NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE Public health concern about influenza virus stems from the potential to kill millions, as documented in the 1918 H1N1 pandemic. Current seasonal influenza virus vaccines elicit an antibody response that is of limited breadth and appears to be of short duration. This project will qualitatively evaluate the germinal center, memory B cell, and long-lived plasma cell responses induced by conventional vs. mRNA-based seasonal influenza vaccination of humans.

PI_NAMEs: ELLEBEDY, ALI HASSAN (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: 1918 influenza pandemic;2019-nCoV;Address;Adult;Affinity;anti-influenza;Antibodies;Antibody Avidity;Antibody Response;Antigens;ATAC-seq;Automobile Driving;B-Cell Antigen Receptor;B-Lymphocytes;Binding;Blood;Bone Marrow;Bone Marrow Aspiration;CD4 Positive T Lymphocytes;Cell Compartmentation;Cells;ChIP-seq;Clinical;Clinical Trials Unit;Clone Cells;cohort;Collaborations;confocal imaging;Core Biopsy;COVID-19 vaccination;Data;Development;differential expression;draining lymph node;Effectiveness;Elderly;Enrollment;experimental study;Fine needle aspiration biopsy;Frequencies;Funding;Gene Expression Profiling;Generations;Genetic Transcription;Hemagglutinin;Human;human old age (65+);Humoral Immunities;Immune;Immunity;Immunization;Immunize;immunogenicity;Immunoglobulin Somatic Hypermutation;imprint;Influenza;Influenza vaccination;influenza virus strain;influenza virus vaccine;influenzavirus;innovation;insight;Institutional Review Boards;Laboratories;Licensing;lipid nanoparticle;Longevity;LoxP-flanked allele;lymphoid structures;Maintenance;Memory B-Lymphocyte;Messenger RNA;Molecular;Molecular Mechanisms of Action;Monoclonal Antibodies;mouse model;Mus;novel;Output;pathogenic microbe;Pathway interactions;Phenotype;Plasma Cells;Plasmablast;programs;Proteins;Proteomics;Public Health;rational design;Reaction;recruit;response;RNA;RNA vaccination;RNA vaccine;Role;Sampling;seasonal influenza;Specificity;Specimen;stem;Structure of germinal center of lymph node;T cell response;Tissue Sample;Universities;Vaccination;Vaccine Antigen;vaccine immunogenicity;vaccine platform;vaccine trial;vaccine-induced antibodies;Vaccines;Virus;Washington

PROJECT_TITLE: Programming Durable Immune Responses To Vaccination

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 JTS-I (S1)]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Overall Narrative Lupus nephritis is a serious manifestation of systemic lupus erythematosus. Through this proposal we seek to better understand the involved processes, produce reliable biomarkers and advance precision medicine to better the lives of people with lupus nephritis.

PI_NAMEs: TSOKOS, GEORGE C (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Antibodies;Autoantibodies;Autoimmune;autoinflammatory;Binding;Bioinformatics;Biological Markers;Biological Products;biomarker development;Budgets;Ca(2+)-Calmodulin Dependent Protein Kinase;Calcium;CCL20 gene;cell injury;cell type;Cells;chemokine;Child;clinical efficacy;Collaborations;cytokine;Development;Elements;End stage renal failure;Endothelial Cells;Environment;Epithelial Cells;experimental study;Exposure to;Guide RNA;High Endothelial Venule;Human;Immune;Immune system;Immunotherapeutic agent;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;interest;interleukin-23;interstitial;Kidney;kidney biopsy;kidney cell;Kidney Diseases;Laboratories;Lupus Nephritis;lymphoid structures;lymphotoxin beta receptor;Mediating;meetings;Membrane;Minority;Molecular;Monitor;Mus;nanoparticle;Needles;novel;Pathogenesis;Pathology;Patients;peripheral blood;Persons;Pharmaceutical Preparations;podocyte;podoplanin;precision medicine;primary lymphoid organ;Process;programs;receptor;Receptor Signaling;Receptor Up-Regulation;receptor upregulation;renal damage;Schedule;secondary lymphoid organ;side effect;Signal Transduction;Stromal Cells;synergism;systemic autoimmunity;Systemic Lupus Erythematosus;targeted delivery;targeted treatment;Testing;therapy development;Tissues;tool;transcriptomics;Treatment Protocols;treatment response;Tubular formation;Tumor Necrosis Factor-Beta;Urine

PROJECT_TITLE: Lupus nephritis: novel insights in the pathogenesis and treatment

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 MR-I (S1)]


NIH_SPENDING_CATS: Autoimmune Disease;Kidney Disease;Lupus

PHR: PROJECT NARRATIVE – Administrative Core A Core A will be responsible for the coordination of all administrative and regulatory aspects of the proposed research.

PROJECT_TERMS: Accounting;Adherence;Administrator;animal care;Animal Welfare;Bibliography;Biometry;Budgets;Communication;Data;data integration;data sharing;Disputes;Ensure;Expenditure;Funding;Generations;Goals;Grant;Human;IACUC;Individual;insight;Institution;Institutional Review Boards;Laboratories;Lupus Nephritis;Maintenance;Manuscripts;medical schools;meetings;member;Monitor;novel;Occupational activity of managing finances;Pathogenesis;Performance;performance site;Preparation;preservation;programs;Progress Reports;Protocols documentation;Records;Regulation;Research;Research Personnel;Resolution;Schedule;Scientific Advances and Accomplishments;scientific organization;Secure;Specialist;Structure;success;symposium;synergism;Travel;United States National Institutes of Health;Work

PROJECT_TITLE: Core A - Admin Core


PHR: CORE B- Narrative Core B will formulate nanoparticles, encapsulate the payloads, and carry out nanoparticle surface conjugation with antibodies to be used by investigators of this program project grant. Core B will advance precision medicine in the treatment of patients with lupus nephritis.

PI_NAMEs: ABDI, REZA  (contact)

PROJECT_TERMS: Acceleration;Address;Antibodies;antibody conjugate;Binding;Blood Vessels;Cadherins;cancer therapy;Cardiovascular Diseases;Cause of Death;CD3 Antigens;Cells;Clinical;clinical effect;combinatorial;Data;Development;Disease remission;dosage;Dose;Dose Limiting;Dyes;Encapsulated;Endocytosis;Epithelial Cells;Equilibrium;ex vivo imaging;experience;Fluorescent Dyes;Glycoproteins;Goals;Grant;Guide RNA;Hand;High Endothelial Venule;Homing;Image;Immune;Immune Targeting;Immune Tolerance;Immunity;Immunosuppressive Agents;Immunotherapeutic agent;Immunotherapy;In Vitro;Infection;Inflammation;Inflammatory;inhibitor;Injury;innovation;insight;interest;interleukin-23;interstitial;Investments;Kidney;Kinetics;Ligands;Lupus Nephritis;lymph nodes;Malignant Neoplasms;Mediating;Medical;Medicine;Metabolic Diseases;Methods;Monoclonal Antibodies;mortality;Mus;nanocarrier;Nanodelivery;nanomedicine;nanoparticle;Nanotechnology;nanotherapeutic;nephrin;nephrogenesis;novel;Nucleosome Core Particle;Organ;Pathogenesis;Pathogenicity;Patients;Peripheral;Permeability;Pharmaceutical Preparations;podocyte;precision medicine;Program Research Project Grants;Protein-Serine-Threonine Kinases;Publishing;receptor;Regulatory T-Lymphocyte;Research Personnel;Series;Serine;Site;Surface;Systemic Lupus Erythematosus;systemic toxicity;T-Lymphocyte;targeted delivery;Testing;Therapeutic;therapeutically effective;tissue injury;Tissues;Toxic effect;trafficking;Treatment Efficacy;Tubular formation;Up-Regulation;Veins;virtual;Work

PROJECT_TITLE: Core B - BWH Nanoparticle Core


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Data Science;Kidney Disease;Lupus;Networking and Information Technology R&D (NITRD)

PHR: NARRATIVE Core C will ensure streamlined data generation, acquisition, quality control, management, and provenance across the PPG. It will generate production-grade highly automated single cell and spatial tissue profiling data; establish streamlined data processing, quality control, management, and provenance; as well as promote best practice, scalable, multi-modal data processing, analysis, and integration. Core C will work closely with the personnel of the Administrative Core, the Cores, and the Projects for efficient and timely data delivery.

PI_NAMEs: VLACHOS, IOANNIS  (contact)

PROJECT_TERMS: Address;Administrative Personnel;arm;Benchmarking;Bioinformatics;Biological Assay;Biostatistics Core;Bypass;Cells;Cellular Assay;Code;cohort;Communities;computerized data processing;cost effectiveness;Data;data acquisition;data integration;data pipeline;Data Provenance;data resource;Deposition;Disease;Disease Progression;Ensure;Environment;Evolution;experience;FAIR principles;Functional disorder;Generations;High Endothelial Venule;high throughput screening;Human;Human Resources;Image;Immune;in vivo;Inflammatory;Infrastructure;Ingestion;insight;interoperability;Kidney;Life Cycle Stages;lipid nanoparticle;Lupus Nephritis;Metadata;Molecular;multidisciplinary;multimodal data;novel;Outcome;Pathogenesis;Patient Monitoring;patient stratification;Patients;Performance;peripheral blood;Population;Procedures;Process;Production;Program Research Project Grants;programs;prospective;Protocols documentation;Quality Control;Research Personnel;Resolution;Resources;Role;Sampling;Sampling Studies;Services;single nucleus RNA-sequencing;targeted treatment;Technology;Testing;Therapeutic Uses;Tissues;Trust;Urine;Work

PROJECT_TITLE: Core C- BIDMC Core


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Kidney Disease;Lupus;Precision Medicine

PHR: A quarter to more than one half of the ~ one million people with systemic lupus will either present with lupus nephritis or they will develop lupus nephritis at some point in the course of their disease. The available treatment approaches and tools to record response to treatment are limited. The project proposes studies in people and mice with lupus nephritis to improve our understanding of pathogenesis, develop precision treatment approaches and high-fidelity biomarkers.

PROJECT_TERMS: Address;Adult;artificial intelligence model;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmune Responses;autoinflammatory;belimumab;Biological Markers;Biological Products;Ca(2+)-Calmodulin Dependent Protein Kinase;Calcineurin inhibitor;Calcium;Cells;chemokine;Child;Clinical;Clinical Data;Clinical Research;cohort;conditional knockout;Cyclophosphamide;cytokine;Data;Development;Diagnosis;Disease;Dose;Drug Delivery Systems;Elements;Environment;Epithelial Cells;experimental study;Exposure to;Genetic;Guide RNA;Hemorrhage;Human;IL17 gene;Immune;immunoregulation;Immunosuppressive Agents;improved;Infection;Inflammation;Inflammatory;Injury;insight;Interleukin-2;interleukin-23;interstitial;Intravenous;Kidney;kidney biopsy;kidney cell;Kidney Diseases;kinase inhibitor;Knockout Mice;Laboratories;Lupus;Lupus Nephritis;lupus prone mice;Measurement;Medicine;metabolic profile;Molecular;Molecular Abnormality;Monitor;Mus;mycophenolate mofetil;nanoparticle delivery;Needles;nephrogenesis;North America;novel;Oral;Pain;Pathogenesis;Pathology;Patients;Peripheral;Persons;Pharmaceutical Preparations;podocyte;precision medicine;Precision therapeutics;prevent;Probability;Production;Program Research Project Grants;Protein-Serine-Threonine Kinases;Proteins;receptor;Receptor Up-Regulation;receptor upregulation;renal damage;Research;response;Risk;Serine;side effect;single-cell RNA sequencing;Steroids;systemic autoimmunity;Systemic Lupus Erythematosus;T-Lymphocyte;targeted delivery;Testing;Tissues;tool;transcriptomics;treatment response;Tubular formation;Up-Regulation;Urine

PROJECT_TITLE: Project 1 - BIDMC


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biotechnology;Clinical Research;Immunotherapy;Kidney Disease;Lupus;Nanotechnology

PHR: Narrative Poor understanding of the pathogenesis of lupus nephritis has delayed the development of effective therapeutics. The project will generate new knowledge on the mechanisms which are involved in the expression of the disease and will propose novel precision medicine therapeutics for its treatment.

PROJECT_TERMS: American;Antibodies;Apical;Automobile Driving;Binding;CD3 Antigens;Cell Communication;Cells;Data;Development;Disease;Disease Outcome;dosage;Drug Kinetics;effector T cell;efficacy testing;Encapsulated;Experimental Designs;Family;Fluorescent Dyes;Freezing;Glycoproteins;High Endothelial Venule;Homing;Human;IL17 gene;Immune;Immune Targeting;immunoregulation;Immunotherapeutic agent;improved;Inflammation;Inflammatory;innovation;insight;interleukin-23;intravenous administration;Kidney;kidney biopsy;Kinetics;Knowledge;Ligands;Lupus Nephritis;lymph nodes;Lymphocyte;Lymphoid Cell;Maintenance;Mediating;Membrane;Molecular;Monoclonal Antibodies;Mus;nano;nanoparticle;nanopolymer;nanotherapeutic;novel;Pathogenesis;Pathway interactions;Patients;Peripheral;Pharmaceutical Preparations;Play;podoplanin;precision medicine;prevent;Property;Proteomics;Protocols documentation;receptor;Receptor Signaling;recruit;Role;Safety;Series;Serum;Signal Pathway;Signal Transduction;small molecule;Stromal Cells;Surface;Systemic Lupus Erythematosus;T-Lymphocyte;targeted delivery;targeted treatment;technology platform;Testing;Therapeutic;therapeutic nanoparticles;therapeutically effective;Time;Tissues;tool;trafficking;transcriptomics;Treatment Efficacy;Tumor Necrosis Factor-Beta;Validation;Veins;venule;zeta potential

PROJECT_TITLE: Project 2 - BWH


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Infectious Diseases

ORG_CITY: STONY BROOK

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: Narrative: MIRA Title: Advanced Single-Cell Protein Analysis with Multiplex in Situ Tagging Array Technology Protein-based single-cell analysis is a fundamental technique but has been underdeveloped in comparison with DNA/RNA sequencing-based technologies. My research program is dedicated to address the technological bottlenecks through an ultrahigh-density multiplex in situ tagging (MIST) array and associated biochemistry, and to initiate single-cell spatial proteomics field, move single-cell prognostics in the clinics and innovate single- microbe detection.

PI_NAMEs: WANG, JUN  (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: Address;Animals;Area;artificial intelligence algorithm;Bacteria;Biochemistry;Biological Assay;Cells;Clinic;Dedications;density;Detection;detection method;Development;Disease;disease prognosis;DNA;Exhibits;Explosion;Genome;Goals;Human;In Situ;innovation;Life;Maps;Membrane Proteins;Microbe;Microspheres;monolayer;Organism;Outcome;particle;pathogen;pathogenic microbe;Physiological;prognostic;programs;Protein Analysis;protein biomarkers;Proteins;Proteome;Proteomics;rapid detection;Reaction;Research;Sampling;Science;Sepsis;Signal Transduction;single cell analysis;single cell proteins;single cell technology;Solid;Specimen;T-Lymphocyte;Techniques;Technology;Tissues;transcriptome sequencing;Viral;Visual

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: OMAHA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative: Investigating the Function of Bacterial Cytoskeletal Elements in the Division and Growth of the FtsZ-less Chlamydia  Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. How Chlamydia divides is an interesting question of fundamental interest to the microbiology field because these bacteria lack the machinery used by most other bacteria to divide. This proposal builds on previous work from the lab to extend our understanding of the function of cytoskeletal elements in Chlamydia.

PI_NAMEs: OUELLETTE, SCOT P (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Antibiotics;antimicrobial;Bacteria;Blindness;Cell Size;Cells;Chlamydia;Chlamydia Infections;Chlamydia trachomatis;Chronic;Cytoskeleton;daughter cell;Dependence;design;Developed Countries;Developing Countries;Development;Disease;Elements;Essential Genes;fascinate;Genes;Genetic;Genome;Goals;Growth;Healthcare Systems;Human;interest;Metabolic;Microbiology;microbiome;Morphology;N-terminal;novel;Organism;pathogen;pathogenic bacteria;Pathway interactions;Pelvic Inflammatory Disease;Phospholipids;Physiological;Process;recruit;Reiter Disease;Research;Sexually Transmitted Diseases;Site;Surface;tool;Trachoma;tubal infertility;Work

PROJECT_TITLE: Investigating the function of bacterial cytoskeletal elements in the division and growth of the FtsZ-less Chlamydia

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ORG_CITY: Aurora

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: The proposed research is relevant to public health because it seeks to improve our fundamental knowledge about essential membrane transporters from humans and bacteria. The results will have the potential for future pharmaceutical development to treat related human diseases. Thus, the proposed research is relevant to NIH’s mission.

PI_NAMEs: ZHENG, HONGJIN  (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Bacteria;Biochemistry;biophysical techniques;CCL21 gene;Cellular biology;design;Development;drug development;Drug Targeting;Future;G-Protein-Coupled Receptors;Goals;Human;human disease;improved;Ion Channel;Knowledge;Life;member;Membrane Proteins;Membrane Transport Proteins;Microbiology;Mission;Molecular;molecular dynamics;multidisciplinary;Pharmacologic Substance;Physiological;Public Health;Research;Siderophores;small molecule;small molecule inhibitor;structural biology;Structure-Activity Relationship;United States National Institutes of Health

PROJECT_TITLE: Mechanistic studies of essential membrane transporters


NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: Cells that have abnormal chromosome numbers and abnormal chromosome structure are major contributors to infertility, birth defects, cancer, and aging. To understand how cells get the wrong number of chromosomes and how chromosomes can become fragmented, it is essential to understand the interactions of the many proteins and the biochemical pathways that drive cell division.

PI_NAMEs: GORBSKY, GARY J. (contact)

PROJECT_TERMS: Aging;Algorithms;Anaphase;Antibodies;Behavior;Biochemical Pathway;Bioinformatics;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;Cell division;Cells;Chromosomal Instability;Chromosome abnormality;chromosome movement;chromosome number abnormality;Chromosome Structures;Chromosomes;cohesion;Complex;Congenital Abnormality;Coupled;Evaluation;Fatigue;Fostering;Genes;Image Analysis;Immunoprecipitation;In Vitro;in vivo;induced pluripotent stem cell;Infertility;innovation;Investigation;Kinetochores;Laboratories;Light;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Mechanics;Mediating;member;Metaphase;Methods;Microscopy;Microtubules;Mitosis;Mitotic;Mitotic Cell Cycle;Molecular;mutant;novel;Pathway interactions;Phenotype;Phototoxicity;Prometaphase;protein degradation;Proteins;Resolution;Role;Source;Structure;Techniques;temporal measurement;Testing;Vertebrates;whole genome;yeast two hybrid system

PROJECT_TITLE: Understanding Cell Division

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative: The present grant application outlines two primary objectives for future study. First, high throughput methods will be employed to identify and map thousands of distinct cross-β cores within LC domains spanning the proteome of human cells. Second, biochemical, molecular biological and biophysical methods will be used to resolve the manner by which transiently self-associated cross-β cores are able to selectively recruit heterologous proteins as a means of building dynamic cellular structures.

PI_NAMEs: MCKNIGHT, STEVEN L (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Accounting;Amino Acids;Applications Grants;Biochemical;Biochemistry;Biological;Biological Process;biophysical chemistry;biophysical techniques;cell growth regulation;Cells;Cellular Structures;Chemicals;Cytoplasm;Cytoplasmic Granules;Disease;Equilibrium;Eukaryotic Cell;experimental study;fused in sarcoma;Future;Gene Transfer;Germany;Glycine;Human;Hydrogels;Intermediate Filament Proteins;Intermediate Filaments;Laboratories;Life;Maps;Mediating;Medical center;Membrane;Methionine;Methods;Mitochondria;Molecular;mRNA Precursor;Mutation;Nervous System Disorder;Neurodegenerative Disorders;Nuclear Pore;Nuclear Pore Complex Proteins;NUP98 gene;oxidation;Permeability;Phase;Phenylalanine;Phosphorylation;Post-Translational Protein Processing;protein TDP-43;Proteins;Proteome;recruit;RNA;RNA Splicing;RNA-Binding Proteins;SCA2 protein;solid state;Specificity;Structure;Thermodynamics;Tyrosine;United States National Institutes of Health;Work

PROJECT_TITLE: A solid state conceptualization of information transfer from gene to message to protein


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Crohn's Disease;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Microbiome;Prevention

ORG_CITY: Newark

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Because the etiology of Crohn's disease (CD) is not well understood, many of its current treatments are focused on systemic immunosuppression, which can increase the risk of serious infections and malignancies1,2. The proposed study will evaluate the relative contributions of genetic risk and of the gut microbiome to CD development, with a focus on identifying microbial signatures of individuals who have never developed CD despite having high genetic risk. We will study whether these microbial signatures and their associated protective phenotype are transferable, with the long-term goal of impacting the development of safer, more effective microbiota-based therapeutics to treat or prevent CD.

PI_NAMEs: CHEN, LEA A (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Address;Affect;Animal Model;Anti-Inflammatory Agents;Behavior;Biological;candidate identification;career;Characteristics;clinical care;clinical development;Cluster Analysis;Coupling;Crohn's disease;cytokine;Data;Development;Dimensions;Disease;disorder risk;disorder subtype;Environment;Environmental Exposure;Environmental Risk Factor;Etiology;experience;Exposure to;Family;Family member;Family Study;fecal transplantation;Functional disorder;Future;Genes;Genetic Determinism;Genetic Predisposition to Disease;Genetic Risk;Genotype;Germ-Free;Goals;gut bacteria;gut inflammation;gut microbes;gut microbiome;Heritability;high risk population;Histology;Human;Human Microbiome;Immune response;Immunosuppression;Incidence;Individual;Infection;Inflammatory Bowel Diseases;insight;Interleukin-10;Intervention;Intestines;Lead;Left;Leukocyte L1 Antigen Complex;Malignant Neoplasms;Maps;Measures;Mediating;Mentors;metabolome;metabolomics;Microbe;microbial;microbial signature;microbiome;microbiome composition;microbiome research;microbiota;Modeling;mouse model;Multiomic Data;Mus;Onset of illness;Organism;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;permissiveness;personalized medicine;Phenotype;polygenic risk score;Population;Predisposing Factor;prevent;Publishing;rational design;Research Personnel;Risk;risk variant;Role;Sampling;Severity of illness;Signal Transduction;System;Testing;Therapeutic;Tissues;Training;transcriptomics;translational scientist;Transplantation;unsupervised clustering

PROJECT_TITLE: The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiodata-Based Therapies

STUDY_SECTION: DDK

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Kidney Disease;Nutrition;Prevention

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. The current proposal will investigate new mechanisms for development of cardiovascular disease in patients with chronic kidney disease. The results will have important implications for clinical care of patients with chronic kidney disease and for design of future research studies aimed at reducing the burden of cardiovascular disease in this high risk population.

PI_NAMEs: ISAKOVA, TAMARA  (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: absorption;Address;adjudication;Adverse event;Ancillary Study;Animals;Area;Arrhythmia;Atrial Fibrillation;Bile Acids;Biological Markers;calcification;Calcitriol;Calcium;cardiac magnetic resonance imaging;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cause of Death;Chronic Kidney Failure;Chronic Kidney Insufficiency;Clinical;clinical care;clinical investigation;Clinical Trials;cohort;Cohort Studies;Collaborations;Complication;coronary artery calcification;Data;Deoxycholic Acid;design;Development;Diagnostic tests;diagnostic tool;Diet;dietary;Dietary Component;Disease;Disease Outcome;disease phenotype;double-blind placebo controlled trial;endoplasmic reticulum stress;epidemiology study;Evaluation;Event;Excretory function;experimental study;Faculty;Fatty acid glycerol esters;Femur;Fibroblast Growth Factor;fibroblast growth factor 23;follow-up;Food;Frequencies;Funding;Future;gut dysbiosis;Health;Heart failure;high risk population;Homeostasis;Image;improved;improved outcome;indexing;Individual;inorganic phosphate;Intake;Intervention;intervention effect;Intervention Studies;Investigation;Kidney;Knowledge;Laboratories;lanthanum carbonate;Leadership;Left Ventricular Hypertrophy;Left Ventricular Mass;Left ventricular structure;Magnetic Resonance Imaging;Measurement;Measures;Medial;medical schools;Medical Students;Medicine;Mentors;Metabolism;mid-career faculty;Midcareer Investigator Award in Patient-Oriented Research;Minerals;Modeling;mortality;mortality risk;Multi-Institutional Clinical Trial;Myocardial;Nephrology;Niacinamide;novel;novel diagnostics;novel strategies;Observational Study;Pathogenesis;Patient Care;patient oriented research;Patients;Physiologic pulse;Placebos;Plasma;prevent;Production;programs;protein intake;Proteins;PTH gene;Public Health;Questionnaires;Randomized;Research;Research Infrastructure;Research Personnel;research study;Research Support;Research Training;response;Risk;Risk Factors;Sampling;Series;Serum;skills;Smooth Muscle Myocytes;Sodium;Subgroup;Testing;Therapeutic;Time;Training;United States National Institutes of Health;Universities;urinary;Vascular calcification;Vascular Smooth Muscle;Work

PROJECT_TITLE: Mentored patient-oriented research of novel mechanisms for cardiovascular disease in patients with chronic kidney disease

STUDY_SECTION: MPOR

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


ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The transient receptor potential vanilloid channels, TRPV2 and TRPV5, contribute to a broad range of physiological and pathophysiological events in human body. The overall goal of this proposal is to understand how TRPV2 and TRPV5 channels are gated by endogenous and exogenous modulators at the atomic level; and to elucidate TRPV2 channel precise molecular function in developing neurons and immune cells.

PI_NAMEs: MOISEENKOVA-BELL, VERA  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: apical membrane;Biological;Biophysics;Cardiovascular Physiology;Cations;Cell Physiology;Cells;Cryoelectron Microscopy;Distal convoluted renal tubule structure;Drug or chemical Tissue Distribution;Electron Microscopy;Electrophysiology (science);Epithelial Cells;Event;Exhibits;Flow Cytometry;Fluorescence Microscopy;Goals;Homeostasis;Human body;Immune;Immunity;interdisciplinary approach;Ions;Kidney;Label;Laboratories;Malignant Neoplasms;Mass Spectrum Analysis;member;Membrane Proteins;Methods;microscopic imaging;Molecular;neuron development;Neurons;particle;Permeability;Peroxidases;Pharmacology;Physiological;Play;programs;Protein Biochemistry;receptor;Research;Role;Structure;TRP channel;TRPV channel;Vanilloid

PROJECT_TITLE: Structure and Function of TRPV channels


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE Proper transport of intracellular cargo to specific cellular locations is carried out by the motor proteins kinesin and dynein that move in opposite directions along microtubule tracks. This bidirectional transport is particularly important in the elongated axons and dendrites of neurons, and defects in bidirectional transport are linked to neurodegenerative diseases such as Alzheimer’s, Huntington’s, and ALS. The goal of this project is to understand the molecular mechanisms underlying bidirectional transport, and to contribute to understanding and treating transport defects underlying neurodegenerative diseases.

PI_NAMEs: HANCOCK, WILLIAM OLAF (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Adaptor Signaling Protein;Address;Affect;Alzheimer's Disease;Axon;Cells;Cilia;ciliopathy;Computer Models;Defect;Dendrites;DNA;Dynein ATPase;Equilibrium;Experimental Models;experimental study;Flagella;genetic regulatory protein;Goals;Huntington Disease;In Vitro;Individual;Intracellular Transport;Investigation;Kinesin;Kinetics;Link;Lipids;Location;mechanical load;Mechanics;Microscopy;Microtubule-Associated Proteins;Microtubules;millisecond;Molecular;Motility;Motor;motor control;nanometer;Neurodegenerative Disorders;Neurons;Organelles;Polymerase;Positioning Attribute;Post-Translational Protein Processing;Property;Proteins;reconstitution;Speed;temporal measurement;tool;Tubulin;Vesicle;vesicle transport;Work

PROJECT_TITLE: Molecular mechanism of bidirectional transport

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


NIH_SPENDING_CATS: Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: Los Angeles

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Hepatitis B virus (HBV) is an important human pathogen that can cause severe liver diseases. There are an estimated 250 million HBV carriers in the world, resulting in nearly 1 million deaths every year. The current HBV treatments are less than satisfactory. The goal our proposed research is to understand the life cycle of HBV, which will be important for improving the treatments for HBV patients.

PI_NAMEs: OU, J.-H. JAMES  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Autophagocytosis;Autophagosome;Biogenesis;Biological;Capsid;Catabolic Process;Cell Culture Techniques;Cessation of life;Chronic;Core Assembly;Core Protein;Development;DNA;DNA biosynthesis;env Gene Products;Gene Silencing;Genes;Genetic Transcription;Genomic DNA;Goals;Grant;Hepatitis B Therapy;Hepatitis B Virus;hepatoma cell;Homeostasis;human pathogen;improved;In Vitro;in vivo;Life Cycle Stages;Liver diseases;Mediating;Membrane;Monomeric GTP-Binding Proteins;Morphogenesis;Multivesicular Body;new therapeutic target;novel;Nucleocapsid;particle;Patients;Persons;prevent;Process;Proteins;Reporting;Research;response;RNA;Role;Site;Surface Antigens;Testing;trafficking;Transfection;Transgenic Mice;Vesicle;Viral;Viral Genome;Viral Packaging;viral RNA;Virion;Virus;Virus Replication

PROJECT_TITLE: Autophagy and the Replication of Hepatitis B Virus

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


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

ORG_CITY: BALTIMORE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE The goal of this proposal is to develop a broad-spectrum Shigella vaccine based on highly conserved proteins IpaB, IpaH and VirG. The antigens will be produced in large amounts (using a cell-free system) and tested for immunogenicity and protective efficacy against multiple Shigella serotypes in animal models. The mechanism of these antibodies’ action at different steps of Shigella invasion will also be tested in vivo and in vitro. This work has the potential to produce a broadly protective Shigella vaccine that can easily be tested in humans.

PI_NAMEs: PASETTI, MARCELA F (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: 5 year old;Adjuvant;Adult;Affect;aluminum sulfate;Animal Model;Antibiotic Resistance;Antibiotics;Antibodies;Antigens;Antimicrobial Resistance;Area;Attenuated;bioweapon;burden of illness;Cavia;Cell Culture Techniques;Cell-Free System;Cells;Child;Clinical;clinical development;Clinical Research;clinical translation;clinically relevant;cost;Country;Data;Day center care;Developed Countries;Development;Diarrhea;diarrheal disease;Disease;Disease Outbreaks;dosage;Dysentery;Epidemiology;Evaluation;experimental study;genetic element;Goals;Growth;Human;Human Milk;IgG1;illness length;Immune Sera;Immunity;Immunization;immunogenic;immunogenicity;Immunoglobulin G;Immunologics;Impaired cognition;In Vitro;in vivo evaluation;Incidence;Infant;Infection;infection risk;Inflammatory;innovation;Institution;Interruption;Intramuscular;Invaded;Laboratories;Life;Lifelong disability;low and middle-income countries;manufacture;manufacturing scale-up;Medical;Methods;Military Personnel;Modeling;Monoclonal Antibodies;mortality;Mothers;Mucous Membrane;Multi-Drug Resistance;Mus;Natural Immunity;Nature;new technology;novel;O Antigens;Oral;Organism;Oryctolagus cuniculus;parenteral administration;Phase;phase 1 study;Placenta;Plasmids;Polysaccharides;Positioning Attribute;pre-clinical;prevent;Production;prophylactic;protective efficacy;Protein Biosynthesis;protein purification;Proteins;Public Health;Reporting;resistant Shigella;Resources;Risk;Role;Rotavirus;screening;serological marker;Serotyping;Serum;Severities;Shigella;Shigella Infections;Shigella Vaccines;Subunit Vaccines;success;System;T cell response;Technology;Testing;tissue culture;tool;Translating;Type III Secretion System Pathway;Vaccine Antigen;vaccine candidate;Vaccines;Virulence;Virulent;Vulnerable Populations;Work

PROJECT_TITLE: Broad spectrum Shigella subunit vaccine based on conserved proteins

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Cardiovascular;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Endometriosis;Estrogen;Heart Disease;Pain Research;Prevention;Women's Health Research

ORG_DEPT: MISCELLANEOUS

PHR: Endometriosis is a debilitating estrogen-dependent gynecological disorder associated with chronic pelvic pain and a myriad of comorbidities associated with systemic inflammation including elevated cardiovascular disease (CVD) risk. We take an integrative physiology approach to examine the role of estrogens and LOX-1 receptor mechanisms mediating the increased CVD risk through parallel inflammatory mechanisms, and to examine two emerging interventions that have shown efficacy for reducing symptoms and long-term CVD risk in women with endometriosis. These studies have the potential to identify clinically relevant therapeutic targets and interventions to decrease CVD burden in women with endometriosis.

PI_NAMEs: ALEXANDER, LACY M. (contact);STACHENFELD, NINA

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: Acceleration;Address;Affect;Age;Atherosclerosis;Biological Markers;Blood Vessels;brachial artery;burden of illness;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Physiology;Cardiovascular system;Caring;Cause of Death;Chronic;chronic pelvic pain;clinically relevant;comorbidity;Conjugated Estrogens;cytokine;density;Disease;effective intervention;effectiveness measure;endometriosis;Endometrium;endothelial dysfunction;Endothelium;epidemiologic data;Estradiol;Estrogen Receptors;Estrogens;experience;experimental study;GNRH1 gene;Goals;Gonadotropin Hormone Releasing Hormone;Gonadotropin Releasing Hormone Inhibitor;Gynecologic;Health;Human;Impairment;improved;in vivo;Infertility;Inflammation;Inflammation Mediators;Inflammatory;Intervention;Lectin;Lipoprotein Receptor;Low-Density Lipoproteins;LOX gene;Measures;Mediating;Metabolism;Modeling;Nature;Nitric Oxide;novel;Oral;Outcome;Oxidants;oxidized LDL receptors;oxidized lipid;Pain;Peripheral;Physicians;Physiological;Physiology;Pre-Clinical Model;Process;Production;Proliferating;receptor;Receptor Activation;reduce symptoms;reproductive;Reproductive Endocrinology;Research;Risk Factors;Role;salicylsalicylic acid;scavenger receptor;Scientist;Selective Estrogen Receptor Modulators;Series;Signal Transduction;Simvastatin;Site;standard care;Symptoms;Syndrome;systemic inflammatory response;Testing;Therapeutic Intervention;therapeutic target;Tissues;Uterine cavity;Vascular Diseases;Vasodilation;Woman;Women's mortality;Women's study

PROJECT_TITLE: Mechanisms and interventions addressing accelerated cardiovascular disease risk in women with endometriosis

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


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

PHR: NARRATIVE The goals of this proposal are 1) Characterize the role of Tfcp2l1 in driving alveolar epithelial progenitor identity in the developing and mature lung and determine its functional role in alveolar regeneration and 2) Determine the functional role of Klf5 in regulating alveolar epithelial regeneration.

PI_NAMEs: MORRISEY, EDWARD E (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: Acute;Acute Lung Injury;Address;Adult;Alveolar;alveolar epithelium;alveolar homeostasis;Alveolus;Area;ATAC-seq;Automobile Driving;Behavior;Biological Assay;cell behavior;Cell Differentiation process;Cell Lineage;Cell Proliferation;cell regeneration;cell type;Cells;Chronic;Chronic Disease;Chronic Obstructive Pulmonary Disease;Communication;Data;Defect;Development;Disease;Environment;Epigenetic Process;Epithelial Cells;epithelial stem cell;epithelium regeneration;extracellular;Family;Gases;Genetic;Genetic Transcription;Goals;Histologic;Homeostasis;Human;idiopathic pulmonary fibrosis;Injury;insight;Intestines;Knowledge;Laboratories;LGR5 gene;Licensing;loss of function;Lung;lung development;Lung Diseases;lung injury;Mesenchymal;Molecular;Mus;Myofibroblast;Natural regeneration;Organoids;Pathway interactions;Pattern;Population;postnatal;precursor cell;Pulmonary alveolar structure;repaired;Reporter;Respiratory System;response to injury;restraint;Role;self-renewal;single cell ATAC-seq;single-cell RNA sequencing;Specific qualifier value;stem cell differentiation;stem cells;Target Populations;transcription factor;transcription regulatory network;Transcriptional Regulation;transcriptome sequencing;Vascular Endothelial Cell;Viral;WNT Signaling Pathway;Work

PROJECT_TITLE: Transcriptional Regulation of Lung Alveolar Regeneration

STUDY_SECTION: LIRR

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Heart Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_DEPT: PHYSIOLOGY

PHR: NARRATIVE Our research program develops and applies innovative mass spectrometry technologies, bioinformatics tools, and methodologies to transform our understanding of cell surface proteins and glycans and answer outstanding questions in stem cell biology and cardiac pathology. Our platforms promote the development of new reagents and strategies to enhance the utility and function of pluripotent stem cell derived cardiomyocytes for a wide range of research and clinical applications and promote the discovery of new strategies for treating advanced heart failure.

PI_NAMEs: GUNDRY, REBEKAH L. (contact)

PROGRAM_OFFICER_NAME: LUNDBERG, MARTHA

PROJECT_TERMS: bioinformatics tool;Biology;biomarker panel;Cardiac;Cardiac Myocytes;Cardiotoxicity;Cell surface;Cell Surface Proteins;cell type;Cells;clinical application;Data;Development;Disease;disease model;drug testing;experience;Future;Genetic;glycoproteomics;Heart;Heart failure;Human;improved;innovation;Ligand Binding;Mass Spectrum Analysis;Membrane;Membrane Glycoproteins;Methodology;Methods;molecular phenotype;Monitor;next generation;novel marker;Outcome Study;Pathology;Patient Care;Patients;Pharmaceutical Preparations;Pluripotent Stem Cells;Polysaccharides;programs;Proteome;Reagent;receptor;remote sensing;Reproducibility;Research;Signal Transduction;Specificity;Speed;stem cell biology;stem cells;System;Technology;technology development;Therapeutic;Tissues;translational study

PROJECT_TITLE: Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease


NIH_SPENDING_CATS: Genetics;Human Genome;Transplantation

ORG_CITY: HOUSTON

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

PHR: Project Narrative The potential of organ transplantation as a lifesaving therapy is limited by the immunosuppression drug- induced toxicities and progressive loss of organ transplants. Our project is designed to uncover the new and fundamental barriers that hinder transplant survival. Our proposed studies will open new opportunities in the development of better therapies for transplant patients, as well as for patients with autoimmune diseases, bone marrow grafts, and cancer.

PI_NAMEs: LI, XIAN CHANG (contact)

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: Address;Adult;Age;Allografting;Apoptosis;Area;aspartylglutamate;ATAC-seq;Autoimmune Diseases;Autoimmunity;Binding;Biogenesis;Biological Assay;Biology;Bone Marrow Transplantation;Breeding;Cells;ChIP-seq;Chromatin;chromatin remodeling;Clinical;Complex;design;Development;effector T cell;Eragrostis;Family;Family member;Fluorescence;FOXP3 gene;Functional disorder;Funding;Gene Modified;Genetic Transcription;genome-wide analysis;glutamylalanine;Goals;helicase;Immune;Immune Tolerance;Immunosuppression;in vivo;inflammatory milieu;Interleukin 2 Receptor;Interleukin-2;JAK3 gene;knock-down;Knowledge;Life;LoxP-flanked allele;Malignant Neoplasms;Maps;Mediating;member;Messenger RNA;Modeling;Motor;mRNA Precursor;mRNA Stability;Mus;Mutation;novel;Organ Transplantation;overexpression;Pathway interactions;Patients;Peripheral;Pharmaceutical Preparations;Phenotype;Positioning Attribute;Productivity;programs;Proteins;receptor;Regulation;Regulatory T-Lymphocyte;Reporter;Reporting;Ribosomes;RNA;RNA Binding;RNA Helicase;RNA immunoprecipitation sequencing;RNA Processing;RNA Splicing;RNA-Binding Proteins;Role;sensor;Signal Transduction;signature molecule;single-cell RNA sequencing;Site;Spliceosomes;Stat5 protein;stress granule;System;Testing;Thymus Gland;Time;tool;Toxic effect;transcription factor;Transcription Factor AP-1;transcriptome;transcriptome sequencing;Translating;Transplant Recipients;Transplantation;transplantation therapy;Transplantation Tolerance;Untranslated Regions;viral RNA

PROJECT_TITLE: Control of dysfunctional Tregs

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Gene Therapy;Genetics;Human Genome;Immunotherapy

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Cellular immunotherapies such as transgenic T-cell receptor (TCR) T-cells are revolutionizing the treatment of multiple cancer types, but there remain significant incidences of treatment failure or relapsed disease after an initial clinical response. I propose that the DNA accessibility of these transgenic T-cells changes over time, can ultimately impair the cells’ anti-cancer functionality, and are associated with treatment failure. This research plan will examine samples of transgenic TCR T-cells from patients receiving them for cancer treatment, and compare the cells’ DNA accessibility, gene expression patterns, and their associated functionality over time with the patients’ response rates to their transgenic cell therapy, and identify factors which are associated with this phenomenon.

PI_NAMEs: NOWICKI, THEODORE SCOTT (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Advisory Committees;anti-cancer;Area;ATAC-seq;Bioinformatics;Biological;bisulfite sequencing;California;cancer immunotherapy;cancer therapy;cancer type;career;cell age;Cell Physiology;Cell Therapy;Cells;Cellular immunotherapy;Characteristics;Chromatin;Classification;Clinical;clinical decision-making;cohort;Committee Members;Computational Biology;cytokine;Cytometry;Cytosine;design;DNA;DNA Methylation;DNA Sequence;DNA sequencing;engineered T cells;epigenetic silencing;epigenomic profiling;epigenomics;experience;Functional disorder;functional loss;Gene Expression;Gene Expression Profile;Generations;Genes;genetic element;Genetic Engineering;Genetic Transcription;Genomic DNA;Goals;Histone Acetylation;Immunotherapy;Impairment;in silico;in vivo;Incidence;instructor;Knowledge;Lead;Learning;Los Angeles;loss of function;Malignant Neoplasms;Mentors;Mentorship;Methodology;Methylation;Monitor;novel;Oncology;Ontology;patient response;Patients;pediatric department;Pediatric Hematology;Peripheral;Phenotype;Positioning Attribute;promoter;Promoter Regions;Recurrent disease;Relapse;Research;Research Personnel;responders and non-responders;response;retroviral transduction;Sampling;skills;Structure;T cell therapy;T-Cell Receptor;T-Cell Receptor Therapy;T-Lymphocyte;Therapeutic;Time;Training;transcriptome sequencing;transcriptomics;transgene expression;Transgenes;Transgenic Organisms;translational study;Treatment Failure;treatment response;Tumor Antigens;Universities;whole genome;Work

PROJECT_TITLE: Functional epigenomics of transgenic cellular immunotherapies for cancer

STUDY_SECTION: NCI

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


ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Candida yeast species cause 80-90% of invasive fungal infections and up to 50% of patients who develop invasive Candidiasis die. Dispersion from Candida biofilms is a unique aspect of these fungal infections associated with mortality and morbidity yet dispersion remains poorly understood and therapeutically untargeted due to a lack of quantitative in vitro assays. We propose to develop an under-oil microfluidic system (UOMS) that will allow high-throughput measurement of dispersive capacity and dispersed cell phenotype in Candida mutants and clinical isolates, allowing the fundamentals of this important virulence process to be understood and explored as a drug target.

PI_NAMEs: BEEBE, DAVID J (contact);MCCLEAN, MEGAN N

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Address;Antibiotics;attributable mortality;Bacterial Infections;Biological Assay;Blood Circulation;Candida;Candida albicans;candida biofilm;candidemia;Candidiasis;Catheters;Cell Count;Cells;Clinical;Collecting Cell;Critical Illness;Death Rate;Devices;Disease;Drug resistance;Drug Targeting;Effectiveness;Environment;Foundations;fungus;Generations;Genetic;Genetic Determinism;Growth;Health Care Costs;Healthcare;Heterogeneity;Human body;Immunocompromised Host;In Vitro;in vitro Assay;in vivo;Incidence;Individual;Infection;infection rate;innovation;instrumentation;Intervention;Libraries;Life;Liquid substance;Measurement;Measures;Methods;Microbial Biofilms;Microfluidic Microchips;Microfluidics;Morbidity - disease rate;mortality;mutant;Mycoses;Neoplasm Metastasis;novel;Oils;operation;pathogenic fungus;Patients;Pharmaceutical Preparations;Phenotype;Physiological;Prevention;Process;Property;screening;Sepsis;Site;Solid;Surface;System;Technology;Therapeutic;tool;Virulence;Virulence Factors;Wettability;Work;Yeasts

PROJECT_TITLE: Under-oil open microfluidic system (UOMS) for studying systemic fungal infection

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Crohn's Disease;Digestive Diseases;Genetics;Immunotherapy;Inflammatory Bowel Disease

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on the development and maintenance of human FOXP3+TREG and TH17 cells, work which will open novel experimental therapeutics including cellular therapy in human Inflammatory Bowel Disease (IBD) and other TH17-related inflammatory diseases (i.e. rheumatologic, neurologic, and dermatologic conditions). Ongoing TREG cell therapy trials and emerging cancer trials of epigenetic regulators will benefit from insight into potential activation of the TH17 phenotype in FOXP3+ cells exposed to the inflammatory milieu. We believe that execution of the experimental plan will realize the new horizon of epigenetic therapies in human immune mediated diseases.

PI_NAMEs: FAUBION, WILLIAM A (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: 3-Dimensional;Adoptive Cell Transfers;Adoptive Transfer;Anti-Inflammatory Agents;Architecture;Articulation;Automobile Driving;Binding;Bioinformatics;Biology;CCCTC-binding factor;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;Cell Therapy;Cells;cellular engineering;Chromatin;Chromatin Loop;Chromatin Structure;Chronic;Clinic;Complex;Crohn's disease;cytokine;Derivation procedure;Dermatologic;Development;Disease;DNA;Drug Targeting;Enhancers;Environment;epigenetic drug;Epigenetic Process;epigenetic therapy;epigenome;epigenomics;ETS Family Protein;Evaluation;Event;experience;Exposure to;FOXP3 gene;gene network;gene repression;Genes;Genetic Transcription;Goals;Grant;gut inflammation;Human;Human Biology;Human Engineering;Immune;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory milieu;insight;Intestines;Investigational Therapies;Kinetics;laboratory development;Lesion;Lymphocyte;Maintenance;Malignant Neoplasms;Mediating;Mus;Neurologic;novel;Pathogenicity;Pathway interactions;Patients;Peripheral;Phenocopy;Phenotype;Polycomb;programs;promoter;Proteins;prototype;Public Health;Publishing;Qualifying;Regulatory T-Lymphocyte;Repression;Repressor Proteins;Research;Risk;Role;Shapes;Signal Transduction;Spleen;Spontaneous colitis;T-Lymphocyte;Testing;Therapeutic;therapeutic evaluation;therapeutic target;Therapy trial;Work

PROJECT_TITLE: Inflammatory cascades disrupt Treg function through epigenetic mechanisms

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(02)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention

PHR: PROJECT NARRATIVE Influenza virus engages cellular factors that are necessary for successful infection. Here we study the function of RNA:protein complexes formed during infection by both viral and host components. These studies will provide insight into the viral and host factors that regulate viral replication and host innate immune responses, and may ultimately identify new targets for therapeutic intervention.

PI_NAMEs: MEHLE, ANDREW  (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: Address;Affect;anti-influenza;Anti-viral Agents;Anti-viral Response;Binding;Binding Proteins;burden of illness;Cells;cellular targeting;Complex;Data;Detection;Development;direct application;disorder control;economic cost;Environment;Equilibrium;Event;experimental study;gene product;genetic association;Goals;Health Care Costs;Healthcare;Immune;immune activation;immunogenic;Impairment;Infection;Influenza;influenza infection;influenza outbreak;influenzavirus;Infrastructure;innate immune pathways;Innate Immune Response;insight;Integration Host Factors;Interferons;Invaded;Knowledge;Medical;Messenger RNA;Molecular;Morbidity - disease rate;mortality;new therapeutic target;novel;novel therapeutic intervention;Nucleic Acids;Nucleoproteins;Outcome;pandemic disease;pathogen;Pathway interactions;Pattern recognition receptor;Pharmacotherapy;prevent;Process;Production;Productivity;protein complex;Proteins;Public Health;public health intervention;Recurrence;Research;response;Ribosomes;RNA;RNA amplification;RNA-Protein Interaction;Role;seasonal influenza;sensor;Severities;Shapes;Strategic Planning;success;Testing;Therapeutic;Therapeutic Intervention;Translations;United States National Institutes of Health;universal influenza vaccine;Vaccination;Viral;Viral Physiology;Viral Proteins;viral RNA;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: RNA:protein interactions that dictate the success of influenza virus infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-B(02)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative: The proposed research is relevant to public health because neurodevelopmental disorders such as brain malformations, epilepsy, or autism can be caused by abnormal stem cell divisions in the developing brain. The outcomes will be relevant to the mission of NINDS to reduce the burden of neurological disease. The fundamental knowledge gained will additionally impact many other areas of biology and health such as development or cancers of other organs.

PI_NAMEs: DWYER, NOELLE D (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Affect;Age;Apical;apical membrane;Apoptosis;Area;autism spectrum disorder;beta catenin;Biological;Biological Assay;Biology;Brain;brain malformation;brain size;Cancer cell line;candidate identification;Cell Cycle;Cell division;Cell Line;Cell Maintenance;Cell Polarity;cell type;Cells;Cellular Assay;Cilia;cilium biogenesis;Complex;Coupling;Data;Daughter;daughter cell;Defect;Development;Dissociation;Epilepsy;Excision;experimental study;Gene Deletion;Gene Mutation;Genes;Genetic;Geometry;Health;Image;In Vitro;in vivo;Individual;innovation;Knowledge;Lead;Link;Long-Term Effects;Malignant Neoplasms;Mediating;Methods;Microcephaly;Microtubules;Mission;Molecular;Morphology;mosaic analysis;mosaic loss;Mothers;mutant;Mutant Strains Mice;Mutation;National Institute of Neurological Disorders and Stroke;nerve stem cell;Nervous System Disorder;neurodevelopment;Neurodevelopmental Disorder;Neurons;neuroregulation;novel;Organ;Organelles;Outcome;Paper;Pathway interactions;Phenotype;Positioning Attribute;Probability;Process;Public Health;Regulation;Reporter;Research;Signal Pathway;Signal Transduction;stem;stem cell division;stem cell expansion;stem cells;stemness;Structure;Surface;System;Testing;Time;Tissues;tool;TP53 gene;transcriptome sequencing;transmission process;Ventricular;WNT Signaling Pathway

PROJECT_TITLE: Abscission regulation of corticogenesis

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Microbiome;Natural Products;Neurosciences

PHR: PROJECT NARRATIVE Pathogens have evolved elaborate mechanisms to sense their environments and, in particular, host neurotransmitters; the sensing of these neurotransmitters is the basis of a novel mode of regulating virulence gene expression. For example, serotonin is a neurotransmitter that is primarily synthesized in the gastrointestinal (GI) tract, which is sensed by pathogens to regulate virulence expression. The related microbiota-derived compound indole is also sensed.

PI_NAMEs: SPERANDIO, VANESSA  (contact)

PROJECT_TERMS: absorption;Anabolism;Animal Model;arm;Bacteria;Behavioral;Binding;Blood flow;Brain;Cells;Chemicals;Chlorides;Citrobacter rodentium;Colitis;Colon;Communication;Cues;Disease;disease prognosis;Engineering;enteric pathogen;Enterochromaffin Cells;Enterocytes;Environment;Enzymes;Epithelial Cells;Escherichia coli EHEC;Excision;Fluoxetine;gastrointestinal;Gastrointestinal Diseases;Gastrointestinal tract structure;Gene Expression;Genes;Genetic Transcription;Grant;gut inflammation;gut-brain axis;host microbiota;Human;Hyperplasia;Immune response;in vivo;in vivo Model;Indoles;Infection;inhibitor;Intestinal Absorption;intestinal barrier;Intestinal Mucosa;Intestines;Knockout Mice;Lamina Propria;Lesion;Mediating;Membrane;microbial;microbiota;Modeling;mouse model;Mus;Muscle Contraction;Names;Neurotransmitters;novel;Nucleic Acid Regulatory Sequences;Orphan;pathogen;Pathogenesis;Pathogenicity Island;pharmacologic;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiology;Potassium;Process;Protein Dephosphorylation;protein-histidine kinase;receptor;Receptor Signaling;Regulation;renal damage;response;reuptake;Role;Serotonin;Serotonin Agonists;serotonin receptor;Shiga Toxin;Signal Pathway;Signal Transduction;Signaling Molecule;Smooth Muscle;Source;Study models;Submucosa;Tissues;transcriptome;Tryptophan;Tryptophan 5-monooxygenase;Tryptophanase;Virulence;virulence gene

PROJECT_TITLE: Tryptophan derivatives in EHEC pathogenesis

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE The incidence of acute and chronic antibody-mediated rejection (ABMR) is increasingly observed in clinical kidney transplants and effective treatment has become one of the most important challenges confronting successful long-term graft survival, but the mechanisms leading to the development of antibody-mediated chronic graft injury and loss remain poorly understood and are hampered by the absence of clinically relevant preclinical models. We have developed novel models of chronic ABMR of kidney allografts that we will utilize to test the hypothesis that in the absence of NK cell activation DSA binding to kidney allograft endothelium stimulates production of myeloid cell recruitment and differentiation factors that skew their function to initiate and promote autoantibody production and chronic graft injury leading to chronic ABMR. We anticipate that the results of the proposed studies will provide novel insights into the components and mechanisms underlying development of antibody-mediated chronic kidney graft injury and identify novel targets and therapeutic strategies to improve kidney graft outcomes.

PI_NAMEs: FAIRCHILD, ROBERT L (contact)

PROGRAM_OFFICER_NAME: KULKARNI, SHILPA S

PROJECT_TERMS: Acute;Allogenic;Allografting;Animal Model;Antibodies;Antibody Repertoire;Antibody Response;Antibody titer measurement;antibody-mediated rejection;Appearance;Attenuated;Autoantibodies;Autoantigens;Binding;Blood capillaries;CCR5 gene;Cell Differentiation process;Chronic;Clinical;clinically relevant;Development;donor-specific antibody;effective therapy;Endothelium;experimental study;Extracellular Matrix;Failure;Fibrosis;Gene Expression Profile;Generations;Goals;graft failure;graft function;Graft Survival;heart allograft;Histopathology;Immunosuppression;improved;Incidence;Infiltration;Inflammatory;Injury;Injury to Kidney;insight;Investigation;Kidney;kidney allograft;Kidney Transplantation;Knowledge;Leukocyte Trafficking;Macrophage;Mediating;Modeling;Molecular;monocyte;morphogens;mouse model;Myeloid Cell Activation;Myeloid Cells;nephrogenesis;new therapeutic target;NK Cell Activation;novel;Organ Transplantation;Outcome;Pathology;Phenotype;Population;post-transplant;Pre-Clinical Model;Production;recruit;Regimen;Renal function;response;Role;Serum;Solid;success;synergism;T-Lymphocyte;Testing;Therapeutic;therapeutically effective;transcriptome;Transplant Recipients;Transplantation;transplantation therapy;Tubular formation;virtual

PROJECT_TITLE: Chronic Antibody-Mediated Rejection of Kidney Allografts


NIH_SPENDING_CATS: Cardiovascular;Rare Diseases

ORG_CITY: LEXINGTON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PI_NAMEs: WU, CONGQING  (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Abdominal Aortic Aneurysm;Address;Angiotensin II;Aorta;Aortic Aneurysm;Aortic Diseases;Aortic Rupture;Apoptosis;biobank;Biology;career development;CASP1 gene;Caspase;Cell membrane;Cell surface;Cells;Cessation of life;Coagulation Process;college;Data;Death Rate;Disseminated Intravascular Coagulation;Event;Genetic;Human;Inflammation;Inflammatory;innovation;Lesion;Macrophage;Mediating;Medical;Medicine;monolayer;Mus;Nature;novel;Pathologic;Phosphatidylserines;prevent;Proteins;Publications;release factor;Research;research and development;Research Personnel;Role;Rupture;Ruptured Abdominal Aortic Aneurysm;septic;Surface;Testing;therapeutic target;Thromboplastin;Thrombus;Tissues;Training

PROJECT_TITLE: Macrophage Pyroptosis in Abdominal Aortic Aneurysm

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Hematology;Neurosciences;Pediatric;Rare Diseases;Sickle Cell Disease;Stroke

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Children with sickle cell disease have a high risk of silent stroke and cognitive deficits caused in part by anemia- induced changes in tissue-level brain blood flow, cerebrovascular reactivity and oxygen extraction. This project will determine if a low-cost, non-invasive technology, known as diffuse optical spectroscopy, is sensitive to changes in the brain associated with these silent strokes and their treatment. Our long-term goal is to develop a low-cost brain monitoring tool that can screen for silent infarct risk in pediatric SCD to facilitate timely therapeutic intervention.

PI_NAMEs: BUCKLEY, ERIN MCGUIRE (contact);GEE, BEATRICE E

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Accounting;Adverse event;Affect;Age;age effect;Anemia;Anesthesia procedures;Blood flow;Blood Flow Velocity;Blood Vessels;Brain;Brain Injuries;Carbon Dioxide;Carrying Capacities;Cell Respiration;cerebral artery;cerebral hemodynamics;Cerebral Infarction;cerebrovascular;Cerebrovascular Circulation;cerebrovascular reactivity;Cerebrum;Child;Childhood;Clinical;Cognitive deficits;comparison control;cost;cost effective;Data;Diffuse;Exhibits;Frequencies;frontal lobe;Goals;gray matter;Hematocrit procedure;hemodynamics;Hemoglobin;high risk;Impairment;improved;In Vitro;indexing;Infarction;Injury;Intervention;Light;light intensity;Link;Magnetic Resonance Imaging;Measures;Metabolic;Metabolic stress;Metabolism;Modality;Monitor;Near-Infrared Spectroscopy;Optics;Oxygen;Patients;Performance;Perfusion;Physiology;portability;Positron-Emission Tomography;Property;response;Risk;Risk Reduction;routine screening;Schools;screening;Screening procedure;Sickle Cell Anemia;Spectrum Analysis;Stimulus;Stroke;Structure;success;Surface;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;tool;Transcranial Doppler Ultrasonography;Transfusion;Treatment Efficacy;treatment optimization;trend;ultrasound;user-friendly;Vasodilation;white matter

PROJECT_TITLE: Diffuse optical spectroscopies to assess cerebral hemodynamics in pediatric sickle cell disease

STUDY_SECTION: ANIE

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Prevention;Social Determinants of Health

ORG_CITY: CAMBRIDGE

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

ORG_STATE: MA

PHR: OTHER PROJECT INFORMATION – Project Narrative The general aim of this project is to exploit the large international variations in health and life circumstances in the US and Europe to better understand the causes for these large differences. The project specifically analyzes health status as indicated by analyses of a very large set of blood samples collected from donors in 13 European countries and links that data to the large differences in socio- economic conditions and health care systems at the national level and, at the individual level, to bio- medical and socio-economic events over the life course.

PI_NAMEs: BOERSCH-SUPAN, AXEL H (contact);CRIMMINS, EILEEN M;WENER, MARK HOWARD

PROGRAM_OFFICER_NAME: CHATTERJI, MINKI

PROJECT_TERMS: aged;Aging;Archives;Biological Assay;Biological Markers;Blood;Blood specimen;blood-based biomarker;Budgets;Cardiovascular Diseases;clinical diagnosis;Cognition;Collection;Country;Data;Data Analyses;Data Collection;data harmonization;Data Reporting;Databases;Diabetes Mellitus;Disease;Dryness;Economic Conditions;Economics;Europe;European;Event;Fostering;Funding;Hand Strength;Health;Health and Retirement Study;Health behavior;health care quality;health difference;Health Status;Health Surveys;Healthcare;Healthcare Systems;Household;human old age (65+);Impaired cognition;Income;Individual;Inflammation;instrumental activity of daily living;International;Intervention;Laboratories;Legal;Life;Life Cycle Stages;life history;Life Style;Link;Lipids;Longitudinal Studies;Measurement;Measures;Mental Health;Non-Insulin-Dependent Diabetes Mellitus;Patient Self-Report;Population;Process;Recording of previous events;Reporting;Respondent;response;Retirement;Sampling;social;socioeconomics;Spottings;Statistical Data Interpretation;Study models;Testing;Universities;user-friendly;Validation;Variant;Venous;Venous blood sampling;Washington;Work

PROJECT_TITLE: Understanding Cross-National Health Differences at Older Ages and Their Causes

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE The fungus Histoplasma causes lung infections in humans, and each year there are about 500,000 new infections, 5,000 people hospitalized, and 800 deaths due to histoplasmosis in the U.S alone. We have discovered that Histoplasma is composed of at least five species and that they differ in how they cause disease and the immune responses they trigger. Our proposal combines the power of population genetics with that of molecular genetics in Histoplasma to identify and understand the genetic basis of alleles involved in differentiation between Histoplasma species.

PI_NAMEs: MATUTE, DANIEL  (contact)

PROJECT_TERMS: Affect;Alleles;Animal Model;Biological Assay;Biological Models;burden of illness;candidate validation;Cell Culture Techniques;Cessation of life;climate change;Clinical;Clinical Data;Collection;Communities;Data;Disease;Evolution;experimental study;Exposure to;fitness;Frequencies;functional genomics;Funding Opportunities;fungal genetics;fungus;Future;Gene Exchanges;Genes;Genetic;genetic approach;genetic manipulation;Genetic Models;genetic variant;Genome;genome wide association study;genome-wide;genomic tools;Genomics;Geographic Locations;Goals;Haploidy;Health;Histoplasma;Histoplasmosis;HIV Seropositivity;Hospitalization;Human;human pathogen;Immune response;In Vitro;in vivo;Infection;interest;Kinetics;Laboratory Study;Life;Lung;Lung Diseases;Lung infections;Macrophage;Maps;Medical;Methods;microbial;Modeling;Molecular Genetics;Mus;Natural Selections;Organism;Outcome;pathogen;Pathogenesis;pathogenic fungus;Pathogenicity;Patient-Focused Outcomes;Patients;Pattern;Persons;Phase;Phenotype;Phylogenetic Analysis;Population;Population Genetics;Portraits;Process;programs;Proliferating;Research;Research Support;Resources;response;Role;sample collection;Sample Size;Sampling;Structure;System;Testing;The science of Mycology;Time;tool;trait;transmission process;Travel;United States;United States National Institutes of Health;Variant;Virulence;Virulence Factors;virulence gene;web portal;Yeasts

PROJECT_TITLE: The evolution of virulence in the fungal pathogen Histoplasma

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Factor XI was identified more than 60 years ago as a blood plasma protein that makes a modest contribution to normal blood coagulation. More recently, it has become evident that factor XI serves as an interface between two powerful host defense mechanisms, and makes significant contributions to thrombotic and inflammatory disorders. The goal of this proposal is to study the biochemistry of factor XI and the related proteins of contact activation, and to understand their contributions to clinically important process such as abnormal blood clotting, inflammation and wound healing.

PI_NAMEs: GAILANI, DAVID  (contact)

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: Academia;Animal Model;Anticoagulants;Area;Biochemistry;Blood coagulation;Blood Coagulation Disorders;Blood flow;Blood Vessels;Clinical;Coagulation Process;Disease;Factor IX;Factor XI;Factor XI Deficiency;Factor XIa;Factor XII;Functional disorder;Gene Duplication;Generations;Goals;Hemophilia B;Hemorrhage;Hemostatic Agents;Hemostatic function;Heparin;High-Molecular-Weight Kininogen;Homologous Gene;Host Defense Mechanism;human population study;Industry;Inflammation;Inflammatory;Innate Immune Response;interest;Kallikrein-Kinin System;Kininogenase;Laboratories;Lead;Modeling;Molecular Biology;mouse model;Mus;novel;Oral;Parents;Peptide Hydrolases;Peptides;Plasma;Plasma Proteins;Positioning Attribute;Prekallikrein;Process;Proteins;Research;response to injury;Role;Sepsis;Structure-Activity Relationship;Study models;System;Therapeutic;Thrombin;thromboinflammation;Thrombosis;thrombotic;Thrombus;Universities;Venous;Vitamin K;Warfarin;Work;wound healing

PROJECT_TITLE: Biochemistry and Pathophysiology of Factor XI and Contact Activation


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: PITTSBURGH

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Aptamers are nucleic acid-based ligands for proteins, which – similar to antibodies – have found applications as research tools, diagnostic agents, as well as therapeutics. We are proposing the development of a new aptamer methodology that enables the selective crosslinking or transfer of functional handles to protein targets. This allows for new biomedical applications of nucleic acids that could previously not be developed.

PI_NAMEs: DEITERS, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Affinity;Amino Acids;Animal Model;Antibodies;Antibody-drug conjugates;Antisense Oligonucleotides;aptamer;Area;Base Sequence;Binding;Binding Proteins;Biological;Biological Models;Biology;Cell model;Cell surface;Cell Surface Proteins;Cells;Chemicals;Chemistry;circulating cancer cell;Collection;cost;covalent bond;crosslink;Data;design;Detection;Development;Diagnostic;Disease;Drug Delivery Systems;Embryo;Engineering;Evaluation;experience;Generations;Goals;Government;Image;Immobilization;Immune response;Immune Targeting;improved;In Vitro;in vivo;Kinetics;Label;Libraries;Ligands;Literature;Mediating;Methodology;Modification;Mus;novel;nuclease;nucleic acid chemical synthesis;nucleic acid-based therapeutics;Nucleic Acids;Nucleotides;Oligonucleotides;Persons;Positioning Attribute;Post-Translational Protein Processing;Preparation;Process;Production;programs;protein degradation;protein purification;Proteins;Rationalization;Reaction;Reagent;Reporting;Research;Research Personnel;residence;RNA vaccine;SARS-CoV-2 spike protein;Site;small molecule inhibitor;Specificity;Structure-Activity Relationship;success;Testing;Therapeutic;Thrombin;Time;tool;transcription factor;Virus;Zebrafish

PROJECT_TITLE: Protein Labeling and Crosslinking by Covalent Aptamers


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

PHR: Narrative Clostridioides difficile is a leading cause of hospital-acquired illness in the United States and produces TcdB, a potent bacterial toxin, in order to cause disease. Our studies seek to understand how TcdB and its variant forms function during infection and use this information to develop preventative and therapeutic treatments for this important human illness.

PI_NAMEs: BALLARD, JIMMY D. (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Accounting;Address;Animal Model;Antigen Presentation;Antigens;Attenuated;Bacterial Toxins;Binding;Biochemical;Cell Communication;Cell Surface Receptors;cell type;Cells;Cessation of life;Characteristics;Clostridium difficile;Complementarity Determining Regions;CRISPR/Cas technology;cytotoxicity;Data;Development;Disease;Endocytosis;Endonuclease I;Epidemic;experimental study;Frequencies;gastrointestinal;gene editing technology;Genes;Glucosyltransferase;Hamsters;Hospitals;Human;Humoral Immunities;immunogenicity;Immunologic Memory;Immunosuppression;In Vitro;in vivo;Infection;inhibitor;insight;Intoxication;Investigation;Knowledge;Mediating;Memory B-Lymphocyte;Molecular;Monomeric GTP-Binding Proteins;mouse model;mutant;Mutation;novel;pathogen;Pathogenesis;Patients;Penetration;Peptides;prevent;programs;Proteins;Publishing;receptor;receptor binding;Receptor Cell;Relapse;Reporting;Reproduction spores;Research;response;Role;Severity of illness;System;Testing;Therapeutic;Time;tissue tropism;Toxic effect;Toxin;Tropism;United States;Vaccination;Vaccine Antigen;Variant;Virulence;Virulence Factors;Work

PROJECT_TITLE: Differential Effects of TcdB1 and TcdB2 in C. difficile disease


NIH_SPENDING_CATS: Aging;Genetics

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative: We plan to investigate the underappreciated influence of the amino acid methionine and its downstream metabolite S-adenosylmethionine on the regulation of cellular signaling and metabolism in response to nutrients. We believe these studies will provide novel insights into the mechanisms of cell growth control by this important amino acid.

PI_NAMEs: TU, BENJAMIN P (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: age-related disease;aging related;Amino Acids;Biochemistry;Biological;Carbon;cell growth;cell growth regulation;Chromatin;Epigenetic Process;Funding;Genes;Genetic;Genetic Transcription;insight;Life;Metabolic;Metabolism;Methionine;Methylation;Modification;novel;Nutrient;Pathway interactions;Phosphorylation;Reaction;response;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Sentinel;Signal Transduction;Sulfur;Sulfur Metabolism Pathway;Translations

PROJECT_TITLE: Metabolic signals regulating cell growth versus survival


NIH_SPENDING_CATS: Cardiovascular;Diabetes;Heart Disease;Heart Disease - Coronary Heart Disease;Nutrition;Obesity

ORG_CITY: PHILADELPHIA

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Obesity/diabetes is the most significant risk factor for ischemic heart injury, a disease with the greatest cause of death, disability, and health care expense in our society. The current application endeavors to define molecular mechanisms responsible for the pathologic communications between diabetic adipocytes (the culprit of obesity-induced diabetes) and diabetic cardiomyocytes (the victim in which injury most significantly contributes to diabetic cardiovascular death). Successful completion of this proposal will identify novel therapeutic strategies capable of blocking/preventing exosome-mediated pathological communications, for the purpose of ultimately ameliorating morbidity and mortality associated with diabetic cardiovascular complications.

PI_NAMEs: MA, XIN-LIANG  (contact);WANG, YAJING

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Acceleration;Adipocytes;adiponectin;ADRBK1 gene;Affect;Animal Model;Animals;Attenuated;Cardiac Death;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cause of Death;cell injury;cell type;Cells;Cessation of life;Circulation;Clinical Trials;Communication;cytotoxic;Data;Development;Diabetes Mellitus;diabetic;diabetic patient;disability;Disease;effective therapy;Endocytosis;exosome;experimental study;extracellular vesicles;Failure;Functional disorder;genetic manipulation;glycemic control;Health;Healthcare;Heart;Heart failure;heart function;Heart Injuries;Hemostatic function;Hyperglycemia;Hyperlipidemia;In Vitro;in vivo;Injury;Intervention;Knock-out;Knowledge;Mediating;Metabolic;Metabolic Diseases;Molecular;Morbidity - disease rate;mortality;Multiple Trauma;Myocardial Infarction;Myocardial Ischemia;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;novel therapeutic intervention;novel therapeutics;obese patients;Obesity;Organ;overexpression;Pathologic;Patients;Persons;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Play;prevent;Production;Publishing;receptor;Regulation;Reporting;Research;response;Risk Factors;Role;Signal Transduction;Societies;Surface;System;Testing;Time;Tissues;Type 2 diabetic;United States;Up-Regulation;uptake;Virulence Factors;Work

PROJECT_TITLE: Targeting Adiponectin for Cardioprotection in the Ischemic Heart

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: PORTLAND

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Insufficient blood flow to the cochlea is a significant pathological factor in the indifferent types of hearing disorders. Hearing loss profoundly affects individuals, causing communication problems, social isolation, and cognitive decline with high incident of Alzheimer's disease. Targeting repair of vessels, in conjunction with other therapies for hair cell regeneration, will open new avenues for hearing restoration.

PI_NAMEs: SHI, XIAORUI  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: 3-Dimensional;Ablation;Acceleration;Action Potentials;Address;Adult;Affect;Afferent Neurons;Aging;Alzheimer's Disease;angiogenesis;Animal Model;Animals;Auditory;Auditory Brainstem Responses;Autoimmune Inner Ear disease;Blood capillaries;Blood flow;blood perfusion;Blood Vessels;Brain;Bromodeoxyuridine;Cell Proliferation;Cells;Cellular Stress;Clinical;Cochlea;Communication;Coupled;Data;deafness;Dementia;Dendrites;density;Dependovirus;Ear;Edema;Endothelial Cells;Enhancers;Extravasation;gene therapy;Gene Transfer;Genes;Genetic;Goals;Grant;Growth;hair cell regeneration;Hair Cells;Health;Hearing;hearing impairment;Hearing problem;hearing restoration;hereditary hearing loss;Homeostasis;Hypoxia;Immunoglobulin G;Immunohistochemistry;Impaired cognition;improved;Individual;Inflammation;intravital fluorescence microscopy;Investigation;Ions;Knowledge;Labyrinth;Leucocytic infiltrate;macromolecule;Maintenance;Measures;Mediating;Methods;microangiography;Microcirculation;microvascular pathology;Modeling;mouse model;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuronal survival;Neurons;noise exposure;normal hearing;novel therapeutics;Nuclear;null mutation;Optics;Organ;otoacoustic emission;Pathologic;Pathology;Pericytes;Phase;phenotypic biomarker;Population;Presbycusis;progenitor;programs;quantitative imaging;repaired;Research;Resolution;response;restoration;Role;Satellite Viruses;Scanning Electron Microscopy;Serotyping;Signal Transduction;Signaling Molecule;Social isolation;sound;spiral ganglion;Structure;success;Switch Genes;Techniques;Testing;Therapeutic;Time;Tissues;Transfection;Vascular Diseases;Vascular Endothelial Growth Factors;Vascular Permeabilities;vector;VEGFA gene;Viral Vector

PROJECT_TITLE: The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function


PHR: NARRATIVE Fcγ receptor IIIa (FcγRIIIa; CD16) on natural killer (NK) cells binds to the Fc region of IgG antibodies opsonized to the surface of virus-infected and cancer target cells via their antigen binding fragments (Fab), thereby inducing clustering of FcγRIIIa to trigger antibody-dependent cytotoxicity (ADCC) against the target cells. We are uniquely positioned to examine how clustering of ligands recognizable by FcγRIIIa and other receptors on the surface of NK cells regulates the efficiency of NK cell ADCC responses. The data produced are expected to shed light on the mechanisms controlling ADCC efficiency to design novel strategies that improve NK cell- based immunotherapies to treat viruses, autoimmune diseases, and cancer.

PI_NAMEs: CAMPBELL, KERRY S;SYKULEV, YURI  (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Affect;Affinity;Antibodies;antibody-dependent cell cytotoxicity;Antigens;Autoimmune Diseases;Avidity;Binding;cancer cell;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Adhesion Molecules;Cell Degranulation;cell killing;Cell Maturation;Cell surface;Cells;Communicable Diseases;crosslink;cytokine;Cytolysis;Cytoplasmic Granules;cytotoxic;Cytotoxic T-Lymphocytes;cytotoxicity;Data;density;design;Development;Diffusion;Disease;Dissociation;Effector Cell;Environment;Fab Immunoglobulins;Fc Immunoglobulins;FCGR3B gene;Goals;Host Defense;Human;IgG1;IgG3;immune function;Immunoglobulin G;Immunologic Receptors;immunological synapse formation;Immunotherapeutic agent;Immunotherapy;improved;Infection;Integrins;Intercellular adhesion molecule 1;kinetic model;Kinetics;Ligands;Ligation;Lipid Bilayers;Lymphocyte;Malignant Neoplasms;Mediating;Meditation;Membrane;membrane model;MHC Interaction;Modeling;Molecular;MS4A1 gene;Names;nanocluster;nanolipoprotein particles;nanoparticle;nanoscale;Natural Killer Cell Immunotherapy;Natural Killer Cell toxicity;Natural Killer Cells;Nature;NK Cell Activation;novel strategies;pathogen;Peptide/MHC Complex;Play;Positioning Attribute;Production;Productivity;Proteins;receptor;Receptor Cell;receptor-mediated signaling;response;rituximab;Role;Signal Induction;Signal Transduction;Structure;Surface;Synapses;synaptic function;synaptogenesis;System;T cell response;T-Lymphocyte;Testing;Therapeutic;tool;tumor;Variant;Virus;Virus Diseases

PROJECT_TITLE: Role of immune receptor clustering in controlling efficacy of antibody-dependent FcγRIIIa-mediated cytotoxicity by NK cells


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Spinal Muscular Atrophy

ORG_CITY: BETHESDA

ORG_NAME: HENRY M. JACKSON FDN FOR THE ADV MIL/MED

PHR: PROJECT NARRATIVE (REVELANCE) Spinal muscular atrophy (SMA) is a neurodegenerative disease and one of the leading inherited causes of infant mortality. While new treatment paradigms have markedly improved motor function and survival in most patients, there has also been a dramatic increase in the number of SMA patients requiring hospitalization for cardiorespiratory care, suggesting that SMN deficiency impairs cardiac function. The studies outlined in this proposal will define the cellular role of SMN in calcium handling and will allow us to identify critical cellular processes that could be targeted to improved outcomes for SMA patients.

PI_NAMEs: BURNETT, BARRINGTON G;FLAGG, THOMAS  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Affect;Age;Alternative Splicing;ATP2A2;Autonomic Dysfunction;axion;Biology;Calcium;Calcium Signaling;Cardiac;Cardiac Myocytes;Cardiology;Cardiopulmonary;Cardiovascular system;care systems;Caring;Cause of Death;Cell Physiology;Cells;Central Nervous System;Child;Clinical;Congenital Heart Defects;Coupling;Critical Care;Data;deep sequencing;Defect;design;Development;Disease;Disease Management;disease model;experience;extend lifespan;Functional disorder;Gene Expression;gene therapy;Genes;Genetic;Goals;Heart;heart defect;heart function;Homeostasis;Hospitalization;Human;imaging approach;Impairment;improved;improved outcome;induced pluripotent stem cell derived cardiomyocytes;Infant Mortality;Inherited;insight;interdisciplinary approach;Kinetics;Live Birth;Messenger RNA;Modeling;Molecular;Morphology;Motor;motor function improvement;Motor Neurons;mouse model;Mus;Muscle;muscle degeneration;Mutation;Myocardium;Neurodegenerative Disorders;neuromuscular;Neuromuscular Diseases;neuron loss;Neurons;novel;Opportunistic Infections;Outcome;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;Performance;Process;Pulmonary Heart Disease;Regulator Genes;Relaxation;Reporting;Resolution;restoration;RNA Splicing;Role;skeletal muscle wasting;SMN deficiency;SMN protein (spinal muscular atrophy);SMN1 gene;Spinal Muscular Atrophy;Spliceosomes;success;Systemic Therapy;Testing;Therapeutic;Tissues;United States

PROJECT_TITLE: Calcium Dysregulation and Cell Function in Spinal Muscular Atrophy

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunotherapy;Kidney Disease;Organ Transplantation;Orphan Drug;Rare Diseases;Transplantation

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: NARRATIVE  Both systemic and local in situ adaptive immune processes drive kidney allograft rejection. In this application, we will use novel methods to study and quantify in situ immune processes and identify immune function in human kidney biopsies, and complement with investigations into systemic and in situ responses in mouse kidney transplant models. These studies should reveal novel rejection mechanisms and identify new therapeutic targets for the treatment of kidney allograft rejection.

PI_NAMEs: CHONG, ANITA S (contact);CLARK, MARCUS RAMSAY

PROJECT_TERMS: Ablation;Acute;adaptive immunity;Address;Allogenic;allograft rejection;Antibodies;Antibody Specificity;antibody-mediated rejection;Antigen Presentation;Antigen-Presenting Cells;Antigenic Specificity;Antigens;Architecture;Autoimmune Diseases;Automobile Driving;B-Cell Antigen Receptor;B-Lymphocytes;Biological Markers;Biopsy;Blood;Cell Communication;Cell Shape;cell type;Cells;Characteristics;Clinic;Clinical;Collaborations;Color;Complement;Complex;convolutional neural network;Coupled;Dendritic Cells;Disease;donor-specific antibody;effector T cell;Ensure;experimental study;genetic signature;Genetic Transcription;Glucocorticoids;Graft Rejection;Helper-Inducer T-Lymphocyte;Heterogeneity;high throughput technology;Human;human disease;human tissue;Immune;immune function;Immunity;Immunoglobulin Variable Region;Immunosuppression;In Situ;Infiltration;Inflammation;Inflammatory;innovation;Investigation;Kidney;kidney allograft;kidney biopsy;Kidney Transplantation;Maps;Measures;Mediating;Methods;molecular targeted therapies;Monoclonal Antibodies;mouse model;Mus;neural network;new therapeutic target;novel;novel strategies;Outcome;Output;Paper;Pathogenicity;Peripheral;peripheral blood;Phenotype;Play;Population;Positioning Attribute;Process;programmed cell death protein 1;Property;Reporting;Resistance;response;Role;secondary lymphoid organ;Seminal;Sensitivity and Specificity;Shapes;single-cell RNA sequencing;Sorting;Specificity;standard of care;Steroid Resistance;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;Testing;Therapeutic Intervention;therapeutically effective;tissue fixing;Tissue Sample;Tissues;transplant model;two photon microscopy

PROJECT_TITLE: Intrarenal B cells in acute kidney allograft rejection


NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: This proposal is expected to significantly advance our understanding of the nature of MDSCs and help develop a c-Rel blocking drug for the treatment of cancer. Therefore, this proposal should advance both scientific knowledge and clinical practice.

PI_NAMEs: PEAR, WARREN S (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: anti-cancer;anti-PD1 antibodies;Antineoplastic Agents;antitumor effect;Applications Grants;Biochemical;Blood;cancer immunotherapy;Cancer Patient;cancer therapy;Cell Differentiation process;Cell Physiology;chromatin remodeling;clinical practice;Collaborations;Combined Modality Therapy;Complex;detector;Development;Disease;Drug Targeting;Effector Cell;efficacy evaluation;Elements;factor C;Family;Genes;Genetic;genetic signature;Genetic Transcription;Genomic approach;genomic locus;Goals;Growth;Heterogeneity;Human;immune checkpoint;Immune checkpoint inhibitor;Immunity;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Individual;Inflammatory;inhibitor;Knock-out;Knowledge;Leukocytes;Lymphoid Cell;Lymphoma;Malignant lymphoid neoplasm;Malignant Neoplasms;Mediating;member;monocyte;Mus;Myelogenous;Myeloid Cells;Myeloid Progenitor Cells;Myeloid-derived suppressor cells;Nature;Neoplasm Metastasis;neoplastic cell;neutrophil;novel;Nuclear;Patients;Pharmacologic Substance;Pharmacotherapy;Play;Population;programmed cell death protein 1;programs;Research Project Grants;Risk Factors;Role;single-cell RNA sequencing;small molecule inhibitor;Specific qualifier value;Spleen;STAT3 gene;success;Suppressor-Effector T-Lymphocytes;Testing;theories;transcription factor;tumor;tumor growth;Tumor Immunity;Tumor Suppressor Proteins;tumorigenesis

PROJECT_TITLE: The c-Rel Checkpoint for Immunosuppression and Immunotherapy


ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: The proposed studies aim to facilitate basic understanding of the role of one important miRNA family in controlling the balance between immunity and tolerance and to explore the biological significance of such miRNA-mediated regulation in multiple immune cell subsets in the adaptive immune system. The results obtained from these studies will not only greatly extend our fundamental knowledge of miRNA-mediated immune regulation but also facilitate future translational research that aims at targeting miRNAs in the immune system as a therapeutic approach to treat different human immunological diseases.

PI_NAMEs: LU, LI-FAN  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adaptive Immune System;adaptive immunity;airway inflammation;Alleles;Allergens;Animal Experimentation;arm;Autoimmunity;B cell differentiation;B-Lymphocytes;BCL6 gene;Binding;Biochemical;Biological;Biological Process;Body Surface;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Differentiation process;Cell Lineage;cell mediated immune response;Cells;Cellular biology;Cellular Immunity;ChIP-seq;combat;crosslink;crosslinking and immunoprecipitation sequencing;cytokine;Data;Development;Disease;disease model;Ensure;Equilibrium;Eragrostis;exhaustion;Family;first responder;Foundations;Funding;Future;gain of function;Gene Expression Regulation;Genes;Genetic;genetic manipulation;Genetic Transcription;Goals;Helper-Inducer T-Lymphocyte;High-Throughput Nucleotide Sequencing;HMGB Family Gene;Homeostasis;Human;Humoral Immunities;Hybrids;Immune;Immune response;Immune system;Immune System Diseases;Immune Tolerance;Immunity;immunological status;Immunologics;Immunoprecipitation;immunoregulation;Impairment;In Vitro;in vivo;Infection;Inflammatory;Knowledge;loss of function;Mediating;member;Memory;Methods;MicroRNAs;miRNA expression profiling;Modeling;Molecular;Mus;novel;old mice;organ growth;Outcome;Physiological;Pilot Projects;Play;Population;Production;Publishing;Reaction;Regulation;Regulatory T-Lymphocyte;Research;response;RNA;Role;Site;Solid;Structure of germinal center of lymph node;T cell differentiation;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Therapeutic;Thymocyte Selection;tissue resident memory T cell;tool;transcription factor;Transcriptional Regulation;transcriptome sequencing;Translational Research;Untranslated RNA;Up-Regulation;Virus Diseases;Work

PROJECT_TITLE: MicroRNA-mediated control of immune responses and tolerance

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative Opioid and stimulant addictions are complex brain diseases for which there are a lack of effective medical treatments. This research will enhance our understanding of how an endogenous neurotransmitter system regulates addictive behaviors and may be targeted pharmacologically to improve outcomes for patients with substance use disorders.

PI_NAMEs: SLOSKY, LAUREN M (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Abstinence;addiction;addiction liability;Addictive Behavior;Address;Agonist;Animal Model;Animals;antagonist;Area;Attenuated;Behavior;Behavioral;beta-arrestin;Biological;Brain;Brain Diseases;brain metabolism;Brain region;Characteristics;Chemicals;Chronic;Clinical;Cocaine;Complement;Complex;Development;Disease;Dopamine;Dopamine D2 Receptor;DRD2 gene;drug addict;Drug usage;Epidemic;Etiology;Evaluation;Exhibits;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Gene Modified;Genetic;Genetic Engineering;genetic manipulation;Genetically Engineered Mouse;Goals;GTP-Binding Proteins;Homeostasis;Hypotension;Image;Imaging technology;improved outcome;In Vitro;infancy;interdisciplinary approach;Knockout Mice;Laboratories;Lead;lead series;Ligands;Link;Mediating;Medical;Mentors;mesolimbic system;Methamphetamine;Molecular Biology;Morphine;Mus;natural hypothermia;neurochemistry;neuroimaging;Neurologic;Neurotensin Receptors;Neurotransmitters;Normalcy;novel;novel therapeutics;Opiate Addiction;Opioid;Outcome;Pathway interactions;Patient-Focused Outcomes;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Physiological;Positioning Attribute;Positron-Emission Tomography;pre-clinical;preservation;Productivity;Property;psychostimulant;Public Health;receptor;Recovery;Relapse;remifentanil;Research;restoration;Running;Self Administration;side effect;Signal Transduction;Signaling Protein;skills;small molecule;Stimulant;stimulant dependence;Substance Use Disorder;System;Testing;Therapeutic;therapeutic target;therapy outcome;tool;Training;treatment strategy;Universities;X-Ray Computed Tomography

PROJECT_TITLE: Leveraging Functional Selectivity in the Neurotensin Receptor 1-Mediated Treatment of Addiction


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_DEPT: DENTISTRY

PHR: PROJECT NARRATIVE Chronic viral infections and cancer are leading causes of morbidity and mortality, but are difficult to treat because responding virus- or tumor-specific T cells become characteristically dysfunctional, or “exhausted.” Since these T cell responses are key determinants of clinical outcomes in these diseases, “immunotherapies” targeting these exhausted T cells have been developed and reduce disease severity for some patients. To improve current limitations in immunotherapy efficacy and develop new therapy strategies, this proposal seeks to resolve key mechanistic details of how exhausted T cell function is restrained in these diseases.

PI_NAMEs: SULLIVAN, MATTHEW AMBROSE (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acceleration;Acetylation;Acute;Adoptive Transfer;Antigens;ATAC-seq;Binding;Binding Proteins;Biology;C-terminal;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cell Proliferation;Cell Surface Proteins;Cells;Characteristics;Chromatin;Chronic;chronic infection;Cleavage Under Targets and Release Using Nuclease;Clinical;Coupled;Data;Development;Disease;DNA Binding Domain;Enhancers;Epigenetic Process;Eragrostis;exhaust;exhaustion;Exhibits;experience;Flow Cytometry;Functional disorder;Genetic Transcription;Goals;Histone H3;HMG-Box Domains;Immune;immune checkpoint blockade;Immune response;Immunotherapy;improved;In Vitro;in vivo;Knowledge;Length;Lymphocytic choriomeningitis virus;Mediating;Memory;Memory impairment;Messenger RNA;Methylation;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;mutant;novel therapeutics;Nuclear Protein;Outcome;overexpression;Pathology;Patients;PD-1 blockade;PD-L1 blockade;Phenotype;Play;Population;Process;programmed cell death ligand 1;programmed cell death protein 1;programs;Proliferating;Property;protein complex;protein expression;Proteins;Proteomics;receptor;Receptor Signaling;recruit;Regulation;Repression;response;restraint;Role;screening;Severity of illness;Signal Pathway;stem cell population;Surface;synergism;System;T cell differentiation;T cell response;T-Lymphocyte;Testing;transcription factor;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;tumor;Viral Cancer;Virus;Virus Diseases

PROJECT_TITLE: Molecular Mechanisms of TOX-mediated Programming of CD8 T Cell Exhaustion

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07C-M(20)]