NIH_SPENDING_CATS: Rare Diseases

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE: Ryanodine receptors facilitate the coupling of nervous excitation to muscle contraction, by releasing calcium ions from intracellular stores in response to depolarization of the plasma membrane. This is an essential process of fundamental importance to human physiology, and dysregulation of intracellular calcium release in skeletal muscle causes diseases such as malignant hyperthermia, central core disease and RyR1-related myopathies. We seek to understand this process at a molecular level, by interrogating the structural and functional regulation of RyR1 by molecules that modulate channel activity allosterically, including the therapeutic dantrolene.

PI_NAMEs: CLARKE, OLIVER BIGGS (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Address;Aging;Allosteric Regulation;Allosteric Site;Binding;Binding Proteins;Binding Sites;Calcium;Calcium Binding;Calcium ion;Calmodulin;Cell membrane;Central Core Myopathy;Clinic;Complex;Coupling;Cresol;Cryoelectron Microscopy;Dantrolene;Data;density;design;Development;Disease;experimental study;Family;flexibility;Genetic Diseases;genetic regulatory protein;Goals;Homeostasis;Human;improved;Ion Channel;Lead;Ligands;Location;Magnesium;Malignant hyperpyrexia due to anesthesia;Maps;Masks;Measures;Mediating;Membrane;Modeling;Molecular;Muscle Contraction;Muscle function;Muscular Atrophy;Mutagenesis;mutant;Mutate;Mutation;Myopathy;particle;Peripheral;Physiological;Physiology;Play;Preparation;Process;Proteins;Proteome;Publishing;receptor;receptor binding;reconstruction;Regulation;Research;Resolution;response;Role;Ryanodine Receptor Calcium Release Channel;Sampling;Sarcoplasmic Reticulum;scaffold;Site;Skeletal Muscle;small molecule;stoichiometry;Structure;Tandem Repeat Sequences;targeted treatment;Testing;Therapeutic;Tissues;Validation;Variant;Work

PROJECT_TITLE: Structural basis for allosteric regulation of RyR1

STUDY_SECTION: BBM

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


ADMINISTERING_IC: GM

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Nutrition;Obesity

ORG_CITY: BATON ROUGE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

ORG_STATE: LA

PI_NAMEs: ALLERTON, TIMOTHY  (contact)

PROJECT_TERMS: Adipose tissue;angiogenesis;Bioenergetics;Biological Assay;Biological Availability;Blood flow;Blood Vessels;Cystathionine;Cytoprotection;Data;Disease;Energy Metabolism;Fat-Restricted Diet;Female;glucose metabolism;High Fat Diet;Human;Hydrogen Sulfide;Knockout Mice;Link;lipid biosynthesis;Lipolysis;Lyase;male;Metabolic;metabolic phenotype;Microdialysis;Mitochondria;Modeling;mouse model;Mus;NG-Nitroarginine Methyl Ester;Nitric Oxide;Nitric Oxide Synthetase Inhibitor;NOS3 gene;novel;Obesity;obesogenic;oxidation;Pathology;Plasma;Production;Resources;Role;Signaling Molecule;Spin Trapping;stable isotope;System;Testing;Vascular Diseases;Wild Type Mouse

PROJECT_TITLE: The Role of Hydrogen Sulfide in Adipose Tissue Function and Angiogenesis


NIH_SPENDING_CATS: Aging;Autoimmune Disease;Building Research Capacity at Institutions with Limited NIH Funding;Diabetes;Nutrition;Obesity

PI_NAMEs: BURKE, SUSAN J. (contact)

PROJECT_TERMS: Acute;Address;Aging;aging related;Beta Cell;Biology;Carnitine Palmitoyltransferase I;Cell Physiology;Diabetes Mellitus;Disease;experimental study;Fatty acid glycerol esters;fatty acid oxidation;Genes;genetic approach;glucose metabolism;High Fat Diet;In Vitro;in vivo;insight;Insulin;Insulin Resistance;insulin secretion;Insulin-Dependent Diabetes Mellitus;islet;Islets of Langerhans;lipid metabolism;Lipids;Metabolic;Metabolic Diseases;Metabolic stress;Metabolism;Mitochondria;mouse model;Mus;novel;Obesity;Organelles;Outcome;oxidation;Pancreas;Proliferating;Role;Tissues;Very Long Chain Fatty Acid

PROJECT_TITLE: Role of fatty acid oxidation in islet beta-cell function


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Nutrition;Rare Diseases

PI_NAMEs: HEDEN, TIMOTHY D. (contact)

PROJECT_TERMS: Disease;glycogen metabolism;Knowledge;Link;Malignant Neoplasms;Metabolic;Molecular Target;mouse model;novel;Primary carcinoma of the liver cells;Role;Route;therapeutically effective

PROJECT_TITLE: Noncanonical glycogen metabolism and hepatocellular carcinoma


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The mounting of an effective and timely adaptive immune response depends on the continuous entry of naïve lymphocytes into lymph nodes via specialized endothelium. The chemoattractants driving migration of lymphocytes across the endothelium into lymph nodes are poorly understood and elucidating the signals mediating this process is important for developing novel and improved immunotherapies that modulate lymphocyte recruitment. We will define the role of oxysterols, which are metabolites of cholesterol, as chemoattractants that promote efficient transendothelial migration of cells into lymph nodes, and thereby advance basic understanding of a fundamental immune cell recruitment process.

PI_NAMEs: CHEN, KEVIN Y (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: 25-hydroxycholesterol;acute infection;adaptive immune response;Adhesions;Adoptive Transfer;Antibody Response;antigen test;Antigens;Area;Autoimmunity;Automobile Driving;B-Cell Activation;B-Lymphocytes;Basal lamina;Binding;Biological Assay;Blood;Blood capillaries;Blood Circulation;BLR1 gene;Capillary Endothelial Cell;Carbohydrates;CCL19 gene;CCL21 gene;CD4 Positive T Lymphocytes;cell motility;cell type;Cells;Cellular Immunity;chemokine;Chemotactic Factors;Cholesterol;Chronic;Circulation;Complement 3d Receptors;Coupled;CXCR4 gene;Data;Defect;Dendritic Cells;Dependence;design;Development;Disease;draining lymph node;Drops;Endothelium;Enzymes;Exhibits;experimental study;Extravasation;Fibroblasts;fMet-Leu-Phe receptor;G-Protein-Coupled Receptors;Generations;Genes;Genetic Transcription;Goals;High Endothelial Venule;Homeostasis;Homing;Hour;Human Herpesvirus 4;Hydroxylation;Immune;Immunization;Immunologic Surveillance;Immunotherapy;improved;In Vitro;in vivo;Infection;Inflammation;Interferons;intravital imaging;Invaded;Knock-out;Knockout Mice;Knowledge;Ligands;lymph nodes;Lymphatic;lymphatic circulation;Lymphocyte;Lymphocytic Infiltrate;Lymphoid Tissue;Malignant Neoplasms;Mediating;Memory;migration;Migration Assay;Mixed Function Oxygenases;Mus;novel;novel therapeutics;Organ;pathogen;Peripheral;Peyer's Patches;postcapillary venule;Process;Property;protein expression;Publishing;receptor;reconstitution;recruit;Reporting;Role;Scanning;selective expression;sialomucins;Signal Transduction;Site;Skin;Stains;Stimulus;Stromal Cells;Surface;T-Lymphocyte;Testing;Toll-like receptors;trafficking;tumor;tumorigenesis;two photon microscopy;vascular addressins;Virus Diseases;Visualization;Work

PROJECT_TITLE: Determining the role of oxysterols in lymphocyte homing to lymph nodes in homeostasis and inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07B-U(20)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Radiation Oncology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Intestinal epithelial integrity is essential for maintaining homeostasis and requires active intestinal stem cells (aISCs) but is often compromised in individuals who must undergo chemotherapy or radiation therapy. This proposal will establish a functional and mechanistic understanding of how the chromatin modifying enzyme Tet1: (1) permits cellular plasticity to replenish the stem cell pool following aISC injury and (2) orchestrates global changes in gene expression through chromatin modifications during changes in intestinal epithelial cell identity. Findings from my studies will provide key insights into the genetic requirements and mechanisms that drive tissue regeneration and inform approaches taken to treat intestinal inflammation and injury.

PI_NAMEs: JANTO, NICOLAS VAUGHAN (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Ablation;Adult;Alleles;Apoptosis;Biological Assay;cancer therapy;CASP3 gene;cell injury;cell type;Cells;chemotherapy;Chemotherapy and/or radiation;Chromatin;chromatin modification;cytotoxic;Data;Data Analyses;Data Set;demethylation;Dioxygenases;Diphtheria Toxin;DNA;DNA Damage;Doxorubicin;Enzymes;epigenomics;Epithelial Cells;epithelial stem cell;Epithelium;epithelium regeneration;Event;experimental study;Exposure to;Faculty;gastrointestinal;Gene Activation;Gene Expression;Genes;Genetic;Genetic Transcription;Genomics;genotoxicity;Global Change;Goals;Growth;gut inflammation;Health;Histology;Homeostasis;In Situ Nick-End Labeling;Individual;Inflammation;Inflammatory Bowel Diseases;Injury;insight;intestinal epithelium;intestinal injury;Intestines;Knock-out;Knockout Mice;LGR5 gene;Malignant Neoplasms;Maps;Measures;Modeling;Morphology;Mouse Embryonic Stem Cells;Mus;Natural regeneration;OLFM4 gene;Organoids;Pathogenicity;Population;Population Control;Positioning Attribute;Process;progenitor;Proliferation Marker;Publishing;Radiation;Radiation therapy;radiation-induced injury;regenerative;Regenerative Medicine;Reporter;Research;response;Risk;Role;seal;Shapes;side effect;Specific qualifier value;Stains;stem cell function;stem cell genes;stem cell population;stem cells;stemness;Testing;Therapeutic;tissue regeneration;Tissues;Training;transcriptome sequencing;transcriptomics;unpublished works;Villus;Work

PROJECT_TITLE: Determining the role of Tet1 in facultative intestinal stem cells

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: SAINT LOUIS

ORG_NAME: FIMBRION THERAPEUTICS, INC.

ORG_STATE: MO

PHR: PROJECT NARRATIVE Urinary tract infections and their complications are common and antibiotic usage for these conditions is a major driver of antimicrobial resistance, so alternative therapeutic strategies are needed. To meet this need, Fimbrion is proposing to develop a drug that recruits naturally occurring human antibodies to the pathogenic bacteria that cause urinary tract infections. This research program will begin the pre-clinical studies necessary to develop this drug as a narrow-spectrum, antimicrobial-sparing, antibody recruiting molecule therapy for the prevention of complicated urinary tract infections.

PI_NAMEs: HIBBING, MICHAEL EINER;MCGRANE, LAUREL  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Acute;Adhesives;Affinity;antagonist;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;Antibodies;antimicrobial;Antimicrobial Resistance;Bacteria;Bacterial Adhesins;Benchmarking;Binding;Biological Availability;Bladder;Blood;carbapenem-resistant Enterobacteriaceae;Case Fatality Rates;Catheters;Cells;clinical candidate;Clinical Treatment;Clinical Trials;Collaborations;combat;commercial application;comorbidity;Complex;Data;design;Development;Dose;Drug Design;Drug Kinetics;Enterobacteriaceae;Epithelium;Extended-spectrum β-lactamase;follow-up;Generations;Goals;Gram-Negative Bacterial Infections;gut microbiome;Half-Life;Health;health care settings;Human;Immune;immune function;Immune system;Immunize;Impairment;Implant;In Vitro;in vitro Assay;in vivo;Infection;Infective cystitis;innovation;Intensive Care;Invaded;Klebsiella pneumoniae;Lead;lead optimization;lead series;Libraries;Long-Term Care;Mannose;Mannose Binding Lectin;Mannosides;Mediating;Microbial Biofilms;Mission;Modeling;Monoclonal Antibodies;mouse model;Multi-Drug Resistance;Mus;nanomolar;novel;novel therapeutics;Oral;Outcome;Parents;pathogen;pathogenic bacteria;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Phase;phase 1 study;Phase Ib Clinical Trial;Pilum;preclinical development;preclinical study;prevent;Prevention;Prevention therapy;programs;Property;Prophylactic treatment;Proteins;prototype;Public Health;recruit;Recurrence;renal scarring;Research;Rhamnose;Risk;Severities;Small Business Innovation Research Grant;small molecule;standard of care;subcutaneous;success;Surface;Testing;Therapeutic;urgent and serious threat;urinary;urinary bladder epithelium;Urinary Catheterization;Urinary tract infection;Urination;Urine;Uropathogen;Uropathogenic E. coli;Virulence Factors

PROJECT_TITLE: FimH-Targeting Antibody-Recruiting Molecules as Novel Drugs for Preventing Complicated Urinary Tract Infections


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Centrioles are at the core of structures that organise cells and enable them to divide properly; they also generate cilia that protrude out of cells in some cases to enable the cells to signal and in others to provide motion. Centrioles are built in the same way in humans and in Drosophila and so, this work aims to use the genetic advantages of Drosophila to study how centrioles are made and how they function in different tissues. This will shed light onto a wide range of human diseases from cancer to the brain developmental defects of microcephaly in which centriole function is perturbed in different ways.

PI_NAMEs: GLOVER, DAVID M (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Affect;Applied Genetics;Biology;Brain;brain abnormalities;Cell Cycle;Cell division;cell type;Cells;Centrioles;Centrosome;Cerebral cortex;Cilia;ciliopathy;cilium biogenesis;Cilium Microtubule;Complex;Cultured Cells;Cytoplasm;Defect;Development;Disease;Drosophila genus;Eukaryota;Flagella;Foundations;Functional disorder;Future;G2 Phase;Generations;Genetic;genetic approach;Germ Cells;Germ Lines;Growth;Heritability;Human;human disease;imaginal disc;Inherited;Interphase;kinetosome;Lead;Leg;Length;Light;male;Malignant Neoplasms;man;Meiosis;Microcephaly;Microtubule Triplet;Microtubules;Mitosis;Molecular;Molecular Biology;Motion;Mutagenesis;Mutation;neurosensory;Nomenclature;Organ;Organelles;organizational structure;Pathology;Pathway interactions;Patients;Phosphorylation;Physiology;Pilot Projects;Procentriole;Process;Prognosis;protein function;Proteins;recruit;Research;Role;Set protein;Signal Transduction;Somatic Cell;Specific qualifier value;sperm cell;Spermatocytes;Spermatogenesis;stem cells;structural biology;Structure;Testing;Tissues;Work

PROJECT_TITLE: Generation of Diverse Centrosomes, Cilia and Flagellae During Development

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Hematology;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: WASHINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative Although most of ovarian cancer patients initially respond to platinum drug-based chemotherapy, up to 80% of patients become refractory to platinum drugs over the time. In this application, we will determine a novel mechanism regulating platinum drug resistance and evaluate effects of a potential new drug to overcome platinum resistance in ovarian cancer. These findings can lead to development of an innovative therapeutic strategy for treatment of platinum drug resistant ovarian cancer patients.

PI_NAMEs: ZHU, WENGE  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Biological Assay;Cancer Biology;cancer cell;Cancer Etiology;Cancer Patient;cancer therapy;Cell Survival;chemotherapy;Clinical;Clinical Oncology;crosslink;Data;Development;Disease;Disease remission;DNA biosynthesis;DNA Interstrand Crosslinking;DNA replication fork;drug discovery;Drug resistance;experimental study;Fanconi Anemia pathway;Fanconi's Anemia;G1 Phase;Genetic;High Mobility Group Proteins;high throughput screening;In Vitro;in vivo;inhibitor;innovation;insight;Laboratory Finding;Lead;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Mediating;Modeling;Molecular;multidisciplinary;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Oncogenes;Operative Surgical Procedures;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phosphorylation;Platinum;Proteins;recruit;Refractory;Regulation;repaired;Reporting;Resistance;Role;Signal Transduction;Site;standard care;Testing;Therapeutic;therapy resistant;Time;tool;translational potential;treatment strategy;tumor;United States;Women's mortality;Yeasts

PROJECT_TITLE: Targeting Fanconi Anemia pathway to overcome platinum drug resistance in ovarian cancer

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Conditions Affecting the Embryonic and Fetal Periods;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn

ORG_CITY: GALVESTON

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: Fetal membranes of the uterine cavity form microfractures (fissures that allow cells and amniotic fluid to leak through) that can disrupt pregnancy in response to infection or other unexpected conditions and lead to preterm birth. In normal pregnancies, these fractures are healed or sealed by cellular mechanisms called transitions, which are not easy to study using traditional cell culture methods because they do not facilitate observation of cell-cell interactions, as in an in utero environment. To study fetal membrane functions, we will recreate the entire cell and extracellular matrix components of the membrane on a chip (organ-on-chip) and study how infection and oxidative stress (factors associated with preterm birth) can disrupt and destabilize membranes, which will improve our knowledge of fetal membrane function as well as generate a methodology that is adaptable to various research fields.

PI_NAMEs: HAN, ARUM ;MENON, RAMKUMAR  (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: Aging;aging mechanism;amnion;Amniotic Fluid;Area;Basement membrane;Biological;Biological Assay;Biological Models;Biomedical Engineering;Birth;bone fracture repair;Cell Communication;Cell Culture Techniques;Cell membrane;Cell model;cell motility;Cell Physiology;Cell Shape;cell type;Cells;Characteristics;design;Development;Devices;Environment;Epithelial Cell Proliferation;Epithelial Cells;epithelial to mesenchymal transition;Epithelium;Exhibits;Experimental Models;Exposure to;Extracellular Matrix;Failure;Fetal Membranes;Fetus;fetus cell;Functional disorder;Generations;Green Fluorescent Proteins;healing;Homeostasis;Impairment;improved;In Situ;in utero;In Vitro;in vitro Model;Infection;Inflammation;Inflammatory;innovation;Intervention;Investigation;Kinetics;Knowledge;Label;Laboratories;Magnetism;Mechanics;Membrane;membrane model;Mesenchymal;Methodology;Methods;Microfluidics;Microscopy;migration;Modeling;Molecular;Monitor;morphometry;multi-photon;multidisciplinary;organ on a chip;Oxidative Stress;Pathologic;Pathway interactions;Physiological Processes;Pregnancy;Pregnancy Complications;premature;Premature Birth;Premature Rupture Fetal Membranes;preterm premature rupture of membranes;Process;Property;prototype;Recycling;repaired;Research;response;risk minimization;Risk Reduction;Role;seal;second harmonic;senescence;senescent cell;Signal Transduction;Site;System;Technology;Testing;Tissues;Transfection;Translating;Urea;Uterine cavity;Width

PROJECT_TITLE: Intercellular interactions define cell migrations and transitions that maintain fetal membrane homeostasis

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative: Social behavior is often prominently affected in many neurocognitive disorders such as major depression, schizophrenia, alcoholism and autism spectrum disorder. Yet, despite its importance, the single-neuronal bases and causal underpinnings of interactive social behavior are still largely unknown. The fundamental new line of investigation proposed here in primates will provide a crucial theory-based framework and roadmap for understanding social behavior and its dysfunction at the single-neuronal, population and circuit-based levels.

PI_NAMEs: WILLIAMS, ZIV  (contact)

PROGRAM_OFFICER_NAME: VAZIRI, SIAVASH

PROJECT_TERMS: Affect;Alcoholism;Amygdaloid structure;Animal Model;Animals;Anterior;Area;autism spectrum disorder;base;Behavior;cingulate cortex;Code;Cues;Dimensions;Disease;Dissociation;Dorsal;Ecology;Elements;experience;experimental study;Facial Expression;field study;Functional disorder;Future;gaze;Human;Individual;Intervention;Investigation;Joints;Learning;Macaca mulatta;Major Depressive Disorder;member;Modeling;neural;neurocognitive disorder;Neurology;neuromechanism;Neurons;neuroregulation;Neurosciences;Outcome;Paint;Parietal;Play;Population;Primates;Psychology;psychosocial;response;Role;Schizophrenia;Site;social;Social Behavior;social cognition;Social Environment;social group;Social Interaction;Specificity;Structure;Techniques;Testing;theories;Time;Time Study;time use

PROJECT_TITLE: A formal group theory-based model in primates for studying interactive social behavior and its dysfunction

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Childhood Obesity;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE A national consortium of diverse high-risk youth rigorously studied throughout puberty will provide foundational knowledge about the pathophysiology of youth-onset T2D. Findings from this work will shed light on the individual, familial, and social factors affecting youth-onset T2D risk which will, in turn, directly inform strategic investments in targeted approaches for prevention and risk management.

PI_NAMEs: DABELEA, DANA  (contact);PERNG, WEI

PROGRAM_OFFICER_NAME: BROADNEY, MIRANDA MARGUERITE

PROJECT_TERMS: Adult;Affect;Age;American Indian community;American Indians;Area Under Curve;Behavior;Behavioral;Beta Cell;Biological;Biological Markers;Biometry;Body mass index;case control;Cell Physiology;Characteristics;Clinical;clinical research site;cohort;Collaborations;Collection;Colorado;critical period;Data;design;Development;Diabetes autoantibodies;Diabetes Mellitus;diabetes risk;diagnostic accuracy;Disease;Disease Progression;emerging adult;Enrollment;ethnic minority population;Ethnic Origin;Etiology;experience;Exposure to;Family history of;Functional disorder;Genetic;Glucose;Goals;high risk;Homeostasis;Hour;Individual;Insulin;insulin sensitivity;Investments;Knowledge;Leadership;Life;maternal diabetes;Modeling;National Institute of Diabetes and Digestive and Kidney Diseases;Navajo;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Obesity Epidemic;obesity in children;OGTT;Overweight;Participant;participant retention;Pathway interactions;Pattern;Phenotype;Physiological;pre-clinical;predictive modeling;prevent;Prevention;Prevention approach;Productivity;Protocols documentation;psychosocial;Psychosocial Factor;Psychosocial Stress;Puberty;Public Health;Race;racial minority population;recruit;Research;Risk;Risk Assessment;Risk Factors;Risk Management;risk prediction;Rural Community;rural residence;sex;social factors;social health determinants;Subgroup;trend;Universities;Visit;Work;Youth

PROJECT_TITLE: Understanding the Pathophysiology of Type 2 Diabetes in Navajo Youth


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Immunization;Infectious Diseases;Vaccine Related

ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Listeria monocytogenes is a foodborne pathogen responsible for the life-threatening disease listeriosis. This work will elucidate novel host pathways activated by the major L. monocytogenes virulence factor, the pore- forming toxin listeriolysin O, to promote host cell invasion and to elicit protective T cell immunity. This knowledge will broadly impact the development of vaccines and novel therapeutic strategies for a wide range of diseases in which pore-forming toxins are employed by pathogens.

PI_NAMEs: AMER, AMAL O;BOYAKA, PROSPER N;DUBEY, PURNIMA ;SEVEAU, STEPHANIE M M (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Adjuvant;anti-cancer;Antigen Presentation;Antigen-Presenting Cells;Antigens;antimicrobial;Bacteria;Binding;Calcium;Calcium Channel;Cancer Vaccines;cathepsin K;Cathepsins;Cell Death;Cell membrane;Cell Physiology;Cell surface;Cell Survival;cell type;Cells;Cholesterol;Communicable Diseases;Complex;Cytolysins;Cytoprotection;Cytoskeletal Proteins;Cytoskeleton;Cytosol;Data;Dendritic Cells;Development;Disease;Endosomes;Epithelial Cells;Event;Excision;Exocytosis;Exposure to;Family;Fluorescence Microscopy;foodborne illness;foodborne pathogen;Genes;Goals;Gram-Positive Bacteria;Histocompatibility Antigens Class II;Homeostasis;Hospitalization;Immune;Immune response;Immunity;In Vitro;in vivo;Infection;Inflammasome;Inflammatory;Injury;Innate Immune Response;Invaded;Knowledge;Laboratories;Length;Libraries;Life;Life Cycle Stages;Listeria;Listeria monocytogenes;Listeria monocytogenes hlyA protein;Listeriosis;Lysosomes;Macrophage;Mediating;Membrane;Modeling;molecular assembly/self assembly;Myopathy;Neurodegenerative Disorders;novel;novel therapeutic intervention;pathogen;Pathogenesis;Pathology;Pathway interactions;Perforation;Phagosomes;Plasma Cells;Play;premature;Process;Property;Protein Kinase C;Proteins;Proteomics;Publishing;rational design;Recombinants;recruit;repaired;Reporting;response;Role;screening;Signal Transduction;Small Interfering RNA;spatiotemporal;Speed;Structure-Activity Relationship;superresolution imaging;superresolution microscopy;T cell response;T-Lymphocyte;Testing;Therapeutic Intervention;Time;Toxin;Toxoids;trafficking;vaccine development;Vaccines;Vacuole;Variant;Virulence;Virulence Factors;voltage;Work

PROJECT_TITLE: Host Responses to the Pore-Forming Toxin Listeriolysin O

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-R(02)M]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: PROVO

ORG_DEPT: CHEMISTRY

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

ORG_STATE: UT

PHR: This proposal develops new methods to identify how age and genetic factors modify brain metabolism and promote neurodegeneration. It is known that many risk factors change metabolism in specific regions of the brain, but how and why these changes occur is unknown. Identifying the region-specific metabolic consequences of known risk factors will allow us to design strategies to quantify risk and stop neurodegeneration before real damage is done.

PI_NAMEs: PRICE, JOHN C. (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Age;age related;age related changes;Aging;Alzheimer's Disease;Alzheimer's disease risk;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Area;Biochemical;Biochemical Pathway;Brain;brain metabolism;Brain region;Cardiovascular system;Clinical;Cognition;Contrast Media;Coupling;Data;Data Set;desensitization;design;Development;diet and exercise;Disease;Environmental Risk Factor;Enzymes;Exhibits;Genetic;Genetic Polymorphism;genetic predictors;Genetic Predisposition to Disease;genetic risk factor;Genotype;High-dimensional Modeling;Hippocampus;imaging modality;Imaging Techniques;in vivo;Individual;Inflammation;insight;Investigation;kinetic model;Knowledge;Life Style;lipid metabolism;lipid transport;Lipids;mass spectrometric imaging;Measures;Memory;Metabolic;Metabolic Control;Metabolic Pathway;Metabolism;Methods;Modeling;Monitor;mouse model;Mus;Nerve Degeneration;novel;Pathway interactions;Pattern;Persons;physiologic stressor;Positron-Emission Tomography;prevent;Probability;Protein Isoforms;Proteins;Proteomics;Regulation;Relative Risks;repaired;Resistance;Risk;Risk Factors;Sampling;Stress;Surface;Synaptic plasticity;System;Techniques;Technology;Testing;Therapeutic;Tissues;Variant

PROJECT_TITLE: Biochemical Consequences of Regiospecific Metabolic Bias in the Brain

STUDY_SECTION: CMND

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Services;Methamphetamine;Opioid Misuse and Addiction;Opioids;Patient Safety;Social Determinants of Health;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE The substance use crisis in the United States increasingly involves the co-use of methamphetamine and opioids together. Given the unique sociodemographic characteristics and co-morbidities associated with co- use, existing hospital-based addiction services may not adequately serve patients who use both substances. This project will quantify patient demographics and outcomes following hospital discharge, by substance use profile, and identify facilitators and barriers to expanding hospital-based addiction services tailored to co-use in the inpatient setting, through a sequential explanatory mixed methods design.

PI_NAMEs: SHEARER, RILEY  (contact)

PROGRAM_OFFICER_NAME: FITZ-RANDOLPH, MARCY ESTHER

PROJECT_TERMS: Accounting;addiction;Address;Administrator;Admission activity;Advocacy;Age;Ambulatory Care;Automobile Driving;Cessation of life;Characteristics;Clinical;Clinical Medicine;Communication;Communities;Community Hospitals;comorbidity;Complex;Consult;Consultations;Cox Proportional Hazards Models;Data;Death Certificates;Death Rate;demographics;design;Development;Educational process of instructing;Effectiveness;Electronic Health Record;Ethnic Origin;Evaluation;experience;Fellowship;Frontline worker;Funding;Future;Gender;Goals;Health;Health Services Accessibility;Health Services Research;Hospital Mortality;hospital readmission;Hospitalization;Hospitals;improved;Individual;individualized medicine;Inpatients;Insurance Coverage;Intervention;Interview;Lead;Length of Stay;Link;Location;Logistics;medication for opioid use disorder;Medicine;Methamphetamine;methamphetamine use;Methods;mortality;National Research Service Awards;Nurses;Opioid;opioid use;Outcome;Overdose;overdose death;Patient Care;Patients;Pattern;Pharmaceutical Preparations;Physicians;polysubstance use;prevent;programs;Provider;Race;Readiness;readmission rates;readmission risk;Research;Research Methodology;Research Personnel;Resources;response;Risk Reduction;Sampling;Services;Shapes;skills;social stigma;Social Workers;sociodemographics;Structure;substance use;Substance Use Disorder;Surveys;Time;Training;treatment services;United States;Work

PROJECT_TITLE: Characteristics and outcomes for hospitalized patients with methamphetamine and opioid co-use: Identifying opportunities for hospital-based addiction services tailored to co-use

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F16-L(20)L]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Human Genome;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: LOUISVILLE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: In retinitis pigmentosa (RP), rod photoreceptors die, leading to blindness. Patients typically come to the clinic with mid/late-stage disease, after many rods have died. We will test the efficacy, efficiency, specificity and safety a gene therapy for this autosomal dominant orphan disease caused the P23H mutation in rhodopsin.

PI_NAMEs: GREGG, RONALD G;MCCALL, MAUREEN A (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Accounting;Affect;Alleles;alternative treatment;Animal Euthanasia;Animal Model;Animals;autosome;Behavior;Biological Models;Blindness;Canis familiaris;Cells;Clinic;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cone;deep sequencing;Development;Disease;Double Strand Break Repair;efficacy evaluation;efficacy testing;Electroretinography;endonuclease;Engineering;experimental study;Eye;Eye diseases;Family suidae;Frequencies;functional decline;gene editing technology;Gene Expression;Gene Mutation;gene therapy;Genes;Genome;genome editing;Genome-wide Unbiased Identification of DSBs Enabled by sequencing;Genomics;Goals;GRK1 gene;Homing;Human;Human Genome;human model;humanized mouse;in silico;individualized medicine;insertion/deletion mutation;interest;Intervention;Measures;Methodology;Modality;Modeling;Morphology;mouse model;Mus;mutant;Mutate;Mutation;Natural History;neglect;Night Blindness;Nonhomologous DNA End Joining;nonhuman primate;North America;nuclease;off-target site;optimal treatments;Organoids;Outcome;Patient Selection;Patients;Photoreceptors;porcine model;pre-clinical;Pre-Clinical Model;preclinical evaluation;Proteins;Rare Diseases;Research Personnel;Rest;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;retinal rods;Retinitis Pigmentosa;Rhodopsin;Rod;Safety;safety assessment;Selection Criteria;Site;Specificity;Structure;subretinal injection;Technology;Therapeutic;Time;timeline;tool;Transgenic Organisms;Vertebrate Photoreceptors;Viral Packaging;Visual;zinc finger nuclease

PROJECT_TITLE: Preclinical evaluation of a homing endonuclease gene therapy for adRP in models of P23H retinopathy.

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: RFA: PA-20-203 TITLE: Illuminating Glial Dysfunction in Alzheimer’s Disease with Optical Coherence Tomography PROJECT NARRATIVE: The majority of cells in the central nervous system are glial cells, which provide support for the health and function of neurons. Glial cell dysfunction occurs in Alzheimer’s disease, but non-invasive measurement of glial health is needed to translate this basic knowledge into enhancements in patient health, obtained through early diagnostic testing or assessment of glia-targeted therapies. We propose the use of a common and non-invasive tool for retinal imaging – optical coherence tomography – to explore a new marker of glial dysfunction in persons living with Alzheimer’s disease, and in Alzheimer’s disease mouse models.

PI_NAMEs: BISSIG, DAVID PHILIP (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta accumulation;Abeta clearance;Adult;Age;age related decline;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Amino Acids;Amyloid;Amyloid beta-Protein;Anatomy;Antibodies;APP-PS1;aquaporin 4;Biological Assay;Biology;biomarker development;Blood Vessels;Brain;California;career;career development;Cell Culture Techniques;Cells;Center for Translational Science Activities;Central Nervous System;Cerebrospinal Fluid;Clinic;Clinical;Clinical Sciences;Clinical Trials;Cognitive;cost;Dementia;Detection;Development;Diagnosis;Diagnostic tests;diagnostic tool;Disease;disease model;Elements;experience;Fellowship;fluid flow;Functional disorder;Funding;Genetic;Genetic Polymorphism;glymphatic dysfunction;glymphatic system;Goals;Health;Human;Image;imaging modality;Impaired cognition;Impairment;improved;In Vitro;Institution;Intercellular Fluid;interstitial;Intervention;knockout animal;Knockout Mice;Knowledge;Light;Link;Location;Measurement;Measures;Mediating;Memory impairment;Mentors;Methods;microscopic imaging;mild cognitive impairment;Modeling;Monitor;monomer;mouse model;Muller's cell;Mus;Mutant Strains Mice;Neurodegenerative Disorders;Neuroglia;Neurologist;Neurology;Neurons;next generation;non-invasive imaging;nonalzheimer dementia;novel;novel diagnostics;novel marker;Ocular Pathology;Optical Coherence Tomography;Osmosis;Outcome;Pathogenesis;Pathologic;Pathway interactions;Patients;Persons;Photoreceptors;Physicians;Physiological;Physiology;Positron-Emission Tomography;Production;Protein Isoforms;Proteins;recruit;Reporting;Research;Research Personnel;Resources;response;Retina;retinal imaging;Rodent;Role;Scientist;Senile Plaques;Signal Transduction;skills;targeted treatment;Techniques;Technology;Testing;tool;Training;Translating;translation assay;translation to humans;translational approach;translational neuroscience;United States National Institutes of Health;Universities;Vision;vision science;wasting;Water;water channel;Water Movements

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Biotechnology;Lung

ORG_CITY: ALBANY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: ALBANY MEDICAL COLLEGE

ORG_STATE: NY

PHR: Abnormal contraction and proliferation of airway smooth muscle contributes to the progression of asthma which affects nearly 25-30 million people in the United Sates and 250 million people worldwide. This research project is to explore previously-unknown mechanisms that control airway smooth muscle contraction, proliferation and asthma pathogenesis using sophisticated biotechnology. Obtaining this knowledge is necessary to develop new strategies to treat the disease.

PI_NAMEs: TANG, DALE D. (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Actins;Affect;airway hyperresponsiveness;Allergens;Asthma;asthmatic;asthmatic airway smooth muscle;Binding Proteins;Biological Process;Biosensor;Biotechnology;cancer cell;Cell Extracts;Cell Physiology;Cell Proliferation;Cell Survival;cell type;Cells;Characteristics;comparison control;Complex;Confocal Microscopy;cytokine;Cytoskeletal Proteins;Cytoskeleton;Data;Development;Disease;Enzymes;Extracellular Matrix Proteins;Extrinsic asthma;FRAP1 gene;functional genomics;Gene Expression Regulation;Goals;Grant;Growth;Growth Factor;Human;Immunoprecipitation;In Vitro;in vivo;Intermediate Filament Proteins;knock-down;Knockout Mice;Knowledge;Laboratories;Lipids;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Muscle Contraction;Nerve;nestin protein;novel therapeutics;Pathogenesis;Pathologic;Pathologic Processes;Pathology;Pathway interactions;Persons;Phosphorylation;Phosphotransferases;Pilot Projects;Play;PLK1 gene;polo-like kinase kinase 1;Process;Proliferating;protein expression;Protein Kinase;Protein-Serine-Threonine Kinases;Proteins;Regulation;Research;Research Project Grants;respiratory smooth muscle;Role;Sampling;Signal Transduction;Smooth Muscle;Smooth Muscle Myocytes;stem;stem cell function;Structure;System;Testing;tool;Translations;United States;Universities

PROJECT_TITLE: PLK1 Regulation of Airway Smooth Muscle

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Human Genome;Liver Disease

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE This project focuses on PPARα, a key regulator of fat metabolism in liver cells, and how it and the related factor HNF4α impact non-alcoholic fatty liver disease (NAFLD), a growing threat to public health related to the epidemics of obesity and diabetes. There are no drugs approved for NAFLD, but those targeting PPARα are strong candidates to be among the first. By using mouse and cell models as well as human liver samples, our genomic and genetics studies will reveal mechanisms of PPARα function related to the pathophysiology and treatment of NAFLD.

PI_NAMEs: LAZAR, MITCHELL A. (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Address;Affect;Agonist;Amino Acids;Atherosclerosis;Binding;Binding Sites;Biology;Cardiometabolic Disease;Cardiovascular system;Cell model;Cessation of life;Choline Deficiency;Chromatin;Cirrhosis;Clinical;clinically relevant;Data;Diabetes Mellitus;dietary;Direct Repeats;Disease;Disease Progression;disorder risk;DNA;DNA Binding;DNA Binding Domain;DNA Sequence;drug development;Drug Targeting;Drug usage;Environment;environmental change;Event;experimental study;Fatty Liver;Fibrates;Fibrosis;Functional disorder;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic approach;genetic association;Genetic Models;Genetic Polymorphism;Genetic Risk;Genetic study;genetic variant;Genetic Variation;Genome;genome-wide;Genomic approach;Genomics;Hepatic;Hepatocyte;High Fat Diet;Hormones;Human;Human Genetics;Hypertriglyceridemia;improved;in vivo;Inbred Strains Mice;individualized medicine;Inflammation;innovation;interest;Knockout Mice;Ligand Binding Domain;Link;lipid metabolism;Liver;Liver Failure;Liver Fibrosis;liver injury;Minority;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;new therapeutic target;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;Nuclear Receptors;Obesity Epidemic;Outcome;Pathogenesis;Pathology;Patients;Peroxisome Proliferator-Activated Receptors;Persons;Pharmaceutical Preparations;Phase;Phenotype;Population;PPAR alpha;Prevalence;Primary carcinoma of the liver cells;Public Health;receptor function;response;Risk Reduction;Role;Sampling;Serum;simple steatosis;Single Nucleotide Polymorphism;Site;Techniques;Testing;Therapeutic;Time;Tissues;tool;transcription factor;treatment response;Triglycerides;Untranslated RNA;Variant;Wild Type Mouse

PROJECT_TITLE: PPARa and related nuclear receptors in non-alcoholic fatty liver disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

PHR: Project Narrative The HIV-1 Gag protein mediates specific genomic RNA packaging during the assembly step of the retroviral lifecycle. The remarkable specificity with which Gag selects this RNA among a vast excess of cellular and spliced viral RNAs remains incompletely understood and is the focus of this work. The high level of sequence conservation in the 5′UTR makes this region especially attractive as a drug target and the results of the studies proposed herein will help guide the design of new therapeutic agents.

PI_NAMEs: MUSIER-FORSYTH, KARIN M (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: 5' Untranslated Regions;Acylation;Adopted;Affect;Binding;Binding Sites;Biological Assay;Biology;Cell Culture Techniques;Cells;Characteristics;Clinical;Computer Models;Conserved Sequence;cost;crosslink;Data;design;dimer;dimethyl sulfate;Drug Targeting;Elements;Ensure;expectation;fitness;Fluorescence Resonance Energy Transfer;gag Gene Products;Genetic Materials;genomic RNA;hammerhead ribozyme;Heterogeneity;HIV-1;Hydroxyl Radical;In Vitro;inhibitor;insight;Kinetics;Label;Life Cycle Stages;Mass Spectrum Analysis;Measures;Mediating;Molecular Conformation;mutant;Mutation;novel strategies;novel therapeutics;Nucleotides;particle;Pharmaceutical Preparations;preference;prevent;Primer Extension;Production;Property;Reporting;RNA;RNA Binding;RNA Conformation;RNA Probes;RNA Splicing;Role;single molecule;Specificity;stoichiometry;Structure;targeted treatment;Testing;Therapeutic;Therapeutic Agents;Transcript;Transcription Initiation Site;Viral;Viral Genome;viral RNA;Virion;Virus Assembly;Virus Replication;Work;Zinc Fingers

PROJECT_TITLE: RNA binding and packaging by retroviral Gag proteins


NIH_SPENDING_CATS: Aging;Cardiovascular;Clinical Research;Contraception/Reproduction;Genetics;Heart Disease;Infertility;Prevention;Women's Health Research

PHR: PROJECT NARRATIVE Infertility affects approximately 10% of women, and recent evidence suggests that infertility is linked with chronic disease, including cardiovascular disease and metabolic syndrome later in life. Changes in gene regulation may proceed the onset of cardiovascular disease and metabolic syndrome, making it an ideal candidate for identifying women at future risk of disease. This would provide an opportunity for early intervention and allow these risks to be discussed as part of infertility evaluations.

PI_NAMEs: KNIGHT, ANNA KAITLYN (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: accelerated epigenetic aging;Acceleration;adverse outcome;Affect;Age;age acceleration;Area;biobank;biological age;Blood specimen;candidate identification;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular risk factor;Cause of Death;cell age;Chronic Disease;Chronology;Clinical Data;Counseling;critical period;Development;Diagnosis;diminished ovarian reserve;Disease;disorder risk;DNA Methylation;Early identification;Early Intervention;Early treatment;embryo cryopreservation;endometriosis;Environment;epigenetic clock;Epigenetic Process;Evaluation;Exhibits;experience;Fertility;fertility preservation;Fertilization in Vitro;Fibroid Tumor;follow-up;Future;Gene Expression;Gene Expression Regulation;Goals;Health;Health Status;healthspan;Hormones;idiopathic infertility;Individual;Infertility;infertility treatment;Inflammation;insight;Intervention;Life;lifetime risk;Link;Literature;Menopause;Metabolic;Metabolic Diseases;Metabolic syndrome;Methylation;Molecular;Morbidity - disease rate;mortality;mortality risk;mullerian-inhibiting hormone;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Onset of illness;oocyte cryopreservation;ovarian dysfunction;ovarian reserve;Pathway interactions;Pattern;personalized medicine;Physiological Processes;Polycystic Ovary Syndrome;Postmenopause;predictive marker;Pregnancy loss;Preimplantation Diagnosis;Prevalence;Prevention;Preventive care;Preventive measure;Prospective cohort;Recurrence;reproductive;Risk;Risk Factors;risk mitigation;screening;Services;Site;Stroke;Time;United States;Woman;Women's mortality;Work

PROJECT_TITLE: Impact of fertility status on epigenetic indicators of future health risk


ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE  Staphylococcal infections have become increasingly difficult to treat partly because more virulent strains have continued to emerge. However, how virulence factors are regulated in staphylococci is still largely unknown. This application aims to advance our understanding of virulence regulation by a protein chaperone through a key regulator, thereby providing a solid foundation for developing new strategies to comeback staphylococcal diseases.

PI_NAMEs: LEE, CHIA Y. (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Affect;Animals;Bacteria;Biochemical;Biological Assay;capsule;Cell Density;Cell surface;Chimeric Proteins;Complex;Data;Disease;DNA Binding;Enabling Factors;Environment;experimental study;extracellular;Foundations;Gene Expression Regulation;Genes;genetic approach;Genetic Transcription;Genus staphylococcus;Goals;Gram-Positive Bacteria;Homeostasis;Human;human pathogen;human tissue;Immune system;in vivo;Infection;insight;Interferometry;Knowledge;Laboratories;Life;Maps;Membrane Proteins;Methods;Modeling;Molecular Chaperones;novel;Operon;Organism;oxidation;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Peptide Hydrolases;Peptides;Pheromone;Play;Polysaccharides;Process;Production;Promoter Regions;protein folding;Proteins;Quality Control;quorum sensing;Regulation;Regulatory Pathway;Regulon;Reporter;Research;RNAIII;Role;sensor;Small RNA;Solid;Staphylococcal Infections;Staphylococcus aureus;Surface;System;Technology;Testing;Toxin;virtual;Virulence;Virulence Factors;virulence gene;Virulent

PROJECT_TITLE: Modulation of Agr system by ClpC chaperone in S. aureus

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Generating adaptive body movements is a fundamental function of the brain that is impaired in motor disorders such as Parkinson’s disease and multiple sclerosis. We propose to study neural circuit mechanisms mediating motor learning using cutting-edge circuit dissection tools in mice.

PI_NAMEs: KOMIYAMA, TAKAKI  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TITLE: Deconstructing Functional Circuits of Motor Cortex During Motor Learning

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Antimicrobial Resistance;Bioengineering;Clinical Research;Genetics;Infectious Diseases;Kidney Disease;Microbiome;Nanotechnology;Organ Transplantation;Transplantation;Urologic Diseases

ORG_CITY: ITHACA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: CORNELL UNIVERSITY

PHR: Urinary tract infections (UTIs), including multi-drug antibiotic-resistant UTIs, occur at an alarmingly high rate after kidney transplantation. The goal of this project is to establish the utility of urinary cell-free DNA as a versatile analyte that can detect a wide range of potential pathogens and can inform drug resistance and host-pathogen interactions. Successful implementation of these studies will lead to a highly informative diagnostic test for UTI which will inform antibiotic stewardship, improve graft and patient outcomes and translate into significant health care cost savings.

PI_NAMEs: DADHANIA, DARSHANA ;DE VLAMINCK, IWIJN  (contact);MASON, CHRISTOPHER EDWARD

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: 16S ribosomal RNA sequencing;Acute;Address;Affect;Algorithms;Antibiotic Resistance;antibiotic resistant infections;Antibiotic susceptibility;Antibiotics;Bacteria;Biochemical;Bioinformatics;Biological Assay;cell free DNA;Cessation of life;Clinical;Clinical Markers;co-infection;cohort;commensal microbes;Communicable Diseases;cost;Cost Savings;Data;design;Development;Diagnosis;diagnosis standard;Diagnostic tests;DNA;DNA sequencing;Drug resistance;epigenetic marker;epigenetic profiling;Evaluation;experience;General Population;genetic approach;Goals;graft function;Health Benefit;Health Care Costs;Immune response;improved;Infection;Injury;Investigation;Kidney Transplantation;Life;Maps;Measurement;Medical;metagenome;metagenomic sequencing;Metagenomics;Methodology;Methylation;microbiome;Monitor;nanopore;novel;novel strategies;pathogen;Patient Monitoring;Patient-Focused Outcomes;Patients;Performance;Persons;Pilot Projects;point of care testing;post-transplant;precision medicine;programs;Prospective cohort;Prospective, cohort study;Questionnaires;Research;Research Design;Resistance;Resolution;response to injury;sample collection;Sampling;Severity of illness;single molecule;Sorting;Specimen;Technology;Testing;Time;tissue injury;tool;Translating;transplant centers;Transplant Recipients;Transplantation;urinary;Urinary Microbiome;Urinary tract infection;Urine;Viral;Visit;Work

PROJECT_TITLE: Metagenomic profiling of urinary cell-free DNA to monitor urinary tract infection after kidney transplantation

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Neurosciences

ORG_CITY: SAN DIEGO

ORG_NAME: SCINTILLON INSTITUTE FOR PHOTOBIOLOGY

PHR: PROJECT NARRATIVE These studies will have implications for developing effective hypothermic drugs that could be used for inducing controlled hypothermia or treat hyperthermia nonresponsive to other treatments.

PI_NAMEs: CHEN, ALBERT ;TABAREAN, IUSTIN VIRGIL (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Animals;Body Temperature;Brain region;Cannabinoids;Cells;Characteristics;Data;Development;Electrophysiology (science);experimental study;Exposure to;extreme heat;Fever;FOS gene;gamma-Aminobutyric Acid;Genetic;Glutamates;Heat Losses;Heat Stress;Heat Stroke;High temperature of physical object;Hyperthermia;Hypothalamic structure;induced hypothermia;Induced Neurons;Ion Channel;Lateral;Measures;Mus;natural hypothermia;neural network;neurochemistry;Neurons;Neurotensin;Optics;optogenetics;parabrachial nucleus;Peripheral;Pharmaceutical Preparations;pharmacologic;Physiologic Thermoregulation;Physiological;pituitary adenylate cyclase activating polypeptide;Play;Population;postsynaptic;Preoptic Areas;Property;Reporting;response;Role;Site;Spinal Cord;Stress;sulfated glycoprotein 2;Telemetry;Temperature;Testing;Therapeutic heat application;tool;Transcript;transcriptomics;Transgenic Model;Vasodilation;Viral Vector

PROJECT_TITLE: Central thermoregulatory mechanisms during heat stress

STUDY_SECTION: BNRS

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


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

PHR: PROJECT NARRATIVE The proposed studies focus on understanding the mechanisms through which macrophage subpopulations contribute to breast cancer growth and progression. This research is relevant to human health because understanding the mechanisms driving tumor cell-stromal interactions during the growth and metastasis of human breast cancers will ultimately lead to the development of novel therapeutic strategies that will improve patient outcome by enhancing initial response, preventing resistance and reducing relapse.

PI_NAMEs: SCHWERTFEGER, KATHRYN L (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: adaptive immune response;Antitumor Response;Automobile Driving;Binding;Bone Marrow Transplantation;Breast Cancer Model;breast cancer progression;Cancer Etiology;cell killing;Cells;Coculture Techniques;cohort;combat;Complex;congenic;Data;defined contribution;Development;Disease;ECM receptor;Environment;Exhibits;experimental study;Extracellular Matrix;Gene Expression Profile;Genetic Models;Goals;Growth;Health;Heterogeneity;Histologic;Homeostasis;Human;Hyaluronan;Immunofluorescence Immunologic;improved;In Vitro;in vivo;Inflammatory Infiltrate;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary gland;Mammary Neoplasms;Mediator;Methods;Modeling;mouse model;Neoplasm Metastasis;neoplastic cell;novel strategies;novel therapeutic intervention;patient prognosis;Patient-Focused Outcomes;Phenotype;Population;Population Heterogeneity;prevent;Primary Neoplasm;Property;Publishing;Relapse;Research;Resistance;response;self-renewal;Signal Transduction;single-cell RNA sequencing;Source;Stromal Cells;Testing;Therapeutic;therapy resistant;Tissues;transcriptomics;Transplantation;tumor;Tumor Cell Invasion;tumor growth;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-associated macrophages;Tumor-Derived;Women's mortality

PROJECT_TITLE: Defining the contributions of Lyve-1 expressing macrophages to breast cancer growth and progression

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


NIH_SPENDING_CATS: Biomedical Imaging;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Human Genome;Liver Disease;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Integrative Polygenic Genetic Studies of Non-alcoholic Fatty Liver Disease Narrative Nonalcoholic fatty liver disease NAFLD is becoming the number one cause of highly prevalent globally and imparts a significant economic burden but has limited therapeutic options due lack of understanding of its etiology. Here we will carry out integrative genome wide association meta analyses to identify genetic variants that causally associate with NAFLD; we will test implicated variants and genes alone and in combination for their ability to (1) predict hepatic steatosis, cirrhosis, and HCC as well as induce hepatic steatosis in liver cells. Results from our work will help define the etiology of NAFLD and inform development of potential therapeutics for this condition.

PI_NAMEs: SPELIOTES, ELIZABETH K (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Adult;Affect;African;Alanine;Alanine Transaminase;Aspartate;Aspartate Transaminase;attenuation;biobank;Biological Markers;causal variant;Cell Line;chronic liver disease;Cirrhosis;cohort;Collection;CRISPR/Cas technology;Data;Development;Diagnosis;Disease;disease diagnosis;disorder subtype;dosage;Economic Burden;Ethnic Origin;Etiology;European;Fatty acid glycerol esters;Fatty Liver;follow-up;Frequencies;Functional disorder;Gene Dosage;gene function;Genes;Genetic;genetic architecture;Genetic study;genetic variant;genome wide association study;genome-wide;genomic locus;Genomics;Goals;Grant;Hepatocyte;Heritability;Heterogeneity;High Prevalence;Hispanic ancestry;Hispanic Populations;Histology;Human;Image;improved;Individual;International Classification of Disease Codes;Knock-out;Link;Lipids;Liver;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver imaging;Magnetic Resonance Imaging;Measures;Medical;Meta-Analysis;Metabolic;Michigan;multi-ethnic;non-alcoholic fatty liver disease;non-invasive imaging;novel;Obesity;overexpression;polygenic risk score;Prevalence;prevent;Prevention;Primary carcinoma of the liver cells;Public Health;Publishing;Risk;risk prediction;Role;Sampling;Serum;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;trait;Variant;Work;X-Ray Computed Tomography

STUDY_SECTION: KNOD

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


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Circadian rhythms control many aspects of physiology and metabolism, but their effects on viral infection are unclear. This work will examine how circadian rhythms influence enteric virus infection and disease in mice.

PI_NAMEs: PFEIFFER, JULIE K (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: adaptive immune response;Animals;Anti-viral Response;ARNTL gene;Binding;Biology;cell type;Cells;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Clock protein;Complex;cost;Coxsackie Viruses;Cues;Dominant-Negative Mutation;Enteral;enteric virus infection;experimental study;Feedback;Gene Expression;Gene Proteins;Genes;ileum;Immune;Immune response;Immunity;Immunodeficient Mouse;Infection;Innate Immune Response;Interferon Receptor;Interferons;Intestines;Intraperitoneal Injections;Light;Link;Mammalian Cell;Mediating;Metabolic;Metabolism;Molecular;Mus;Oral;pathogen;Pathologic;Periodicity;Physiological Processes;Physiology;Population;Process;Production;promoter;Proteins;response;Signal Transduction;Signaling Protein;STAT1 gene;STAT1 protein;Time;Tissues;transcription factor;Transcriptional Regulation;vaccination strategy;Viral;Viral Physiology;Viral Proteins;viral RNA;Virus;Virus Diseases;Virus Replication;Wild Type Mouse;Work

PROJECT_TITLE: Circadian control of enteric virus infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-W(02)M]


ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Narrative The focal point of this project is to understand how transcription factors regulate the function of diverse astrocyte subpopulations in the aging brain. Given that astrocyte function is linked to a wide spectrum of neurological disease states, including Alzheimer’s and other neurodegenerative diseases, these studies are likely to reveal new mechanisms that can be applied to the understanding and possible treatment of these disorders. The transcription factor that we are studying, Sox9 and the astrocyte subpopulations that it regulates, have been implicated in a host of neurological disorders, underscoring the direct connections between these studies and associated disease states.

PI_NAMEs: DENEEN, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Address;Affect;age related;Aging;aging brain;Alleles;Alzheimer's Disease;Anatomy;Area;Astrocytes;Bacterial Artificial Chromosomes;Blood - brain barrier anatomy;Brain;Brain region;Cell surface;ChIP-seq;Coupled;Data;Deterioration;Disease;Endowment;Evolution;Exhibits;gene network;Genes;Genetic;genetic approach;Genetic Transcription;Goals;Hippocampus;in vivo;Knockout Mice;Label;Link;Metabolic;Molecular;Molecular Profiling;Morphology;mouse model;Mus;Nature;Nervous System Disorder;Neurodegenerative Disorders;Neuroglia;Neurons;Neurosciences;neurotransmission;novel;olfactory bulb;Pathologic;Physiological;Physiology;Play;Population;Property;prospective;Reporter;response to injury;Role;single-cell RNA sequencing;synaptogenesis;transcription factor

PROJECT_TITLE: Defining Roles for Astrocyte Subpopulations in the Aging Brain


NIH_SPENDING_CATS: Biotechnology;Cooley's Anemia;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Orphan Drug;Rare Diseases;Sickle Cell Disease

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: NARRATIVE Induction of fetal hemoglobin in adult red blood cells could serve as a functional cure for sickle cell disease and beta-thalassemia, which are among the most common single gene disorders in the world, continue to exhibit unmet clinical need, and affect populations impacted by health disparities. Recently a new molecular mechanism has been discovered to silence fetal hemoglobin in adult red blood cells based on a gene called ZNF410. This proposal explores the hypothesis that targeting ZNF410 could be a promising approach to therapeutically induce fetal hemoglobin—by understanding how ZNF410 controls gene expression, investigating the biological functions of ZNF410, and evaluating small molecules that degrade ZNF410.

PI_NAMEs: BAUER, DANIEL EVAN (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Adult;Affect;Alleles;Animal Model;Animals;beta Thalassemia;Binding;Biological;Biological Assay;Biological Process;Bypass;Cell model;Cells;CHD4 gene;Chemicals;Chromatin;Clinical;Clinical Trials;CRISPR screen;Dedications;Defect;derepression;Development;Disease;drug development;Elements;Erythrocytes;Erythroid;Erythropoiesis;Evaluation;Event;Exhibits;Fetal Hemoglobin;functional genomics;Future;gamma Globin;Gene Expression;Gene Expression Regulation;gene repression;Gene Targeting;gene therapy;Genes;Genome;Genomics;Goals;Growth;health disparity;Hematology;Hematopoiesis;Hematopoietic;hematopoietic engraftment;Hemoglobin;Hemoglobin concentration result;Hemoglobinopathies;Homeostasis;Human;immune modulating agents;immunoregulation;In Vitro;in vivo;inhibitor;Investigation;Knock-out;Lead;lenalidomide;Libraries;Logic;Mendelian disorder;Molecular;Molecular Genetics;Molecular Target;mouse development;Mus;Mutation;novel;Nucleosomes;NuRD complex;Orthologous Gene;Pharmaceutical Chemistry;Pharmacotherapy;Phenotype;pomalidomide;Population;promoter;protein complex;protein degradation;Proteins;Regulation;Regulator Genes;Regulatory Element;Reporter;Repression;Rest;Role;Safety;scale up;screening;Sickle Cell Anemia;small molecule;Structure-Activity Relationship;success;System;targeted treatment;Therapeutic;therapeutic evaluation;Therapeutic Index;therapeutic target;TNFSF5 gene;tool;Toxic effect;transcription factor;Transcription Repressor;ubiquitin ligase;Upstream Enhancer;Xenograft procedure

PROJECT_TITLE: Targeting ZNF410 for HbF reactivation

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative Cyclin C-CDK8 and C-CDK19 kinases were implicated to perform cancer-promoting functions. This proposal will examine the molecular roles played by these proteins in promoting cancer growth, acting within the host immune system, and the utility of inhibiting these proteins in cancer treatment.

PI_NAMEs: SICINSKI, PETER  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Ablation;adaptive immune response;adaptive immunity;Address;Affect;Alanine;Allografting;Alpha Interleukin 2 Receptor;Amino Acids;Animals;anti-cancer;anti-CTLA4 antibodies;anti-PD-1;anti-tumor immune response;antitumor effect;Antitumor Response;Binding;Biochemical;cancer cell;Cancer Model;Cancer Patient;cancer therapy;Catalytic Domain;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Culture Techniques;Cell Lineage;Cells;Clinical;Clinical Trials;CLN1 gene;CLN2 gene;CLN3 gene;Combined Modality Therapy;Complementary DNA;Complex;Cultured Cells;cyclin C;cyclin G1;Cyclin-Dependent Kinases;Cyclins;Cytotoxic T-Lymphocytes;Development;effector T cell;Endothelial Cells;Enterobacteria phage P1 Cre recombinase;experimental study;Gatekeeping;genetic approach;Genetic Transcription;Growth;Half-Life;Human;IL2RA gene;IL2RB gene;Immune;immune checkpoint blockade;Immune response;Immune system;Immunocompromised Host;In Vitro;in vivo;inhibitor;Interleukin 2 Receptor;Interleukin-2;Interleukin-4;Knockout Mice;Laboratories;Link;LoxP-flanked allele;Lymphoid Cell;Malignant Neoplasms;Maps;Mediating;Mediator;Memory;Modality;Molecular;mouse genetics;Mus;Mutation;NKTR gene;novel;Oncogenes;Outcome;overexpression;paralogous gene;Patients;Peripheral;peripheral lymphoid organ;Phosphorylation;Phosphotransferases;Play;Polyubiquitination;Protein Complex Subunit;Proteins;Regulatory T-Lymphocyte;Research;RNA Polymerase II;Role;Saccharomyces cerevisiae;Signal Transduction;Site;small molecule;small molecule inhibitor;systemic toxicity;T cell differentiation;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Testing;therapeutic target;thymocyte;Thymus Gland;Transcript;transcription factor;tumor;Tumor Immunity;Tumor Promotion;tumorigenesis;ubiquitin-protein ligase;Up-Regulation;Wild Type Mouse;Work;Xenograft procedure;Yeasts;ZNF145 gene

PROJECT_TITLE: Cyclin C-CDK8/19 kinases in development and in cancer

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Clinical Research;Lung;Neurosciences;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Noradrenergic mechanisms are increasingly linked to adult organ pathologies. We have recently detected this process in fibrotic rodent lung models and in samples from patients with Idiopathic Pulmonary Fibrosis. The current application explores the mechanistic and therapeutic ramifications of our discovery with the hope of gaining new insights into this challenging disease.

PI_NAMEs: HERZOG, ERICA L (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Adrenergic Agents;Adult;Animal Model;antagonist;Biology;Caring;Catabolism;Cells;Cicatrix;Clinical;Complication;cost;Cues;DCC gene;Dependence;Disease;effective therapy;Enzymes;Epithelial Cells;experience;Extracellular Matrix;Family;Fibroblasts;Fibrosis;fibrotic lung;gain of function;Gene Modified;Genetic;Grant;Human;human disease;idiopathic pulmonary fibrosis;Immunology;improved;Injury;insight;Intervention;knock-down;Knock-out;Knockout Mice;Link;Literature;loss of function;Lung;lung repair;Lung Transplantation;Macrophage;Mediating;member;Methaqualone;microCT;mimetics;Modeling;Monoamine Oxidase A;mouse model;Mus;Nerve;nerve supply;Nerve Tissue;Neurosciences;noradrenaline transporter;noradrenergic;Norepinephrine;Organ;Outcome;overexpression;Pathogenesis;Pathogenicity;Pathology;Patients;Pattern;Peripheral;pharmacologic;Process;Progressive Disease;Proliferating;Pulmonary Fibrosis;receptor;Recycling;Reporter;Rodent;Sampling;Scientist;side effect;single cell sequencing;Slice;solute;Structure of parenchyma of lung;Testing;Therapeutic;Tissue Sample;Tissues;Translating;Transplantation;Vision

PROJECT_TITLE: Noradrenergic mechanisms of IPF

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-G(03)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emergency Care;Hematology;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: OWINGS MILLS

ORG_NAME: ASELL, LLC

ORG_STATE: MD

PHR: Project Narrative CellRADx is a handheld, rapid, easy-to-use biodosimetry device that will integrate cell-based biomarker assays and immunoassays of radiation injury biomarkers with novel algorithms to fill the unmet public health and medical needs to 1) distinguish individuals exposed to potentially lethal levels of radiation, 2) assess severity of radiation injuries in tissues and organs, and 3).predict early and late effects of acute radiation exposure during and after a public health radiation/nuclear emergency. The successful development and deployment of CellRADx will allow first responders and health authorities to 1) quickly screen (i.e., <2 Gy vs >2 Gy exposure) and triage individuals in a radiation mass casualty incident so that potentially limited medical countermeasures can be administered to those individuals most in need, and 2) predict acute- and late-effects of radiation tissue injuries so that medical treatments can be administered to decrease morbidity and mortality. The potential of CellRADx to help save many lives and enable timely medical treatment decisions will dramatically increase the Public Health emergency response capabilities for the United States.

PI_NAMEs: KOWALSKI, RICHARD JOSEPH (contact)

PROGRAM_OFFICER_NAME: VEDAMONY, MERRILINE M

PROJECT_TERMS: Acute;Address;Algorithms;alpha-amylase;authority;biodosimetry;Biological Assay;Biological Markers;Blood;Blood Cells;Blood specimen;Bone Marrow;cell analyzer;Cell surface;Cells;Cellular Morphology;clinically relevant;Complete Blood Count;Complex;Country;Data;Detection;detection method;Development;Devices;Diagnostic;Diagnostic Equipment;Discrimination;Dose;Emergency response;Emergency Situation;Event;Exposure to;Failure;Fingers;first responder;FLT3 ligand;Goals;handheld equipment;Health;Hematology;Hematopoietic;Hematopoietic System;Human;Immunoassay;Immunodiagnostics;improved;indexing;Individual;inflammatory marker;innovation;instrument;irradiation;Late Effects;Leukocytes;mass casualty;Measures;Medical;medical countermeasure;Microscopy;Microspheres;minimally invasive;mobile application;mobile computing;Morbidity - disease rate;morphological criteria;mortality;National Institute of Allergy and Infectious Disease;Needs Assessment;novel;Nuclear;Nuclear Accidents;Organ;Physiological;Plasma;point of care;point-of-care diagnostics;portability;predictive marker;Public Health;public health emergency;Radiation;Radiation Accidents;Radiation Dosage;Radiation Dose Unit;radiation effect;Radiation exposure;Radiation induced damage;Radiation Injuries;Radiation Toxicity;Radiology Specialty;research and development;Risk;Risk Assessment;risk prediction;Safety;Salivary;Salivary Glands;Serum amyloid A protein;Severities;stem cells;System;Technology;Testing;Time;tissue injury;Tissues;Triage;United States;United States National Institutes of Health;Whole Blood

PROJECT_TITLE: Research and Development of a Hand-held, Rapid, Point-of-Care Radiation Biodosimetry Triage Device and Integration of Soluble and Cell-surface Radiation Injury Biomarker Assays


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Older adults commonly have impairments related to aging, such as issues with memory or walking, but often these aren’t measured as part of routine medical care. We created an app called GeriKit, which can be used on a mobile phone or tablet computer, to make it easier for clinicians to measure these impairments. In the proposed study we will evaluate whether GeriKit can be used to predict what happens to patients, and also add new instruments to improve the app, all of which will provide new opportunities for junior scientists who are focused on aging research.

PI_NAMEs: DODSON, JOHN A (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Activities of Daily Living;Acute;Acute myocardial infarction;Adverse effects;adverse outcome;Affect;Age;Aging;aging related;American;Android;Apple;Assessment tool;Award;Awareness;Body System;Cardiology;career;career development;Caring;Cellular Phone;clinical decision-making;Clinical Trials;Cognition Disorders;Cohort Studies;Complex;computer science;Delirium;Development;digital applications;digital health;Disease;Drug Kinetics;Elderly;Electronic Health Record;experience;Extramural Activities;Faculty;Fatigue;Feedback;Fellowship Program;frailty;Funding;Geriatric Assessment;Geriatric Nursing;Geriatrics;Goals;Health;Health Status;hearing impairment;Heart failure;Hemorrhage;Hemostatic Agents;hospital readmission;Hospitalization;Impaired cognition;Impairment;improved;Inflammation;Information Technology;Infrastructure;Injury;instrument;Knowledge;Lead;Link;Liver diseases;Measures;Mediating;Medical;Medical center;Medical History;Medical Students;medication compliance;meetings;Memory;Mentors;Methods;Monitor;mortality;Myocardial Ischemia;new technology;next generation;observational cohort study;older adult;older patient;Operating System;Operative Surgical Procedures;Orthopedics;Outcome;Patient Care;Patients;Phenotype;Population;population health;Prevalence;Professional Organizations;prognostication;programs;Research;Research Project Grants;Risk;risk stratification;Sampling;Scientist;secondary outcome;Self Care;Series;skills;Sleep Disorders;Societies;Specialist;standard of care;Structure;student training;System;Tablet Computer;Teacher Professional Development;Testing;Time;tool;Training;Training Programs;usability;Visual impairment;Walking;Work

PROJECT_TITLE: Midcareer award in aging-related subspecialty research


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

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT SUMMARY Alzheimer's disease (AD) affects half the US population over the age of 85 and the costs are staggering in human and financial terms. Multiple lines of evidence suggest the involvement of human brain immune cells in AD; however, the mechanisms remains unknown. The proposed studies will generate high-dimensional omics data in human brain immune cells, including single cell analysis, that will inform us about the etiopathogenetic mechanisms of immune cells on AD.

PI_NAMEs: HAROUTUNIAN, VAHRAM ;ROUSSOS, PANAGIOTIS  (contact);SCHADT, ERIC E

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Address;Affect;Age;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Animals;ATAC-seq;Brain;brain cell;brain tissue;Cell Nucleus;Cell Separation;cell type;Cells;chromosome conformation capture;Clinical;Communities;cost;CRISPR/Cas technology;Data;Data Analyses;Data Set;design;Development;Disease;DNA;epigenetic variation;epigenome;Fluorescence-Activated Cell Sorting;Freezing;Functional disorder;Future;Gene Expression;gene regulatory network;Generations;Genes;genetic association;genetic variant;Genome;genome sequencing;Genomic approach;Genomics;Goals;Haplotypes;high dimensionality;HLA-DRB1;Human;human tissue;human very old age (85+);Immune;immunological diversity;induced pluripotent stem cell;Innate Immune System;innovation;insight;Joints;Light;Measurement;Methods;Microglia;Molecular;Molecular Profiling;mouse model;multidimensional data;Multiomic Data;multiscale data;Mus;Myelogenous;Nerve Degeneration;Neurobiology;neuroinflammation;neuropathology;neuroprotection;novel;Pathogenesis;Pathway interactions;Phenotype;Population;protein expression;Proteins;Proteome;Proteomics;PTPRC gene;Quantitative Trait Loci;Research;Resolution;Resources;Risk Factors;risk variant;Role;selective expression;single cell analysis;single cell ATAC-seq;single-cell RNA sequencing;Site;System;Taxonomy;Testing;Transcriptional Regulation;transcriptome sequencing;TREM2 gene;TYROBP gene;Untranslated RNA;whole genome;Work

PROJECT_TITLE: Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer Disease


NIH_SPENDING_CATS: Infectious Diseases;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: PROJECT NARRATIVE Targeting the Genus Leishmania with Small Molecules  Our research focus is the development of a new therapy for the parasitic disease leishmaniasis. We have a proof-of-concept and preliminary structure activity relationships (SAR) validating a new antileishmanial chemotype, and the overarching project goal is to expand this SAR and optimize the compounds and their formulations to evaluate lead drug candidates against the disease’s two different clinical manifestations: visceral leishmaniasis and cutaneous leishmaniasis. The work scope will also include important mechanism-of-action and target deconvolution studies that will contribute basic knowledge to the field of leishmania parasitology.

PI_NAMEs: BROWN, LAUREN ELAINE;SCHAUS, SCOTT EDWARD (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Academia;Address;Adhesives;Adverse effects;Affect;Affinity;alternative treatment;American;Amphotericin B;analog;Antimony;Antineoplastic Agents;Antiparasitic Agents;Behavior;biocompatible polymer;Biological Assay;Biology;Bone Marrow;Boston;Cells;Chemicals;chemotherapy;Clinical;Collaborations;Country;Cutaneous;Cutaneous Leishmaniasis;cytotoxic;deep sequencing;design;Development;Disease;Dose;drug candidate;Drug Delivery Systems;drug discovery;Drug Kinetics;Drug Targeting;ear infection;Exhibits;Experimental Models;Formulation;Genetic;genome analysis;Goals;Grant;Hospitalization;human disease;Immune system;improved;In Vitro;in vivo;Infection;innovation;Knock-out;Knowledge;Laboratory Finding;Lead;lead series;Leishmania;Leishmania donovani;Leishmaniasis;Lesion;liposomal formulation;Liver;Macrophage;Medical;member;meter;Methodology;Military Personnel;Miltefosine;Modeling;Molecular Target;monocyte;Mucocutaneous leishmaniasis;Mucous Membrane;Mutation;nanomolar;neglect;novel therapeutics;Oklahoma;Oral;Organ;Organism;Outcome;Parasite resistance;Parasites;Parasitic Diseases;Parasitology;Penetration;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;Phlebotominae;Population;Populations at Risk;pre-clinical;Predisposition;programs;Reagent;Regional Disease;Reporting;Research;Resistance;Route;screening;Series;side effect;Skin;skin ulcer;small molecule;Spleen;Structure-Activity Relationship;Techniques;Teratogens;Testing;Texas;Therapeutic;Topical application;Toxic effect;transmission process;Universities;Validation;vector;Visceral;Visceral Leishmaniasis;Work;Yeasts

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Caregiving Research;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Kidney Disease;Pain Research;Palliative Care

ORG_CITY: MADISON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Improving access to palliative care for older adults with life-limiting kidney disease is a public health priority because 1) it affects large numbers of people, 2) it can reduce unwanted intensive treatments and improve quality of life and 3) there is public demand to improve end-of-life care delivery. This project aims to address this priority by testing an intervention—a communication tool plus clinician training in its use—designed to improve decision making and facilitate receipt of palliative care for patients with life-limiting illness, specifically kidney failure. Given trends in the number of older patients starting dialysis, the intervention proposed in this study could impact more than 200,000 older Americans annually with end-stage kidney disease.

PI_NAMEs: SCHWARZE, MARGARET  (contact)

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: Address;Admission activity;Affect;American;Award;Awareness;Businesses;care delivery;Caregivers;Caring;Cessation of life;Chronic Disease;chronic pain;Cluster randomized trial;cohort;Collaborations;Communication;Communication Tools;Control Groups;Data;Decision Aid;Decision Making;design;Development;Dialysis patients;Dialysis procedure;Educational process of instructing;efficacy study;Emergency department visit;end of life;end of life care;End stage renal failure;end-of-life communication;Enrollment;Evaluation;experience;Exposure to;Family member;Fatigue;Future;Glomerular Filtration Rate;Goals;Government;group intervention;Health;Healthcare;Hospitalization;Hour;human old age (65+);Impaired cognition;Improve Access;improved;innovation;Intensive Care Units;Intervention;Kidney Diseases;Kidney Failure;Length of Stay;Life;Measurement;Measures;Mediating;member;Mental Depression;multidisciplinary;Nature;novel;older adult;older patient;Operative Surgical Procedures;Outcome;Pain;palliating symptoms;Palliative Care;Patient Care;Patients;Persons;Pilot Projects;pilot test;Positioning Attribute;Procedures;Prognosis;provider communication;Proxy;public health priorities;Quality of life;Randomized;randomized, clinical trials;Recording of previous events;reduce symptoms;Reporting;Research;secondary outcome;shared decision making;Site;Societies;Specialist;Surgeon;Symptoms;Testing;Time;tool;Training;Training Programs;treatment as usual;treatment choice;trend;Uncertainty;Waiting Lists

PROJECT_TITLE: Best Case/Worst Case: A Multisite Randomized Clinical Trial of Scenario Planning for Patients with End-Stage Kidney Disease

STUDY_SECTION: NRCS

STUDY_SECTION_NAME: Nursing and Related Clinical Sciences Study Section[NRCS]


ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE: Are there simple rules for how humans should choose plants to eat for supporting the gut microbiome? One observation has been that the diversity of consumed plant species is linked to the abundance and activity of different bacterial species in the gut. Here, we will test if this finding extends across different human populations, as well as compare the effects of diets that focus on either plant diversity or fiber intake.

PI_NAMEs: DAVID, LAWRENCE ANTHONY (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Affect;Age;Bacteria;Bayesian Modeling;Biological Assay;Carbohydrates;Complement;Complex;Computer Models;Consumption;cost effective intervention;Data;Data Set;design;detection method;Diet;dietary;Dietary Assessment;dietary guidelines;Dietary intake;Dietary Intervention;Disease;DNA sequencing;Eating;Ecology;Ecosystem;Engineering;Enteral;Fiber;fitness;Food;genomic data;Genomics;Goals;Growth;Guidelines;gut bacteria;gut microbes;gut microbiome;gut microbiota;Health;Human;Human Activities;improved;in vitro Assay;in vivo;in vivo Model;Individual;Inflammatory;Ingestion;innovation;Intake;Knowledge;Link;Measures;member;Methods;Microbe;microbial;microbiome;microbiome analysis;microbiome composition;microbiome research;Modeling;Modernization;Morphologic artifacts;mouse model;Nationalities;novel;Nutrient;Nutritional;Pattern;Phytonutrients;Plants;Policies;Population;Public Health;Race;rational design;Recommendation;Research;Resources;response;sex;Shapes;Socioeconomic Status;Specimen;Structure;System;Techniques;Testing;theories;tool;Work

PROJECT_TITLE: Dietary plant diversity and the human gut microbiome

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE The current project examines the neural basis of Braille reading in proficient congenitally blind adults, late blind readers with varying degrees of proficiency and blind children learning to read, using fMRI and high-density diffusion imaging (dMRI). These studies of Braille literacy provide insights into human brain plasticity and the neural basis of culture.

PI_NAMEs: BEDNY, MARINA  (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TITLE: Neural basis of Braille literacy in blind adults and children


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

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PUBLIC HEALTH RELEVANCE Pancreas cancer is a leading cause of cancer mortality with few effective therapies. This project will develop a novel combination immunotherapy that we show has pronounced therapeutic activity in a rationale preclinical animal model and uncover the mechanistic basis for the observed antitumor effects to change the standard of care for pancreas cancer patient treatment.

PI_NAMEs: STROMNES, INGUNN MARGARETE (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Address;Affinity;Agonist;Amino Acids;Animal Model;Animals;anti-PD-L1;antigen-specific T cells;Antigens;antitumor effect;Bone Marrow;Cancer Etiology;cancer therapy;CD8-Positive T-Lymphocytes;CD8B1 gene;cell killing;Cell Physiology;cell type;Cells;cellular targeting;Chimera organism;Chronic;Clinical;Clinical Trials;Clone Cells;Combination immunotherapy;Combined Modality Therapy;cytokine;Cytokine Receptors;Cytokine Signaling;Data;design;Detection;Diagnosis;Disease;Disparate;effective therapy;effector T cell;engineered T cells;Engineering;Event;exhaust;exhaustion;Failure;Fibroblasts;Functional disorder;Genes;Goals;Granzyme;Human;Immune;immune checkpoint blockade;Immunologic Surveillance;Immunotherapy;Impairment;In Vitro;in vivo;Infiltration;Inflammatory;Interferon Type II;Interleukin-10;Knowledge;Lead;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;mesothelin;mortality;Mus;Myeloid Cells;Myeloid-derived suppressor cells;Neoplasm Metastasis;neoplastic cell;novel;Outcome;outcome disparities;overexpression;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;Patients;PD-1 inhibitors;PD-L1 blockade;PDL1 pathway;Peripheral;Pilot Projects;Positioning Attribute;pre-clinical;Production;programmed cell death protein 1;programs;Proteins;public health relevance;rare cancer;Research;Resistance;response;Role;safety testing;Series;Signal Transduction;single-cell RNA sequencing;standard of care;T cell differentiation;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;therapy resistant;Time;TNF gene;TNFRSF5 gene;tool;transcription factor;translational approach;tumor;Tumor Antigens;tumor eradication;Tumor Escape;tumor immunology;tumor microenvironment

PROJECT_TITLE: Mechanisms of immunotherapy response and resistance in pancreatic ductal adenocarcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Cancer;Genetics;Prevention

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE The RAS genes are commonly mutated in a broad spectrum of human cancers. Thus, the goal of this proposal to elucidate how mutations in these genes initiate cancer has important implications for early detection and prevention for a significant portion of cancer patients.

PI_NAMEs: COUNTER, CHRISTOPHER M (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Address;Alleles;Bacteria;Biological Assay;Biological Models;Biology;Cancer Biology;cancer initiation;Cancer Patient;cancer type;Carcinogen exposure;carcinogenesis;cell type;Cells;Clinical;clinically relevant;Data;de novo mutation;Disease;Dissection;Early Diagnosis;Engineering;Event;Family;Frequencies;Genes;Genetic;Genetic Induction;Genetically Engineered Mouse;Goals;Human;in vivo;Individual;individual response;Induced Mutation;innovative technologies;insight;Investigation;KRAS oncogenesis;KRAS2 gene;Lesion;Lung;Malignant Neoplasms;Methods;Modeling;Monitor;mouse model;Mus;Mutagenesis;mutant;Mutate;Mutation;Nature;next generation sequencing;Normal Cell;novel;Oncogenes;Oncogenic;Pathologic Mutagenesis;Pattern;Population;Positioning Attribute;potential biomarker;prevent;Prevention;Process;Protein Isoforms;Proteins;Publishing;RAS driven tumor;RAS genes;Refractory;Reporting;response;Severities;Signal Transduction;single-cell RNA sequencing;therapeutic target;Tissues;tumor;tumor initiation;Tumor-Associated Process;tumorigenesis;tumorigenic;Urethane

PROJECT_TITLE: Genetic dissection of oncogenic RAS-driven tumor initiation in vivo

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Clinical Research;Pediatric

ORG_CITY: MIAMI

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: NARRATIVE  The Authentic Bioinformatics in the Classroom (ABC) Project has the overall goal of developing bioinformatics and biomedical research interests and skills of high school students from underrepresented backgrounds by integrating this content to high school biology. Students will work on basic science discovery as well as cutting edge research questions related to COVID-19 while learning high school biology. The desired outcome is to stimulate an increase in students from underrepresented groups that go on to pursue STEM careers including biomedical sciences and bioinformatics.

PI_NAMEs: KRAMER, LAIRD ;LIBERLES, JESSICA  (contact)

PROGRAM_OFFICER_NAME: BECK, LAWRENCE A

PROJECT_TERMS: Active Learning;Advisory Committees;Awareness;Basic Science;Bioinformatics;Biological;Biological Sciences;Biology;Biomedical Research;biomedical scientist;career;Career Choice;Chemistry;Clinical;Clinical Research;Collaborations;Community of Practice;Computers;COVID-19;Data;Data Science;design;Development;Educational Curriculum;Educational Models;Educational process of instructing;Educational workshop;evidence base;Evolution;experience;Faculty;Florida;Future;Goals;Heredity;high school;High School Faculty;High School Student;innovation;interest;Investigation;Knowledge;laboratory equipment;Lead;Learning;learning community;learning materials;Modeling;Organism;Outcome;Pattern;peer;peer coaching;Physics;Preparation;Process;Research;role model;school district;Schools;Science;Scientist;Services;skills;Specialist;STEM career;STEM field;Structure;student participation;Students;teacher;teacher community;Teacher Professional Development;Teaching Method;tool;Training;trait;undergraduate student;Underrepresented Populations;Underrepresented Students;Variant;Work

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


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

PHR: Project Narrative Malignant gliomas are the most common brain cancer in adults. Although patients with mutations in the isocitrate dehydrogenase 1 gene have better survival, they inevitably succumb to glioma recurrence and progression. This project explores the underlying mechanism of an inherited vulnerability within this type of glioma for treatment with FDA-approved drug.

PI_NAMEs: HUANG, L. ERIC (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: 19q;Acetylation;Acute Myelocytic Leukemia;Adult;Apoptosis;Arsenic Trioxide;Astrocytoma;ATRX gene;Brain;cancer type;Cancer Vaccines;Cell Cycle Arrest;Cell Death;Cells;Cellular Stress;Classification;Clinical Trials;Communities;Development;efficacy testing;Event;FDA approved;Genes;Genetic;Genomics;Glioma;Gliomagenesis;Glutathione Metabolism Pathway;Goals;Growth;Human;improved;In Vitro;in vivo;Inherited;inhibitor;insight;Intrahepatic Cholangiocarcinoma;Investigation;Iron;Isocitrate Dehydrogenase;Knock-out;Knowledge;Lipid Peroxidation;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;metabolic abnormality assessment;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;mouse model;Mus;mutant;Mutation;NADP;nerve stem cell;novel;oligodendroglioma;Oncogenes;Organoids;Outcome;Oxidation-Reduction;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pre-Clinical Model;precision drugs;Precision therapeutics;Prevalence;Reactive Oxygen Species;Reagent;Recurrence;Reporting;Research;Resources;Role;Sampling;senescence;sensor;single-cell RNA sequencing;stem cell differentiation;temozolomide;three dimensional cell culture;Tissues;TP53 gene;Treatment Efficacy;tumor;Tumor Suppression;tumorigenesis;Variant;virtual

PROJECT_TITLE: Exploring p53-mediated ferroptosis to treat IDH1-mutant glioma

STUDY_SECTION: CNBT

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Mental Health;Neurosciences;Pediatric;Substance Misuse

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Substance use initiation during adolescence is often associated with risky behaviors driven by heightened reward sensitivity, but increased susceptibility to substance abuse may also depend in part on the persistence of reward-associated memories. This proposal aims to determine how reward states – both in the lab and in the real-world – modulate lasting memories that can carry over to guide future behaviors from childhood to adulthood. This work holds the potential to define cognitive and neural mechanisms through which rewarding experiences persist in memory across adolescence, which may provide insights into vulnerability to substance use disorders and ultimately inform possible interventions to support healthy development.

PI_NAMEs: COHEN, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: PARIYADATH, VANI

PROJECT_TERMS: addiction;Address;Adolescence;Adolescent;Adult;Affect;Affective;Age;age related changes;Behavior;behavior influence;Behavioral;Brain;career;career development;Child;Child Abuse;Childhood;Cognitive;cognitive neuroscience;Computer Models;Consummatory Behavior;Corpus striatum structure;Data;Decision Making;Dependence;Desire for food;Development;Development Plans;Dopamine;Ecological momentary assessment;Enrollment;Exhibits;experience;Foundations;Functional Magnetic Resonance Imaging;Future;Goals;high reward;Hippocampus;Hour;Image;insight;Intervention;Knowledge;knowledge base;Lead;Learning;Link;Maintenance;Measures;Mediating;Memory;memory encoding;memory process;memory retrieval;mesolimbic system;Methodology;Methods;Modeling;motivated behavior;Motivation;multimodality;Multivariate Analysis;neural;Neurocognitive;neuroimaging;neuromechanism;Neuronal Plasticity;Neurosciences Research;novel;Outcome;Participant;Patient Self-Report;Pattern;Physical activity;Predisposition;progression risk;Psychological reinforcement;Research;Research Project Grants;Rest;Retrieval;Rewards;Risk;Risk Behaviors;Risk Taking;Rodent;Severity of illness;Shapes;Signal Transduction;skills;Sleep;stem;Stimulus;Substance abuse problem;substance use;Substance Use Disorder;substance use prevention;System;Thinking;Training;transition to adulthood;Translating;translational approach;Ventral Tegmental Area;Work

PROJECT_TITLE: Neurocognitive mechanisms of reward - motivated memory persistence across age

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]