NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The long-term objective of this collaboration is to discover the essential logic and underlying molecular mechanisms that drive planar cell polarity (PCP) signaling, a highly conserved pathway that is a critical component of normal heart development. Previously applied experimental approaches have proven unable to untangle the interlocking feedback loops that are thought to underlie PCP signaling. We describe novel genetic, biochemical, imaging and computational modeling approaches that will reveal both the underlying molecular logic and mechanistic basis for this critical component of normal heart development.

PI_NAMEs: AXELROD, JEFFREY D. (contact);DUNN, ALEXANDER R

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: Aorta;Binding;Biochemical;Biological Assay;Biological Models;biophysical analysis;biophysical techniques;Cadherins;Cardiac;cardiogenesis;Cell division;cell motility;Cell Polarity;Cell-Cell Adhesion;Cells;Cellular Structures;Collaborations;Complex;Computer Models;Congenital Abnormality;congenital heart abnormality;conotruncal heart defect;Core Protein;Coupled;Data;deafness;Defect;Development;Dictyostelium;Disease;Dissection;Distal;Dorsal;Double Outlet Right Ventricle;Drosophila genus;Dsh protein;Epithelium;Feedback;fly;Generations;Genetic;genetic approach;genetic manipulation;Genetic study;Heart;Heart Atrium;Heart Diseases;Human;Image;Individual;insight;intercalation;Intercellular Junctions;interdisciplinary approach;Knowledge;Left ventricular structure;Lipids;Logic;lung development;Mesenchymal;Microscopy;migration;Molecular;molecular asymmetry;molecular scale;Morphogenesis;nanodisk;Neural Tube Defects;neutrophil;novel;Oranges;Organ;Organism;Outcome;Pathology;Pathway interactions;Physical condensation;planar cell polarity;polarized cell;Process;prospective;Pulmonary artery structure;reconstitution;Recording of previous events;Resolution;Right ventricular structure;Role;Saccharomycetales;Scaffolding Protein;segregation;Septate;Signal Pathway;Signal Transduction;single molecule;Situs Inversus;System;Techniques;theories;Therapeutic Intervention;Time;Tissues;tool;Translating;Transposition of Great Vessels;Tube;Venous;Vertebrates;Work;Yeasts

PROJECT_TITLE: A multidisciplinary approach to understanding feedback and clustering in PCP signaling

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Human Genome;Immunotherapy;Lung;Lung Cancer;Prevention;Skin Cancer

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE With the revolutionary discovery of immunotherapy as a highly effective treatment for cancer, the immune system, and specifically the interaction between CD8 T cells and HLA molecules, has emerged as an essential player in cancer treatment, but its role in early tumorigenesis is understudied. Germline HLA heterozygosity been shown to improve tumor immunogenicity and thus response to immunotherapy as well as lower susceptibility to viral infection, but its role in cancer risk is unknown. This proposed research will use large, diverse clinical and genomic datasets and an in vivo model of HLA-mediated immune surveillance to implicate germline HLA zygosity in cancer risk, potentially identifying an important biomarker for increased cancer screening, and provide insights into the mechanism of HLA-mediated immune surveillance of early tumors to guide treatment and prevention strategies.

PI_NAMEs: CHOWELL, DIEGO ;SAMSTEIN, ROBERT M (contact)

PROGRAM_OFFICER_NAME: SIMONDS, NAOKO ISHIBE

PROJECT_TERMS: Acute Myelocytic Leukemia;Affect;Aftercare;Alleles;Allogenic;antigen binding;Antigen Presentation;Antigens;Autoimmunity;Binding;biobank;Biological Markers;Cancer Etiology;Cancer Model;cancer prevention;cancer risk;cancer therapy;cancer type;Carcinogens;CD8-Positive T-Lymphocytes;Cell surface;Characteristics;Clinical;Clinical Data;Communicable Diseases;Cutaneous Melanoma;Cytometry;Data Set;Databases;Development;diverse data;DNA biosynthesis;DNA Damage;DNA Sequence Alteration;DNA sequencing;effective therapy;Environmental Exposure;Environmental Risk Factor;Etiology;Fostering;Genes;Genetic;Genetic Determinism;Genetic study;Genetic Variation;genomic data;Genotype;Germ Lines;Goals;Hematopoietic Stem Cell Transplantation;Heterozygote;Histocompatibility Antigens Class I;Histocompatibility Antigens Class II;HLA Antigens;Homozygote;Human;Human Genetics;human model;Immune;immune cell infiltrate;immune checkpoint blockade;Immune response;Immune system;Immunogenetics;immunogenicity;Immunologic Surveillance;Immunoprevention;immunoregulation;Immunotherapy;improved;in silico;In Vitro;in vivo Model;Individual;Inherited;insight;Institution;Lesion;Loss of Heterozygosity;Lung;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mediating;Melanoma;Modeling;Molecular;mouse model;Mus;Mutation;neoantigens;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;Outcome;Patients;Peptides;phenotypic data;predictive marker;Predisposition;premalignant;Prevention strategy;Probability;Process;Prospective cohort;protein aminoacid sequence;Replication Error;Research;response;Risk;Risk Factors;Role;Screening for cancer;single-cell RNA sequencing;Smoking;smoking exposure;Solid Neoplasm;Specificity;System;T-Lymphocyte;Testing;therapeutic target;Tobacco;transcriptome sequencing;treatment strategy;tumor;tumorigenesis;Ultraviolet Rays;Urethane;UV Radiation Exposure;Vaccines;Validation;Variant;Vertebrates;Virus Diseases

PROJECT_TITLE: Immunogenetic determinants of cancer risk

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-Q (80)]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Clinical Research;Data Science;Disability Research;Hearing Loss;Machine Learning and Artificial Intelligence;Neurosciences;Prevention

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: Project Narrative Traditional methods for estimating exposure-hearing relations, which typically use pure-tone average hearing thresholds to define the outcome, may not comprehensively capture useful information encompassed by the shape of the audiogram across the range of frequencies; since existing statistical methods are insufficient for analysis of the audiogram shape data, we will develop analytical methods for estimating exposure-hearing relations when the outcomes are hearing phenotypes characterized by audiogram shapes. In addition, current analytic methods rely on either pure-tone audiometry data or self-reported hearing data as the outcome, but not both; these two outcome measures are in fact complementary, and we will develop statistical methods for integrating the pure-tone audiometric data and self-reported data. We will apply the hearing data analysis methods to the Conservation of Hearing Study within the Nurses’ Health Study II, the Medical University of South Carolina Hearing Study, and the National Health and Nutrition Examination Survey (NHANES), and user-friendly software developed to implement all new methods will be made publicly available.

PI_NAMEs: WANG, MOLIN  (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Acquired Deafness;analytical method;Auditory Threshold;Categories;Classification;Clinical;Complex;complex data;Data;Data Analyses;Data Reporting;Data Set;Development;Disabling condition;Ear;Environment;Epidemiologist;epidemiology study;Evaluation;Frequencies;Hand;Hearing;hearing impairment;Hearing problem;hearing range;Hearing Tests;improved;Individual;insight;learning strategy;Life;Literature;Longitudinal cohort study;Longitudinal Studies;Measures;Medical;Methods;Modeling;modifiable risk;multidimensional data;National Health and Nutrition Examination Survey;novel;Nurses' Health Study;Outcome;Outcome Measure;Participant;Patient Self-Report;Pattern;Persons;Phenotype;population based;Presbycusis;prevent hearing loss;preventive intervention;Publishing;Pure-Tone Audiometry;Reporting;Research;Risk Factors;Shapes;software development;sound;South Carolina;Specific qualifier value;Statistical Methods;Structure;supervised learning;training data;Universities;unsupervised learning;user friendly software;user-friendly;Variant;Work

PROJECT_TITLE: What Causes Hearing Loss: Advancing the Methods

STUDY_SECTION: ASPB

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel B Study Section[ASPB]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Vancomycin is the most common first-line empiric coverage for suspected late-onset sepsis in preterm infants, even though (1) national guidelines recommend against such use, (2) such use offers no added advantage, and (3) is linked to a rise in infections with vancomycin resistant pathogens. Using a mixed-methods approach we will implement a vancomycin-reducing protocol in preterm infants across 13 neonatal intensive care units in two large healthcare networks. By critically investigating factors influencing the implementation of the protocol and reduction of unnecessary vancomycin use in this multi-center study, we will provide a road map for the broader implementation of vancomycin reducing protocols across NICUs in the United States

PI_NAMEs: MUKHOPADHYAY, SAGORI  (contact)

PROGRAM_OFFICER_NAME: MILLER, MELISSA

PROJECT_TITLE: Implementing vancomycin-sparing regimens in preterm infants

STUDY_SECTION: HSQR

STUDY_SECTION_NAME: Healthcare Patient Safety and Quality Improvement Research[HSQR]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Immunotherapy;Neurosciences;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: POJECT NARRATIVE Glioblastoma (GBM) is the most common and the most lethal primary malignant brain tumor. Immunotherapeutic strategies represent promising new therapeutic tools as they seek to promote an effective antitumor immune response against a patient’s own tumor. In this proposal, we take advantage of the relatively immune-rich microenvironment of RAF-driven glioma to investigate novel determinants of the glioma-associated immune response, including microglia, macrophages, and T cells.

PI_NAMEs: PHILLIPS, JOANNA  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: anti-PD-1;anti-tumor immune response;Antigen Presentation;Antigen Presentation Pathway;Antigen-Presenting Cells;antigen-specific T cells;Brain;Brain Neoplasms;CD8-Positive T-Lymphocytes;Cell Maturation;Characteristics;chemokine;Chemotaxis;Collection;comparative;CXCL14 gene;CXCR4 gene;Data;Dendritic Cells;Effectiveness;Genetic Transcription;Glioblastoma;Glioma;Goals;Human;Immune;Immune response;Immunocompetent;Immunologic Memory;immunological diversity;immunomodulatory therapies;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;in vivo;Interferon Type I;Laboratories;Lymphocyte Depletion;Macrophage;Malignant neoplasm of brain;Maps;Microglia;Modeling;Molecular;mouse model;Mus;Myelogenous;Myeloid Cells;neoplastic cell;novel;novel therapeutics;Outcome;Patients;Phenotype;Population;programs;recruit;Resolution;Role;Sampling;Shapes;Signal Transduction;spatial relationship;System;T cell infiltration;T cell response;T-Cell Activation;T-Lymphocyte;Technology;Testing;Therapeutic;tool;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Tumor-associated macrophages;tumor-immune system interactions

PROJECT_TITLE: Regulating the glioma immune microenvironment

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CN-S (03)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: SAN DIEGO

ORG_DEPT: BIOLOGY

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: Narrative: MEF2 is a protein the controls many processes in the body including muscle and neural development, and mutations affecting MEF2 can result in human disease. Our project will define at the molecular level how MEF2 proteins work inside the cell to control gene expression, and why mutations in MEF2 cause disease.

PI_NAMEs: CRIPPS, RICHARD MATTHEW (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Adult;Affect;Animals;Attenuated;Binding;Biological Models;C-terminal;Cells;Chest;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Complex;Data;Deacetylase;Development;Disease;Docking;Drosophila genus;Engineering;Epigenetic Process;Family;fly;Gene Expression;Gene Family;Genes;Genetic;genetic analysis;genetic manipulation;Genetic Screening;Genome;genome-wide;genome-wide analysis;Health;Heart Diseases;Human;human disease;imaginal disc;in vivo;insight;knock-down;Location;MAP Kinase Gene;Measures;Mediating;member;Mental disability;Modification;Molecular;Molecular Genetics;Muscle;Muscle Development;muscle enhancer factor-2A;Muscle function;mutant;Mutation;Myoblasts;myocyte-specific enhancer-binding factor 2;myogenesis;neurodevelopment;novel;Nucleosomes;p38 Mitogen Activated Protein Kinase;Pathogenicity;Phosphorylation;Play;Post-Translational Protein Processing;premature;prevent;Process;promoter;Protein Isoforms;Proteins;Rapid screening;Regulation;Research;restraint;Role;Site;Specific qualifier value;Structural Genes;Testing;Time;tissue culture;transcription factor;tumor progression;Variant;Wing;Work

PROJECT_TITLE: Molecular genetic analysis of MEF2 function in Drosophila

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ORG_CITY: Los Angeles

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVES This project aims to translate a new cancer imaging biomarker of cell proliferation ([18F]FMAU) to the clinic. This biomarker could provide high-accuracy assessment of tumor response to treatment, improving the care of cancer patients, better guiding therapy selection (when multiple options are available), and providing a powerful research tool for discovery and development of new cancer treatments. Through a synergistic academic- industrial partnership, the overall goal of this project is to make this biomarker more widely available via novel droplet radiochemistry technology and to set the stage to enable wide clinical studies.

PI_NAMEs: CHEN, KAI  (contact);JONES, JASON ;VAN DAM, ROBERT MICHAEL

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Adoption;Amendment;analog;Animal Experiments;Antineoplastic Agents;Biological Markers;cancer care;cancer cell;cancer imaging;Cancer Model;Cancer Patient;cancer therapy;cancer type;Cell Proliferation;Cells;cGMP production;Clinic;Clinical;Clinical Data;Clinical Research;clinical translation;Clinical Trials;Colon Carcinoma;commercialization;Correlation Studies;Corrosives;cost;Cyclic GMP;Data;density;Detection;Development;Diagnosis;DNA;Dose;Drug Design;Ensure;Feedback;fluorodeoxyglucose positron emission tomography;Future;glucose metabolism;Goals;Image;imaging biomarker;improved;In Vitro;Individual;Industry;industry partner;Infection;Inflammation;innovation;interest;Isotopes;Location;Malignant Breast Neoplasm;Malignant Neoplasms;manufacture;Measures;Monitor;Multi-Institutional Clinical Trial;nanoDroplet;neoplastic cell;novel;nucleoside analog;Oncology;Outcome;Patient Care;patient population;Patient Recruitments;Patient-Focused Outcomes;Performance;Positron-Emission Tomography;pre-clinical;Pre-Clinical Model;preclinical study;Process;Production;prototype;Radiochemistry;Reaction;Reagent;recruit;Research;Research Personnel;response;S-Phase Fraction;scale up;Selection for Treatments;Specificity;success;synergism;Technology;Testing;Therapeutic;Time;Tissues;tool;Tracer;Training;Training Programs;Translating;Translations;treatment response;tumor;tumor growth;uptake

PROJECT_TITLE: Enabling translation of cancer cell proliferation PET imaging via droplet radiochemistry technology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CTH-E (57)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Orthopoxviruses;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Mpox is a zoonotic infectious disease caused by Mpox virus, which has been endemic in Africa and has recently caused an ongoing global health emergency involving 100 countries around the world. There are currently no FDA-approved drugs that target Mpox virus, and while there are some options available to use repurposed drugs, these antivirals have a low barrier to resistance, resulting in a lack of efficacious drugs for the treatment and prevention of Mpox virus. The goal of this project is to utilize exceptional expertise in drug discovery, high- throughput assay development, screening technologies, and mechanism of action studies towards the discovery of innovative antivirals that target Mpox virus.

PI_NAMEs: FU, HAIAN ;SARAFIANOS, STEFAN G (contact);SCHINAZI, RAYMOND FELIX

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: 2019-nCoV;Address;adefovir;Africa;analog;Anti-viral Agents;assay development;Attenuated;Binding Sites;Biological Assay;Biology;Case Study;Cell Culture Techniques;Cells;Centers for Disease Control and Prevention (U.S.);Central Africa;Chemicals;Chemistry;Chicago;Cidofovir;Clinical;clinical candidate;Collection;Communicable Diseases;community transmission;Containment;Country;Cytomegalovirus;cytotoxicity;Data;data submission;design;Development;Disease Outbreaks;DNA-Directed RNA Polymerase;Dose;drug development;drug discovery;drug repurposing;Drug Targeting;Engineering;experimental study;FDA approved;Future;Gene Targeting;global health emergency;Goals;Golgi Apparatus;Hepatitis B Virus;Hepatitis C virus;Herpesviridae;high risk population;high throughput screening;HIV;HIV Seropositivity;Human;Immunodiagnostics;improved;innovation;Investigational Drugs;Lead;lead candidate;Libraries;Ligands;Lipids;Membrane;meter;miniaturize;Modified Vaccinia Virus Ankara;Monkeypox;Monkeypox virus;multidisciplinary;mutant;novel therapeutics;Nucleosides;Orthopoxvirus;pathogen;Pathology;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacology;Pharmacotherapy;Population;Poxviridae;preclinical development;Prevention;Process;Prodrugs;protein structure;Proteomics;Protocols documentation;Public Health;public health emergency;Reporter;Reporting;Resistance;resistance mutation;reverse genetics;Ribonucleosides;Safety;screening;Simplexvirus;Smallpox;smallpox eradication;Speed;Structure;Structure-Activity Relationship;Technology;Tenofovir;Testing;Therapeutic;United States;United States Food and Drug Administration;Vaccination;vaccine effectiveness;Vaccinee;Vaccines;Vaccinia virus;Validation;validation studies;vector;Viral;Viral Genes;Viral Proteins;virology;virtual screening;Virus;Virus Diseases;Virus Inhibitors;Virus Replication;World Health Organization;Zoonoses

PROJECT_TITLE: Discovery of Antivirals Targeting Mpox Virus

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Obstructive Pulmonary Disease;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE The proposed research will first develop the automated image processing pipeline needed to convert inhale/exhale CT image pairs into perfusion, ventilation, and VQ functional information using state-of-the-art deep learning methods. We will employ the functional information to develop machine learning models for quantifying COPD severity and predicting 5-year survival. Unlike existing approaches, our novel CT-derived functional imaging VQ markers are robust to patient breathing effort, and therefore have the potential to better inform both clinical decision making and assessments of therapeutic efficacy.

PI_NAMEs: CASTILLO, EDWARD  (contact);NAIR, GIRISH BALACHANDRAN;ZHAO, LILI

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Address;Adopted;airway obstruction;Area;Blood;Blood Vessels;Breathing;Cause of Death;Chronic Obstructive Pulmonary Disease;Clinical;clinical application;clinical decision-making;computer generated;Computing Methodologies;convolutional neural network;Data;deep learning;Deterioration;Development;Discipline of Nuclear Medicine;Disease;Disease Progression;E-learning;Early Intervention;Economic Burden;Event;Exhalation;Functional Imaging;Future;Genetic;genetic epidemiology;Goals;Health;Health Status;heuristics;Image;image processing;image registration;imaging approach;imaging biomarker;imaging Segmentation;improved;indexing;Inhalation;Label;Learning;Literature;Lobar;Lobe;Location;longitudinal dataset;Lung;lung lobe;lung volume;machine learning model;machine learning prediction;Malignant neoplasm of lung;Mathematics;Measures;Methodology;Methods;Modeling;Morbidity - disease rate;Morphology;mortality;mortality risk;Motion;novel;Observational Study;Patients;Perfusion;perfusion imaging;phenotypic data;physical model;Physics;Physiological;Population;Process;progression risk;Pulmonary Emphysema;Pulmonary Function Test/Forced Expiratory Volume 1;Quality of life;quantitative imaging;Recovery;Reporting;Reproducibility;Research;Research Design;risk prediction;Scanning;Scheme;Scoring Method;Severity of illness;small airways disease;software development;Staging;Testing;Training;training data;Treatment Efficacy;United States;unsupervised learning;Variant;ventilation;Vital capacity;X-Ray Computed Tomography

PROJECT_TITLE: CT-Derived Functional Imaging for Predicting Disease Progression in COPD

STUDY_SECTION: ASPA

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel A Study Section[ASPA]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: DAVIS

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative We propose to develop a miniaturized imaging device that can record brain activity in high resolution over the cortex in freely-behaving animals. Using this device, we will study how multiple regions of the brain function together in mice during behavioral tasks and how the visual cortex in head-unrestrained macaques mediates visual perception. This new imaging device will enable research on how different brain regions support behavior, and on mechanisms and treatments of various neurological disorders.

PI_NAMEs: WEI, XUEXIN ;YANG, WEIJIAN  (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: 3-Dimensional;Address;Adoption;Algorithms;Animal Behavior;Animal Model;Animals;area striata;Behavior;Behavioral;Benchmarking;Brain;Brain region;brain tissue;Calcium;Cells;Chronic;cognitive function;Computational algorithm;computerized data processing;computing resources;cost;cranium;Custom;Data;deep learning;deep learning algorithm;design;Development;Devices;empowerment;experimental study;Feedback;Functional Magnetic Resonance Imaging;Future;Head;high resolution imaging;Image;image reconstruction;imager;Imaging Device;In Vitro;in vivo;Individual;innovation;insight;Investigation;large scale data;Lateral;lens;Light;light scattering;Lighting;Macaca;Measures;Mediating;meter;Microscope;millimeter;miniaturize;Monitor;Monkeys;multi-electrode arrays;Mus;Nature;Nervous System Disorder;neural;neural circuit;neural patterning;neuroimaging;neuronal circuitry;Neurons;Neuropil;Neurosciences;neurotransmission;new technology;Noise;novel;Ocular Fixation;Optical Methods;Optics;Performance;Photons;Population;Research;Resolution;response;Running;Sampling;scale up;sensor;Signal Transduction;spatiotemporal;Speed;Study models;Techniques;Testing;Thick;Thinness;Time;Tissues;two-photon;Validation;Visual Cortex;Visual Perception;visual stimulus;Visualization;Work

PROJECT_TITLE: Synthetic mesoscope to image large-scale neural activity with near-single-cell resolution in freely-behaving animals

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: NARRATIVE The XKR proteins play a central role in the transport of the phosphatidylserine lipid to the external surface of dying (apoptotic) cells, where it acts as the key cue for their recognition and clearance by immune surveillance cells. Despite recent progress in elucidating the structure of XKR proteins, our ability to recognize their functions in human physiology and to design targeted pharmacological interventions is limited by our poor understanding of the mechanisms that regulate their activity. The goal of our project is to overcome these limitations by determining how the XKR proteins transport these lipids and how their activity is regulated in cells.

PI_NAMEs: ACCARDI, ALESSIO  (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TITLE: Structural basis of apoptotic scrambling

STUDY_SECTION: BBM

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


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: DURHAM

ORG_DEPT: CHEMISTRY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative  Biological function - including respiration, biocatalysis and programmed cell death - rely on charge transfer reactions within the cell. Extracellular charge transfer, in contrast, underlies the function of some bacteria and bacterial colonies, yet is very poorly understood. Our study uses theory, modeling, and simulation to describe the nature of extracellular charge transfer, with the aims of informing future strategies to combat bacterial pro- liferation and to interface living and abiotic structures for applications in biomolecular sensing, biomedicine, and biotechnology.

PI_NAMEs: BERATAN, DAVID  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TITLE: Mapping of Electron Tunneling Pathways in Proteins

STUDY_SECTION: MSFA

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Chronic Obstructive Pulmonary Disease;Climate-Related Exposures and Conditions;Genetics;Lung;Prevention

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Project Narrative This study represents a novel and significant advance for air pollution epidemiology through characterizing the dose of BC in human respiratory system as well as its dose-response relationships with lung aging and mortality. The findings will inform future research with the focus on ambient BC modeling and establishment of its dose- response relationships with lung deposition as well as health effects, facilitating the development of novel air quality metrics based on BC to mitigate health risks and address climate change.

PI_NAMEs: BELINSKY, STEVEN A;LENG, SHUGUANG  (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acceleration;Address;Affect;Aging;aging biomarker;Air;Air Pollution;airway remodeling;Algorithms;Archives;Aromatic Polycyclic Hydrocarbons;Benchmarking;Biological;Biological Assay;Biomass;Carbon;Carbon Black;Cessation of life;Chemicals;Chronic Obstructive Pulmonary Disease;Climate;climate change;cohort;Collection;Deposition;Development;disability;DNA Repair;Dose;ds-DNA;Environment;Epidemiology;epigenetic aging;Epigenetic Process;flexibility;follow-up;Fossil Fuels;gene panel;genome wide association study;Geography;Goals;Health;Hispanic Populations;Human;Image;indexing;Individual;innovation;inter-individual variation;Knowledge;Lung;machine learning algorithm;Macrophage;Malignant neoplasm of lung;Measures;member;Methods;Methylation;Modeling;mortality;Not Hispanic or Latino;novel;particle;Particulate Matter;Pathway interactions;Phenotype;premature;Process;promoter;Public Health;Publishing;pulmonary function decline;Respiratory physiology;Respiratory System;response;Risk;Risk Assessment;Risk Factors;risk stratification;Sampling;screening;sex;Slide;Smoker;Spirometry;Sputum;Sputum Cytology Screening;Study Subject;Time;Training;United States;World Health Organization

PROJECT_TITLE: Impact of Macrophage Carbon Load and Epigenetic Aging on Lung Function Decline and Mortality

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Brain Disorders;Cerebral Palsy;Clinical Research;Clinical Trials and Supportive Activities;Congenital Structural Anomalies;Dystonia;Neurodegenerative;Neurosciences;Pain Research;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Cerebral Palsy (CP) is the #1 cause of childhood onset motor disability, with over 11,000 infants diagnosed annually in the U.S. This proposal seeks to identify children with a subtype of CP who will best respond to a neurosurgical intervention to improve clinical outcomes.

PI_NAMEs: THOMAS, SRUTHI PANDIPATI (contact)

PROGRAM_OFFICER_NAME: BONNER, JOSEPH FRANCIS

PROJECT_TERMS: Activities of Daily Living;Address;Affect;Area;Assessment tool;Baclofen;Brain;Brain Injuries;brain magnetic resonance imaging;brain malformation;caregiving;Categories;Cerebral Palsy;Characteristics;Child;Childhood;Classification;Clinical;clinical outcome assessment;Clinical Trials;cohort;comorbidity;Corticospinal Tracts;Data;Data Analyses;Data Set;Deformity;design;Development;Diagnosis;Diffusion Magnetic Resonance Imaging;Dimensions;Dose;Dystonia;efficacious treatment;Encephalomalacia;Environment;Family;Future;Gliosis;Goals;Hemorrhage;Heterogeneity;Image;Impairment;Implantable Pump;improved;Infant;Injury;interest;Intervention;Lesion;Literature;Magnetic Resonance Imaging;malformation;Maps;Masks;Measures;Medical Care Costs;Meta-Analysis;Methodology;Motor disability;Muscle Contraction;muscle stiffness;Muscle Tonus;National Institute of Child Health and Human Development;National Institute of Neurological Disorders and Stroke;neurosurgery;Outcome;Outcome Measure;Pain;Parents;Pathway interactions;Patient Outcomes Assessments;Patient Selection;Patients;Pattern;pediatric dystonia;Personal Satisfaction;Persons;Population;Population Heterogeneity;prospective;Protocols documentation;Quality of life;recruit;Research;Resources;response;Severities;spasticity;standard of care;Standardization;statistics;Strategic Planning;success;Techniques;Titrations;treatment response;white matter;white matter injury;Work

PROJECT_TITLE: Intrathecal baclofen and pediatric dystonia.

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: AR

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Genetics;Human Genome;Lupus;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Short interspersed elements are a type of genomic repeats that can form double stranded RNA capable of activating the immune system in a way similar to that of a viral state. We will study the role of these repeats in idiopathic inflammatory myopathies, which can lead to new insights into the molecular nature of disease and ultimately lead to better therapeutics. In the long term, this can also lead to a better understanding of autoimmunity.

PI_NAMEs: NAJJAR, RAYAN  (contact)

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: 7SL RNA;ADAR1;Adenosine;Adjuvant;Adult;Adverse effects;Affect;Alternative Splicing;Alu Elements;Amino Acyl-tRNA Synthetases;ATAC-seq;Autoantibodies;Autoantigens;Autoimmune Diseases;Autoimmunity;autoreactive B cell;Award;Awareness;Binding;Bioinformatics;bioinformatics tool;Biology;career;Cell Lineage;cell type;Cells;Clinical;Code;Communication;Complement;Complex;Computational Biology;computer program;Data;Data Set;Dermatomyositis;Development;Disease;DNA-Directed RNA Polymerase;Doctor of Philosophy;Double-Stranded RNA;early onset;Elements;Ensure;Environment;epigenome;Event;Generations;Genes;Genetic Transcription;Genome;Genomics;Goals;Human Genome;Idiopathic Inflammatory Myopathies;IgA Deficiency;Immune;Immune system;immunogenic;immunogenicity;Immunology;improved;Incubated;Inflammatory;Infrastructure;inhibitor;Innate Immune System;Inosine;insight;Interferon Type I;Interferons;Interleukin-6;Introns;knock-down;Knowledge;Mentors;Methodology;Modeling;Molecular;multidisciplinary;Muscle;Mutation;Mutation Detection;Myositis;Nature;novel;nucleofection;overexpression;Paramyxovirus;Pathogenesis;Pathogenicity;Patients;Peripheral Blood Mononuclear Cell;prevent;Process;Production;Proteins;pseudotoxoplasmosis syndrome;Research;Research Personnel;rheumatologist;Risk;RNA;RNA Editing;RNA Splicing;Role;Sampling;Scientist;sensor;Short Interspersed Nucleotide Elements;Signal Recognition Particle;Signal Transduction;single cell analysis;single-cell RNA sequencing;Site;skills;Small Interfering RNA;Specificity;statistics;Structure;systemic autoimmune disease;Systemic Lupus Erythematosus;Technology;Testing;Therapeutic;Training;Training Programs;Transcript;transcriptome;transcriptome sequencing;Transfer RNA;United States National Institutes of Health;Universities;Up-Regulation;Variant;Viral;Washington

PROJECT_TITLE: Using Bioinformatics Methodologies to Explore the Role of Short Interspersed Elements in the Pathogenesis of Idiopathic Inflammatory Myopathies

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Cervical Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Health Services;Infectious Diseases;Prevention;Primary Health Care;Rare Diseases;Sexually Transmitted Infections;Women's Health Research

ORG_DEPT: OTOLARYNGOLOGY

PHR: PROJECT NARRATIVE While there are effective, widely available methods for cervical cancer screening, there are no such screening programs for human papillomavirus (HPV)-related oropharyngeal cancer (OPC), even though there are more cases per year of OPC than there are of cervical cancer. Exciting new ways of detection are using peripheral blood collected in a clinical setting; however, if remote self-sampling could be reliably used instead, it would offer a non-invasive alternative for screening the general population and for post-treatment monitoring of patients with HPV-related OPC. Screening using saliva, oral rinse, and urine sampling 1) offers the advantage of making mailed sample collection possible, 2) increases the likelihood of regular screening, even for those living in remote geographic areas or with limited health care access, and 3) potentially prevents late diagnosis of OPC which requires more aggressive treatment with serious lifelong consequences and early non-cancer mortality.

PI_NAMEs: STURGIS, ERICH MADISON (contact)

PROGRAM_OFFICER_NAME: BACCAGLINI, LORENA

PROJECT_TERMS: Adult;advanced disease;Aftercare;aged;aggressive therapy;anti-cancer research;Antibodies;antibody test;Biological Assay;Biological Markers;Blood;Blood specimen;blood-based biomarker;Cancer Patient;cancer prevention;cancer recurrence;cancer risk;Cervical Cancer Screening;Characteristics;Clinic;Clinical;Clinical Trials Design;cohort;Collection;Controlled Clinical Trials;Data;design;Detection;Development;Diagnosis;Disease;DNA;Enzyme-Linked Immunosorbent Assay;Foundations;Funding;General Population;Geographic Locations;Goals;health care availability;high risk;high risk population;Home;HPV oropharyngeal cancer;HPV screening;HPV-High Risk;Human Papilloma Virus Vaccination;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papillomavirus 16;Image;Incidence;Individual;Infection;Malignant neoplasm of anus;Malignant neoplasm of cervix uteri;Malignant Neoplasms;malignant oropharynx neoplasm;men;Methods;middle age;migration;Monitor;mortality;Natural History;novel;Oncogenic;Oncoproteins;Oral;oral HPV;Outcome;Patient Monitoring;Patients;Peer Review Grants;Performance;peripheral blood;Persons;Population;population based;Prevalence;prevent;Prospective, cohort study;public health priorities;Publications;Reference Standards;Research Institute;Risk;Risk Factors;risk prediction;Saliva;saliva sample;sample collection;Sampling;screening;Screening for cancer;screening program;Serum;Shipping;Site;statistics;success;System;Testing;Texas;tumor;Urine;Vaccination;Woman;Work

PROJECT_TITLE: HPV-related Oropharyngeal Cancer Screening and Monitoring through Remote Self-Sampling

STUDY_SECTION_NAME: Special Emphasis Panel[ZDE1 YM (07)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: PROJECT NARRATIVE This proposal will investigate the mechanisms regulating the production and activity of platelets, the main mediators of blood clotting. We aim to understand how platelet generation is altered during aging. The findings will inform strategies for mitigating platelet-related disorders such as stroke and thrombosis that frequently plague the elderly.

PI_NAMEs: FORSBERG, CAMILLA  (contact)

PROGRAM_OFFICER_NAME: COGLIATI, TIZIANA PAOLA

PROJECT_TERMS: age related;age related changes;aged;Aging;aging population;Automobile Driving;B-Lymphocytes;biological adaptation to stress;Biological Assay;Blood coagulation;Blood Coagulation Disorders;Blood Platelets;Bypass;Cardiovascular Diseases;Cells;Coagulation Process;CRISPR interference;Disease;drivers of aging;Elderly;Elements;Environment;Epigenetic Process;epigenetic regulation;epigenetic silencing;Erythrocytes;experimental study;Exposure to;fitness;FLT3 gene;Functional disorder;functional outcomes;gain of function;Generations;Goals;Half-Life;Health;Hematopoietic;Hematopoietic Cell Production;hematopoietic hierarchy;Hematopoietic Stem Cell Specification;Hematopoietic stem cells;Hemorrhage;Hemostatic function;In Situ;in vivo;Individual;Inherited;Intervention;intravital microscopy;Life;Longevity;Maintenance;Measures;Mediating;Mediator;Megakaryocytes;Megakaryocytopoieses;Mitochondria;Molecular;Morbidity - disease rate;mouse model;Mus;novel;old mice;Outcome;Pathway interactions;Physiological;Physiology;Plague;Platelet Count measurement;platelet function;Play;Population;prevent;Process;Production;progenitor;Property;Proteome;Regulation;Regulatory Element;Risk;Role;Source;stem cell population;stem cells;Stress;Stroke;T-Lymphocyte;Testing;Thrombocytopenia;thrombocytosis;Thrombosis;Tomatoes;Transplantation;young adult

PROJECT_TITLE: Defining the cause and consequence of aging-specific platelet specification from hematopoietic stem cells

STUDY_SECTION: CMAD

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


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Lymphatic Research;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Stochastic fate specification, in which a cell randomly chooses between two or more fates, is critical for diversifying visual photoreceptors, olfactory receptors, motor neurons, immune cells, and stem cells. Breakdowns in these regulatory mechanisms contribute to vision disorders, anosmia, autism, immunodeficiencies, and lymphoma, emphasizing the need to investigate the molecular underpinnings of this biological process. Using the fly eye as a model, we will characterize the roles of transcriptional and chromatin dynamics and cell-cell signaling in stochastic photoreceptor fate specification.

PI_NAMEs: JOHNSTON, ROBERT JOHN (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Ablation;Address;Affect;Anosmia;autism spectrum disorder;Bacteria;Biological Process;Buffers;Cell Differentiation process;cell fate specification;cell type;Cells;Chromatin;Chromatin Remodeling Factor;color detection;Data;Development;Disease;DNA;Drosophila eye;Ectopic Expression;Enhancers;Erinaceidae;experimental study;Eye;Eye Development;fly;Gene Expression;Gene Expression Regulation;gene regulatory network;Generations;Genes;Genetic Transcription;genomic locus;Goals;Human;Image;Immune;immunodeficiency;intercellular communication;Interneurons;Lymphoma;member;Modeling;Molecular;Morphology;mosaic;Motor Neurons;Mus;mutant;Nature;Neurons;Noise;olfactory receptor;olfactory sensory neurons;Pathway interactions;Pattern;Photoreceptors;precursor cell;Probability;Proteins;Regulation;Reporter;Repression;Retina;Rhodopsin;RNA;Role;Signal Pathway;Signal Transduction;Specific qualifier value;stem cells;System;Testing;Tissues;transcription factor;Transcription Repressor;Transcriptional Regulation;Undifferentiated;Vision Disorders;Visual impairment;visual photoreceptor;Visualization

PROJECT_TITLE: Mechanisms controlling stochastic gene expression during eye development

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Aging;Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Cardiac regeneration post-injury is critically dependent on cardiomyocyte (CM) proliferation and the involvement of multiple biological processes. Our present proposal emphasizes using modified mRNA (modRNA) based delivery of a PSAT1 to induce robust CM proliferation and activate its pleiotropic effects during the cardiac remodeling process. The project will investigate the efficacy of global or cell-specific PSAT1 modRNA approach for reversal of acute or chronic post-MI heart failure (Aim 1), uncover the novel molecular signaling mechanisms by which PSAT1 induces CM proliferation and role of serine synthesis pathway in CM proliferation and cardiac regeneration in MI model (Aim 2 and 3).

PI_NAMEs: MAGADUM, AJIT  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Acute;Adult;Apoptosis;beta catenin;Biological Assay;Biological Process;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cell Cycle;Cell Nucleus;Cell Proliferation;Cells;Cessation of life;Chronic;Cicatrix;Clinical;clinical application;Data;Databases;Development;Diagnosis;DNA Damage;Dose;Embryo;Enzymes;exosome;extracellular;extracellular vesicles;Family suidae;functional loss;Gene Delivery;gene therapy;Genes;Genome;Glucose;Heart;Heart failure;heart function;Heart Injuries;human induced pluripotent stem cells;improved;In Vitro;in vitro Assay;in vivo;Induced Cardiomyocytes;induced pluripotent stem cell;inhibitor;Injury;Isotopes;Knockout Mice;Link;Lower Organism;Mediating;Messenger RNA;Metabolic;Modeling;Molecular;mouse model;mRNA delivery;mRNA Expression;multidisciplinary;Mus;Muscle Cells;Myocardial;Myocardial Infarction;Myocardial Ischemia;Natural regeneration;Nature;Newts;novel;Nuclear Translocation;nucleotide metabolism;old mice;Outcome;overexpression;Oxidative Stress;Pathologic;Pathway interactions;Patients;Persons;Phosphoserine aminotransferase;Physiologic pulse;pleiotropism;postnatal period;Prevention;Process;Prognosis;Proliferating;Proteins;Proteomics;reconstitution;regenerative;Regenerative capacity;response;Role;Serine;Signal Pathway;Signal Transduction;Small Interfering RNA;success;Testing;Therapeutic;Time;Trans-Activators;transcriptome sequencing;Zebrafish

PROJECT_TITLE: PSAT1 modified mRNA induces cardiac repair post-ischemic heart injury

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Data Science;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Patient Safety;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative Older adults with Alzheimer's Disease and Related Dementias along with other chronic conditions face substantial care coordination challenges due to their cognitive impairments and complex care needs, making them particularly vulnerable to the negative outcomes associated with care fragmentation. This proposal uses social network analysis and electronic health record data to uncover the interdependent network of relationships between clinicians involved in coordinating care across settings and over time, as well as the contribution of such clinician relationship networks to disparities in health outcomes for this population. Greater transparency in these networks has the potential to inform and empower patients, assist clinicians, and optimize health system operations to advance healthcare quality, efficiency, and equity for patients vulnerable to care fragmentation.

PI_NAMEs: WEI, SIJIA  (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: 3-Dimensional;Address;Affect;Aging;Alzheimer's disease related dementia;Area;Award;Bioinformatics;care coordination;care fragmentation;Care given by nurses;career;Caregivers;Caring;Characteristics;Chronic;Chronic Care;cohort;Collaborations;Communication;Communities;Competence;Complex;cost;Data;Data Science;Disparity;Electronic Health Record;empowerment;Equity;Evolution;experience;Face;Family;Friends;Goals;Health;health care quality;health disparity;health equity;Health Services;Health Services Accessibility;Health Services Research;Health system;Healthcare;Hospitalization;human old age (65+);Impaired cognition;improved;Individual;individual patient;informal care;innovation;insight;Intervention;Managed Care;Maps;Measures;Medical;Medical Errors;Memory;Mentors;Mentorship;Methodology;Methods;Modeling;mortality;multiple chronic conditions;Natural Language Processing;Nurses;older adult;operation;Outcome;Outcomes Research;Pathway Analysis;Pathway interactions;Patient Care;Patient Care Team;Patients;Peripheral;Personal Satisfaction;Population;Positioning Attribute;Primary Care;Process;programs;racial minority;Research;Research Personnel;Risk;Science;Site;social;Social Environment;social health determinants;Social Network;social relationships;Social Sciences;Standardization;Structure;Surveys;System;Testing;Text;Time;tool;Training;United States National Institutes of Health;Work

PROJECT_TITLE: Identifying Hidden Relational Processes that Fragment Care for Older Adults with ADRD and Multimorbidity: A Social Network Analysis Approach

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Nanotechnology

ORG_CITY: CLEMSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: PROJECT NARRATIVE Liver transplantation is the only definitive therapy available for treatment of inherited metabolic diseases affecting the liver, but it has severe drawbacks. We aim to directly compare different delivery approaches for introducing gene editing reagents into hepatocytes combined with a novel approach for selecting edited hepatocytes in the liver using transient administration of acetaminophen as a novel treatment for familial hypercholesterolemia. We will study the repopulation potential, capacity of edited hepatocytes to overcome immunity to gene editing reagents in the liver, and extent that our approach reverses the disease in a mouse model.

PI_NAMEs: COTTLE, RENEE NICOLE (contact)

PROGRAM_OFFICER_NAME: FLEG, JEROME L

PROJECT_TERMS: Acetaminophen;Address;adenovirus mediated delivery;Affect;ANGPTL3 gene;Autologous;Back;Cardiovascular Diseases;cardiovascular disorder risk;Cell Maintenance;Cells;Cholesterol;Clinical Trials;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Cytochrome P450;Cytotoxic T-Lymphocytes;Dependovirus;Disease;disease phenotype;Electroporation;Engineering;Familial Hypercholesterolemia;Fever;Foundations;Genes;Genetic Engineering;genome editing;genotoxicity;Hematopoietic stem cells;Hepatocyte;hepatocyte engraftment;Human;Immune response;Immunity;immunogenic;immunogenicity;Impairment;in vivo;Inherited;Insertional Mutagenesis;knock-down;LDL Cholesterol Lipoproteins;lipid nanoparticle;Liver;Liver diseases;liver injury;liver transplantation;Long-Term Effects;loss of function mutation;low density lipoprotein triglyceride;Low-Density Lipoproteins;Major Histocompatibility Complex;Malignant Neoplasms;Mediating;Medicine;Membrane Proteins;Messenger RNA;Metabolic;Metabolic Diseases;Metabolism;Methods;mouse model;Mus;NADPH-Ferrihemoprotein Reductase;novel;novel strategies;Oxidoreductase;Patients;Peptides;Persons;Plasma;Population;premature;programs;Reagent;Research;Resected;Resistance;Ribonucleoproteins;Risk;Selection for Treatments;Specificity;T cell response;T-Lymphocyte;Testing;Therapeutic;Time;Toxic effect;Transplantation;Triglycerides;Viral;Work

PROJECT_TITLE: Nonviral Delivery of CRISPR-Cas9 into Hepatocytes Combined with APAP Selection for Treatment of Familial Hypercholesterolemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (81)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Heart Disease;Nutrition;Obesity;Physical Activity;Prevention

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Insulin resistance and endothelial dysfunction are major etiological factors in the development of obesity, type 2 diabetes, and cardiovascular disease (CVD). Extracellular vesicles (EVs) have emerged as potential mediators of vascular insulin resistance, and this project will examine the role of plasma EVs from lean normal glucose tolerant (NGT), obese NGT and obese T2D participants on EV uptake and vascular function in culture and on mouse resistance/microcirculatory blood vessels before and after insulin-stimulation. We will also address differential roles of insulin signaling proteins and miRNA/small RNAs that are carried by EVs across these groups before and after exercise training to discern clinical relevance of an insulin-mediated EV mechanism that has potential to identify novel mechanisms for prevention/treatment of chronic disease.

PI_NAMEs: ERDBRUEGGER, UTA  (contact);MALIN, STEVEN K

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Address;Adult;Affect;Animal Model;arterial stiffness;Arteries;Attenuated;Blood;Blood Glucose;Blood Platelets;Blood Pressure;Blood Vessels;Body fat;Body mass index;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Cells;Chronic Disease;Classification;clinically relevant;Closure by clamp;comparison control;contrast enhanced;Data;Dependence;Development;Disease Progression;Distant;dosage;Dose;Dyslipidemias;Endothelial Cells;endothelial dysfunction;Endothelium;Etiology;euglycemia;Exercise;exercise training;extracellular vesicles;Flow Cytometry;Fostering;Foundations;Functional disorder;Future;glucose tolerance;glucose uptake;Health;Human;Hyperglycemia;Hyperinsulinism;Hypertension;Image;Impairment;improved;In Vitro;in vivo;in vivo evaluation;in vivo Model;indexing;individualized medicine;Infusion procedures;inhibitor;insight;Insulin;Insulin Receptor;Insulin Resistance;insulin sensitivity;insulin signaling;Intervention;Ischemia;Link;Mass Spectrum Analysis;Measures;Mediating;Mediator;Metabolic;Metabolic syndrome;Microcirculation;MicroRNAs;Modeling;Morbidity - disease rate;mortality;Mus;Myography;new therapeutic target;NG-Nitroarginine Methyl Ester;Nitric Oxide;Non-Insulin-Dependent Diabetes Mellitus;NOS3 gene;novel;Obesity;obesity development;Participant;Pathologic;Patients;Persons;pharmacologic;Phenotype;Physiologic pulse;Physiology;Plasma;precision medicine;pressure;prevent;Prevention;prospective;Proteins;Resistance;response;Risk Reduction;RNA;Rodent;Role;Sampling;Signal Transduction;Signaling Molecule;Signaling Protein;Small RNA;System;Testing;Thinness;Time;Tissues;tool;Training;transcriptome sequencing;Translating;Trees;ultrasound;United States;uptake;Vascular Diseases;Vasodilation;vesicular release;Western Blotting;Work;wortmannin

PROJECT_TITLE: Extracellular Vesicles, Insulin Action and Exercise on Vascular Function in Type 2 Diabetes

STUDY_SECTION: HSDO

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: This research addresses a critical, relevant public health concern as it will provide a platform to develop new antivirals that can target type I fusion proteins, which we are applying to the highly pathogenic viruses SARS- CoV-2, RSV, Nipah virus and MERS. This new class of antivirals is based on small, highly stable computationally designed proteins. A tight coupling between computation and experiments will also allow the development of data-driven protein design algorithms.

PI_NAMEs: STRAUCH, EVA-MARIA  (contact)

PROGRAM_OFFICER_NAME: BASU, DIPANWITA

PROJECT_TERMS: 2019-nCoV;Address;Affect;Algorithm Design;Algorithms;Animal Model;Animals;Anti-viral Agents;Appearance;Back;Binding;Biological Assay;Biological Products;C-terminal;Cell Culture Techniques;Cellular Membrane;Chimeric Proteins;Cholesterol;Complex;Computing Methodologies;Coronavirus;Coupling;Custom;Data;Data Set;deep learning;design;Development;Digit structure;Disease;dosage;Ebola;Ensure;Evaluation;experimental study;feeding;fitness;Generations;High temperature of physical object;HIV;immunogenicity;improved;In Vitro;in vivo;in vivo evaluation;Infection;Influenza;inhibitor;insight;large datasets;Location;Machine Learning;Membrane;Membrane Fusion;Mesocricetus auratus;Methodology;Methods;Middle East Respiratory Syndrome;Middle East Respiratory Syndrome Coronavirus;mimetics;Modeling;Molecular;Molecular Conformation;mouse model;Mutation;nanomolar;Network-based;neural network;Nipah;Nipah Virus;Output;pandemic preparedness;pathogenic virus;Pathogenicity;Peptide Hydrolases;Peptides;Pneumovirus;Protein Chemistry;Protein Engineering;protein protein interaction;Proteins;protocol development;Protocols documentation;prototype;Public Health;Publishing;Recovery;Research;respiratory infection virus;Respiratory syncytial virus;SARS-CoV-2 inhibitor;scaffold;Serum;Severe Acute Respiratory Syndrome;Site;structural biology;Structure;success;Surface;Technology;Therapeutic;Variant;Vertebral column;Viral;Viral Proteins;Virus;Virus Inhibitors;Work;Yeasts

PROJECT_TITLE: Computational design and development of small protein inhibitors


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Genetics;Human Genome;Lupus;Precision Medicine

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Narrative Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with variable presentation of symptoms and inconsistent response to therapy. Here, we propose to use highly innovative single cell epigenomic, transcriptomic, and proteomic analyses to map the cell-type-specific molecular and genetic basis underlying SLE heterogeneity. We expect our findings to shed light on the pathogenic states in specific immune cell subsets stratifying SLE patients, which, in turn, will create new opportunities for therapies directed toward each specific patient subgroup. 2

PI_NAMEs: YE, CHUN JIMMIE (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Affect;African ancestry;Aftercare;Asian ancestry;Asian population;autoimmune rheumatologic disease;B-Lymphocytes;base;Blood capillaries;Body System;California;cell type;Cells;Cellular biology;Characteristics;Chromatin;chronic autoimmune disease;clinical phenotype;cohort;Collection;Computing Methodologies;CRISPR interference;CRISPR-mediated transcriptional activation;Data;Development;Diagnosis;Disease;Disparity;Environmental Exposure;epidemiology study;epigenome;epigenomics;Ethnic Origin;Exhibits;experience;Female;Flare;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;genetic variant;Genets;Genome;genome wide association study;granulocyte;Heterogeneity;Hispanic ancestry;Human;Immune;Immunologics;Immunologist;Individual;innovation;insight;Interferons;Knowledge;Lupus;lymphocyte trafficking;male;Maps;Membrane Proteins;Messenger RNA;Methods;Molecular;multi-ethnic;multimodality;multiple omics;Nature;novel;novel strategies;Onset of illness;Organ;Outcome;Pathogenicity;Pathway interactions;patient stratification;patient subsets;Patients;Peripheral Blood Mononuclear Cell;Population Analysis;Prognosis;Proteomics;Quality of life;Quantitative Trait Loci;Resolution;Resources;response;Rheumatism;Sampling;Science;Self Administration;Sex Bias;single cell genomics;single cell sequencing;single-cell RNA sequencing;Symptoms;Systemic Lupus Erythematosus;T-Lymphocyte;Technology;Testing;Tissues;transcriptome;transcriptomics;treatment response;Variant;Women's prevalence

PROJECT_TITLE: Mapping the cell-type-specific molecular and genetic basis of lupus using single cell multiomics

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Skin Cancer

ORG_CITY: SALT LAKE CITY

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE  Over the past 12 years, the therapeutic landscape for melanoma patients has been transformed by the success of FDA-approved immuno-oncology and pathway-targeted therapeutics. However, major challenges remain in pharmacologic targeting of mutationally-activated NRAS oncoprotein signaling in melanoma patients who are either ineligible for, or who fail first-line immunotherapy. To address this challenge, we propose to employ state-of-the-art experimental systems to design and evaluate new, rationally targeted therapeutic strategies to directly target NRAS oncoprotein signaling in melanoma, with the long-term goal of rendering melanoma a chronic or curable disease.

PI_NAMEs: MCMAHON, MARTIN  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Address;antitumor effect;Antitumor Response;Apoptosis;Autophagocytosis;bcr-abl Fusion Proteins;Biochemical;Biochemistry;Biology;BRAF gene;Bypass;cancer cell;cancer diagnosis;Cancer Patient;Cell Cycle;Cell Line;Cell Reprogramming;Cellular biology;Chronic;Clinical Trials;clinically relevant;Companions;comparison control;Complex;Cyclophilin A;Cytoprotection;cytotoxic;Data;design;Development;Disease;Disease Resistance;Drug resistance;Drug Targeting;Epidermal Growth Factor Receptor;experimental study;FDA approved;Foundations;Genetic;Genetic Engineering;Goals;Growth;Guanosine Triphosphate;Human;Hydroxychloroquine;Immune system;Immunooncology;Immunotherapy;improved;inhibitor;innovation;interest;Knowledge;KRAS2 gene;Lysosomes;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;MAP2K1 gene;Medicine;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Molecular;Molecular Biology;mouse model;Mus;Mutation;novel;Oncogenes;Oncogenic;Oncoproteins;Pathway interactions;patient derived xenograft model;patient prognosis;patient response;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Physicians;PIK3CG gene;Play;pre-clinical;Pre-Clinical Model;RAS driven cancer;Ras Inhibitor;Recurrence;Refractory;Regimen;Research;Research Personnel;Resistance;resistance mechanism;Resources;response;Role;Safety;Scientist;Signal Induction;Signal Pathway;Signal Transduction;Skin Cancer;STK11 gene;success;System;targeted treatment;Testing;Therapeutic;tool;Toxic effect;Translating;Treatment Efficacy;treatment strategy;tumor;Tumor Suppressor Proteins;tumorigenic;Xenograft procedure

PROJECT_TITLE: Targeting Oncogenic NRAS, BRAF plus PI3'-Kinase Signaling for Melanoma Therapy

STUDY_SECTION: MCTC

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics C Study Section [MCTC]


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

ORG_CITY: STANFORD

ORG_DEPT: PATHOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Maintaining homeostasis of the neural stem cell pool is fundamental to the development and integrity of the nervous system. By providing insights into the mechanism of how the evolutionarily conserved Notch signaling pathway acts in a non-canonical manner to regulate neural stem cell homeostasis, this study has the potential to lead to deeper understanding of the development and maintenance of the nervous system and inform the development of novel therapy for brain tumors and a range of neurological conditions where altered Notch signaling has been implicated.

PI_NAMEs: LU, BINGWEI  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: 2019-nCoV;Alleles;Biological Assay;Brain;Brain Diseases;Brain Neoplasms;c-myc Genes;Cancer Biology;cancer stem cell;carcinogenesis;cell behavior;Cell division;cell growth;Cell Maintenance;Cell Nucleus;Cells;clinically relevant;clinically significant;Code;Complex;Cytosol;Deacetylase;Defect;Development;Drosophila genus;effective therapy;Electron Transport;Ensure;Equilibrium;Event;fly;FRAP1 gene;Funding;Genetic;Glioblastoma;Goals;Growth;Homeostasis;Human;In Vitro;in vivo;insight;Investigation;Link;loss of function;Maintenance;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Mental disorders;Mitochondria;Modeling;Molecular;mouse model;Mus;mutant;Nerve Regeneration;nerve stem cell;Nervous System;neuroblast;Neurodegenerative Disorders;Neurodevelopmental Disorder;Neurologic;neuroregulation;Neurosciences;Neurosphere;notch protein;Notch Signaling Pathway;novel;novel therapeutics;Numbness;Oncogenic;Pathway interactions;Peptide Synthesis;PINK1 gene;Process;progenitor;Proliferating;Proto-Oncogene Proteins c-akt;Quality Control;Regulation;Reporter;Ribosomes;Role;Sampling;self-renewal;Signal Pathway;Signal Transduction;Signaling Molecule;Sirtuins;spatiotemporal;stem cell biology;stem cell growth;stem cell homeostasis;stem cells;stemness;Study models;System;Testing;transcription factor;Transcriptional Regulation;Transgenic Organisms;Translations;tumor initiation;tumorigenesis;ubiquitin-protein ligase

PROJECT_TITLE: Genetic control of neural stem cell homeostasis

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Physical Activity;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Biomedical research often involves the collection of error-prone, complex, high-dimensional functional and scalar data. We will develop novel approaches to survival analysis using Bayesian and frequentist frameworks to correct for biases in physical activity and dietary intake assessments and thus improve understanding of the intricate relationships among energy balance, obesity, type 2 diabetes, and mortality. Our models will inform personalized recommendations for PA and DI and address health disparities in vulnerable populations, and public use software that implements our models will allow researchers to apply our methods in diverse biomedical settings.

PI_NAMEs: ZOH, ROGER SAI (contact)

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Acceleration;Address;Adult;African American;aged;Attenuated;Biomedical Research;biracial;Characteristics;cohort;Collection;comorbidity;Complex;complex data;Computer software;Data;Demographic Factors;Dependence;Devices;Diagnosis;Dietary Assessment;Dietary intake;discrete time;energy balance;Event;Failure;follow-up;General Population;Guidelines;Health;health disparity;Heterogeneity;high dimensionality;improved;Intake;Intervention;Joints;Linear Regressions;Measurement;Measures;Methods;Modeling;modifiable lifestyle factors;monitoring device;mortality;Noise;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obesity;Outcome;Patient Self-Report;Patient-Focused Outcomes;Pattern;Physical activity;Reasons for Geographic And Racial Differences in Stroke;Recommendation;Regression Analysis;Research Personnel;Seasons;semiparametric;Statistical Methods;Subgroup;Survival Analysis;survival prediction;Tail;Time;time interval;treatment effect;Variant;Vulnerable Populations;wearable device;Work

PROJECT_TITLE: Novel Bayesian assessments of device-based physical activity and self-reported dietary intake in joint models of all-cause mortality and type 2 diabetes in a cohort of biracial older US adults

STUDY_SECTION: ASPB

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel B Study Section[ASPB]


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

ORG_CITY: IRVINE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative Pancreatic tumors consist of many diverse cell types engaged in crosstalk mechanisms to support cancer cell growth and survival. Our work has identified metabolically distinct subpopulations of pancreatic cancer cells that exchange nutrients to support resistance to mitochondrial inhibition. This proposal will define the factors underpinning metabolic heterogeneity in pancreatic cancer cells and use a combination of metabolic inhibitors to sensitize pancreatic tumors to therapeutics.

PI_NAMEs: HALBROOK, CHRISTOPHER J. (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: adaptive immune response;Anabolism;Anti-Inflammatory Agents;Antimetabolites;asparaginase;Asparagine;Automobile Driving;Behavior;biological adaptation to stress;cancer cell;Cancer Cell Growth;Cell Line;Cell Physiology;Cell Survival;cell type;Cells;Chemoresistance;chemotherapy;Clinical Treatment;Coculture Techniques;Combined Modality Therapy;comparative efficacy;Data;Deposition;desensitization;design;Disease;effective therapy;Electrons;Epithelium;Equilibrium;experimental study;extracellular;Extracellular Matrix;Fibroblasts;Follow-Up Studies;gemcitabine;Genetic;Goals;Growth;Heterogeneity;histone methylation;Histones;Human;Hypermethylation;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune Targeting;Immunocompetent;Immunosuppression;Impairment;in vivo;inhibitor;insight;Kinetics;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Mesenchymal;Metabolic;Metabolism;Mitochondria;mitochondrial metabolism;Modeling;Molecular;mortality;Mus;Myeloid Cells;Nucleotides;Nutrient;Oncogenic;Organoids;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;Pathway interactions;Patients;pharmacologic;Physiology;Population;pre-clinical;prevent;Production;programs;Proliferating;Pyrimidine;Research;Research Proposals;Resistance;response;Signal Pathway;Signal Transduction;single cell analysis;Solid Neoplasm;Stable Populations;standard of care;Stress;Stromal Cells;Supplementation;support network;Techniques;Therapeutic;therapy resistant;tool;treatment response;tumor;tumor microenvironment;Tumor-associated macrophages;Work

PROJECT_TITLE: Targeting Metabolic Crosstalk in Pancreatic Cancer

STUDY_SECTION: CCB

STUDY_SECTION_NAME: Cancer Cell Biology Study Section[CCB]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative We will identify the non-protein-coding regions of the genome that play an important role in tumor initiation and growth by modulating the expression of protein-coding regions. We will develop innovative computational methods that will make it feasible to identify these regions in metastatic cancer patients using non-invasive liquid biopsies. We will use high-throughput CRISPR screens to understand the impact of perturbation of thousands of regions and also probe their roles in specific contexts, such as resistant to therapy in breast cancer patients.

PI_NAMEs: KHURANA, EKTA  (contact);SANJANA, NEVILLE

PROGRAM_OFFICER_NAME: DIVI, RAO L

PROJECT_TERMS: Apoptosis;Aromatase Inhibitors;Automobile Driving;base editing;biomarker discovery;Biopsy;Breast;Breast Cancer Patient;Cancer Cell Growth;cancer genetics;Cancer Patient;cancer subtypes;Catalogs;cell free DNA;Cell Line;cell type;Cells;Chromatin;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Communities;Complex;Computing Methodologies;Coupled;CRISPR interference;CRISPR screen;CRISPR-mediated transcriptional activation;Data;Disseminated Malignant Neoplasm;DNA;DNA Sequence;DNA sequencing;Down-Regulation;Enhancers;Epigenetic Process;epigenome;epigenomics;Event;Evolution;experience;Funding;Gene Expression;Generations;Genes;Genome;genome sequencing;Genomics;Growth;innovation;liquid biopsy;Machine Learning;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Maps;method development;Methods;multiple omics;Mutation;Neoplasm Metastasis;Nucleosomes;Oncogenes;Oncogenic;Oncologist;Open Reading Frames;Patients;Plasma;Play;Primary Neoplasm;promoter;Promoter Regions;protein expression;Regulatory Element;Repression;Research;Resistance;resistance mechanism;Resolution;Role;Sample Size;Sampling;Science;Signal Transduction;single cell sequencing;Site;Solid Neoplasm;Techniques;Technology;Testing;therapy resistant;transcriptome;tumor;tumor growth;tumor initiation;Tumor Tissue;Untranslated Regions;Untranslated RNA;Up-Regulation;Variant;whole genome;Work

PROJECT_TITLE: Computational and experimental methods for scalable identification of oncogenic non-coding regions

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Nutrition;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Dry eye is a widespread condition that significantly impacts the elderly population globally. Inflammation of the lacrimal gland, responsible for producing aqueous tears, often correlates with aging. This proposal aims to elucidate the cellular and molecular mechanisms underlying calorie restriction and explore its impact on progenitor cell function and gland regeneration.

PI_NAMEs: DE PAIVA, CINTIA S.;MAKARENKOVA, HELEN P. (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Address;Adult;Affect;age related;age related changes;aged;Aging;aging process;aging related;Agonist;Animals;Anti-Inflammatory Agents;Antibodies;aqueous;Atlases;B-Lymphocytes;Blurred vision;Caloric Restriction;Cell Death;Cell Density;cell injury;cell type;Cells;Cholesterol Esters;Chronic;cognitive function;comparative;cytokine;Data;dietary restriction;Disease;Dry Eye Syndromes;Elderly;Epithelial Cells;epithelial stem cell;experimental study;extend lifespan;eye dryness;Female;Fenofibrate;Film;Flow Cytometry;functional decline;Functional disorder;gain of function;Gene Expression;Genes;genetic manipulation;Gland;Goals;Goblet Cells;Growth;Health;Human;IL18 gene;Immune;immune activation;immune cell infiltrate;Immune response;Impairment;improved;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Injury;Interleukin-1 beta;Interleukins;Intervention;Investigation;irritation;Lacrimal gland structure;Lentivirus;Life Expectancy;lipid metabolism;Lipids;Liver X Receptor;loss of function;Macrophage;male;Malnutrition;Mental Health;Metabolic;Mitochondria;mitochondrial metabolism;Molecular;Moods;Morphology;mouse model;Mus;Mutant Strains Mice;nano-string;Natural regeneration;novel;novel marker;old mice;older adult;Organoids;Paraffin;Pathway interactions;Phase;Phenotype;Play;Population;PPAR alpha;Prevalence;Process;Production;Proliferating;protective effect;Publications;Quality of life;Regenerative capacity;repaired;reparative process;Research;Role;RXR;Sampling;Secretory Cell;Short-Term Memory;Signal Transduction;single-cell RNA sequencing;Slide;Source;Spatial Distribution;Stains;stem cell biomarkers;stem cell differentiation;stem cell function;stem cell growth;stem cells;Testing;Therapeutic;Tissues;TNF gene;transcriptomics;Up-Regulation;Western Blotting

PROJECT_TITLE: Investigating the anti-inflammatory mechanisms of calorie restriction in the aged lacrimal gland

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-S (02)]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Niemann-Pick type C (NPC) is a rare neurodegenerative and metabolic disease triggered by aberrant trafficking and partitioning of cholesterol in lysosomes. This proposal will combine mTORC1 manipulations with high throughput functional genomics and metabolomics to deepen our understanding of NPC drivers, with relevance to common neurodegenerative diseases such as Alzheimer’s.

PI_NAMEs: ZONCU, ROBERTO  (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Alzheimer's Disease;apolipoprotein E-4;Autophagocytosis;Binding;Biochemical;Bioinformatics;Brain;Cell Membrane Permeability;Cell model;Cells;Cellular Metabolic Process;Cellular Structures;Cessation of life;Chemicals;Cholesterol;cholesterol trafficking;Complex;Coupled;CRISPR screen;Dedications;Defect;design;detection of nutrient;Disabling;Disease;disease model;driving force;Eating;Endoplasmic Reticulum;Ensure;Equilibrium;Event;Failure;Fatty acid glycerol esters;FRAP1 gene;Functional disorder;functional genomics;Functional impairment;G-Protein-Coupled Receptors;Gatekeeping;Generations;Genetic;genome-wide;Goals;Growth;GTPase-Activating Proteins;Health;Homeostasis;Hydrolase;Impairment;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Integral Membrane Protein;Laboratories;Link;lipid biosynthesis;Lipids;Lysosomes;Mass Spectrum Analysis;Membrane;Membrane Proteins;Metabolic;Metabolic Diseases;Metabolism;metabolomics;Microglia;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Modeling;Molecular;Morphogenesis;mouse model;Mutation;Names;Neimann-Pick's Disease Type C;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuronal metabolism;neuronal survival;Neurons;novel;NPC1 gene;Nutrient;Organelles;Organoids;Pathogenesis;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;pharmacologic;Phosphotransferases;Play;Process;Proteins;Proteolysis;Proteomics;proteotoxicity;Quality Control;recruit;Regulation;Research Personnel;resilience;Resistance;Role;sensor;Signal Transduction;Site;Stress;Structure of thyroid parafollicular cell;Therapeutic;therapeutic target;trafficking

PROJECT_TITLE: Deciphering and disabling lysosome-dependent mechanisms of neurodegeneration

STUDY_SECTION: CMND

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


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative: Heart failure is a major public health problem in the United States and around the world. In this research, we apply complementary genetic and gene-expression approaches to identify novel genes and pathways that predispose individuals to heart failure. Importantly, we will integrate the approaches of Mendelian rare variant analyses with findings from Genome Wide Association Studies (GWAS). We further carry out functional validation studies using explanted hearts and patients’ hiPSC-cardiomyocytes.

PI_NAMEs: MANICHAIKUL, ANI WANG;TAYLOR, MATTHEW R (contact)

PROGRAM_OFFICER_NAME: YARDEN, RONIT I

PROJECT_TERMS: Affect;American;Atlases;Biological;Biological Markers;Biological Process;Biology;Candidate Disease Gene;candidate selection;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cell Nucleus;Cessation of life;Complex;cost;Data;Data Set;Development;Diagnosis;differential expression;Dilated Cardiomyopathy;Disease;Disease susceptibility;disease-causing mutation;disorder risk;DNA;DNA Sequence Alteration;exome sequencing;Failure;Family;follow-up;Foundations;Future;gene discovery;Gene Expression;Gene Expression Profiling;Genes;Genetic;Genetic Transcription;genetic variant;genome wide association study;genome-wide analysis;Genomics;Goals;Health;Heart;Heart failure;High Prevalence;high risk;Hospitalization;Hospitals;Human;human induced pluripotent stem cells;human old age (65+);hypertensive;Individual;Investigation;Knowledge;Low Prevalence;Maps;Mediating;Modeling;Mutation;Myocardial Ischemia;National Heart, Lung, and Blood Institute;novel;novel therapeutic intervention;Overlapping Genes;Pathogenesis;Pathway interactions;Patients;Public Health;Publishing;Quantitative Trait Loci;rare mendelian disorder;rare variant;Research;Research Design;Resources;Risk;risk variant;RNA;RNA Sequences;Sampling;Signal Transduction;Susceptibility Gene;Testing;Tissues;Trans-Omics for Precision Medicine;Transcript;transcriptome;transcriptome sequencing;transcriptomics;United States;Validation;validation studies;Variant;whole genome;Work

PROJECT_TITLE: Integrative genomic and transcriptomic investigation of human heart failure mechanisms

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Prevention;Women's Health Research

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE Background parenchymal enhancement (BPE) is a promising new marker of breast cancer risk that has been studied almost exclusively using magnetic resonance imaging, an expensive screening modality that is indicated primarily for women with high risk of breast cancer. We propose here to measure BPE quantitatively using contrast-enhanced mammogram (CEM), a rapidly emerging screening modality that is more affordable and generalizable than MRI, and assess the potential of BPE measured on CEM as a marker of breast cancer risk. Our long-term goal is to use our new, objective measure of BPE on CEM to improve assessment of breast cancer risk, enabling personalization of breast cancer screening to detect breast cancer earlier and ultimately reduce breast cancer mortality.

PI_NAMEs: WATT, GORDON PATRICK (contact)

PROGRAM_OFFICER_NAME: ZHU, CLAIRE

PROJECT_TERMS: Accounting;Address;Agreement;American College of Radiology;Area;Board Certification;Body mass index;Breast;Breast Cancer Detection;breast cancer diagnosis;Breast Cancer Early Detection;Breast Cancer Epidemiology;Breast Cancer Risk Factor;breast imaging;cancer diagnosis;cancer risk;Case/Control Studies;Clinical;Collaborations;Contralateral Breast;contrast enhanced;Contrast Media;density;Diagnosis;Early Diagnosis;Ethnic Origin;Frequencies;Goals;high risk;high risk population;High Risk Woman;Image;imaging biomarker;improved;Information Systems;Injections;Machine Learning;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mammographic Density;Mammographic screening;Mammography;Matched Case-Control Study;Measurement;Measures;Metabolic;Methods;Modality;Modeling;Modification;mortality;Newly Diagnosed;novel marker;Outcome;Participant;Patients;Population;Population Heterogeneity;pressure;prevent;Process;Prospective Studies;Race;radiologist;Radiology Specialty;Random Allocation;Reader;Recording of previous events;Reporting;Reproducibility;Reproductive History;Research;Risk;Risk Assessment;Risk Marker;Roentgen Rays;Schedule;screening;screening guidelines;success;Testing;Tissues;tomosynthesis;uptake;Woman

PROJECT_TITLE: Quantitative background parenchymal enhancement, measured on contrast-enhanced mammogram, as a novel marker of breast cancer risk

STUDY_SECTION: CHD

STUDY_SECTION_NAME: Cancer and Hematologic Disorders Study Section[CHD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Mental Health;Neurosciences;Pediatric

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative The overarching goal of this project is to harness the unique multimodal infant MRI data collected via the Baby Connectome Project (BCP) and a set of infant-centric computational tools developed at the University of North Carolina at Chapel Hill for investigating structural and functional connectomes, tissue macrostructure and mi- crostructure, and their interplay during early brain development. Successful completion of this project will em- power the neuroscience community with improved understanding of the development of structure and function of the human brain during its infancy.

PI_NAMEs: YAP, PEW-THIAN  (contact)

PROGRAM_OFFICER_NAME: KING, ERIN MICHELE

PROJECT_TERMS: 5 year old;Acceleration;Algorithms;Anatomy;Area;Automobile Driving;Award;Birth;Brain;brain size;Cerebral cortex;Characteristics;Child;Cognition;Communities;computerized tools;connectome;contrast imaging;critical period;Data;Dedications;Deposition;Development;Diffusion;diffusion anisotropy;Diffusion Magnetic Resonance Imaging;empowerment;Exhibits;Functional Magnetic Resonance Imaging;Geometry;Goals;Growth;Human;improved;Individuality;infancy;Infant;Investigation;Language;Language Development;Learning;Life;Magnetic Resonance Imaging;Measurement;Microscopic;Minnesota;Modality;Modeling;Morphology;Motor;multimodality;Nature;Neurites;Neuroanatomy;Neurodevelopmental Disorder;neuronal cell body;Neurosciences;North Carolina;Pathway interactions;Pattern;postnatal;Process;psychologic;public repository;Research;Research Personnel;Resolution;response;Role;secondary analysis;Specific qualifier value;Structure;Surface;Thick;Time;Tissues;tool;tractography;trait;Universities;virtual;Vision;vision development;Visual;white matter

PROJECT_TITLE: Multifaceted Characterization of Early Human Brain Development

STUDY_SECTION: EITN

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


NIH_SPENDING_CATS: Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: SURGERY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Severe burn victims and patients suffering from congenital sweat gland deficiencies are unable to properly maintain body temperature, which can lead to hyperthermia, heat stroke, brain damage, and potentially death. Restoring the capacity of these patients to thermoregulate requires the ability to regenerate skin with functional sweat glands that are precisely regulated by the nervous system. This proposal will uncover novel molecular mechanisms of neuronal control in sweat gland development, advancing our understanding of skin and sweat gland regeneration and the development of therapeutics to treat patients with sweating deficiency.

PI_NAMEs: LU, CATHERINE PEI-JU (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: 3-Dimensional;Ablation;Acetylcholine;Affect;ATAC-seq;beta-2 Adrenergic Receptors;Binding;Body Temperature;Brain Injuries;Burn injury;Calcium;Cell Culture System;Cell Differentiation process;cell fate specification;Cell Maintenance;Cells;Cessation of life;Chemicals;conditional knockout;Data;Defect;Denervation;Development;Duct (organ) structure;Ductal Epithelial Cell;Eccrine Glands;epidermal stem cell;Equilibrium;Fluorescence-Activated Cell Sorting;Gene Expression;Gland;gland development;Glandular Cell;Heat Stroke;Heterogeneity;Homeostasis;Human;Hyperthermia;Image;Imaging technology;insight;Knockout Mice;Light;Long-Term Effects;Mediating;Modeling;Molecular;Morphogenesis;Morphology;mouse genetics;mouse model;Multipotent Stem Cells;Mus;Muscarinic Acetylcholine Receptor M3;Myoepithelial cell;Natural regeneration;Nerve;nerve supply;Nervous System;Neurons;Neurotoxins;neurotransmission;neurotransmitter release;Neurotransmitters;Norepinephrine;novel;Organ failure;Oxidopamine;Pathway interactions;Patients;Persons;Physiologic Thermoregulation;progenitor;Proliferating;protein expression;receptor binding;regenerative therapy;response;Role;sarcolipin;severe burns;Signal Transduction;single-cell RNA sequencing;Skin;skin regeneration;Skin Tissue;Specific qualifier value;stem cell fate;stem cell fate specification;stem cells;Sweat Glands;Sweating;Testing;therapeutic development;Tissue Engineering;Tissues;Transcriptional Regulation;Water;Work

PROJECT_TITLE: Molecular mechanisms in sweat gland innervation

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Aging;Alcoholism, Alcohol Use and Health;Cardiovascular;Heart Disease;Substance Misuse

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Excessive binge alcohol intake has been widely recognized as a strong risk factor for atrial fibrillation (AF), [especially a significant AF trigger in the aging population]. While alcohol is known to enhance inflammation, the ineffectiveness of anti-inflammation clinical therapies in clinical trials for AF patients demonstrates the urgent need to understand the detailed underlying mechanisms of alcohol and inflammation-associated AF. This proposal is designed to fill this knowledge gap by identifying stress-response c-Jun N-terminal kinase JNK2 as an important nodal point in alcohol-provoked inflammation-associated AF development and the results from this proposal will form a strong foundation toward achieving our long-term goal of developing novel therapies to treat and prevent AF.

PI_NAMEs: AI, XUN  (contact)

PROGRAM_OFFICER_NAME: DUNTY, JR, WILLIAM

PROJECT_TERMS: Address;aged;Aging;aging population;Alcohol abuse;Alcohol consumption;alcohol exposure;Alcoholic Intoxication;Alcohols;Animal Model;Anti-Cytokine Therapy;Apoptosis;Arrhythmia;Atrial Fibrillation;Attention;binge drinking;Biochemistry;biological adaptation to stress;Biological Assay;calmodulin-dependent protein kinase II;Cardiac;Cardiac Electrophysiologic Techniques;Cardiovascular Diseases;Cells;Clinical;Clinical Data;Clinical Trials;Complex;confocal imaging;cytokine;Data;design;Development;Diagnosis;Discipline;Disparate;drug discovery;Economic Burden;Education;Effectiveness;Electrophysiology (science);Engineering;Etiology;Evaluation;FDA approved;Feedback;Foundations;Functional disorder;Future;Gene Transfer;Genetic;Goals;Heart;Heart Atrium;high risk;Holidays;Human;IL1R1 gene;Immunoprecipitation;in vivo;Inflammasome;Inflammation;Inflammatory;innovation;insight;Interleukin-1 beta;Internet;Intervention;JNK-activating protein kinase;Knock-out;Knowledge;Light;Link;MAPK8 gene;MAPK9 gene;Maps;Measurement;Mediating;Modification;Molecular;Morbidity - disease rate;mortality;mouse model;multidisciplinary;Mus;Muscle Cells;Nodal;novel;novel therapeutics;older adult;Optics;Organ;Organ Donor;Organelles;Oryctolagus cuniculus;Outcome;Paint;patch clamp;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Phosphotransferases;Play;prevent;Proliferating;Proteomics;Public Health;Reporting;Risk;Risk Factors;Role;RyR2;Signal Pathway;Signal Transduction;Site;Societies;Specific qualifier value;stress kinase;stressor;superresolution imaging;Syndrome;Testing;Therapeutic;therapeutic evaluation;Therapeutic Intervention;therapeutic target;Tissues;TNF gene;translational potential;Western Blotting;young adult

PROJECT_TITLE: The JNK2-NLRP3 nexus in atrial fibrillation and its anti-AF therapeutic potentials

STUDY_SECTION: TDPS

STUDY_SECTION_NAME: Therapeutic Development and Preclinical Studies Study Section[TDPS]


ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: Project Narrative Our proposal will reveal basic understanding of cardiac fibrosis that will lead to heart failure and examine the tissue-specific role of the genes regulated in cardiac diseases. Finally, we will develop new therapeutic approaches to overcome cardio fibrosis using novel NRP1 inhibitors (NRP1i) and novel targeted liposomal formulations and develop novel therapies to overcome one of the most common myocardial pathologies, which is an unmet clinical need.

PI_NAMEs: MUKHOPADHYAY, DEBABRATA  (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Adult;Angiotensin-Converting Enzyme Inhibitors;Arrhythmia;Blood flow;Candidate Disease Gene;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cells;Cicatrix;Clinical;clinical practice;Collaborations;Combined Modality Therapy;comparison control;coronary fibrosis;Cytometry;Data;Death Rate;differential expression;Diffuse;digital;Drug Kinetics;Endothelial Cells;Fibrosis;Formulation;Functional disorder;Future;Gene Expression Profile;Genes;Grant;Heart;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Heart Injuries;Hypertrophic Cardiomyopathy;Hypoxia;improved;In Vitro;Inflammation;inhibitor;injured;Injury;interdisciplinary approach;interstitial;KDR gene;knock-down;Ligands;lipid nanoparticle;liposomal formulation;Mediating;Mediator;MicroRNAs;Modeling;Molecular;Mus;Myocardial;Myocardial dysfunction;Neuropilin-1;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Nuclear RNA;Outcome;Pathogenesis;Pathology;Pathway interactions;Pattern;Pharmacodynamics;Phenotype;receptor;Recovery;Recovery of Function;Regulation;Regulator Genes;response;RNA analysis;Role;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;small molecule inhibitor;spatiotemporal;Stimulus;success;Systolic heart failure;targeted treatment;Therapeutic;Tissues;Toxic effect;Trademark;Transforming Growth Factor beta;tumor-immune system interactions;Validation;Zebrafish

PROJECT_TITLE: Distinct Pathways of VPF/VEGF Receptors

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Clinical Research;Estrogen;Heart Disease;Menopause;Mental Health;Prevention;Sleep Research;Social Determinants of Health;Women's Health Research

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Poor sleep, which occurs in nearly half of adults and disproportionately affects women and especially racial/ethnic minority women, significantly increases the risk of cardiovascular disease and all-cause mortality. While sleep duration and quality have been well-studied in relation to cardiac risk, little is known about the cardiovascular implications of sleep timing and variability in bedtimes and wake times among non-shift workers, particularly in diverse populations of women across various stages of life (e.g., pre- and post- menopausal). This project will determine the prevalence of objectively-measured sleep variability in two diverse, well-phenotyped cohorts of women, associations of sleep variability with cardiovascular health, whether these associations vary by race/ethnicity and/or menopausal status, and potential mechanisms underlying these associations, to inform the development of public health guidance on sleep that may reduce the burden of cardiovascular disease among women.

PI_NAMEs: AGGARWAL, BROOKE ANNE (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: actigraphy;Address;adequate sleep;Adult;Affect;Age;American Heart Association;Behavior;Blood Pressure;blood pressure elevation;Blood Vessels;Body Composition;brachial artery;Cardiac;Cardiac health;cardiometabolic risk;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;caregiving;Cessation of life;child bearing;Circadian Rhythms;Clinical;cohort;Cohort Studies;Communities;Cross-Sectional Studies;Data;Development;Diet;Disproportionately impacts women;Eating;endothelial dysfunction;Endothelium;Enrollment;ethnic diversity;ethnic minority;Ethnic Minority Women;Ethnic Origin;experience;Face;Female;follow-up;Geography;Guidelines;Health;Health Campaign;Health Care Costs;high risk;High Risk Woman;Hormonal Change;Hypertension;Incidence;Inflammation;inflammatory marker;Life;Life Style;lifestyle factors;Link;Lipids;longitudinal analysis;Measures;Mediating;Menopausal Status;Menopause;Mental Depression;modifiable behavior;Mood Disorders;Morbidity - disease rate;mortality;motherhood;New York City;Obesity;Outcome;Perimenopause;Phenotype;poor sleep;Population Heterogeneity;Postmenopause;Postpartum Period;Pregnancy;Premenopause;Prevalence;primary outcome;Prospective Studies;psychosocial;Psychosocial Factor;Public Health;public health relevance;Race;racial diversity;racial minority;racial minority women;Recommendation;recruit;Registries;Reporting;Reproductive History;reproductive hormone;Research;Risk;Risk Factors;Risk Reduction;Sampling;Schedule;secondary outcome;sex;Sleep;sleep behavior;Sleep Deprivation;Sleep Disorders;Sleep disturbances;sleep pattern;sleep quality;Stress;Time;vascular inflammation;Vasomotor;Weight;Woman;Women's cohort;young woman

PROJECT_TITLE: Sleep Variability and Cardiometabolic Health Among Women

STUDY_SECTION: LHB

STUDY_SECTION_NAME: Lifestyle and Health Behaviors Study Section[LHB]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Digestive Diseases;Inflammatory Bowel Disease

ORG_CITY: LOUISVILLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Project Narrative Urolithin A (UroA) is a microbial metabolite and treatment with UroA attenuated colitis in pre-clinical models without exhibiting toxicity. Current proposal investigates the mechanisms of selective activation of intestinal epithelial cell AHR-NLRP6 axis by microbial metabolite UroA in regulating gut barrier function under inflammatory bowel diseases (IBD) conditions. Identifying such novel mechanisms and compounds that restore gut homeostasis and block unwarranted inflammation would offer new therapeutic options to control IBD.

PI_NAMEs: JALA, VENKATAKRISHNA RAO (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Affect;Affinity;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Attenuated;Biopsy;Cell Differentiation process;Cell Lineage;cell type;Cells;Colitis;Crohn's disease;Data;Epithelial Cells;Exhibits;Family member;Flare;Functional disorder;Generations;Genes;GKLF protein;Goblet Cells;gut homeostasis;gut inflammation;Homologous Gene;Human;IL18 gene;improved;Inflammation;Inflammatory;Inflammatory Bowel Diseases;interleukin-18 receptor;interleukin-22;intestinal barrier;intestinal epithelium;intestinal homeostasis;Intestines;Knock-out;Knowledge;Ligands;Lymphoid Cell;Mathematics;Mediating;Mediator;microbial;mouse model;Mucin-2 Staining Method;Mucins;Mucous body substance;murine colitis;Mus;Natural regeneration;novel;novel therapeutics;nucleotide receptor;Nucleotides;Pathogenesis;Pathologic;Pathway interactions;Patients;Persons;Physiological;Play;Population;pre-clinical;Pre-Clinical Model;Process;Production;protective effect;protective pathway;Protein Family;receptor;Regulation;restoration;Role;Sampling;Signal Pathway;Signal Transduction;stem cells;Testing;Therapeutic;Tissues;Toxic effect;Tracer;transcription factor;Transgenic Mice;Ulcerative Colitis;Up-Regulation

PROJECT_TITLE: AHR-NLRP6 interactions in gut barrier dysfunction and colitis

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]