NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Hearing Loss;Neurosciences;Rare Diseases;Usher Syndrome

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: NARRATIVE The advent of successful gene therapy for certain retinal disorders and our extensive knowledge of the dozens of genes involved in hereditary hearing loss, together raise hope that gene therapy can be used to treat genetic forms of hearing loss. For instance mutations in the PCDH15 gene cause Usher syndrome type 1F, a devastating deafness, blindness and balance disorder. While we and others have achieved success in mouse models using gene therapy for short genes that will fit in adeno-associated virus (AAV) vectors, PCDH15 is a long gene that does not fit into AAV; thus we propose to engineer short “mini-PCDH15” proteins, to test rescue of hearing and balance in mice, and to test localization and toxicity in nonhuman primates. 1

PI_NAMEs: COREY, DAVID P;INDZHYKULIAN, ARTUR  (contact);SOTOMAYOR, MARCOS

PROGRAM_OFFICER_NAME: WATSON, BRACIE

PROJECT_TERMS: adeno-associated viral vector;adenovirus mediated delivery;Antibodies;Binding;Biological Assay;biophysical properties;Biophysics;Birth;Blindness;C-terminal;CDH23 gene;Cells;Clinic;Clinical Treatment;Clinical Trials;Cochlea;Code;congenital deafness;Cryoelectron Microscopy;deafness;Dependovirus;Development;dimer;Dimerization;Disease;Ear;efficacy testing;Elasticity;Electron Microscopy;Engineering;equilibration disorder;Equilibrium;Evaluation;experimental study;Extracellular Domain;Eye;gene therapy;Genes;Genetic;genetic deafness;Hair Cells;Hearing;hearing impairment;hereditary blindness;hereditary hearing loss;Histopathology;Human;improved;in silico;In Vitro;Inherited;Injections;Knock-out;Knockout Mice;Knowledge;Labyrinth;Length;light microscopy;link protein;Love;Macaca fascicularis;Measures;Mechanical Stress;mechanotransduction;Mendelian disorder;Methods;models and simulation;molecular dynamics;Molecular Motors;Morphology;Motor;mouse model;Mus;mutant;Mutate;Mutation;N-terminal;nanoscale;Negative Staining;Neonatal;neonatal mice;Nervous System Disorder;nonhuman primate;Nonmuscle Myosin Type IIA;novel;Parents;Pathology;Patients;PCDH15 gene;Performance;Persons;Phenotype;preclinical evaluation;preservation;Protein Chemistry;Protein Engineering;protein purification;Proteins;rapid technique;Retinal Diseases;Running;simulation;Single-Gene Defect;structural biology;Structural Models;Structural Protein;Structure;success;Testing;therapeutic gene;Toxic effect;Usher Syndrome;Variant;Vestibular function;Vestibular Hair Cells;vestibular system;vestibulo-ocular reflex;Wild Type Mouse;X-Ray Crystallography

PROJECT_TITLE: Development of Gene Therapy for Hereditary Deafness using Rational Protein Engineering

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: MINNEAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: The project will create a comprehensive educational training program on the best practices for successfully navigating the translational pathway for neural medical devices. Our program will provide (1) virtual ‘sprints’ through a series of freely-available video lectures with topical exercises and round-table discussions and (2) three-day workshops with program faculty that will provide participants with hands-on exercises designed around relevant case studies and participant interests.

PI_NAMEs: FRENCH, JENNIFER ;JOHNSON, MATTHEW DOUGLAS (contact);JUNG, RANU ;NETOFF, THEODEN I;WELLE, CRISTIN G

PROGRAM_OFFICER_NAME: GROSS, BROOKS ANDREW

PROJECT_TERMS: Acceleration;Adherence;Adoption;Applications Grants;Awareness;bench to bedside;Biological Models;Businesses;Cancer Education Grant Program;Case Study;Catalogs;Clinical;Clinical Trials;Clinical Trials Design;cohort;commercialization;Communities;Coupled;Dedications;design;Development;Devices;Education;Educational Curriculum;Educational workshop;efficacy study;Engineering;Exercise;experience;Faculty;Failure;Feedback;first-in-human;follow-up;Foundations;Funding;Funding Opportunities;Future Generations;good laboratory practice;Grant;Healthcare Systems;Hour;human study;Hybrids;ideation;Incubators;innovation;Innovation Corps;Intellectual Property;interest;Knowledge;Lead;Learning;lectures;Link;Marketing;Medical Device;meetings;Mentors;Mentorship;Modeling;neural;Neural Pathways;neurotechnology;Nursing Faculty;online course;online resource;Outcome;Outcome Measure;Participant;Persons;Postdoctoral Fellow;pre-clinical;Pre-Clinical Model;Process;programs;Regulatory Affairs;Research Project Grants;Resources;safety study;Scientist;Secure;Series;Solid;success;System;Techniques;Technology;technology development;Testing;Thinking;Training;Training and Education;Training Programs;Translating;Translations;United States National Institutes of Health;Update;virtual;Work

PROJECT_TITLE: Educational Program on Translating Neural Medical Devices

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders C Study Section[NSD-C]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Hypertension;Patient Safety;Pediatric;Prevention

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Pediatric in-hospital cardiac arrest is associated with extremely high morbidity and mortality and is estimated to affect at least 6,000 children per year. In an effort to prevent cardiac arrest in the pediatric intensive care unit, physicians have adopted the practice of administering small doses of epinephrine to reverse acute hypotension; however, little is known about the efficacy, safety or optimal dosing associated with this practice. To better characterize the use of peri-arrest epinephrine, we propose a prospective, randomized, dose-effect trial in patients with acute profound hypotension in the pediatric intensive care unit which may ultimately lead to saving lives and decreasing disability in pediatric patients.

PI_NAMEs: ROSS, CATHERINE  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Acute;Address;Admission activity;Adopted;Adverse event;Affect;Age;American Heart Association;Awareness;Bioethics;Biometry;Blood Pressure;blood pressure elevation;Bolus Infusion;career;Child;Childhood;Clinical;clinical practice;Clinical Research;Clinical Trials;Clinical Trials Design;Critical Care;Critical Illness;Data;Death Rate;design;disability;Disclosure;dosage;Dose;Double-Blind Method;Education;Epinephrine;Event;experience;Family;Frequencies;Funding;Future;General Population;Goals;Guidelines;Heart Arrest;Heart Diseases;Hematological Disease;hemodynamics;Hospital Mortality;Hospitals;Hour;Hypertension;Hypotension;improved;Informed Consent;Institution;Intensive Care Units;Intervention;Journals;Left;Lung Diseases;Measures;medical schools;Methods;Mission;Morbidity - disease rate;mortality;National Heart, Lung, and Blood Institute;Neurologic;novel;Observational Study;Outcome;Parents;Pathway interactions;Patients;Pediatric Intensive Care Units;pediatric patients;Phase;phase III trial;Physicians;Population;posters;prevent;Prevention;prospective;Public Health;Publications;Publishing;Qualitative Research;Randomized;Recommendation;Reporting;Research Personnel;Research Project Grants;Research Training;Resuscitation;Risk;risk minimization;Safety;Science;secondary outcome;severe injury;social media;Standardization;Surveys;Survivors;Testing;Titrations;Training;United States;United States Food and Drug Administration;Visual;willingness

PROJECT_TITLE: Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(MA)]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Clinical Research;Infant Mortality;Lung;Neonatal Respiratory Distress;Neurosciences;Orphan Drug;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases

ORG_CITY: BLOOMINGTON

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: The very preterm neonate is at risk for a discrete set of medical complications due to their unique physiology and vulnerability. Our ability to predict those who will experience life-changing complications is extremely limited. Our work will identify biologic compounds (i.e., metabolic biomarkers) that will improve diagnostics, lead to more effective therapeutic agents, and create a precision approach to the clinical management of this vulnerable population.

PI_NAMEs: JELLIFFE-PAWLOWSKI, LAURA LEE;ROGERS, ELIZABETH E;RYCKMAN, KELLI K. (contact)

PROGRAM_OFFICER_NAME: GUMINA, DIANE LAURA

PROJECT_TERMS: 10 year old;37 weeks gestation;Benchmarking;Biological;Biological Markers;Birth;Brain Death;Bronchopulmonary Dysplasia;California;Caring;Cerebral Palsy;Cessation of life;Characteristics;Climacteric;Clinical;clinical care;Clinical Management;clinical practice;Clinical Trials;cost estimate;Counseling;Data;Death Rate;Decision Making;Diagnostic;Disease;Etiology;extreme prematurity;Family;Gestational Age;Goals;hemodynamics;high risk;Hospital Mortality;hospital performance;Hour;improved;Individual;Infant;Infant Care;Infant Mortality;Intervention;intraventricular hemorrhage;Iowa;late onset sepsis;Lead;Life;Life Experience;Lifelong disability;Measures;medical complication;Metabolic;metabolic profile;Modeling;Morbidity - disease rate;mortality;mortality risk;Necrotizing Enterocolitis;Neonatal;Neonatal Intensive Care Units;neonatal morbidity;Neonatal Mortality;Neonatal Screening;neonate;Neurodevelopmental Impairment;Newborn Infant;novel;Operative Surgical Procedures;Outcome;Patent Ductus Arteriosus;patient population;patient variability;Pattern;Pediatric Hospitals;Periventricular Leukomalacia;personalized approach;Physiology;predictive modeling;Pregnancy;Premature Birth;Premature Infant;preterm newborn;prospective;Protocols documentation;Research;research clinical testing;Retinopathy of Prematurity;Risk;risk prediction;risk prediction model;risk stratification;Sampling;Sepsis;Severity of illness;Severity of Illness Index;System;Therapeutic Agents;therapeutically effective;Time;United States;Universities;Variant;Vulnerable Populations;Work

PROJECT_TITLE: Targeted metabolic profiling to predict major morbidity in very preterm newborns

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE The laboratory mouse is an important model system for investigating the genetics and biological principles of cancer and as a preclinical platform for testing new therapeutic approaches to treating cancer in humans. The Mouse Models of Human Cancer database (MMHCdb) is a unique compendium of expertly curated knowledge about diverse mouse strains that model human cancer. The data and analysis tools provided by MMHCdb are designed to help researchers realize the translational potential of mouse models.

PI_NAMEs: BULT, CAROL J (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Adopted;Affect;Alleles;analysis pipeline;Animal Model;base;Basic Cancer Research;Bioinformatics;bioinformatics resource;Biological;Biological Models;Biology;cancer genetics;Cancer Model;cancer therapy;Catalogs;cBioPortal;Clinical Research;clinically relevant;Collaborations;Collection;Communities;Community Outreach;Complex;Computer software;Data;Data Aggregation;Data Analyses;Data Commons;Data Discovery;data ecosystem;data integration;data platform;data standards;database design;Databases;design;Development;Educational workshop;Electronics;Engraftment;Ensure;European;Evolution;Feedback;Frequencies;Funding;Gene Expression;Genes;Genetic;Genetic Research;Genetically Engineered Mouse;genomic data;genomic platform;Genomics;Goals;Growth;Histopathology;Human;human cancer mouse model;Human Genetics;human model;humanized mouse;Image;Immune;improved;in vivo;in vivo Model;Inbreeding;Informatics;Infrastructure;insight;International;Investigation;knowledge curation;knowledgebase;Laboratory mice;Literature;Machine Learning;Maintenance;Malignant Neoplasms;metadata standards;Mission;Modeling;Modernization;Molecular Genetics;Molecular Profiling;mouse development;mouse model;Mouse Strains;Mus;mutant;Names;Nomenclature;novel therapeutic intervention;Oncogenes;online resource;outreach;patient derived xenograft model;Pattern;Peer Review;Pharmaceutical Preparations;Phenotype;Play;pre-clinical;Predisposition;Process;public health relevance;Reaction Time;Research Personnel;Resources;response;Review Literature;Role;Security;Semantics;Services;social media;software development;Standardization;Strategic Planning;symposium;Testing;tool;translational cancer research;translational potential;treatment response;tumor;Tumor Biology;Tumor Suppressor Proteins;tumorigenesis;usability;Variant;Visualization;web app;web site;Work

PROJECT_TITLE: Mouse Models of Human Cancer Database

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Liver Disease and Cirrhosis;Clinical Research;Data Science;Digestive Diseases;Drug Abuse (NIDA only);HIV/AIDS;Harm Reduction for Substance Misuse;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Prescription Drug Misuse;Prevention;Rural Health;Social Determinants of Health;Substance Misuse

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative / Public Health Relevance  The southern US remains heavily burdened and disproportionately affected by HIV transmission, acute and chronic HCV, and the opioid epidemic. Applying the proposed epidemiologic modeling methods to harmonized individual and contextual data from multiple surveillance systems and creating platforms for sharing these “big data” and analyses will enhance the understanding of HIV epidemiology in the region, elucidate differences between rural and urban settings, and improve targeting of HIV and HCV prevention activities. This research will be novel and high-impact, generating evidence to inform and strengthen programs and policies to tackle HIV/HCV transmission and opioid fatalities across the South and nationwide.

PI_NAMEs: REBEIRO, PETER F (contact)

PROGRAM_OFFICER_NAME: DUNSTON, SHEBA KING

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute Hepatitis;Acute Hepatitis C;Address;Affect;Alabama;Antibodies;Antigens;Area;assault;Behavior;Behavioral;Big Data;causal model;Centers for Disease Control and Prevention (U.S.);Cessation of life;Characteristics;Chronic Hepatitis C;Classification;co-infection;Collaborations;comorbidity;contextual factors;County;COVID-19;COVID-19 pandemic;dashboard;Data;data dissemination;data platform;Disease;Disease Outbreaks;Epidemic;epidemiological model;Epidemiologist;Epidemiology;epidemiology study;Event;fetal;Funding;Future;Health;Hepatitis C;Hepatitis C co-infection;Hepatitis C Incidence;Hepatitis C Transmission;Hepatitis C virus;heterogenous data;high reward;high risk;HIV;HIV diagnosis;HIV risk;HIV/AIDS;HIV/HCV;improved;Incidence;indexing;Indiana;Individual;informatics infrastructure;injection drug use;interest;Intervention;Kentucky;Laboratories;Laws;Legal;Link;Literature;mathematical model;Methods;Mind;Modeling;Monitor;mortality;Naloxone;Needle-Exchange Programs;Neighborhoods;novel;Nucleic Acid Amplification Tests;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid injection;opioid overdose;opioid policy;opioid use;Outcome;outcome disparities;Overdose;overdose death;overdose prevention;pandemic preparedness;Pattern;Persons;Pharmaceutical Preparations;Policies;Population;Populations at Risk;Poverty;predictive modeling;Predisposition;Pregnant Women;Prescription drug overdose;prescription opioid;prevent;Prevention;Prevention Research;Probability;programs;Proxy;Public Health;public health intervention;public health relevance;Reporting;Research;Research Personnel;Resources;Risk;Risk Behaviors;Role;Rural;rural area;Rural Community;Rural Population;rural residence;rural setting;Scourge;sharing platform;social health determinants;sociodemographics;Source;South Carolina;substance use;Surveillance Program;syndemic;System;Tennessee;Territoriality;Time;Translating;transmission process;Transportation;United States National Institutes of Health;Update;urban area;Urban Community;urban setting;Viral;Virginia;virus testing;West Virginia;Work

PROJECT_TITLE: Harnessing big data to arrest the HIV/HCV/opioid syndemic in the rural and urban South

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: NEW HAVEN

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: RELEVANCE: Many important bacterial pathogens such as Salmonella, Yersinia, Shigella, E. coli, Pseudomonas aeruginosa, Burkhodleria spp., Chlamydia spp., and Bordetella pertussis possess specialized nanomachine known as the type III protein secretion system, which is essential for their ability to cause disease. This machine “injects” bacterial proteins into the cells of the host to alter cellular functions for the pathogen’s benefit. This project intends to study how this nanomachine works. The understanding of the mechanisms by which the type III secretion nanomachine works can lead to the development of broadly active anti infective strategies.

PI_NAMEs: GALAN, JORGE E (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Anti-Infective Agents;Apoptosis;ATP phosphohydrolase;Bacteria;Bacterial Proteins;base;bean;Biochemical;Biological Assay;Biology;Bordetella pertussis;Cell membrane;Cell Physiology;Cells;Chlamydia;Collaborations;Color;Complex;Cryoelectron Microscopy;Cytoplasmic Structures;Development;Disease;Elements;Escherichia coli;Eukaryotic Cell;fascinate;Filament;Fluorescence;Fluorescence Microscopy;follow-up;Funding;Grant;Image;imaging study;improved;In Situ;Inflammation;Injections;Innate Immune Response;insight;interest;Interphase;Intestines;Ions;Knowledge;Laboratories;Location;Macrophage;Maps;Mediating;Membrane;Membrane Structure and Function;Molecular Conformation;Monitor;Mutagenesis;mutant;nanomachine;Needles;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Pathogenicity Island;Pathway interactions;Phenotype;Play;Process;Progress Reports;protein activation;Protein Secretion;Protein translocation;Proteins;Protons;Pseudomonas aeruginosa;Public Health;Research Project Grants;Resolution;Rest;Role;Salmonella;Salmonella typhimurium;secretion process;Shapes;Shigella;Signal Transduction;single molecule;Sorting;Structure;System;Time;Type III Secretion System Pathway;ultra high resolution;Virulence;Work;Yersinia

PROJECT_TITLE: Mechanisms of Type III protein secretion

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Caregiving Research;Chronic Obstructive Pulmonary Disease;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Palliative Care;Telehealth

ORG_CITY: BIRMINGHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative COPD is the third leading cause of death in older Americans, and older adults with COPD rarely receive proactive geriatrics-palliative care before the end of life. This study will refine and pilot test a telehealth, palliative nurse coach-led geriatrics-palliative care intervention for older adults with COPD and their family caregivers. The results will support a fully-powered randomized controlled trial that will seek to improve the health and well-being of older adults with COPD and their family caregivers.

PI_NAMEs: IYER, ANAND SATHYAN (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Acceleration;acceptability and feasibility;Address;Age;Aging;aging brain;American;Award;Biology of Aging;career development;Caring;Cause of Death;Chronic Obstructive Pulmonary Disease;Clinic;clinical implementation;Clinical Trials;Communities;coping;Data;Decision Making;Development;disability;Disease Outcome;Doctor of Philosophy;effectiveness/implementation trial;Elements;end of life;Epidemic;Evaluation;experience;Family Caregiver;formative assessment;functional independence;Geriatrics;Gerontology;Goals;Health;Health Services Accessibility;Hybrids;implementation facilitation;implementation science;implementation/effectiveness;improved;improved outcome;innovation;International;Intervention;Knowledge;leadership development;Life;Lung;Measures;Mentored Clinical Scientist Development Program;Mentors;middle age;Modeling;National Heart, Lung, and Blood Institute;novel;Nurses;older adult;Older Population;Oncology;Outcome;palliative;Palliative Care;Participant;patient engagement;patient oriented;Patients;Personal Satisfaction;personalized intervention;Phase;pilot test;Policies;Positioning Attribute;primary outcome;Procedures;programs;Quality of life;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;recruit;Research;research and development;Research Personnel;Research Priority;rural area;secondary outcome;Self Care;skills;Social isolation;Societies;Southeastern United States;Specialist;Surveys;Symptoms;Techniques;telehealth;telephone session;Testing;theories;Training;underserved area;United States;United States Agency for Healthcare Research and Quality;United States National Institutes of Health;Work

PROJECT_TITLE: Aging Well with COPD through Geriatrics-Palliative Care


ORG_CITY: HOUSTON

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

ORG_STATE: TX

PHR: Project Narrative In this project we will determine the role of reprogramming of tumor microenvironment (TME) by p38 MAPK inhibition to promote a robust dendritic cell-driving antitumor immunity to prevent acquired resistance in adoptive cell therapy. We propose to use the clinically tested p38 inhibitor, Ralimetinib, to divert the immunosuppressive TME by combining it with CAR T cells, which enhance tumor antigen presentation, provoke type I IFN signatures in TME and hence eliminates resistant tumor cells to prevent the acquired resistance. This study may thus uncover a novel mechanism for preventing tumor relapse in cancer immunotherapy. Data from our proposed Aims may yield critically needed evidence that repurposing the clinically tested Ralimetinib from targeting p38 MAPK in tumor cells toward that of immune cells may induce a complete and durable response in adoptive cell therapy. This translationally relevant work could then lay the foundation for future clinical trials.

PI_NAMEs: LU, YONG  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Adoptive Cell Transfers;Antigen Presentation;Antigens;Automobile Driving;Bone Marrow;cancer cell;cancer immunotherapy;Cancer Patient;Cancer Relapse;CD19 gene;Cell Differentiation process;Cell Lineage;Cells;Characteristics;chimeric antigen receptor T cells;Clinical;Clinical Trials;Data;Dendritic Cells;Development;differentiation in vitro;Drug resistance;Foundations;Future;genetic signature;Genetic Transcription;Glioblastoma;Granulocyte-Macrophage Colony-Stimulating Factor;Immune;Immunity;immunogenic;Immunotherapy;In Vitro;in vivo;Infiltration;inhibitor;Interferons;Lead;leukemia/lymphoma;Lymphoma;Macrophage;Malignant neoplasm of pancreas;MAP Kinase Gene;Mediating;Melanoma;mimicry;Molecular;Multiple Myeloma;Mus;Myeloid Cells;Nature;neoplastic cell;novel;p38 Mitogen Activated Protein Kinase;Patients;Population;PPAR gamma;PPAR Pathway;prevent;Process;Production;programs;Recurrence;Relapse;Reporting;Repression;Resistance;response;Role;Signal Repression;Signal Transduction;Solid Neoplasm;Somatic Mutation;T cell therapy;T-Lymphocyte;Testing;TNFRSF5 gene;TNFSF4 gene;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;Viral;Work

PROJECT_TITLE: P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative Animals can utilize two distinct types decision making strategies: i) a “model-free” strategy that relies fully on past experiences to guide future choices, and ii) a “model-based” strategy that employs a learned model of the world to infer structure about their environment and make predictions about the future. This project aims to uncover how we initially learn models of the world in order to make model-based decisions, how such an internal model is stored and used in the brain, and how an initially poorly learned model can be improved through tailored training. Understanding the neural mechanisms that underpin learning models is a basic scientific question that can lead to improved treatments for neuropsychiatric disorders that produce aberrant decision making, such as schizophrenia and bipolar disorder.

PI_NAMEs: HOCKER, DAVID  (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Address;Affect;Animal Behavior;Animals;Behavior;Behavioral;Behavioral Model;Biological;Biology;Bipolar Disorder;Brain;career;career development;Chalk;Cognitive;Collaborations;Communication;Complex;Computational Technique;Computer Models;Cues;Decision Making;deep neural network;deep reinforcement learning;Dependence;Development Plans;Educational workshop;Electrophysiology (science);Environment;Exhibits;experience;Experimental Designs;experimental study;Exposure to;Faculty;Future;Goals;Health;Implant;improved;insight;Institution;Knowledge;Learning;learning strategy;Link;Machine Learning;Maps;Modeling;neural;neural circuit;neural model;Neural Network Simulation;neuromechanism;Neurons;neuropsychiatric disorder;Neurosciences;New York;novel;Performance;Population;Population Dynamics;Positioning Attribute;Preparation;present value;Procedures;Process;Protocols documentation;Psychological reinforcement;Psychology;Rattus;recurrent neural network;Research;Research Personnel;response;Rewards;Rodent;Rodent Model;Role;Schizophrenia;Science;Statistical Models;Structure;Subgroup;symposium;System;Testing;Therapeutic;Training;Universities;Water;Weight;Work

PROJECT_TITLE: Acquiring cognitive maps: how brains learn hidden structure

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Understanding the mechanisms that enable pancreatic cancer to progress unimpeded by the immune system would inform on the complex biology of this intractable disease and help to identify potential strategies for therapeutic intervention. The studies proposed here will test the novel hypothesis that fatty acid signaling within pancreatic cancer cells controls expression of genes whose products signal to the surrounding microenvironment and suppress immune-mediated tumor growth control. Together, these studies will help us understand the mechanistic basis of growth-permissive tumor-stromal interactions in the pancreatic tumor microenvironment, and may identify novel, druggable targets to help achieve therapeutic benefit in patients.

PI_NAMEs: SHERMAN, MARA H. (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: anti-tumor immune response;Antineoplastic Agents;Arachidonic Acids;Aspartate Transaminase;Binding;Biological Assay;Biology;cancer cell;CD8-Positive T-Lymphocytes;Cell Proliferation;Chromatin;Clinical;clinical translation;Coculture Techniques;Combined Modality Therapy;Complex;conventional therapy;Data;Development;Disease;DNA Sequence Alteration;druggable target;Enhancers;Enzymes;Exclusion;experimental study;Fatty Acids;Fostering;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;genome-wide;Goals;Growth;Heterogeneity;Immune;Immune Evasion;Immune system;immunomodulatory therapies;immunoregulation;Immunosuppression;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Infiltration;Inflammatory;inhibitor;Ligands;Link;Lymphoid;Malate-Aspartate Shuttle Pathway;Malignant neoplasm of pancreas;Mediating;Mitochondria;Molecular;mouse model;mutant;mutational status;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;novel;novel therapeutics;Nuclear Receptors;Outcome;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;paracrine;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;Pattern;permissiveness;pharmacologic;Phenotype;precision medicine;preclinical evaluation;prevent;Process;Productivity;programs;Proteins;rational design;Regulation;Role;Shapes;Signal Transduction;Solid Neoplasm;Specimen;Stromal Neoplasm;System;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;transcription factor;Transcriptional Regulation;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Promotion;Tumor Suppression;tumor-immune system interactions;Work

PROJECT_TITLE: Fatty acid signaling in the pancreatic tumor microenvironment

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIR-W(01)Q]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Most patients with acute myeloid leukemia (AML) eventually die when their disease becomes resistant to conventional or even newer treatments, some of which include an inhibitor of FLT3, called gilteritinib, and an inhibitor of BCL2, called venetoclax. We are testing novel therapeutic combinations involving these drugs, and our proposed studies will employ expansive proteogenomic studies to define biomarkers that can be used to predict and detect resistance to these drug combinations. The ultimate goal will be to deliver better therapies and outcomes for patients with AML.

PI_NAMEs: DRUKER, BRIAN J;PIEHOWSKI, PAUL D;TYNER, JEFFREY WALLACE (contact)

PROGRAM_OFFICER_NAME: HILTKE, TARA

PROJECT_TERMS: acquired drug resistance;Acute Myelocytic Leukemia;Archives;arm;aurora B kinase;Automobile Driving;Azacitidine;BCL2 gene;biobank;Biological Assay;Biological Markers;Biological Process;Biology;biomarker validation;CD14 gene;CD34 gene;Cell Differentiation process;Cell Line;cell type;Cells;chemotherapy;Clinical;clinical material;clinical predictors;Clinical Research;clinical translation;clinical trial enrollment;Clinical Trials;Collection;Complex;CRISPR screen;Data;data integration;Decitabine;Dependence;Development;Disease;Disease remission;Drug Approval;Drug Combinations;Drug Modelings;drug relapse;Drug resistance;drug resistance development;drug response prediction;drug sensitivity;Early Diagnosis;Elderly Acute Myeloblastic Leukemia;Exhibits;Exposure to;FLT3 gene;FLT3 inhibitor;Generations;Genes;Genetic;genome-wide;Genomics;Goals;Hematologic Neoplasms;improved;inhibitor;inhibitor therapy;innovation;insight;leukemia;MEKs;Metabolic;Metabolism;metabolomics;Methods;Modeling;monocyte;Mutation;novel;novel drug combination;novel strategies;novel therapeutics;Outcome;participant enrollment;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phosphoproteins;phosphoproteomics;Population;pre-clinical;pre-clinical research;predictive marker;predictive panel;prevent;progenitor;prospective;Proteins;proteogenomics;Proteomics;Publishing;Regimen;Relapse;Residual Neoplasm;Resistance;resistance mechanism;response;response biomarker;Role;Sampling;Signal Transduction;specific biomarkers;Specimen;standard of care;Stromal Cells;Technology;Testing;therapy resistant;Training;transcriptomics;Translating;treatment strategy;tumor;tumor microenvironment;Validation;Work

PROJECT_TITLE: Proteogenomic characterization of early and late resistance mechanisms in acute myeloid leukemia


NIH_SPENDING_CATS: Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Kidney Disease;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE This research proposes to investigate how long noncoding RNAs (lncRNAs), a diverse class of RNAs with poorly understood functions, contribute to the pathogenesis of cancer, a leading cause of death in the United States. In particular, we will study the role of lncRNAs in renal cell carcinoma (RCC), a deadly malignancy with limited effective treatment options. A better understanding of noncoding RNAs could enable the development of new therapeutic strategies for cancer patients.

PI_NAMEs: MENDELL, JOSHUA T (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Alleles;Alternative Splicing;Animal Model;Animals;Binding;Biogenesis;Biology;Bone Marrow Transplantation;Breeding;Cancer Biology;cancer cell;Cancer Patient;cancer type;Cause of Death;Cell Line;Cell model;Cell Nucleolus;Cell Proliferation;Characteristics;Code;Collaborations;Colorectal Neoplasms;Constitution;CRISPR interference;Custom;Cytoplasm;Data;Development;Diagnosis;differential expression;Disease;effective therapy;Elements;experience;experimental study;Genes;Genetic Engineering;Genomics;Growth;Hematopoietic;Hematopoietic Neoplasms;Human;Impairment;in vivo;knock-down;Knockout Mice;Knowledge;Length;Libraries;loss of function;Malignant - descriptor;Malignant Neoplasms;Maps;Mediating;Molecular;Molecular Mechanisms of Action;mouse model;Mus;novel;novel therapeutic intervention;Nucleotides;overexpression;Pancreas;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;Phenocopy;Phenotype;Physiological;Physiology;Play;Predisposition;premature;prevent;Production;Proliferating;Proteins;Proteomics;regeneration model;Renal Carcinoma;Renal Cell Carcinoma;Research;Resolution;Resources;Ribosomal RNA;Ribosomes;RNA;Role;Shwachman-Diamond syndrome;skeletal abnormality;Testing;therapeutic target;tissue injury;tissue regeneration;Tissues;Transcript;transcriptome sequencing;Translations;tumor;tumor growth;tumor progression;Tumor Promotion;United States;Untranslated RNA;urologic;Variant

PROJECT_TITLE: The role of long noncoding RNA CRNDE in normal physiology and cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Schizophrenia;Serious Mental Illness;Sleep Research

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative. Cognitive impairments in Schizophrenia (SCZ) have been linked to abnormalities in specific sleep oscillations—sleep spindles and slow waves—, in multiple studies, although most of the evidence is in chronic patients. As first steps towards translating these observations into novel interventions, we aim to demonstrate that: 1) spindle and slow wave deficits are present alongside impairments in cognition in early course patients (EC-SCZ); 2) sleep and cognitive defects are associated with one another; 3) spindles and slow waves can be manipulated and acutely enhanced through closed-loop auditory stimulation (CLAS) during sleep in EC-SCZ patients; and 4) CLAS-related changes in sleep oscillations are associated with cognitive changes in these patients.

PI_NAMEs: FERRARELLI, FABIO  (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Acoustic Stimulation;Acute;Affect;auditory stimulus;Brain;Chronic;Chronic Schizophrenia;Clinical;Cognition;Cognitive;cognitive change;cognitive control;Cognitive deficits;cognitive function;cognitive performance;comparison group;Correlative Study;Crossover Design;Data;density;Diagnosis;disability;Disease;Double-Blind Method;Early Intervention;Early treatment;Electroencephalography;functional outcomes;Goals;Health Care Costs;Impaired cognition;Impairment;improved;improvement on sleep;Individual;Intervention;Laboratories;Link;Measures;memory consolidation;Motor;Napping;Neurobiology;non rapid eye movement;novel;Onset of illness;Participant;Patients;Performance;Research;Role;Schizophrenia;Short-Term Memory;Sleep;sleep spindle;Stage II Sleep;System;Task Performances;Translating;Waxes;wireless;wireless electronic;Work

PROJECT_TITLE: Establishing that sleep spindle and slow wave deficits are present, are associated with cognitive dysfunction, and can be acutely manipulated in early course schizophrenia

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


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

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative: Advanced age is the greatest risk factor for the onset and progression of Alzheimer's disease and for the lethality of viral infections, most recently SARS-CoV-2. We are using the powerful genetics of the nematode C. elegans to better understand the biological mechanisms of aging and to discover novel therapeutic targets to counteract age-related human diseases, including Alzheimer's disease and ADRD protein aggregation diseases, and responses to viral infection.

PI_NAMEs: RUVKUN, GARY B (contact)

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: 2-tyrosine;2019-nCoV;Adrenal Glands;age-related disease;Aging;aging mechanism;Alleles;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid beta-Protein;Anatomy;Aneuploidy;Animals;anti aging;Anti-viral Response;Asparagine;Aspartic Acid;Aspartic Endopeptidases;Biogenesis;Biological;Bortezomib;Caenorhabditis elegans;Capsid Proteins;Cell Nucleus;cell type;Cells;Cessation of life;Chimeric Proteins;Client;Complex;Coupled;deep sequencing;Defect;Development;Dexamethasone;Dioxygenases;Disease;Dopamine;dopaminergic neuron;Drug Metabolic Detoxication;Elderly;Electrons;Enzymes;extend lifespan;Face;Felis catus;fusion gene;Future;gain of function;Gases;Gene Dosage;Gene Expression;Genes;Genetic;genetic analysis;genetic element;genetic pedigree;Genetic Recombination;Genetic Risk;Genome;Genomics;glycosylation;Homeostasis;Human;human disease;Hyperoxia;Immunity;Informatics;insulin signaling;Interferons;Intestines;Lacrimal gland structure;life span;Ligand Binding Domain;Location;Longevity;Mammals;Mediating;Messenger RNA;Methylation;Methyltransferase;Mitochondria;mitochondrial dysfunction;mitochondrial genome;mitochondrial membrane;Modeling;Molecular;Monitor;multicatalytic endopeptidase complex;Muscle;mutant;Mutation;nematode genetics;neoplastic cell;neuronal survival;Neurons;new therapeutic target;NF-kappa B;Nuclear;Nuclear Hormone Receptors;Oocytes;Output;Oxygen;Parkin;Parkinson Disease;Partial Pressure;Pathway interactions;Peptide Hydrolases;Peptide N-Glycosidase;Phosphotransferases;Phylogenetic Analysis;Phylogenetic Pattern;PINK1 gene;Polysaccharides;Production;Proteasome Inhibitor;protein aggregation;Protein Kinase;Proteins;proteostasis;Receptor Gene;response;Risk Factors;risk variant;RNA;RNA Helicase;RNA Interference;RNA methylation;RNA Virus Infections;SARS-CoV-2 spike protein;Secretory Cell;Small Interfering RNA;Small RNA;Stress;Sum;System;Testing;Tissues;transcription factor;transcriptome sequencing;tRNA Methyltransferases;Tyrosine;ubiquitin ligase;Up-Regulation;Viral;Viral Genome;Viral Proteins;Virion;Virus;Virus Diseases;Virus Integration;Virus Replication;Vitellogenins

PROJECT_TITLE: Genetic and Molecular Basis of Longevity

STUDY_SECTION: CMAD

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


NIH_SPENDING_CATS: Bioengineering;Genetics;Lung

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE The mammalian respiratory system undergoes cyclical mechanical strain as part of its normal function. We hypothesize that the lung has evolved specific epigenetic and transcriptional mechanisms to maintain cellular fate in the face of mechanical strain from normal respiration and these pathways are altered in the response to injury and disease. In this proposal, we aim to address key unanswered questions in cell fate regulation in lung development and regeneration.

PI_NAMEs: MORRISEY, EDWARD E (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: 3-Dimensional;Actins;Acute Lung Injury;Address;Adult;Agreement;Alveolar;alveolar epithelium;Alveolus;Architecture;Biomechanics;biophysical techniques;Blood capillaries;Breathing;Cell Fate Control;Cell Lineage;Cell Nucleus;cell type;Cells;Chemicals;Chromatin;Collaborations;Complex;Cytoplasm;Cytoskeleton;Data;Disease;Endothelial Cells;Endothelium;Epigenetic Process;Epithelial Cells;experience;Extracellular Matrix;flexibility;Gases;Genes;Genetic;genetic approach;Genetic Transcription;Genome;genome-wide;Health;Homeostasis;In Vitro;in vivo;Injury;Laboratories;life span;Ligation;Lung;lung development;lung regeneration;Manuscripts;mechanical signal;Mechanics;mechanotransduction;Mesenchymal;Modeling;Movement;Mus;Natural regeneration;novel;Nuclear;Nuclear Envelope;Pathway interactions;Periodicity;Play;Positioning Attribute;prevent;Principal Investigator;Publishing;Pulmonary alveolar structure;Pulmonary Surfactants;Recording of previous events;Research Personnel;Respiration;Respiratory System;response;response to injury;Role;single-cell RNA sequencing;stem cell differentiation;Stretching;Technology

PROJECT_TITLE: Mechanical signaling through the nuclear membrane in lung alveolar health

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Cancer;Emerging Infectious Diseases;Genetics;Infectious Diseases;Networking and Information Technology R&D (NITRD);Rare Diseases;Tuberculosis

ORG_CITY: MADISON

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: The computational methodologies we develop will be applicable to a broad range of conformational changes of RNA polymerases with biomedical relevance. In particular, oxidative DNA lesions cause transcriptional mutagenesis of RNA Polymerase II that contributes to tumor growth in skin cancer, and mechanistic insights from this work will help uncover a route to address the adverse effects of these DNA lesions. In addition, antibiotics against Mycobacterium tuberculosis (Mtb) often target the dynamic motion of its RNA polymerase, and this work will provide mechanistic insights to facilitate the rational design of new antibiotics fighting drug resistance of Mtb.

PI_NAMEs: HUANG, XUHUI  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Adverse effects;Algorithms;Antibiotics;base;Biochemical;Biological;Biophysics;Cessation of life;code development;Communities;Complex;computer framework;Computer software;Computing Methodologies;Coupling;Cryoelectron Microscopy;Development;discrete time;DNA;DNA Damage;DNA lesion;DNA-Directed RNA Polymerase;Drug resistant Mycobacteria Tuberculosis;Equation;Event;experimental study;fighting;flexibility;Foundations;Gene Expression;Genetic Transcription;guanidinohydantoin;inhibitor;innovation;insight;Knowledge;Length;Lesion;Memory;Methodology;Methods;Modeling;Molecular;Molecular Conformation;molecular dynamics;Motion;Mutagenesis;Mycobacterium tuberculosis;Mycobacterium tuberculosis complex;novel;operation;Outcome;Polymerase;Protocols documentation;rational design;RNA Polymerase II;Roentgen Rays;Role;Rotation;Route;Scheme;Series;Skin Cancer;System;Testing;theories;Thermus;Time;time interval;Transcription Initiation;Tuberculosis;tumor growth;Work

PROJECT_TITLE: Theory and Modeling of Functional Conformational Changes of RNA Polymerases

STUDY_SECTION: MSFA

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


NIH_SPENDING_CATS: HIV/AIDS;Immunization;Prevention;Vaccine Related;Vaccine Related - AIDS

PHR: NARRATIVE Changing the course of the HIV-1 pandemic requires an effective HIV-1 vaccine that most probably will have to elicit antibodies against HIV-1 envelope glycoproteins (Envs). Here we will study differences and similarities in the shape of Envs from different HIV-1 strains and build a mechanistic model for how these differences evolve and generated in vivo, and what is required to recognize the diverse shapes of HIV-1 Envs. Our study will provide insights into the biology of HIV-1 entry and lay a new groupwork for understanding HIV Env function & inhibition.

PI_NAMEs: HERSCHHORN, ALON  (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: Adopted;Affect;Amino Acids;Antibodies;Antibody Therapy;Antigens;Archives;Binding;Binding Sites;Biology;Cells;Complex;Cryoelectron Microscopy;design;Development;Electrons;Elements;Epitopes;Evolution;flexibility;Generations;Glycoproteins;Goals;Heterogeneity;HIV;HIV envelope protein;HIV Envelope Protein gp120;HIV Infections;HIV-1;HIV-1 vaccine;improved;in vivo;Inpatients;insight;Kinetics;Knowledge;latent HIV reservoir;Maps;Measures;Mediating;Modeling;Molecular;Molecular Conformation;Mutation;neutralizing antibody;pandemic disease;Pathway interactions;Patients;Persons;preventive intervention;Preventive vaccine;Probability;Publishing;resistant strain;Resolution;Shapes;single-molecule FRET;Source;Spectrum Analysis;Structure;targeted treatment;Testing;therapeutic development;Therapeutic Intervention;Time;Translating;transmission process;V3 Loop;Vaccine Design;Vaccines;Variant;Viral;Virus;Work;working group

PROJECT_TITLE: Dissecting the Conformational Flexibility of HIV-1 Envelope Glycoproteins

STUDY_SECTION: HVCD

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


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

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative The intestinal epithelium is a rapidly regenerating tissue that relies actively cycling intestinal stem cells (ISCs) to support tissue renewal. Here we explore the central hypothesis that extrinsic niche changes contribute to functional impairment in ISCs during aging. Through our studies, we aim to improve our understanding of stem cell niche factors and how to mobilize ISCs for tissue repair.

PI_NAMEs: YAN, KELLEY  (contact)

PROJECT_TERMS: Acceleration;Achievement;adenoma;adult stem cell;age related;age related changes;age related decline;Aging;APC mutation;Area;base;Biochemical;Cell Compartmentation;Cell Count;Cell Maintenance;Cell Physiology;cell type;Cells;Clonal Expansion;Clone Cells;Coculture Techniques;Colorectal Neoplasms;crypt cell;Data;Epithelium;Exhibits;fitness;functional decline;Functional disorder;Functional impairment;Genetic Transcription;Homeostasis;Impairment;improved;in vivo;Injury;insight;Intervention;intestinal epithelium;Intestines;LGR5 gene;Ligands;Maintenance;Malignant Neoplasms;Mesenchymal;Mesenchyme;Modeling;Molecular;mouse genetics;Mutation;Natural regeneration;Nature;Neoplasms;novel;old mice;Oncogenic;Organoids;Parabiosis;Pathway interactions;pharmacologic;Physiology;Population;Positioning Attribute;prevent;programs;regeneration function;Regenerative capacity;repaired;Reporting;Reserve Stem Cell;Risk;Role;sample fixation;self-renewal;Signal Transduction;single cell analysis;Somatic Mutation;stem cell biology;stem cell function;stem cell niche;stem cell replacement;stem cell self renewal;stem cells;Testing;Time;tissue regeneration;tissue repair;tissue stem cells;Tissues;tool;tumor initiation;tumorigenesis;WNT Signaling Pathway;Youth

PROJECT_TITLE: Intestinal Stem Cell Function During Aging and Tumor Initiation

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: AUSTIN

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative.  Fragile X syndrome (FX) is associated with deficits in social and spatial behaviors, yet the neural mechanisms responsible for these impairments remain poorly understood. Hippocampal areas CA2 and CA1 are key brain regions for sociality and spatial memory, respectively. In this project, we aim to uncover neurophysiological disturbances in CA2 and CA1 that may underlie impaired social and spatial cognition in FX and may point toward new symptom-specific treatment targets.

PI_NAMEs: BRAGER, DARRIN H;COLGIN, LAURA L (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Address;Affect;Area;autism spectrum disorder;Behavior;Biochemical;Brain;Brain region;Cells;Code;Cognition;cognitive function;Data;Defect;Dendrites;effective therapy;Electrophysiology (science);Environment;Event;Exhibits;experience;experimental study;Feedback;Fire - disasters;Fragile X Syndrome;Functional disorder;Goals;hippocampal pyramidal neuron;Hippocampus;Impaired cognition;Impairment;In Vitro;in vivo;Individual;Inherited;insight;Intellectual functioning disability;Interneurons;Intervention;Knock-out;Knockout Mice;Knowledge;Lead;Learning;Learning Disabilities;Location;Long-Term Potentiation;Measures;Memory;Memory impairment;Modeling;multisensory;Mus;neocortical;neuromechanism;Neurons;Neuropeptides;neurophysiology;non rapid eye movement;novel;operation;Output;Oxytocin;patch clamp;Pattern;pharmacologic;Physiology;place fields;Play;Population;Property;Pyramidal Cells;Rattus;Regulation;response;Rest;Rodent Model;Role;sensory stimulus;Sleep;Slice;social;Social Behavior;Social Phobia;Spatial Behavior;spatial memory;Stimulus;Structure;Symptoms;Synapses;Synaptic plasticity;Techniques;Testing;Time;tool;transmission process;Whole-Cell Recordings

PROJECT_TITLE: Investigating mechanisms underlying impaired social and spatial cognition in rodent models of Fragile X syndrome


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Diabetes;Mental Health;Mental Illness;Nutrition;Obesity;Physical Activity;Prevention

ORG_CITY: BATON ROUGE

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

ORG_STATE: LA

PHR: PROJECT NARRATIVE Insulin resistance and depressive symptoms are conditions that are interdependent, particularly, in the elderly (> 70 years). A low glycemic index (GI) diet and exercise (D+E) program increases insulin sensitivity in older adults with obesity, but the effect on apathy in depression is unknown. This carefully designed series of specific aims will determine: 1) whether a low GI diet D+E program reduces apathy in the elderly; 2) whether the reduction in apathy is mediated by changes in insulin sensitivity; and 3) the potential of a novel low GI D+E intervention using whole soybean pods to promote sustainability of the intervention.

PI_NAMEs: REBELLO, CANDIDA JOAN (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Address;Adherence;Adult;adult obesity;age related neurodegeneration;Age Years;Aging;Area;Articulation;Award;Behavior;Behavioral;Biological;Biological Markers;Biology of Aging;chronic depression;Clinical;clinical practice;Cognitive;Data;depressive symptoms;design;Development;Diabetes Mellitus;Diet;diet and exercise;Dietary Fiber;Dietary Intervention;Dose;efficacy testing;Elderly;Emotional;Epidemiology;Excretory function;Exercise;exercise intervention;exercise program;exercise regimen;Fatty acid glycerol esters;feeding;Fiber;Food;food consumption;Funding;Future;geriatric depression;Glucose;glucose metabolism;glycemic control;Glycemic Index;Grant;Health;healthy aging;improved;Individual;insight;Insulin Resistance;insulin sensitivity;Intervention;Investigation;Knowledge;lifestyle intervention;Maximum Tolerated Dose;Measures;Mediating;Mental Depression;Modeling;Motivation;Mus;novel;nutrition;Obesity;older adult;Outcome;Pathway interactions;Phytonutrients;Population;Positioning Attribute;programs;psychosocial;Randomized, Controlled Trials;Research;response;Series;skills;social;Socioeconomic Factors;soy;Soybeans;Statistical Data Interpretation;Testing;therapeutic target;therapy design;Training;Volatile Fatty Acids

PROJECT_TITLE: Lifestyle intervention to treat apathy in older adults


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Neurosciences;Patient Safety;Stroke

ORG_CITY: CHICAGO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The purpose of the application is to develop a robust, non-invasive, flexible MRI imaging suite to quantitatively characterize cerebral hemodynamics pre and post-revascularization surgery without exogenous contrast agents. Cerebral revascularization patients could benefit from this imaging suite to personalize a revascularization strategy and prevent or reduce postoperative complications and improve clinical outcomes.

PI_NAMEs: YAN, LIRONG  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Algorithms;Anastomosis - action;Aneurysm;Angiography;arterial spin labeling;Arteries;Blood flow;Blood Vessels;Cause of Death;Cephalic;cerebral hemodynamics;Cerebral Revascularization;Cerebrovascular Disorders;Chronic;Clinical;clinical imaging;clinical practice;Complex;Consensus;Contrast Media;design;Development;Digital Subtraction Angiography;disability;Disease;Economic Burden;Evaluation;feeding;flexibility;Four-dimensional;Goals;hemodynamics;Image;Imaging Device;imaging modality;improved;Individual;Ischemic Stroke;Knowledge;Label;Legal patent;Magnetic Resonance Imaging;Maps;Measures;Methods;Moyamoya Disease;non-invasive imaging;novel;Operative Surgical Procedures;Outcome;Patient Care;Patients;Pattern;Performance;Perfusion;perfusion imaging;Perioperative;Phase;Physiologic pulse;Postoperative Complications;Postoperative Period;predict clinical outcome;preservation;prevent;Quantitative Evaluations;quantitative imaging;Radial;reconstruction;Resolution;Resources;revascularization;revascularization surgery;Risk;Risk Reduction;Rotation;Scanning;spatiotemporal;Standardization;stroke risk;Techniques;Territoriality;Time;Tissues

PROJECT_TITLE: Quantitative ASL MR angiography and perfusion imaging for cerebral revascularization

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Liver Cancer;Liver Disease;Orphan Drug;Radiation Oncology;Rare Diseases

PHR: NARRATIVE Radiation therapy has become an increasingly effective liver cancer treatment technique, especially after the introduction of stereotactic body radiation therapy (SBRT), which can deliver large and focused radiation doses to liver tumors to achieve superior tumor control and survival. However, current clinical practices usually treat a volume much larger than the actual tumor (with treatment margins up to 15 mm beyond the tumor boundary) to account for the uncertainties in liver tumor localization. Successful completion of the proposed work will generate a contrast-agent-free and non-invasive x-ray imaging technique for accurate 4D liver tumor localization, which will lead to substantial treatment volume/margin reduction to boost the safety, viability and efficacy of SBRT.

PI_NAMEs: ZHANG, YOU  (contact)

PROGRAM_OFFICER_NAME: ZHANG, YANTIAN

PROJECT_TERMS: 3-Dimensional;3D Print;Affect;Anatomy;biomechanical model;Biomedical Engineering;Blood Vessels;Breathing;cancer therapy;Cirrhosis;Clinic;Clinical;clinical practice;Clinical Research;clinical translation;Cone;cone-beam computed tomography;Contrast Media;Data;Dose;Effectiveness;Elasticity;Elements;four-dimensional computed tomography;Generations;Goals;Image;image guided;Imaging Techniques;Implant;improved;innovation;Institution;Invaded;Lead;Liver;Liver Cirrhosis;liver function;Liver neoplasms;Location;Malignant neoplasm of liver;Manuals;Medical;Metastatic Neoplasm to the Liver;Methods;migration;Modeling;Motion;Nodal;Normal tissue morphology;Operative Surgical Procedures;Organ;Patients;Positioning Attribute;prevent;Process;prospective;Prospective Studies;Protocols documentation;Radiation;Radiation Dose Unit;Radiation therapy;Reference Standards;research clinical testing;Research Project Grants;Respiration;Respiratory Diaphragm;response;Risk;Roentgen Rays;Safety;Site;Study models;System;Targeted Radiotherapy;Techniques;Technology;Therapeutic;Tissues;Toxic effect;Training;tumor;Uncertainty;vector;Work;Workload;X-Ray Medical Imaging

PROJECT_TITLE: Accurate 4D Liver Tumor Localization for Radiotherapy using Contrast-Agent-Free X-ray Imaging and Liver Biomechanical Modeling

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: This project will provide information on the DNA repair capacity of MUTYH variants in a comprehensive manner that will provide insight into their cancer-causing potential. In addition, this work will evaluate the influence of MUTYH variants on the response to DNA damaging agents that will translate directly to development of appropriate treatment strategies for patients harboring defective MUTYH.

PI_NAMEs: DAVID, SHEILA SUE (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: 3-Dimensional;Address;Adenine;Alkylating Agents;Alkylation;Alleles;amino group;APC gene;Applications Grants;base;Base Excision Repairs;Base Pairing;Binding;Biological Assay;C-terminal;cancer type;carcinogenesis;Categories;Cells;Cellular Assay;Chemistry;Chromatin;Clinical;cofactor;Colorectal Cancer;Complex;cytotoxic;cytotoxicity;Defect;Deoxyguanosine;Detection;Development;DNA;DNA Damage;DNA Repair;DNA sequencing;early onset colorectal cancer;Enzymatic Biochemistry;Escherichia coli;Excision;Exhibits;experimental study;Functional disorder;Genes;Genomics;in vitro activity;Inherited;innovation;insight;Laboratories;Lesion;Link;Location;Major Groove;Malignant Neoplasms;Mammalian Cell;Measurement;Mediating;Metals;Methylnitronitrosoguanidine;Molecular;Mutation;novel;novel therapeutic intervention;Nucleic Acids;Nucleosomes;oxidative damage;oxidative DNA damage;Patients;Phleomycins;Play;polyposis;Predisposition;prevent;repaired;Reporting;response;Role;sensor;single molecule;Site;Somatic Mutation;sugar;Syndrome;Therapeutic;therapeutic DNA;Toxic effect;Translating;treatment strategy;tumor;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis;Ultraviolet Rays;Variant;variant of unknown significance;Work;XPA gene;Zinc

PROJECT_TITLE: DNA Damage Repair by MUTYH and MUTYH Variants Associated with Colorectal Cancer


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_NAME: JACKSON LABORATORY

PHR: OVERALL—PUBLIC HEALTH RELEVANCE Human aging is influenced by genetic factors, whereby differences in longevity as well as changes in health and disease risk with time are linked to variation in individuals' genetic codes. The Jackson Laboratory Nathan Shock Center will develop resources to encourage the use of a wider range of mouse models in aging research. Resources—including aged mouse models that mirror human genetic variation, metabolic and microbiome data, and methods to reveal genetic factors tied to human aging—will be available to the scientific community, accelerating research to understand and ultimately prolong healthy human aging.

PI_NAMEs: CHURCHILL, GARY A;KORSTANJE, RONNY  (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Acceleration;Advisory Committees;age related;age-related disease;aged;Aging;aging related;Alleles;animal old age;Animals;behavioral phenotyping;Biological;Biology of Aging;Candidate Disease Gene;candidate validation;career development;Cell Aging;Chromosome Mapping;Collaborations;Communities;Complex;Computer Assisted;Data;Data Analyses;data dissemination;data management;Databases;Disease;disorder risk;Educational workshop;Ensure;Environmental Risk Factor;experience;extend lifespan;Funding;Genes;Genetic;Genetic Code;Genetic Models;Genetic Research;Genetic Variation;Geropathology;Geroscience;Goals;Health;healthspan;healthy aging;Heart;Histologic;Human;Human Genetics;Image Analysis;Inbred Strain;Individual;Information Resources;insight;Institution;Joints;Leadership;life span;Link;Liver;Longevity;Lung;Machine Learning;Maps;Mentorship;Metabolic;Methods;microbiome;mouse genetics;mouse model;Mus;next generation;novel;old mice;open source;Pathology;Peer Review;Pharmaceutical Preparations;phenome;Phenotype;phenotypic data;Physiological;Pilot Projects;Polygenic Traits;Population;Principal Investigator;Process;programs;Protocols documentation;public health relevance;Publications;Qualifying;Quality Control;Research;research and development;Research Personnel;Resources;response;Role;Sampling;senescence;senolytics;Shock;Statistical Methods;Structure;symposium;System;Technology;The Jackson Laboratory;Time;Tissue Sample;Tissues;tool;Training;trait;user-friendly;Validation;Variant;Visit;web site

PROJECT_TITLE: Nathan Shock Center for Excellence in Basic Biology of Aging


NIH_SPENDING_CATS: Aging

PI_NAMEs: KORSTANJE, RONNY  (contact)

PROJECT_TERMS: Affect;age-related disease;Aging;aging process;aging related disease;Applications Grants;Award;Biological;Biological Models;biological systems;Biology of Aging;Body System;Budgets;career;career development;Cells;cohort;Collaborations;Communities;Data;design;Environment;experimental study;Faculty;Foundations;Funding;Funding Agency;Genes;Genetic;Geroscience;Goals;Grant;healthy aging;innovation;insight;Institution;Laboratories;Longevity;meetings;Mentorship;Molecular;mouse genetics;Mus;Pathway interactions;Phenotype;Play;Process;programs;Publications;Research;research and development;Research Personnel;Resources;Role;Scientist;Shock;success;Systems Biology;Talents;Technology;The Jackson Laboratory;Tissues;Work;Writing

PROJECT_TITLE: Research Development Core


ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE The overall goal of this R01 application is to understand the role of RIPK2, a key initiator and propagator of inflammatory signaling, in clinically relevant animal models of ischemic stroke. The proposed research is relevant to public health because it will help understand the potential therapeutic value of RIPK2 inhibitors to reduce brain damage and improve neurological recovery following stroke. This proposal is relevant to the NINDS's mission that pertains to developing significant knowledge in basic research that will create the foundation for treating ischemic stroke and reducing the burden of this neurological disease.

PI_NAMEs: CANDELARIO-JALIL, EDUARDO JESUS (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Ablation;Acute;Address;Adult;aged;Alteplase;Animal Model;Animals;Apoptosis;Attenuated;Basic Science;behavioral outcome;Benzamides;blood-brain barrier permeabilization;Brain;Brain Injuries;Brain Ischemia;Cause of Death;Cell Death;Cell Lineage;cell type;Cells;chemokine;Chronic;clinically relevant;Coagulation Process;cognitive function;comorbidity;CRISPR/Cas technology;cytokine;Data;Dementia;Dendritic Cells;Diabetes Mellitus;Dose;Enterobacteria phage P1 Cre recombinase;Excision;Exons;Financial Hardship;Flow Cytometry;Foundations;functional outcomes;genome editing;glial activation;Goals;Healthcare Systems;Hour;Immune;immune cell infiltrate;Immunoassay;Impairment;improved;improved outcome;in vivo;Industry;Infarction;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;inhibitor;Injury;innovation;Intervention;Invaded;Ischemia;Ischemic Brain Injury;Ischemic Penumbra;Ischemic Stroke;kinase inhibitor;Knockout Mice;Knowledge;Label;Lifelong disability;LoxP-flanked allele;Macrophage;Magnetic Resonance Imaging;Measures;Mechanics;Microglia;Mission;Modeling;Molecular;monocyte;Mouse Strains;Mus;Myelogenous;Myeloid Cells;nano-string;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neuroinflammation;Neurologic;Neurologic Deficit;neurological recovery;neuronal survival;Neurons;neuroprotection;Neuroprotective Agents;new therapeutic target;novel;novel drug class;Obesity;old mice;Outcome;Pathology;Pathway interactions;Patients;Pattern;Peripheral;pharmacologic;Phase;Phenotype;Phosphotransferases;post stroke;Process;Production;Protac;Proteins;Public Health;Receptor Inhibition;Receptor-Interacting Serine/Threonine Protein Kinase 2;recruit;Reperfusion Therapy;Research;response;RIPK2 gene;Rodent;Role;Sensorimotor functions;sex;Signal Transduction;Site;Stroke;stroke model;stroke outcome;stroke patient;stroke therapy;success;Tamoxifen;Technology;Therapeutic;Thrombectomy;thrombolysis;Time;tool;Tracer;Western Blotting;Wild Type Mouse

PROJECT_TITLE: Role of RIPK2 in the neuroinflammatory response to ischemic stroke

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


PI_NAMEs: CHURCHILL, GARY A (contact)

PROJECT_TERMS: Address;Aging;Animals;Biology of Aging;Communication;Communities;cost;Data;data dissemination;data resource;Dedications;design;Effectiveness;Ensure;Equilibrium;experience;Faculty;Faculty Recruitment;Funding;Genetic Research;Goals;Group Meetings;Human Resources;improved;Institution;Interest Group;Internet;Joints;Laboratories;meetings;member;mouse model;Mus;novel;outreach;Phenotype;Policies;Principal Investigator;pro-aging;programs;Protocols documentation;Qualifying;Quality Control;Recommendation;recruit;Research;Resource Development;Resource Sharing;Resources;Services;Shock;Site;skills;Statistical Methods;Structure;success;symposium;System;The Jackson Laboratory;Thinking;Time;Training;United States National Institutes of Health;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Aging;Genetics

PROJECT_TERMS: Age Months;Aging;aging process;animal resource;Animals;Anxiety;Award;Behavioral;behavioral health;Biological Assay;Biology of Aging;Biometry;Blood specimen;Chromosome Mapping;Clinical;Clinical Research;Communication;Communities;Complex;Data;Databases;Development;Dietary Intervention;Ensure;Equilibrium;Female;Funding;Genetic;genetic analysis;Genetic study;Genetic Variation;Goals;Hand Strength;healthspan;Hematology;Human;Immune;Inbred Strain;Inbreeding;Intervention;Intervention Studies;Kidney;Laboratories;life span;male;Methods;migration;Modeling;mouse genetics;mouse model;Mus;novel;old mice;Organ;outreach;phenome;Phenotype;physical conditioning;Pilot Projects;Population;programs;Quality Control;Quantitative Trait Loci;Reproducibility;Research;research and development;Research Personnel;Resolution;Resources;response;senescence;senolytics;Shock;Testing;The Jackson Laboratory;Time;Tissue Sample;Tissues;trend;web site;Women's cohort;Work

PROJECT_TITLE: Animal and Phenotyping Core


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease;Regenerative Medicine;Transplantation

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Proper biliary epithelial cell (BEC) specification is essential as it allows intrahepatic bile duct formation and proper liver function. This proposal will establish a deep functional understanding of how the transcription factor Sox9 regulates: (1) BEC specification during development and (2) BEC expansion following liver damage. Our studies will define the requirement of Sox9 in establishing proper intrahepatic BEC networks during development and ductular reaction which will help develop an understanding of basic mechanisms of liver repair that can be used to identify novel targets for therapeutics.

PI_NAMEs: HRNCIR, HANNAH ROSE (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: 3-Dimensional;Ablation;Acute;Adult;Alagille Syndrome;Alternative Therapies;Apoptosis;Bile Acids;bile duct;Bile fluid;Biliary;Biliary Atresia;Biochemistry;Biological Assay;Biology;Cell Differentiation process;Cell Maintenance;Cell Physiology;Cellular Morphology;Characteristics;Chronic;Combined Modality Therapy;conditional knockout;Data;Development;Duct (organ) structure;end stage liver disease;Epithelial Cells;Epithelium;Exhibits;experimental study;Faculty;Failure;Fibrosis;Genetic;Genetic Transcription;Goals;graft failure;Hepatocyte;Heterogeneity;Histology;Homeostasis;Immunohistochemistry;Impairment;improved;Injury;intrahepatic;Intrahepatic bile duct;Knock-out;Knockout Mice;Liver;Liver diseases;liver function;liver injury;Liver Regeneration;liver repair;liver transplantation;Mediating;Medical;Morphogenesis;Morphology;mouse model;Mus;Natural regeneration;new therapeutic target;novel;Organ Donor;Organoids;Patient-Focused Outcomes;Patients;Phenotype;Play;Population;Positioning Attribute;Prevalence;Proliferating;Reaction;Recovery;regenerative;Regenerative capacity;Regenerative Medicine;Regulation;Reporting;Research;Risk;Role;Secure;Serum;single-cell RNA sequencing;Specific qualifier value;stem cell function;Testing;Tissue imaging;tissue regeneration;Tissues;Training;transcription factor;Transcriptional Regulation;Transgenes;Transplantation;United States;Work

PROJECT_TITLE: Establishing Sox9 as a regulator of intrahepatic bile duct development and regeneration


ORG_CITY: BAR HARBOR

PROJECT_TERMS: 16S ribosomal RNA sequencing;Acceleration;Address;Adoption;Age;Aging;aging mechanism;aging related;aging related disease;analytical tool;Animals;Biology of Aging;Collaborations;Communities;Computer software;Data;Data Analyses;Data Collection;data dissemination;data management;Data Management Resources;data quality;data resource;data sharing;data tools;Databases;Deposition;Development;Ensure;Epigenetic Process;Expression Profiling;Funding;Gene Expression Profiling;Genetic;Genetic Variation;Genomics;Genotype;Geroscience;Goals;healthspan;improved;Inbreeding;Infrastructure;insight;interactive tool;Laboratories;large scale data;life span;Longitudinal Studies;Measurement;member;metagenomic sequencing;Methods;microbiome;Modeling;Molecular;mouse model;Mus;Online Systems;operation;outreach;phenome;Phenotype;Pilot Projects;Procedures;programs;Proteomics;public repository;Publications;Quality Control;rate of aging;Research;Research Design;Resources;sample archive;Services;Shock;Shotguns;Source;Statistical Data Interpretation;stool sample;System;Technology;The Jackson Laboratory;Tissues;tool;Training;Transcript;transcriptome sequencing;transcriptomics;Update;web site;Work

PROJECT_TITLE: Data and Statistical Core


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: LEXINGTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: The proposed research is relevant to public health because it is expected to identify molecular targets that can be exploited to repair the blood-brain barrier after seizure-induced neuroinflammation and dysfunction. This therapeutic strategy is expected to improve seizure control in patients with epilepsy. Thus, the proposed research is relevant to the part of the NIH/NINDS mission that pertains to developing fundamental knowledge that will help reduce the burden of neurological disease.

PI_NAMEs: BAUER, BJOERN  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Agonist;Arachidonate 5-Lipoxygenase;Attenuated;Automobile Driving;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood capillaries;Brain Diseases;Cell Adhesion Molecules;cerebral capillary;Characteristics;Chronic;Clinical;clinical translation;Combined Modality Therapy;cyclooxygenase 2;Data;Data Reporting;Development;Disease;Endothelium;Epilepsy;evidence base;expectation;Extracellular Matrix Proteins;Extravasation;Feedback;FPR2 gene;Functional disorder;Funding;glutamatergic signaling;Glutamates;Goals;Human;improved;in vivo;Individual;Inflammation;innovation;Intervention;Knockout Mice;Knowledge;Lead;Learning;Leukocytes;Leukotrienes;Link;Lipoxygenase;LOX gene;Matrix Metalloproteinases;Mediating;Mission;Modeling;Molecular Target;mouse model;Mus;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neuroinflammation;Neurons;neurotransmitter release;neurovascular;new therapeutic target;novel;novel therapeutic intervention;Pathway interactions;Patients;Prostaglandins;Proteins;PTGS2 gene;Public Health;Publishing;Rattus;repaired;Research;Research Personnel;Seizures;Signal Transduction;Symptoms;Testing;Therapeutic;Therapeutic Intervention;therapy design;Tight Junctions;translational potential;United States National Institutes of Health;vascular inflammation

PROJECT_TITLE: Novel Therapeutic Strategies to Resolve Neurovascular Inflammation and Repair Blood-Brain Barrier Dysfunction in Epilepsy


NIH_SPENDING_CATS: Aging;Bioengineering;Cost Effectiveness Research;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

PI_NAMEs: MAHONEY, JOHN MATTHEW (contact)

PROJECT_TERMS: Age;age related;age related changes;Age related pathologies;aged;Aging;analysis pipeline;Animals;anti aging;Biology of Aging;Body System;Cell Proliferation;Chronic;Clinical;clinical phenotype;Clinical Trials;clinically relevant;Communities;Computer Assisted;Cost Effectiveness Analysis;Data;Disease;early onset;end of life;experimental study;frailty;Funding;Generations;Geropathology;Geroscience;Goals;healthy aging;Heart;Histologic;Histopathology;Image Analysis;interest;Intervention;intervention effect;Kidney;Knock-out;Lesion;Liver;Lung;Machine Learning;Manuals;Measures;mesangial cell;Modeling;Molecular;Mus;neoplastic;neural network;novel;old mice;open source;Organ;Pathologist;Physiological;pre-clinical research;Process;quantitative imaging;Research;Research Personnel;research study;Resources;Sampling;Scanning;Services;Severities;Shock;Slide;Stains;Structure of parenchyma of lung;System;Testing;Tissues;tool;Training;user-friendly;Validation;women versus men

PROJECT_TITLE: Image Analysis Core


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Childhood Obesity;Clinical Research;Machine Learning and Artificial Intelligence;Maternal Health;Microbiome;Nutrition;Obesity;Pediatric;Pregnancy;Prevention;Women's Health Research

ORG_CITY: CINCINNATI

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PROJECT NARRATIVE Using powerful technologies, we will comprehensively study the impact of maternal obesity and health on breastfeeding and the composition of human milk, and how they affect child growth and health. This project is enabled by using samples and data from ongoing birth cohorts including 1,615 Cincinnati mother-infant pairs.

PI_NAMEs: MORROW, ARDYTHE L (contact)

PROGRAM_OFFICER_NAME: ROSS, SHARON A

PROJECT_TERMS: Academy;Address;Adolescent;Affect;Age;Aliquot;American;Award;Bar Codes;Biological Markers;Biological Process;biological systems;biomarker validation;Birth;Blood;Body mass index;Breast Feeding;Child;Child Health;cohort;Collection;comorbidity;Complex;cryogenics;cytokine;Data;Data Analyses;Data Collection;data repository;Data Science;Data Set;Databases;design;Diet;Discipline;Discipline of obstetrics;Ecology;Enrollment;Environment;Epidemic;epidemiology study;Exclusive Breastfeeding;Fatty Acids;follow-up;Funding;Funding Mechanisms;Funding Opportunities;Goals;Growth;Health;health knowledge;hormone regulation;Human Milk;Immunity;immunoregulation;Impairment;Infant;Infant Health;infant nutrition;Infection;Inflammation;Inflammatory;inflammatory marker;Investigation;Lactation;Leptin;Life;Machine Learning;Maternal Health;maternal obesity;Measures;Metabolic;Metabolic Marker;metabolome;metabolomics;microbiome;microbiome analysis;Milk;milk production;Modeling;mother nutrition;Mothers;multiple omics;National Institute of Allergy and Infectious Disease;National Institute of Child Health and Human Development;next generation;Obesity;Obesity Epidemic;obesity in children;offspring;Oligosaccharides;Outcome;Pediatrics;Peptides;Phenotype;Population Heterogeneity;predictive marker;Pregnancy;Pregnant Women;prenatal;prepregnancy;Proteins;Proteomics;Public Health;Publishing;Qualifying;Questionnaires;Recommendation;Records;Reporting;Research;Research Design;Research Personnel;Research Priority;Residual state;Risk;sample collection;Sampling;Scientist;Serum;Standardization;statistical and machine learning;success;System;Systems Biology;Techniques;Technology;Testing;Third Pregnancy Trimester;Translations;U-Series Cooperative Agreements;United States Public Health Service;Variant

PROJECT_TITLE: MOM2CHild Study: Leveraging systems biology toward discoveries in Maternal Obesity, Milk, and Translation To Child Health


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: RALEIGH

ORG_DEPT: BIOLOGY

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: NARRATIVE Despite the thousands of chemicals used in commerce, our understanding of their effects on human health is not well understood. The Comparative Toxicogenomics Database (CTD) is a unique, publicly available resource that provides information about human exposures and how these exposures influence our genes, our biology, and ultimately our health. This project will build on our established infrastructure to expand the data content and analysis capacity of CTD to provide new insights into the complex relationship between our environment and human diseases.

PI_NAMEs: DAVIS, ALLAN PETER;MATTINGLY, CAROLYN J. (contact);WIEGERS, THOMAS

PROGRAM_OFFICER_NAME: DUNCAN, CHRISTOPHER GENTRY

PROJECT_TERMS: Address;Anatomy;Asthma;base;Biological;Biological Process;Biology;biomedical resource;Chemical Actions;Chemical Exposure;Chemicals;Chronic;Chronic Disease;Code;Commerce;Communities;comparative;Complex;Computer software;Data;data complexity;data integration;data resource;Data Set;database design;Databases;Dedications;design;Development;Diabetes Mellitus;Disease;disease phenotype;diverse data;Ensure;Environment;Environmental Exposure;Environmental Health;Environmental Risk Factor;Etiology;Evaluation;experience;exposed human population;Exposure to;Funding;Genes;Genetic;Goals;Growth;Health;Human;human disease;Hypertension;improved;Infrastructure;innovation;insight;Investments;Knowledge;knowledgebase;Literature;Malignant Neoplasms;Manuals;novel;Obesity;Outcome;Pathway interactions;Peer Review;Performance;Phenotype;preservation;Productivity;Proteins;Research;research and development;Resources;response;Review Literature;Software Design;Structure;System;text searching;Therapeutic Intervention;therapeutically effective;Time;tool;Toxic effect;Toxicogenomics;United States National Institutes of Health;web-based tool;Widespread Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-T(55)R]


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;Biodefense and Related Countermeasures;Brain Disorders;Dementia;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Vector-Borne Diseases;West Nile Virus

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

PHR: Project Narrative West Nile Virus (WNV) can cause severe and long-lasting neurological disease, with an initial infection in the hippocampus resulting in some of the neuropathology and neuroinflammation seen in Alzheimer's disease (AD). In this proposal, we will test the hypotheses that prior exposure to the WNV worsen AD-related behavioral alterations, cognitive injury, neuropathology, and that these effects are apolipoprotein E isoform-dependent and are associated with neuroinflammation. The generated results will facilitate the identification of novel biomarkers and targets for novel therapeutic strategies for AD and other age-related neurodegenerative disorders, including those of mixed etiology dementias (MED).

PI_NAMEs: HIRSCH, ALEC J;RABER, JACOB  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: 3' Untranslated Regions;Acceleration;Age;age effect;Age Months;age related neurodegeneration;Alleles;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid peptide;Animals;Anti-Inflammatory Agents;Antiinflammatory Effect;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Arctic mutation;Attenuated;Behavioral;behavioral phenotyping;Binding;Binding Proteins;Body Temperature;Brain;Capsid Proteins;Cells;Centenarian;Cerebrum;chemokine;Chickenpox;Cholesterol Homeostasis;Circadian Rhythms;Cognitive;cognitive performance;cohort;Communicable Diseases;cytokine;Dengue Virus;Disease Progression;DNA Methylation;Dose;entorhinal cortex;Episodic memory;Euthanasia;Exposure to;Flavivirus;Genes;Genetic;Genomics;glial activation;Hepatitis C virus;Hepatitis E virus;Herpes zoster disease;Herpesvirus 1;hippocampal atrophy;Hippocampus;HIV-1;Homeostasis;Human;Human Amyloid Precursor Protein;Human Herpesvirus 4;human model;Impaired cognition;Impairment;improved;Infection;Inflammation;Inflammatory;Injury;Interferons;Interleukins;Klebsiella pneumoniae;Knock-in;Knock-in Mouse;Late Onset Alzheimer Disease;Learning;Lipids;Long-Term Effects;Macrophage;Malaria;Measures;Microglia;middle age;millimeter;mixed dementia;mouse model;Mus;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neuroinflammation;neuron loss;neuropathology;neurotropic;new therapeutic target;novel;novel marker;novel therapeutic intervention;old mice;Pathogenesis;Patients;Peptides;Performance;Pilot Projects;Plasma;Play;Predisposition;Presynaptic Terminals;Process;Production;Promoter Regions;Protein Isoforms;Purkinje Cells;Reporting;response;Risk;Risk Factors;Role;Senile Plaques;sensor;Stimulus;Synapses;synuclein;targeted treatment;Temperature;Testing;Time;Up-Regulation;uptake;Very low density lipoprotein;Viral Genome;Virus;Virus Diseases;Virus Inhibitors;West Nile viral infection;West Nile virus;Wild Type Mouse;wireless

PROJECT_TITLE: Role of human apolipoprotein E isoforms in long-term effects of West Nile Virus exposure on Alzheimer's disease-related behavioral alteration, cognitive injury, neuroinflammation, and neuropathology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-Z(55)R]


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Enhancing healthy lifespan is one of the key challenges of the 21st century. Metformin is an anti-diabetic drug proposed to be a candidate therapy to target aging in humans, and we identified metformin-mimetic peptide drug candidates and will test if they are involved in the anti-aging effects of metformin, which in turn can potentially help define individuals that will respond to metformin and possibly serve as alternative healthspan-enhancing treatments. Our studies will define a completely novel direction in understanding the actions of metformin on delaying aging, and will establish novel biomarkers as well as complementary/alternative anti-aging approaches.

PI_NAMEs: COHEN, PINCHAS  (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: age effect;age related;Aging;aging related;aging related disease;anti aging;Anti-diabetic Drugs;Attenuated;Bioinformatics;Blood Glucose;Cell Line;cell type;Chronic;Clinical;cohort;Collaborations;Complex;cytokine;Cytoprotection;Data Set;diabetic;Disease;drug candidate;Fatty acid glycerol esters;four-arm study;Gene Expression Profile;genome wide association study;Genotype;glucose metabolism;healthspan;Hepatocyte;High Fat Diet;Human;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;knock-down;life span;Liver;liver biopsy;Mediating;Metabolism;Metformin;middle age;mimetics;Mitochondria;Mitochondrial DNA;mitochondrial genome;model organism;Mus;Muscle;Names;Non-Insulin-Dependent Diabetes Mellitus;novel;novel marker;old mice;Open Reading Frames;Pathway interactions;Peptides;peptidomimetics;Principal Investigator;Production;Reactive Oxygen Species;Regulation;Respiratory Chain;response;Risk;RNA;Scandinavian;Signal Transduction;Single Nucleotide Polymorphism;Small Interfering RNA;System;Testing;Therapeutic;Tissues;Transcript;transcriptome;transcriptome sequencing;Variant;Weight;Weight Gain

PROJECT_TITLE: Metformin-Regulated Mitochondrial Peptides and their Effects on Aging


NIH_SPENDING_CATS: Aging;Nutrition

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: 8. PROJECT NARRATIVE This application is focused on understanding the role that lipids play in regulating adipose senescence. The studies address how immune cells affect adipocytes lipolysis and how fatty acids regulate SIRT1 and oxidative stress. Oxidative stress in turn produces reactive lipids that induce senescence in preadipocytes. The work will establish that intracellular fatty acids, particularly monounsaturated fatty acids, are potential bioregulators of senescence and represent an untapped therapeutic opportunity.

PI_NAMEs: CAMELL, CHRISTINA  (contact)

PROJECT_TERMS: 4 hydroxynonenal;Address;Adipocytes;Adipose tissue;Affect;Age;age related;age-related disease;aged;Aging;aging process;aging related;aging related disease;Aldehydes;antioxidant enzyme;Antioxidants;Attenuated;attenuation;Automobile Driving;B-Lymphocytes;beta-Galactosidase;Binding;Biology;Catecholamines;CCL2 gene;Cell Aging;Cells;Cellular biology;chemical property;Complex;Deacetylation;Diet;Diffuse;DNA;Down-Regulation;Enzymes;Fatty Acids;Fibroblasts;Genetic;Genetic Transcription;hallmarks of aging;healthspan;Hexenal;Hormonal;Immune;Impairment;Infiltration;Inflammation;Inflammatory;insight;interest;Intervention;Laboratories;Length;Link;lipid metabolism;Lipid Peroxidation;Lipids;Lipolysis;Macrophage;Memory;Metabolic;Metabolic Diseases;Mitochondria;Molecular;Monounsaturated Fatty Acids;mouse model;novel;Oxidative Stress;Phenotype;Physiological;Play;Process;Production;programs;Protein Dephosphorylation;Proteins;Publishing;Regulation;response;Role;senescence;senescent cell;senolytics;sex;Signal Transduction;SIRT1 gene;Site;Testing;Therapeutic;Time;Tissues;Triglycerides;unpublished works;Visceral;Viscosity;Work

PROJECT_TITLE: Inflammation, Lipid Metabolism and Senescence


NIH_SPENDING_CATS: Aging;Cardiovascular;Disability Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: ORLANDO

ORG_NAME: ADVENTHEALTH ORLANDO

PHR: PROJECT NARRATIVE Older adults experience a loss of mobility that leads to disability, which is a serious health care issue in an aging US population. Mitochondrial respiration is a key property of skeletal muscle that supports walking speed, physical function and fitness in older adults. The primary goal of this project is to explore the role of mitochondrial DNA (mtDNA) in age related changes in muscle oxidative capacity and physical function.

PI_NAMEs: COEN, PAUL MARTIN;DELANY, JAMES P (contact);TRANAH, GREGORY J.

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Address;Admixture;Adult;African;African American;African American population;African American Women;African Women;age related changes;aged;Aging;Alzheimer's Disease;Amerindian;Ancillary Study;Basal metabolic rate;Biological;Biopsy;Biopsy Specimen;Blood;Blood Cells;cardiorespiratory fitness;cardiovascular fitness;Caucasians;Clinical;cohort;Complex;Data;design;disability;disability risk;DNA;East Asian;Etiology;European;exercise training;experience;fitness;Freezing;Genetic;Genetic Epistasis;Genome;genome wide association study;Genomics;Goals;Haplogroup;Haplotypes;Healthcare;heteroplasmy;High Prevalence;Human;human disease;improved;Incidence;Individual;Inherited;Knee Osteoarthritis;Link;Longevity;Longitudinal Studies;men;metabolic rate;Mitochondria;Mitochondrial DNA;Mitochondrial Proteins;Mobility decline;Mobility disability;Muscle;Muscle function;Muscle Mitochondria;Mutate;Mutation;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;older adult;personalized approach;Phenotype;phenotypic data;Physical activity;Physical Fitness;Physical Function;Physiological;Play;Population;precision medicine;prevent;Property;Race;racial determinant;racial difference;Respiration;response;Risk;Role;Sampling;Single Nucleotide Polymorphism;Site;Skeletal Muscle;targeted treatment;Thinness;Time;Training Programs;Variant;Walking;walking speed;White Women;Woman

PROJECT_TITLE: Impact of mitochondrial genetics on muscle oxidative capacity, fitness, and mobility in older adults

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Infant Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Loss of function mutations in RBFOX2 gene are identified in infants with hypoplastic left heart syndrome. Our goals are to determine how loss of RBFOX2 function leads to cardiovascular developmental defects observed in hypoplastic left heart syndrome patients. Our findings are expected to pave the way for novel therapies to restore RBFOX2 function in hypoplastic left heart syndrome patients in the future.

PI_NAMEs: KUYUMCU-MARTINEZ, MUGE NESLIHAN (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: 3' Untranslated Regions;Ablation;Address;Adhesions;Advanced Development;Affect;Alternative Splicing;Antisense Oligonucleotides;Aorta;aortic valve;Binding;Cardiac;Cardiac Myocytes;Cardiac Surgery procedures;cardiogenesis;Cardiovascular system;Cell Adhesion;cell motility;Cell Physiology;Cell Proliferation;Cells;Circulation;clinically relevant;Common Ventricle;Complementary DNA;conditional knockout;congenital heart abnormality;Congenital Heart Defects;Custom;Death Rate;Defect;design;Development;Developmental Process;Disease;Embryonic Heart;Endothelial Cells;Etiology;Exhibits;Extracellular Matrix;Focal Adhesions;Future;gene correction;Gene Expression;gene function;Generations;Genes;Genetic;Genetic study;Goals;Health;Heart;Heart failure;Heart Transplantation;Human Genetics;Hypoplastic Left Heart Syndrome;Impairment;Infant;innovation;insight;Introns;Knock-in;Knockout Mice;Knowledge;Left;Left ventricular structure;Length;Link;loss of function;loss of function mutation;Mediating;Mesenchymal;migration;Mitochondria;Mitral Valve;Molecular;mortality;mouse model;mRNA Precursor;Mus;mutant;Myoblasts;Myocardial;nanopore;Neurofibromin 2;novel;novel therapeutics;Operative Surgical Procedures;Pathogenicity;Pathology;Patients;Phenotype;Poly A;Polyadenylation;prevent;Proliferating;Property;Protein Isoforms;Regulation;Reporting;Right ventricular structure;RNA;RNA-Binding Proteins;Role;Series;Side;Signal Pathway;Signal Transduction;Site;Syndrome;Techniques;Testing;Therapeutic;Tissues;Transcript;Work

PROJECT_TITLE: The role of RNA binding proteins in heart development and congenital heart defects

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-C(02)]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Infectious Diseases;Kidney Disease;Organ Transplantation;Transplantation

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Under the HIV Organ Policy Equity (HOPE) Act, kidneys from donors with HIV can be used for transplant in recipients with HIV. Early studies of this practice demonstrate excellent short-term patient survival and survival of the transplanted organ; however, kidney rejection rates were high and long-term outcomes are unknown. This research will compare HIV+ and HIV- donor kidney transplant in HIV+ recipients in order to determine 1) the impact of HIV+ donor kidneys on rejection and 2) long term outcomes, and also includes scientific studies designed to improve our understanding of rejection in people with HIV and the general population.

PI_NAMEs: DURAND, CHRISTINE MARIE (contact);SEGEV, DORRY L.

PROGRAM_OFFICER_NAME: HAYES, DEBORAH

PROJECT_TERMS: Antibodies;antibody-mediated rejection;antiretroviral therapy;Autoantibodies;Basic Science;Biological Assay;CD3 Antigens;CD4 Lymphocyte Count;Cells;chemokine;co-infection;cohort;cross reactivity;cytokine;Cytomegalovirus;Data;data management;data registry;detection assay;Development;Donor person;donor-specific antibody;Enrollment;Ensure;Equity;Event;experience;follow-up;General Population;Generations;graft function;Graft Survival;Histologic;HIV;Hospitalization;Human;Immunologics;Immunoprecipitation;Immunosuppression;improved;improved outcome;Infection;Inflammation;Inflammatory Response;Infrastructure;insight;Intervention;isoimmunity;Kidney;Kidney Transplantation;Knowledge;Longterm Follow-up;Mediating;Memory;microbial;Modeling;Monitor;Multicenter Trials;novel;operation;Organ;Organ Procurements;Organ Transplantation;Outcome;pathogen;Pathway interactions;Patients;Persons;Phage Display;Policies;primary endpoint;Prophylactic treatment;Proteins;Research;Research Design;response;Risk;Risk Factors;Safety;safety and feasibility;Sample Size;Selection Criteria;Sorting;success;T-Cell Receptor;T-Lymphocyte;Time;Toxin;transplant centers;Transplant Recipients;Transplantation;trend;trial comparing;Viral;Viremia;Virion;Virulence Factors;Virus;Virus Diseases;Wait Time;Work

PROJECT_TITLE: Kidney Transplantation from Donors with HIV: Impact on Rejection and Long-term Outcomes


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Digestive Diseases;Mental Health;Mental Illness;Neurosciences

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: RELEVANCE Anxiety and depression are leading mental illnesses often linked to stress and systemic immune state by unknown mechanisms. Here, we will study the effects of gastrointestinal inflammation and stress by modeling these inputs separately and in combination in mice and comprehensively examining their effects on behavior and brain reward/aversion circuitry function. We will also study a novel underlying signal transduction pathway as a critical mechanism mediating this comorbidity and test a number of interventions to rescue the maladaptive effects of inflammation and stress, possibly providing a path to therapeutic interventions.

PI_NAMEs: BIBB, JAMES A (contact)

PROGRAM_OFFICER_NAME: TONELLI, LEONARDO HERALDO

PROJECT_TERMS: Address;adducin;Adult;Affect;Anxiety;Basal Ganglia;Behavior;Behavioral;behavioral response;Biochemical;biological adaptation to stress;Brain;brain circuitry;Brain region;burden of illness;Cell Physiology;cell type;Chemical Models;chemically induced colitis;Chronic;Clinical;comorbidity;Corpus striatum structure;Critical Pathways;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;disability;Dopamine;Dopamine D1 Receptor;DRD2 gene;Dynorphins;experience;Exposure to;Female;Fiber;Functional disorder;gastrointestinal;gastrointestinal function;Goals;Health;Immune;Immune system;Impairment;in vivo;Inflammation;Inflammation Mediators;Inflammatory Bowel Diseases;Inflammatory Response;inhibitor;innovation;Intervention;kappa opioid receptors;Knock-out;Link;male;Mediating;Mental Depression;Mental disorders;Mental Health;Modeling;Molecular;Mood Disorders;mortality;multiple omics;Mus;neurobehavior;neurobehavioral;neurobiological mechanism;neurochemistry;neuronal excitability;Neurons;neurophysiology;neuropsychiatric disorder;neuropsychiatry;neurotransmission;novel;novel therapeutic intervention;Nucleus Accumbens;Pathway interactions;Patients;Peripheral;pharmacologic;Phosphorylation;Photometry;Process;psychological symptom;Research;Rewards;Risk;Risk Factors;Role;sex;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Stress;stressor;Structure;Suicide;Synapses;Synaptic plasticity;systemic inflammatory response;targeted treatment;Testing;Therapeutic Intervention;tool;Transgenic Organisms;Ventral Striatum;Visceral

PROJECT_TITLE: Peripheral Inflammation and Stress Drive Ventral Striatal Maladaptations

STUDY_SECTION: BNRS

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