ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Viral infections including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have placed a substantial strain on the health care system and have broad impacts on the health of US veterans. Due to the influence host factors have on outcomes post- infection, we will assess the impact of genetic and epigenetic factors on comorbidities and long-term outcomes among people with viral infection (acute, chronic, and resolved). Using the massive sample size, centralized electronic health records, and multi-ethnic population from the Million Veteran Program (MVP), we will employ advanced analytical approaches to identify genetic and epigenetic markers and molecular systems underlying the susceptibility, progression, and outcomes of HIV, HCV and SARS-CoV-2 infection. These results will provide substantial insight into the impact of infectious diseases on the health and lifespan of veterans with viral infections, improving diagnostic and therapeutic approaches to multi-morbidity and the aging process.

PI_NAMEs: MARCONI, VINCENT CHARLES (contact)

PROJECT_TERMS: 2019-nCoV;accelerated epigenetic aging;Acceleration;Acute;advanced analytics;Affect;age acceleration;age related;Aging;aging process;Algorithms;Anti-viral Therapy;Biological Aging;Chronic;Chronic Disease;Chronic Kidney Failure;chronic liver disease;Communicable Diseases;comorbidity;Congestive Heart Failure;Coronary heart disease;COVID-19 impact;Data;Diabetes Mellitus;Diagnostic;Disease;Disease Outcome;Disease Progression;disorder risk;DNA Methylation;Electronic Health Record;Epigenetic age;epigenetic clock;epigenetic marker;Epigenetic Process;epigenome-wide association studies;Ethnic Population;General Population;Genetic;Genetic Markers;Genetic Predisposition to Disease;genetic variant;genome wide association study;genomic locus;Health;Healthcare Systems;healthspan;Heart failure;Hepatitis C;Hepatitis C virus;HIV;HIV Infections;Human;Human Genetics;Human Genome;Immune;Immune response;Immune system;Immunologics;improved;Individual;Infection;Infectious Agent;Inflammatory;insight;Integration Host Factors;Intervention;Life Expectancy;life span;Link;Liver Cirrhosis;Liver Fibrosis;longitudinal analysis;Measurement;Mediation;Mendelian randomization;methylation biomarker;Modeling;Modification;Molecular;Morbidity - disease rate;mortality;multi-ethnic;Multiomic Data;multiple chronic conditions;novel marker;Organ;Outcome;pathogen;Pathway interactions;Persons;Phenotype;Population Heterogeneity;precision medicine;Predisposition;Prevention;Process;Prognosis;programs;Quality of life;response;Risk Factors;Role;Sample Size;SARS-CoV-2 infection;Site;Stroke;System;Therapeutic;Veterans;Virus Diseases

PROJECT_TITLE: Host Genetic and Epigenetic Factors of the Progression, Comorbidities and Outcomes of Viral Infection


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: DALLAS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Heart disease remains the number one cause of death worldwide, due to the inability of the injured adult heart to regenerate. Since the neonatal heart can efficiently regenerate following severe injury, we seek to understand the molecular basis of the neonatal regenerative response of the heart and its silencing with age to provide the capability of rebuilding cardiac muscle or regenerating the myocardium after injury.

PI_NAMEs: BASSEL-DUBY, RHONDA ;OLSON, ERIC N (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Adult;Age;Aging;angiogenesis;biological adaptation to stress;Cardiac;cardiac aging;Cardiac Myocytes;cardiac regeneration;cardiac repair;Cause of Death;cell type;Chromatin;cytokine;Data Set;Development;Disease;endoplasmic reticulum stress;Epicardium;epigenome;functional restoration;Gene Expression;Genes;Genetic Transcription;Global Change;Goals;Heart;Heart Diseases;heart function;Heart Injuries;improved;In Vitro;in vivo regeneration;injured;Injury;Knowledge;Macrophage;Maps;Mediating;Molecular;Myocardium;Natural regeneration;Neonatal;neonatal mice;Paracrine Communication;Pathway interactions;Play;Process;Proliferating;regeneration function;regeneration potential;regenerative;Regenerative capacity;Regenerative response;response;severe injury;single-cell RNA sequencing;Testing;Time;Transcription Coactivator;transcription factor;Transcription Repressor;Transcriptional Regulation

PROJECT_TITLE: Transcriptional Control of Neonatal Heart Regeneration

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Precision Medicine;Prostate Cancer;Urologic Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE The goal of this project is to investigate a new molecular imaging approach for novel measurements of drug target inhibition in an early-phase feasibility clinical trial in prostate cancer patients with bone metastases. While this early stage feasibility trial focuses on prostate cancer, these methods are designed to be applicable to other metastatic cancer MRI studies and in general to other cancer investigations.

PI_NAMEs: AGGARWAL, RAHUL ;VIGNERON, DANIEL B (contact)

PROGRAM_OFFICER_NAME: ZHANG, HUIMING

PROJECT_TERMS: 3-Dimensional;Address;advanced disease;advanced prostate cancer;Affect;androgen independent prostate cancer;Androgen Receptor;Androgens;antagonist;Biological Markers;biomarker driven;Biopsy;bone;Bone Diseases;Bone Pain;bone turnover;Bromodomains and extra-terminal domain inhibitor;burden of illness;cancer genomics;Cancer Model;Cancer Patient;Cessation of life;Clinical;Clinical Trials;cytopenia;Data;design;Detection;detector;Development;Disease;Disseminated Malignant Neoplasm;Down-Regulation;drug development;Drug Targeting;early phase trial;Early treatment;Enrollment;enzalutamide;Evaluable Disease;Evaluation;Feasibility Studies;feasibility trial;FOLH1 gene;Fracture;Generations;Goals;Health;Hypercalcemia;Image;imaging approach;imaging biomarker;imaging modality;improved;in vivo;ineffective therapies;inhibitor;Interdisciplinary Study;Investigation;investigator-initiated trial;Lactate Dehydrogenase;Letters;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Measurement;Measures;Mediating;Medical;Metabolic;metabolic imaging;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Methods;Molecular;molecular imaging;Monitor;Morbidity - disease rate;Neoplasm Metastasis;new therapeutic target;Noise;novel;novel strategies;novel therapeutics;Pathway interactions;Patient imaging;patient population;Patients;Pharmacotherapy;Phase;PIK3CG gene;Positron-Emission Tomography;pre-clinical;Prediction of Response to Therapy;Pyruvate;Renal Carcinoma;Research;Resistance;response;Running;Serum;Serum Markers;serum PSA;side effect;Signal Transduction;Site;stable isotope;targeted treatment;Techniques;Technology;Testing;Therapeutic Intervention;therapy development;therapy resistant;Time;tool development;Translating;treatment effect;Treatment Effectiveness;treatment response;Tropical Disease;United States National Institutes of Health;Widespread Disease

PROJECT_TITLE: Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will elucidate molecular regulation of HIV-specific T cell dysfunction, which will inform development of T cell-based HIV cure approaches, facilitate evaluation of immune responses in patients and clinical trial participants, improve clinical monitoring for risk of HIV rebound, and provide fundamental insights into immunobiology that can also be applied to the treatment of other infections and cancer. Thus, the proposed research is relevant to the NIH’s mission because it will generate fundamental knowledge that will advance the prevention and cure of human diseases.

PI_NAMEs: WALKER, BRUCE D (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Address;AIDS prevention;Antigens;antiretroviral therapy;Binding;biobank;Biological Markers;Blood;Bone Marrow;CCR5 gene;CD8-Positive T-Lymphocytes;Cell Therapy;Cells;checkpoint receptors;Chronic;chronic infection;Clinical;clinical trial participant;combat;comparative;Containment;cost;Couples;CXCR4 gene;cytotoxic CD8 T cells;Data;Development;Disease;Disease remission;Epigenetic Process;epigenetic profiling;Epitopes;Evaluation;exhaustion;experimental study;Functional disorder;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic Transcription;Heterogeneity;HIV;HIV Infections;human disease;immune activation;immune checkpoint;immune checkpoint blockade;Immune response;Immunobiology;Immunotherapy;Impairment;improved;In Situ;Individual;Infection;innovation;insight;Intervention;Intrinsic factor;Knowledge;Lymphocyte Activation;Lymphocyte Function;Lymphoid Tissue;Maintenance;Malignant Neoplasms;Mediating;Mission;Molecular;Molecular Target;Monitor;multiple omics;Mutation;novel;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Population;posttranscriptional;predictive marker;prevent;Prevention;Prevention strategy;Provirus Integration;Public Health;rational design;Regulation;Regulatory Pathway;Research;Resolution;response;restoration;Risk;Sampling;Signal Transduction;specific biomarkers;Specimen;success;superinfection;Systemic infection;Systems Biology;T-Cell Development;T-Lymphocyte;Therapeutic Intervention;Tissue Stains;Tissues;Transplantation;United States National Institutes of Health;Validation;Variant;Viral;viral rebound;Viral reservoir;Viremia

PROJECT_TITLE: Understanding and Reversing T Cell Dysfunction to Control and Eliminate Persistent HIV Reservoirs


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Machine Learning and Artificial Intelligence;Neurosciences;Pediatric

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE To better assess fetal neurological health, novel tools are needed to automatically and efficiently obtain high- quality HASTE fetal brain volumes and to characterize 3D fetal whole-body motion. We propose to leverage convolutional neural network (CNN) models to develop i) a “self-driving” engine on the scanner that assesses fetal head motion and image quality to efficiently acquire high-quality coherent fetal brain volumes; ii) an automatic tracking and characterization of fetal whole-body motion in stacks of 2D echo-planar images (EPI volumes). The ability to obtain efficient high-quality coherent fetal brain volumes and to characterize fetal motion, both independent of the user, will enable local assessment and triage of fetuses with suspected abnormalities such as Chiari II malformations to specialized treatment centers as well as facilitate large population-based studies to understand the impact of maternal substance abuse disorder, maternal obesity, or even infectious disease, such as COVID-19, on early brain development.

PI_NAMEs: ADALSTEINSSON, ELFAR ;GRANT, PATRICIA ELLEN (contact)

PROGRAM_OFFICER_NAME: LIU, GUOYING

PROJECT_TERMS: 3-Dimensional;Address;Anatomy;Archives;Automobile Driving;Behavior;Behavioral;Body part;Brain;brain abnormalities;brain magnetic resonance imaging;brain volume;Clinical;Clinical Research;clinically relevant;cognitive function;Collaborations;Collection;Communicable Diseases;Complex;convolutional neural network;COVID-19;Data;Databases;Defect;Deposition;Development;Diagnosis;Disease;Echo-Planar Imaging;Ensure;Environmental Exposure;Environmental Impact;Eye;fetal;Fetus;foot;Gestational Age;Head;Health;Human;Image;Imaging Device;improved;Intervention;Joints;Leg;Lesion;Life;Limb structure;Location;Magnetic Resonance Imaging;malformation;maternal obesity;Measures;Morphologic artifacts;Motion;motor deficit;Movement;neonatal brain;Nervous System Disorder;Nervous System Physiology;Network-based;Neural Network Simulation;Neurologic;novel;Opioid;Outcome;Paraplegia;Pathology;Performance;Phase;Population Study;Positioning Attribute;postnatal;Pregnancy;prospective;Prospective Studies;Protocols documentation;reconstruction;Resolution;response;Sampling;Scanning;Series;sex;Site;Slice;Specialized Center;Spinal;Spinal Dysraphism;Stratification;Structure;Substance abuse problem;success;T2 weighted imaging;Testing;Time;tool;Training;treatment center;Triage;ultrasound;Update

PROJECT_TITLE: Fetal MRI: robust self-driving brain acquisition and body movement quantification

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative The role of mitochondrial calcium uniporter complex in the regulation of cardiac function and energetics in rat remains unknown. This proposal intends to fill this knowledge gap. We will use a rat model that is genetically altered in cardiac specific mitochondrial calcium uniporter complex to obtain mechanistic insights into the regulation of this complex under healthy and failing heart. The findings from the proposed studies will provide novel insight for developing new therapeutic strategy to ameliorate cardiac injury and heart failure.

PI_NAMEs: CSORDAS, GYORGY  (contact);SHEU, SHEY-SHING

PROJECT_TERMS: Ablation;Acute;Address;adrenergic stress;Affect;Affinity Chromatography;Area;Bioenergetics;biological adaptation to stress;calcium uniporter;Cardiac;Cardiac Myocytes;Cardiotoxicity;Charge;Chronic;cohort;Complex;conditional knockout;Coupling;crista membrane;Data;design;dimer;disabled;Disease;Dominant-Negative Mutation;EFRAC;Energy Metabolism;Ensure;Equilibrium;Failure;fighting;Functional disorder;Funding;Generations;Genetic Models;Goals;Health;Heart;Heart Diseases;Heart failure;heart function;Heart Injuries;Injury;Inner mitochondrial membrane;insight;intermolecular interaction;Ischemia;Isoproterenol;Knock-out;Knowledge;Literature;Location;Mediating;Membrane;Mitochondria;Mitochondrial Matrix;Mitochondrial Membrane Protein;Modeling;Molecular;mouse genetics;Mouse Strains;Mus;Muscle Cells;mutant;N-terminal;novel;novel therapeutic intervention;Organelles;Outer Mitochondrial Membrane;overexpression;Oxidative Stress;paralogous gene;Pathogenicity;Pathologic;Phenotype;Play;preservation;prevent;Production;protein protein interaction;Proteins;Proteomics;Publishing;pyruvate dehydrogenase;Rattus;recruit;Regulation;Reperfusion Injury;Reperfusion Therapy;Role;Route;Sarcoplasmic Reticulum;scaffold;sensor;Signal Transduction;Stress;stress tolerance;Surface;System;Tail;Testing;Therapeutic;Toxic effect;Transgenic Organisms;Translating;uptake;Work;Workload

PROJECT_TITLE: Mitochondria-SR Tethering: Its Role in Cardiac Bioenergetics and Ca2+ Dynamics

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Clinical Research;Hematology;Lung

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Oxygen transport is a fundamental feature of higher order life forms. In humans an oxygen transport cascade transfers oxygen from the air to the tissues, and many diseases affect key steps in this cascade. Central to this process is the oxygen binding molecule hemoglobin. In this application I seek to explore 1) how changes in the affinity of hemoglobin for oxygen affects oxygen transport in humans, and 2) if changing the affinity of hemoglobin for oxygen might help patients with specific diseases that are marked by limitations in pulmonary and tissue oxygenation.

PI_NAMEs: JOYNER, MICHAEL J (contact)

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: Acute;Address;Affect;Affinity;Air;Altitude;Binding;Blood;CCL4 gene;Chronic;Clinic;Clinical;Complex;Congestive Heart Failure;Defect;design;Disease;Dissociation;drug repurposing;Educational process of instructing;Elements;Evolution;experience;experimental study;flexibility;follow-up;healthy volunteer;Hemoglobin;Human;Hypoxia;idiopathic pulmonary fibrosis;insight;Left;Life;Lung;Measures;Mitochondria;Molecular;Molecular Medicine;Muscle Mitochondria;Nature;Oxygen;oxygen transport;Patients;Pharmaceutical Preparations;Physiological;Physiology;Population;Process;Property;Pulmonary Diffusing Capacity;Qualifying;Regulation;response;Risk Taking;Sentinel;System;tissue oxygenation;Tissues;Translating;translational potential;Translations;Variant;Work of Breathing

PROJECT_TITLE: Variant Hemoglobin and Cardiorespiratory Regulation in Humans


NIH_SPENDING_CATS: Cancer;Infectious Diseases;Rare Diseases;Skin Cancer

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project narrative Merkel cell polyomavirus (MCPyV) is the most recently discovered human oncogenic virus that can cause a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). We recently discovered that MCPyV infection induces robust innate immune responses, which in turn repress viral amplification and spread. In this study, we will investigate how MCPyV interfaces with the host immune response to achieve persistent infection and how disruption of the host innate immunity contributes to MCC tumorigenesis.

PI_NAMEs: YOU, JIANXIN  (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: 3-Dimensional;antagonist;Architecture;Award;Biological Assay;Biological Response Modifiers;Cell Culture System;Cell Culture Techniques;Cell Proliferation;Cellular Tropism;chronic infection;Clustered Regularly Interspaced Short Palindromic Repeats;cytokine;Data;Death Rate;Dermal;Development;DNA;Dominant-Negative Mutation;driver mutation;effective therapy;Elderly;epidemiology study;Equilibrium;Etiology;Event;Failure;Fibroblasts;gene function;General Population;Genes;Genetic Transcription;Genome;Goals;Host Defense Mechanism;Human;Immune;Immune response;Immune signaling;Immune system;Immunity;Immunocompromised Host;immunosuppressed;Immunosuppression;In Vitro;Incidence;Individual;Infection;innate immune pathways;Innate Immune Response;innate immune sensing;Innate Immune System;Interferons;Knock-out;Knowledge;Malignant Neoplasms;Mediating;Merkel cell carcinoma;Merkel Cells;metaplastic cell transformation;Modeling;Molecular;multidisciplinary;Mus;Natural Immunity;novel;novel strategies;Nucleic Acids;Oncogenic;Oncogenic Viruses;pathogen;Pathologic;Pathway interactions;Pattern;Play;Polyomavirus;Polyomavirus Infections;Population;Premalignant Cell;prevent;Productivity;Proliferating;Repression;Research;Risk;Role;sensor;Signal Pathway;Signal Transduction;Signaling Protein;Skin;Skin Cancer;Stimulation of Cell Proliferation;Stimulator of Interferon Genes;Supporting Cell;System;Testing;tool;Tropism;tumor;Tumor Suppressor Proteins;tumorigenesis;UV carcinogenesis;Viral;Viral Genome;Virus;Virus Diseases;virus related cancer;Virus Replication;Xenograft Model

PROJECT_TITLE: Merkel cell polyomavirus infection, host response, and viral oncogenic mechanism

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Neurosciences

ORG_DEPT: NEUROSURGERY

PHR: Project Narrative Evidence from rodent studies, computational modeling, and our recently published human data implicate a unique class of neurons in the hippocampus (`time cells’) in the representation of temporal information critical for episodic memory processing, a form of memory especially sensitive to the effects of Alzheimer’s Disease. We propose to address critical gaps in understanding of human time cells, including the participation of time cells in neuronal assemblies and how time cells support serial recall memory. Finally, we propose a unique paradigm using cholinergic modulation (intravenous scopolamine) to alter time cell activity, including theta phase precession.

PI_NAMEs: LEGA, BRADLEY C (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Address;adjudication;Affect;Alzheimer's Disease;Animals;Anterior;Anti-Cholinergics;Articulation;Behavioral;Biological Assay;Brain;cell assembly;Cell model;Cells;cholinergic;Code;Collection;Computer Models;Data;Data Set;Degenerative Disorder;detection method;Disease;Drops;Electroencephalography;Elements;entorhinal cortex;Epilepsy;Episodic memory;Event;Exhibits;expectation;experience;experimental study;Fire - disasters;flexibility;Functional disorder;Goals;Hippocampus;Human;human data;innovation;Intravenous;Measures;medial temporal lobe;Memory;Memory Disorders;memory encoding;memory process;memory recall;Methods;Microelectrodes;millisecond;Modeling;nerve supply;Neurons;neurosurgery;novel;Participant;Patients;Pattern;Performance;Pharmaceutical Preparations;pharmacologic;Phase;Physiological;Population;predictive modeling;Property;Publishing;Ramp;Research;Rodent;Rodent Model;Role;Scopolamine;stem;Structure;success;Supporting Cell;Testing;Time;Work

PROJECT_TITLE: Behavioral and pharmacological manipulation of time cell activity in the human mesial temporal lobe


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BUFFALO

ORG_NAME: VA WESTERN NEW YORK HEALTHCARE SYSTEM

ORG_STATE: NY

PHR: Over two decades following the Persian Gulf War, up to 250,000 veterans are plagued by chronic conditions, including debilitating respiratory symptoms. Dysregulated inflammation is a hallmark of Gulf War respiratory illness (GWRI) shared with related lung diseases, notably COPD. Yet, no underlying etiology has been identified and no reliable treatment is available. While airway microbiota and alveolar macrophages are key to immunoregulation in COPD, their roles in GWRI remain unexplored. This proposal will be the first investigation into the role of the airway microbiome and alveolar macrophage dysfunction in the pathogenesis of GWRI. Study will further integrate epidemiologic exposures, particularly deployment-related inhalation, and investigate extra-pulmonary macrophage function to determine if GWRI macrophage dysfunction is compartmentalized. Comprehensive identification of innate immune defects and airway microbiota will provide a critical step toward designing immunotherapeutic treatments to improve outcomes of patients with GWRI.

PI_NAMEs: BERENSON, CHARLES S (contact)

PROJECT_TERMS: Address;Adult;airway inflammation;Alveolar Macrophages;Antibiotics;Area;Award;Bacterial Antigens;bacteriome;Biological Process;Bronchiolitis;Bronchoalveolar Lavage;Bronchodilator Agents;Chronic;Chronic Obstructive Pulmonary Disease;Clinical;clinical epidemiology;Defect;Defense Mechanisms;demographics;design;Diffuse;Disease Progression;Epidemiology;Etiology;Evaluation;Fatigue;Functional disorder;Goals;Gulf War;Gulf War veteran;Human;human disease;Immune;immune function;Immune System Diseases;Immunologics;immunoregulation;Immunotherapeutic agent;Impairment;improved;improved outcome;Inflammation;inflammatory lung disease;Inhalation;Innate Immune Response;interest;Interruption;Investigation;Link;Lung;Lung Diseases;lung microbiome;lung microbiota;Macrophage;microbiome;microbiome alteration;microbiome composition;microorganism interaction;Musculoskeletal;neglect;Neurocognitive Deficit;novel strategies;Outcome;Participant;pathogen;Pathogenesis;Patient-Focused Outcomes;Persian Gulf;Persian Gulf Syndrome;Phagocytes;Phagocytosis;Pseudomembranous Colitis;pulmonary function;Pulmonary Inflammation;recruit;Regulation;Research;research clinical testing;Research Design;respiratory;Respiratory Disease;respiratory microbiome;respiratory microbiota;respiratory pathogen;Respiratory Signs and Symptoms;response;restoration;Role;Signal Transduction;Steroids;Symptoms;Testing;Therapeutic;therapeutic target;transcriptome;translational impact;Veterans;Volunteer Group

PROJECT_TITLE: Alveolar macrophage dysregulation in the pathogenesis of Gulf War respiratory illness


ORG_CITY: DURHAM

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: The proposed research is relevant to public health because this project will dissect the mechanisms underly- ing immune responses after cardiac arrest and resuscitation. This is relevant to the NIH’s mission because knowledge obtained from the proposed research will inform the development of novel post-resuscitation care strategies to improve outcome of cardiac arrest patients, which will advance the Nation’s capacity to protect and improve health.

PI_NAMEs: YANG, WEI  (contact)

PROGRAM_OFFICER_NAME: SOPKO, GEORGE

PROJECT_TERMS: Acute;Address;Admission activity;Adrenal Glands;Anti-Inflammatory Agents;Antibiotic Therapy;apoptosis in lymphocytes;B-Lymphocytes;Bacterial Counts;biobank;Blood specimen;Brain;Cardiopulmonary Resuscitation;Caring;Cessation of life;Clinical;clinical outcome measures;Clinical Research;clinically relevant;clinically significant;cytokine;Data;Death Rate;Development;Disease;functional outcomes;Future;Genetic;Glucocorticoid Receptor;Glucocorticoids;Goals;Health;Healthcare;Heart Arrest;Homeostasis;Hour;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Immune;Immune response;Immune system;Immune System Diseases;immunomodulatory strategy;immunopathology;immunoregulation;Immunosuppression;Impairment;improved;improved outcome;Incidence;Infection;infection rate;Inflammasome;Inflammatory;Inflammatory Response;insight;Intensive Care Units;Knockout Mice;Knowledge;Link;Literature;Lung;Lymphocyte;Lymphocyte Function;Lymphopenia;Lymphopoiesis;Mediating;Mission;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Neurosecretory Systems;novel;novel therapeutic intervention;old mice;older patient;Outcome;Outcome Study;Pathology;Pathway interactions;patient population;Patients;pharmacologic;Phase;Phenotype;Pilot Projects;Pituitary Gland;Prognosis;prophylactic;Public Health;Recovery of Function;Reporting;Research;Resources;Resuscitation;Role;sex;Stress;Survivors;Syndrome;T-Lymphocyte;Testing;tool;United States National Institutes of Health;Work

PROJECT_TITLE: Immunosuppression after cardiac arrest and resuscitation

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ADMINISTERING_IC: ES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: The BREATHE (Bridging Research, Lung Health, and the Environment) Children's Center aims to translate decades of research and put science into practice with novel communication strategies that inform and engage students, community members, health professionals, and policymakers. The Kids BREATHE Lung Health Dashboard incorporates data visualization and tracking to educate and engage the public; the Lung Health Ambassador Program delivers an educational curriculum with training to empower individuals to advocate for environmental interventions; and the Lung Health Corps provides a network of motivated volunteers to advance children's environmental respiratory health in their communities. In building these tools, the BREATHE Center investigators will engage early stage investigators from diverse backgrounds to build a pipeline of future leaders promoting children's environmental respiratory health.

PI_NAMEs: KOEHLER, KIRSTEN ANNE;MCCORMACK, MEREDITH C (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: Address;Advocacy;Advocate;American Lung Association;Baltimore;career;Child;Childhood Asthma;Cities;Communication;Communication Tools;Communities;Country;COVID-19;COVID-19 pandemic;dashboard;data visualization;Development;Education;Educational Curriculum;empowerment;Environment;Environmental Exposure;Environmental Hazards;Environmental Health;environmental health disparity;environmental intervention;Environmental Risk Factor;evidence base;Evidence based intervention;Foundations;Future;General Population;Goals;Grant;Health;Health Disparities Research;Health education;Health Professional;Health Sciences;High School Student;improved;Individual;Infant;Intervention;Knowledge;Lead;lung health;Maps;Maryland;member;Mentors;Methods;Mission;Modeling;National Institute of Environmental Health Sciences;next generation;novel;novel strategies;Pilot Projects;Policies;Policy Maker;Population;programs;Recording of previous events;Research;Research Personnel;Resources;respiratory;Respiratory Disease;respiratory health;response;Risk;Risk Reduction;SARS-CoV-2 infection;Schools;Science;Scientist;student participation;Students;success;Techniques;tool;Training;Translating;translational framework;translational goal;Translations;United States Environmental Protection Agency;urban setting;Visualization;volunteer;Work;Youth

PROJECT_TITLE: BREATHE - Bridging Research, Lung Health, and the Environment - Children's Center


NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: MCCORMACK, MEREDITH C (contact)

PROJECT_TERMS: Acceleration;Air Pollution;Area;Arts;Back;Biometry;career;career networking;Child;Child Health;Communication;Communication Tools;Communities;community engaged research;community engagement;COVID-19;dashboard;Data;data visualization;Dedications;Development;Education;Educational Curriculum;Effectiveness;Ensure;Environment;Environmental Exposure;Environmental Health;environmental health disparity;Epidemiology;Event;evidence base;experience;Fostering;Foundations;Funding;Future;Future Generations;Goals;Health;health management;Health Policy;Health Professional;Individual;International;Intervention;Leadership;lung health;medical schools;Medicine;meetings;member;Mentors;Mission;National Institute of Environmental Health Sciences;next generation;novel;online course;Pediatrics;Physicians;Policy Maker;Predisposition;Process;Productivity;programs;Public Health Schools;Qualifying;Request for Applications;Research;Research Personnel;Resources;respiratory health;Risk Reduction;Schools;Science;Scientist;student participation;symposium;Translating;Translational Research;Translations;United States National Institutes of Health;Universities;Vision;volunteer;Work

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Disability Research;Hearing Loss;Neurosciences;Rehabilitation

ORG_CITY: CHAPEL HILL

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: The relevance of this project to public health is that it advances our understanding of the hearing difficulties experienced by older listeners, both with and without hearing loss, in everyday settings where multiple sound sources are present at the same time. Social wellbeing relies on the ability to communicate in this complex soundscape so it is essential to understand the spatial hearing skills necessary to function successfully in these environments. The findings of this project will be directly relevant to the public health challenge of addressing the communication difficulties experienced by the burgeoning older population.

PI_NAMEs: GROSE, JOHN H (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Acoustics;Address;Adult;Age;age effect;Auditory;Auditory system;Behavioral;Binaural;binaural hearing;Brain;Clinical;Cochlea;Cochlear Hearing Loss;Cognitive;Communication;Communication difficulty;Complex;Consensus;Dependence;design;Ear;Electrophysiology (science);Environment;Event;Exhibits;experience;experimental study;Functional disorder;Goals;Hearing;hearing impairment;innovation;Location;Masks;Measures;middle age;neural;normal hearing;novel;Older Population;Outcome;Participant;Performance;Peripheral;Phase;Play;Predisposition;Psychophysics;Public Health;Role;segregation;senescence;skills;Social Well-Being;sound;Source;Speech;speech in noise;Speech Intelligibility;speech recognition;Structure;Testing;Time;Work

PROJECT_TITLE: Binaural Processing and Spatial Hearing: Effects of Age and Hearing Loss

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Lung;Pediatric

PI_NAMEs: HANSEL, NADIA N (contact)

PROJECT_TERMS: Address;Attention;Award;Behavioral Sciences;career;career development;catalyst;Child;Child Health;Childhood;Clinical Trials;Collaborations;Communication;Communities;community engaged approach;community engaged research;Dedications;design;Development;Education;Educational process of instructing;Educational workshop;Ensure;Environment;Environmental Exposure;Environmental Health;Epidemiology;Equipment;Equipment and Supplies;experience;Faculty;Feedback;Fostering;Foundations;General Population;Goals;Health;implementation science;Infrastructure;innovation;Institution;International;Learning;lung health;Medicine;meetings;member;Mentors;Mission;Modeling;multidisciplinary;next generation;novel;Outcome;Pilot Projects;Policies;Process;programs;Pulmonology;Recording of previous events;Request for Applications;Research;Research Personnel;Resources;respiratory health;Review Committee;Science;Scientist;senior faculty;social;success;Time;Training;Translations;Trust

PROJECT_TITLE: Development Core


NIH_SPENDING_CATS: Clinical Research;Lung;Pediatric;Prevention;Social Determinants of Health

PROJECT_TERMS: Address;Adoption;Advocacy;Advocate;Area;Baltimore;Behavioral;career development;Child;Childhood Asthma;Cities;Communication;Communication Tools;Communities;Country;COVID-19;COVID-19 pandemic;dashboard;Data Display;design;Development;Educational Curriculum;empowerment;Environment;Environmental Exposure;Environmental Hazards;Environmental Health;environmental health disparity;Environmental Risk Factor;Epidemiology;evidence base;Feedback;Fostering;Foundations;Future;General Population;Goals;Health;Health education;Health Policy;Health Professional;High School Student;improved;innovation;Intervention;Investments;Knowledge;lung health;Maps;member;Modeling;National Institute of Environmental Health Sciences;novel;Policies;Policy Maker;programs;Public Policy;Reporting;Research;Research Personnel;respiratory health;response;Risk;Risk Reduction;Schools;Science;student participation;Students;success;symposium;Time;tool;Training;Translating;translational framework;Translations;Universities;urban setting;volunteer;web-based tool;Youth

PROJECT_TITLE: Translation Core


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

ORG_CITY: SAINT LOUIS

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: Hepatitis B virus (HBV) chronically infects ~290 million people world-wide and kills ~900,000 annually by inducing liver failure or liver cancer, but current therapies are not curative and only partially suppress disease progression. HBV replicates by coordinate action of the viral reverse transcriptase and ribonuclease H (RNaseH) activities, but the effects of the RNaseH on viral biology are very poorly understood despite the RNaseH being an attractive unexploited drug target. Here, we will use our unique recombinant HBV RNaseH, RNaseH assays, and inhibitors to define the RNaseH’s effects on viral replication, the spectrum of RNaseH resistance mutations that are selected by RNaseH inhibitors, and how the RNaseH affects HBV’s interactions with cells.

PI_NAMEs: TAVIS, JOHN E (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Address;Affect;analog;Biological Assay;Biology;Capsid;Cell Culture Techniques;Cells;Chronic;Circular DNA;Clinical;Collection;Communication;Complex;Data;detection limit;Development;Disease Progression;DNA;DNA biosynthesis;DNA Viruses;DNA-Directed DNA Polymerase;drug discovery;Drug Targeting;endoplasm;Endoplasmic Reticulum;Enzymes;fitness;genetic regulatory protein;Genome;Hepatitis B;Hepatitis B Therapy;Hepatitis B Virus;Hepatitis B virus Pol Protein;Heteroduplex DNA;improved;Infection;inhibitor;Interferons;Kinetics;Link;Liver Failure;Malignant neoplasm of liver;monomer;Mutation;novel therapeutics;Nuclear;Patients;Persons;Pharmaceutical Preparations;Play;Protein Isoforms;Proteins;Recombinants;Recycling;Resistance;Resistance development;resistance mutation;response;Reticulum;Reverse Transcription;Ribonuclease H;RNA;RNA-Directed DNA Polymerase;Role;screening;Site;Time;tool;Translations;Trefoil Motif;tumorigenesis;Viral;viral DNA;viral fitness;Viral Genome;viral RNA;Virion;Virus;Virus Integration;Virus Replication;Work

PROJECT_TITLE: HBV RNaseH inhibitors: Effects on HBV biology and resistance development

STUDY_SECTION: DDR

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHARLESTON

ORG_DEPT: SURGERY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: NARRATIVE Adoptive T cell immunotherapy studies predominantly comprise of terminally differentiated T cells with effector memory (Tem) phenotype, which have a limited life span. We believe higher expression of thioredoxin and thioredoxin regulated thiols is key to the central memory (Tcm) phenotype, which has been associated with better tumor control. This proposal will comprehensively establish thioredoxin regulated thiols and antioxidant capacity as biomarker for identifying T cells that persist longer in vivo and will also emphasize that `anti-oxidant help' is central in generation of robust anti-tumor memory T cell response - which is of immediate translational significance.

PI_NAMEs: MEHROTRA, SHIKHAR  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Acids;Adoptive Cell Transfers;Adoptive Transfer;alpha ketoglutarate;Antioxidants;Biological Markers;Cell surface;Cells;Citric Acid Cycle;Clinic;Clinical;Complement;Crossbreeding;Data;Development;Effectiveness;Ensure;Epigenetic Process;Epitopes;Event;Exhibits;experimental study;FRAP1 gene;Generations;glucose uptake;Glycolysis;Human;Human Engineering;Immunosuppression;Immunotherapy;improved;in vitro activity;in vivo;innovation;inorganic phosphate;Knockout Mice;Knowledge;Learning;life span;Malignant Neoplasms;Measures;Mediating;Membrane Potentials;Memory;Metabolic;Metabolic Pathway;metabolic phenotype;Metabolism;mitochondrial membrane;mitochondrial metabolism;Mouse Strains;Mus;Outcome;overexpression;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;Pathway interactions;Patients;Pentosephosphate Pathway;Phenotype;Population;Post-Translational Protein Processing;programs;Property;Protocols documentation;Recombinants;Recurrent tumor;Reporting;response;Retroviral Vector;Role;Signaling Molecule;Stem cell pluripotency;stemness;subcutaneous;Sulfhydryl Compounds;Surface;T cell differentiation;T cell response;T cell therapy;T memory cell;T-Cell Development;T-Lymphocyte;Transcription Factor AP-1;Transgenic Mice;Transgenic Organisms;translational potential;Treatment Efficacy;tumor;tumor growth;Tumor Immunity;tumor microenvironment;TXN gene

PROJECT_TITLE: Anti-oxidant and Metabolic Phenotype in Regulating Tumor Specific T cell Memory Response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-A(55)R]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Disability Research;Dissemination and Implementation Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE Individuals without intellectual disability make up the fastest-growing subgroup of autism spectrum disorders, but as few as 9% reach full functional independence as adults. This project tests the effectiveness of a novel school-based executive function intervention for transition-age youth with autism, to improve flexible problem- solving and planning skills that drive pivotal adult outcomes. If successful, the proposed project will demonstrate the widespread effectiveness and feasibility of an accessible intervention to improve transition outcomes for youth with autism that can be rapidly disseminated and implemented by schools across the nation.

PI_NAMEs: KENWORTHY, LAUREN  (contact)

PROGRAM_OFFICER_NAME: BURSTEIN, MARCY ELLEN

PROJECT_TERMS: access disparities;Adaptive Behaviors;Adherence;Adolescence;adolescent with autism spectrum disorder;Adoption;Adult;Advocacy;Advocate;Aftercare;Age;Area;autism spectrum disorder;Behavior;Behavioral;Caring;Cognitive;college;Communities;Community Trial;Data;design;Development;dosage;Education;effective intervention;Effectiveness;effectiveness evaluation;effectiveness testing;effectiveness trial;effectiveness/implementation trial;Emotions;Evaluation;evidence base;Evidence based intervention;Evidence based practice;Executive Dysfunction;executive function;Failure;falls;Family;flexibility;follow-up;functional independence;Funding;Future;future implementation;Goals;high school;Human Resources;Impairment;implementation determinants;implementation evaluation;implementation facilitators;implementation strategy;implementation trial;improved;improved outcome;Individual;individuals with autism spectrum disorder;Intellectual functioning disability;Intervention;K-Series Research Career Programs;Knowledge;Link;Mental Health Services;Methods;Mission;Modeling;Monitor;National Institute of Mental Health;neural network;Neuronal Plasticity;novel;Outcome;Penetration;Persons;physical conditioning;Population;Prefrontal Cortex;Prevalence;primary outcome;Problem Solving;process evaluation;psychiatric symptom;Public Health;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Research;Research Personnel;response;Risk;Schools;secondary outcome;Secondary Schools;Services;skills;social skills;Social support;Societies;Stress;Students;Subgroup;success;System;Techniques;Teenagers;Therapeutic;therapy design;Thinking;Time;Time Management;transition to adulthood;Youth

PROJECT_TITLE: A hybrid effectiveness-implementation trial of a school based executive function treatment for transition age youth with autism


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: UTICA

ORG_NAME: MASONIC MEDICAL RESEARCH LABORATORY, INC

PHR: NARRATIVE Cardiomyocytes (CMs) are the building blocks and function units of the heart, and their loss or dysfunction is the root of heart failure. Pathologic stress within the heart activates CM innate immune responses, which are beneficial for tissue repair, but can also cause cardiac inflammation and myocardial damage including CM dysfunction or death. In this proposal, we will determine the roles of YAP and IRF2BP2 in the regulation of CM innate immune responses, and evaluate the potency of these two proteins as novel druggable targets for treating acute myocardial infarction disease.

PI_NAMEs: LIN, ZHIQIANG  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acceleration;Acute myocardial infarction;Adult;Binding;Binding Proteins;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiogenesis;Cardiomyopathies;cell type;Cells;Cessation of life;ChIP-seq;Chronic;clinical application;cofactor;Complex;cytokine;Data;Disease;efficacy testing;Exposure to;Functional disorder;gain of function;Genes;genetic corepressor;Genetic Transcription;Goals;Growth;Heart;Heart Diseases;Heart failure;heart function;Heart Injuries;Immune;Immune signaling;In Situ;in vitro activity;in vivo;Inflammatory;Injury;innate immune pathways;Innate Immune Response;Innate Immune System;innovation;Interferon Regulatory Factor 2;Invaded;Ischemia;Knock-in Mouse;Lipopolysaccharides;loss of function;Maintenance;MAP3K7 gene;Mediating;Methods;Modeling;Molecular;Mus;myocardial damage;Myocardial Infarction;Myocardial Ischemia;Myocarditis;nanoparticle;new therapeutic target;NF-kappa B;novel;novel therapeutic intervention;overexpression;pathogen;Pathogenesis;pathogenic bacteria;Pathologic;Pathway interactions;Pattern;Pattern recognition receptor;Phosphotransferases;Process;Production;Proteins;Publishing;Reactive Oxygen Species;Regulation;Reperfusion Injury;Reperfusion Therapy;Reporting;restraint;Role;Signal Pathway;Signal Transduction;Stress;System;Testing;therapeutic target;tissue repair;TLR4 gene

PROJECT_TITLE: YAP and IRF2BP2 regulation of cardiomyocyte innate immune responses

STUDY_SECTION: BBHV

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Wound Healing and Care

ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Epithelial cell function is crucial for the human body. Many diseases such as metastatic cancer manifest through aberrant surface delivery of proteins in epithelial cells or overgrowth of epithelial tissues. The proposed research will provide insights into fundamental regulatory processes that govern epithelial polarity, which is necessary to enable development of novel strategies to treat or to prevent human diseases.

PI_NAMEs: FOLSCH, HEIKE  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Amino Acids;Apical;apical membrane;Area;autosome;basolateral membrane;Biochemical;Biochemistry;Biological;Biological Assay;Cell Adhesion Molecules;Cell membrane;cell motility;Cell Physiology;Cell Polarity;Cells;Chronic;Clathrin Adaptors;Complement;Complex;Crohn's disease;Development;Disease;Disseminated Malignant Neoplasm;Elements;Endocytosis;Endosomes;Epithelial Cells;Epithelium;Exocytosis;experimental study;Focal Adhesions;Growth;Growth Hormone Receptor;Health;Homeostasis;Human;Human body;human disease;hypercholesterolemia;Imaging Techniques;Inflammation;innovation;insight;Integrins;intestinal epithelium;Kidney Diseases;Laboratories;Lipids;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Microscopy;migration;Molecular;monolayer;Monomeric GTP-Binding Proteins;Nature;novel;novel strategies;Nutrient;Organ;Organizational Change;phosphoinositide-3,4,5-triphosphate;Phosphotransferases;photoactivation;Play;Polycystic Kidney Diseases;Post-Translational Protein Processing;prevent;Process;Proteins;receptor;Receptor Signaling;recruit;Recycling;Reporting;Research;Role;Sorting;Speed;Surface;Testing;Tissues;TLR3 gene;trafficking;trans-Golgi Network;uptake;Vesicle;Waste Products;Work;wound;wound healing

PROJECT_TITLE: Role of Membrane Trafficking in Epithelial Homeostasis

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer

PHR: Project narrative The NRF2 transcription factor orchestrates cellular anti-oxidant response, promoting a reductive environment that is generally required for unchecked proliferation. Surprisingly, in ~16% of non small cell lung cancer (NSCLC) cell lines, NRF2 activation leads to a severe block in growth resulting from a decrease in mitochondrial metabolism and electron transport chain dysfunction. The goal of this application is to use a suite of advanced metabolomic, chemical-proteomic and genomic technologies to understand how the NRF2 regulated cellular environment is detrimental to cell proliferation and to test the efficacy of activating NRF2 in vivo to block NSCLC growth.

PI_NAMEs: BAR-PELED, LIRON  (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: anti-cancer therapeutic;Antioxidants;Applications Grants;Aspartate;Biochemical;Biologic Characteristic;Biological Assay;Biological Markers;Biology;biomarker identification;cancer cell;Cancer cell line;Cancer Model;Cancer Patient;cancer therapy;cancer type;cell growth;Cell Proliferation;Cells;Chemicals;cohort;Companions;Complex;CRISPR screen;Cysteine;Dependence;Drug Metabolic Detoxication;efficacy evaluation;efficacy testing;Electron Transport;Environment;Enzymes;Equilibrium;experimental study;Foundations;Functional disorder;functional genomics;Gene Deletion;Generations;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;Growth;Homeostasis;Impairment;In Vitro;in vivo;insight;Lead;lung cancer cell;Maintenance;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Mediating;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;Mitochondria;mitochondrial metabolism;Modeling;Modification;mutant;Mutation;next generation;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Oncogenic;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Patients;pharmacologic;Pharmacology;Play;Point Mutation;potential biomarker;Production;Proliferating;protein function;Proteins;Proteomics;Reactive Oxygen Species;reconstitution;Regulation;Research;Respiration;response;Role;Series;Signal Transduction;Signal Transduction Pathway;Signaling Protein;small molecule inhibitor;Stress;Supplementation;synergism;Technology;Testing;Therapeutic;therapeutic development;therapeutic evaluation;transcription factor;transcriptomics;translational therapeutics;tumor growth;Tumor Suppressor Proteins;Work

PROJECT_TITLE: Deciphering the Role of Reductive Stress in Non Small Cell Lung Cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Biotechnology;Cancer

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: In this R01 award, we propose to develop highly potent, selective and efficacious small‐molecule degraders of STAT3 for the treatment of human cancer.

PI_NAMEs: WANG, SHAOMENG  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Address;Affinity;angiogenesis;Antibodies;anticancer activity;Antineoplastic Agents;Antisense Oligonucleotides;Award;cancer cell;Cancer cell line;cancer therapy;cell growth;Cell Line;Cell Nucleus;Cell Survival;Clinical;clinical development;Clinical Trials;Complex;cytokine;Data;design;Development;dimer;Dimerization;Dose;Down-Regulation;Drug Kinetics;Drug resistance;Drug Targeting;early phase clinical trial;Evaluation;Genes;Genetic Transcription;Goals;Growth;Growth Factor;Human;human cancer mouse model;human disease;Immune Evasion;In Vitro;in vitro activity;in vivo;inhibitor;intravenous administration;Invaded;Investigation;Laboratories;Lead;Leukemic Cell;Lymphoma cell;Malignant Neoplasms;Mediating;Medicine;member;Metabolic;monomer;Mus;Neoplasm Metastasis;neoplastic cell;novel therapeutic intervention;novel therapeutics;Oncogenic;Performance;Pharmaceutical Preparations;Pharmacodynamics;Phosphorylation;Play;preclinical development;Prognosis;Proliferating;Protac;protein degradation;Protein Family;Proteins;Proteomics;Reporting;response;Role;Schedule;screening;Signal Induction;Signal Transduction;small molecule;small molecule inhibitor;Solid;STAT protein;STAT1 gene;Stat3 protein;Stat5 protein;Structure;Technology;Testing;Therapeutic;therapeutic target;therapy development;Tissues;Toxic effect;Transactivation;transcription factor;tumor;tumor initiation;Tumor Tissue;tumor xenograft;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Small-molecule STAT3 degraders

STUDY_SECTION: DMP

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


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

NIH_SPENDING_CATS: Behavioral and Social Science;Mental Health

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: The proposal requests funds for travel expenses of graduate students and postdoctoral researchers to attend annual meetings of the International Society for Developmental Psychobiology (ISDP). This addressed the critical need for adequate numbers of highly trained scientists to meet the nation’s biomedical and behavioral research agenda, as well as promoting translational research by emphasizing the integration of basic and clinical research approaches.

PI_NAMEs: SWITHERS, SUSAN E (contact)

PROGRAM_OFFICER_NAME: MACHLIN, LAURA STONER

PROJECT_TERMS: Address;Attention;Award;Basic Science;Behavior;Behavioral;behavioral and social science;Behavioral Research;Biological Factors;Biomedical Research;Brain;Categories;Clinical;Clinical Research;Collaborations;Congresses;Development;Developmental Process;developmental psychobiology;Discipline;Disease;educational atmosphere;Ensure;Ethnic Origin;Fostering;Foundations;Funding;Gender;Gender Identity;Goals;graduate student;Grant;Human;innovation;Insurance;interest;International;Journals;meetings;member;Mentors;Mentorship;Mission;Molecular;multidisciplinary;National Institute of Child Health and Human Development;Neurosciences;next generation;Oral;Organism;Persons;Postdoctoral Fellow;posters;pre-doctoral;programs;Psyche structure;Psychiatrist;Psychiatry;Publishing;Race;recruit;Request for Proposals;Research;Research Personnel;Science;Scientific Societies;Scientist;Senior Scientist;Sex Orientation;social science research;Societies;Son;Source;Students;symposium;Talents;Thinking;Training;Translational Research;Travel;Trust;undergraduate student;United States National Institutes of Health;Universities;virtual;Vision

PROJECT_TITLE: Expanding engagement and mentorship of developing scientists through ISDP Annual Meeting participation

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Biobehavioral and Behavioral Sciences Study Section[CHHD-H]


ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Preservation of genome integrity is crucial during development, normal cellular function, and tumor suppression, and the DNA damage repair and cell division cycle pathways are at the heart of an interconnected web of molecular mechanisms. Deeper understanding of these mechanisms is required for more advanced therapeutic interventions and genetic engineering technologies. This project seeks to take on the most challenging and important questions in double-strand break repair, the cell cycle, and how myriad diverse pathways converge in the course of tumorigenesis.

PI_NAMEs: MIRMAN, ZACHARY KENNETH (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Address;Antineoplastic Agents;Award;Biochemistry;Biological;Biology;BRCA1 gene;Cancer Biology;cancer cell;Cancer Etiology;Cancer Model;cancer therapy;Cell Cycle;Cell division;Cell division phases;cell growth regulation;Cell Physiology;Cells;Cellular biology;cellular development;chemotherapy;Choices and Control;Chromatin;Chromosomal Rearrangement;Chromosome Condensation;Chromosome Segregation;Chromosomes;clinically relevant;Complex;Computer Analysis;Coupled;cytotoxicity;Data;Data Set;daughter cell;Detection;Development;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Primase;DNA Repair;Double Strand Break Repair;drug action;drug sensitivity;Ensure;Excision;experience;FDA approved;Gene Targeting;Genetic;Genetic Engineering;Genetic Transcription;Genome;genome integrity;Genome Stability;Genomic Instability;genotoxicity;Goals;Heart;high throughput screening;Homeostasis;homologous recombination;homologous recombination deficiency;Human;human data;Immune system;improved;In Vitro;in vivo;in vivo Model;inhibitor;insight;Internet;Learning;Lesion;Licensing;Light;Maintenance;Malignant Neoplasms;mammalian genome;Methods;Microscopy;Mitosis;Modeling;Molecular;Molecular Conformation;mouse model;Mus;mutant;Mutation;Normal Cell;novel;novel strategies;p53-binding protein 1;Pathway interactions;Patients;Pharmaceutical Preparations;Phase;Polymerase;Postdoctoral Fellow;preservation;Proteins;Proteolysis;Radiation therapy;recruit;repaired;Research;Research Project Grants;Resected;Resistance;response;Role;Sampling;screening;segregation;shift work;Signal Transduction;stem cell biology;synergism;Technical Expertise;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;therapy outcome;Topoisomerase;Topoisomerase Inhibitors;tumor;Tumor Suppression;Tumor Suppressor Proteins;tumorigenesis;Work

PROJECT_TITLE: Genome Integrity Through the Cell Cycle in Homeostasis and Cancer


ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI VA MEDICAL CENTER RESEARCH

ORG_STATE: OH

PHR: The research is relevant to the VA because it addresses a common incurable disease, chronic obstructive pulmonary disease (COPD), which afflicts as many as forty percent of the veteran population. COPD is an incurable disease punctuated by disease exacerbations, usually attributed to infectious insults, which accelerate morbidity and mortality. This project examines the plasticity of immune cell populations that we show predict COPD exacerbations. The research will perform longitudinal studies in COPD patients to define the natural history of natural killer cell plasticity and function and examine the effects of smoking and other disease co-variables in the susceptibility to exacerbations. The successful completion of this project is expected to lead to novel insight and discoveries that will better inform clinicians in the treatment of COPD patients. This contribution would decrease the morbidity and mortality, and enhance the quality of life in COPD patients.

PI_NAMEs: BORCHERS, MICHAEL  (contact)

PROJECT_TERMS: Acceleration;Accounting;Activated Natural Killer Cell;Acute;adaptive immunity;Address;Biological Markers;Cell Physiology;Cell surface;Cells;Chronic;Chronic Obstructive Pulmonary Disease;cigarette smoke;cohort;Complex;cytokine;cytotoxicity;Data;Data Analyses;dimensional analysis;Disease;Disease Progression;effective therapy;Environmental Exposure;Exhibits;Failure;FCGR3B gene;Flow Cytometry;Functional disorder;Future;Heart failure;Heterogeneity;high dimensionality;Homeostasis;Immune;immune function;Immune response;Immune system;Individual;individual variation;Infection;Inflammation;Inflammatory;Injury;innovation;insight;Interferon Type II;Ligands;longitudinal analysis;Longitudinal Studies;longitudinal, prospective study;Lung;Lymphocyte;military veteran;Molecular;Morbidity - disease rate;mortality;Natural History;Natural Immunity;Natural Killer Cells;NCAM1 gene;never smoker;non-smoker;novel;pathogen;Patients;Phenotype;Population;Population Heterogeneity;Predisposition;preservation;Production;Proliferating;prospective;pulmonary function;pulmonary function decline;Quality of life;receptor;Recording of previous events;Research;response;Risk;Severities;Smoker;Smoking;Structure;Testing;Time;Veterans

PROJECT_TITLE: Natural Killer Cell Subpopulations in COPD Exacerbations


NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences;Rehabilitation

ORG_CITY: Aurora

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: The neural mechanisms underlying motor and cognitive impairments in multiple sclerosis (MS) patients are largely unknown. This project uses novel synthesis of approaches in oligodendrocyte biology and neurophysiology, to evaluate how myelin loss affects neuronal circuit function and elucidate the effectiveness of remyelination therapies on restoring neural function and behavior.

PI_NAMEs: HUGHES, ETHAN GARRETT (contact);WELLE, CRISTIN G

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Acceleration;Affect;Animals;Area;Axon;Behavior;Behavior Therapy;Behavioral;behavioral impairment;Biology;blood oxygen level dependent;Brain;Central Nervous System;central nervous system demyelinating disorder;Central Nervous System Diseases;cerebral atrophy;clinically relevant;cognitive function;Data;Demyelinations;Effectiveness;efficacy testing;Equilibrium;Functional disorder;Functional Imaging;Functional Magnetic Resonance Imaging;Goals;gray matter;Health;Impaired cognition;Impairment;improved;in vivo;Individual;Inflammatory;Injury;Learning;Lesion;Monitor;Motor;motor behavior;Motor Cortex;motor disorder;motor impairment;motor learning;mouse model;Movement;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;myelination;neural;neural circuit;neuromechanism;neuronal circuitry;neuronal excitability;Neurons;neurophysiology;Neurophysiology - biologic function;Neuropsychology;novel;novel strategies;novel therapeutics;Oligodendroglia;Pattern;Performance;Persons;pharmacologic;physically handicapped;Physiology;Population;Recovery;Recovery of Function;recruit;remyelination;repaired;restoration;Role;skills;spatiotemporal;Techniques;Thalamic structure;therapeutic candidate;therapeutically effective;Time;Treatment Efficacy;United States;Visualization;white matter;White Matter Disease

PROJECT_TITLE: The role of myelination in cortical circuit function and motor behavior

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


PHR: PROJECT NARRATIVE This research proposal will dramatically improve the understanding of brain aneurysm occlusion, and complications such as side branch occlusion and elevated risks of thromboembolic complications, as well as provide new tools necessary to advance the field of flow diversion for treating intracranial aneurysms, allowing clinicians using current technologies to optimize outcomes and minimize complications, and investigators and engineers to develop improved devices, ultimately improving outcomes of treating brain aneurysms.

PI_NAMEs: CEBRAL, JUAN R;KADIRVEL, RAMANATHAN  (contact);KALLMES, DAVID F

PROGRAM_OFFICER_NAME: KOENIG, JAMES I

PROJECT_TERMS: 3-Dimensional;Acceleration;Achievement;Acute;Address;Adverse event;Aftercare;Aneurysm;Animal Model;Arteries;Biological;biomarker discovery;Blood specimen;Blood Vessels;Brain Aneurysms;cell motility;Circle of Willis;circulating microRNA;Clinical;clinical application;clinical implementation;Clinical Research;clinical translation;Complex;Complication;Computer Models;Data;density;Deposition;Device Designs;Device or Instrument Development;Device Safety;Devices;Distal;Endothelium;Engineering;Evaluation;Event;Fibrin;Fibrinogen;follow-up;Funding;Future;Generations;Growth;healing;hemodynamics;Hemorrhage;Image;implantation;improved;improved outcome;in silico;in vitro Model;in vivo;individual patient;innovation;Interdisciplinary Study;Internal carotid artery structure;Intracranial Aneurysm;Ischemia;Knowledge;Legal patent;Liquid substance;microRNA biomarkers;Modeling;molecular imaging;Monitor;Morphology;multidisciplinary;multimodality;Neck;next generation;novel;Oryctolagus cuniculus;Outcome;Parents;Patient Care;patient variability;Patients;Perforation;Physiologic pulse;Platelet Activation;platelet function;point of care;prevent;Proteins;repository;Reproducibility;Research Personnel;Research Proposals;response;Risk;Risk Factors;Role;Ruptured Aneurysm;Safety;Side;Statistical Methods;stent thrombosis;Stroke;Superior Mesenteric Artery Branch;Superior mesenteric artery structure;System;Technology;Testing;therapeutic target;Thrombin;Thrombosis;thrombotic complications;Tissue Engineering;tool;Translational Research;translational research program;Work

PROJECT_TITLE: Computational and Biological Approach to Flow Diversion

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


ADMINISTERING_IC: DE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Chronic Pain;Dental, Oral, and Craniofacial Disease;Neurosciences;Pain Research

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The output of our pain-modulatory system works to facilitate or inhibit pain, but dysfunction of the system contributes to the development of chronic pain conditions. If we are to develop better treatments, it is essential that we understand how noxious information reaches the pain-modulatory system. By identifying and mapping the functional input of pain-transmission systems to the pain-modulatory circuit, we can gain new insight into how pain-modulating systems are recruited and modulated in acute and chronic pain.

PI_NAMEs: DE PRETER, CAITLYNN  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Absence of pain sensation;Acute;Acute Pain;adeno-associated viral vector;Anatomy;Animals;Area;Attention;Attenuated;Behavioral;Brain;Brain region;Brain Stem;Cells;central pain;Chronic;chronic pain;chronic pain management;chronic painful condition;Clinical;Collaborations;Communication;Complement;Complex;craniofacial;Data;Development;dorsal horn;Electrophysiology (science);Equilibrium;Exhibits;Experimental Designs;experimental study;Exposure to;Face;Freund's Adjuvant;Functional disorder;Goals;Head;Hyperalgesia;Hypersensitivity;In Vitro;in vivo;Inflammation;inflammatory pain;Injections;insight;Link;Maps;Masseter Muscle;Mechanical Stimulation;Mediating;Mentors;Migraine;Neurons;new therapeutic target;Nociception;optogenetics;orofacial;Orofacial Pain;Output;Pain;pain inhibition;Pain management;Pain Research;Pathway interactions;Persistent pain;Physiological;Positioning Attribute;recruit;Research Personnel;response;Role;sensory input;Signal Transduction;skills;Spinal;Spinal cord posterior horn;Structure;System;Temporomandibular Joint Disorders;Testing;Training;transmission process;Trigeminal Neuralgia;Trigeminal System;Withdrawal;Work

PROJECT_TITLE: Direct and Indirect Nociceptive Inputs to Brainstem Pain-Modulating Neurons

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: Project Narrative: Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancies with the majority (>70%) of patients that cannot be cured with contemporary therapies, and thus effective novel therapeutics are urgently needed. The major goal of this application is to develop highly effective, selective and clinically applicable small- molecule inhibitors targeting FTO (the fat mass and obesity-associated protein, which is a major eraser of a common type of RNA methylation), and to assess the therapeutic efficacy/potential of FTO inhibitors, alone or in combination with other therapeutic agents, in treating unfavorable-risk AMLs with FTO overexpression; the underlying cellular and molecular mechanisms will also be elucidated. Thus, the success of this project may lead to the development of effective novel therapeutic strategies to treat unfavorable-risk AMLs (including refractory or relapsed AMLs) with FTO overexpression.

PI_NAMEs: CHEN, JIANJUN  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: 11q23;Acute Myelocytic Leukemia;acute myeloid leukemia cell;analog;anti-cancer;antitumor effect;Basic Science;Binding;Biology;Blast Cell;cancer cell;cancer therapy;cancer type;CD34 gene;Cell Line;Cells;clinical application;combinatorial;crosslinking and immunoprecipitation sequencing;Cyclic GMP;Cytogenetics;Data;design;Development;Disease Progression;druggable target;Enzyme Inhibition;epidemiology study;epitranscriptome;Exhibits;experience;fat mass and obesity-associated protein;FLT3 gene;Genetic;Goals;Hematopoietic Neoplasms;high risk;Human;In Vitro;in vivo;inhibitor;innovation;leukemia;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant Neoplasms;manufacture;Medical;Medicine;Messenger RNA;MLL-rearranged leukemia;Modeling;Modification;Molecular;Mus;mutant;Mutate;Myelogenous;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;NPM1 gene;Obesity;Oncogenic;Overweight;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacologic Substance;Play;Prognosis;Property;Protein Inhibition;Protein Overexpression;Proteins;Proteomics;Refractory;Relapse;relapse patients;Renal Carcinoma;Reporting;Research Design;Research Personnel;response;Risk;RNA;RNA methylation;Role;self-renewal;side effect;Signal Pathway;Signal Transduction;Single Nucleotide Polymorphism;small molecule;small molecule inhibitor;Specificity;stem;Structure;success;Talents;Testing;Therapeutic;Therapeutic Agents;therapeutically effective;Toxic effect;Transcript;transcriptome sequencing;Translational Research;Treatment Efficacy;Treatment Failure;Validation;Variant;Xenograft procedure

PROJECT_TITLE: Targeting FTO to treat acute myeloid leukemia

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Substance Misuse;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The research to be carried out by the ICAP at Columbia University Clinical Trials Unit (CTU) and its five clinical research sites in New York City, Eswatini, and Western Kenya will substantially advance the scientific agendas of all four DAIDS networks by contributing to the development of effective HIV prevention, treatment, and care interventions targeted to the populations most affected by HIV in the US and globally. The ICAP CTU will develop new research concepts; actively participate in network protocols, scientific committees, and working groups; and assure robust accrual and retention of diverse participants in network studies. By pursuing an innovative and comprehensive approach to research on HIV prevention and therapeutics, the ICAP CTU will contribute to achieving long and heathy lives for people living with HIV and to a substantial reduction in the number of new HIV infections globally.

PI_NAMEs: EL-SADR, WAFAA M. (contact);JUSTMAN, JESSICA E.

PROGRAM_OFFICER_NAME: GUBB, STEPHANIE MAJER

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adolescent;Affect;Africa South of the Sahara;AIDS prevention;authority;Behavior Therapy;Behavioral;black men who have sex with men;Caring;Characteristics;Child;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;co-infection;Collaborations;Communities;community advisory board;community engagement;Community Health Education;comorbidity;County;data management;Dedications;design;Development;Education;Epidemic;Ethics;experience;Foundations;girls;global health;Goals;Health Services Accessibility;High Risk Woman;HIV;HIV Infections;implementation science;improved;Incidence;Individual;Infection;Injecting drug user;innovation;Institution;International;Intervention;Kenya;Knowledge;Laboratories;Latino;Life;Link;men;men who have sex with men;men who have sex with men and women;New York;New York City;novel;older adult;outreach;Participant;Pathogenesis;Performance;Persons;Pharmacy facility;Phase;Population;Positioning Attribute;Postpartum Women;Pregnant Women;Prevalence;Prevention;Prevention Research;Principal Investigator;Procedures;Protocols documentation;Public Health;Public Health Schools;quality assurance;Quality of life;recruit;Reporting;Research;Research Personnel;response;Risk;Science;Scientific Advances and Accomplishments;Seasons;Site;skills;Social Behavior;Staff Development;stem;Structure;Therapeutic;Therapeutic Research;tool;Training;transmission process;United States;United States National Institutes of Health;Universities;Vertical Disease Transmission;women of color;working group;young adult;young woman;Youth

PROJECT_TITLE: ICAP Clinical Trials Unit


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Mental Health;Mental Illness;Prevention;Suicide;Suicide Prevention;Violence Research

PHR: Narrative Unprecedented increases in suicide in almost every US state are alarming, and rigorous data science and modeling is needed to develop novel methods for understanding, quantifying, and forecasting suicide outbreaks and transform prevention efforts by identifying high risk areas and groups. Outbreaks of suicide occurring within small geographic areas and after high-profile suicide media coverage suggest that mathematical models capable of simulating suicide as a contagious process are needed to better understand and quantify these dynamics and target prevention efforts that reduce epidemic transmission. The present project leverages four large troves of geospatially-tagged suicide data to estimate spatial and temporal clustering and to develop and validate model systems that simulate anomalous suicide outbreaks, infer critical epidemiological parameters associated with suicide contagion, and forecast future suicide activity in the US, thus providing stakeholders with intervention-ready information. 1

PI_NAMEs: KEYES, KATHERINE M. (contact);SHAMAN, JEFFREY L

PROGRAM_OFFICER_NAME: LUSHIN, VICTOR

PROJECT_TERMS: Address;Adolescent and Young Adult;Adult;age group;age stratification;Algorithms;Area;Bayesian Analysis;Bayesian Modeling;Biological Models;Cessation of life;Cluster Analysis;Communicable Diseases;Communities;Community based prevention;completed suicide;contagion;Coupled;Data;data modeling;Data Science;Data Sources;Detection;Development;disease model;Disease Outbreaks;dynamic system;Environment;Epidemic;Epidemiologist;Epidemiology;Event;Feeds;Firearms;Future;Geographic Locations;Geography;Goals;Health Care Costs;high risk;Hospitals;Hot Spot;ideation;Individual;innovation;Intervention;Length;Life Expectancy;mathematical model;Mental disorders;Methods;Modeling;models and simulation;new outbreak;Non-linear Models;novel;older adult;Opioid;Outcome;Ownership;Persons;Prevention;Process;Property;Psychiatric epidemiology;Public Health;Recording of previous events;Registries;Reporting;response;Risk;Risk Factors;Role;Schools;Science;Seasons;Series;Signal Transduction;simulation;Space-Time Clustering;Statistical Models;Stream;suicidal;suicidal behavior;suicidal risk;Suicide;suicide model;Suicide prevention;suicide rate;surveillance data;System;Temperature;Testing;Time;transmission process;trend;United States;US State;vector;Violence;Vital Statistics;Weather;Work

PROJECT_TITLE: Suicide as a contagion: modeling and forecasting emergent outbreaks

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Cerebrovascular;Neurosciences

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE  Perivascular fibroblasts (PVFs) reside within perivascular spaces of the adult murine brain, are identified by expression of Collagen-1 and Platelet-derived growth factor receptors (PDGFR)a and PDGFRb, and have almost exclusively been studied in the context of stroke and injury. However, almost nothing is known about PVF developmental origins and timing, or the cellular and molecular mechanisms involved in their development. This will be the focus of my investigations, and the results from this work will allow for novel tools and methods for studying the homeostatic and disease-related functions of PVFs.

PI_NAMEs: JONES, HANNAH ELIZABETH (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: 3-Dimensional;Address;Adult;Appearance;Arteries;arteriole;Astrocytes;Biochemical;Biological Assay;Blood capillaries;Blood Vessels;Brain;brain health;Cell Line;cell motility;Cell Physiology;cell type;Cells;Central Nervous System;Central Nervous System Diseases;central nervous system injury;central nervous system vasculature;Cerebrospinal Fluid;Cerebrovascular system;Cicatrix;Collagen;Color;Data;Dependence;Development;Diameter;Disease;Ensure;ex vivo imaging;Fibroblasts;Fluid Balance;fluid flow;Future;glymphatic function;glymphatic system;Goals;Homeostasis;Human;Immune;Immunologics;improved;in vivo;inhibitor;Injury;interest;Investigation;Knowledge;Label;Laboratories;Ligands;Liquid substance;Maintenance;Maps;Meninges;Metabolic;Methods;migration;Modeling;Molecular;mouse development;Mus;Nervous System Physiology;Neurodegenerative Disorders;novel;Nutrient;Optical Methods;Optics;Oxygen;Pathway interactions;Pericytes;Platelet-Derived Growth Factor;Platelet-Derived Growth Factor Receptor;Population;postnatal;postnatal development;Process;Proliferating;receptor;Reporter;Rodent;Role;Signal Transduction;Slice;Smooth Muscle Myocytes;stem;Stroke;Subarachnoid Space;System;Testing;Tissues;tool;Tracer;Training;Transgenic Mice;Vascular blood supply;Vascular Smooth Muscle;Veins;venule;Visualization;wasting;Work

PROJECT_TITLE: Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Infectious Diseases;Neurosciences;Rare Diseases

PHR: PROJECT NARRATIVE Bacterial meningitis is the most common serious infection of the central nervous system (CNS) and a major cause of death and disability worldwide, especially in children. Disruption and dysfunction of the blood-brain barrier (BBB) is a hallmark event in the pathophysiology of bacterial meningitis. My research proposal seeks to elucidate the molecular mechanisms of BBB disruption during bacterial infection as well as identify and characterize the bacterial and host factors involved in this process.

PI_NAMEs: DORAN, KELLY S (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Address;Adult;Age;Antibiotic Therapy;Bacterial Adhesins;Bacterial Infections;Bacterial Meningitis;Biochemical;Biological Models;Blocking Antibodies;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;blood-brain barrier disruption;blood-brain barrier penetration;blood-brain barrier permeabilization;Brain;Brain Edema;brain endothelial cell;Cause of Death;Cell Adhesion;Cell Line;Cell Physiology;Cell Surface Receptors;Central Nervous System;Central Nervous System Diseases;Central Nervous System Infections;Ceramides;Cerebral endothelium;cerebral vein;cerebrovascular;Child;Clinical;Cytoskeleton;Data;Development;disability;Disease;Disease Progression;Endothelial Cells;Endothelium;Epidermal Growth Factor Receptor;epithelial to mesenchymal transition;Event;Failure;Functional disorder;Human;human model;human pathogen;Immune signaling;In Vitro;in vivo;in vivo Model;Infection;inhibitor;Integration Host Factors;Intermediate Filament Proteins;Intracranial Hypertension;Invaded;knock-down;Knockout Mice;Life;Lipids;MAP Kinase Gene;Mediating;Membrane Microdomains;Meningitis;Mitogen-Activated Protein Kinases;model organism;Molecular;mortality;Natural Immunity;Neoplasm Metastasis;Neurologic;Neurological outcome;neuropathology;neuroprotection;Newborn Infant;novel;Nutrient;Outcome;overexpression;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Patients;Penetration;Peptide Initiation Factors;Process;programs;Publishing;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Research Proposals;Role;Seizures;Signal Pathway;Signal Transduction;Snails;Streptococcal Infections;Streptococcus adhesin;Streptococcus Group B;Survivors;Tight Junctions;Tissues;transcription factor;Transcription Repressor;Up-Regulation;Vimentin;Work;Zinc Fingers

PROJECT_TITLE: Modulation of Blood-Brain Barrier Defense and Dysfunction during Bacterial Meningitis

STUDY_SECTION: HIBP

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Bipolar Disorder;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative Executive dysfunction, which involves difficulties with attention, organizing, and regulating behavior, is a debilitating and understudied problem in bipolar disorder. This study will use advanced brain imaging tools to examine whether excessive activation of immune markers in the brain (glial cells), adversely impact neural circuits that are critical for executive functioning. The resulting data may help to identify novel neuroimmune treatment targets for executive dysfunction in bipolar disorder.

PI_NAMEs: PETERS, AMY  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Active Biological Transport;Adult;Afferent Pathways;Age;Attention;Attenuated;Autopsy;Basal Ganglia;Behavior;Binding;Bipolar Disorder;Brain;brain circuitry;brain control;brain dysfunction;Brain imaging;career;career development;Clinical;clinical translation;clinically significant;Cognition;Cognitive;Cognitive deficits;cognitive performance;cognitive testing;Consultations;cytokine;Data;density;Development;Disabling;Disinhibition;Encephalitis;Ensure;Executive Dysfunction;executive function;Exhibits;experience;follow-up;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Future;glial activation;Goals;human imaging;Imaging Device;imaging study;Imaging technology;Immune;immune activation;Immunologic Markers;Immunology;Immunotherapy;improved;Impulsivity;in vivo;indexing;Individual;Inflammation;Inflammatory;inflammatory marker;innovation;Investigational Therapies;knowledge base;Link;Magnetic Resonance Imaging;Measurement;Measures;Mental Depression;Mentors;Mentorship;Methodology;molecular imaging;Mood Disorders;multimodality;National Institute of Mental Health;neural;neural circuit;Neurobehavioral Manifestations;Neurobiology;Neuroglia;neuroimaging;Neuroimmune;neuroimmunology;neuroinflammation;Neurons;neuroregulation;novel;Organ;Participant;Performance;Peripheral;Positron-Emission Tomography;Prefrontal Cortex;Productivity;programs;Proteins;Psychoneuroimmunology;radioligand;Radiopharmaceuticals;receptor;Research;Research Project Grants;response;Rest;Role;Scanning;Schizophrenia;Self Destructive Behavior;Specificity;statistics;success;suicidal;tool;Training;translational scientist;Unemployment;Visualization;Work

PROJECT_TITLE: Neuroinflammation and Executive Function in Bipolar Disorder: A PET-fMRI Study

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

PHR: Project Narrative L-2-hydroxyglutarate (L2HG) is a metabolite that accumulates in cardiovascular cells that do not receive sufficient oxygen. The role of this small molecule in human metabolism is unknown, but we believe it allows cells to minimize the adverse effects of low oxygen on reducing potential and cell function. Thus, our studies will focus on the role of L2HG as a defense against cell injury and dysfunction under conditions of limited oxygen availability.

PI_NAMEs: LOSCALZO, JOSEPH  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: 6-Phosphofructo-2-kinase;Address;Adverse effects;alpha ketoglutarate;Back;Biochemical;Brain Hypoxia-Ischemia;Buffers;cancer cell;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular system;Cell Hypoxia;cell injury;Cell Physiology;Cells;Citric Acid Cycle;cofactor;Cultured Cells;Cytoprotection;cytotoxicity;Data;Dependence;Echocardiography;Endothelial Cells;Endothelium;Eukaryota;experimental study;extracellular;Fructose-2,6-bisphosphatase;Functional disorder;G6PD gene;Generations;Genetic;Glucose;Glutathione Disulfide;glutathione peroxidase;Glycolysis;Goals;GPX3 gene;Heart;heart function;Heterozygote;Homozygote;Human;Hypoxia;In Vitro;in vivo;inhibitor;Injury;inorganic phosphate;insight;Ischemia;Knock-out;Mass Spectrum Analysis;Measures;Mediating;Metabolic;Metabolism;metabolomics;Molecular;mouse model;Mus;Myocardial;myocardial hypoxia;NADH;NADP;NADPH Oxidase;normoxia;novel;Organ;overexpression;Oxidases;oxidation;Oxidation-Reduction;Oxidoreductase;Oxygen;Pathway interactions;Pentosephosphate Pathway;Perfusion;pharmacologic;Phosphotransferases;Preparation;preservation;Protein Isoforms;Reaction;Reactive Oxygen Species;Reperfusion Therapy;response;Role;Small Interfering RNA;small molecule;Stress;Testing;Time

PROJECT_TITLE: L-2-Hydroxyglutarate and Metabolic Remodeling in Hypoxia

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: MASSI/ BOSCO – NARRATIVE Mutations in profilin-1 (PFN1), an actin binding protein, cause the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) through an unknown mechanism. Using complementary biophysical and cell biology approaches, we will rigorously test the hypothesis that ALS mutations perturb the dynamics, protein-binding interactions, and solubility of PFN1 in a manner that contributes to ALS pathogenesis.

PI_NAMEs: BOSCO, DARYL ANGELA;MASSI, FRANCESCA  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: 3-Dimensional;Acceleration;Actin-Binding Protein;Actins;Affect;Affinity;Amyotrophic Lateral Sclerosis;Binding;Binding Proteins;Binding Sites;Biochemical;Biological;Biological Assay;Biophysics;Categories;Cells;Cellular biology;Chimera organism;Communication;Complex;Computer Simulation;Coupling;Cytoskeletal Proteins;Cytoskeleton;Data;Defect;Diagnosis;Disease;Exhibits;experimental study;falls;Fluorescence Spectroscopy;Gene Mutation;Genes;in silico;In Vitro;Inherited;innovation;Link;link protein;Mammalian Cell;Measures;member;Molecular Conformation;molecular dynamics;Motion;Motor Neurons;multidisciplinary;mutant;Mutation;Neurodegenerative Disorders;novel;Pathogenesis;Pathway interactions;Phenotype;Play;polymerization;Polymers;Population;Process;profilin;profilin 1;Proline;protein aggregation;Protein Dynamics;Protein Family;Protein Region;Proteins;proteostasis;Publishing;Relaxation;Research;Research Personnel;Resolution;RNA Processing;Roentgen Rays;Role;screening;small molecule;Solubility;Specificity;Stress Fibers;Structure;Symptoms;synergism;Testing;Thermodynamics;trafficking;Variant;Work

PROJECT_TITLE: Impact of ALS-linked mutations on the structure, dynamics and function of profilin-1

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: PHARMACOLOGY

PHR: Aberrant protein Poly-ADP-ribosylation (PARylation) signaling is known to cause the misregulation of biomolecular condensation and this underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the structural aspects of this process are elusive. In this proposal, we will develop a chemical footprinting approach to characterize the structural dynamics of PARylation-regulated phase-transition in the context of ALS and FTD.

PI_NAMEs: YU, YONGHAO  (contact)

PROGRAM_OFFICER_NAME: SHEWMAKER, FRANK PAUL

PROJECT_TERMS: Acetylation;Acylation;Address;ADP ribosylation;Alzheimer's Disease;Alzheimer's disease related dementia;Amino Acids;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Animal Model;Benchmarking;Binding;Binding Proteins;Biological;biological adaptation to stress;Biological Process;biophysical techniques;biophysical tools;brain dysfunction;C9ORF72;Cell Death;Cell Nucleus;Cells;Cellular Stress;Cessation of life;Chemicals;Data;Defect;density;Diffuse;DNA;DNA Damage;DNA Repair;Electron Microscopy;Enzymes;experience;Family;FDA approved;fly;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Genes;Genetic;Genotoxic Stress;genotoxicity;Heterogeneous-Nuclear Ribonucleoproteins;Human;Imidazole;In Vitro;Induced pluripotent stem cell derived neurons;inhibitor;Length;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Messenger RNA;Methods;Modeling;Modification;Molecular;Molecular Conformation;Mutate;Mutation;Nature;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;Neurons;neurotoxic;Neurotoxins;Nitrogen;novel;Nuclear;Nuclear Pore;Nuclear Protein;Nucleic Acids;Organelles;Oxygen;Parkinson Disease;Pathogenesis;Pathologic;Pathway interactions;pharmacologic;Phase Transition;Physical condensation;Poly Adenosine Diphosphate Ribose;Poly(ADP-ribose) Polymerases;Polymers;Post-Translational Protein Processing;Process;programs;protein aggregation;Protein Analysis;Proteins;Proteome;Publishing;Reaction;Reagent;Recombinants;Regulation;response;RNA;Role;self assembly;Series;Side;Signal Transduction;Site;small molecule;spatiotemporal;Stimulant;Stress;Structure;Surface;Translations;Work

PROJECT_TITLE: A Chemical Footprinting Approach towards Poly-ADP-Ribosylation-regulated Biomolecular Condensation


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Cardiovascular;Climate-Related Exposures and Conditions;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Social Determinants of Health

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

PHR: Project Narrative: The proposed studies will determine whether there are causal effects of exposure to air pollutants and temperature on mortality, heart attacks and strokes and whether those effects persist below current ambient standards. They will also identify whether there are interactions between the different exposures, whether some particle components are more toxic that others, and whether error in exposure estimates either prevents the identification of effects at low levels or biases effect estimates upwards. This will be done using state of the art mixture, causal modeling and measurement error methods, uniquely combining them for the first time.

PI_NAMEs: SCHWARTZ, JOEL D (contact)

PROGRAM_OFFICER_NAME: CUI, YUXIA

PROJECT_TERMS: Acute;Address;Admission activity;Advisory Committees;Age;Air;Air Pollutants;Air Pollution;ambient air pollution;analytical method;Atrial Fibrillation;Attenuated;base;burden of illness;causal model;Censuses;Cessation of life;China;Chronic;climate variability;cohort;cost;Critiques;Data;Data Set;Death Certificates;Death Rate;design;Detection;Dose;epidemiology study;Equity;Event;experience;Exposure to;fine particles;Health;health disparity;Hospitalization;hospitalization rates;India;Individual;Joints;large datasets;Measurement;Measures;Medicaid;Medicare;Medicare/Medicaid;Methods;Modeling;Morbidity - disease rate;mortality;Myocardial Infarction;Nature;Neighborhoods;Nitrates;Nitrogen Dioxide;novel;Observational Study;Outcome;Ozone;Participant;particle;pollutant;Pollution;Population;prevent;Public Health;Quasi-experiment;Recommendation;Records;Resolution;response;Risk;Risk Estimate;Science;Scoring Method;simulation;Stroke;Subgroup;Sulfate;Techniques;Temperature;Time

PROJECT_TITLE: Identifying low dose measurement error corrected effects of multiple pollutants using causal modeling

STUDY_SECTION: CHSA

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


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Orphan Drug;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Tuberculosis

PHR: Project Narrative The Chicago Clinical Trials Unit (CCTU) is a consortium of four Clinical Research Sites committed to ground- breaking research and dynamic community engagement that will make prevention, treatment and/or cure of HIV, tuberculosis, hepatitis B, and their associated complications, a public health reality.

PI_NAMEs: ACHENBACH, CHAD J (contact)

PROGRAM_OFFICER_NAME: SOUTHARD, COURTNEY MEAGAN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adolescent;Adolescent Medicine Trials Network;Adult;AIDS clinical trial group;AIDS prevention;Antibodies;antiretroviral therapy;Area;Award;Behavioral;behavioral study;black men who have sex with men;Caring;Chicago;cis-female;Cities;Clinical;clinical center;Clinical Research;clinical research site;Clinical Trials Network;Clinical Trials Unit;co-infection;Collaborations;Communities;community advisory board;community engagement;community research;comorbidity;cooking;Cost Control;County;Dedications;Development;Disease remission;disenfranchised population;drug-sensitive;effective therapy;Elderly;Elements;Ensure;Epidemic;epidemiology study;Ethics;experience;Funding;Geography;Health;Healthcare;Hepatitis;Hepatitis B;high risk;HIV;HIV diagnosis;HIV vaccine;HIV/AIDS;Homelessness;Hot Spot;Human Resources;Infrastructure;innovation;Institution;Interruption;Investments;Laboratories;Latinx;Leadership;Mediating;men who have sex with men;Midwestern United States;Monitor;multidisciplinary;multimodality;National Institute of Allergy and Infectious Disease;novel;novel therapeutics;operation;outreach;Performance;Persons;Pharmacy facility;Phase;Population;Population Heterogeneity;Populations at Risk;Positioning Attribute;pre-exposure prophylaxis;Pregnant Women;Prevalence;Prevention;Prevention Research;Prevention strategy;Productivity;programs;Protocols documentation;Provider;Public Health;quality assurance;racial minority;Regulation;Research;Research Ethics;Research Infrastructure;Research Personnel;Research Priority;research study;Resistance;Resource Sharing;Resources;Rights;Risk;safety net;Science;Scientific Advances and Accomplishments;segregation;sexual minority;Site;social;Social Behavior;Structure;synergism;System;Technology;Testing;Therapeutic;Therapeutic Clinical Trial;Tissue Sample;transgender;treatment strategy;Tuberculosis;United States National Institutes of Health;Universities;Wellness Center;Work;Youth

PROJECT_TITLE: Chicago Clinical Trials Unit


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Radiation Oncology;Rare Diseases

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE These studies seek to understand if targeting integrins in myeloid cells can impact therapeutic responsiveness to immunotherapy in pancreas cancer. A better understanding of how integrins regulate innate immune control of T lymphocytes and ultimately response to therapy, can help us refine ongoing therapeutic approaches targeting this disease.

PI_NAMEs: DENARDO, DAVID G (contact);GUPTA, VINEET

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Agonist;anti-PD1 therapy;beta-Chemokines;cancer clinical trial;Cancer Model;cancer type;Cellular Immunity;checkpoint therapy;chemokine receptor;Chemotherapy and/or radiation;Clinic;Clinical;clinical development;Clinical Trials;combat;Combined Modality Therapy;Data;Disease;disease model;Disease Progression;drug repurposing;Exclusion;Functional disorder;Genetic;granulocyte;Immune;Immunity;Immunologic Memory;Immunotherapy;Impairment;improved;Infiltration;Inflammation;Inflammatory;Integrins;ITGAM gene;Macrophage;Macrophage Colony-Stimulating Factor Receptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Molecular;Molecular Mechanisms of Action;monocyte;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Neoplasm Metastasis;novel strategies;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Pathology;Patients;pharmacologic;Phase;Phenotype;pre-clinical;Pre-Clinical Model;programs;Radiation therapy;recruit;Research Personnel;Resistance;response;Sampling;Signal Transduction;small molecule;STING agonists;success;Survival Rate;T cell infiltration;T cell response;T-Lymphocyte;targeted agent;targeted treatment;Testing;Therapeutic;Therapeutic Agents;Tissues;TNFRSF5 gene;tool;trafficking;Translating;translational approach;Treatment Efficacy;treatment response;tumor;Tumor Immunity;Tumor-associated macrophages

PROJECT_TITLE: Exploiting Integrin Signaling to Overcome Resistance to Immunotherapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]