardiovascular health;Cardiovascular Physiology;Cardiovascular system;career;caucasian American;Cause of Death;Cessation of life;Characteristics;circadian;Circadian Rhythms;Communities;cost;Cues;Depressed mood;Development;Doctor of Philosophy;emotion regulation;Emotional;Emotions;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Environment;Enzymes;Etiology;Event;Evidence based intervention;Exercise;Exertion;Future;Goals;habituation;Health;Health Expenditures;Heart Diseases;Heart Rate;Hemostatic function;Human;Hydrocortisone;Hypertension;improved;Incidence;Intervention;Knowledge;Labor Forces;Laboratories;Lead;Light;Lighting;Link;Lipids;Measures;Medication Management;Melatonin;Mentors;Moderate Exercise;Moods;mortality;Mus;parent grant;Pathway interactions;Periodicity;Phase;Physiological;Physiology;Plasma;platelet function;Prevention;productivity loss;Protocols documentation;Psyche structure;psychosocial;Psychosocial Stress;Questionnaires;Race;receptor;Recovery;Recurrence;Reporting;Research;response;Rest;Risk;Role;Rotation;Salivary;Schedule;Scientist;shift work;Sleep;Sleep Wake Cycle;Standardization;Stress;stress management;stress reactivity;stressor;Stroke;System;Testing;Time;Training;Translating;Variant;Wakefulness;Work

PROJECT_TITLE: Role of the circadian rhythm on endocannabinoid response to an acute stress

STUDY_SECTION: MCBS

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


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Endocrine Disruptors;Foodborne Illness;Nutrition;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: The Seychelles Child Development Study (SCDS) is the largest prospective study specifically designed to examine the potential health risks associated with prenatal methylmercury (MeHg) exposure in a population of high fish consumers. It has made critical and novel contributions to our understanding of MeHg toxicity risks. The 30-year history of the SCDS has resulted in a unique and vast repository of biological data and population characteristics. The proposed enrichment and sharing of these data provides a critical opportunity to further study underlying mechanisms of MeHg toxicity and to examine the long-term dynamics of MeHg exposure across the life course.

PI_NAMEs: VAN WIJNGAARDEN, EDWIN  (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: 13 year old;Address;Aging;Antinuclear Antibodies;Asthma;Attention;Autoimmune Responses;Benefits and Risks;biobank;Biochemistry;Biological;Biological Markers;Biometry;Blood Pressure;Blood specimen;Brain;Child;Child Development;clinically relevant;cognitive function;cognitive performance;cohort;Cohort Studies;Collection;Consumption;Data;data access;Data Collection;data dictionary;Data Discovery;data harmonization;data sharing;data standards;database structure;Databases;design;Development;developmental toxicity;Diet;Eating;Enrollment;Epidemiology;Equilibrium;Etiology;fatty acid metabolism;Fishes;follow-up;Foundations;Funding;Future;Genes;Genetic;Glutathione;Hair;Health;Health behavior;health determinants;Height;Hip region structure;Human Genetics;Hypersensitivity;immune function;Immunoglobulins;improved;International;Investigation;Investments;Life Cycle Stages;Link;Longitudinal Studies;Mammals;Masks;Measures;Medical History;Metabolism;Methylmercury Compounds;methylmercury exposure;Mothers;Neurotoxins;Northern Ireland;novel;Nutrient;nutrition;Nutritional Biochemistry;Oceans;Ontology;Outcome;Oxidative Stress;Participant;Persons;Phenotype;Physical assessment;Physical Function;Physical Performance;Play;Polyunsaturated Fatty Acids;Population;Population Characteristics;Predisposition;Pregnancy;prenatal;Preparation;preservation;Prospective Studies;Public Health;Questionnaires;Recording of previous events;Records;recruit;repository;Research;Resources;Risk;Risk Factors;Role;Sampling;Schools;Science;Sea;Serum;Seychelles;sociodemographic factors;sociodemographics;Source;statistics;stem;success;Sweden;Symptoms;Toxic effect;Toxicology;Translational Research;trend;Uncertainty;United States National Institutes of Health;Update;Visualization;Weight

PROJECT_TITLE: Leveraging Investments in the Seychelles Child Development Study to Enable Novel Investigations of Long-Term MeHg Exposure, Toxicity Mechanisms, and Health across the Life Course


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Foodborne Illness;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Kidney Disease

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE In many regions of the world, agricultural workers are dying at high rates due to a mysterious kidney disease, their kidneys irreversibly scarred without an obvious insult. We plan to investigate the cause of this epidemic of a chronic kidney disease of unknown cause, with parallel epidemiologic and molecular tools, basing our work in Sri Lanka, because it is a ‘hotspot’ where the causative exposure is likely to exist in abundance. However, since other regions of the world, including the U.S., are affected, our multi-disciplinary approach has the potential to identify and prevent an unknown cause of kidney disease affecting vulnerable agricultural populations worldwide.

PI_NAMEs: ANAND, SHUCHI  (contact)

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Accounting;acute infection;Address;Adult;Affect;agricultural community;Agricultural Workers;Agriculture;Agrochemicals;Archives;Area;Autoimmune Diseases;Balkan Nephropathy;biobank;Biological;Biopsy;Blood;California;Canes;Categories;Cessation of life;Chlorinated Hydrocarbons;Chronic Kidney Failure;Cicatrix;Classification;Climate;Clinical;cohort;Communicable Diseases;Consumption;Costa Rica;Coupled;Data;Diazinon;Dichlorodiphenyl Dichloroethylene;Disease;drinking;drinking water;El Salvador;End stage renal failure;Endosulfan;Environmental Risk Factor;Epidemic;Epidemiology;epidemiology study;Etiology;Experimental Models;Family member;Farm;farmer;field study;Fresh Water;Future;Gene Expression;Gene Expression Profile;Guatemala;Guidelines;Heat Stress;Histology;Household;Hypersensitivity;improved;India;Individual;Industry;Injury;interdisciplinary approach;interest;International;Investigation;Kidney;kidney biopsy;Kidney Diseases;Link;Mass Spectrum Analysis;Measures;meetings;Molecular;Molecular Analysis;multidisciplinary;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Environmental Health Sciences;Nephrons;nephrotoxicity;Nicaragua;Organophosphates;Participant;Pathologist;Pathway interactions;Patients;Pattern;Persons;Population;premature;prevent;prospective;Prospective cohort;Protocols documentation;Reaction;Recommendation;Recording of previous events;recruit;Regulation;Relative Risks;Renal function;Reporting;response;response to injury;Rice;Risk;risk prediction;Running;Sampling;scaffold;Severities;single-cell RNA sequencing;Site;Specific qualifier value;Specimen;Sri Lanka;sugar;Testing;Texas;tool;Toxic Environmental Substances;transcriptome sequencing;transcriptomic profiling;Transplantation;Tubular formation;Urine;Vulnerable Populations;Water consumption;water sampling;Water Supply;well water;Work

PROJECT_TITLE: Chronic kidney disease of unknown etiology: applying a multidisciplinary approach to investigate the world's most common tubulointerstitial kidney disease

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


NIH_SPENDING_CATS: Clinical Research;Emergency Care;Health Services;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: In this collaborative network proposal, we outline a consolidated network of local hospitals representing the community, public, federal, and academic healthcare environments. This network will be supplemented by additional regional and national academic medical centers for additional tertiary care patient enrollment capability.

PI_NAMEs: JAMES, MICHAEL L.;LIMKAKENG, ALEXANDER TAN (contact)

PROGRAM_OFFICER_NAME: SCOTT, GRETCHEN CARLYLE

PROJECT_TERMS: Academic Medical Centers;Accident and Emergency department;Acute;African American;Age;Basic Science;bench-to-bedside translation;Budgets;Cardiac;Caring;Clinical;Clinical and Translational Science Awards;clinical center;Clinical Research;clinical research site;Clinical Trials;Collaborations;Communities;community engaged research;Community Medicine;Conduct Clinical Trials;Contracts;Critical Care;Dedications;demographics;Electronic Health Record;Electronics;Emergency Care;Emergency Medicine;Emergency research;Emergency treatment;Enrollment;Environment;experience;Financial cost;flexibility;Funding;Geography;Goals;Health system;Healthcare;Hospitals;Individual;Infrastructure;innovation;Institution;interdisciplinary collaboration;Investments;Latinx;Leadership;Learning;Longterm Follow-up;Lung;Medical emergency;medical specialties;Medicine;member;Methodology;Mission;Neurologic;Neurological emergencies;Office Surgery;operation;Oregon;participant enrollment;patient population;Patients;Population Heterogeneity;Pragmatic clinical trial;Procedures;recruit;Research;Research Institute;Research Personnel;Research Support;Resources;Role;Running;Services;Singapore;Site;System;Talents;tertiary care;translational pipeline;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Mid-Atlantic praGmatic NETwork for Inclusive Clinical trials in emergency care (MAGNETIC)


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative The overall goal of this project is to collect and disseminate critical data on cognitive, physical, and sensory functioning and risk for Alzheimer's Disease and Related Dementias (ADRD) in Wave VI of the National Longitudinal Study of Adolescent to Adult Health (Add Health), when participants will be in their mid-40s. These new data, when combined with Add Health's existing collection of extraordinarily rich multi-level and longitudinal measures and its new Wave VI data, will facilitate the scientific community's understanding of the interplay of social, economic, behavioral, and biological factors that influence cognitive, physical, and sensory functioning in midlife and lead to ADRD in later life. Moreover, because Add Health is a diverse nationally representative sample, adding these data to Wave VI will greatly increase understanding of cognitive, physical, and sensory functioning within key health disparity populations in the United States.

PI_NAMEs: AIELLO, ALLISON E;HUMMER, ROBERT A (contact)

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: Activities of Daily Living;Adolescence;Adolescent;Adult;Affect;aging population;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Behavioral;Biological;Biological Factors;Biological Markers;Biological Testing;Blood;Cognition;Cognitive;cognitive function;cognitive testing;cohort;Collection;Communities;Companions;Country;Coupled;Data;Data Collection;dementia risk;Development;Diabetes Mellitus;Disparity;Drug usage;early adolescence;Early identification;Early Intervention;Economics;Education;ethnic diversity;experience;Foundations;Future;Gait;Goals;Health;Health and Retirement Study;health disparity populations;Hearing;Hypertension;Impaired cognition;innovation;instrument;late life;Life Cycle Stages;Longitudinal Studies;Measurement;Measures;middle age;National Longitudinal Survey of Adolescent to Adult Health;Nerve Degeneration;Obesity;Online Systems;Participant;Pathway interactions;Persons;Physical assessment;Physical Function;physically handicapped;Population;prevent;prospective;Protocols documentation;racial diversity;Research;Research Personnel;response;Risk;Risk Factors;Risk Marker;Sampling;Scientific Advances and Accomplishments;Sensory;Signs and Symptoms;Smell Perception;Smoking;social;Surveys;Symptoms;Testing;Time;trend;United States;Validation;Venous;Vision

PROJECT_TITLE: National Longitudinal Study of Adolescent to Adult Health (Add Health): Wave VI Cognition and Early Risk Factors for Dementia Project


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_DEPT: CHEMISTRY

PHR: Project Narrative The ability to profile ribosome occupancies genome-wide has transformed our understanding of protein synthesis and translational regulation. Through structure-based design, we propose to develop new chemical tools to enable rapid profiling of ribosome occupancies while preserving the integrity of the mRNA transcript, allowing the study of ribosomes relative to one another on single molecules. We expect that such approaches will enable the simultaneous, streamlined profiling of ribosome positions and mRNA levels in any cell type while offering new perspectives on ribosome co-positioning.

PI_NAMEs: LIAU, BRIAN  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Acylation;Address;adduct;Automobile Driving;Benchmarking;Binding;Bypass;Cell Line;cell type;Cells;Chemicals;Chemistry;Clinical;Complex;crosslink;Cryoelectron Microscopy;Data Set;design;Digestion;Disease;Drops;Elements;Emerging Technologies;Emetine;Energy consumption;Event;Foundations;Functional disorder;Future;genome-wide;high reward;high risk;Hydroxyl Radical;improved;In Vitro;inhibitor;innovation;insight;Label;Mammalian Cell;Maps;Measures;meetings;Messenger RNA;Methods;Mission;Modification;Movement;Mutation;National Institute of General Medical Sciences;natural product derivative;Natural Products;next generation sequencing;novel;Photoaffinity Labels;Physiological;Polyribosomes;Positioning Attribute;preservation;Process;Protein Biosynthesis;Proteins;Protocols documentation;Relaxation;Research Proposals;Resolution;Reverse Transcription;ribosome profiling;Ribosomes;RNA;RNA Splicing;RNA-Protein Interaction;Sampling;Signal Transduction;single cell technology;single molecule;Site;small molecule;Structure;success;System;Technology;Testing;tool;Transcript;transcriptome sequencing;Transfer RNA;Translating;translation assay;Translational Regulation;Translational Repression;Translations;Variant

PROJECT_TITLE: Genome-wide Mapping of Ribosome Occupancies with Inhibitor-Induced mRNA Covalent Labeling

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_CITY: CHICAGO

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative Despite the increasing prevalence of stroke and resulting disability, the field of neurorehabilitation lacks both effective treatment options and the mechanistic knowledge base to facilitate functional motor recovery. Bilateral motor priming is a promising intervention which has been shown to enhance the effects of upper limb (UL) training for people with moderate to severe hemiparesis, but the neural mechanisms underlying its impact remain unknown. The proposed research will investigate neurophysiological changes in the brain following a bilateral motor priming and UL training intervention to learn how priming works and ultimately improve our ability to address the devastating functional consequences of a neurological insult.

PI_NAMEs: KING, ERIN  (contact)

PROGRAM_OFFICER_NAME: BONNER, JOSEPH FRANCIS

PROJECT_TERMS: Activities of Daily Living;acute stroke;Address;Aerobic Exercise;Area;arm;arm function;Back;behavior measurement;Behavioral;behavioral outcome;Bilateral;Brain;Chronic;chronic stroke;Clinical Trials;computerized data processing;constraint induced movement therapy;Control Groups;Data;Data Analyses;Data Collection;design;disability;Dose;Educational Intervention;effective therapy;Equipment;experience;experimental group;experimental study;follow-up;Frequencies;functional improvement;functional restoration;Funding;Goals;Hand;Hand functions;hemiparesis;Hour;Human;Human Resources;Impairment;improved;Individual;informal learning;insight;Intervention;Intervention Trial;Ipsilateral;Kinesiology;knowledge base;Laboratories;Learning;Manuscripts;Measures;Methods;Motor;motor function improvement;motor recovery;Movement;Nervous System;Nervous System Disorder;Neurologic;neurological rehabilitation;neuromechanism;Neuronal Plasticity;neurophysiology;noninvasive brain stimulation;Outcome;Participant;Persons;Physical therapy;Pilot Projects;post intervention;post stroke;Preparation;Prevalence;Process;Publishing;Quality of life;Randomized;Recovery;Recovery of Function;recruit;Rehabilitation therapy;Reporting;Research;Rest;Robotics;Secondary to;Stroke;stroke hemiparesis;stroke rehabilitation;stroke survivor;Structure;Techniques;Testing;Therapeutic;Therapeutic Intervention;Time;Training;Training Programs;Transcranial magnetic stimulation;treatment arm;treatment effect;Treatment Efficacy;treatment optimization;Universities;Upper Extremity;upper limb hemiparesis;Work;Wrist

PROJECT_TITLE: Effects of Bilateral Motor Priming and Task Specific Training on Corticomotor Excitability and Transcallosal Inhibition in People with Upper Limb Hemiparesis Secondary to Stroke


ORG_DEPT: ANESTHESIOLOGY

PHR: Public Health Relevance Statement The proposed research is relevant to public health because this project will evaluate cerebroprotective effects of promising therapeutic interventions in ischemic stroke. This is relevant to the NIH’s mission because knowledge obtained from the proposed research will be the basis for potential clinical trials to improve long-term neurologic function of stroke survivors, which will advance the Nation’s capacity to protect and improve health.

PI_NAMEs: SHENG, HUAXIN  (contact);YANG, WEI

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute;Adjuvant;Affect;Age;Animal Behavior;Animal Model;Animals;Behavior;behavior test;Biological;Blinded;Brain;Brain Injuries;brain tissue;Cephalic;cerebroprotection;Clinical;Clinical Trials;clinically relevant;Collaborations;combat;comorbidity;Custom;Data Analyses;Data Reporting;data sharing;Dedications;design;disease model;drug testing;effective intervention;efficacy evaluation;efficacy testing;Eligibility Determination;Ensure;Equipment;experience;Experimental Designs;experimental study;Filament;Freezing;Goals;Guidelines;Health;Human Resources;Hypertension;Image;improved;Infarction;Infrastructure;Institution;Intervention;intervention effect;Ischemia;Ischemic Stroke;Knowledge;Laboratories;Long-Term Effects;Magnetic Resonance Imaging;Mechanics;Medical;meetings;Metabolic;Middle Cerebral Artery Occlusion;Mission;Modeling;Monitor;Mus;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;Nervous System Physiology;Neurologist;Operative Surgical Procedures;Outcome Assessment;Outcome Measure;Physiology;pre-clinical;pre-clinical assessment;preclinical evaluation;preclinical imaging;Preclinical Testing;Procedures;Protocols documentation;provider intervention;Public Health;public health relevance;Qualifying;Quality of life;Randomized;Rattus;recruit;Reperfusion Injury;Reperfusion Therapy;Research;Research Infrastructure;Research Personnel;Resources;response;Rodent Model;Scientist;sex;Site;skills;Statistical Methods;Stroke;stroke model;stroke outcome;stroke patient;stroke survivor;stroke therapy;stroke trials;success;Testing;Therapeutic;Therapeutic Intervention;Thrombectomy;Tissues;Training;Treatment Efficacy;United States;United States National Institutes of Health;Universities;Work;Writing

PROJECT_TITLE: Duke Testing Site for Stroke Preclinical Assessment Network


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Human cytomegalovirus (HCMV) infects the majority of people, and like all herpesviruses, remains with an individual for life. Following initial infection, HCMV remains quiet, although during circumstances that affect one’s immune system, the virus can reawaken from this silent state, which often leads to disease. In this proposal, we will interrogate the underlying biological mechanisms by which HCMV manipulates host cell signaling pathways to balance between the quiescent and reawakening stages of infection.

PI_NAMEs: O'CONNOR, CHRISTINE M (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Adult;Affect;Attenuated;Binding;Biological;Biological Models;Biological Process;Biology;cell growth regulation;Cell Line;Cells;cellular targeting;Child;Chromatin;Coupled;CREB1 gene;Cues;Cytomegalovirus;Cytomegalovirus Infections;Data;derepression;Development;Disease;Enhancers;Ensure;Environment;Equilibrium;Event;experimental study;Fetal Development;Foundations;FRAP1 gene;Future;G-Protein-Coupled Receptors;gene product;gene repression;Genetic Transcription;Hematopoietic;Hematopoietic stem cells;Herpesviridae;Human;Immune system;Immunocompetent;Immunologic Surveillance;immunological status;Immunologics;In Vitro;Individual;Infection;latent infection;latent virus activation;Life;Lytic;Lytic Phase;lytic replication;Maintenance;Mediating;Modeling;Molecular;mortality;novel;novel strategies;novel therapeutics;organ transplant recipient;Outcome;pathogen;Pathway interactions;Periodicals;Persons;Phase;Population;preservation;prevent;Primary Infection;Process;promoter;Publishing;reactivation from latency;receptor function;Recombinants;recruit;Regulation;Repression;Research;Secure;SETDB1 gene;Signal Pathway;Signal Transduction;Stress;System;Testing;Time;Transactivation;transcription factor;Transcription Factor AP-1;United States;Viral;Viral Proteins;Virus;Virus Latency

PROJECT_TITLE: HCMV GPCR functions during latency and reactivation

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Data Science;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE  `Phenotyping Heart Failure through Analysis of Secondary Data' will advance personalization of heart failure management by a) identifying important heart failure subpopulations and b) developing highly accurate models predicting prognosis and targeted treatment response. We will accomplish this by applying artificial intelligence and machine learning analysis to large, well-described datasets from clinical trials, observational studies, and real-world electronic health records. This design will produce robust, reusable predictive and biological models of heart failure that can be delivered directly to doctors and patients via implementation in the electronic health record.

PI_NAMEs: KAO, DAVID PETER (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Artificial Intelligence;Biological Markers;Biological Models;Cardiac;Cessation of life;Characteristics;Clinical;clinical application;Clinical Data;clinical data warehouse;clinical practice;Clinical Research;clinical risk;Clinical Trials;cohort;Colorado;comorbidity;Complex;Coupled;Data;data harmonization;data resource;Data Set;Data Sources;design;Development;Diagnosis;Disease;diverse data;Electronic Health Record;epidemiology study;Event;Framingham Heart Study;Functional disorder;Future;Goals;Guidelines;health disparity;Health system;Heart failure;Hospitalization;improved;Individual;individual patient;Industry;insight;Intervention;Knowledge;Left Ventricular Ejection Fraction;Linear Models;Machine Learning;machine learning method;machine learning model;Medical;Meta-Analysis;Methods;model generalizability;Modeling;novel;Observational Study;Outcome;patient population;Patient Selection;Patients;Patterns of Care;Performance;Phenotype;Physiological;point of care;Population;predict clinical outcome;prediction algorithm;predictive modeling;Predictive Value;Prognosis;randomized, clinical trials;Regression Analysis;Resources;Risk Factors;secondary analysis;study population;supervised learning;Survival Analysis;survival prediction;targeted treatment;Testing;treatment response;Universities;unsupervised learning;Validation;virtual

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Project Narrative All living systems require protein synthesis of messenger RNAs, but unfortunately there are limited techniques to study this universal and highly dynamic process in living cells. The proposed work develops novel applications of full-length messenger RNA sequencing technologies for the study of protein synthesis, with the goal of enabling researchers and clinicians to readily visualize, study, and understand protein synthesis. Resulting technologies will be broadly applicable to the study of human health and disease, in model systems as well as medically relevant settings.

PI_NAMEs: ARRIBERE, JOSHUA  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Affect;Algorithms;base;Behavior;Binding;Biological Models;Biology;Cells;Chemicals;clinical application;Complex;Computational algorithm;Data;Detection;Development;Devices;Diagnostic;Disease;Equipment;Free Ribosome;Frequencies;Goals;Health;Human;improved;In Vitro;in vivo;Individual;interest;Investigation;Laboratories;Length;Life;markov model;Measurement;Medical;Messenger RNA;Methods;model organism;Modeling;Modification;Monitor;mRNA sequencing;mRNA Translation;nanopore;novel;Nucleic acid sequencing;Organism;Performance;Phenotype;Polyribosomes;Population;Process;Protein Analysis;Protein Biosynthesis;Protein Isoforms;Protocols documentation;Reagent;Research Personnel;Ribosomal Proteins;ribosome profiling;Ribosomes;RNA;Sampling;Scientist;sequencing platform;single molecule;Site;System;Techniques;Technology;Time;tool;Transcript;transcriptome;transcriptome sequencing;translation assay;Translations;Visualization;Work

PROJECT_TITLE: Polysome Shadowing

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


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;Caregiving Research;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Palliative Care;Prevention;Social Determinants of Health;Violence Research

ORG_CITY: Waltham

ORG_NAME: EDUCATION DEVELOPMENT CENTER, INC.

PHR: Project Narrative Elder mistreatment (EM) is a prevalent and devastating public health issue that affects an estimated one in ten older adults in the US and up to 55% of older adults with dementia. Currently, due to lack of basic research on the topic, there are no EM screening tools designed specifically for persons with dementia. This project seeks to leverage existing data on a well-characterized sample of older adults with dementia to provide the basic evidence needed for the subsequent development, refinement, and adaptation of tools for screening and responding to EM in the growing population of people with dementia.

PI_NAMEs: LEES HAGGERTY, KRISTIN  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Active Learning;Address;Affect;Aging;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Applied Psychology;Area;Basic Science;Behavioral Model;Behavioral Symptoms;care providers;caregiver depression;caregiver strain;Caregivers;caregiving;Caring;Characteristics;Clinical;Clinical Trials Design;Code;community setting;cost;Cross-Sectional Studies;Data;Data Set;Databases;Dementia;dementia care;Dementia caregivers;demographics;Dependence;design;Development;Doctor of Philosophy;Education;Elder Abuse;Ethics;evidence base;experience;Family;Focus Groups;Frequencies;Future;Generations;Goals;Grant;Health;Health Policy;Health Professional;Health Psychology;High Prevalence;Impaired cognition;implementation science;improved;insight;Intervention;Knowledge;Lead;Logistic Regressions;longitudinal dataset;loved ones;maltreatment;Managed Care;Manuscripts;Measures;Medical Records;Mental Depression;Mentors;Mentorship;Methodology;Modeling;modifiable risk;Modification;older adult;Outcome;patient health information;Patients;Persons;Policy Making;Population;population health;Positioning Attribute;Prevalence;prevent;Primary Care;primary care provider;Productivity;programs;protective factors;Provider;Public Health;Records;Research;Research Personnel;Research Project Grants;response;Risk;Risk Factors;Safety;Sampling;Science;screening;Screening procedure;Severities;Severity of illness;skills;sociodemographics;Specialist;Subgroup;therapy development;tool;Training;United States;United States National Institutes of Health;Work;Writing

PROJECT_TITLE: Characterizing Elder Mistreatment Among Older Adults with Dementia

STUDY_SECTION: AGCD

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Prevention;Social Determinants of Health;Substance Misuse

PHR: Public Health and Relevance Young men who have sex with men (YMSM) are the largest HIV transmission group in the U.S. and are the only group were rates of diagnoses are increasing. Non-injection drug use is an important risk factor for HIV infection in this group. The objective of this proposal is to sustain and enhance a large and innovative cohort of YMSM and their serious sexual partners in order to delineate multilevel influences on HIV and substance use. This cohort will serve as a strong resource platform for a wide range of future innovative research efforts and will inform implementation and optimization of HIV and drug abuse interventions for YMSM.

PI_NAMEs: MUSTANSKI, BRIAN  (contact)

PROGRAM_OFFICER_NAME: DUNSTON, SHEBA KING

PROJECT_TERMS: 20 year old;Address;Adolescence;Adolescent and Young Adult;Adult;Age;Age Years;aging related;Agreement;AIDS prevention;Area;Behavior;biobehavior;Biological;Biological Markers;Biological Process;cardiovascular disorder risk;Caring;Cells;Characteristics;Chicago;Clinical;cohort;Cohort Studies;comorbidity;Continuity of Patient Care;cooking;County;Coupled;Data;Development;Diagnosis;Disparity;Disparity population;Drug abuse;drug of abuse;Drug usage;emerging adult;Enrollment;Epidemic;Epigenetic Process;falls;Fentanyl;Funding;Future;Grant;Health;health disparity;HIV;HIV diagnosis;HIV disparities;HIV Infections;HIV risk;Immune;implementation barriers;implementation research;implementation science;improved;Incidence;Infection;Inflammation;Injectable;innovation;insight;interest;Intervention;late life;Latino;Location;Longitudinal Studies;marijuana decriminalization;marijuana legalization;Measures;member;men of color;men who have sex with men;Methods;Midwestern United States;Minority;minority stress;minority stressor;Modeling;Monitor;Morbidity - disease rate;National Institute of Drug Abuse;novel;Outcome;Output;Participant;Pathogenicity;Pattern;Pharmaceutical Preparations;Phylogenetic Analysis;Physiologic pulse;Physiological;Play;pre-exposure prophylaxis;Prevention;Preventive;Process;Productivity;protective factors;Public Health;Publications;Radar;Recording of previous events;recruit;repository;Research;Research Design;Research Personnel;Resources;response;Risk;Risk Behaviors;Risk Factors;Sampling;Science;Sentinel Surveillance;sex;Sexual Partners;social;social stigma;Specimen;Stress;substance use;success;systemic inflammatory response;Training;transmission process;trend;United States National Institutes of Health;uptake;Vacuum;Viral;Work;young men who have sex with men

PROJECT_TITLE: Multilevel Influences on HIV and Substance Use in a YMSM cohort


ED_INST_TYPE: SCH OF HOME ECON/HUMAN ECOLOGY

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

ORG_CITY: FORT COLLINS

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: COLORADO STATE UNIVERSITY

PHR: PROJECT NARRATIVE The ability to drive a car safely is critical for older adults to maintain functional independence and is often compromised when age-related neurological disorders occur. The proposed studies will pioneer the investigation of behavioral fluctuations in motor and cognitive performance to identify and predict driving deficits in stroke survivors with mild cognitive impairment. This research will lay the groundwork to identify sensitive, behavioral markers that provide early detection of decline in driving function.

PI_NAMEs: LODHA, NEHA  (contact)

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: Acceleration;Affect;age related;Aging;aging population;aging related;Alzheimer's Disease;Alzheimer's disease related dementia;Ankle;Automobile Driving;baby boomer;behavior measurement;Behavioral;Blood Vessels;career;Clinical Data;Clinical Trials;Clinical Trials Design;Cognitive;Cognitive aging;cognitive development;cognitive performance;cognitive process;Cognitive Science;cognitive task;cognitive testing;Colorado;Complex;Computers;Data;Dementia;Development;Diagnosis;driving performance;Early Diagnosis;Elements;Executive Dysfunction;Exercise;experience;functional decline;Functional impairment;functional independence;Goals;Health;Impaired cognition;impaired driving performance;Impairment;improved;indexing;Individual;individual variation;innovation;interest;International;Intervention;Investigation;Knowledge;Licensing;life span;Measures;Mentors;Methodology;mild cognitive impairment;Modeling;Motor;motor control;motor impairment;Movement;neglect;Nervous System Disorder;Nervous System Trauma;Neurologic;Neurologist;neurophysiology;novel;novel strategies;older adult;Outcome;Participant;Performance;post stroke;pre-clinical;predictive marker;primary outcome;Process;processing speed;professor;Psychologist;Quality of life;Research;Research Personnel;Science;statistics;Stroke;stroke survivor;Survivors;System;Technology;Testing;Training;Universities;Work

PROJECT_TITLE: Investigating cognitive-motor variability to predict driving performance in stroke survivors with MCI

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE This proposal will investigate astrocyte-mediated neuron cell death in glaucoma, a slowly progressive neurodegenerative disease of aging that affects vision. These studies will deliver a comprehensive understanding of astrocyte-neuron interactions during disease, highlight why neurons are susceptible to death, and characterize how specific lipids secreted by a subset of astrocytes drives death of neurons, highlighting possible novel therapeutic targets. Our goal is to work towards innovative future treatments that target astrocytes in glaucoma and other neurodegenerative diseases of aging.

PI_NAMEs: LIDDELOW, SHANE  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: activating transcription factor 3;Acute;Address;Affect;aging related disease;Apoptosis;Astrocytes;Automobile Driving;Autopsy;Axon;axon injury;BBC3 gene;biological adaptation to stress;Blindness;CASP3 gene;Cell Death;Cell Death Induction;cell type;Cells;Central Nervous System;Cessation of life;Characteristics;Chronic;combinatorial;CRISPR screen;Development;Disease;Electrophysiology (science);endoplasmic reticulum stress;Enzymes;Excision;Eye;Eye diseases;Eye Injuries;Future;Genes;Genetic;Glaucoma;Goals;Health;Human;Immune response;improved;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammation;Injury;innovation;insight;ischemic injury;Knock-out;knockout animal;Knockout Mice;Lipids;Maintenance;Maps;Mediating;Mediator;Modeling;mouse model;Mus;Nerve Crush;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuronal cell body;Neurons;neurotoxic;neurotoxicity;Neurotoxins;neurotransmission;neurotrophic factor;new therapeutic target;Nonesterified Fatty Acids;novel;novel strategies;Optic Nerve;Optic Nerve Injuries;Pathologic;Pathway interactions;Patients;Peripheral;pharmacologic;Phenotype;Phosphotransferases;Physiologic Intraocular Pressure;Physiological;Predisposition;preservation;prevent;Production;protein activation;protein kinase R;Proteins;Puma;regeneration following injury;Reporting;Research;Resistance;response to injury;Retina;Retinal Degeneration;Retinal Ganglion Cells;Rodent Model;Role;saturated fat;Stress;Synapses;Testing;Thalamic structure;Time;Tissues;tool;Toxic effect;virtual reality system;Vision;Visual Acuity;Western Blotting;Work

PROJECT_TITLE: Neurotoxicity of Reactive Astrocyte-secreted Lipids in Neurodegenerative Disease


NIH_SPENDING_CATS: Asthma;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Human Genome;Lung;Precision Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE  People with asthma and chronic bronchitis suffer due to excessive amounts of lung mucus and persistent inflammation, and have no available treatment options. In this proposal, we will address this problem by studying how memory of past inflammation in lung basal stem cells may drive chronic inflammation and excessive mucus. Findings from this proposal have great potential to improve the lives of people with excessive mucus production due to lung disease, and may provide a basis to cure asthma.

PI_NAMEs: PEZZULO, ALEJANDRO ANTONIO (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Acute;Address;Affect;Air;Airway Disease;airway epithelium;airway inflammation;Anti-Inflammatory Agents;Area;Asthma;asthmatic;Basal Cell;biobank;Biological Markers;Cause of Death;cell type;Cells;Chromatin;Chronic;Chronic Bronchitis;chronic inflammatory lung disease;clinical practice;curative treatments;cytokine;Data;Development;Disease;Disease susceptibility;Drug Targeting;Environment;epigenetic memory;Epigenetic Process;epigenome;epigenomics;Epithelium;Failure;Genetic;Genetic Transcription;Goals;Goblet Cells;Health;Hospitalization;HSP 90 inhibition;Human;IL17 gene;Immune;Immune system;Immunologic Memory;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;inflammatory lung disease;Inhalation;innate immune function;inter-individual variation;Ion Transport;Life;Liquid substance;Lung;Lung Diseases;Memory;memory acquisition;Metaplasia;microorganism;Mission;Mitotic;Modification;Mucous body substance;mucus hypersecretion;National Heart, Lung, and Blood Institute;Nose;novel;particle;Persons;Phenotype;postmitotic;precision medicine;Predisposition;Production;Pulmonary Inflammation;Quality of life;Research;resilience;Resistance;Respiratory Failure;response;Severities;Smoking;stem cells;Testing;therapeutic target;TNF gene;Tracheobronchial;transcriptome;transcriptomics;Translating;Virus

PROJECT_TITLE: Epigenetic mechanisms of inflammatory memory propagation in human airway epithelia

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Gene Therapy;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BALTIMORE

ORG_DEPT: PSYCHIATRY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: NARRATIVE It has been demonstrated that CAG repeat targeting phosphorodiamidate morpholino oligomers (PMOs) and brain derived neurotrophic factor (BDNF) are therapeutically beneficial for Huntington's disease, while their potential clinical application may be limited by their inability to cross blood brain barrier (BBB). However, human iPSCs produce abundant exosomes with considerable BBB crossing potential. We propose to generate engineered iPSC-derived exosomes for brain targeted delivery of PMOs as well as BDNF, and further evaluate its efficacy in suppression of mutant Huntingtin protein and neurotoxicity in HD striatal neuron and zQ175 knock- in mouse model.

PI_NAMEs: LI, PAN  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Affect;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Behavioral;Binding;blood-brain barrier crossing;blood-brain barrier penetration;Brain;Brain Diseases;Brain region;Brain-Derived Neurotrophic Factor;CAG repeat;Cell secretion;Cells;Chemicals;Clinical;clinical application;clinical translation;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;Corpus striatum structure;Cyclic GMP;Dedications;delivery vehicle;Development;Disease;disease phenotype;effective therapy;efficacy evaluation;efficacy study;Emotional;Encapsulated;Engineering;exosome;extracellular;Foundations;Future;Genes;genome editing;Glycoproteins;homologous recombination;Human;Human Engineering;human induced pluripotent stem cells;Huntington Disease;Huntington gene;in vivo;individual patient;induced pluripotent stem cell;Injections;Investigation;Knock-in Mouse;Length;manufacture;Mesenchymal Stem Cells;mouse model;Movement;Mus;mutant;Nerve Growth Factors;Neurodegenerative Disorders;Neurons;neurotoxic;neurotoxicity;neurotrophic factor;novel;novel therapeutic intervention;overexpression;Pathway interactions;patient derived induced pluripotent stem cells;Penetration;Peptides;phosphorodiamidate morpholino oligomer;polyglutamine;preclinical development;prevent;Procedures;Production;Property;Prosencephalon;Proteins;Rabies;Reporting;RNA;RNA Splicing;Small Interfering RNA;Solid;Source;Spinal Puncture;success;Surface;targeted delivery;Testing;Therapeutic;Therapeutic Studies;Toxic effect;Translating;Translations;Treatment Efficacy;Viral

PROJECT_TITLE: Brain-targeted delivery of therapeutic molecules by exosomes derived from engineered human iPS cells: a potential therapeutic approach for Huntington's disease


ORG_CITY: CLEVELAND

PHR: PROJECT NARRATIVE – O’CONNOR, CHRISTINE M. Human cytomegalovirus (HCMV) infects the majority of people, and like all herpesviruses, remains with an individual for life. Following initial infection, HCMV remains quiet, although during circumstances that affect one’s immune system, the virus can reawaken from this silent state, which often leads to disease. In this proposal, we will interrogate the underlying biological mechanisms by which HCMV manipulates host cell signaling pathways to help the virus maintain the quiescent stage of infection.

PROJECT_TERMS: Adult;Affect;Anti-viral Therapy;Attenuated;attenuation;Binding;Biological;Biological Models;Biological Process;Biology;Cells;cellular targeting;Child;Chromatin;Complex;Coupled;Cytomegalovirus;Cytomegalovirus Infections;Data;Development;Disease;Early Promoters;EPHA2 gene;experimental study;Fetal Development;Foundations;Future;G-Protein-Coupled Receptors;Gene Silencing;Genes;Genetic Transcription;Goals;Hematopoietic;Hematopoietic stem cells;Herpesviridae;Human;Immune system;Immunocompetent;Immunocompromised Host;Immunologics;improved;In Vitro;Individual;Infection;Integration Host Factors;Knowledge;latent infection;Life;Lytic;Maintenance;MAP Kinase Gene;Mediating;MEKs;Modeling;Molecular;Morbidity - disease rate;mortality;mutant;novel;novel strategies;novel therapeutics;organ transplant recipient;Outcome;pathogen;Pathogenesis;Pathway interactions;Persons;Population;prevent;Primary Infection;Production;promoter;reactivation from latency;Recombinants;recruit;Repression;Signal Pathway;Signal Transduction;Signaling Molecule;Stress;Supporting Cell;Testing;transcription factor;Transcription Factor AP-1;United States;Up-Regulation;Viral;Virus;Virus Activation;Virus Latency;Work;YY1 Transcription Factor

PROJECT_TITLE: Manipulation of host factors that promote HCMV latency

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


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;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Health Disparities and Racial or Ethnic Minority Health Research;Lymphatic Research;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Increased levels of a protein fragment called amyloid-β (Aβ) are associated with greater risk of Alzheimer’s disease, so an intervention that reduces Aβ levels may help prevent the disease. However, the field lacks nonpharmaceutical, safe and affordable approaches to reduce Aβ. Our initial findings indicate that daily sessions involving slow-paced breathing decrease levels of Aβ in healthy adults’ blood; this project aims to investigate the mechanisms and the impact on cognition in African Americans and European Americans aged 50-70.

PI_NAMEs: MATHER, MARA  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Abeta synthesis;Acceleration;active control;active control group;Adrenergic Agents;Adult;Affect;African American;African American population;Age;aged;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;American;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Amyloid deposition;Amyloidosis;arm;Baroreflex;Biofeedback;Biological Markers;Blood;Blood Vessels;Brain;Brain Injuries;Breathing;cerebrospinal fluid flow;Clinical Trials;Cognition;Cognitive;cognitive task;cohort;Discrimination;Disease;Double-Blind Method;Drug Targeting;Early Intervention;ethnic difference;Ethnic Origin;European;Foundations;Frequencies;Future;Genetic Transcription;glymphatic clearance;glymphatic system;Heart Rate;heart rate variability;Hippocampus;Impaired cognition;Impairment;improved;Influentials;innovation;Intervention;intervention cost;intervention effect;Learning;Measures;Mediating;middle age;Modeling;neocortical;Neurobiology;noradrenergic;older adult;Outcome;Participant;Pathologic;Pathologic Processes;Pathway interactions;Patients;Perception;Performance;personalized strategies;Pharmaceutical Preparations;Phase;Phase II Clinical Trials;Plasma;Play;post intervention;pre-clinical;prevent;Protein Fragment;Proteins;Randomized;randomized trial;recruit;Reporting;Research;Risk;sex;side effect;Signal Transduction;success;Synaptic plasticity;System;tau Proteins;Testing;Training;Vagus nerve structure;wasting;young adult

PROJECT_TITLE: Effects of Resonance-Frequency Breathing on Preclinical Alzheimer’s Disease Biomarkers and Cognition

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-H(55)R]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Radiation Oncology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: UROLOGY

PHR: PROJECT NARRATIVE The process of salivation, which aids digestion and performs an indispensable role in lubricating and protecting the oral cavity, is disrupted in several conditions including radiation therapy for head-and-neck cancer. We have discovered a two-way signaling circuit between salivary gland surface cells and underlying support cells, and have found that activity of this circuit is essential for salivary gland maintenance and function. In our proposed research we will test the possibility that precise activation of this circuit may protect against and stimulate recovery from radiation-induced salivary gland damage.

PI_NAMEs: BEACHY, PHILIP A (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: Ablation;Acinar Cell;Adult;Adverse effects;Aging;Antidotes;Artificial Saliva;Atrophic;Bladder;cancer therapy;Cell Lineage;Cell Physiology;Cell surface;cell type;Cells;Clinical;Data;Deglutition;Digestion;Disease;Engineering;Epigenetic Process;Epithelial Cells;epithelial stem cell;Epithelium;Erinaceidae;Esthesia;Exposure to;Family member;Feedback;Functional disorder;Genetic;Genetic Models;genome-wide;Goals;Head and Neck Cancer;Homeostasis;Host Defense;Human;In Situ Hybridization;in vivo;Injury;injury and repair;Intestines;irradiation;Knowledge;Ligands;Macrophage;Maintenance;Major salivary gland structure;Mediating;Mesenchymal;Mesenchyme;Methods;Minor;Molecular;Molecular Conformation;mouse genetics;mouse model;Mus;Myoepithelial cell;nanobodies;Natural regeneration;nerve supply;novel strategies;Oral;Oral cavity;Oral health;Oral mucous membrane structure;Organ;Parotid Gland;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Physiological;Play;preservation;Process;progenitor;programs;Radiation;Radiation Injuries;radiation recovery;Radiation therapy;receptor;Recovery;regenerative;Regenerative capacity;repaired;Research;Residual state;Resolution;response;restoration;Risk;Role;Saliva;saliva secretion;salivary cell;Salivary Gland Tissue;Salivary Glands;side effect;Signal Pathway;Signal Transduction;Signaling Protein;single cell ATAC-seq;Sjogren's Syndrome;smoothened signaling pathway;Speech;Submandibular gland;Supporting Cell;Taste Perception;Testing;Therapeutic;therapeutic target;tissue repair;Tissues;transcriptomics;tumor;unpublished works;Well in self;Work;Xerostomia

PROJECT_TITLE: Salivary gland response to Desert hedgehog signaling as an antidote to damage from therapeutic radiation

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


ED_INST_TYPE: SCHOOLS OF NURSING

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

PHR: PROJECT NARRATIVE This study addresses a critical public health need to discover ways to delay functional disability related to Alzheimer’s disease and related dementias. The RSELVES Study will examine patterns of engagement in physical and social activities over time among older adult spouses/partners in South Texas and Oregon using digital data from their homes and smartphones. We will determine the extent to which these dyadic patterns of activity engagement and support from spouses may help delay or accelerate functional decline (and impact well-being) among older adults at risk of developing Alzheimer’s disease and their spouses/partners.

PI_NAMEs: ANDERSON, LYNDSEY MEDORA (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Acceleration;Activities of Daily Living;Address;Aging;aging and technology;Alzheimer's Disease;Alzheimer's disease related dementia;Attention;Cellular Phone;Clinical;Clinical assessments;Cognition;Cognitive;cohort;Compensation;Computers;cooking;Couples;daily functioning;Dementia;dementia risk;Development;Diagnosis;diagnostic criteria;digital;digital data;Disablement;Distress;Evaluation;experience;Family member;follow-up;Frequencies;functional decline;Functional dependence;functional disability;Functional impairment;functional loss;Goals;Health;Heterogeneity;high risk;Home;Hygiene;Impaired cognition;Impairment;Individual;innovation;Life;Long-Term Care;Longitudinal Studies;Maintenance;Measures;member;Mental Health;Modeling;Moods;Natural History;Neurodegenerative Disorders;novel;novel strategies;older adult;Older Population;Oregon;Pattern;Personal Satisfaction;Persons;Phase;Physical activity;pre-clinical;preservation;Process;prospective;Proxy;Public Health;Quality of life;recruit;remote assessment;remote sensing;Reporting;Research;Risk;sensor;social;South Texas;Spouses;Surveys;Symptoms;Technology;technology platform;theories;Time;walking speed

PROJECT_TITLE: The RSELVES Study: Remote Sensing of (older adult partners') Engagement in Life and Variability in Everyday Support

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Cardiovascular;Social Determinants of Health

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Narrative This program will continue to provide short-term research training experiences for undergraduate students from groups underrepresented in the biomedical sciences workforce. The focus is on research training related to the cardiovascular system with an emphasis on teams of investigators involved in translational research, taking advantage of the broad, multidisciplinary cardiovascular research ongoing at Wake Forest School of Medicine (WFSM). The goals are to maintain student interest in a Bachelor’s degree in a MSTEM field and to foster transition to advanced degrees as a means of increasing biomedical science workforce diversity.

PI_NAMEs: DIZ, DEBRA I (contact);SOTO PANTOJA, DAVID R.

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Address;Aging;Animals;Bachelor's Degree;Basic Science;Biological Markers;Biomedical Research;biomedical scientist;Blood Pressure;Blood Vessels;Cardiac;Cardiovascular Diseases;Cardiovascular system;career;Career Choice;Clinical Research;clinically relevant;Collaborations;Communication;Communities;Complement;Critical Thinking;Degree program;Development;Diabetes Mellitus;Dimensions;disability;Disadvantaged;Doctor of Philosophy;doctoral student;Educational process of instructing;Engineering;Environment;equity, diversity, and inclusion;Ethnic Origin;Evaluation;Event;expectation;experience;Exposure to;Extramural Activities;Faculty;fetal;Fostering;Goals;graduate student;Health Disparities Research;health disparity;health equity;Health Occupations;Heart Diseases;Heart Rate;Housing;Human;Hypertension;improved;Individual;Institution;Interdisciplinary Study;interest;Interview;Investigation;Journals;Kidney;Kidney Diseases;Laboratories;Letters;Life;life span;Literature;Mathematics;matriculation;Measurable;Medical;medical schools;Medical Students;Medicine;member;Mentors;Metabolism;multidisciplinary;Neonatal;next generation;Obesity;Oncology;Oral;Outcome;Participant;Pathway interactions;peer coaching;Peer Review;Positioning Attribute;Post Graduate Year;Postbaccalaureate;Postdoctoral Fellow;posters;precision medicine;Productivity;programs;Publications;racial minority;recruit;Reproducibility;Research;research faculty;Research Personnel;Research Project Grants;Research Training;Resources;responsible research conduct;Rural;satisfaction;Science;Scientist;senior faculty;skill acquisition;skills;social;Social support;Structure;student participation;Students;success;summer research;symposium;Technology;Time Management;Training;Translational Research;Transportation;ultrasound;undergraduate research experience;undergraduate student;Underrepresented Minority;Underrepresented Populations;urban setting;Vascular Diseases;Vocational Guidance;Woman;women faculty;Work;Writing

PROJECT_TITLE: Excellence in Cardiovascular Sciences Summer Research-Renewal


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Diabetes;Dissemination and Implementation Research;Health Services;Networking and Information Technology R&D (NITRD);Patient Safety;Primary Health Care;Telehealth

PHR: Clinic-based chronic disease management is insufficient for some patients, resulting in clinic-refractory chronic diseases. Mobile monitoring-enabled telehealth can improve patient self-management and guide provider care outside of the clinic setting, but is not used in practice due to key evidence gaps. This proposal will address this pressing clinical problem by overcoming critical barriers to use of mobile monitoring-enabled telehealth for clinic-refractory diabetes and hypertension.

PI_NAMEs: CROWLEY, MATTHEW J.;SHAW, RYAN JEFFREY (contact)

PROGRAM_OFFICER_NAME: MCNAMARA, KAREN MARIE

PROJECT_TERMS: active comparator;Address;Blood Pressure;Care given by nurses;care providers;care seeking;Caring;Characteristics;Chronic Disease;Clinic;Clinical;clinical practice;cohort;Cohort Studies;comorbidity;compare effectiveness;comparison intervention;Complex;cost;Data;data integration;Diabetes Mellitus;Diet;Disease;Disease Management;Dissemination and Implementation;Effectiveness;Electronic Health Record;Emergency Situation;Evaluation;Event;Exhibits;Glycosylated hemoglobin A;health data;Health system;high risk;high risk population;Hospitalization;Hypertension;implementation barriers;implementation facilitators;improved;innovation;Insulin;Intervention;intervention cost;Interview;Measures;Medication Management;Methods;Modeling;Monitor;Non-Insulin-Dependent Diabetes Mellitus;novel;Nurses;Outcome;patient safety;patient-provider contact;Patients;Pharmaceutical Preparations;Population;predictive tools;prevent;primary outcome;Process;psychosocial;randomized trial;Refractory;Regimen;Regulation;Reimbursement Mechanisms;Risk;secondary outcome;Self Management;skills;Stream;Subgroup;System;Technology;telehealth;telemonitoring;tool;treatment as usual;Uncertainty;Visit;Weight;Work

PROJECT_TITLE: EXpanding Technology-Enabled, Nurse-Delivered Chronic Disease Care (EXTEND)

STUDY_SECTION: CMPC

STUDY_SECTION_NAME: Clinical Management of Patients in Community-based Settings Study Section[CMPC]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Machine Learning and Artificial Intelligence;Orphan Drug;Prevention;Rare Diseases;Tuberculosis;Tuberculosis Vaccine;Vaccine Related

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: NARRATIVE: Tuberculosis remains among the most common causes of death from an infectious disease worldwide. This proposal will test a novel “enhanced prime and pull” strategy designed to enhance the efficacy of the current BCG vaccine against tuberculosis.

PI_NAMEs: FLYNN, JOANNE L. (contact);LIN, PHILANA LING

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: Acute Disease;acute infection;aerosolized;Aerosols;Agonist;Animal Model;Animals;Area;B-Lymphocytes;Bacille Calmette-Guerin vaccination;BCG Vaccine;Bioinformatics;biomarker identification;Blood;Cause of Death;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;cell type;Cells;Cessation of life;Communicable Diseases;comparative efficacy;comparison control;Control Groups;cytotoxic;cytotoxicity;Data;design;Disease;Dose;Frequencies;Genetic Transcription;Granuloma;HIV;Human;Immune;Immune response;immunogenicity;Immunologic Markers;Immunologics;Immunology;improved;Industry Collaboration;Infection;Infection prevention;insight;Interleukin-15;Intravenous;intravenous administration;Lung;Lung Diseases;Lymphocyte;Macaca mulatta;Machine Learning;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediastinal lymph node group;Mediating;Methods;Microbiology;Modeling;Modernization;Monitor;Mucosal Immune Responses;multidimensional data;mycobacterial;Mycobacterium tuberculosis;Myeloid Cells;nonhuman primate;novel;novel vaccines;Outcome;Pathology;PET/CT scan;Population;prevent;Prevention;Proliferating;Pulmonary Inflammation;Randomized;recruit;Regimen;Research;response;Role;Route;Scourge;single-cell RNA sequencing;Site;SIV;success;Surrogate Markers;T-Lymphocyte;Techniques;Testing;Tissues;tool;translation to humans;translational potential;Tuberculosis;Tuberculosis Vaccines;Vaccinated;Vaccination;vaccination outcome;vaccination protocol;vaccine efficacy;vaccine immunogenicity;vaccine strategy;vaccine-induced immunity;Vaccines;Virulent;X-Ray Computed Tomography

PROJECT_TITLE: Enhancing cytotoxic lymphocytes in a TB vaccine strategy

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Immunotherapy;Rare Diseases

ORG_CITY: BOSTON

ORG_DEPT: DENTISTRY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Oral cancer represents a significant societal burden. In this project, we propose to identify the key underlying causes of oral cancer by investigating changes in the chromatin environment brought about by an enzyme, lysine-specific demethylase 1 (LSD1). We anticipate that this study will increase knowledge about the biology of oral cancer, explore a synergistic combination of effective therapy, and lead to the development of novel treatment strategies for this pernicious disease.

PI_NAMEs: BAIS, MANISH  (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: Address;Animal Model;anti-cancer research;anti-PD-1;anti-PD-L1 antibodies;anti-PD1 therapy;Attenuated;attenuation;Biology;Breast;cancer stem cell;carcinogenesis;Carcinoma in Situ;cell type;Cells;Cessation of life;Chromatin;Clinical;clinically relevant;Collaborations;connective tissue growth factor;Data;design;Development;Disease;Dysplasia;effective therapy;Environment;Enzymes;Epidermal Growth Factor Receptor;Epigenetic Process;epigenome;Epithelium;experience;Family Felidae;Future;Genetic;Goals;high risk;histone demethylase;Human;IL-6 inhibitor;IL6 gene;Immune;immune checkpoint;Immunotherapy;in vivo;inhibitor;Interleukin-6;JAK2 gene;KDM1A gene;Keratin;Knockout Mice;Knowledge;Lead;Lesion;Leukoplakia;Malignant - descriptor;malignant mouth neoplasm;Malignant Neoplasms;malignant phenotype;Medicine;Modification;mouse model;mouth squamous cell carcinoma;Mus;Neoplasms;Nivolumab;Normal tissue morphology;novel;Nuclear;Oral;Oral cavity;oral tissue;Pathologic;Pathway interactions;patient derived xenograft model;Patients;PD-1 inhibitors;pharmacologic;Phenotype;Positioning Attribute;prevent;programmed cell death ligand 1;programmed cell death protein 1;programs;promoter;Proteomics;Publishing;Recurrence;Resistance;Role;Sampling;Signal Induction;Signal Transduction;single-cell RNA sequencing;STAT3 gene;stem;stem cells;Testing;Therapeutic;Therapeutic Studies;therapy resistant;Time;Tissue Sample;Tongue;Topical application;translational study;Translations;treatment strategy;tumor;tumor progression;United States;Up-Regulation;Work

PROJECT_TITLE: Mechanism of LSD1 Function and Its Therapeutic Application for Progressive Oral Malignancy

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ORG_CITY: HERSHEY

ORG_DEPT: PEDIATRICS

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Wiskott-Aldrich syndrome (WAS) is associated with high mortality from infections, autoimmunity, and cancer. We have uncovered a new mechanism for the causation of WAS, whose full delineation has the potential to identify a new biomarker and therapy for WAS.

PI_NAMEs: VYAS, YATIN M (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Actins;adaptive immune response;Affect;Antibody-mediated protection;Apoptosis;atopy;Autoimmune;Autoimmunity;B-Lymphocytes;Binding;Biological Markers;CD4 Positive T Lymphocytes;Cell Nucleus;Cell Physiology;Cells;Cellular Immunity;Chromatin;Clinical;clinical phenotype;congenital immunodeficiency;Coupled;Cytoplasm;Cytoskeleton;Data;Defect;Development;Diagnostic;Disease;disease model;DNA;DNA Damage;DNA Double Strand Break;DNA Polymerase II;Double Strand Break Repair;Ensure;Equilibrium;Etiology;Event;F-Actin;Fibroblasts;Fostering;Functional disorder;Gene Mutation;Genes;Genetic Transcription;Genome Stability;Genomic Instability;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Helper-Inducer T-Lymphocyte;Histones;Human;human disease;human model;Hybrids;immune function;Immune System Diseases;immunodeficiency;Immunologic Deficiency Syndromes;Infection;Inflammatory;Innate Immune Response;insight;Interferon Type II;Knowledge;Link;Location;Lymphocyte;Malignant lymphoid neoplasm;Malignant Neoplasms;Mediating;Messenger RNA;Monitor;mortality;mRNA Precursor;Nerve Degeneration;neural;novel;Nuclear;nucleic acid structure;Pathology;Pathway interactions;Patients;Phenotype;Physical condensation;Play;polymerization;Polymers;prevent;prognostic;Prognostic Marker;Protein Deficiency;Proteins;Publishing;repaired;Research;Research Support;RNA;RNA Splicing;Role;Severities;Severity of illness;Shapes;Signal Pathway;Single-Stranded DNA;SRSF2 gene;T-Lymphocyte;Testing;Th2 Cells;Therapeutic;Wiskott-Aldrich Syndrome;Wiskott-Aldrich syndrome protein

PROJECT_TITLE: Mechanisms of R loop-mediated genome instability in Wiskott-Aldrich syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-K(52)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Mental Health;Neurosciences;Prevention;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: The goal of the current application is to characterize functionally distinct non-coding regulatory elements in major neuronal types for which rare and common variant risk loci are most enriched in neuropsychiatric disorders, identify their target genes, and elucidate how noncoding variants affect the transcription of key genes for neuronal cell identity and activity-regulated signaling networks. The proposed research has the potential to develop an innovative approach and unravel the neurobiological functions of the vast but in the brain largely unexplored non-coding sequences of the human genome, which is relevant to the mission of NIH to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability.

PI_NAMEs: YANG, NAN  (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Affect;Alleles;artificial neural network;autism spectrum disorder;Autopsy;Binding;Biochemical;Biological;Biological Assay;Biological Models;Biological Process;Biology;Brain;Brain Diseases;brain tissue;Cell model;cell type;Cells;chromatin modification;chromosome conformation capture;Chromosome Mapping;cohort;Complex;Coupled;Data;Derivation procedure;Development;Diagnosis;disability;Disease;disorder risk;DNA Sequence;Elements;Enhancers;Epigenetic Process;epigenomics;Etiology;excitatory neuron;family burden;Foundations;Functional disorder;Future;Gene Expression;Genes;Genetic;Genetic Drift;Genetic Engineering;Genetic Transcription;genetic variant;Genome;Genome Mappings;genome wide association study;genome-wide analysis;Genomics;Glutamates;Goals;Heritability;Human;human disease;Human Genetics;Human Genome;human model;human pluripotent stem cell;improved;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;inhibitory neuron;innovation;insight;interdisciplinary approach;Investigation;Knowledge;Link;Maps;Measures;Mental disorders;Methodology;Mission;Molecular;Nervous System Disorder;Neurobiology;Neurons;neuropsychiatric disorder;next generation sequencing;novel;novel therapeutic intervention;novel therapeutics;Pluripotent Stem Cells;Population;prevent;Process;programs;promoter;Regulatory Element;Reporter;Research;Research Personnel;Resolution;Resources;Rest;Risk;risk variant;Role;Sampling;Schizophrenia;Signal Transduction;Societies;socioeconomics;Specificity;stem;stem cell technology;Stimulus;System;Technology;Testing;Tissues;transcription factor;Translating;United States National Institutes of Health;Untranslated RNA;Validation;Variant;Work

PROJECT_TITLE: Functional mapping of noncoding regulatory variants in human neuronal subtypes


ORG_CITY: PHILADELPHIA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Platelets are small circulating blood cells that are important in bleeding cessation, and in formation of blood clots that cause heart attacks and strokes which are a leading cause of morbidity and mortality in the United States. This project focuses on defining the mechanisms by which platelets and coagulation form clots and could lead to novel ways to prevent thrombotic disorders and have an impact in other disease states that involve platelets including Covid19.

PI_NAMEs: ESSEX, DAVID W (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: acute coronary syndrome;Address;Agonist;Antibodies;Anticoagulants;Binding;Blood Cells;Blood coagulation;Blood Platelets;Blood Vessels;Clot retraction;Coagulation Process;COVID-19;Cysteine;Disease;disulfide bond;disulfide bond reduction;endoplasmic reticulum glycoprotein p72;Endothelial Cells;Endothelium;Enzymes;Equilibrium;ERp57;Event;extracellular;Extracellular Protein;Family;Fibrin;Fibrinogen;Generations;Hemorrhage;Hemostatic function;Human;Immune checkpoint inhibitor;in vivo;Injury;insight;Integral Membrane Protein;Integrins;Isomerism;Knockout Mice;Lasers;Mass Spectrum Analysis;Mediating;member;Membrane;Modeling;Molecular Conformation;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Infarction;novel;oxidation;Pathway interactions;Phosphatidylserines;Platelet Activation;Platelet aggregation;Platelet Aggregation Inhibition;platelet function;prevent;Protein Disulfide Isomerase;Proteins;receptor;Recombinants;Regulation;Role;Signal Transduction;Site;Stroke;Sulfhydryl Compounds;Surface;Techniques;Thrombosis;Thrombus;translocase;United States;vascular injury;Vascular System;Wild Type Mouse;Work

PROJECT_TITLE: The Transmembrane Protein Disulfide Isomerase TMX1 Negatively Regulates Thrombosis

STUDY_SECTION: HTBT

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


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

ORG_CITY: EAST LANSING

ORG_DEPT: PSYCHOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because knowledge about sex-specific regulation of social play by oxytocin will advance our understanding of sex-specific regulation of behavior and will be informative for the social play deficits and the sex-biases in incidence, symptom severity, and treatment responses seen in social disorders, most notably in autism spectrum disorder. This knowledge may also be informative for sex- specific therapeutic uses of oxytocin-based agents in the treatment of social dysfunction. The proposed research is relevant to the mission of NIMH to transform the understanding and treatment of mental illnesses.

PI_NAMEs: VEENEMA, ALEXANDRA H. (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Adolescent;antagonist;ASD patient;autism spectrum disorder;autistic children;Behavior;Brain;Brain region;Cells;Child;Data;Dose;Drug Targeting;Electrophysiology (science);Etiology;Exhibits;extracellular;Female;gamma-Aminobutyric Acid;Genetic;Globus Pallidus;Goals;high reward;Human;improved;Incidence;individuals with autism spectrum disorder;innovation;insight;Knowledge;Life;male;Mediating;Mental disorders;Methods;Mission;National Institute of Mental Health;neural;neural circuit;Neural Pathways;Neurons;novel;Nucleus Accumbens;Outcome;Oxytocin;Oxytocin Receptor;paraventricular nucleus;Pathway interactions;Phenotype;Play;Population;Property;Public Health;rabies viral tracing;Rattus;Receptor Signaling;recruit;Regulation;Research;response;Rewards;Role;Severities;sex;Sex Bias;Sex Differences;Signal Transduction;social;social deficits;Social Functioning;Social skills development;Symptoms;Synapses;System;targeted treatment;Testing;Therapeutic;Therapeutic Uses;Time;tool;treatment response;virtual;women versus men

PROJECT_TITLE: Oxytocin neural circuitry involvement in juvenile social play

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]