ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: We will conduct studies to better understand the function of AV node macrophages in order to advance our long-term translational goal to one day develop macrophage-targeted therapeutics as a new option for conduction disorders. We will implant pacemakers into Cd11bDTR mice and pace them for up to three months after macrophage depletion, investigating the recovery of conduction and tissue macrophages. The acquired mouse data will finally undergo rigorous examination for translatability to humans using patient samples.

PI_NAMEs: HULSMANS, MAARTEN  (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Ablation;Adopted;Apoptosis;Atrioventricular Block;atrioventricular node;Autopsy;Biological Assay;Biomedical Engineering;Cardiac;Cardiac Myocytes;Cause of Death;Cells;clinically relevant;Communication;Confocal Microscopy;Connexin 43;Connexins;Coupling;CSF3 gene;Data;Devices;Diphtheria Toxin;Disease;Dose;Electrocardiogram;Electrophysiology (science);Etiology;experimental study;Extracellular Matrix;Fibrosis;Genetic;Granulocyte-Macrophage Colony-Stimulating Factor;Heart;Heterogeneity;Heterozygote;Human;Image;Immune;Immunology;Implant;improved;in vivo;Incidence;Infusion procedures;Injections;Interleukin-4;Location;Macrophage;Macrophage Colony-Stimulating Factor;Maps;Mediating;Monitor;monocyte;mortality;multiphoton microscopy;Mus;Muscle Cells;Myeloid Cells;novel;Optics;optogenetics;Pacemakers;Parabiosis;Patients;Phenotype;Population;Process;Proliferating;Protocols documentation;Publishing;Recovery;Recovery of Function;Research;Role;Sampling;single-cell RNA sequencing;Somatotropin;Source;Spatial Distribution;Stains;Stromal Cells;System;targeted treatment;Techniques;Telemetry;Testing;Time;tissue stem cells;Tissues;translational goal;Work

PROJECT_TITLE: Cardiac resident macrophages in AV node conduction

STUDY_SECTION: MPPA

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


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Cancer Genomics;Estrogen;Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: MINNEAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Breast cancer recurrence remains a significant health burden for women undergoing long-term endocrine therapy following diagnosis with luminal (ER+) breast cancer. The goal of these studies is to reveal how steroid hormone receptors become dysregulated during metabolic and cell fate transitions that contribute to breast cancer progression, escape from ER-targeted therapies, and dissemination as long-lived cancer stem or stem- like cells capable of successful metastatic spread. Non-ER mediators of these reversible epigenetic events are highly targetable as part of future combination therapies.

PI_NAMEs: LANGE, CAROL A (contact);OSTRANDER, JULIE H

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: ATAC-seq;Biological Markers;Breast;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Model;breast cancer progression;Breast Cancer Treatment;Cancer Patient;cancer recurrence;cancer stem cell;Cells;Chicago;ChIP-seq;Chromatin;chromatin remodeling;Collaborations;Combined Modality Therapy;Complex;Cytometry;Cytoplasm;Data;Diagnosis;Disease;Disease Resistance;Disease-Free Survival;Endocrine;Ensure;Epigenetic Process;epigenetic regulation;Estrogen Receptors;Estrogens;Event;Follow-Up Studies;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Health;hormone therapy;Hypoxia;in vitro Model;in vivo;innovation;Intervention;knock-down;Knowledge;Link;Longevity;Lung;Malignant Breast Neoplasm;Mammary Neoplasms;Mass Spectrum Analysis;Mediating;Mediator;Metabolic;Metabolism;Metastatic breast cancer;Modeling;mortality;Mouse Mammary Tumor Virus;mouse model;NCOA3 gene;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Nuclear;Oncogenes;Oncogenic;overexpression;Pathway interactions;Patients;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Population;Positive Lymph Node;prevent;Process;Progesterone;Progesterone Receptors;programs;Proliferating;promoter;protein complex;Protein Kinase;Receptor Signaling;recruit;Recurrence;Resistance;Resistance development;Resolution;Risk;Role;scaffold;Signal Pathway;Signal Transduction;Signaling Molecule;Specific qualifier value;stem;stem cells;stem-like cell;steroid hormone receptor;Steroid Receptors;Stress;Tamoxifen;Target Populations;targeted treatment;Testing;therapy duration;therapy resistant;Time;Transcription Coactivator;transcriptome;transcriptome sequencing;Transgenic Mice;tumor;tumor metabolism;tumorigenesis;Woman;Work

PROJECT_TITLE: SRC-3/PELP1 complexes drive stem-like phenotypes in luminal breast cancer

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: CHICAGO

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ILLINOIS INSTITUTE OF TECHNOLOGY

ORG_STATE: IL

PHR: PROJECT NARRATIVE  This project aims to develop a new class of antibiotics targeted against Vibrio cholerae’s respiratory complex Na+-NQR. This enzyme is essential for several bacterial pathogens and it is absent in the human cell, which makes it an ideal drug target.

PI_NAMEs: JUAREZ, OSCAR  (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: analog;Animal Model;Anti-malarials;Antibiotics;Antipsychotic Agents;Automobile Driving;Bacterial Infections;bacterial metabolism;Binding;Binding Sites;Biochemistry;Biological;cell motility;Cell Physiology;Cells;Cellular biology;Cholera;Communicable Diseases;Complex;Computer Analysis;Coupled;Crystallization;Data;design;Development;Diarrhea;Docking;Dose;Drug Design;drug development;Drug Efflux;Drug Targeting;drug-like compound;Enzyme Inhibitor Drugs;Enzymes;Equilibrium;Evolution;Family;Foundations;Free Energy;functional group;Gastrointestinal Diseases;gastrointestinal infection;Generations;Growth;Human;human disease;Human Genome;Immune system;improved;in vivo;Infection;inhibitor;Institution;Intestines;Ions;iterative design;Lead;lead optimization;Libraries;Life;Malaria;Mammalian Cell;Membrane;Metabolism;Methods;Microbe;microbial;Microbiology;microorganism;Mitochondria;Modeling;Multi-Drug Resistance;Multienzyme Complexes;Multiple Bacterial Drug Resistance;mutant;Na(+)-K(+)-Exchanging ATPase;NADH;novel;novel antibiotic class;novel therapeutics;Nutrient;Oxidation-Reduction;Oxidoreductase;pandemic disease;pathogen;pathogenic bacteria;Pathogenicity;Pattern;Performance;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;pharmacophore;Phenothiazines;Phenotype;Physiology;Play;Predisposition;Process;process optimization;Production;Property;Proteins;Psychoses;Reactive Oxygen Species;Regulation;resistance mechanism;resistant strain;respiratory;respiratory enzyme;Role;Rotation;scaffold;Site;Sodium;Solid;Specificity;structural biology;Structure;Testing;Toxic effect;Toxin;Ubiquinone;uptake;Vibrio cholerae

PROJECT_TITLE: DEVELOPMENT OF A NOVEL CLASS OF ANTIBIOTICS AGAINST VIBRIO CHOLERAE NA+-NQR

STUDY_SECTION: DDR

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Comparative Effectiveness Research;Cost Effectiveness Research;Emerging Infectious Diseases;Health Services;Infectious Diseases;Patient Safety;Prevention;Rare Diseases;Tuberculosis

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

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

ORG_STATE: MA

PHR: NARRATIVE This research is intended to provide individually- and locally-tailored evidence on TB risks, to optimize TB prevention services in the United States and internationally. We will conduct analyses of empirical data, and develop and train mathematical models to simulate individual and population level TB outcomes. Based on this evidence, we will develop web-based interfaces predicting the health benefits, risks, and costs of LTBI screening and treatment, and the population-level effects of user-defined TB control strategies. 1

PI_NAMEs: MENZIES, NICOLAS A (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, KAREN A

PROJECT_TERMS: Acceleration;Address;Adverse event;Age;Area;Calibration;Categories;Characteristics;Cities;Clinical;clinical decision-making;Clinical Management;Communicable Diseases;Communities;Companions;Computer Models;computerized tools;cost;Cost Control;cost effectiveness;cost estimate;cost-effectiveness ratio;Costs and Benefits;Country;Data;data tools;Death Rate;Decision Making;Demography;Diabetes Mellitus;Diagnosis;Disease;Disease Progression;disorder risk;End stage renal failure;Epidemiology;evidence base;Exclusion;Face;Future;Health;Health Benefit;health economics;Health Services Accessibility;high risk population;HIV;Homeless persons;immune function;Immunocompetence;Impairment;Imprisonment;improved;Incidence;incremental cost-effectiveness;Individual;Infection;interest;International;Intervention;intervention effect;latent infection;Location;mathematical model;Modeling;models and simulation;Mycobacterium tuberculosis;NIH Program Announcements;novel;Online Systems;Outcome;Patient-Focused Outcomes;Patients;Pattern;Persons;Policies;Policy Maker;Policy Making;Population;Population Group;Population Sizes;predictive modeling;Prevalence;Prevention;prevention service;Preventive service;Preventive therapy;Preventive treatment;Probability;programs;reactivation from latency;Reporting;Research;residence;Risk;Risk Factors;risk prediction;screening;Series;Services;sex;Software Tools;Specific qualifier value;Specificity;Testing;Time;tool;Training;Translating;transmission process;Treatment outcome;trend;Tuberculosis;United States;United States National Institutes of Health;user-friendly;Variant;Visualization;web based decision aid;web based interface;web-based tool;Work

PROJECT_TITLE: Optimal targeting for individual and population-level TB prevention

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Prevention;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: VANCOUVER

ORG_COUNTRY: CANADA

ORG_FIPS: CA

ORG_NAME: UNIVERSITY OF BRITISH COLUMBIA

ORG_STATE: BC

ORG_ZIPCODE: V6T 1Z3

PHR: PROJECT NARRATIVE Despite alarmingly high prevalence of gender-based violence experienced by women living with HIV (WLWH), and evidence suggesting that women are falling behind men in all HIV continuum of care outcomes in many US and other high-income settings, there remains a lack of research to mitigate and address the role of violence on HIV clinical outcomes. The need to develop innovative trauma- and violence-informed approaches that can be tailored to HIV care and the unique needs of WLWH to optimize HIV clinical outcomes has taken on a new urgency and significance in the wake of the COVID-19 crisis. The goal of the proposed study is therefore to use innovative methods to characterize the complex relationships between gender-based violence and HIV clinical outcomes, define key components of differentiated HIV care models that mitigate these relationships, and provide important implications for informing and developing future trauma- and violence- informed HIV care and practice interventions for WLWH.

PI_NAMEs: DEERING, KATHLEEN ;SHANNON, KATE  (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adherence;Area;Biological;Canada;care outcomes;Caring;Charge;cis-female;cis-male;cisgender;Cities;Clinical;clinical practice;Cognitive;cohort;Communities;community violence;Complex;Continuity of Patient Care;Country;COVID-19 impact;COVID-19 pandemic;Cross-Sectional Studies;Data;Databases;Development;Disclosure;Disease;Disparity;Economics;Emotional;Environment;Epidemiologic Methods;epidemiology study;experience;Failure;falls;Future;gender disparity;gender-based violence;Goals;Government;Health;health assessment;Health Insurance;Healthcare;High Prevalence;HIV;HIV/AIDS;improved;Income;Inequity;innovation;Interpersonal Violence;Intervention;Interview;intimate partner violence;Link;Location;Maps;marginalization;Mediating;Mediator;Medical;men;Mental Depression;Meta-Analysis;Methods;Modeling;Monitor;Needs Assessment;North America;novel;Outcome;Policies;Prevalence;prospective;psychological violence;psychosocial;Public Health;Recording of previous events;Research;Research Design;Research Priority;Role;Safety;Science;Self Efficacy;Sexual Health;sexual violence;Shoulder;Site;social;Social Distance;social epidemiology;social stigma;Social support;Surveys;syndemic;Testing;transgender;transgender women;Trauma;Validation;verbal;Violence;Viral Load result;Woman

PROJECT_TITLE: Social and structural violence and HIV care continuum outcomes: Developing a trauma-informed HIV care intervention among WLWH

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


ORG_CITY: Nashville

ORG_DEPT: PHYSIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE The synaptic ion channels, known as AMPA receptors, are critical for learning, memory, and cognition, and thus they are considered as effective targets for drugs that could alleviate symptoms of various neurological and psychiatric disorders. We propose to reveal the molecular mechanism of AMPA receptor auxiliary subunit function using cryo-EM and electrophysiology, which in turn could guide rational design of new therapeutic compounds.

PI_NAMEs: NAKAGAWA, TERUNAGA  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: Adopted;Agonist;Alanine;Alzheimer's Disease;AMPA Receptors;Architecture;autism spectrum disorder;Brain;Characteristics;Cognition;Complex;conflict resolution;Cryoelectron Microscopy;Data;desensitization;Detergents;Diameter;Drug Targeting;Electrophysiology (science);Environment;Ethane;experimental study;Exposure to;Glutamate Agonist;Glutamate Receptor;Glutamates;Goals;Hippocampus;Human;inhibitor;insight;Ion Channel;Ion Channel Gating;Kinetics;Knowledge;Learning;Ligands;Limbic Encephalitis;Lipid Bilayers;Lipids;Liquid substance;Measurement;Mediating;Memory;Mental disorders;mimetics;Missense Mutation;Modeling;Molecular;Molecular Conformation;mutant;Mutate;Mutation;nanodisk;Nervous System Disorder;neurotransmission;neurotransmitter release;Neurotransmitters;novel therapeutics;Outcome;Outcome Study;pharmacologic;Physiological;Play;Preparation;rational design;receptor;receptor function;reduce symptoms;Regulation;Resolution;response;Role;Seizures;Shapes;Side;Signal Transduction;Specimen;Stroke;Structure;Synapses;Synaptic plasticity;Synaptic Transmission;Testing;Therapeutic;Time;trafficking

PROJECT_TITLE: Mechanism of functional modulation of glutamate receptors by their auxiliary subunits

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Mental Health;Prevention;Screening and Brief Intervention for Substance Misuse;Social Determinants of Health;Substance Misuse;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Relevance: The main purpose of this study is to understand how exposure to intimate partner violence (IPV) affects women's abilities to self-manage their HIV on a daily basis (i.e., adhere to antiretroviral medication), engage in longitudinal HIV care, and achieve and sustain viral suppression. The study will also evaluate the effect of an IPV-health focused intervention on women's HIV care engagement that aims to build awareness of the IPV-health association and provide strategies/resources to promote resilience.

PI_NAMEs: MEYER, JAIMIE ;SULLIVAN, TAMI P (contact)

PROJECT_TERMS: Address;Adherence;Adoption;Adult women;Affect;Anti-Retroviral Agents;Anxiety;Attention;Awareness;care outcomes;Caring;Characteristics;Chronic;Chronic Disease;Clinic;Cluster randomized trial;Collaborations;community collaboration;community organizations;community partners;community violence;Connecticut;Continuity of Patient Care;Cross-Sectional Studies;Data;Data Collection;Detection;Development;Disease;Ecological momentary assessment;emotion regulation;Enrollment;experience;Exposure to;Face;Follow-Up Studies;Frequencies;Funding;Future;Health;high risk population;HIV;HIV risk;improved;inattention;Individual;Intervention;Interview;intimate partner violence;longitudinal design;Mediating;medication compliance;member;Mental Depression;Mental Health;Meta-Analysis;Methods;mhealth interventions;modifiable risk;Outcome;outreach;partner violence;Patients;Pattern;Pharmaceutical Preparations;Process;Productivity;promote resilience;protective effect;protective factors;Protocols documentation;Provider;psychiatric comorbidity;Psychiatric therapeutic procedure;psychologic;Public Health;Randomized;recruit;Research;Resources;Risk;Risk Reduction;scale up;screening and brief intervention;screening, brief intervention, referral, and treatment;Self Efficacy;Self Management;sexual risk behavior;Social support;Specialist;standard of care;Subgroup;substance use;Substance Use Disorder;Target Populations;Testing;Time;tool;Training;trauma symptom;treatment as usual;Treatment outcome;Violence;violence exposure;violence victimization;Viral;Woman;women's outcomes

PROJECT_TITLE: Identifying Modifiable Risk and Protective Processes at the Day-Level that Predict HIV Care Outcomes Among Women Exposed to Partner Violence


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Kidney Disease;Organ Transplantation;Racial and Ethnic Minority Health Research;Social Determinants of Health;Transplantation

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: NARRATIVE Home dialysis and kidney transplantation are effective treatments for kidney failure, but they are underused, particularly among racial/ethnic minority populations and those living in areas with greater social disadvantage. In 2021, the Medicare program implemented payment incentives to increase access to these treatments in a randomly selected 30% of regions across the US. This project examines the impact of these pay-for- performance incentives on racial, ethnic, and socioeconomic disparities in home dialysis and access to kidney transplantation.

PI_NAMEs: PATZER, RACHEL E;TRIVEDI, AMAL N. (contact)

PROGRAM_OFFICER_NAME: PATEL, ANURADHA DIPAK

PROJECT_TERMS: access disparities;Address;Adult;American;Area;Caring;Clinical Data;Control Groups;cost;Dialysis procedure;Disadvantaged;Disparity;Donor person;effective therapy;End stage renal failure;Equity;ethnic disparity;ethnic minority;ethnic minority population;Ethnic Origin;Evaluation;financial incentive;flexibility;Goals;Health;health equity;Health Services Accessibility;Hemodialysis;Home;Hour;improved;Incentives;innovation;Insurance;Insurance Coverage;Kidney;Kidney Diseases;Kidney Failure;Kidney Transplantation;Lead;Life;Measurement;Measures;Medicaid;Medicare;Medicare/Medicaid;Minority;Modeling;mortality;neighborhood disadvantage;Neighborhoods;novel;Observational Study;Outcome;Patients;payment;Performance;Policies;Policy Maker;Population;primary outcome;programs;Provider;Quality of Care;Quality of life;Race;racial disparity;racial minority;racial minority population;Random Allocation;Randomized;Registries;Resources;Risk;Risk Factors;safety net;social;social disparities;socioeconomic disparity;Testing;transplant centers;Transplantation;treatment choice;Treatment Failure;United States Centers for Medicare and Medicaid Services;Waiting Lists;Work

PROJECT_TITLE: Impact of Randomized Payment Incentives on Disparities in Home Dialysis and Kidney Transplantation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-N(02)]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: CINCINNATI

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: NARRATIVE During infection, the human pathogen Pseudomonas aeruginosa (PA) expresses two periplasmic proteins, a catalase (KatB) and an ankyrin repeat protein (AnkB), in response to exogenous H2O2 mediated by the innate immune system. The overall goal of this proposal is to understand how AnkB interacts with KatB for the optimal detoxification of exogenous H2O2. Completion of these studies is important for understanding the response of PA during host infection and could lead to new clinical targets to treat hospital acquired infections.

PI_NAMEs: KOVALL, RHETT ALLEN (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Ankyrin Repeat;Ankyrins;Antibiotic Resistance;bactericide;Behavior;Binding;Biochemical;Biological Assay;Biological Process;Biophysics;Burn injury;catalase;Chronic Obstructive Pulmonary Disease;Clinical;Cysteine;Cystic Fibrosis;Cytoplasm;Data;design;diabetic ulcer;Disease;disulfide bond;DNA Binding;DNA Damage;Drug Metabolic Detoxication;Escherichia coli;Eukaryota;Exposure to;Fractionation;Genes;Genetic;Genetic Transcription;Goals;Gram-Negative Bacteria;Heme;heme 1;heme a;heme-binding protein;human disease;human pathogen;human tissue;Hydrogen Peroxide;Immune response;In Vitro;in vitro testing;in vivo;Infection;Innate Immune Response;Innate Immune System;insight;interdisciplinary approach;Link;Macrophage;Mediating;Medical;Microbial Biofilms;Microbial Physiology;Modeling;monomer;Multi-Drug Resistance;mutant;neutrophil;Nosocomial Infections;novel;Operative Surgical Procedures;Operon;opportunistic pathogen;Oxidants;pathogenic bacteria;periplasm;Periplasmic Proteins;Phagocytes;Prokaryotic Cells;protein protein interaction;protein purification;Proteins;Proton-Motive Force;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;public health relevance;Recombinants;Resistance;Respiratory Burst;response;Roentgen Rays;Role;Structure;Testing;Trans-Activators;translational study;Urinary tract infection

PROJECT_TITLE: Structure-function analysis of a catalase/ankyrin tandem from Pseudomonas aeruginosa necessary for resistance to hydrogen peroxide

STUDY_SECTION: MSFC

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


ORG_CITY: HANOVER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: NARRATIVE Cytokines and chemokines are small, secreted proteins that trigger immune activation to control infections or cancer or inhibit immune responses to prevent autoimmunity. In some cases, the same cytokine can have either activating or inhibiting effects. We propose to dissociate the pleotropic effects of the prototypical cytokine IL-2 by directing it to selectively interact with either activating or inhibitory cells and to extend its therapeutic half-life in the context of tumor immunity and autoimmunity.

PI_NAMEs: HUANG, YINA HSING (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Address;Affinity;Alpha Interleukin 2 Receptor;Amino Acids;Autoimmune Diseases;Autoimmunity;Benchmarking;Binding;Blood;C-terminal;cancer cell;cancer immunotherapy;Cancer Model;Cancer Patient;cell type;Cells;chemokine;chronic autoimmune disease;Circulation;Clinic;Clinical;Clinical Treatment;Clinical Trials;combinatorial;Complex;Continuous Infusion;cost effective;Coupling;crosslink;cytokine;Cytokine Receptors;Cytokine Signaling;cytokine therapy;cytotoxic CD8 T cells;Dependence;design;dimer;Disease;Dissociation;disulfide bond;Disulfides;DNA Sequence Alteration;Dose;Drug Kinetics;effector T cell;efficacy evaluation;Engineering;Exhibits;experience;Fc Receptor;Filtration;Fluorescence-Activated Cell Sorting;Future;Generations;Genetic;Geometry;Goals;Half-Life;Human;IL2 gene;immune activation;Immune response;immune stimulatory agent;immunodeficiency;immunogenicity;Immunosuppressive Agents;Immunotherapy;improved;in vitro Assay;in vivo;Infection Control;Inflammatory;Insulin-Dependent Diabetes Mellitus;interest;Interferon-beta;Interleukin 2 Receptor;Interleukin-2;interleukin-23;Kidney;Label;Leukocytes;Libraries;Link;Longevity;Lupus Nephritis;Lymphocyte Activation;Malignant Neoplasms;manufacture;Measures;Mediating;Melanoma;Metastatic Melanoma;Modeling;Molecular;Multiple Sclerosis;Mus;Mutation;Natural Killer Cells;neonatal Fc receptor;patient subsets;Patients;pleiotropism;polypeptide;prevent;Progression-Free Survivals;Proliferating;Property;protein purification;Protein Secretion;Proteins;prototype;Psoriatic Arthritis;Quality Control;receptor;receptor recycling;Recombinant Cytokines;recurrent infection;Recycling;Regimen;Regulatory T-Lymphocyte;Relapse;Renal Carcinoma;response;Role;Saccharomyces cerevisiae;Safety;Scanning;Serum Albumin;Site;Specificity;success;Surface;Symptoms;Systemic Lupus Erythematosus;T cell response;T-Lymphocyte;Therapeutic;Therapeutic Uses;Toxic effect;Tumor Immunity;Variant

PROJECT_TITLE: Directing Cytokine Specificity Through Co-translational Carrier Coupling

STUDY_SECTION: CMIA

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


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

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project narrative The GEF-H1 innate immune pathway is essential for intracellular microbial recognition and controls innate and adaptive immune mechanisms for host defense. The outcomes of the proposed experiments will define the mechanisms by which GEF-H1 is activated by entero- invasive pathogens and peptidoglycan recognition. The goal is to define pathway specific interactions of GEF-H1 with receptors and signaling intermediaries that control anti-microbial transcriptional programs and immunity.

PI_NAMEs: REINECKER, HANS-CHRISTIAN  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Acetylation;Actins;adaptive immune response;adaptive immunity;Affinity;Amino Acid Motifs;antimicrobial;Binding;Biological Models;Bone Marrow;cell type;Cells;Chimera organism;Complex;coping;Cytoskeleton;Deacetylation;Defense Mechanisms;defense response;Detection;Epithelial Cells;Epithelium;Event;experimental group;experimental study;Family member;Genetic;Genetic Transcription;Goals;HDAC6 gene;Host Defense;Host Defense Mechanism;Human;Immune;immune activation;Immune response;Immune signaling;Immunity;Infection;inhibitor;innate immune pathways;Innate Immune Response;intestinal epithelium;Intestines;Listeria monocytogenes;Macrophage;Mediating;microbial;Microtubule Stabilization;Microtubule stabilizing agent;Microtubules;Monitor;Monoclonal Antibodies;Mus;Myelogenous;Natural Immunity;Outcome;pathogen;Pathway interactions;Pattern Recognition;Pattern recognition receptor;Peptides;Peptidoglycan;peptidoglycan receptor;Phenotype;Phosphorylation;Positioning Attribute;programs;Protein Dephosphorylation;Proteome;receptor;Reporter;Research Design;response;Role;Signal Transduction;single-cell RNA sequencing;Specific qualifier value;System;T-Lymphocyte;three-dimensional modeling;transcriptome sequencing;uptake;Variant

PROJECT_TITLE: Innate Immune Defense Mechanisms in the Intestine

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ORG_DEPT: DERMATOLOGY

PHR: Human polyomaviruses cause a number of devastating diseases, including Merkel cell carcinoma and trichodysplasia spinulosa. Our preliminary studies have revealed that thes polyomaviruses produce circular ribonucleic acid (RNA) “messenger” molecules, which can be detected in affected patient tissues. This proposal explores how these circular RNAs are regulated and how they may function to promote viral diseases.

PI_NAMEs: WANG, RICHARD C (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Activator Appliances;Affect;Applications Grants;Binding Proteins;Biology;Candidate Disease Gene;Cells;circular RNA;Co-Immunoprecipitations;Code;Collaborations;Complex;Data;Diagnostic;Disease;DNA Tumor Viruses;DNA Virus Infections;DNA Viruses;ds-DNA;Elements;experimental study;Future;Genes;Genetic Transcription;Genome;Goals;high risk;Human;human disease;Human Papillomavirus;In Vitro;knock-down;Knowledge;Mediating;Merkel cell carcinoma;Merkel Cells;MicroRNAs;Modeling;Modification;Mutagenesis;novel;novel diagnostics;Oncoproteins;pathogen;Pathogenesis;Pathway interactions;Patients;Physiological;Play;Polymerase;Polyomavirus;Polyomavirus Infections;Polyomaviruses Middle T Proteins;Property;Proteins;Qualifying;Regulation;Resistance;response;RNA;RNA metabolism;RNA Splicing;Role;Signal Transduction;Site-Directed Mutagenesis;Small Interfering RNA;success;Therapeutic;Tissues;trait;Trans-Activators;Transactivation;transcriptome;Translating;Translations;tumor;Viral;Viral Genome;Viral Pathogenesis;virology;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Regulation and Function of Human Polyomavirus circular RNAs

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Nanotechnology;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: MIAMI

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: NARRATIVE The suboptimal protective rate of RTS’S urges us to exploit novel antigens and approaches to fight against malaria. Since Anopheles FREP1 FBG domain is important for malaria transmission, it is an ideal target for a new malaria transmission-blocking vaccine. We will enhance the malaria transmission-blocking efficacy by linking critical epitopes on FREP1 FBG domain with a novel molecular adjuvant.

PI_NAMEs: LI, JUN  (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Address;Adjuvant;Anopheles Genus;Antibodies;Antigens;Area;Binding;Biological Assay;Blood;C-terminal;Carrier Proteins;Chimeric Proteins;Clinical;Clinical Trials;Collaborations;Communities;Culicidae;Data;Drug resistance;Epitopes;feeding;Fibrinogen;fighting;Future;Genes;Goals;Immune response;improved;in vivo;industry partner;Ingestion;inhibiting antibody;Insecticide Resistance;insight;Intervention;Invaded;Kenya;Life Cycle Stages;Link;Malaria;malaria infection;malaria transmission;malaria transmission-blocking vaccine;Malaria Vaccines;Membrane;Midgut;Molecular;Monoclonal Antibodies;multidisciplinary;Mus;nanoparticle;new technology;novel;novel strategies;Oocysts;Orthologous Gene;Oryctolagus cuniculus;Parasite resistance;Parasites;Parasitic infection;Patients;Peptides;Plasmodium;Plasmodium falciparum;Plasmodium vivax;polyclonal antibody;Predisposition;protective efficacy;Proteins;Sequence Alignment;Site-Directed Mutagenesis;Techniques;Testing;tool;transmission blocking;transmission process;transmission-blocking vaccine;Universities;Vaccinated;Vaccination;Vaccine Antigen;vaccine development;Vaccines

PROJECT_TITLE: Anopheles FBG: a novel malaria transmission-blocking vaccine target

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Asthma;Biotechnology;Lung

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE During an asthma attack, bands of muscle that encircle the bronchial tubes contract and squeeze on the air- way passage, narrowing or sometimes completely shutting it. Because current treatments are not adequately effective in preventing such “bronchoconstriction”, we conceived an entirely new type of drug that will catalyze the degradation of the contractile motor protein within airway muscle, thereby paralyzing the muscle and pre- venting its contraction. In this project, we will synthesize and test prototypes of these novel compounds, in an effort to provide proof-of-principle that this new drug strategy can prevent bronchoconstriction in both human airways and living mice.

PI_NAMEs: SNYDER, SCOTT ALAN;SOLWAY, JULIAN  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acetylcholine;Acute;airway muscle;American;analog;Anesthesia procedures;Antineoplastic Agents;Asthma;asthma exacerbation;Binding;Biological Assay;bronchial epithelium;Bronchoconstriction;Bronchoconstrictor Agents;C57BL/6 Mouse;Cardiac;Cardiac Myocytes;care costs;Cells;constriction;Contracts;design;Development;Direct Costs;Disease;Dose;Economics;editorial;Epithelial Cells;Epithelium;Evaluation;experimental study;Facilities and Administrative Costs;Goals;Half-Life;Human;Impairment;In Vitro;in vivo;Incubated;Length;Lung;Measures;Mechanical ventilation;methacholine;Morbidity - disease rate;Motor;multicatalytic endopeptidase complex;Mus;Muscle;Muscle Cells;Muscle Contraction;Muscle Fibers;Myosin ATPase;non-muscle myosin;novel;novel therapeutics;Paralysed;Persons;Pharmaceutical Preparations;Play;preclinical development;prevent;Prevention;Process;programs;Protac;Protein Isoforms;Proteins;prototype;Pulmonary Hypertension;recruit;Reporting;Residual state;respiratory smooth muscle;response;scaffold;Series;Side;skeletal;Slice;small molecule;Smooth Muscle;Smooth Muscle Myocytes;Smooth Muscle Myosins;Symptoms;Testing;Thalidomide;Trachea;Treatment Protocols;Tube;ubiquitin-protein ligase;Ubiquitination;Western Blotting

PROJECT_TITLE: Smooth Muscle Myosin PROTACs as a Novel Treatment for Asthma

STUDY_SECTION: LCMI

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


ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: NARRATIVE Antiretroviral therapies are able to control HIV replication, but they are unable to fully restore health or a normal immune status owing to the persistence of latently infected cells. This application proposes to use a highly multi- disciplinary approach, including antibody-binding assays, structural investigations, and single-molecule fluorescence imaging to elucidate the interaction between HIV-1 Env and easily-elicited non-neutralizing antibodies that induce antibody-dependent cellular cytotoxicity. This research will enable exploitation of this under-utilized strategy to develop new means of eliminating the latent HIV reservoir.

PI_NAMEs: FINZI, ANDRES ;MUNRO, JAMES B (contact);ROUILLER, ISABELLE

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adopted;Adoption;Affect;Antibodies;Antibody Activation;antibody-dependent cell cytotoxicity;Antigens;antiretroviral therapy;Binding;Binding Sites;Biological Assay;Bone Diseases;Cardiovascular Diseases;Cells;Characteristics;comorbidity;Cryoelectron Microscopy;Data;design;Development;Elements;emerging virus;Enzyme-Linked Immunosorbent Assay;Epidemic;Epitopes;Event;experience;fluorescence imaging;Fluorescence Resonance Energy Transfer;Future;Generations;Glycoproteins;Goals;Health;HIV;HIV Envelope Protein gp120;HIV Infections;HIV-1;HIV-1 vaccine;Image;Immune;Immunoglobulin A;immunological status;Impaired cognition;improved;In Vitro;Individual;Infection;insight;interdisciplinary approach;Interruption;Investigation;latent HIV reservoir;Mediating;Molecular;Molecular Conformation;novel;novel strategies;novel therapeutics;Plasma;Predisposition;prevent;prophylactic;protective efficacy;Research;Research Personnel;response;single molecule;Structure;success;Techniques;Testing;Thailand;vaccine trial;Viral;Viral reservoir;Virus;Virus Replication;X-Ray Crystallography

PROJECT_TITLE: Characterizing HIV-1 Env conformations susceptible to attack by non-neutralizing antibodies

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: BIRMINGHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The assembly of human cytomegalovirus (HCMV) is exceedingly complex with the final step in assembly being the acquisition of the viral envelope, the outer component of the virus. To date the interactions between viral proteins that lead to virion envelopment are unknown. In this project, we will identify interactions between viral proteins during virus envelopment with a goal of defining mechanism that could potentially aid in the development of antiviral therapeutic agents and more effective vaccines.

PI_NAMEs: BRITT, WILLIAM JARVIS (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Acute;Anti-viral Therapy;antiviral drug development;Biochemistry;Capsid;Cell membrane;Cells;Cellular Membrane;Child;Complex;Cryoelectron Microscopy;Cytomegalovirus;Cytomegalovirus Infections;Cytoplasm;Data;Dose Limiting;Endosomes;Ensure;env Gene Products;Generations;Glycoproteins;Goals;Golgi Apparatus;Herpesviridae;Human;Image;Immunocompromised Host;in utero;Individual;Infant;interest;Licensing;Lipids;Malignant - descriptor;Membrane;Membrane Protein Traffic;Metabolic;Microtubule-Organizing Center;Microtubules;Modification;Morbidity - disease rate;Morphogenesis;mortality;mutant;Mutation;novel;particle;Pathway interactions;Phenotype;Post-Translational Protein Processing;Production;protein protein interaction;protein transport;Proteins;recombinant virus;Recycling;Reporting;response;Role;Site;stoichiometry;Stress;Structural Protein;Structure;Testing;Therapeutic Agents;therapeutic development;Toxic effect;trafficking;trans-Golgi Network;vaccine strategy;Vaccines;Vacuole;Viral;Viral Proteins;Virion;Virus;Virus Assembly;Virus Diseases;Virus Replication

PROJECT_TITLE: Tegument Envelope Protein Interactions in CMV Envelopment

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


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

ORG_CITY: NOTRE DAME

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Project Narrative This project will study the immunological underpinnings and origins of alloreactivity and acute cellular rejection of transplanted tissues. Success here will help advance our understanding of rejection and set the stage for advances in treatment and prevention.

PI_NAMEs: BAKER, BRIAN M (contact);HILDEMAN, DAVID A

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: Acute;Adrenal Cortex Hormones;Affect;Alloantigen;allograft rejection;Allografting;Antigen-Presenting Cells;Area;Autoimmunity;Automobile Driving;Back;Binding;Biological;Biology;Biopsy;Calcineurin inhibitor;candidate identification;CD8-Positive T-Lymphocytes;Cells;Cellular biology;Clonal Expansion;Clone Cells;Complex;Consensus;cross reactivity;Cytomegalovirus;Data;differential expression;Disease;End stage renal failure;Epitopes;established cell line;experimental study;Genes;Goals;Graft Rejection;high reward;high risk;Homologous Gene;Human;Human Herpesvirus 4;Immunobiology;Immunologics;Immunosuppression;Individual;Infection;infection risk;insight;kidney allograft;Kidney Transplantation;Knowledge;Ligands;Link;Malignant Neoplasms;Maps;Mediating;Memory;metaplastic cell transformation;Mixed Lymphocyte Culture Test;Monitor;Morbidity - disease rate;mortality;Nature;novel therapeutics;Pathway interactions;Patients;Peptide Library;Peptide/MHC Complex;Peptides;Peripheral Blood Mononuclear Cell;Persons;pharmacologic;Play;premature;Prevention;Quality of life;Regimen;response;Role;screening;single-cell RNA sequencing;Specificity;success;Surface;T cell response;T cell therapy;T memory cell;T-Cell Activation;T-Cell Depletion;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Therapeutic immunosuppression;therapeutic target;Tissue Transplantation;Tissues;Toxic effect;transcriptome;transcriptomics;Transplant Recipients;Transplantation;Urine;Viral;Virus;Virus Diseases;Work

PROJECT_TITLE: Decoding human T-cell allospecificity

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


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Mutations in the gene MYT1L have been recently discovered to cause autism spectrum disorder and intellectual disability in patients. This project uses human pluripotent stem cell models to produce neurons, as well as a mouse model of the mutation, to study the function of the MYT1L gene. The goals are to understand how mutation of MYT1L leads to disruption of the development and function of brain cells, and to test whether gene therapy-like approaches can restore normal function in these models, with the hope that this understanding could chart a course towards targeted therapies for patients.

PI_NAMEs: KROLL, KRISTEN L (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: Amino Acids;ATAC-seq;autism spectrum disorder;Behavioral;Biological Models;Brain;brain cell;brain control;causal variant;Cell Line;Cells;Cellular Assay;Central Nervous System;Central Nervous System Diseases;ChIP-seq;Chromatin;Chronic;Clinical;clinical translation;cohort;Complex;Development;Disease;Dysmorphology;exome;experimental study;Family;Gene Expression;gene function;gene therapy;Genes;Genetic;genetic approach;Genetic study;Genetic Transcription;Genomics;Goals;Human;Human Genetics;human model;human pluripotent stem cell;Hyperactivity;in vitro Model;in vivo Model;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;innovation;insight;Intellectual and Developmental Disabilities Research Centers;Intellectual functioning disability;Investigation;Knock-in;loss of function;Methods;Methyl-CpG-Binding Protein 2;Modality;Modeling;Molecular;Motor;mouse model;Mus;mutant;Mutation;mutation carrier;nervous system development;neural circuit;Neuroanatomy;neurodevelopment;Neurodevelopmental Disorder;Neuronal Differentiation;Neurons;novel strategies;overexpression;Pathogenicity;Patients;Phenotype;Physiological;Physiology;Population;Prevalence;Process;remediation;Repression;Rett Syndrome;Role;Seizures;Speech Delay;stem cell model;stereotypy;Structure;Syndrome;System;targeted treatment;Testing;Therapeutic;therapeutic development;therapy development;Time;tool;transcriptome sequencing;Variant

PROJECT_TITLE: Genomic and functional characterization of ASD and ID-associated MYT1L mutation


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Genetics;Infectious Diseases;Nanotechnology;Prevention;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BLACKSBURG

ORG_DEPT: ZOOLOGY

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: PROJECT NARRATIVE  The most successful invasive mosquito species Aedes albopictus is a vector of dangerous arboviruses, such as dengue, Chikungunya, and Zika. Unlike other mosquitoes, Ae. albopictus can easily adapt to different natural environments and climates because of its remarkable ability to develop a photoperiodic diapause under cold environmental conditions. To better understand the wide phenotypic plasticity of this mosquito and to facilitate the development of new technologies for mosquito control, this project will create haplotype-resolved chromosome-scale genome assemblies for multiple strains of Ae. albopictus and identify chromosomal rearrangements associated with adaptations of this mosquito to different environments.

PI_NAMEs: SHARAKHOVA, MARIA  (contact)

PROJECT_TERMS: Aedes;Americas;Anopheles Genus;Antarctica;arboviral disease;Arboviruses;Asia;Asian;Biological;Biology;Breeding;chikungunya;Chikungunya fever;Chinese;Chromosomal Rearrangement;Chromosome inversion;Chromosomes;Climate;climate zone;contig;Country;Culicidae;Dangerousness;Dengue;Dengue Fever;Development;Diapause;Disease;Disease Outbreaks;disease transmission;DNA Probes;Environment;Epidemic;Epidemiology;Europe;Fluorescent in Situ Hybridization;France;Genes;Genetic;Genetic study;Genome;Genome Mappings;genome-wide;Genomics;Geographic Locations;Goals;Grant;Haplotypes;Health;Hi-C;Hybrids;improved;Infection;Invaded;Italy;Laboratories;male;Maps;Measures;Methods;Mexico;Mitotic Chromosome;Mosquito Control;Mosquito-borne infectious disease;nanopore;new technology;North America;Panama;Parents;Phenotype;photoperiodicity;physical mapping;Population;prevent;Public Health;Quantitative Trait Loci;reference genome;Reporting;scaffold;South American;Southeastern Asia;Southern Europe;Spain;success;Technology;Testing;Tigers;trait;transmission process;United States National Institutes of Health;Variant;vector;vector control;ZIKA;zika fever

PROJECT_TITLE: Haplotype-resolved genome assemblies and chromosomal rearrangements in arboviral vector Aedes albopictus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-V(02)]


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

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE With this project, we aim at answering a fundamental question: are antibiotic persisters responsible for the relapse of infection after cessation of antibiotic treatment, with a specific focus on Salmonella Typhimurium, a powerful model intracellular pathogen. A CRISPR‐based recorder recently adapted in the lab will be used to record in the bacterial genome of persisters the state of growth‐arrest, thus leaving an indelible genetic scar in CRISPR arrays that is perpetuated and detectable in their progeny, allowing us to assess whether relapsors in mice stem from persisters. If successful, this approach will be broadly applicable to other pathogens, and will be of the utmost importance to determine the most efficient way of targeting persistent infections and counteract the generation of antibiotic resistance.

PI_NAMEs: HELAINE, SOPHIE  (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: acute infection;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Bacteria;Bacterial Genome;Biological Models;Bone Marrow;Cells;chronic infection;Cicatrix;Clustered Regularly Interspaced Short Palindromic Repeats;design;Development;Drug resistance;Fluorescence;Future;Generations;Genes;Genetic;Genetic Markers;Genome;Genotype;Goals;Growth;Health;Human;improved;Infection;Laboratories;Length;Macrophage;microbial;Modeling;Mus;Mutation;Mycobacterium tuberculosis;Organ;pathogen;pathogenic bacteria;Pathogenicity;persistent bacteria;Pharmaceutical Preparations;Phenotype;Physiology;prevent;Public Health;Records;Regimen;Relapse;Reporting;Research;Resistance;Role;Route;Salmonella;Salmonella enterica;Salmonella infections;Salmonella typhimurium;Signal Transduction;Source;stem;Stress;Symptoms;Testing;Therapeutic;Time;tool;Treatment Failure;Variant

PROJECT_TITLE: Recording the role of persisters in infection relapse

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The assembly of diverse antigen receptor genes through DNA recombination across vast distances is essential for immunity. The applicant shows preliminary data that different antigen receptor loci use distinct underlying mechanisms for long-range recombination. He proposes to test his hypothesis that the direction through which these chromosomal loci compact to facilitate long-range recombination dictates the relative contributions of two distinct fundamental mechanisms of recombination.

PI_NAMEs: BASSING, CRAIG H (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: adaptive immunity;Antigen Receptors;Architecture;Binding;Biology;CCCTC-binding factor;Cells;chromosome conformation capture;Chromosome Pairing;Chromosome Structures;Chromosomes;cohesin;Data;Development;Diffusion;DNA Damage;Elements;endonuclease;Enhancers;experimental study;Foundations;Frequencies;Gene Expression;gene repair;Genes;Genetic Recombination;Genetic Transcription;Genome;genomic locus;Genomics;human disease;IgK;Immunity;innovation;insight;interest;Lymphocyte;Mammals;Mediating;Modeling;Modification;Mus;Mutation;next generation sequencing;Outcome;Peptide Signal Sequences;Population;Positioning Attribute;prevent;promoter;protein complex;Publishing;Receptor Gene;repaired;response;Role;Scanning;segregation;Structure;Study models;Testing;thymocyte;Tissues;transcription factor;V(D)J Recombination

PROJECT_TITLE: Exploring a Functional Role of Chromosome Loop Extrusion Direction on Regulating Genome Biology


ADMINISTERING_IC: AG

FUNDING_MECHANISM: SBIR-STTR RPGS

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);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Sleep Research

ORG_CITY: EUGENE

ORG_NAME: BRAIN ELECTROPHYSIOLOGY LABORATORY COMPANY, LLC

ORG_STATE: OR

PHR: Disordered sleep in aging may be an important risk factor for developing Alzheimer's Disease. This project will provide researchers and clinicians with a technology to allow patients to improve deep sleep at home, through a simple headband to measure brain activity and to synchronize the brain waves of deep sleep with electrical currents. Based on 2015 estimates from the Alzheimer's Association, if improved deep sleep can delay the onset of Alzheimer's Disease by 5 years, this will reduce the number of Alzheimer's cases by 5.7 million and save $367 billion in health care costs in the US.

PI_NAMEs: TUCKER, DON M (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Acute;Address;Adult;Age;Aging;Alzheimer's Disease;Alzheimer's disease risk;amnestic mild cognitive impairment;Amyloid beta-Protein;behavior measurement;Bluetooth;Brain;Cephalic;Classification;Clinical Trials;Clinical Trials Design;cloud based;Cloud Service;Cognitive Therapy;Communication;Computer software;Controlled Clinical Trials;cost effective;Data;Data Analyses;Databases;Dedications;Dementia;design;detection platform;Devices;Docking;Electric Stimulation;Electric Stimulation Therapy;Electroencephalography;Excretory function;Exercise;glymphatic clearance;Goals;Guidelines;Health;Health Care Costs;Home;Home environment;Human;Impairment;improved;improvement on sleep;Length;Link;Machine Learning;machine learning classification;Measures;Memory;memory consolidation;Memory impairment;Memory Loss;mild cognitive impairment;Monitor;Nerve Degeneration;neurophysiology;Neurotoxins;older adult;Older Population;Outcome;Outcome Measure;Participant;Patients;Performance;Persons;pharmacologic;Phase;Phase II Clinical Trials;phase II trial;Physicians;Physiologic Monitoring;Placebo Control;Placebos;Plasma;poor sleep;Populations at Risk;portability;primary outcome;Protocols documentation;prototype;Randomized;Reporting;Research Personnel;response;Risk Factors;Safety;secondary outcome;Site;Sleep;Sleep Architecture;Sleep Deprivation;Sleep Disorders;sleep health;sleep quality;sleep spindle;Sleep Stages;Sleeplessness;software development;success;System;Tablets;tau Proteins;Technology;TensorFlow;Testing;therapy design;tool;Training;Treatment Protocols;trial planning;United States National Institutes of Health;usability;verification and validation;wireless;Work

PROJECT_TITLE: Home Sleep Therapy System for Mild Cognitive Impairment


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Endocrine Disruptors;Estrogen;Infectious Diseases;Malaria;Nutrition;Obesity;Pediatric;Prevention;Rare Diseases;Social Determinants of Health;Vector-Borne Diseases

ORG_CITY: MONTREAL

ORG_NAME: MCGILL UNIVERSITY

ORG_STATE: QC

ORG_ZIPCODE: H3A 0G4

PHR: 8. PROJECT NARRATIVE PUBLIC HEALTH RELEVANCE STATEMENT  The prevalence of overweight and obesity has dramatically increased in developing countries such as South Africa while age at puberty onset has been decreasing. Evidence suggests that exposure to insecticide that interfere with endocrine function may play a role. We propose to evaluate whether exposure to DDT and pyrethroids, which are commonly used as part of Indoor Residual Spraying programs in developing countries is associated with body composition and timing and tempo of puberty in a birth cohort of 752 rural South African children.

PI_NAMEs: CHEVRIER, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: 2 year old;Acceleration;Address;Adult;Africa;African;Age;aged;Androgen Antagonists;androgenic;Animals;Area;Biological Markers;Birth;Body Composition;Body fat;Body mass index;Body measure procedure;boys;Child;Child Development;China;chlorohydrocarbon insecticide;Clinical;cohort;Cohort Studies;Community Networks;Complex;Country;Data;Delayed Puberty;Developed Countries;Developing Countries;Development;Dichlorodiphenyl Dichloroethylene;Diet;Dose;early onset;Endocrine;Endocrine Disruptors;Energy Intake;Environment;Environmental Estrogen;Epidemiology;Estradiol;estrogenic;experience;Exposure to;Female;Follicle Stimulating Hormone;girls;Growth;Health;High Prevalence;high risk sexual behavior;HIV;Hormones;Human;human data;Income;Infection;Insecticides;International;Knowledge;Leptin;low and middle-income countries;Luteinizing Hormone;Malaria;male;Malignant Neoplasms;Malnutrition;Marketing;Measurement;Measures;Mental disorders;Metabolic syndrome;Methods;Modeling;obese person;Obesity;obesity in children;obesogenic;Overweight;overweight child;Physical activity;Policy Maker;Population;postnatal;Poverty;Pregnancy;prenatal exposure;Preschool Child;Prevalence;programs;Property;pubertal timing;Puberty;public health relevance;pyrethroid;Reporting;reproductive;Research Infrastructure;residence;Residual state;Rodent;Rural;Sampling;Serum;Skinfold Thickness;South Africa;South African;Southern Africa;Testosterone;trend;Trichloroethanes;United Nations;Urine;Weight;World Health Organization

PROJECT_TITLE: Exposure to Insecticides and Child Growth and Pubertal Development in a South African Population Exposed Through Indoor Residual Spraying

STUDY_SECTION: KNOD

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Stroke

ORG_CITY: Loma Linda

ORG_NAME: LOMA LINDA UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative Germinal matrix hemorrhage (GMH), affects approximately twenty percent of all infants delivered before 32 weeks of gestation and 12,000 newborns develop this condition in the United States each year. The overall goal of this proposal is to explore endogenous phagocytic mechanisms that quickly resolve hematoma after hemorrhagic stroke, thereby improving outcomes in this patient population.

PI_NAMEs: TANG, JIPING  (contact)

PROGRAM_OFFICER_NAME: KOENIG, JAMES I

PROJECT_TERMS: absorption;Acute;Affect;Age;Agonist;Annexin A1;antagonist;Attenuated;Blood coagulation;Blood Vessels;Brain hemorrhage;Brain Injuries;CD36 gene;Central Nervous System;Cerebrospinal Fluid;Chronic;Circulation;Clinical Management;clinical translation;clinically relevant;Coagulation Process;Data;Development;effective therapy;Female;FPR1 gene;FPR2 gene;Functional disorder;G-Protein-Coupled Receptors;Genes;Genetic Transcription;Goals;Hematoma;Hemorrhage;Hydrocephalus;improved;improved outcome;infancy;Infant;Inflammation;knock-down;lipoxin A4;Literature;Live Birth;Macrophage;male;MAP Kinase Gene;MAPK3 gene;Membrane Glycoproteins;Microglia;monocyte;Morbidity - disease rate;mortality;neonatal brain;Nervous System Physiology;Neurologic Deficit;Neurological outcome;neuroprotection;Newborn Infant;Outcome;p38 Mitogen Activated Protein Kinase;Pathway interactions;patient population;Patients;Perinatal subependymal hemorrhage;Phagocytes;Phagocytosis;Phagocytosis Induction;Phenotype;Play;post stroke;pre-clinical;Pregnancy;Premature Infant;Primary Cell Cultures;protective effect;Protein phosphatase;receptor;Recovery;recruit;Reducing Agents;Regimen;Research;Resolution;Rodent;Rodent Model;Role;Rupture;scavenger receptor;Signal Pathway;Signaling Protein;Specificity;Stroke;Subependymal;Testing;Therapeutic;Therapeutic Agents;Treatment Protocols;United States;Up-Regulation;Ventricular

PROJECT_TITLE: Harnessing blood clot clearance mechanisms after germinal matrix hemorrhage

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative The goal of this proposal is to define the mechanism of a new strategy of immunotherapy: peptide alarm therapy. Further investigations will test the potential for synergizing peptide alarm therapy with other immunotherapies and for testing abscopal effects in mouse cancer models, followed by evaluation of peptide alarm therapy-induced sensing and alarm functions in human tumor explants. Successful execution should provide the necessary information to proceed with a clinical trial for the treatment of human cancer.

PI_NAMEs: MASOPUST, DAVID  (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Abscopal effect;Adaptive Immune System;Address;Adjuvant;Anatomy;anti-cancer;anti-PD-L1;Antibodies;Antigen Presentation;antiviral immunity;arm;cancer immunotherapy;Cancer Model;Cell Physiology;Cells;Clinical;Clinical Treatment;Clinical Trials;Common Neoplasm;cytokine;Data;Distant;Environment;Evaluation;experience;fighting;Future;Goals;Human;immune checkpoint blockade;Immune system;Immunity;immunogenic;Immunotherapeutic agent;Immunotherapy;in vivo;Infection;Innate Immune System;Investigation;Malignant Neoplasms;Measurable;Melanoma Tumor;memory retention;Modeling;Mus;Natural Killer Cells;neoantigens;neoplasm immunotherapy;novel strategies;Patients;Peptides;Phenotype;Preparation;prevent;Primary Neoplasm;Productivity;programmed cell death ligand 1;Recrudescences;recruit;Recurrence;response;Role;Site;Solid Neoplasm;sound;Surveys;synergism;T cell response;T memory cell;T-Lymphocyte;Testing;tissue resident memory T cell;Tissues;tumor;Tumor Biology;tumor growth;tumor microenvironment;tumor-immune system interactions;Viral;Virus;Virus Diseases

PROJECT_TITLE: Repurposing TRM for tumor immunotherapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: PORTLAND

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

PHR: Project Narrative NAIPs are immunological receptors that activate the NAIP/NLRC4 inflammasomes to initiate inflammation in response to Gram-negative bacterial infections. They play key roles in infectious diseases, autoinflammatory diseases, and a wide range of metabolic disorders. Elucidating the molecular basis of NAIP receptors in inflammasome regulation will provide important new insights into the development of clinical drugs to treat these diseases.

PI_NAMEs: ZHANG, LIMAN  (contact)

PROJECT_TERMS: Address;Advanced Development;Apoptosis;Architecture;autoinflammation;autoinflammatory diseases;Bacteria;Bacterial Proteins;Binding;Binding Sites;Biochemical;CASP1 gene;Caspase;Cell Death;Cell membrane;Cell surface;Cells;Clinical Drug Development;Communicable Diseases;Complex;Cryoelectron Microscopy;cytokine;Data;Detection;Development;Disease;effective therapy;Environment;Exhibits;extracellular;Family;Flagellin;Gram-Negative Bacteria;Gram-Negative Bacterial Infections;Human;IL18 gene;Immune response;Immunologic Receptors;Inflammasome;Inflammation;Inflammatory;Innate Immune System;insight;Interphase Cell;Learning;Legionella pneumophila;Leucine-Rich Repeat;Ligand Binding;Ligands;Macrophage activation syndrome;Malignant Neoplasms;Metabolic Diseases;Modeling;Molecular;Molecular Conformation;Mus;Mutation;Mutation Analysis;N-terminal;Needles;novel;novel therapeutic intervention;Nucleotides;pathogen;Pathogenicity;Pathway interactions;Play;polymerization;Polymers;prevent;Process;protein complex;Protein Family;Proteins;Reaction;receptor;recruit;Regulation;Reporting;Research;Resolution;response;Rod;Role;Salmonella;Salmonella typhimurium;Science;Signal Transduction;Specificity;Spinal Muscular Atrophy;Structure;Testing;Type III Secretion System Pathway;Work

PROJECT_TITLE: Elucidating the Structural Mechanisms of NAIP Receptors in Bacterial Detection and Inflammasome Activation

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

PHR: Narrative This Research Career Scientist (RCS) application by Robert Mauck of the Corporal Michael J. Crescenz VA Medical Center in Philadelphia seeks support for a research program focused on issues of high relevance to the Veteran population. Dr. Mauck develops novel regenerative tools to improve outcomes and restore function in Veterans whose mobility has been compromised by musculoskeletal (MSK) injury or degeneration. Dr. Mauck develops novel material and stem cell- based therapeutics that are intended to speed the repair or replace cartilage, meniscus, and disc, and his team is actively translating these technologies into pre-clinical large animal models and humans. In addition to his scientific pursuits, Dr. Mauck is committed to supporting the next generation of VA- based scientists, and has mentored several clinicians/scientists to Career Development Awards through the RR&D Service.

PI_NAMEs: MAUCK, ROBERT L (contact)

PROJECT_TERMS: Academy;Acceleration;Address;adult stem cell;American;analog;Anatomy;Animal Model;Area;articular cartilage;Award;Biocompatible Materials;Biological;Biomechanics;Biomedical Engineering;Biomimetics;biophysical properties;Biophysics;Black race;Book Chapters;career;Cartilage;cartilage repair;Cell Nucleus;Cells;Cellular Infiltration;Chondrogenesis;clinical application;Coculture Techniques;college;Communication;Custom;Degenerative polyarthritis;Dense Connective Tissue;Development;Disabling;Doctor of Philosophy;Drug Delivery Systems;editorial;Education;Elements;Engineering;Environment;Epitopes;Extracellular Matrix;fabrication;follow-up;Foundations;functional restoration;Gait;General Population;Goals;Goat;Growth;healing;Health;Human;Hydrogels;implantation;improved;improved outcome;In Vitro;in vivo;Incidence;interest;International;Intervertebral disc structure;intervertebral disk degeneration;joint function;Joints;Journals;K-Series Research Career Programs;Knee;Laboratory Research;Length;Manuscripts;Maps;Measures;mechanical behavior;mechanical load;Mechanics;Medical;Medical center;Medicine;member;Meniscus structure of joint;Mentors;Mesenchymal Stem Cells;Methods;military veteran;Mission;Modeling;Molecular Analysis;Musculoskeletal;Musculoskeletal Diseases;musculoskeletal injury;nanofiber;Natural regeneration;Nature;next generation;novel;Nuclear;nucleus pulposus;Orthopedic Surgery;Orthopedics;Pain;Paper;patient population;Pennsylvania;Phenotype;Philadelphia;Population;Porosity;pre-clinical;Privatization;Prize;Production;professor;programs;Property;Publications;Publishing;regenerative;Regenerative Medicine;regenerative therapy;Rehabilitation therapy;repaired;Reporting;Research;Research Personnel;scaffold;Science;Scientist;Series;Services;Signal Transduction;Societies;Speed;stem cell function;stem cell therapy;stem cells;Structure;Structure-Activity Relationship;Surgeon;System;Technology;technology development;Time;Tissue Engineering;tissue regeneration;Tissues;tool;Translating;translational medicine;Translational Research;Translations;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;Vertebral column;Veterans;Work

PROJECT_TITLE: RR&D Research Career Scientist Award Application

STUDY_SECTION_NAME: Research Career Scientist[RRD7]


NIH_SPENDING_CATS: Genetics

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Project Narrative When immune cells sense pathogens they respond by rapidly producing defense factors to protect the organism. This response involves transmitting the extracellular sensing cue to a specific set of defense genes (only dozens of genes among tens of thousands) in the 2-meter long genome. Our goal is to understand the mechanisms that enable this rapid cellular programming for inflammatory responses, to gain insights into immunity and autoimmunity.

PI_NAMEs: JOSEFOWICZ, STEVEN ZVI (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: activating transcription factor 1;Amino Acids;Amplifiers;Autoimmunity;Biochemical;Biology;cell type;Cells;CHEK1 gene;Chromatin;Complex;Cues;Dedications;Dependence;Disease;DNA;DNA Damage;DNA Polymerase II;DNA Topoisomerases;Environmental Risk Factor;Epigenetic Process;epigenetic regulation;epigenomics;Event;experimental study;extracellular;Gene Expression;gene induction;Genes;Genetic Transcription;Genome;Goals;Histone Code;Histone H3;Histone H3.3;Histones;Human;Immune;Immunity;in vivo;Inflammation;Inflammatory;Inflammatory Response;insight;Knowledge;Link;Macrophage;Mediating;Memory;meter;Molecular;mutant mouse model;Mutation;novel;Oncogenic;Organism;Paper;pathogen;Pathway interactions;Phosphorylation;Polymerase;Positioning Attribute;Post-Translational Protein Processing;protein H(3);Proteins;recruit;response;Role;Serine;Signal Pathway;Signal Transduction;Site;Specificity;Speed;Tail;Therapeutic;therapeutic target;Time;Tissues;Topoisomerase;Training;Transcription Coactivator;transcription factor;transmission process;tumor;upstream kinase;Variant;Yeasts

PROJECT_TITLE: Cooption of the DNA Damage Response For Epigenetic Regulation of Inflammation

STUDY_SECTION: CMIB

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Emerging Infectious Diseases;HIV/AIDS;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease;Rare Diseases;Tuberculosis

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: NARRATIVE The laboratory studies proposed in this application will have a direct beneficial effect on the health of millions of patients worldwide who are infected with HIV, TB and Hepatitis B, transforming the treatment of patients with these infections. The clinical research conducted by the ACTG will lead to significantly reduced morbidity and mortality, particularly among populations disproportionately affected by HIV/AIDS and tuberculosis.

PI_NAMEs: ALDROVANDI, GRACE M (contact)

PROGRAM_OFFICER_NAME: LIVNAT, DANIELLA

PROJECT_TERMS: Address;Affect;AIDS clinical trial group;antiretroviral therapy;Area;assay development;Biological Assay;Biological Markers;Clinical;Clinical Research;Clinical Trials;Collaborations;comorbidity;Data Coordinating Center;Disease remission;DNA Repository;Evaluation;Genomics;Health;Hepatitis B;HIV;HIV/AIDS;human DNA;Immunology;improved;Infection;innovation;International;Intervention;Knowledge;Laboratories;laboratory experience;Laboratory Research;Laboratory Study;Leadership;Measures;Morbidity - disease rate;mortality;Neurologic;new therapeutic target;novel;operation;Pathogenesis;Patients;Pharmacology;Population;Procedures;programs;Protocols documentation;Research;Research Personnel;Research Priority;Research Support;Safety;Scientific Advances and Accomplishments;Site;Specimen;Standardization;Testing;Therapeutic;Total Quality Management;Training and Education;Training Programs;Training Support;treatment guidelines;Tuberculosis;United States National Institutes of Health;virology

PROJECT_TITLE: AIDS Clinical Trial Group Laboratory Center


ORG_CITY: DAVIS

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Resistance to next generation anti-androgen agents such as enzalutamide and abiraterone occurs frequently and the mechanisms are incompletely understood. This application is aimed to understand the roles and the underlying mechanisms of Wnt5A signaling in resistant prostate cancer, and develop novel treatment strategies by targeting Wnt5A to treat advanced prostate cancer and overcome resistance to anti-AR therapies.

PI_NAMEs: GAO, ALLEN C. (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: abiraterone;advanced prostate cancer;Androgen Antagonists;androgen independent prostate cancer;Anti-androgen Therapy;Biological Availability;Biomedical Engineering;Cancer Patient;carcinogenesis;cell growth;Cells;Chronic;Clinical Data;clinical development;Clinical Research;Data;Development;Disease;Down-Regulation;Drug resistance;effective therapy;efficacy evaluation;enzalutamide;experimental study;Future;Generations;Goals;Growth;In Vitro;in vivo;inducible gene expression;inhibitor;knock-down;Knowledge;LNCaP;Malignant neoplasm of prostate;Mediating;Metastatic Neoplasm to the Bone;Modeling;next generation;novel;novel strategies;novel therapeutic intervention;Patients;Pharmaceutical Preparations;Play;prostate cancer cell;prostate cancer progression;Resistance;Resistance development;RNA;Role;Signal Transduction;Small Interfering RNA;small molecule inhibitor;Specimen;System;Testing;therapeutic target;therapy resistant;Tissues;Toxic effect;Transfer RNA;Translating;treatment strategy;tumor;tumor growth;tumor xenograft;Up-Regulation;Variant;WNT Signaling Pathway

PROJECT_TITLE: Therapeutic targeting Wnt5A signaling for advanced prostate cancer

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Lung

ORG_CITY: ALBANY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: Project Narrative: Given the strong and independent association between COPD mortality and locomotor muscle dysfunction, the proposed research is relevant to public health because the elucidation of the mechanisms regulating muscle dysfunction and dysregulated metabolism in that setting are ultimately expected to lead to better COPD outcomes. Indeed, a benefit of SDH and AMPK-modulating drugs on COPD-driven muscle dysfunction could have direct positive impacts on patients’ prognosis, which is relevant to the NIH mission.

PI_NAMEs: JAITOVICH, ADOLFO ARIEL (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: 5'-AMP-activated protein kinase;Acceleration;Activities of Daily Living;Address;Anabolism;Animal Diseases;Animal Model;Animals;Attenuated;Biogenesis;biological adaptation to stress;Biological Assay;Blood;Carbon Dioxide;Catabolism;Cell Respiration;Cells;Cessation of life;Chronic;Chronic Obstructive Pulmonary Disease;Clinical;Complex;coping;Data;Dedications;disability;disease model;Disease Outcome;Down-Regulation;Drug Modulation;Environment;Event;Exercise;experimental study;Exposure to;Fatigue;Fiber;Functional disorder;gain of function;Gene Deletion;Generations;Genetic;Goals;Hospitalization;Hypercapnia;improved;Knock-out;Long-Term Effects;loss of function;Lung Diseases;Measures;Mediating;Metabolic;Metabolic dysfunction;metabolic phenotype;Metabolism;Mission;Mitochondria;Modeling;Molecular;mortality;mouse model;Mus;Muscle;Muscle Cells;Muscle Fibers;muscle form;Muscle function;Muscle Weakness;Muscular Atrophy;Myopathy;Outcome;Oxidative Stress;Oxygen Consumption;patient prognosis;Patient-Focused Outcomes;Patients;Phenotype;prevent;Process;Property;protein degradation;protein metabolism;Proteins;Proteomics;Public Health;Publishing;Pulmonary Emphysema;Quality of life;Recovery;Regulation;Reporting;Research;Respiration;respiratory;Role;Skeletal Muscle;STK11 gene;Succinate Dehydrogenase;Toxic effect;Transgenic Animals;United States National Institutes of Health

PROJECT_TITLE: Metabolic regulation of hypercapnic chronic obstructive pulmonary disease (COPD)-driven skeletal muscle dysfunction

STUDY_SECTION: SMEP

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


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Brain Disorders;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: PHOENIX

ORG_NAME: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER

ORG_STATE: AZ

PHR: PROJECT NARRATIVE: This goal of this proposal is to investigate Parkinson’s-related changes in brain networks using a robust functional magnetic resonance imaging method, which increases sensitivity to brain activity and informs on microvascular function. This method will be used to characterize changes with Parkinson’s disease in preclinical models, as well as investigate changes in brain networks with specific biochemical modulations. These studies will provide insight into the underlying causes of altered brain networks observed in Parkinson’s disease.

PI_NAMEs: STOKES, ASHLEY M (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Acute;alpha synuclein;Back;Basal Ganglia;base;Behavioral;Biochemical;Biological Markers;Blood Vessels;Brain;Chronic;Clinical;clinical phenotype;clinical translation;Clinical Trials;Contrast Sensitivity;Control Groups;Coupled;Coupling;Detection;Development;diagnostic value;Disease;disease model;Disease Progression;Dopamine;dopaminergic neuron;Dorsal;Early Diagnosis;Etiology;Functional disorder;Functional Magnetic Resonance Imaging;Future;Genetic;genetic manipulation;Genetic Techniques;Goals;Healthcare;imaging biomarker;imaging modality;Imaging Techniques;improved;insight;Intervention;L-DOPA induced dyskinesia;Levodopa;Link;locus ceruleus structure;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measures;Methods;Modality;Modeling;Motor;motor symptom;Nature;network dysfunction;Neurodegenerative Disorders;neuronal circuitry;Neurons;neuropathology;neurophysiology;Neurotransmitters;neurovascular coupling;non-motor symptom;noradrenergic;novel;Oxidopamine;Parkinson Disease;Parkinsonian Disorders;Pathologic;Patients;Perfusion;pharmacologic;Play;Population;potential biomarker;pre-clinical;Pre-Clinical Model;pre-formed fibril;preclinical study;prognostic value;Progressive Disease;receptor;Research;Rest;Rodent Model;Role;Sensitivity and Specificity;side effect;Signal Transduction;standard care;Structure;synuclein;synucleinopathy;Techniques;Technology;Testing;Therapeutic;Time;translational therapeutics;Translations;Validation

PROJECT_TITLE: Multi-scale functional connectivity in preclinical models of Parkinson's disease

STUDY_SECTION: EITN

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


NIH_SPENDING_CATS: Hematology

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: PROJECT NARRATIVE  Platelets are anucleate cells that circulate in the blood and play critical roles in bleeding, stroke and cardiovascular disease (the number 1 killer in the US). Platelet function depends on internal compartments known as alpha granules, which are not well understood. Thus, elucidating the formation of platelet alpha granules is necessary to understand platelet function and the development of new therapeutic strategies for disease treatment and prevention.

PI_NAMEs: DI PIETRO, SANTIAGO MAURO (contact)

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: Actins;Address;Alpha Granule;angiogenesis;Angiogenesis Inhibitors;Arthrogryposis;Biochemical;biochemical tools;Biogenesis;Blood;Blood Coagulation Disorders;Blood Platelets;Bone Marrow;Cardiovascular Diseases;Carrier Proteins;Cell Culture Techniques;Cells;Cellular biology;Child;Cholestasis;Collaborations;Complex;CRISPR/Cas technology;Cytoplasmic Granules;Data Set;design;Development;Disease;Endocytosis;Endoplasmic Reticulum;Endosomes;experimental study;Gene Targeting;Genes;Genetic;Genetic Diseases;Goals;Golgi Apparatus;Health;Hemorrhage;Hemostatic Agents;Hemostatic function;Hospitals;Human;Human Genetics;Impairment;Inflammation;innovation;insight;kidney dysfunction;Knowledge;Letters;Lung;Lysosomes;Malignant Neoplasms;Mediating;Megakaryocytes;Membrane Proteins;Methods;Molecular;Morbidity - disease rate;mortality;mouse model;Mutate;Mutation;Myelofibrosis;novel;novel therapeutic intervention;Organelles;Pathway interactions;Patients;Physiological;Platelet Activation;Platelet aggregation;platelet function;Play;polymerization;Polymers;Population;population based;Positioning Attribute;precursor cell;Prevention;Process;Protein Biosynthesis;Proteins;Publications;Publishing;recruit;Research;response;Role;segregation;Site;SNAP receptor;Sorting;stem cells;Stroke;Syndrome;syntaxin;System;Testing;Thrombosis;Time;time use;trafficking;transcriptome sequencing;Universities;Vesicle;Visualization;Washington;Work;wound healing

PROJECT_TITLE: Molecular Mechanisms of Platelet Alpha Granule Biogenesis

STUDY_SECTION: HT

STUDY_SECTION_NAME: Hemostasis and Thrombosis Study Section.  Committee was terminated on 11/30/2020. [HT]


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Skin Cancer

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: FDA-approved BRAF inhibitors that target effectively mutated monomeric BRAF elicit remarkable clinical responses in BRAFV600E mutant melanoma, however, activated BRAF dimers remain poorly targeted, a fact that leads to limited progression free survival in melanoma and other tumors such as colorectal and thyroid with oncogenic BRAF signaling. Our proposal addresses this significant unmet medical need. We propose to use our expertise in drug discovery and unique insights into BRAF structure and regulation, to identify the next- generation BRAF inhibitors with high specificity for BRAFV600E dimers that will ultimately serve as prototype therapeutics.

PI_NAMEs: GAVATHIOTIS, EVRIPIDIS  (contact)

PROJECT_TERMS: Address;Binding;Biochemical;Biological Assay;Biophysics;BRAF gene;cancer cell;Cell Line;Cells;Clinical;clinically relevant;Colorectal;Colorectal Cancer;Colorectal Neoplasms;computational pipelines;Computing Methodologies;design;Development;dimer;Dimerization;Drug Design;drug development;drug discovery;Drug Kinetics;Drug resistance;experimental study;FDA approved;Feedback;Generations;Goals;Guanosine Triphosphate;Homo;Hybrids;improved;in silico;In Vitro;in vivo;inhibitor;innovation;insight;Investigation;Knowledge;Lead;lead optimization;Light;Malignant neoplasm of thyroid;Malignant Neoplasms;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Mediating;Medical;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Melanoma Tumor;Modeling;monomer;multidisciplinary;Mus;mutant;Mutate;Mutation;neoplastic cell;next generation;novel;Oncogenic;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Play;Process;Prognosis;Progression-Free Survivals;Property;prototype;PTPN11 gene;Quantitative Structure-Activity Relationship;Regulation;Resistance;resistance mechanism;response;RNA Splicing;screening;Series;Signal Transduction;Solid;Specificity;Structure;Therapeutic;Therapeutic Index;Thyroid Gland;thyroid neoplasm;Toxic effect;Translating;tumor;Validation;Variant;Xenograft Model

PROJECT_TITLE: Allosteric inhibitors targeting oncogenic BRAF V600E dimers


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

PHR: The research in this CDA2 proposal will address fundamental gaps in knowledge about [how to optimize the] management of urinary tract infections (UTIs), which are one of the most common complications experienced by Veterans with chronic neurologic disorders that affect bladder functioning (`neurogenic bladder'). Inappropriate UTI management causes diminished patient functioning and quality of life through adverse effects of inappropriate antibiotic use. [My project will support the development of a novel multifaceted patient- centered intervention to improve UTI management in patients with neurogenic bladder. Such an intervention could optimize UTI management via improved patient-provider communication and patient recognition and understanding of UTI signs and symptoms. Improved UTI management leads to more appropriate diagnosis and antibiotic use which, in turn, improves rehabilitative health, reduces illness and disability from infections and antibiotic side effects, and optimizes quality of life for these high priority Veteran populations.]

PI_NAMEs: FITZPATRICK, MARGARET A (contact)

PROJECT_TERMS: Adherence;adverse drug reaction;Adverse effects;adverse outcome;Affect;Anatomy;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Attitude;Bacteria;Bacteriuria;Belief;Bladder;Bladder Dysfunction;career;Caring;catalyst;Catheters;Cessation of life;Characteristics;Chronic;Chronic disability;chronic neurologic disease;Clinical;clinical decision support;clinical outcome measures;Clinical Treatment;Clostridium difficile;cohort;Communicable Diseases;Complex;computable phenotypes;Data;Development;Diagnosis;Diarrhea;disability;Disabling condition;Disease Management;Drainage procedure;Effectiveness of Interventions;Electronic Health Record;Ensure;Esthesia;evidence base;evidence based guidelines;expectation;experience;Foundations;functional improvement;Future;Geographic Locations;Goals;Guidelines;Health;high risk;Hospitals;Impairment;improved;Increased frequency of micturition;Infection;infection management;innovation;instrument;Intervention;Kidney Calculi;kidney dysfunction;kidney infection;Knowledge;Laboratories;Measures;medical specialties;Methods;military veteran;mortality;multi-drug resistant pathogen;multimodality;Multiple Bacterial Drug Resistance;Multiple Sclerosis;Nervous System Disorder;Nervous System Trauma;Neurogenic Bladder;novel;Outcome;Outcome Measure;Parkinson Disease;Patient Care;Patient Education;patient engagement;patient expectation;patient oriented;Patient Outcomes Assessments;patient population;patient subsets;patient-clinician communication;Patients;Persons;Population;prevent;Provider;provider adherence;provider factors;Qualitative Methods;Quality of life;Rehabilitation Outcome;Rehabilitation therapy;Reporting;Research;Research Personnel;Retrospective cohort study;Risk;Sepsis;Services;Shapes;side effect;Signs and Symptoms;Spinal cord injury;Spinal Dysraphism;Stroke;successful intervention;Surveys;Symptoms;Testing;treatment guidelines;urinary;Urinary tract;Urinary tract infection;Validation;Variant;Veterans

PROJECT_TITLE: Optimizing Management of Urinary Tract Infections in Patients with Neurogenic Bladder through Improved Knowledge of Provider Practice and Patient-reported Outcomes

STUDY_SECTION_NAME: Career Development Program - Panel II[RRD9]


ORG_CITY: SEATTLE

ORG_NAME: BENAROYA RESEARCH INST AT VIRGINIA MASON

ORG_STATE: WA

PHR: PROJECT NARRATIVE  Systemic lupus erythematosus is a complex autoimmune disease characterized by the presence of circulating autoantibodies to nucleic acids and proteins with which they associate. Signaling by cell surface receptors called Toll-like receptors on specific immune cells, plasmacytoid dendritic cells and B cells, promotes the development of lupus, and we have discovered a novel protein that controls this process. In this proposal, we will further define this new mechanism for control of lupus pathogenesis.

PI_NAMEs: HAMERMAN, JESSICA A (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Antibody Formation;Antibody Response;Antigen-Antibody Complex;Antigens;Area;Attention;Autoantibodies;Autoimmune Diseases;autoreactive B cell;B-Cell Activation;B-Cell Acute Lymphoblastic Leukemia;B-Lymphocyte Subsets;B-Lymphocytes;Biological;Biological Assay;Cell Maturation;Cell Surface Receptors;cell type;Cells;Complex;conditional knockout;cytokine;Data;Dendritic Cells;Development;Disease;disease model;Docking;Endosomes;Generations;Genes;Human;human disease;human model;Immune;immune activation;Immune response;Immune signaling;Immunoglobulin G;In Vitro;in vivo;Inflammatory;Interferon alpha;Interferons;Ligands;Lupus;lupus-like;Macrophage;Measures;Methods;Modeling;mouse model;Mus;novel;Nucleic Acids;Pathogenesis;pathogenic autoantibodies;PIK3CG gene;Plasma Cells;pleiotropism;Process;Production;Proliferating;Proteins;Regulation;response;Role;Signal Transduction;SLEB1 gene;Systemic Lupus Erythematosus;T cell response;therapeutic target;TLR7 gene;Toll-like receptors

PROJECT_TITLE: BCAP regulation of TLR7/9 signaling in Lupus

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


PHR: The research objective of this proposal is to elucidate the role of disc nutrition via the vertebral endplate in the initiation and progression of disc degeneration, and in the response of patients with back pain to non-operative treatment. The proposed research builds on Dr. Gullbrand’s previous research experience in animal models, disc nutrition and imaging, while allowing her to develop new skills and expertise in disc biology and clinical research. The proposed research is complimentary to the objectives of her mentors’ VA-funded research efforts in this area. This Career Development Award proposal identifies a mentoring team, career development and research activities that will support Dr. Gullbrand in transitioning towards a position as an independent VA investigator.

PI_NAMEs: GULLBRAND, SARAH E (contact)

PROJECT_TERMS: active duty;Adult;Affect;analog;Animal Model;Animals;Area;Articular Range of Motion;Atomic Force Microscopy;Back Pain;Biochemistry;Biological Assay;Biology;Blood Vessels;bone;Bone Density;Cadaver;career development;Caregivers;Caring;Cartilage;Cells;chronic pain;Clinical;Clinical Research;Clinical Treatment;contrast enhanced;Convection;Custom;density;Devices;Diffusion;disability;Disability scale;disc regeneration;distraction;Economic Burden;efficacious treatment;Etiology;Euthanasia;experience;Faculty;Fibrocartilages;fluid flow;functional outcomes;Funding;Gene Expression Profiling;General Population;Goals;Health;Heart;Histology;Homeostasis;Human;Image;improved;in vivo;Incidence;Intervertebral disc structure;intervertebral disk degeneration;K-Series Research Career Programs;Knowledge;Link;Location;Low Back Pain;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Measures;mechanical load;mechanical properties;Mechanics;Mentors;Microfils;Military Personnel;mineralization;Modeling;Motion;Needles;nucleus pulposus;Nutrient;nutrition;Nutritional;Oryctolagus cuniculus;Outcome;Pain;pain relief;Pathway interactions;patient response;Patient-Focused Outcomes;Patients;Physical therapy;Play;Positioning Attribute;predictive tools;Prevalence;Property;Puncture procedure;Questionnaires;regenerative;Regimen;Research;Research Activity;Research Personnel;response;Role;Sampling;Severities;skills;small molecule;social;Source;Spectroscopy, Fourier Transform Infrared;Spinal;spine bone structure;Stroke;Structure;success;Time;Tissue Engineering;Training;Transport Process;Travel;treatment strategy;United States;vertebra body;Vertebral column;Veterans;Visual;Waste Products;wasting;Weight-Bearing state;Work

PROJECT_TITLE: The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration

STUDY_SECTION_NAME: Career Development Program - Panel I[RRD8]


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

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Using sequencing analyses of human cancer genomes, we previously identified a form of extensive chromosomal rearrangement called the Tandem Duplicator Phenotype (TDP), which is found in ~50% of triple- negative breast cancers, as well as ovarian and endometrial cancers. To understand how different types of TDPs are formed in mammary tissues and then evolve in established breast tumors, our research will use genome sequencing analyses and exploit genetically engineered mouse models and cultured human breast cancer cells. The insights we gain into TDP formation and evolution will ultimately support clinical development of new TDP- targeting cancer treatments.

PI_NAMEs: LIU, EDISON TAK-BUN (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Address;Affect;anti-cancer research;anti-PD-1;Biological Markers;Biological Models;Biology;BRCA1 gene;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;breast tumorigenesis;Cancer cell line;cancer genome;Cancer Patient;cancer therapy;CCNE1 gene;Cell Line;Cells;Chromatin;Chromosomal Rearrangement;Classification;Clinical;Clinical Data;clinical development;Communities;Computer Analysis;conditional knockout;Data Set;Derivation procedure;Development;DNA;DNA biosynthesis;DNA replication fork;DNA Structure;Endometrial Carcinoma;Engineering;Enterobacteria phage P1 Cre recombinase;Evolution;G-Quartets;Gene Mutation;Generations;Genes;Genetic;Genetic Anticipation;genetic element;Genetically Engineered Mouse;Genome;genome sequencing;genome-wide;Genomic Instability;Genomic Segment;Genomics;Goals;Growth;Harvest;Human;Hybrids;Immunooncology;In Vitro;in vivo;in vivo Model;Individual;Injections;insight;Knockout Mice;Lead;Lentivirus;Link;Location;longitudinal analysis;loss of function;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;mammary;Mammary gland;Mammary Neoplasms;Maps;Meta-Analysis;Modeling;Molecular;Monitor;mouse model;Mus;neoantigens;Null Lymphocytes;Organoids;p53-binding protein 1;Pathway interactions;Pattern;pharmacologic;Phenotype;pre-clinical;precision oncology;premalignant;Protein Deficiency;Proteins;recombinase;repaired;replication stress;Research;Resources;response;RNA;Role;Shapes;Site;Source;Structure;Testing;Therapeutic;timeline;Tissues;TP53 gene;transcriptome;treatment response;triple-negative invasive breast carcinoma;tumor;tumorigenesis

PROJECT_TITLE: Genomic Biology of the Tandem Duplicator Phenotype in Mouse and Human Cancers

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Cancer;Clinical Research;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Malaria;Pediatric;Pediatric Cancer;Rare Diseases;Vector-Borne Diseases

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE Endemic Burkitt's lymphoma (BL), the most prevalent childhood cancer in Equatorial Africa, is a rapidly growing B-cell malignancy that is ultimately fatal if untreated. The knowledge gained by this study will improve the understanding of the etiology of endemic BL which will ultimately allow for the design of tools aimed at the prevention of BL.

PI_NAMEs: SAMAYOA REYES, GABRIELA M (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: activation-induced cytidine deaminase;Acute;Africa;Africa South of the Sahara;African Burkitt's lymphoma;B lymphoid malignancy;B-Cell Activation;B-Lymphocyte Subsets;B-Lymphocytes;BACH2 gene;Binding;Biology;Burkitt Lymphoma;C-Myc Translocation;cancer cell;Cell Line;Cell Nucleus;Cell Separation;Cells;Cellular biology;Characteristics;Child;Childhood;Circulation;Clinical;cofactor;Complex;cytokine;Cytolysis;Cytoplasm;Data;design;Disease;DNA;EBV reactivation from latency;Enzyme Activation;Epstein-Barr Virus latency;Epstein-Barr Virus-Related Malignant Neoplasm;Etiology;Event;Falciparum Malaria;Flow Cytometry;Frequencies;Genetic Transcription;Genome;Goals;Heme;hemozoin;high risk;Human Herpesvirus 4;IGH@ gene cluster;improved;Individual;infected B cell;Infection;Kenya;Knowledge;Life;Ligands;Link;Lymphocyte;Lytic;Lytic Virus;Malaria;malaria infection;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Memory B-Lymphocyte;Methylation;methylome;Modeling;Molecular;MYC gene;nanopore;pathogen;Peripheral Blood Mononuclear Cell;Phenotype;Plasma;plasma cell differentiation;Plasma Cells;Plasmodium falciparum;Population;Prevention;Research;Risk;RNA;Role;Sampling;Site;Structure of germinal center of lymph node;synergism;Testing;Time;Tonsil;tool;Transcript;transcription factor;tumorigenesis;Variant;Viral;Viral Load result;Viremia;Virus

PROJECT_TITLE: The synergistic contributions of EBV and malaria to the etiology of Burkitt lymphoma

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE This project is relevant to public health because 74 million US adults have undiagnosed prediabetes and 7.3 million have undiagnosed type 2 diabetes despite routine diabetes screening in clinical practice. Racial/ethnic minorities and those with known prediabetes are at increased risk for type 2 diabetes and experience screening disparities that contribute to delayed diagnoses and worse health outcomes. This proposal evaluates a screening strategy that supplements visit-based screening with a population health patient- outreach intervention to improve overall screening rates and decrease disparities in diabetes screening using specific messaging for racial/ethnic minorities and those with known prediabetes.

PI_NAMEs: BOWEN, MICHAEL EDWARD (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: Address;Adult;Affect;arm;automated intervention;Black Populations;case finding;Clinic;Clinical;clinical decision support;Clinical effectiveness;clinical practice;Communities;Complement;cost;cost effective;cost effectiveness;Cost Effectiveness Analysis;design;Detection;Development;Diabetes Mellitus;diabetes risk;Diagnosis;Direct Costs;Disparity;disparity reduction;effectiveness evaluation;efficacy evaluation;Electronic Health Record;Equity;ethnic diversity;ethnic minority;Ethnic Origin;Ethnic Population;Evaluation;evidence base;experience;Feedback;Focus Groups;Goals;Health system;Healthcare Systems;high risk;high risk population;Hispanic Populations;improved;Intervention;intervention cost;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;novel;outcome disparities;outreach;patient engagement;patient outreach;patient screening;Patients;Pilot Projects;poor health outcome;population health;Population Heterogeneity;pragmatic trial;Prediabetes syndrome;primary care clinic;primary care patient;Process;Program Effectiveness;programs;Provider;Public Health;Race;racial disparity;racial diversity;racial minority;Randomized;Randomized, Controlled Trials;response;Risk;Risk Assessment;safety net;screening;screening disparities;Screening for cancer;screening guidelines;screening program;Subgroup;Testing;three-arm study;treatment as usual;Visit

PROJECT_TITLE: Development and Evaluation of EHR-enabled Population Health Outreach Strategies to Improve Diabetes Screening in a Safety-net Health System:  a Pragmatic Randomized Controlled Trial

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The success of the mRNA vaccine platform in the context of COVID19 has sparked interest in its use for other viral diseases. Here we propose a general strategy for improving mRNA vaccines that enables the mRNA-encoded proteins assemble into more natural virus-like structures. These modifications will empower mRNA vaccines to raise better, longer-lasting antibody responses while reducing the amount of mRNA required in each dose.

PI_NAMEs: FARZAN, MICHAEL R. (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: 2019-nCoV;Acting Out;adaptive immunity;Adenovirus Vector;Animals;antagonist;Antibody Formation;Antibody Response;Antibody titer measurement;antigen binding;antigen test;Antigen-Presenting Cells;Antigens;Behavior;Capsid Proteins;Carrier Proteins;Cell Fraction;Cell Line;Cell membrane;Cells;cellular transduction;Characteristics;chicken egg;Communicable Diseases;COVID-19;COVID-19 vaccine;Data;design;Development;DNA;Dose;draining lymph node;Effectiveness;efficacy testing;empowerment;env Gene Products;Eukaryotic Cell;exosome;experimental study;extracellular vesicles;Feline Immunodeficiency Virus;Fluzone;Formulation;Glycoproteins;Hemagglutinin;HIV;HIV-1;Human;Immune;immunogenic;immunogenicity;Improve Access;improved;in vivo;Influenza A virus;influenza virus vaccine;Injections;interest;Interferons;iterative design;manufacturing process;Membrane;Messenger RNA;microvesicles;Modification;Molecular Conformation;mRNA delivery;mRNA lipid nano particle vaccine;Mus;Nonstructural Protein;panacea;pathogen;Patients;Performance;Pfizer-BioNTech COVID-19 vaccine;Preparation;prevent;process optimization;Production;Proteins;Recombinants;Reporting;Resistance;resistance mechanism;response;RNA vaccine;Route;Sampling;SARS-CoV-2 spike protein;scaffold;Serum;Site;Structure;Subunit Vaccines;success;Tail;Tertiary Protein Structure;Testing;tissue culture;Transfection;Translating;Vaccinated;vaccine delivery;vaccine efficacy;vaccine immunogenicity;vaccine platform;Vaccines;vector vaccine;Viral;Viral Antigens;Viral Envelope Proteins;Viral Matrix Proteins;Viral Proteins;Viral Vaccines;Virus;Virus Diseases;Work

PROJECT_TITLE: Improving mRNA vaccines with extracellular vesicle-associated immunogens

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]