ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE The proposed study of colorectal cancer is intended to fill important gaps in the free radical theory of cancer. The study will provide novel insights into the time-varying effect of oxidative stress on tumorigenesis along the cancer continuum, the first evidence linking oxidative stress and clinical outcomes in cancer survivors, and much needed information for identification of target populations, which will have high translational potential for the development of tailored strategies for chemoprevention and patient care of colorectal cancer.

PI_NAMEs: CHEN, QINGXIA ;YANG, GONG  (contact)

PROGRAM_OFFICER_NAME: CARRICK, DANIELLE M

PROJECT_TERMS: 8-hydroxyguanosine;Accounting;Advanced Malignant Neoplasm;Aftercare;American;Animal Model;Antioxidants;Asian;Biochemical;Blood;cancer cell;Cancer Patient;Cancer Prognosis;cancer risk;cancer survival;Cancer Survivor;carcinogenesis;cell injury;Chemoprevention;Chemopreventive Agent;chemotherapy;Chinese;Clinical;cohort;Cohort Studies;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;cytotoxic;design;Development;Diagnostic;Diet;DNA;epidemiology study;Ethnic Population;European;F2-Isoprostanes;follow-up;Follow-Up Studies;Free Radicals;hazard;healing;Health;Human;In Vitro;insight;Intake;Joints;Link;Lipid Peroxidation;Longterm Follow-up;male health;Malignant Neoplasms;Measurement;Measures;Molecular Epidemiology;Nature;novel;Oncogenic;Oncologist;Outcome;oxidation;oxidative damage;Oxidative Stress;Oxidative Stress Induction;Participant;Patient Care;Patients;Phase;Pilot Projects;Population;Publishing;Radiation therapy;randomized, clinical trials;Research Personnel;Risk;RNA;Role;Sample Size;Sampling;Science;sex;Supplementation;System;Target Populations;theories;Time;translational potential;tumor;tumorigenesis;Urine;Woman;Women's Health;Work

PROJECT_TITLE: Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: DURHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: SURGERY

ORG_FIPS: US

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE A protective HIV-1 vaccine is needed to halt the spread of the pandemic. This Program will move into manufacturing a rapid vaccine platform that presents multiple copies of neutralizing antibody targets to the immune system. This vaccine platform will hasten progress towards finding a protective HIV-1 vaccine.

PI_NAMEs: SAUNDERS, KEVIN O (contact)

PROGRAM_OFFICER_NAME: VIJH, SUJATA

PROJECT_TERMS: activation-induced cytidine deaminase;Affinity;Amino Acids;Animal Model;Antibodies;Antibody Affinity;Antigens;Avidity;B-Cell Antigen Receptor;B-Lymphocytes;Binding;Binding Sites;Biomanufacturing;booster vaccine;Cell Line;Cell Lineage;Chimeric Proteins;Clinical Trials;Complex;Consumption;cross reactivity;Data;design;Development;Doctor of Philosophy;Documentation;Electron Microscopy;Ensure;Enzyme Activation;Enzymes;experience;Ferritin;Frequencies;Future;Gene Fusion;Generations;Goals;Good Manufacturing Process;Helicobacter pylori;HIV Antigens;HIV vaccine;HIV Vaccine Trials Network;HIV-1;HIV-1 vaccine;Human;humanized mouse;Immune system;Immunization;immunogenic;immunogenicity;Immunologics;Immunology;improved;Industry;Infection;Influenza Hemagglutinin;innovation;Investigational New Drug Application;Knock-in Mouse;Lead;Link;Macaca mulatta;manufacture;Molecular Conformation;Mutation;nanoparticle;Nature;Negative Staining;neutralizing antibody;nonhuman primate;Outcome;pandemic disease;Pharmaceutical Preparations;Phase I Clinical Trials;phase I trial;Process;process optimization;Production;programs;Qualifying;quality assurance;Reaction;Regimen;SARS-CoV-2 spike protein;Series;Serum;Site;Somatic Mutation;sortase;Statistical Data Interpretation;Structure;Structure of germinal center of lymph node;Testing;Time;Toxic effect;trafficking;transpeptidation;trial planning;United States Food and Drug Administration;vaccination strategy;Vaccine Design;vaccine evaluation;vaccine platform;vaccine trial;vaccine-induced antibodies;Vaccines;Viral;Virion

PROJECT_TITLE: Conjugate nanoparticle platform development for HIV-1 envelope immunogens


NIH_SPENDING_CATS: Bioengineering;Biotechnology;HIV/AIDS;Immunization;Nanotechnology;Prevention;Vaccine Related;Vaccine Related - AIDS

PROJECT_TERMS: Acceleration;Accounting;Advisory Committees;Agreement;Antibodies;Antigens;B-Lymphocytes;Budgets;Cell Lineage;Clinical Trials;Communication;conflict resolution;Data;Data Analyses;data management;Data Provenance;data sharing;Development;Ensure;expectation;Expenditure;experience;Experimental Designs;Ferritin;Funding;Goals;Good Manufacturing Process;Grant;Guidelines;HIV-1;HIV-1 vaccine;Human;Human Resources;IACUC;Immune response;Infrastructure;Institution;Institutional Policy;interest;Lead;Measures;meetings;member;Monitor;nanoparticle;National Institute of Allergy and Infectious Disease;next generation sequencing;Occupational activity of managing finances;Outcome;Participant;Phase I Clinical Trials;Policies;Practice Guidelines;Preparation;Production;programs;Proteins;Protocols documentation;Publications;quality assurance;Regulation;Reporting;Research;Research Personnel;Resources;Rights;Risk;Site;sortase;Supervision;Testing;United States Food and Drug Administration;United States National Institutes of Health;Universities;vaccine development;vaccine platform;Vaccine Research;Vaccines

PROJECT_TITLE: Administrative Core


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE The majority of emerging viral diseases result from the zoonotic transmission of pathogen from animals to humans. While the innate immune system plays a critical role in limiting cross-species transmissions, cellular determinants mediating this effect have yet to be fully described. This study aims to identify and characterize novel cellular factors responsible for limiting viral replication in human cells.

PI_NAMEs: POSTON, DANIEL  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Address;Animals;Anti-Retroviral Agents;Anti-viral Agents;Biological Assay;Biological Models;Candidate Disease Gene;Cells;Co-Immunoprecipitations;cofactor;CRISPR screen;CRISPR/Cas technology;cross-species transmission;Data;design;Emerging Communicable Diseases;Epidemic;experimental study;Future;Genes;global health;Goals;Health;HIV;HIV-2;Host Defense;Human;Human Cell Line;immunodeficiency;Individual;Infection;Infectious Agent;Innate Immune System;insight;Interferon Type I;Interferons;Life Cycle Stages;Macaca;Mediating;Methods;Monitor;Natural Immunity;nonhuman primate;novel;pathogen;pathogenic virus;Play;Primate Lentiviruses;Primate Retrovirus;Production;Proteins;Publishing;Resistance;Role;screening;Screening procedure;SIV;System;tool;transmission process;TRIM5 gene;Tropism;Viral;Viral Physiology;Viral Proteins;viral transmission;Virus;Virus Diseases;Virus Replication;Work;Zoonoses

PROJECT_TITLE: Elucidating antiviral defenses against diverse immunodeficiency viruses using a novel, high-throughput CRISPR/Cas9 screening method.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F17-P(20)L]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;HIV/AIDS;Immunization;Nanotechnology;Prevention;Vaccine Related;Vaccine Related - AIDS

PROJECT_TERMS: Adopted;Affinity;Antibodies;Antibody Affinity;Antibody Binding Sites;Antibody Formation;Antibody Response;Antigens;Autologous;B-Cell Antigen Receptor;B-Lymphocytes;Binding Sites;booster vaccine;Cell Lineage;Cloning;Codon Nucleotides;cross reactivity;Cyclic GMP;design;Development;Effectiveness;Engineering;Enzymes;expectation;Failure;Ferritin;Genes;HIV Antigens;HIV-1;Human;humanized mouse;Immunization;Immunize;immunogenicity;in vivo evaluation;innovation;Knock-in Mouse;Link;Macaca;manufacture;member;Molecular Conformation;Monoclonal Antibodies;mouse model;Mutation;nanoparticle;neutralizing antibody;next generation sequencing;non-Native;nonhuman primate;novel;phase I trial;Phenotype;Positioning Attribute;Probability;Process;Production;Protein Subunits;Proteins;Reaction;Recombinants;Regimen;Research;research clinical testing;Running;self assembly;Serum;Somatic Mutation;sortase;Surface;Technology;transpeptidation;vaccination strategy;Vaccine Design;Vaccines;Virus

PROJECT_TITLE: Project 1. Optimization and in vivo evaluation of HIV-1 Env trimer sortase A-conjugated nanoparticles


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: Newark

ORG_DEPT: MISCELLANEOUS

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative HIV-1 reverse transcriptase (RT) is a central target for antiviral treatment of AIDS and detailed knowledge of its structure and function has important clinical and biological consequences. Reverse transcriptase inhibitors figure prominently in almost all HIV/AIDS treatment regimens, including combination therapies that are used in highly-active antiretroviral therapy (HAART) and pre-exposure prophylaxis (PrEP) as well. The proposed studies will enhance opportunities for targeting known and new sites on RT, both as the mature enzyme and during morphogenetic stages in which RT forms part of long precursor polyproteins.

PI_NAMEs: ARNOLD, EDWARD  (contact)

PROGRAM_OFFICER_NAME: BRIDGES, SANDRA H

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Anti-HIV Agents;Architecture;Bacteria;Binding;Biochemical;Biochemistry;Bioinformatics;Biological;biophysical analysis;biophysical properties;biophysical techniques;Biophysics;Chemical Structure;Clinical;Collaborations;Colorado;Combined Modality Therapy;Complement;Complex;Computer Models;Consensus;Cryoelectron Microscopy;Crystallization;Crystallography;Data;data submission;DBL Oncoprotein;design;design and construction;Deuterium;dimer;DNA;DNA biosynthesis;Double-Stranded RNA;drug action;Drug Design;Drug resistance;Drug Targeting;ds-DNA;Engineering;Enzymes;experimental study;follow-up;Grant;Highly Active Antiretroviral Therapy;HIV;HIV Infections;HIV-1;HIV/AIDS;Hydrogen;improved;inhibitor;inhibitor therapy;innovation;insight;Knowledge;Label;Letters;Licensing;light scattering;Maps;Maryland;Metals;Methodology;Methods;milligram;Molecular;Molecular Biology;Molecular Conformation;Molecular Probes;monomer;Morphogenesis;Nature;non-nucleoside reverse transcriptase inhibitors;novel strategies;nucleic acid structure;Nucleic Acids;nucleoside inhibitor;Nucleosides;Nucleotides;Peptide Hydrolases;Pharmaceutical Preparations;pol Gene Products;Polyproteins;pre-exposure prophylaxis;Production;Protein Engineering;protein expression;Proteins;Publications;Research;Research Personnel;Resistance;resistance mutation;Reverse Transcriptase Inhibitors;Reverse Transcription;RNA;RNA primers;RNA-Directed DNA Polymerase;Role;Sampling;Series;Site;small molecule;Structure;System;Time;Treatment Protocols;Viral;Virion;Virus Assembly;Visualization;Work;X-Ray Crystallography

PROJECT_TITLE: Evolving understanding of HIV-1 reverse transcriptase structure, function, and inhibition.

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Nanotechnology;Prevention;Vaccine Related;Vaccine Related - AIDS

PI_NAMEs: DICKENS, JASON  (contact)

PROJECT_TERMS: 2019-nCoV;Acceleration;Adopted;Affinity;Antibodies;Antibody Response;Antigens;Binding;Binding Sites;Cell Line;cGMP production;Chimeric Proteins;Clinical Trials;Complex;Consumption;cost;Cyclic GMP;design;Development;Enzymes;Evaluation;expectation;experimental study;Ferritin;Funding;Future;Generations;Genes;Goals;Grant;HIV Vaccine Trials Network;HIV-1;HIV-1 vaccine;Human;human pathogen;Immune response;Immune system;immunogenicity;Immunology;Infection;innovation;iterative design;Link;manufacture;Methods;misfolded protein;Molecular Conformation;nanoparticle;nanoparticle drug;Nature;neutralizing antibody;pathogen;Pharmaceutical Preparations;Phase I Clinical Trials;phase I trial;polypeptide;preservation;Process;Production;programs;Protein Engineering;Proteins;Recombinants;Regimen;Reproducibility;Research;research clinical testing;response;Safety;safety and feasibility;Series;sortase;Specificity;stability testing;Staphylococcus aureus;Surface;System;Testing;Time;Toxicology;Translating;Vaccination;vaccine candidate;Vaccine Design;vaccine development;Vaccines;Viral Vaccines;Work

PROJECT_TITLE: Project 2. cGMP manufacture of HIV-1 Env trimer sortase A-conjugated nanoparticles


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Infectious Diseases;Microbiome

ORG_CITY: Princeton

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PRINCETON UNIVERSITY

PHR: RELEVANCE (See instructions):  Bacterial pathogens require quorum sensing for infection. An important practical aspect of these  investigations is the development of anti-quorum-sensing therapies including new phage therapies as  alternatives to traditional antibiotics.

PI_NAMEs: BASSLER, BONNIE L (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Achievement;Affect;Antibiotics;Automobile Driving;Award;Bacteria;Bacteriophages;Behavior;Biological Assay;Biology;Cells;combat;Communication;Communities;Complex;Crystallography;Cues;Cytolysis;Detection;Development;Eukaryota;extracellular;flasks;Fluorescence Microscopy;Funding;Genes;Genetic Transcription;Goals;gut microbes;Health Promotion;Homologous Gene;Human;human disease;Human Microbiome;Image;imaging platform;imaging system;in vitro Bioassay;in vivo;Individual;Infection;Instruction;interspecies communication;Investigation;Knowledge;Lasers;Learning;Life;Life Cycle Stages;Life Style;Light;Lytic;mechanical drive;Mediating;Microbe;Microbial Biofilms;microbial host;microbiome;Molecular;Monitor;Morphology;Mutagenesis;mutant;New Territories;pathogen;pathogenic bacteria;Pathway interactions;Phase;Phototoxicity;Physiological;Planet Earth;Population Density;Process;Production;programs;Proteins;quorum sensing;Receptor Gene;Reporter;Research;resilience;Resolution;response;Role;Sensory;Shapes;Signaling Molecule;Site;small molecule;Surface;Vibrio cholerae;Viral;Work

PROJECT_TITLE: Intra- and Inter- Species Communication in Bacteria

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Contraception/Reproduction;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Immune cells in a mother’s uterus help the embryo receive the blood and nutrients it needs to grow. When a fetus fails to grow in the womb, both mother and fetus are in danger of death or major disability. This project will provide important information about how specialized immune cells called macrophages help the uterus to nurture the fetus throughout pregnancy, keeping mother and fetus safe from harm.

PI_NAMEs: GORDON, SCOTT MICHAEL (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acceleration;adaptive immune response;adverse pregnancy outcome;Advisory Committees;Affect;American;ATAC-seq;Award;Biochemical;Biochemistry;Bioinformatics;Biological;Blood;career development;Cells;Cellular Immunology;cellular targeting;Cessation of life;Child Support;Chromatin;Clinical;conditional knockout;congenital infection;cost;cytokine;Cytokine Signaling;Data;Development;disability;Disease;Distal;Doctor of Philosophy;Embryo;Ensure;Environment;Enzyme-Linked Immunosorbent Assay;epigenomics;Exposure to;Faculty;Fellowship;fetal;Fetal Development;Fetal Growth Retardation;Fetal health;Fetus;Flow Cytometry;Foundations;Functional disorder;functional outcomes;Funding;Genes;Genetic Transcription;Goals;Growth;health of the mother;healthy pregnancy;Homeostasis;Human;IL2RB gene;Immune;Immunity;Immunologics;Immunologist;in vivo;in vivo Model;Inflammation;Inflammatory;inflammatory modulation;innovation;instructor;interest;Interferons;Interleukin-10;Interleukin-15;interleukin-15 receptor;International;Investigation;K-Series Research Career Programs;Kinetics;Knockout Mice;Knowledge;Life;Literature;Lymphocyte;Macrophage;Maternal Health;maternal outcome;Maternal-Fetal Exchange;Mediating;Mentors;Mentorship;Methods;Molecular;Mothers;mouse model;Mus;Myeloid Cells;Natural Immunity;Natural Killer Cells;Neonatal;Neonatology;next generation sequencing;novel;Nutrient;Outcome;Oxygen;Pathway interactions;Pediatric Hospitals;Pediatrics;Pennsylvania;perinatal medicine;Personal Satisfaction;Philadelphia;Phosphorylation;Physicians;Placenta;Placental Biology;Placentation;Play;Population;Pre-Eclampsia;Pregnancy;Pregnancy Complications;Pregnancy Outcome;Productivity;Property;Public Health;reproductive;Reproductive Biology;Reproductive Immunology;Research;Research Personnel;Residencies;Resources;response;Role;Scientist;Shapes;Signal Transduction;STAT3 gene;Stat5 protein;Techniques;Testing;Training;transcriptome sequencing;transcriptomics;Universities;Uterus;Vascular remodeling;Viral;Virus Diseases;Western Blotting;Work

PROJECT_TITLE: Functions for novel IL-15-responsive macrophages in the uterus during pregnancy

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE The Pitt-Ohio State Clinical Trials Unit is a collaborative effort that will support the DAIDS HIV/AIDS research networks with a particular focus on critical areas of research in HIV therapy and prevention including: control of HIV replication in the absence of ART (“ART-free remission”), long-acting treatment for HIV; prevention and treatment of non-infectious comorbidities and hepatitis B; and HIV prevention strategies including pre-exposure prophylaxis, multipurpose technologies, broadly neutralizing antibodies and vaccines.

PI_NAMEs: KOLETAR, SUSAN L;MELLORS, JOHN W;RIDDLER, SHARON  (contact)

PROGRAM_OFFICER_NAME: COATES, CINDY KAREN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Administrative Efficiency;Affect;AIDS clinical trial group;AIDS prevention;Anti-Retroviral Agents;Appalachian Region;Area;clinical research site;clinical trial enrollment;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;Communities;community advisory board;comorbidity;County;Disease remission;Enrollment;Ensure;Epidemic;epidemic preparedness;Evaluation;follow-up;Goals;Grant;Hepatitis B;HIV;HIV prevention trials network;HIV therapy;HIV vaccine;HIV Vaccine Trials Network;HIV/AIDS;Immunology;implementation science;Individual;Intervention;Laboratories;Leadership;medical specialties;member;Mentors;Modality;Monitor;neutralizing antibody;neutralizing vaccine;novel;Ohio;Participant;Pennsylvania;Performance;Population;Populations at Risk;Poverty;pre-exposure prophylaxis;Prevention;Prevention strategy;Productivity;Protocols documentation;Records;recruit;Research;Research Personnel;Research Priority;research study;Scientific Advances and Accomplishments;skills;System;Technology;Therapeutic;Universities;virology;West Virginia

PROJECT_TITLE: Pitt-Ohio State Clinical Trials Unit


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

ORG_CITY: GALVESTON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: Project Narrative The fact that a small subset of HIV infected individuals develop broadly neutralizing antibodies (bnAbs) capable of neutralizing 98% of HIV viruses gives substantial promise that an HIV vaccine is possible. However, there has been a lack of understanding of the biophysical constraints of the germinal center microenvironment (GCME), which is the arena in which B cells compete to develop into bnAb producing B cells. We aim to uncover the composition of the extracellular space within the GCME, with the goal of identifying novel biophysical constraints and metabolic pathways that may be recruited during vaccination to elicit generation of bnAb producing B cells.

PI_NAMEs: ABBOTT, ROBERT KOEHLER (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Achievement;Address;Adenosine;ADORA2A gene;Affect;Affinity;Animal Model;Antibodies;Antibody Response;Antigens;Autoimmunity;Avidity;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocytes;Biological Models;Biology;biophysical properties;Biophysics;Cell Culture Techniques;Cell model;Cellular biology;Characteristics;Clone Cells;Coin;Complex;Cues;design;Engineering;Epitopes;Event;extracellular;Extracellular Space;fitness;Frequencies;Future;G-Protein-Coupled Receptors;Generations;Genes;Germ Lines;Goals;Helper-Inducer T-Lymphocyte;HIV;HIV envelope protein;HIV Seronegativity;HIV vaccine;Human;Hypoxia;Immune response;Immunization;Immunoglobulin Somatic Hypermutation;Immunologics;immunoregulation;improved;In Vitro;Individual;Influenza Hemagglutinin;insight;interest;Intervention;Island;Knowledge;Learning;Licensing;Measurement;Measures;Metabolic;Metabolic Pathway;Microdialysis;Microscopic;Modeling;multi-photon;Mus;Mutate;Nature;neutralizing antibody;novel;Outcome;Pathway interactions;pharmacologic;Phase;Phylogenetic Analysis;Physiological;Play;Population;pressure;public health intervention;Purinergic P1 Receptors;Reaction;recruit;response;Role;Series;Signal Transduction;small molecule;Specialized Center;Structure;Structure of germinal center of lymph node;success;System;Temperature;tumor hypoxia;tumor microenvironment;Vaccination;Vaccine Antigen;Vaccine Design;vaccine immunogenicity;Vaccines;Vascular Endothelial Growth Factors;Virus;Work

PROJECT_TITLE: Revealing the Biophysics of the Germinal Center Microenvironment


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Using random germline mutagenesis and tumor growth screening in mice, we have identified several mutations that confer cancer resistance. We now focus on understanding mechanisms of resistance in mice with two of these mutations, advancing our work to the point of translational application. We will also extend mutagenesis and screening to identify still more cancer resistance mutations, and mechanistically analyze those that operate by effects on the immune system.

PI_NAMEs: BEUTLER, BRUCE A (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Ablation;Acceleration;Affect;Alleles;Animals;anti-PD1 antibodies;Antibodies;Antigen Presentation;Antigen-Presenting Cells;Autoantigens;autosome;Biological Assay;Bone Marrow Transplantation;Cancer Etiology;cancer genome;Cancer Model;cancer therapy;cancer transplantation;causal variant;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;central tolerance;Chimerism;clinical application;Cloning;Code;Complex;CRISPR/Cas technology;Defect;Dendritic Cells;Detection;Embryo;Enrollment;Epithelium;Ethylnitrosourea;Failure;Frequencies;functional mimics;Generations;Genes;Genetic;genetic pedigree;Genome;Genome Stability;Genotype;Germ Lines;Germ-Line Mutation;Histocompatibility;Histocompatibility Antigens Class I;Histocompatibility Antigens Class II;Homozygote;House mice;Human;humanized mouse;Hyperplasia;Immune;Immune response;Immune system;Immunologics;Inbred Mouse;Inbred Strain;Individual;Induced Mutation;interest;Knockout Mice;male;Malignant Neoplasms;Maps;Measures;Mediating;Meiosis;Melanoma;Melanoma Cell;MHC Class I Genes;MHC Class II Genes;Minor;Missense Mutation;Mus;Mutagenesis;Mutagens;mutant;Mutant Strains Mice;Mutate;Mutation;Myelogenous;neoantigens;neoplastic cell;Nitrosourea Compounds;nonsynonymous mutation;novel;novel strategies;Nuclear;Nutritional;Patients;Peptides;Phenotype;Point Mutation;Population;prevent;Productivity;Proteins;Reaction;refractory cancer;Regulatory T-Lymphocyte;repository;Resistance;resistance allele;resistance mechanism;resistance mutation;RNA Splicing;Safety;screening;Screening for cancer;Site;Skin graft;stem;subcutaneous;synergism;T cell therapy;T-Lymphocyte;targeted cancer therapy;Testing;Therapeutic;therapeutic development;Thymus Gland;Transcript;Translating;translational applications;translational study;tumor;tumor growth;Tumor Volume;Vascularization;Work

PROJECT_TITLE: Cancer Resistant Mice

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Social Determinants of Health;Suicide

ORG_CITY: Rio de Janeiro

ORG_COUNTRY: BRAZIL

ORG_FIPS: BR

ORG_NAME: FUNDACAO OSWALDO CRUZ

PHR: PROJECT NARRATIVE Psychiatric disorders in youth are very difficult to predict and prevent but addressing the drivers of mental illness during the developmental phase of the life course offers a critically important opportunity to reduce the global burden of mental disorders in youth people and over the life course. In this project we will investigate social drivers, pathways and mechanisms through which a large cash transfer program is associated with better mental health outcomes among youth, thus attempting to reveal avenues for prevention, using an unprecedent cohort of over 100 million in Brazil. Results from this innovative project are expected to inform policymakers in ways of addressing the burden of mental illness through social protection programs for youth.

PI_NAMEs: MACHADO, DAIANE BORGES (contact)

PROGRAM_OFFICER_NAME: VEDHAM, VIDYA

PROJECT_TERMS: Achievement;Address;Adult;Affect;African;Age;aged;Alcohol consumption;Appointment;Behavior;Behavioral;beneficiary;Big Data;Black Populations;Brazil;Child;cohort;Communities;cost effectiveness;Country;COVID-19;COVID-19 pandemic effects;Data;Data Set;design;Development;Diagnosis;Disease;early life exposure;Economic Recession;Economics;Education;effective therapy;Effectiveness;Emotional;Equation;Equity;Ethnic Origin;experience;Exposure to;Family;Future;Gender;Health;Health care facility;health data;health disparity;Health Services;Health Services Accessibility;Healthcare;Hospitalization;Household;Improve Access;improved;improved outcome;Impulsivity;Incidence;Income;Individual;innovation;intergenerational;Intervention;Life;Life Cycle Stages;Link;Long-Term Effects;longitudinal dataset;low and middle-income countries;Low income;Mediator;meetings;Mental disorders;Mental Health;Methodology;Modeling;models and simulation;mortality;Municipalities;Neighborhoods;Notification;Outcome;pandemic disease;Pathway interactions;Persons;Phase;Policies;Policy Maker;Population;Poverty;Prevalence;prevent;Prevention;Program Effectiveness;programs;Qualifying;Race;reducing suicide;response;scale up;Schools;simulation;social;Social Change;Social Protection;social vulnerability;socioeconomics;Specific qualifier value;Subgroup;Suicide;Testing;Time;trend;United States;Violence;violence exposure;Vulnerable Populations;Woman;Youth

PROJECT_TITLE: The impact of social drivers, conditional cash transfers and their mechanisms on mental health of the young: an integrated retrospective and forecasting approach using the 100 million Brazilian Cohort


NIH_SPENDING_CATS: Autoimmune Disease;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Inflammatory Bowel Disease;Microbiome;Nutrition

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE Non-typhoidal Salmonella serotypes are a common cause diarrheal disease in the United States, with a cost of $0.5 to $2.3 billion per year due to lost productivity and the cost of medical care. This application will support studies on how Salmonella colonizes the mammalian intestinal tract and causes disease symptoms. A better understanding of the molecular mechanisms that influence bacterial colonization is expected to aid in the development of new intervention strategies.

PI_NAMEs: WINTER, SEBASTIAN E (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Acids;Acute;Address;Animal Disease Models;Animal Model;bacterial metabolism;Bacterial Model;Biochemical;Carbon;Cell Physiology;Citric Acid Cycle;Colitis;commensal bacteria;cost;Development;Diarrhea;diarrheal disease;Disease;Energy Metabolism;enteric pathogen;Environment;Epithelium;Equilibrium;Fumarates;Gastroenteritis;Genes;Genetic;Goals;Growth;gut colonization;gut inflammation;gut microbiota;Gut Mucosa;Immune response;Immunocompetent;In Vitro;in vivo;Individual;Infection;Inflammation;Inflammatory;Inflammatory Response;innovation;Intervention;Intestines;Isomerism;Large Intestine;Lead;Medical Care Costs;Metabolic;metabolic abnormality assessment;Metabolism;Methods;Microbe;microbial;microbiota;microbiota composition;migration;Modeling;Molecular;Mucous Membrane;murine colitis;Nature;neutrophil;Nitrogen;non-typhoidal Salmonella;novel;Nutritional;Operon;Organism;Oxidants;oxidation;Oxygen;pathogen;Pathogenesis;pathogenic bacteria;pathogenic microbe;Pathway interactions;Phase;Population;Productivity;rational design;Regulation;Repression;Research;Respiration;Salmonella;Salmonella enterica;Salmonella typhimurium;Serotyping;sugar;Symptoms;Tartrates;Testing;Time;Toxin;United States;Variant;Virulence;Virulence Factors;Work

PROJECT_TITLE: Central metabolism of Salmonella in the inflamed gut

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


ED_INST_TYPE: OVERALL MEDICAL

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: Inappropriately activated Ras lies at the center of more than a third of all tumors and the RASopathy spectrum of birth defects, yet Ras itself is relatively undruggable, with key partners and the contexts in which they are used poorly understood. This proposal seeks to understand the mechanisms of Ras effector switching and the role served by its neglected partners in diverse biological functions, using the invertebrate experimental animal C. elegans as a simple model to delineate molecular and cellular mechanisms. The long-term goal of this work is to define biomarkers and druggable targets for therapeutic interventions into birth defects and tumors.

PI_NAMEs: REINER, DAVID  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TITLE: Understanding Ras effector switching and roles of Ras>RalGEF>Ral in development

STUDY_SECTION: MRAC

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: ATHENS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Apramycin is an unusual aminoglycoside antibiotic with minimal oto- and nephrotoxicity and minimal susceptibility to common mechanisms of aminoglycoside resistance. As such it is currently in clinical trials in Europe and the USA under development for the treatment of multidrug-resistant bacterial infections. Nevertheless, resistance to apramycin is expected to eventually surface because of its susceptibility to a single isoform of an aminoglycoside modifying enzyme, the aminoacetyltransferase AAC(3)-IV. This proposal, through a combination of design, chemical synthesis, and antibacterial and antiribosomal screening, test the hypothesis that improved analogs of apramycin based on the streptamine core (as opposed to the existing 2-deoxystreptamine core) can be designed and prepared that overcome the inherent susceptibility to AAC(3)-IV without loss of the broad-spectrum activity or minimal toxicity of the parent.

PI_NAMEs: CRICH, DAVID  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: aminoglycoside acetyltransferase;Aminoglycoside Antibiotics;Aminoglycoside resistance;Aminoglycosides;analog;Anti-Bacterial Agents;Antibiotics;apramycin;Bacterial Infections;Biological Assay;carbapenem resistance;Carbapenem-resistant Acinetobacter;Cells;chemical synthesis;Chemistry;Clinical;clinical candidate;Clinical Trials;Communicable Diseases;Complex;Continuous Ambulatory Peritoneal Dialysis;Cytoplasm;design;Development;Engineering;Ensure;Enzyme-Linked Immunosorbent Assay;Enzymes;Epithelial Cells;Escherichia coli;Europe;Evaluation;experience;Feedback;Genes;glycosylation;Goals;Gram-Negative Bacteria;Hospitalization;Human;Hybrids;improved;in vivo;Incubated;Infection;Isoenzymes;Kidney;LCN2 gene;Literature;Measures;Methods;Methyltransferase;Microscopic;Mitochondria;Modification;Monitor;Multi-Drug Resistance;mutant;nephrotoxicity;novel;Organism;ototoxicity;Parents;pathogen;Positioning Attribute;Predisposition;Protein Biosynthesis;Protein Isoforms;Protein Synthesis Inhibition;Publishing;Rattus;Reaction;Recombinants;Resistance;resistance mechanism;Ribosomes;Route;screening;Series;Site;Structure;Surface;Testing;therapy development;Toxic effect;translation assay;Tubular formation

PROJECT_TITLE: Evaluation of Streptamine Analogs to Overcome Resistance to Apramycin

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DDR-C(01)]


NIH_SPENDING_CATS: Cancer;Genetics;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: Project Narrative: SMARCB1 (SNF5), a subunit of SWI/SNF chromatin remodeling complexes, is specifically mutated in nearly all cases of malignant rhabdoid tumor, a highly lethal cancer of early childhood. Recent studies have revealed that genes encoding SWI/SNF complex subunits are mutated in nearly 25% of all human cancers, demonstrating that investigations of SMARCB1 function have broad cancer relevance. The proposed studies are designed to determine the normal function of SMARCB1, to define the mechanisms by which SMARCB1 mutations cause cancer, and to explore novel approaches for circumventing therapeutic resistance in these aggressive cancers.

PI_NAMEs: ROBERTS, CHARLES  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: antagonist;ATP Hydrolysis;ATP phosphohydrolase;Automobile Driving;Binding;Biological;Bromodomain;cancer cell;Cancer cell line;Cancer Etiology;cancer predisposition;Cell division;Cell Fate Control;Cell Proliferation;Cells;Childhood;Chromatin;Chromatin Remodeling Factor;Chromatin Structure;Clinical Trials;Complex;CRISPR screen;Cues;Data;Dependence;design;Development;DNA;Drug resistance;early childhood;Enhancers;epigenetic memory;Epigenetic Process;Excision;EZH2 gene;Foundations;Funding;Genes;Genetic Transcription;Genetically Engineered Mouse;genome-wide;genomic locus;Genomics;Goals;head-to-head comparison;Hereditary Malignant Neoplasm;Heritability;Histone Acetylation;histone modification;Histone-Lysine N-Methyltransferase;Histones;Human;In Vitro;in vivo Model;inhibitor;innovation;insight;Interphase;Investigation;Link;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Memory;Mitosis;Mitotic;Modeling;Monitor;Mus;mutant;Mutate;Mutation;Normal Cell;novel;novel strategies;Nucleosomes;Oncogenic;Pathway interactions;Phenotype;Phosphorylation;Polycomb;promoter;Proteins;Regulation;Regulator Genes;Reporting;Repression;Repressor Proteins;Resistance;resistance mechanism;response;Rhabdoid Tumor;Role;Sarcoma;SMARCA4 gene;SMARCB1 gene;Specific qualifier value;SWI/SNF Family Complex;Syndrome;Testing;Therapeutic;therapy resistant;Transcriptional Activation;Transcriptional Regulation;tumor;Tumor Cell Line;Tumor Suppressor Proteins;tumorigenesis;virtual;Work

PROJECT_TITLE: The function of Snf5 (SMARCB1), an epigenetic tumor suppressor


NIH_SPENDING_CATS: Cancer;Skin Cancer

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The precise patterning of cells that make up most complex organisms relies on an ancient cellular communication strategy called the Hedgehog signaling pathway. This pathway is absolutely critical to the development of organisms as diverse as sea squirts to humans, and disruption in normal signaling causes many cancers. This research program will uncover the fundamental mechanism that enables cells to sense the Hedgehog signal, laying the foundation for the discovery of drugs for regenerative medicine and various cancers.

PI_NAMEs: MANGLIK, AASHISH  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Adult;antagonist;Basal cell carcinoma;Binding;Binding Sites;Biochemical;Biochemistry;Biophysics;Body System;Brain;Cells;Childhood;Cholesterol;Communication;Complex;Cryoelectron Microscopy;Data;design;Development;Erinaceidae;Extracellular Domain;Foundations;Genetic Transcription;hedgehog signal transduction;Human;In Vitro;inhibitor;insight;Integral Membrane Protein;Link;Lipid Binding;Lipids;Malignant Neoplasms;Mass Spectrum Analysis;Medulloblastoma;Membrane;Modeling;Molecular;Molecular Conformation;molecular dynamics;Mutagenesis;nanobodies;NMR Spectroscopy;Organism;Pathway interactions;Pattern;Pharmaceutical Preparations;Physiological;Predisposition;programs;Publishing;Regenerative Medicine;Regulation;Repression;Research;Resistance;resistance mechanism;Resolution;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Site;Skin Carcinoma;smoothened signaling pathway;Sterols;structural biology;Structure;Therapeutic;Tissues;Transmembrane Domain;tumor;Urochordata;X-Ray Crystallography

PROJECT_TITLE: Mechanisms of Smoothened Activation in Hedgehog Signaling

STUDY_SECTION: MIST

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


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Lung;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: ITHACA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative SARS-CoV2 is an ongoing global pandemic that targets the most vulnerable members of our society with persistent, overwhelming inflammation of the lungs that can eventually cause respiratory failure and death. However, the specific factors that act locally in the lungs to determine disease severity remain unknown. These studies will contribute powerful new tools to obtain clinically relevant information about macrophages, the predominant immune cells in SARS-CoV2 infection, including whether they prevent repair of lung damage during infection, and whether they may be potential drug targets to reduce disease severity and death in humans infected with SARS-CoV2.

PI_NAMEs: GLUDISH, DAVID W (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Alveolar;Alveolar Macrophages;Alveolus;Animal Model;Animals;Award;Behavior;Biological Assay;Biology;Body System;Boston;career;Cell Death;Cells;cellular targeting;Cessation of life;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;college;Communicable Diseases;Comparative Pathology;Coronavirus;COVID-19 severity;COVID-19 susceptibility;Cues;Cultured Cells;Discipline;Disease;Disease Progression;DNA;Drug Targeting;Engineering;Enterobacteria phage P1 Cre recombinase;Environment;epithelial repair;Epithelium;Faculty;Focal Infection;Functional disorder;Funding;Germ Lines;Growth;high throughput screening;Histologic;Histopathology;HIV;HIV/TB;Human;human model;Hyaluronan;Immune;Immunology;Impairment;improved;In Vitro;in vivo;Infection;Inflammation;interdisciplinary approach;interest;Interferons;Intervention;Investigation;Laboratories;Learning;Length;long-term sequelae;Longitudinal Studies;Lung;Lung Diseases;lung injury;lung pathogen;lung repair;Macrophage;Maps;Measures;medical schools;member;Mentors;Microbiology;Molecular;monocyte;mouse genetics;mouse model;Mus;Mycobacterium tuberculosis;Nature;Neutralization Tests;Neutralizing antibody assay;novel;Organ;Organoids;Outcome;Output;pandemic disease;Paramyxovirus;Pathogenicity;Pathologist;Pathology;Pediatric Hospitals;Peptide Hydrolases;Pharmaceutical Preparations;Phase;Phenotype;Physicians;pneumocyte;Positioning Attribute;post SARS-CoV-2 infection;Post-Acute Sequelae of SARS-CoV-2 Infection;post-doctoral training;Postdoctoral Fellow;Predisposition;prevent;Productivity;Proteins;Publishing;Pulmonary Inflammation;Pulmonary Pathology;Recovery;recruit;repaired;Replicon;Reporter;Reporting;Research;respiratory;Respiratory Failure;RNA;RNA-Directed RNA Polymerase;Route;SARS-CoV-2 infection;SARS-CoV-2 pathogenesis;Science;Scientist;Severity of illness;Societies;stem cell biology;Stimulus;System;tenure track;Testing;Therapeutic;Time;tool;Training;transcriptomics;Universities;vaccine discovery;Variant;Vero Cells;Veterinarians;Veterinary Anatomy;Veterinary Medicine;Viral;Viral Pathogenesis;Viral Proteins;viral RNA;Virion;virology;Virus;Virus Diseases;Virus Replication;Virus Shedding;Work

PROJECT_TITLE: Novel animal models to dissect how lung macrophages contribute to SARS-CoV2 alveolar pathology and respiratory failure


ED_INST_TYPE: HOSPITALS

ORG_CITY: HOUSTON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Project Narrative  Ferroptosis is an iron-dependent form of nonapoptotic cell death that is induced by excessive lipid peroxidation. The objectives of this application are to determine the mechanisms by which ferroptosis inactivation contributes to radioresistance in KEAP1-mutant lung cancer cells and to assess the combination of radiotherapy and ferroptosis inducers in treating KEAP-mutant lung cancers. Our proposed studies will have a significant impact on both our understanding of the fundamental mechanisms of ferroptosis and radiation biology and our ability to target ferroptosis-related radioresistance in cancer treatment.

PI_NAMEs: GAN, BOYI  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Antioxidants;Apoptosis;cancer therapy;Cell Death;Communities;comparative;Complement;CRISPR screen;Data;Development;effectiveness evaluation;Genetic;Genetic Transcription;Goals;Heart Injuries;Human;Immune system;inhibitor;innovation;Iron;Link;Lipid Peroxidation;lung cancer cell;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Medical;mouse model;mutant;Mutate;Mutation;Normal tissue morphology;novel;novel therapeutic intervention;Outcome;Pathway interactions;pre-clinical;Publications;radiation resistance;Radiation therapy;radiation-induced lung injury;Radiobiology;radioresistant;refractory cancer;Resistance;response;Role;Testing;therapeutically effective;Translating;Translations;tumor;Tumor Biology;tumor growth;Tumor Suppression

PROJECT_TITLE: Targeting ferroptosis in radioresistance in lung cancer: mechanisms and preclinical translation

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ORG_CITY: STANFORD

ORG_DEPT: BIOPHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: Narrative: The molecular principles governing how T cell receptors recognize and signal in response to peptide-MHC antigens have important applications in human health. We wish to exploit T cell receptor/peptide-MHC structure and binding chemistry to develop technologies for TCR ligand identification and TCR signal tuning that will have direct translational impact in cancer immunotherapy, autoimmunity and infectious disease.

PI_NAMEs: GARCIA, KENAN CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Adoptive Cell Transfers;Affinity;Agonist;Amino Acids;Ankylosing spondylitis;Antibodies;Antigens;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmunity;Binding;Biological Models;Biology;Blood;Bypass;cancer immunotherapy;Cancer Patient;cell killing;Cells;Chemistry;Clinic;clinical translation;Clinical Trials;Clone Cells;Communicable Diseases;Complex;cross reactivity;Development;Disease;Docking;Engineering;Exhibits;Experimental Models;Geometry;Health;HLA-B27 Antigen;Homeostasis;Human;Immune;Immune system;Immunotherapeutic agent;Immunotherapy;improved;insight;Libraries;Ligands;Malignant Neoplasms;MHC antigen;Modeling;Molecular;Mus;novel;novel strategies;Orphan;Pathogenicity;Patients;Peptide/MHC Complex;Peptides;Phase;Physiological;preservation;Property;Protein Engineering;Rapid screening;Reagent;receptor;Receptor Signaling;Refractory;Regulatory T-Lymphocyte;response;Role;screening;Signal Transduction;Source;Specificity;Structure;System;T-Cell Receptor;T-Lymphocyte;TCR Activation;Technology;Testing;Tissues;Toxic effect;translational impact;tumor;Vaccines;Validation;Yeasts

PROJECT_TITLE: Structural correlates of T cell receptor signaling

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: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Genetics;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: HERSHEY

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative Over 2 million people in the United States abuse opioids, and overdose deaths involving synthetic opioids are on the rise. Despite undergoing addiction treatment, many individuals continue to relapse, necessitating the development of new therapeutics and a deeper understanding of the underlying neurobiology. The current proposal will provide evidence for guiding novel treatments by investigating precise neuromolecular mechanisms in opioid addiction.

PI_NAMEs: FOX, MEGAN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: NAIR, SUNILA GOPI

PROJECT_TERMS: Abstinence;addiction;Attention;Automobile Driving;Award;Back;Behavior;Brain Diseases;bridge program;cell type;Complex;cost;Data;designer receptors exclusively activated by designer drugs;Development;Dopamine;Dopamine D1 Receptor;dopaminergic neuron;Drug abuse;Drug Addiction;Drug Exposure;drug of abuse;drug relapse;Drug usage;experience;Fentanyl;fentanyl seeking;fentanyl self-administration;fentanyl use;Fluorescent in Situ Hybridization;Funding;gamma-Aminobutyric Acid;Genetic;genetic manipulation;Genetic Transcription;health economics;Home;In Situ Hybridization;Incidence;Individual;insight;Intake;knock-down;Learning;Mentors;Molecular;Molecular Biology;Molecular Profiling;Molecular Target;mouse model;Mus;National Institute of Drug Abuse;Neurobiology;Neurons;novel;novel therapeutics;Nucleus Accumbens;Opiate Addiction;Opioid;opioid abuse;opioid mortality;Opioid Receptor;opioid use;overdose death;overexpression;Pathway interactions;Periodicity;Persons;Pharmaceutical Preparations;Phase;Physiological;Play;Postdoctoral Fellow;prescription opioid abuse;Procedures;programs;Relapse;Research;response;reward circuitry;Rewards;Ribosomes;RiboTag;Role;Scanning;Self Administration;Synapses;synthetic opioid;Testing;Therapeutic;tool;Training;training opportunity;transcriptome sequencing;Translating;translatome;United States;Ventral Tegmental Area;Viral;Virus;Work

PROJECT_TITLE: Circuit-specific molecular mechanisms in fentanyl use and relapse


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Tuberculosis;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: CITY OF INDUSTRY

ORG_NAME: PUBLIC HEALTH FOUNDATION ENTERPRISES

PHR: Project Narrative The San Francisco Bay Clinical Trials Unit will conduct HIV vaccine, prevention and treatment trials in San Francisco with a broad community engagement reach throughout the San Francisco Bay area. By bringing together leading scientists and a diverse community in the San Francisco Bay Area, this research unit will continue to develop ways to prevent and treat HIV infections and work towards an effective HIV vaccine, new pre-exposure prophylaxis agents, multipurpose prevention technologies, new TB therapies, and an HIV cure.

PI_NAMEs: BUCHBINDER, SUSAN  (contact);HAVLIR, DIANE V

PROJECT_TERMS: Adherence;Affect;AIDS clinical trial group;AIDS prevention;Anti-Retroviral Agents;Antibodies;Area;Automobile Driving;behavioral and social science;Behavioral Sciences;Black Populations;Caring;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;Communication;Communities;community engagement;data quality;design;Development;Disease remission;Drug user;efficacy trial;Enrollment;Ensure;Epidemic;Epidemiology;ethnic disparity;ethnic minority;experience;Generations;Goals;Grant;Grooming;Hepatitis;Hepatitis B;HIV;HIV diagnosis;HIV Infections;HIV vaccine;HIV Vaccine Trials Network;Home;improved;Infection;Inflammation;Infrastructure;Injectable;Injecting drug user;Journals;Latinx population;Leadership;Location;Manuscripts;men who have sex with men;Mentorship;neutralizing antibody;Output;Persons;Phase;Population;Population Heterogeneity;Positioning Attribute;pre-exposure prophylaxis;prevent;Prevention;Prevention Protocols;Prevention strategy;Prevention trial;Principal Investigator;Process;programs;Protocols documentation;Publications;racial disparity;racial minority;Records;recruit;Research;Research Infrastructure;Research Personnel;Role;Running;San Francisco;Science;Scientist;Site;social science research;Structure;Talents;Technology;Textiles;Training;training opportunity;transgender;Transportation;Treatment Protocols;treatment trial;Tuberculosis;tuberculosis treatment;Vaccine Research;vaccine trial;Vaccines;Vaginal Ring;Viral;Work;working group

PROJECT_TITLE: San Francisco Bay Clinical Trials Unit (CTU)


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative  We have recently shown that HIV-1 integrase (IN) enzyme binds to the viral RNA genome during virion maturation and ensures its proper encapsidation inside viral capsid lattice. Here we propose to unveil the molecular details of IN-RNA interactions, how IN binding to the viral genome ensures accurate placement of the genome within the capsid lattice and how infected cells sense and respond to viruses generated upon inhibition of IN-RNA interactions. This project will provide new knowledge about the key non-catalytic function of HIV-1 IN in virion maturation and help in the development of therapeutics that can complement integrase strand-transfer inhibitors that target the catalytic function of IN.

PI_NAMEs: KUTLUAY, SEBLA B. (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Anti-Retroviral Agents;Anti-viral Agents;Binding;Biochemical;Biological Assay;C-terminal;Capsid;Cells;Cementation;Clinical;Complement;Complex;CRISPR screen;Data;Defect;Dependence;Development;Distal;Drug resistance;Electron Microscopy;Electrostatics;empowerment;Ensure;Enzymes;Evolution;experimental study;Funding;Generations;Genome;Goals;Guide RNA;Highly Active Antiretroviral Therapy;HIV-1;Human Activities;In Vitro;inhibitor;Innate Immune Response;Integrase;Integrase Inhibitors;Kinetics;Knowledge;Life Cycle Stages;Location;Mediating;Molecular;Morphogenesis;Mutagenesis;mutant;Mutation;Nature;novel;Nucleic Acids;Nucleocapsid;Outcome;particle;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;physical separation;Play;premature;Publishing;Regulation;Reporting;Resistance;Reverse Transcription;RNA;RNA Binding;RNA Degradation;RNA Recognition Motif;RNA-Directed DNA Polymerase;Role;Sampling;Small Interfering RNA;Specificity;Testing;Therapeutic;therapeutic development;therapeutic target;tool;Vaccines;Variant;Viral;Viral Genome;viral RNA;Virion;Virus;Virus Replication;Work

PROJECT_TITLE: Regulation and Targeting of HIV-1 Integrase-RNA Interactions


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

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Stress alters reward processing and decision-making, increasing the risk of developing neuropsychiatric disorders. The fundamental mechanisms of stress-induced alterations remain poorly understood, but likely involve a disruption of dopamine system, which underlies many neuropsychiatric disorders. This study will provide mechanistic insights into stress-induced dysregulation of dopamine signaling and reward processing to speed the transition from basic research to more translational models of chronic stress and the development of novel treatments for stress-related disorders.

PI_NAMEs: OSTROUMOV, ALEXEY  (contact)

PROGRAM_OFFICER_NAME: VAZIRI, SIAVASH

PROJECT_TERMS: Acceleration;Action Potentials;acute stress;Affect;Anatomy;Anesthesia procedures;Animals;Anions;Association Learning;Attenuated;aversive conditioning;Basic Science;Behavior;Behavioral;Brain;Brain region;Chlorides;Chronic stress;Complex;Data;Decision Making;Desire for food;Development;Disinhibition;Dopamine;dopamine system;dopaminergic neuron;Down-Regulation;Electrophysiology (science);Exposure to;Fire - disasters;gamma-Aminobutyric Acid;Hyperactivity;Impairment;improved;Incentives;Individual;insight;Label;Lateral;Learning;Link;Measures;Medial;Mediating;Molecular;Motivation;neuroadaptation;neuronal excitability;Neurons;neuropsychiatric disorder;neurotransmission;novel;Nucleus Accumbens;optogenetics;Pathway interactions;Pattern;pharmacologic;Phase;Population Heterogeneity;Process;Psychological reinforcement;Psychopathology;Rat Transgene;Rattus;Receptor Activation;Regulation;response;reward circuitry;reward processing;Rewards;Risk;Risk Factors;Rodent;Role;signal processing;Signal Transduction;Specificity;Speed;Stimulus;Stress;stress related disorder;Stress Tests;synaptic inhibition;Synaptic plasticity;translational model;transmission process;Ventral Tegmental Area

PROJECT_TITLE: The Impact of Stress-induced KCC2 Downregulation on Mesolimbic Dopamine Signaling and Reward Processing

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;Lung

ORG_CITY: PHILADELPHIA

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative  Chronic rhinosinusitis affects up to 16% of the population in the United States and is among the most common reasons people seek medical attention. Solitary chemosensory cells (SCCs), akin to type II taste cells in the tongue (responsible for taste transduction) and tuft cells in the mouse gut (responsible for local inflammation) are enriched in the sinus epithelium in those with chronic rhinosinusitis with nasal polyps, however, little is known about their role in human mucosal inflammatory diseases. This proposal will characterize and identify taste and inflammatory pathways related to SCC differentiation and expansion in chronic rhinosinusitis and explore how SCC signaling through epithelial ion channels affects mucosal immune function, which may reveal novel therapeutic targets for the treatment of chronic rhinosinusitis.

PI_NAMEs: KOHANSKI, MICHAEL AARON (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: Address;Affect;Agonist;Airway Disease;airway inflammation;airway repair;anti-microbial peptide;Area;Asthma;Award;Basal Cell;Bioinformatics;Biology;biomarker validation;Bone Marrow;Brush Cell;Calcium Signaling;career;Cell Culture Techniques;Cell Differentiation process;Cell Physiology;Cells;channel blockers;chronic rhinosinusitis;clinical practice;cohort;Complex;Coupled;Cyclic AMP;Data;Defensins;Disease;Epithelial Cells;Epithelial Physiology;epithelial repair;Epithelium;experience;experimental study;Flow Cytometry;Foundations;Funding;Gene Expression;Gene Expression Profiling;Genes;Goals;GTP-Binding Proteins;Head and Neck Surgery;Helminths;Histopathology;Human;immune function;Immunity;Immunofluorescence Immunologic;Immunology;improved;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;injured;insight;interest;Interleukin-13;Intestines;Ion Channel;Knock-out;Knowledge;Lavage;Lentivirus;Ligands;Mechanics;Mediating;Medical;medical attention;medical schools;Membrane;Mentors;Mentorship;Modeling;Mouse Strains;Mucosal Immune Responses;Mucous Membrane;multidisciplinary;Mus;Nasal Polyps;new therapeutic target;Nose;Nose Diseases;novel;Observational Study;Otolaryngology;paracrine;Paracrine Communication;Pathway interactions;patient subsets;Patients;Pennsylvania;Persons;phenotypic biomarker;phosphoric diester hydrolase;Phosphotransferases;Physiological Processes;Polyps;Population;Potassium;Potassium Channel;professor;Property;Proteins;Protocols documentation;Pyroglyphidae;rat Gnat3 protein;Regulation;repaired;Research;Research Personnel;Resistance;respiratory;respiratory health;response;Role;Sampling;Sensory;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Sinus;skills;small hairpin RNA;Sorting;Stimulus;Surgical Management;Taste Buds;Taste Perception;taste transduction;Testing;Tissues;Tongue;Trachea;Training;transcription factor;transcriptome sequencing;TRPM5 gene;United States;Universities;Work;wound;wound closure;X Chromosome

PROJECT_TITLE: Solitary Chemosensory Cell Regulation of Airway Inflammation and Repair

STUDY_SECTION: MCBS

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF HOUSTON

PHR: NARRATIVE The rise of antibiotic tolerance is one of the most critical global public health threats of the 21st century. Bacterial persisters, which are reversible drug tolerant cells that have been observed in every bacterial species studied so far, contribute to this problem significantly. The eradication of persister cells could aid in curing recurrent and chronic infections; therefore, the main theme of this proposed study is to therapeutically challenge persister cells by exploring a global, self-digestion-mediated persister formation mechanism in bacterial species.

PI_NAMEs: ORMAN, MEHMET A. (contact)

PROJECT_TERMS: Address;Affective;Antibiotic susceptibility;Antibiotic Therapy;antibiotic tolerance;Antibiotics;ATP-Dependent Proteases;Bacteria;Biological Assay;Cell Density;Cells;Cellular biology;Cellular Stress;Chemicals;chronic infection;Clinical;Clinical Trials;clinically relevant;cohort;Communicable Diseases;Cyclic AMP;cystic fibrosis patients;Data;Development;Digestion;driving force;Drug resistance;Drug Tolerance;Electrons;Environment;Escherichia coli;Exposure to;extracellular;Fluorescence-Activated Cell Sorting;Gene Deletion;Goals;Green Fluorescent Proteins;Growth;Health;Hospitals;Hypoxia;Immune system;improved;in vivo;Infection;inhibitor;innovation;Investigation;Laboratories;Maps;Measurement;Mediating;Medical;Metabolic;Metabolism;metabolomics;Methods;Microbial Biofilms;microorganism;model organism;Modeling;Morbidity - disease rate;mortality;mouse model;mutant;non-genetic;novel;Nutrient;Nutrient Depletion;opportunistic pathogen;Outcome;overpopulation;Oxidation-Reduction;pathogenic bacteria;Pathogenicity;Pathway interactions;Patients;Peptide Hydrolases;persistent bacteria;Phase;Phenotype;Plasmids;Population;preclinical trial;prevent;Process;programs;prospective;protein degradation;Proteins;Pseudomonas aeruginosa;Public Health;Recurrence;recurrent infection;Recycling;repaired;Reporter;Research;Ribonucleases;RNA;RNA Degradation;Role;screening;Signal Transduction;Signal Transduction Pathway;small molecule libraries;Source;Stains;Starvation;Stress;Technology;Testing;Therapeutic;Toxin;transmission process;Variant

PROJECT_TITLE: Characterizing a Self-Digesting-Mediated Reversible Drug Tolerance Mechanism in Bacteria


ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: PROJECT NARRATIVE Our studies are aimed at the identification of innovative agents capable of antagonizing anti-apoptotic proteins Bfl-1 and Mcl-1, responsible for cancer cell resistance. We will optimize the novel, irreversible Bfl-1 and Mcl-1 agents that we have recently discovered, and subsequently we will use pharmacological studies to assess their potential anti-cancer activity against melanoma and leukemia.

PI_NAMEs: PELLECCHIA, MAURIZIO  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Affinity;antagonist;anti-cancer therapeutic;anticancer activity;Apoptosis;Apoptotic;BAX gene;BCL-2 Protein;BCL2 gene;BCL2L1 gene;BCL2L11 gene;BH3 Domain;BH3 peptide;Binding;cancer cell;Cancer cell line;cancer therapy;Cell Death;Cell Death Inhibition;cell injury;Cell Line;Cell Membrane Permeability;Cell Survival;Cells;chemotherapy;Chronic Lymphocytic Leukemia;clinically relevant;cytochrome c;design;Development;Disulfides;drug discovery;Family;Goals;Human;Immunotherapy;in vivo;Induction of Apoptosis;inhibitor;innovation;Laboratories;Lead;leukemia;Leukemic Cell;Lymphoma cell;MCL1 gene;Mediating;Melanoma;member;Methods;mitochondrial membrane;Mus;neoplastic cell;novel;Oncogenes;Outer Mitochondrial Membrane;overexpression;Peptides;pharmacologic;Pharmacology Study;PMAIP1 gene;preference;prevent;Primary Neoplasm;protein expression;Protein Family;protein protein interaction;Proteins;Radiation;Reporting;Research;Resistance;Role;Route;Sampling;Scheme;Sentinel;Signal Transduction;small molecule;Specificity;Structure;Structure-Activity Relationship;Surface;targeted agent;Therapeutic;therapeutic target;tool;Tumor Cell Line;Visit

PROJECT_TITLE: Mcl-1/Bfl-1 in apoptosis and signal transduction: a structure/function approach

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


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

ORG_CITY: CLEVELAND

ORG_DEPT: DERMATOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Candida auris has emerged as a global threat causing serious invasive infections worldwide with mortality approaching nearly 60 percent. Because C. auris colonizes the skin and acts as a nidus of infection, developing therapies that can concurrently target skin and exhibit systemic efficacy will be highly innovative and desirable. Recently, a new class of antifungals termed fungerps have been developed, and a second-generation fungerp-SCY-247 is under development as a potential systemic therapeutic option for Candida infection; we propose to investigate whether SCY-247 will exhibit differentiating fungicidal properties including the ability to cross the BBB and work systemically, and as an effective cutaneous treatment for C. auris.

PI_NAMEs: GHANNOUM, MAHMOUD A (contact);MCCORMICK, THOMAS S

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, SUMAN

PROJECT_TERMS: 5 year old;adaptive immune response;Address;Affect;Amphotericin B;Animals;anti-fungal agents;Antifungal Therapy;antimicrobial;Azoles;Blood - brain barrier anatomy;blood-brain barrier crossing;blood-brain barrier penetration;Brain;Cancer Patient;Candida;Candida albicans;Candida auris;Candida glabrata;Centers for Disease Control and Prevention (U.S.);Central Nervous System Infections;Classification;Clinical;Collection;comparative efficacy;cranium;Cutaneous;Data;Death Rate;design;Development;Disseminated candidiasis;Dose;Drug Kinetics;efficacy evaluation;Evaluation;Exhibits;Fermentation;Fluconazole resistance;Flucytosine;Fungal Meningitis;fungicide;Generations;Geographic Locations;guinea pig model;hemiacetal;Immunocompromised Host;improved outcome;In Vitro;in vivo;Individual;Infection;Injections;Innate Immune Response;innovation;insight;intravital microscopy;Kidney Failure;Label;Marketing;member;Methods;Modality;Modeling;Monitor;mortality;mouse model;Mucous Membrane;Mycoses;Nosocomial Infections;novel therapeutics;Oral;Oral Examination;pathogen;Pathogenicity;Patients;Pharmaceutical Preparations;Phase I Clinical Trials;Polyenes;Pre-Clinical Model;preclinical study;Predisposition;Property;Protocols documentation;Public Health;Reporting;Resistance;Resistant candida;resistant strain;Resolution;screening;Sepsis;Skin;Skin colonization;standard of care;Terpenes;Testing;Therapeutic;therapy development;Toxicology;transmission process;Transplant Recipients;Work

PROJECT_TITLE: Development and evaluation of a second-generation fungerp for systemic and cutaneous C. auris infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-B(83)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Mental Health;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE  Cognitive decline is a growing global health concern due to unprecedented increases in the aging population. This proposal will test whether certain neural “hubs” may play unique roles in cognitive functions and treatment outcomes in Parkinson’s disease, a major risk factor for dementia. Studying the effects of Parkinson’s disease on white matter integrity related to cognition will generate clinically useful insights into the subtype, prognosis, and pathophysiology of cognitive decline.

PI_NAMEs: BROWN, GREGORY L (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Accounting;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Attention;Attentional deficit;Basal Ganglia;Benign;Brain;Brain region;career;Clinical;Cognition;Cognitive;cognitive change;Cognitive deficits;cognitive function;cognitive performance;Cognitive Therapy;cohort;Corpus striatum structure;cost effective;Data;Data Set;Dedications;Deep Brain Stimulation;demented;Dementia;dementia risk;Development;Diffusion;Digit structure;Disease;Engineering;Environment;Equipment;Exhibits;extend lifespan;Extracellular Space;Fiber;follow-up;Foundations;Functional disorder;Future;global health;healthy aging;Hippocampus;Impaired cognition;improved;Incidence;insight;Institution;Investigation;Knowledge;Levodopa;Longitudinal cohort;Magnetic Resonance Imaging;Measures;Memory;memory recall;Mentors;motor disorder;neural;neural circuit;Neurocognitive;Neurodegenerative Disorders;neuroimaging;Neuropsychological Tests;Neurosciences;novel;Outcome;Parietal;Parkinson Disease;Pathology;Patients;Pattern;Pharmaceutical Preparations;Physicians;Play;Population;Positioning Attribute;Process;profiles in patients;Prognosis;progression marker;Public Health;Recording of previous events;Research;Research Subjects;Resources;response;Role;Short-Term Memory;skills;Syndrome;Techniques;Technology;Testing;Therapeutic;tractography;Training;Treatment outcome;treatment response;treatment strategy;Visuospatial;Water;white matter;white matter damage

PROJECT_TITLE: The Striatum and Hippocampus: "Hubs" of White Matter Connections in Parkinson's Disease Cognitive Decline


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Maternal Health;Orphan Drug;Patient Safety;Pediatric;Prevention;Rare Diseases;Tuberculosis;Women's Health Research

ORG_CITY: PORT-AU-PRINCE

ORG_COUNTRY: HAITI

ORG_FIPS: HA

ORG_NAME: GHESKIO CENTER

PHR: Project Narrative: GHESKIO is a Haitian organization dedicated to research, service, and training in HIV/AIDS with a 37 year track record of NIH-funded clinical research. The GHESKIO Clinical Trials Unit has two clinical research sites in Port au Prince and will conduct research in two NIAID networks: The adult HIV/AIDS therapeutic clinical trials group and the maternal-adolescent-pediatric HIV/AIDS trials group. The goal is to improve the treatment of HIV, tuberculosis, and HIV complications across the lifespan in pregnant women, adolescents, children, and adults of all ages in Haiti and around the world.

PI_NAMEs: PAPE, JEAN WILLIAM (contact)

PROGRAM_OFFICER_NAME: SOUTHARD, COURTNEY MEAGAN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adherence;Adolescent;Adult;Age;Anti-Retroviral Agents;Antibody Therapy;antiretroviral therapy;bactericide;Cardiovascular Diseases;Cardiovascular system;Caring;Child;Childhood;Chronic;Chronic Disease;Clinic;Clinical Research;clinical research site;Clinical Trials Cooperative Group;Clinical Trials Unit;co-infection;cohort;Communication;Communities;community intervention;data management;Dedications;Development;Dietary Intervention;Disease remission;Drug Kinetics;Drug resistance;Drug resistance in tuberculosis;Early treatment;effectiveness trial;Enrollment;Evaluation;experience;Family;Female;Funding;Goals;Growth;Haiti;Haitian;HIV;HIV-infected adolescents;HIV/AIDS;HIV/TB;Hospitals;hypertension control;Immunity;improved;Infant;Inpatients;International Maternal Pediatric Adolescent AIDS Clinical Trials;Intervention;isoniazid;Isoniazid resistance;Laboratories;Laboratory Research;Lead;life span;male;Maternal-Child Health Centers;Multidrug-Resistant Tuberculosis;National Institute of Allergy and Infectious Disease;neonatal infection;Neurologic;Newborn Infant;novel;Participant;patient population;Patients;pediatric human immunodeficiency virus;pediatrician;Pharmaceutical Preparations;Pharmacy facility;Phase;Population;Pregnant Women;Prevalence;prevent;programs;Prophylactic treatment;Prostitution;recruit;Regimen;Research;Research Infrastructure;Research Personnel;Research Priority;rifapentine;Safety;safety study;Services;Site;Slum;Therapeutic;Therapeutic Clinical Trial;Therapeutic Trials;Training;Training Programs;treatment optimization;treatment trial;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Tuberculosis Vaccines;United States National Institutes of Health;Viral;Vulnerable Populations

PROJECT_TITLE: GHESKIO Clinical Trials Unit


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases;Tuberculosis

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

PHR: Project Narrative This proposal investigates how the bacterium that causes tuberculosis (TB) in humans, Mycobacterium tuberculosis, has the unique ability to evade being killed by our immune system and is able to persist for long periods of time in its host as a latent infection. Latent infections can be reactivated—especially in the immune compromised—to the highly contagious, active form of TB and accelerate spread of the disease. Therefore, it is important to understand how latent tuberculosis develops and how it becomes reactivated because globally the number of deaths caused by M. tuberculosis now exceeds those caused by the HIV/AIDS virus.

PI_NAMEs: WOYCHIK, NANCY ANN (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, KAREN A

PROJECT_TERMS: Acceleration;anti-toxin;antimicrobial;assault;Bacteria;Bioinformatics;Biological;Biology;Biotin;Cause of Death;cell growth;Cells;Characteristics;Chemicals;Chemistry;Computational Biology;Consensus Sequence;Data;design;Detection;Disease;Endoribonucleases;Exhibits;Exposure to;Family;Family member;Genes;Genetic;genome-wide;Goals;Growth;Harvest;HIV;HIV/AIDS;Human;Immune;Immune response;Immune system;improved;Individual;insight;Knowledge;Laboratories;latent infection;M. tuberculosis genome;Macrophage;Mass Spectrum Analysis;Mediating;member;Metabolic;metabolic rate;Molecular;multidisciplinary;Mycobacterium tuberculosis;National Institute of Allergy and Infectious Disease;novel therapeutics;Operon;Organism;Physiologic Monitoring;Physiological;Physiology;prevent;Protein Biosynthesis;protein complex;Proteins;Proteome;Research;response;Ribosomal RNA;RNA;Role;Signal Transduction;Site;Specificity;Strategic Planning;Stress;System;Technology;Testing;Therapeutic;Time;tool;Toxin;transcriptome;transcriptome sequencing;Transfer RNA;Tuberculosis;Validation;Work

PROJECT_TITLE: Transcriptome and proteome remodeling by Mycobacterium tuberculosis MazF toxins


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SALT LAKE CITY

ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

ORG_STATE: UT

PHR: Diabetes Mellitus (DM) is a global epidemic and heart failure (HF) is the leading cause of death in diabetics. The prevalence of DM in US veterans is higher than their civilian counterparts. Cardiac metabolism is central in the pathophysiology of both DM and HF but our understanding of the metabolic adaptations when they coexist is very limited. HF patients with DM undergoing therapy with left ventricular assist devices (LVAD) present a unique opportunity, as human cardiac tissue and serum become available, both before and after intervention. These samples become extremely more informative when we prospectively associate cardiac recovery with molecular/metabolic changes while on LVAD support. Using the novel and powerful method of non-radioactive 13C metabolic flux studies we will interrogate the dynamic cardiac metabolism and associated mechanisms implicated in myocardial recovery in human HF with DM.

PI_NAMEs: DRAKOS, STAVROS GEORGE (contact)

PROJECT_TERMS: Animal Model;beta-Hydroxybutyrate;Carbon;Cardiac;Cardiovascular system;Cause of Death;Cessation of life;Circulation;Citric Acid Cycle;Clinical;Clinical Trials;complex chronic conditions;Congestive Heart Failure;Data;Development;Diabetes Mellitus;diabetic;Disease;Epidemic;Event;fatty acid oxidation;flexibility;Functional disorder;functional improvement;Gene Expression;Gene Expression Profiling;General Population;Glucose;glucose uptake;Heart;Heart failure;heart function;heart metabolism;Heart-Assist Devices;Homeostasis;Hospitalization;Human;human model;Impairment;implantation;improved;improved outcome;in vivo;indexing;Infusion procedures;inhibitor;insight;Intervention;ketogenesis;Ketones;Label;left ventricular assist device;Left Ventricular Ejection Fraction;Link;Lipolysis;Liver;Metabolic;Metabolism;Methods;Molecular;Mus;Myocardial;Myocardial tissue;Myocardium;NADP;new therapeutic target;non-diabetic;novel;novel strategies;Outcome;oxidation;Oxidation-Reduction;Pathway interactions;Patients;Pentosephosphates;Pharmaceutical Preparations;Plasma;Population;Prevalence;Production;Prognosis;prospective;protein expression;Pyruvate;Recovery;Reporting;restoration;Risk;Role;Sampling;Serum;Sodium;Source;Stable Isotope Labeling;Structure;symporter;Testing;Therapeutic Intervention;Tissues;Tracer;Up-Regulation;uptake;Veterans

PROJECT_TITLE: Understanding Myocardial Recovery in Diabetes and Heart Failure


ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: It is estimated that up to 20% of young veterans have had a traumatic brain injury (TBI), yet little is known about the impact of TBI over the long term. This project aims to utilize medical information obtained through VA medical centers to investigate the long-term effects of TBI. We have assembled a database of nearly 2 million veterans (including all veterans with a TBI), and plan to expand and use this resource to study various TBI outcomes such as neurodegenerative disease and mental health diagnoses. We also plan to develop models that will guide clinicians toward better care and prevention of TBI associated outcomes. This line of investigation is vital not only to anticipate and plan for individual, VA, and U.S. public health burden from military-service related problems, but also to inform VA and other healthcare systems about how to best use resources and target interventions to improve the care of veterans and to reduce the risk of long-term consequences.

PI_NAMEs: YAFFE, KRISTINE  (contact)

PROJECT_TERMS: adverse outcome;Age;Brain Injuries;care systems;Caring;Characteristics;Chronic;Clinical;clinical care;Collaborations;comorbidity;Complex;cost;Data;Data Pooling;data repository;Data Set;Data Sources;Databases;Dementia;dementia risk;Diagnosis;early onset;epidemiology study;Ethnic Origin;Evolution;follow-up;Gender;Goals;health care service utilization;Healthcare Systems;Image;improved;Individual;Intervention;Investigation;Long-Term Effects;longitudinal course;Medical;Medical center;Mental Health;mild traumatic brain injury;Military Personnel;military service;Modeling;mortality;Nerve Degeneration;Nervous System Trauma;Neurodegenerative Disorders;neurosensory;novel;Outcome;Patients;Pharmaceutical Preparations;Phenotype;physical conditioning;Positioning Attribute;Post-Traumatic Stress Disorders;Prevention;prognostic model;prognostication;prospective;Public Health;Race;repository;Research Personnel;resilience;Resources;Risk;Risk Factors;Risk Reduction;risk stratification;Socioeconomic Status;Subgroup;Substance abuse problem;Time;tool;Translating;Traumatic Brain Injury;Update;Veterans;Work

PROJECT_TITLE: VA-DoD Long-Term Impact of Military-Relevant Brain Injury Consortium (LIMBIC): Epidemiology Study

STUDY_SECTION: RRDB

STUDY_SECTION_NAME: Brain Injury[RRDB]


PHR: Project Narrative This project investigates the role of a novel receptor that is selectively expressed on CD8+ T cells with rapid innate-like functions. The obtained results may allow us to better predict vaccine outcomes and develop more effective strategies to enhance immunity against infection.

PI_NAMEs: GRIMSON, ANDREW W;RUDD, BRIAN DAVID (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adopted;Adult;aged;Antigens;B-Lymphocytes;Behavior;Bone Marrow;Cattle;CD6 antigen;CD8-Positive T-Lymphocytes;Cell Compartmentation;Cells;Complex;crosslink;Cues;Data;Development;Environment;Extracellular Domain;Family suidae;fetal;Fetal Liver;fetus cell;Genes;Hematopoietic stem cells;Immune system;Immunity;Immunology;Impairment;Infection;Inflammation;Injections;innovation;interest;Life;Ligand Binding;Link;Maps;mature animal;Mediating;member;Memory;Modeling;mouse model;Mus;Neonatal;novel;pathogen;Pathway interactions;Pattern;Peripheral;Phenotype;Play;Population;protein protein interaction;Proteins;Publishing;Reagent;receptor;Reporter;Research;response;Role;scavenger receptor;selective expression;Sheep;Signal Transduction;SRCR proteins;System;T cell differentiation;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;Thymus Gland;tool;transcriptomic profiling;vaccination outcome;Vaccines;Work

PROJECT_TITLE: The role of CD163L1 in CD8+ T cells

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


FUNDING_MECHANISM: OTHERS

ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

PHR: NARRATIVE Dr. Haghighi's genomics research focuses on how environmental signals or insults are interpreted by the genome through epigenetics. Epigenetics is the bridge connecting the environment and genetics, regulating gene expression and cellular response to environmental cues throughout our lifespan. Specifically, she is interested in how physical and/or psychosocial stress throughout the lifespan can induce epigenetic abnormalities leading to neuropathological and psychiatric symptoms. Traumatic brain injury represents a physical stress, and psychosocial stressors often precipitate depression and heightened suicide risk. Using both animal and human studies, she investigates the role of such stressors using genomics approaches to identify the underlying molecular mechanisms in such disorders. Her successes in building productive collaborations within the VA Health System and the Department of Defense to support our TBI and suicide genomics research programs demonstrates Dr. Haghighi's continued leadership capabilities in building a strong suicide clinical and research program at the VA.

PI_NAMEs: HAGHIGHI, FATEMEH G (contact)

PROJECT_TERMS: Acute;Affect;American;Animals;Anxiety;Area;Automobile Driving;Autopsy;Award;Big Data;Biological;Biological Assay;Biological Markers;blast exposure;Blindness;Blood - brain barrier anatomy;Brain;Brain region;career;Cause of Death;Cerebellum;Cessation of life;Childhood;Chronic;Chronic stress;Clinical;Clinical Research;Cognitive deficits;Collaborations;combat;Complex;Computer Models;Computing Methodologies;Cues;Data;Department of Defense;Development;Disease;DNA analysis;DNA mapping;DNA Methylation;DNA methylation profiling;Doctor's Degree;early onset;Environment;Environmental Exposure;Environmental Risk Factor;Epigenetic Process;epigenome;Etiology;Exhibits;Exposure to;Funding;gene environment interaction;Gene Expression;Generations;Genes;Genetic;Genetic Diseases;Genetic study;Genetic Transcription;Genome;genome-wide;Genomic approach;Genomics;Health system;Healthcare;Human;Immunity;Incidence;Individual;Inflammatory;Injury;insight;interest;Investigation;Journals;Laboratories;Large-Scale Sequencing;Leadership;life span;machine learning algorithm;Macular degeneration;mammalian genome;Medical;Medical center;medical specialties;Mental Depression;Mental disorders;Methods;Methylation;methylation pattern;mild traumatic brain injury;Military Personnel;military veteran;Molecular;Molecular Profiling;Nature;Neocortex;neuroinflammation;Neurons;neuropathology;neuropsychiatric disorder;Physician Executives;Post-Traumatic Stress Disorders;Prefrontal Cortex;Productivity;programs;Proteomics;psychiatric symptom;Psychiatric therapeutic procedure;Psychosocial Stress;psychosocial stressors;Publications;Publishing;Research;Research Personnel;response;Risk Factors;Rodent;Role;Sampling;Science;Scientist;Seminal;Signal Transduction;Sleep disturbances;Stargardt's disease;Statistical Models;stem;Stress;stressor;success;suicidal;suicidal behavior;suicidal risk;Suicide;suicide brain;suicide victim;Symptoms;Technology;Tissues;transcriptome sequencing;transcriptomics;Traumatic Brain Injury;United States;United States National Institutes of Health;Universities;Veterans;whole genome;Work

PROJECT_TITLE: CSR&D Research Career Scientist Award Application


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Prostate cancer is the most common cancer of Veterans and will take the lives of 1 in 41 men. Each of these tumors is driven by a unique combination of mutations of inherited as well as non-inherited origin. Precision oncology identifies these drivers in order to exactly target the most effective therapy available. The drivers are diverse and can also reveal cancer risks in the family, often unanticipated. Inherited drivers occur more often among men with a family history of prostate cancer and men with metastatic prostate cancer. Although prostate cancer has greater heritable risk than any other common cancer, its broad diversity has also proven to be a formidable obstacle for traditional family-based study to reveal its inherited causes. The knowledge base for decision-making in precision care of prostate cancer remains very limiting. This study uses a novel design to investigate men with familial prostate cancer in order to further build this knowledge base for the care of Veterans.

PI_NAMEs: SMITH, JEFFREY R. (contact)

PROJECT_TERMS: Affect;Age;Aggressive course;Algorithms;Alleles;biobank;Breast;Breast Cancer Detection;cancer care;cancer genetics;cancer risk;Caring;case control;Case/Control Studies;causal variant;Clinical;clinical predictive model;clinical predictors;Data;Data Set;Death Rate;Decision Making;design;Diagnosis;Disease;disorder risk;Distant;DNA;early onset;effective therapy;Environmental Exposure;Familial disease;Familial prostate cancer;Family;Family history of;Foundations;Gene Frequency;Genes;Genetic;Genetic Heterogeneity;Genetic Models;genetic pedigree;Genetic Population Study;genetic testing;genetic variant;genome wide association study;genome-wide;genomic locus;Genomic Segment;Germ Lines;Germ-Line Mutation;Goals;Guidelines;Haplotypes;Hereditary Malignant Neoplasm;Heritability;Heterogeneity;Heterozygote;high risk;identity by descent;improved;Individual;Inherited;innovation;International;Investigation;knowledge base;Linkage Disequilibrium;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;man;Maps;meetings;men;Metastatic Prostate Cancer;Modeling;Mutation;mutation carrier;National Comprehensive Cancer Network;novel;Oncology;Onset of illness;Pathogenicity;Patients;Pattern;personalized care;precision oncology;Precision therapeutics;predictive tools;prognostic;prostate cancer risk;protective allele;Recording of previous events;Research;Research Design;Risk;risk prediction model;risk variant;segregation;Sentinel;Signal Transduction;standard of care;study population;Subgroup;Therapeutic;Trans-Omics for Precision Medicine;tumor;Variant;Veterans;whole genome

PROJECT_TITLE: The Genetic Origin of Hereditary Prostate Cancer


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Arterial stiffness is linked to hypertension, poor BP control, and cardiovascular disease (CVD) events. Many older Veterans have suboptimally controlled blood pressure, in part because of inconsistent guideline recommendations for BP treatment goals and fear of side-effects from pharmacotherapy. Exercise and administration of sublingual nitroglycerin acutely alter arterial stiffness. We hypothesize that arterial reserve, determined by change in arterial stiffness measures following acute exercise or administration of sublingual nitroglycerin, will be greater in those with controlled blood pressure than in those with poorly controlled blood pressure or those without high blood pressure. A non-invasive arterial stress test that evaluates dynamic arterial stiffness in older hypertensive Veterans could determine who will better tolerate more aggressive BP goals, minimizing CVD events with fewer adverse side-effects.

PI_NAMEs: GEPNER, ADAM D (contact)

PROJECT_TERMS: Activities of Daily Living;Acute;Age;age related;Aging;aging related;Anti-Hypertensive Agents;arterial stiffness;Arteries;Biological Markers;Biomechanics;Blood flow;Blood Pressure;blood pressure control;blood pressure medication;blood pressure reduction;Blood Vessels;Cardiology;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;care coordination;career;Caring;Cessation of life;Cladribine;Clinical Research;Clinical Trials Design;Collaborations;Collagen;Communities;Control Groups;cooking;Cross-Sectional Studies;Data;Deposition;Diagnosis;Educational Curriculum;Elastin;Elderly;Endothelium;Event;Exercise;exercise capacity;Exercise Physiology;Fright;Functional disorder;Funding;Future;Geriatrics;Goals;Guidelines;Health system;Home;Human;Hypertension;hypertension control;hypertension treatment;hypertensive;improved;Individual;Injury;Intervention;Knowledge;Laboratories;Link;Liquid substance;Measures;Mechanics;Mentors;Mentorship;Multi-Ethnic Study of Atherosclerosis;multidisciplinary;Myocardial Infarction;National Heart, Lung, and Blood Institute;Nature;Nitroglycerin;normal aging;novel;older adult;older patient;Older Population;overtreatment;Participant;Pathology;Patients;Pattern;Pharmaceutical Preparations;Pharmacology Study;Pharmacotherapy;Physical Function;Physiology;Polypharmacy;primary care clinic;Property;Prospective Studies;Quality of life;randomized, clinical trials;Recommendation;recruit;Regimen;Reproducibility;Research;Research Personnel;response;Rest;Risk;Scientist;sex;side effect;skills;Specialist;Stress;Stress Tests;Stroke;Structure;Sublingual drug administration;System;Techniques;telehealth;Testing;tool;Training;Training Activity;Vasodilator Agents;Veterans;Wages

PROJECT_TITLE: Assessing Functional Arterial Stiffness in Older Hypertensive Veterans


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Pediatric;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Pertussis, caused by Bordetella pertussis, is a serious respiratory disease that has re-emerged in epidemic form in recent years. In this project we will investigate how a host response to infection by B. pertussis affects disease outcomes in infant mouse models. This will identify potential therapeutic targets that will help in the treatment of pertussis and potentially save the lives of infected infants.

PI_NAMEs: CARBONETTI, NICHOLAS H (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Admission activity;Adolescent;Adult;Affect;Age;age group;age related;Animal Model;Bacterial Infections;Biology;Bordetella pertussis;Cessation of life;Coughing;cytokine;Data;Disease;Disease Outcome;Dose;effective therapy;Epidemic;Gene Expression;Hospitalization;Human;Immune response;immunodeficiency;Infant;infant infection;Infant Mortality;Infection;Inflammation;Inflammatory;Interferon Receptor;Interferon Type II;Interferons;Knockout Mice;Leukocytosis;Lung;Modeling;mouse model;Mus;Nature;novel;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Pathology;Pathway interactions;Pediatric Intensive Care Units;Pertussis;Phase;Play;Predisposition;protective effect;Pulmonary Hypertension;receptor;Resistance;Respiratory Disease;Respiratory Signs and Symptoms;response;Role;Signal Pathway;Signal Transduction;Systemic disease;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;transcriptome sequencing;transcriptomics;Vaccination;Viral;Wild Type Mouse

PROJECT_TITLE: Age-dependent role of interferon lambda in protection against pertussis lethality in infants

STUDY_SECTION: HIBP

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


NIH_SPENDING_CATS: Hematology;Infectious Diseases;Sepsis

PHR: The metabolism of anti-microbial white blood cells called macrophages can become dysregulated during infection, leading to sepsis, a severe disease that can be fatal. Our proposed study seeks to identify the underlying mechanism for the metabolic changes associated with sepsis so that new drugs can be developed that normalize the host response to infection.

PI_NAMEs: PRANTNER, DANIEL JOSEPH;VOGEL, STEFANIE N. (contact)

PROJECT_TERMS: Acute;adduct;Aerobic;aerobic glycolysis;Aldehyde Reductase;antimicrobial;Automobile Driving;Bacteremia;Biological Markers;Cell Respiration;Cells;Cessation of life;Chronic;Complex;cytokine;Data;Disease;Drug Metabolic Detoxication;Electron Transport Complex III;Enzymes;evidence base;Exhibits;Fatality rate;functional plasticity;Genes;glucose transport;glycation;Glycolysis;Goals;Hyperglycemia;Hypoxia;Immune response;Impairment;In Vitro;in vivo;Infection;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inorganic phosphate;Interferon Type II;Interferons;Invaded;Isomerase;Lactoylglutathione Lyase;Leukocytes;Lipids;Lipopolysaccharides;Lung;Macrophage;Mediating;Mediator;Metabolic;Metabolism;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Mitochondrial Proteins;Modeling;Mus;new therapeutic target;novel;novel therapeutics;overexpression;Oxidative Phosphorylation;Oxygen;pathogen;Patients;Peptide Hydrolases;Phase;Phenotype;prevent;Production;programs;Proteins;Pyruvaldehyde;Reaction;Reactive Oxygen Species;Reporting;response;Role;Secondary to;Sepsis;septic patients;Septic Shock;Serum;Severity of illness;Signal Pathway;Signal Transduction Pathway;Stimulus;Stress;Testing;Therapeutic;therapeutic evaluation;Tissues;transcription factor;Translating;Treatment Efficacy;Warburg Effect

PROJECT_TITLE: Methylglyoxal-induced macrophage metabolic dysregulation in sepsis

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


ORG_CITY: CHAMPAIGN

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative Staphylococci are leading causes of antibiotic-resistant infections acquired in both healthcare and community settings. The viruses that infect these bacteria (staphylococcal phages) and the immune systems targeted against them have profound and contrasting impacts on staphylococcal survival and pathogenic potential. The proposed research will identify and characterize previously unknown immune systems in staphylococci as well as mechanisms by which these and other defenses spread, thereby enabling the development of more effective therapeutics and improved healthcare outcomes.

PI_NAMEs: HATOUM, ASMA  (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;Bacteria;Bacteriophages;Binding Sites;Biochemical;Bioinformatics;care outcomes;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;combat;community setting;Development;Distal;Effectiveness;Environmental Risk Factor;Excision;fitness;Genes;Genetic;genetic approach;Genetic Recombination;Genome;Genomic Islands;genomic locus;Genomic Segment;Genomics;Genus staphylococcus;Goals;health care settings;helicase;Horizontal Gene Transfer;Human;Immune system;Immunity;improved;Infection;Infectious Skin Diseases;Innate Immune System;insight;Knowledge;Light;Lytic;Maps;Mediating;Medical Device;Methicillin Resistance;model organism;Molecular;novel;nuclease;Operon;Organism;overexpression;Pathogenesis;Pathogenicity;Pathogenicity Island;Pathway interactions;recombinase;Regulon;Research;Site;Skin;skin microbiome;Soft Tissue Infections;Source;Staphylococcus aureus;Staphylococcus epidermidis;Staphylococcus Phages;stem;System;Testing;Therapeutic;therapeutically effective;Toxin;Virulence;Virulence Factors;Virus;Work

PROJECT_TITLE: Mechanisms of anti-phage defenses and their mobilization in staphylococci

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


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

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative Age related vitamin B1 (thiamine) insufficiency and subsequent hypometabolism can promote debilitating neurotoxicity and hallmarks of Alzheimer’s disease pathology. This application proposes to better understand the mechanism initiating neurological damage as a consequence of thiamine insufficiency. The proposed research is relevant to public health and the NIH’s mission, because it is expected to increase our understanding of age-related neurodegeneration from a nutritional and etiological prospective and will set the foundation for therapeutic approaches that limit progression and maintain cognitive health.

PI_NAMEs: ZASTRE, JASON A (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;AD transgenic mice;Address;age related;age related changes;age related neurodegeneration;Age-associated memory impairment;alcohol use disorder;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Apoptotic;Astrocytes;Attenuated;Autopsy;beta secretase;beta-site APP cleaving enzyme 1;Bioenergetics;biological adaptation to stress;Blood;Brain;cell injury;cell type;Cells;Cerebrum;Chronic;chronic alcohol ingestion;Coenzymes;cofactor;Cognitive;cognitive function;Coupled;Cre driver;Dementia;Deterioration;Diabetes Mellitus;Disease;Energy Metabolism;Ensure;Enzymes;Etiology;Foundations;Future;Gene Expression;Genes;Genetic Transcription;glucose metabolism;Goals;Grant;Health;Hippocampus;Histologic;hypoxia inducible factor 1;Impaired cognition;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;insight;Investigation;Ischemia;knock-down;Knock-out;Knowledge;Link;Magnetic Resonance Imaging;Mediating;Mediator;Metabolic;Metabolic Activation;Metabolic Diseases;Metabolic dysfunction;Metabolism;Methodology;micronutrient deficiency;Mission;molecular phenotype;mouse model;Nerve Degeneration;Nervous System Trauma;Neurodegenerative Disorders;Neuronal Hypoxia;Neurons;neuropathology;neurotoxicity;Nutritional;Obesity;Outcomes Research;Oxidative Stress;Pathologic;Pathway interactions;Patients;Process;Procollagen-Proline Dioxygenase;prophylactic;prospective;Public Health;Publishing;Research;response;RiboTag;Role;Stress;Supplementation;Testing;Thalamic structure;Therapeutic;therapeutic target;Thiamine;Thiamine Pyrophosphate;transcription factor;transcriptome sequencing;transcriptomics;United States National Institutes of Health

PROJECT_TITLE: Implications of Metabolic Dysfunction during Thiamine Insufficiency

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]