ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Autoimmune Regulator (Aire) has been demonstrated to be essential for central tolerance in the thymus by inducing tissue specific antigen expression in medullary thymic epithelial cells (mTECs), but little is known about the role of extrathymic Aire in peripheral immune tolerance. Since extrathymic Aire-expressing cells (eTACs) are transcriptionally and functionally similar to both mTECs and migratory dendritic cells, they could play a unique role in the maintenance of immune homeostasis as distinct populations of tolerogenic antigen presenting cells. Studying the biology of eTACs and peripheral Aire will help further elucidate the function of Aire and define basic peripheral tolerance mechanisms, which may have significance for a range of clinical applications from autoimmunity to tumor immunity to maternal-fetal tolerance.

PI_NAMEs: WANG, JIAXI  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acceleration;Adaptive Immune System;aged;anergy;Antigen Presentation;Antigen Presentation Pathway;Antigen-Presenting Cells;Antigens;ATAC-seq;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmunity;autoreactive T cell;B-Lymphocytes;Bioinformatics;Biology;California;career;CD4 Positive T Lymphocytes;CD80 gene;CD86 gene;Cell Count;Cell Physiology;cell type;Cells;central tolerance;Chromatin;clinical application;Coculture Techniques;Complex;Data;Data Set;Dendritic Cells;Development;Diabetes Mellitus;Diphtheria Toxin;Education;Environment;Experimental Autoimmune Encephalomyelitis;Fellowship;fetal;Flow Cytometry;fluorophore;Funding;G6PC2 gene;Generations;Genes;Genetic;Genetic Transcription;Genomics;Helper-Inducer T-Lymphocyte;Hematopoietic;Histology;Homeostasis;Host Defense;Human;Immune;Immune system;Immune Tolerance;Immunology;in vitro testing;in vivo monitoring;Incubated;Institution;Insulin;Interleukin-10;Knock-out;Knockout Mice;Laboratories;lymph nodes;Maintenance;Measures;Mentors;Methods;MHC Class II Genes;migration;Monitor;mouse model;multiple omics;Mus;Mutation;novel;Organ;Organism;Orphan;overexpression;Paint;Pancreas;pathogen;Peptides;Peripheral;peripheral tolerance;Phenotype;Physiologic pulse;Play;Polyglandular Autoimmune Syndrome Type I;Population;Population Biology;prevent;programs;Proliferating;promoter;Proteins;Reaction;receptor;Regulator Genes;Regulatory T-Lymphocyte;Reporter;Research;research and development;Research Project Grants;response;Retinoic Acid Receptor;RNA;Role;San Francisco;secondary lymphoid organ;Self Tolerance;Serum;single-cell RNA sequencing;skills;Skin;Sorting;Spleen;Surface;System;T-Cell Proliferation;T-Lymphocyte;Testing;Thymic epithelial cell;Thymus Gland;Tissues;tool;Training;Transgenic Mice;Tumor Immunity;Universities;uptake;Venus;Vertebrates;Work

PROJECT_TITLE: Defining the Role of Aire in eTACs and its Contribution to Peripheral Immune Tolerance


ADMINISTERING_IC: MD

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunotherapy;Precision Medicine;Women's Health Research

ORG_CITY: DOVER

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DELAWARE STATE UNIVERSITY

ORG_STATE: DE

PHR: Narrative. Triple negative breast cancer (TNBC) is a particularly aggressive breast cancer subtype, disproportionately seen in African Americans, and in contrast to other breast cancer subtypes, there are no current targeted therapies. One goal of this research is to develop non-antibody protein-based targeted immunotherapeutics that are personalized for virtually any TNBC patient, and trigger immune cells to seek out and destroy TNBC cells. Protein immunotherapeutics are designed for long in vivo lifetime, which rival monoclonal antibodies, and use existing serum antibodies to kill TNBC cells. A second goal of this research is to develop a low-cost paper based diagnostic platform that will be used to rapidly identify which protein immunotherapeutics are best suited to serve as a combination therapy for a given TNBC patient, and monitor the therapeutic efficacy of the combination over the course of treatment.

PI_NAMEs: MCNAUGHTON, BRIAN RICHARD (contact)

PROJECT_TERMS: Affect;Affinity;African American population;African American Women;aggressive breast cancer;Antibodies;antibody-dependent cell cytotoxicity;Antineoplastic Agents;Appointment;Binding;Biological Markers;Biological Products;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;cancer cell;cancer immunotherapeutics;cancer immunotherapy;cancer subtypes;Cell surface;Cell Surface Proteins;Cell Surface Receptors;Cells;Childhood;Clinic;clinically significant;Combination immunotherapy;Combined Modality Therapy;Complex;cost;Delaware;design;Development;Devices;Diagnostic Equipment;diagnostic platform;Disease;Disparity;Drug Costs;drug discovery;Drug usage;Effectiveness;Epidermal Growth Factor Receptor;Escherichia coli;Estrogen Receptors;Excretory function;experimental study;Generations;Goals;Health equity research;High Risk Woman;Hormone Receptor;hormone receptor-positive;hormone therapy;Human;Immune;Immune mediated destruction;Immune system;Immunotherapeutic agent;Immunotherapy;improved;in vivo;Incidence;Left;Localized Disease;Low income;Malignant Breast Neoplasm;Malignant Neoplasms;Mammalian Cell;Marketing;Mastectomy;Measures;member;Mental association;Methods;Minority Groups;Monitor;Monoclonal Antibodies;Mutate;nanobodies;new technology;novel strategies;Operative Surgical Procedures;Outcome;Paper;Patient-Focused Outcomes;Patients;personalized approach;personalized medicine;personalized therapeutic;Phage Display;Pharmaceutical Preparations;Population;precision drugs;Production;Progesterone Receptors;Proteins;Radiation;receptor;recruit;Reporter;Research;Serum;side effect;Signal Transduction;Source;survival outcome;targeted treatment;Techniques;Technology;Testing;Therapeutic;Tissues;Trastuzumab;Trauma;Treatment Efficacy;Treatment outcome;triple-negative invasive breast carcinoma;tumor;Vaccination;virtual;Woman;Work

PROJECT_TITLE: Integrating Low-Cost Paper-Based Devices and Personalized Immunotherapeutics to Treat Triple Negative Breast Cancer


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Data Science;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Precision Medicine;Prevention

ORG_CITY: Nashville

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE The epidemic of screen- or incidentally detected indeterminate pulmonary nodules (IPNs) presents a substantial public health problem and is associated health care costs of $28 billion annually as well as increased burden on patients in the form of anxiety, morbidity from diagnostic procedures, excessive radiation, and death from missed lung cancer. Clinical predictive models represent an opportunity to reduce this public health burden by noninvasively estimating the probability of malignancy and segregating IPNs into clinically actionable risk groups, thereby reducing the risk of mismanaging IPNs. By leveraging machine learning/deep learning techniques to analyze data that are multi-modal and longitudinal, this project works towards a future where predictive models are used at scale to improve patient outcomes by aiding earlier diagnosis of malignancy and reducing the diagnostic burden of benign IPNs.

PI_NAMEs: LI, THOMAS ZHIHE (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Advanced Malignant Neoplasm;Algorithms;Anxiety;anxiety reduction;Aptitude;Archives;Area;Artificial Intelligence;artificial intelligence method;artificial intelligence model;Award;Benign;Big Data;biomedical informatics;Biometry;cancer imaging;cancer subtypes;career;Cessation of life;Characteristics;chest computed tomography;Classification;Clinical;Clinical Informatics;Clinical Management;clinical phenotype;clinical predictive model;Clinical/Radiologic;clinically actionable;cohort;cost efficient;Data;Decision Making;deep learning;design;Diagnosis;Diagnostic;Diagnostic Errors;Diagnostic Procedure;Disease;Early Diagnosis;electronic health data;Engineering;Environment;Epidemic;Evaluation;Exhibits;explainable artificial intelligence;Fellowship;Future;Goals;Growth;Health Care Costs;health record;Healthcare Systems;high dimensionality;high risk;Histologic;Histology;Histopathology;Image;Image Analysis;improved;Incidence;Indolent;innovation;Institution;Intervention;Joints;Laboratories;Language;Learning;learning strategy;lens;low dose computed tomography;Lung;Lung Adenocarcinoma;lung cancer screening;Lung nodule;Machine Learning;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Measurement;Measures;Medical;Medical History;Medical Imaging;Mentors;Metastatic Neoplasm to the Lung;Methods;Modality;Modeling;Modernization;Morbidity - disease rate;mortality;multimodal data;multimodality;Nodule;noninvasive diagnosis;novel;novel strategies;Oncology;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;Performance;personalized approach;Phenotype;Physicians;Positioning Attribute;precision oncology;predictive modeling;Predictive Value;Probability;prospective;Prospective cohort;Public Health;Radiation;Radiologic Finding;Radiology Specialty;radiomics;Recording of previous events;Records;Research;Resources;Retrospective cohort;Risk;Risk Reduction;risk stratification;Scientist;screening;segregation;serial imaging;Smoking;Smoking History;standard of care;Standardization;Subgroup;success;symposium;Techniques;Time;Training;tumor;Universities;Vision;Work;X-Ray Computed Tomography

PROJECT_TITLE: Risk stratifying indeterminate pulmonary nodules with jointly learned features from longitudinal radiologic and clinical big data

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F18-L(20)L]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Immunotherapy;Lung;Rare Diseases

ORG_CITY: SEATTLE

ORG_NAME: BENAROYA RESEARCH INST AT VIRGINIA MASON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Acute respiratory distress syndrome (ARDS) is a feared complication of critical illness that can frequently lead to prolonged mechanical ventilation and death. ARDS is a heterogeneous syndrome and treatment for patients is largely supportive. This project will determine whether the immune checkpoint proteins PD-1 and PD-L1 play a role in ARDS pathophysiology and can identify a biologic signature of patients at higher risk for poor outcomes.

PI_NAMEs: MIKACENIC, CARMEN R (contact)

PROGRAM_OFFICER_NAME: ZHOU, GUOFEI

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Affect;Alveolar;Alveolar Macrophages;Anti-Inflammatory Agents;Antigens;Bilateral;Binding;Biological;Biological Markers;Bronchoscopy;Cell membrane;Cell Physiology;Cell surface;Cells;Centrifugation;Cessation of life;circulating biomarkers;Clinical;Clinical Trials;Cluster Analysis;cohort;Complication;cost;Critical Illness;cytokine;Cytometry;Data;Defect;differential expression;Enrollment;experience;Fright;Functional disorder;Heterogeneity;high dimensionality;high risk;Hypoxemia;IL17 gene;IL8 gene;Immune;immune checkpoint;Immune checkpoint inhibitor;immune function;Immune response;immunoregulation;Immunosuppression;Impairment;Infiltration;Inflammation;Inflammatory;inhibitor;Injury;Intensive Care Units;Interferon Type II;Interleukin-6;Knowledge;Lead;Leukocytes;Ligands;Link;Liquid substance;Long term disability;Lung;lung injury;Macrophage;Measurement;Measures;Mechanical ventilation;Mediating;Medical;Medical center;microvesicles;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mortality risk;Mus;Nature;novel;Operative Surgical Procedures;Outcome;participant enrollment;Pathogenicity;Pathway interactions;patient subsets;Patients;peripheral blood;personalized approach;Pharmacologic Substance;Phenotype;Plasma;Play;Production;prognostication;programmed cell death ligand 1;programmed cell death protein 1;Proliferating;protein expression;Proteins;Proteomics;Pulmonary Inflammation;receptor;Receptor Signaling;recruit;Regulatory T-Lymphocyte;Resolution;Respiratory Failure;response;Risk;Risk Factors;RNA Splicing;Role;Sepsis;Severities;Severity of illness;side effect;Signal Transduction;Stains;Study Subject;Subgroup;Surface;Syndrome;T cell regulation;T cell response;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;Thoracic Radiography;tissue injury;Tissues;Trauma;United States;unsupervised clustering;Validation;Variant;ventilation;Ventilator;vesicular release

PROJECT_TITLE: Immune Checkpoints in Acute Respiratory Distress Syndrome (IC-ARDS)

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Biomedical Imaging;Building Research Capacity at Institutions with Limited NIH Funding;Data Science;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Osteoarthritis;Osteoporosis;Prevention;Racial and Ethnic Minority Health Research;Sarcopenia;Social Determinants of Health

PHR: Program Director/Principal Investigator (Last, First, Middle): Makrogiannis, Sokratis Narrative Age-related and metabolic diseases, such as type-2 diabetes, cardiovascular diseases, sarcopenia, osteoporosis, and osteoarthritis, have become a worldwide epidemic, and affect the quality of life of millions. To give a global perspective, roughly 343.8 million people in the world have type-2 diabetes today, and 175 million don’t know they have diabetes at all. This project will contribute novel and non-invasive medical image analysis techniques for studying the human body composition and its changes with increasing age, to achieve timely diagnosis of these pathologies. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

PI_NAMEs: MAKROGIANNIS, SOKRATIS  (contact)

PROJECT_TERMS: 3-Dimensional;Abdomen;Acceleration;Address;Adipose tissue;Adult;Advanced Development;Affect;Age;age related;age-related disease;Aging;Agreement;Anatomy;Architecture;Area;Artificial Intelligence;Atlases;automated image analysis;Baltimore;biological age;Black race;Body Composition;Body Regions;bone;Bone Density;Bone structure;Cardiovascular Diseases;Classification;Clinical Data;clinical decision-making;clinical imaging;Clinical Trials;Communities;Computer Assisted;Computer software;Coronary Arteriosclerosis;cost effective;Data;Data Set;deep learning;Degenerative polyarthritis;Descriptor;design;Deterioration;Development;diabetes control;Diabetes Mellitus;Diagnosis;Diagnostic;Dictionary;Disease;disease diagnosis;Epidemic;epidemiology study;ethnic minority;Female;Health Care Costs;health care quality;Health equity research;Hispanic;Human;Human body;Image;Image Analysis;imaging biomarker;imaging study;Imaging technology;improved;in vivo;Infiltration;innovation;interest;Intervention;Joints;learning strategy;Link;Longitudinal Studies;Lower Extremity;Machine Learning;machine learning method;Magnetic Resonance Imaging;male;Manuals;mathematical methods;Measures;Medical Imaging;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic rate;Metabolic syndrome;Methods;Microscopic;Minority Access;Minority Groups;Mobility decline;Modernization;Monitor;Morphology;morphometry;Muscle;muscle form;muscle strength;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;novel;Obesity;open source;Osteoporosis;Participant;Pathologist;Pathology;Pattern;Persons;pharmacologic;Phenotype;Physiological;preservation;Prevalence;Principal Investigator;Process;Prognosis;programs;Property;Quality of life;quantitative imaging;racial minority;radiological imaging;radiologist;radiomics;Reader;Research;research and development;Risk;Risk Factors;Risk Reduction;sarcopenia;Skeletal Muscle;Software Tools;Source Code;statistical learning;Stroke;substantia spongiosa;Techniques;Testing;Therapeutic;Time;Tissues;Training;Underserved Population;United States;Visualization;Work;X-Ray Computed Tomography

PROJECT_TITLE: Machine Learning-based Imaging Biomarkers for Metabolic and Age-related Diseases


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

PHR: PROJECT NARRATIVE Health disparities among underserved populations are multifactorial, and it is now recognized that disparities in sleep health in addition to social determinants of health are important contributors. This study seeks to understand the intersection of these relationships on functional outcomes. The results of this study will further substantiate key drivers of sleep disparities for racial/ethnic minorities to reduce health disparities and advance health equities.

PI_NAMEs: BROWNLOW, JANEESE A (contact)

PROJECT_TERMS: actigraphy;Adult;Affect;aged;Anxiety;Behavioral;Biological;blood pressure elevation;Centers for Disease Control and Prevention (U.S.);Characteristics;Chronic;Cities;Clinical;Communities;culturally appropriate intervention;Data;Delaware;Discrimination;Disease;Disparity;Environment;Environmental Risk Factor;ethnic minority;ethnic minority population;Exhibits;Female;functional outcomes;Goals;Health;health disparity;health equity;Health equity research;high body mass index;Home;Hour;Human;Individual;Interview;Investigation;Link;Maintenance;male;Mental Depression;Mental disorders;Mental Health;Monitor;Neighborhoods;novel;Outcome;Pathway interactions;Pattern;Perception;Physical activity;physical conditioning;Physical Examination;Physiological;Play;Polysomnography;Population;Process;Psyche structure;Public Health;Quality of life;Questionnaires;racial disparity;racial health disparity;racial minority;racial minority population;Recommendation;Reduce health disparities;REM Sleep;Reporting;Risk;Risk Factors;Risk Marker;Role;Scheme;Screening procedure;Series;Severities;Sleep;Sleep Deprivation;sleep health;sleep quality;Sleeplessness;Slow-Wave Sleep;social;Social Conditions;social determinants;Social Environment;social health determinants;Stress;Structure;System;Underserved Population;urban area;Visit

PROJECT_TITLE: An Investigation of Mental, Physical, and Sleep Health: The Role of Social Determinants


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Childhood Injury;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Unintentional Childhood Injury

ORG_CITY: DETROIT

ORG_DEPT: PSYCHIATRY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Narrative  Anxiety disorders are the most common mental illness in the United States and begin to emerge during adolescence. Experiences of childhood trauma are a potent risk factor for anxiety disorders in youth, however, the mechanisms supporting this link are poorly characterized. This study will investigate the impact of childhood trauma on the biochemical mechanisms maintaining cognitive control in the presence of threat, and may aid in identifying novel therapeutic targets and improving care for anxious youth.

PI_NAMEs: FRANCE, JOHN  (contact)

PROGRAM_OFFICER_NAME: SABBAGH, JONATHAN JACOB

PROJECT_TERMS: Adolescence;Adolescent;Affect;Age;Amygdaloid structure;Anterior;Anxiety;Anxiety Disorders;anxiety symptoms;anxious;Biochemical;Biochemistry;career;Caring;Childhood;childhood anxiety;cingulate cortex;Cognition;Cognitive;cognitive ability;cognitive control;cognitive process;cohort;Collaborations;community center;Control Groups;Cues;Dedications;design;Development;Dorsal;Eligibility Determination;Emotional;Enrollment;Ensure;Equilibrium;experience;Exposure to;Face;Female;France;Fright;Functional Magnetic Resonance Imaging;Future;Glutamates;Goals;hemodynamics;Hyperactivity;Impairment;improved;in vivo;innovation;Investigation;Link;Magnetic Resonance Spectroscopy;Measures;Mental disorders;Mentorship;Methodology;negative affect;neural;neurobiological mechanism;Neurobiology;neuroimaging;neuromechanism;Neurons;neurotransmission;new therapeutic target;novel;Participant;pediatric trauma;Pharmacotherapy;Process;psychologic;Psychopathology;Qualifying;recruit;Research;response;Risk;Risk Factors;Role;Scanning;Shapes;sustained attention;Synapses;Technology;Testing;Therapeutic;therapeutic target;tool;Training;training project;Trauma;trauma exposure;United States;urban setting;Visual;Vulnerable Populations;Youth

PROJECT_TITLE: The Role for in vivo Glutamate Modulation in Maintaining Cognitive Control in Trauma-Exposed Adolescents


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Networking and Information Technology R&D (NITRD)

PI_NAMEs: WENTZIEN, DERALD  (contact)

PROJECT_TERMS: Area;Behavioral;Behavioral Research;bioimaging;Bioinformatics;biomedical informatics;Biomedical Research;Biometry;career networking;Caregivers;Cells;Center for Translational Science Activities;Clinical Research;Collaborations;Communities;community partners;complex data;Computer software;Consultations;Core Facility;Data;Data Collection;data infrastructure;data management;Data Security;Data Set;Delaware;Development;Discipline;Discourse analysis;Educational workshop;Electrophysiology (science);Ensure;Epidemiologist;Epidemiology;experience;Faculty;Family;Focus Groups;Funding;Goals;Grant;Health;Health Disparities Research;health disparity;health equity;Health equity research;human subject;Infrastructure;Institution;Institutional Review Boards;Interview;Investigation;Knowledge;Link;Medical Informatics;Methodology;Methods;Microscopy;Participant;Perception;Persons;phenomenological models;Pilot Projects;Policy Maker;Population Research;Productivity;Program Evaluation;programs;Protocols documentation;Qualitative Evaluations;Qualitative Methods;Qualitative Research;Research;Research Design;Research Infrastructure;Research Personnel;Research Project Grants;Research Support;Research Training;Resources;Services;social;Social Sciences;Software Tools;sound;theories;Time;United States National Institutes of Health

PROJECT_TITLE: Research Capacity Core


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease;Substance Misuse

ORG_CITY: INDIANAPOLIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Alcohol-associated liver disease (ALD) is a major public health problem in the United States. This application examines the mechanisms by which the FK506-binding protein-51 (FKBP5) mediates the pathogenesis of alcohol-induced liver injury. The results of our application have the potential to identify a new therapeutic approach for ALD by targeting FKBP5.

PI_NAMEs: LIANGPUNSAKUL, SUTHAT  (contact)

PROGRAM_OFFICER_NAME: GAO, PETER

PROJECT_TERMS: 5' Untranslated Regions;Address;Alcohol consumption;alcohol related problem;alcohol risk;Alcoholic Liver Cirrhosis;Alcoholic Liver Diseases;Alcohols;Animal Model;biological adaptation to stress;Cell model;cell type;Cells;Chromosome 6;Chromosome Arm;chronic liver disease;Complex;CpG Islands;CXCL1 gene;Data;Diet;differential expression;Disease;Down-Regulation;drinking;epigenetic regulation;Ethanol;Family;FK506 binding protein 5;Gene Expression;Genes;Goals;Health;Hepatocyte;Immunophilins;insight;Knock-out;Knockout Mice;Kupffer Cells;Lead;Link;Liver;Liver diseases;liver transplantation;Mediating;Mental Depression;Mental disorders;Metabolic;Methylation;Modeling;Molecular;Molecular Chaperones;mouse model;mRNA Expression;Mus;novel;novel therapeutic intervention;Nuclear Translocation;Pathogenesis;Pathway interactions;Patients;Phosphorylation;Post-Traumatic Stress Disorders;Process;Promoter Regions;protective effect;Protein Dephosphorylation;protein expression;Proteins;Public Health;Regulation;Risk Factors;Role;Sampling;Secondary to;Series;Signal Transduction;single-cell RNA sequencing;Stress;stressor;Tacrolimus Binding Proteins;Testing;Therapeutic Intervention;Transcript;transcriptome sequencing;United States;Up-Regulation;upstream kinase;Wild Type Mouse

PROJECT_TITLE: FKBP5 in the pathogenesis of alcohol-associated liver disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Substance Misuse

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: PURDUE UNIVERSITY

PHR: PROJECT NARRATIVE: The present study will assess the impact of a history of alcohol dependence on the onset and severity of behavioral and neuropathological deficits associated with Alzheimer's disease. This project will also assess single-cell whole-brain connectivity and whole-brain Aβ deposits in transgenic mice that model Alzheimer's after a history of alcohol dependence and unveil the neuronal networks that are responsible for cognitive and emotional changes that are associated with Alzheimer's disease. This project will further identify whether Memantine is an effective treatment for deficits associated with Alzheimer's disease that are exacerbated by alcohol dependence.

PI_NAMEs: KIMBROUGH, ADAM J (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: Accounting;Address;Affect;Affective;Age;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol research;alcohol use disorder;Alcohols;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;anxiety-like behavior;Area;associated symptom;Behavior;Behavioral;Behavioral Symptoms;Brain;Brain region;Cells;Chronic;Clinical Research;Cognitive;Cognitive deficits;cognitive function;cognitive testing;cohort;Consumption;Data;Dementia;Deposition;design;drinking;early onset;effective therapy;Emotional;Ethanol;experimental study;Functional disorder;graph theory;Guidelines;Heavy Drinking;Human;Impaired cognition;Incidence;Individual;Injections;Location;Measures;Memantine;morris water maze;mouse model;Mus;Nerve Degeneration;neural network;Neurodegenerative Disorders;Neurologic Symptoms;Neurons;neuropathology;NMDA receptor antagonist;novel;object recognition;Pre-Clinical Model;pre-clinical research;Preventive measure;Preventive treatment;Process;Recording of previous events;reduce symptoms;Reporting;Risk Factors;Role;Saline;Senile Plaques;Severities;Stains;Structure;Symptoms;Synapses;targeted treatment;Testing;therapeutic development;Tissues;Transgenic Mice;Treatment Effectiveness;treatment guidelines;treatment strategy;vapor;Wild Type Mouse;young adult

PROJECT_TITLE: Identifying the relationship between alcohol and Alzheimer's Disease

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

PROJECT_TERMS: Adoption;Applications Grants;Award;Awareness;Back;Behavior;Behavioral;Behavioral Sciences;burden of chronic illness;Cardiovascular Diseases;career networking;Cause of Death;Cessation of life;Chronic;Communicable Diseases;Communities;community based research;community center;community engaged research;community engagement;COVID-19 disparity;COVID-19 mortality;COVID-19 pandemic;Data;Delaware;Department of Defense;Development;Diabetes Mellitus;disability;disadvantaged background;Disadvantaged minority;disparity reduction;Education;Educational Curriculum;Educational workshop;effective intervention;empowerment;Ensure;Epidemiology;experience;Faculty;faculty support;Fostering;Foundations;Funding;Grant;Health;health determinants;Health Disparities Research;health disparity;health equity;Health equity research;health outcome disparity;Health Promotion;Health Sciences;Hypertension;improved;Individual;Inequity;Infection;informal support;infrastructure development;innovation;Institution;institutional capacity;Interdisciplinary Study;Intervention;investigator training;Knowledge;Lead;Life Cycle Stages;Life Style;Link;low socioeconomic status;member;Mentors;Minority Groups;minority health;Mission;Morbidity - disease rate;mortality;Neurosciences Research;Obesity;Online Systems;Outcome;pandemic disease;Peer Review;Pilot Projects;Play;Process;Productivity;programs;Publications;Publishing;racial disparity;Recommendation;recruit;Reduce health disparities;Research;Research Personnel;Research Project Grants;Research Subjects;Research Support;Research Training;Resources;Risk;Risk Factors;Role;Running;SARS-CoV-2 infection;Science;Scientist;social;social factors;Social Sciences;socioeconomic disadvantage;Structure;success;Support System;symposium;Translational Research;Underrepresented Populations;United States National Institutes of Health;Work;Writing

PROJECT_TITLE: Investigator Development


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Sleep Research;Substance Misuse

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: During abstinence, recovering alcoholics experience severe and chronic insomnia that leads them to drink again because alcohol acts as a sedative and hypnotic. The cause of the insomnia is not known but may represent an imbalance of brain neurons regulating waking and sleep. We will use deep-brain imaging and pharmacogenetics to identify and correct the activity of brain neurons in an animal model of alcohol dependence.

PI_NAMEs: BLANCO-CENTURION, CARLOS A. (contact)

PROGRAM_OFFICER_NAME: KUMAR, SHAILESH

PROJECT_TERMS: Abstinence;Affect;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol exposure;alcohol prevention;alcohol relapse;alcohol use disorder;Alcohol withdrawal syndrome;Alcohols;Animal Model;Area;Arousal;Behavior;Biological Assay;Brain;Brain imaging;Cells;Chronic;chronic alcohol ingestion;Chronic Alcoholic Intoxication;Chronic Insomnia;Data;designer receptors exclusively activated by designer drugs;Development;Disparity;Dopamine;Dose;drinking;Electrophysiology (science);experience;falls;FOS gene;Functional Magnetic Resonance Imaging;gamma-Aminobutyric Acid;Histamine;Homeostasis;Hyperactivity;hypnotic;hypocretin;Hypothalamic structure;Image;imaging modality;improved;improvement on sleep;In Vitro;in vivo;innovation;Knowledge;Label;Link;Maintenance;Measurement;Measures;Modeling;mouse model;Mus;Neurobiology;Neurons;Neurosciences;non rapid eye movement;Pathologic;Persons;Pharmacogenetics;Phase;Phenotype;preference;problem drinker;Publishing;receptor;REM Sleep;Research;screening;sedative;Serotonin;sex;Sleep;Sleep disturbances;sleep regulation;Sleeplessness;Slice;Synapses;Testing;Time;tool;Withdrawal

PROJECT_TITLE: Hypothalamic Neuronal Activity During Insomnia Induced by Chronic Ethanol Exposure

STUDY_SECTION: BNRS

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


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

PI_NAMEs: DILLARD, DOROTHY  (contact)

PROJECT_TERMS: Acceleration;Address;Advocacy;Affect;African American population;Ally;Area;Attention;Automobile Driving;Award;career;Clinical Research;Collaborations;Communication;Communities;community center;community consultation;community engaged research;community engagement;Community Networks;community partners;community partnership;Consultations;County;Delaware;Disparity;Dissemination and Implementation;dissemination strategy;Educational Curriculum;Educational Materials;Effectiveness of Interventions;Ensure;experience;Faculty;Focus Groups;Funding;Goals;Grant;Health;Health Disparities Research;health equity promotion;Health equity research;health inequalities;Health Occupations;Health Priorities;health science research;Healthcare;Historically Black Colleges and Universities;Human;improved;Infrastructure;Knowledge;Life Cycle Stages;Measures;member;minority communities;Minority Groups;minority health;minority health disparity;Mission;Needs Assessment;Outcome;Pilot Projects;Play;Policies;Positioning Attribute;prevent;programs;Publications;Quality of life;Questionnaires;Research;Research Activity;Research Personnel;Research Project Grants;Research Support;Resources;Rural;Science;Services;skills;Students;System;Training;Translating;Translation Process;Translational Research;Translations;Trust;Underrepresented Minority;Underrepresented Populations;underserved community;United States National Institutes of Health;Universities;university student;uptake;Voice

PROJECT_TITLE: Community Engagement & Dissemination Core


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Lung;Prevention;Rare Diseases;Substance Misuse;Tuberculosis

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative Tuberculosis (TB) is major causes of disease and death in the world, especially in India, and occurs more frequently among persons living with HIV. People with unhealthy alcohol use may have problems with managing their TB or HIV. We are testing whether an intervention that focuses on alcohol reduction at the same time people with TB and HIV are getting treatment for TB can improve their clinical outcomes and overall health.

PI_NAMEs: CHANDER, GEETANJALI ;GUPTA, AMITA  (contact)

PROGRAM_OFFICER_NAME: ROACH, DEIDRA

PROJECT_TERMS: Accounting;Acquired Immunodeficiency Syndrome;Address;Adherence;Adoption;Affect;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;alcohol intervention;alcohol misuse;Alcohols;antiretroviral therapy;arm;Behavior Therapy;Behavioral;Biological Markers;care seeking;Caring;Cessation of life;Clinic;Clinical;co-infection;Cognitive Therapy;comparative effectiveness;Conduct Clinical Trials;cost;cost effectiveness;Counseling;Country;disability-adjusted life years;Disease;Disease Outcome;drinking;effective intervention;Effectiveness;effectiveness evaluation;effectiveness outcome;effectiveness-implementation RCT;effectiveness/implementation study;Epidemiologist;Ethanol;evidence base;Failure;Funding;General Population;Goals;Health;Health Personnel;Health system;Heavy Drinking;High Prevalence;HIV;HIV/AIDS;HIV/TB;Hospitals;Hybrids;implementation determinants;implementation framework;implementation measures;implementation outcomes;improved;improved outcome;Incidence;Income;incremental cost;incremental cost-effectiveness;India;Individual;innovation;Intervention;low and middle-income countries;Maintenance;Manuals;Measures;medication compliance;Methods;mortality;motivational enhancement therapy;multidisciplinary;Outcome;Outcome Measure;Patient Self-Report;Patients;Persons;Policies;poor health outcome;Population;Predisposition;prevent;Primary Infection;Provider;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;recruit;reduced alcohol use;Research;Resources;Risk;RNA;Scientist;social stigma;Sputum;Testing;therapy adherence;Time;treatment adherence;treatment as usual;Treatment Cost;Treatment Failure;Treatment outcome;Tuberculosis;tuberculosis treatment;United States National Institutes of Health;Viral;Work

PROJECT_TITLE: Hybrid trial for Alcohol reduction among people with TB and HIV in India (HATHI)

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Clinical Research;Genetics;Machine Learning and Artificial Intelligence;Mental Health;Pediatric;Prevention;Regenerative Medicine;Social Determinants of Health;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE  We know that exposure to excess stress can produce long-term effects that influence health and increase risk of developing common age-related disorders. Our goal is to better understand the phenomenon of biological embedding of stress – the process by which stress “gets under our skin” to produce permanent changes in biology. We have advanced the hypothesis that the effects of stress may extend all the way down to the level of stem/progenitor cells – the cells that continually replenish our tissues and organ systems. Our project will test this hypothesis in stem/pro- genitor cells obtained from child tissues (umbilical cord blood and cord tissue) at the time of birth, and measure key cellular processes in these stem/progenitor cells that relate to genomic integrity and bioenergetic function (telomere and mitochondrial biology systems) using a unique, translational approach (in vitro to in vivo physiology) in a novel stem cell culture system from these human newborn tissue samples. We expect our study findings to suggest avenues to better optimize long-term health and well-being.

PI_NAMEs: BOYLE, KRISTEN ELIZABETH;ENTRINGER, SONJA ;WADHWA, PATHIK D (contact)

PROGRAM_OFFICER_NAME: WEINBERG, DAVID H

PROJECT_TERMS: Activities of Daily Living;Address;adult stem cell;adverse birth outcomes;Age;age-related disease;Aging;allostatic load;Animals;Antioxidants;Attenuated;Basic Science;Behavioral;biobank;biobehavior;Bioenergetics;Biological;Biological Markers;Biological Phenomena;Biology;Biophysics;Birth;Body mass index;Body System;Cell Culture System;Cell Culture Techniques;Cell Differentiation process;Cell Line;Cell Physiology;cell type;Cells;cellular targeting;Characteristics;Child;Chronic stress;classification trees;Clinical Investigator;Cord Blood stem cells;Coupled;Data;Development;Diet;differentiation in vitro;Embryo;Endocrine;Ensure;Epigenetic Process;Ethnic Origin;experimental study;Exposure to;fetal;Follow-Up Studies;Functional disorder;Future;Gene Expression;Gene Expression Profile;Generations;Genetic Predisposition to Disease;genome integrity;gestational weight gain;Goals;Growth;Health;Hematopoietic stem cells;Human;human stem cells;Hydrogen Peroxide;Immune;imprint;In Vitro;in vivo;Individual Differences;Inflammatory;innovation;Intervention;intrapartum;Knowledge;Life;life span;Long-Term Effects;Machine Learning;maternal stress;Measures;Mesenchymal;Mesenchymal Stem Cells;Metabolic;Methods;Mitochondria;Modification;Molecular;Mothers;Newborn Infant;novel;offspring;Oxidative Stress;Parents;Pathway interactions;Personal Satisfaction;personalized intervention;personalized predictions;Phenotype;Physical activity;Physiological;Physiology;Placenta;Population;Population Heterogeneity;predictive modeling;Predisposition;Pregnancy;prepregnancy;primary outcome;Process;prognostic;prospective;psychosocial;Publishing;Race;Reactive Oxygen Species;recruit;regression trees;repository;Research Design;Research Personnel;resilience;Resolution;Resource Sharing;response;Resveratrol;Risk;senescence;sex;shared repository;Skin;Sleep;Social support;sociodemographics;Spirometry;Standardization;stem;stem cell biology;stem cells;Stress;Stromal Cells;System;Systems Biology;Telomerase;telomere;Testing;Time;Tissue Sample;Tissues;translational approach;transmission process;Umbilical Cord Blood;Variant

PROJECT_TITLE: Stress and Human Stem/Progenitor Cells: Biobehavioral Mechanisms

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Spinal Muscular Atrophy

ORG_CITY: NEW HAVEN

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Survival Motor Neuron protein (SMN) deficiencies cause Spinal Muscular Atrophy (SMA), the most common genetic cause of infant and toddler mortality. Although therapies have been developed to restore SMN proteins in patients, the function of SMN that critically compromises motor neurons has not been identified. Our recently published and preliminary data suggest a novel and fundamental molecular mechanism for SMN’s activities: the formation of biomolecular condensates (BMCs) that potentially explain the disease and could be druggable.

PI_NAMEs: NEUGEBAUER, KARLA M (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Affect;Affinity;Amino Acids;Arginine;arginine methyltransferase;Axon;axonal pathfinding;Binding;Binding Proteins;Binding Sites;Biochemistry;Biological Assay;Biotinylation;Cell Nucleus;Cell Physiology;Cells;Cellular Stress;Chemicals;Complement;Cytoplasm;Data;dimethylarginine;Disease;Embryo;Embryonic Development;Etiology;fluorescence imaging;Genetic;Genetic Transcription;genome editing;globular protein;Goals;grasp;Health;Image;Infant;inhibitor;insight;Ligand Binding;Ligands;Location;Mass Spectrum Analysis;Mediating;Methylation;Microscopy;Missense Mutation;Modification;Molecular;mortality;Motor;Motor Neurons;Mus;Muscle;mutant;Mutation;Nervous System Disorder;neuromuscular system;Neurons;novel;novel strategies;novel therapeutic intervention;Nuclear;Optics;Patients;Phenotype;Physical condensation;Play;Positioning Attribute;Post-Translational Protein Processing;protein complex;Protein Deficiency;protein function;Proteins;Publishing;RNA;RNA Processing;Role;scaffold;Site;SMN protein (spinal muscular atrophy);Source;Specific qualifier value;Specificity;Spinal Muscular Atrophy;Stress;Structure;Testing;Time;tissue/cell culture;Tissues;Toddler;Translations;Zebrafish

PROJECT_TITLE: DMA-Tudor interaction modules: a novel approach to Survival Motor Neuron protein (SMN) and Cajal body function

STUDY_SECTION: CMND

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


ADMINISTERING_IC: AI

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Cystic Fibrosis;Immunization;Infectious Diseases;Lung;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE This is a proposal to support a patient-oriented research program focused on the role of bacteriophages in bacterial infections. The PI hopes to develop greater expertise in translational research, enhance his mentoring skills, and broaden the scope and impact of his trainees’ work.

PI_NAMEs: BOLLYKY, PAUL L (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Advisory Committees;Air;Antibiotic Resistance;antibiotic tolerance;Antibiotics;Antibodies;Antibody-mediated protection;Antimicrobial Resistance;Bacteria;Bacterial Infections;Bacteriophages;Binding;career;career development;Chronic;chronic infection;Clinical;Clinical Research;Communities;Cystic Fibrosis;cystic fibrosis patients;Cytolysis;Dedications;Development;Diffusion;Elements;emerging antimicrobial resistance;Epithelial Cells;Faculty;Family suidae;Genetic Diseases;Genomics;Goals;Growth;Health;Human;Human body;human subject;Immunization;Individual;Infection;Inhalation;Knowledge;Liquid substance;Longitudinal cohort;Lung infections;Mediating;Medical;Medical Residency;Medical Students;Mentors;microbial;Microbial Biofilms;Microbiology;Modeling;molecular sequence database;monocyte;Mus;National Heart, Lung, and Blood Institute;National Institute of Allergy and Infectious Disease;natural antibodies;new therapeutic target;novel;Outcome;pathogenic bacteria;patient oriented research;Patients;Penetration;Phagocytosis;physician-scientist training program;Physicians;Polymers;prevent;Production;Productivity;programs;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Publishing;Reporting;Research;Research Personnel;resistance gene;Resources;respiratory colonization;Respiratory Disease;Respiratory Tract Infections;response;Role;Scientist;skills;Sputum;Surface;Technical Expertise;Testing;Thick;Time;Training;Translational Research;translational research program;treatment strategy;vaccine development;vaccinology;Virus;Vocational Guidance;Work;wound;Wound Infection

PROJECT_TITLE: Studies on bacteriophages in respiratory diseases

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Microbiome;Pneumonia;Pneumonia and Influenza

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: Project narrative Influenza infection is a deadly disease that is often complicated by a secondary bacterial pneumonia, which is a significant contributor to the morbidity and mortality. Antibiotics do not help the viral illness, and our work demonstrates it causes harm by altering the commensal organisms in the gastrointestinal tract to increase the susceptibility to bacterial pathogens. This study will understand how antibiotics altered the fungal colonies in the gut that affect the lungs immunity to pathogens and aim to lead to novel therapeutics that can target the mediators of this effect.

PI_NAMEs: CHEN, PETER  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Acute;Adoptive Transfer;Affect;Allergic;allergic response;Alveolar Macrophages;Antibiotic Therapy;Antibiotics;Bacteria;Bacterial Pneumonia;bacterial resistance;bacteriome;Cessation of life;Chronic;clinical practice;Colitis;commensal bacteria;Communities;cytokine;Data;Development;Disease;dysbiosis;eosinophil;Eosinophilia;Epidemic;Epithelial Cells;Epithelium;Feces;fighting;Functional disorder;fungus;Gastrointestinal tract structure;Gnotobiotic;Goals;Grant;gut microbiota;Helminths;high risk;Homeostasis;Human;Immune;immune function;Immune system;Immunity;Immunocompetent;immunoregulation;Impairment;In Vitro;in vitro Model;in vivo;Infection;Inflammatory;Inflammatory Response;Influenza;influenza infection;influenza pneumonia;influenzavirus;innate immune function;Interferon Type II;Lung;lung injury;Macrophage;Mediating;Mediator;Medical;Medicine;methicillin resistant Staphylococcus aureus;Methods;microbiome alteration;Modeling;Morbidity - disease rate;mortality;mouse model;Mucous Membrane;Mus;mycobiome;novel therapeutics;Nutritional;Organism;pathogen;pathogenic bacteria;Pathology;Patients;Phenotype;Pneumonia;Predisposition;pressure;Preventive measure;programs;prophylactic;Publishing;Pulmonary Inflammation;Pulmonary Pathology;Recovery;recruit;regenerative cell;Regulation;Risk;Role;Saccharomyces cerevisiae;Sampling;Serum;Signal Transduction;Staphylococcus aureus infection;superinfection;Testing;Tissues;translational study;Uric Acid;Veins;Viral;Virus Diseases;Work

PROJECT_TITLE: Fungal dysbiosis regulation of post-influenza bacterial pneumonia

STUDY_SECTION: LCMI

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


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

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: NARRATIVE We have identified a novel mechanism of oncogene activation where double PIK3CA mutations in cis increase cell signaling and sensitivity to drugs that target PIK3CA, compared to single mutations. The proposed research will investigate the mechanisms of activation and regulation of double mutations, their crosstalk with the estrogen receptor in breast cancer, and modulation of new substrates in the cell. This work will unveil new mechanisms of PIK3CA function and inhibition in cancer.

PI_NAMEs: VASAN, NEIL  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Advisory Committees;Alleles;alpelisib;Amino Acids;anti-cancer research;Binding;Biochemical;Biological Process;Breast;Breast Cancer Cell;Breast Cancer Patient;Breast Oncology;cancer cell;candidate marker;career;career development;Cell model;Cell Physiology;Cells;Clinic;clinical training;Clinical Trials;Complex;Credentialing;Double Effect;Drug Targeting;Environment;Epigenetic Process;Estrogen receptor positive;Estrogen Receptors;experience;experimental study;Family;Generations;Genetic Transcription;genomic biomarker;Global Change;Goals;Growth;Guanosine Triphosphate;histone methyltransferase;Histone-Lysine N-Methyltransferase;Human;Hyperactivity;improved;In Vitro;in vivo;inhibitor;Institution;International;Investigation;Investments;Knock-in;Lipid Binding;Lipids;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;medical schools;Medicine;Membrane;Membrane Lipids;Memorial Sloan-Kettering Cancer Center;Mentors;Mentorship;Metastatic breast cancer;MLL gene;Modeling;mouse model;mutant;Mutate;Mutation;novel;Oncogene Activation;Oncogenes;overexpression;Pathway interactions;Patients;Phase;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiology;PI3K/AKT;PIK3CA gene;PIK3CG gene;Positioning Attribute;pre-clinical;Progression-Free Survivals;Protein Biochemistry;Protein Kinase;Proteomics;Proto-Oncogene Proteins c-akt;randomized, clinical trials;Receptor Protein-Tyrosine Kinases;Recombinants;reconstitution;Recurrence;Regulation;Research;response;response biomarker;Sampling;Science;Scientist;Secure;Services;Signal Pathway;Signal Transduction;standard of care;structural biology;tenure track;Testing;Training;Work

PROJECT_TITLE: Investigating a hierarchical model for PI3K activation and inhibition in breast cancer by double PIK3CA mutations in cis

STUDY_SECTION: NCI

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


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

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Infections with the enteric bacterial pathogen Shigella are the second leading cause of diarrheal deaths globally and the emergence of antibiotic resistant Shigella strains increasingly limits our ability to treat infections. Our studies will define novel anti-Shigella human immune programs that are inhibited by virulence factors produced by Shigella. Therefore, our studies will determine whether pharmacological targeting of these Shigella virulence factors has the potential to be used as as a novel treatment option for Shigellosis.

PI_NAMEs: COERS, JOERN  (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Alleles;Anti-Bacterial Agents;Antibiotic Resistance;antimicrobial;Bacteria;bacterial genetics;Bacterial Interference;bactericide;Binding;Binding Proteins;Biochemical;Biological Assay;Breeding;Cell Culture Techniques;Cells;Cessation of life;Child;cofactor;Cues;cytokine;Cytoplasm;Cytosol;Data;Defense Mechanisms;Detergents;Diarrhea;Disease;Drug resistance;druggable target;Dynamin;Dysentery;Eating;Encapsulated;Engineering;Enteral;enteric pathogen;Enzymes;Epithelial Cells;extracellular;GBP1 gene;gene function;Genes;Genetic;genetic approach;Genetic Predisposition to Disease;Goals;Gram-Negative Bacteria;guanylate;gut inflammation;Host Defense;Human;IFNGR1 gene;Immune;Immune Evasion;Immune response;Immunity;In Vitro;in vivo;Infection;Inflammatory;inhibitor;Interferon Type II;Interferons;Intestines;Invaded;Lipid A;lipopolysaccharide-binding protein;Lipopolysaccharides;low and middle-income countries;Lymphocyte;Mediating;member;Membrane;microbial;Microcapsules drug delivery system;Modeling;Modification;Monitor;mouse model;multidisciplinary;Mus;mutant;novel;Oral;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;pharmacologic;Physiological;Predisposition;Prevalence;programs;Property;Protein Family;Proteins;Receptor Signaling;recruit;Resistance;resistant Shigella;Role;Shigella;Shigella flexneri;Shigella Infections;Signal Transduction;Surface;Testing;therapeutic target;Type III Secretion System Pathway;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Virulence;Virulence Factors;Work

PROJECT_TITLE: Interferon-inducible cell-autonomous immunity to cytosolic bacterial pathogens

STUDY_SECTION: BHI

STUDY_SECTION_NAME: Bacterial-Host Interactions Study Section [BHI]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: HINES

ORG_NAME: EDWARD HINES JR VA HOSPITAL

ORG_STATE: IL

PHR: Nearly 360,000 individuals suffer an episode of sudden cardiac arrest every year in the United States. Many are Veterans given their high prevalence of risk factors for sudden cardiac arrest. Because current resuscitation techniques promote survival with good neurological function in less than 10%, there is a pressing need for new interventions. We plan to examine in a clinically relevant swine model whether drugs known as gliflozins given during cardiac arrest could reduce damage to the heart and brain leading to improved survival with good neuro- logical function. Gliflozins were initially developed for type 2 diabetes mellitus but recently shown effective for heart failure. We found in our research laboratory that administration of empagliflozin attenuates cardiac injury leading to better post-resuscitation cardiac function. We herein propose to comprehensively assess in a swine model the effects of empagliflozin on initial resuscitation and survival with good neurological function. Because gliflozins are clinically available, our findings could lead to rapid clinical translation through the repurposing path.

PI_NAMEs: GAZMURI, RAUL JAIME (contact)

PROJECT_TERMS: Adult;Adverse effects;Affect;Animal Model;Attenuated;attenuation;Blood;Blood flow;Brain;Calcium;Cardiac;Cardiopulmonary Resuscitation;Cardiovascular system;Cause of Death;Cell Signaling Process;Cells;Cerebrovascular Circulation;Chest;Child;Cholesterol;Circulation;Clinical;clinical translation;clinically relevant;Coronary;Coronary Arteriosclerosis;design;Diabetes Mellitus;Dose;drug repurposing;Epinephrine;experimental study;Extracorporeal Circulation;Generations;Glucose;Heart;Heart Arrest;Heart failure;heart function;Heart Injuries;hemodynamics;High Prevalence;Hour;Human;Hypertension;Impairment;improved;Individual;inhibitor;Injury;Intervention;Ischemia;ischemic injury;Laboratory Research;Left;Left Ventricular Function;Mediating;Medicine;Metabolic;Mitochondria;Molecular;Myocardial;Myocardium;Natural regeneration;Nervous System Physiology;neurological recovery;Non-Insulin-Dependent Diabetes Mellitus;Organ;out-of-hospital cardiac arrest;Outcome;Oxygen;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;porcine model;Protein Isoforms;Protocols documentation;Reactive Oxygen Species;Reperfusion Injury;Research;Resuscitation;Risk Factors;Science;Secure;Signal Pathway;Signal Transduction;Smoking;Sodium;Sodium-Hydrogen Antiporter;symporter;Techniques;tissue injury;Tissues;Translating;Translations;United States;Universities;Vasoconstrictor Agents;Vasopressins;Ventricular;Ventricular Fibrillation;Veterans;Work

PROJECT_TITLE: Attenuation of Reperfusion Injury by Gliflozins During Cardiac Arrest Leading to Improved Post-Resuscitation Myocardial Function and Survival


FUNDING_MECHANISM: OTHERS

ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: PROJECT NARRATIVE Inflammatory bowel disease, comprised of Crohn’s disease and Ulcerative colitis, impacts an estimated 600 per 100,000 veterans causing significant morbidity (malabsorption, bloody diarrhea, strictures, fistulas, infection, and surgical resection) as well as mortality (increased rates of colorectal cancer with decreased survival). Medical therapy has improved but relapse remains common and is not well understood. The luminal surface of the intestinal epithelium is covered with a densely-packed array of microvilli that function in nutrient absorption and host defense. Crohn’s patients have decreased levels of proteins that maintain the structural integrity of the intestinal microvilli in areas of the gut without significant inflammation. In this proposal we will perform experiments using Crohn’s patient biopsy tissue, patient-derived enteroid culture, and in vivo mouse experiments to understand how defects in microvilli contribute to Crohn’s relapse and infection.

PI_NAMEs: MEENDERINK, LESLIE M (contact)

PROJECT_TERMS: Actins;Adhesions;Affect;American;Apical;apical membrane;Apoptosis;Architecture;Area;Automobile Driving;Bacteria;Bacterial Adhesion;Bacterial Infections;Biological Models;Biology;Biopsy;Brush Border;Bundling;Celiac Disease;Cell Line;Cell membrane;Cell Physiology;cell type;Cells;Cellular biology;cellular microvillus;Cellular Structures;Chronic;Colitis;Colonoscopy;Colorectal Cancer;colorectal cancer risk;Complex;Crohn's disease;Data;Defect;density;Diarrhea;Disease;Enterococcus faecalis;Enterocytes;Epithelial Cells;epithelial repair;Epithelium;Excision;experimental study;Fistula;Foundations;Funding;Fusobacterium nucleatum;Goals;Growth;gut inflammation;gut microbes;Hair;healing;Hemorrhagic colitis;Homeostasis;Host Defense;host-microbe interactions;Imaging Techniques;Immune system;Immunology;Immunotherapy;improved;in vivo;in vivo Model;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;Intestinal Diseases;intestinal epithelium;Intestines;Knockout Mice;Lighting;Link;Malabsorption Syndromes;Malignant Neoplasms;Medical;Membrane;Mentors;Mentorship;Messenger RNA;Microbe;microbial;Microscopic;Microscopy;Microvillus inclusion disease;Modeling;Morbidity - disease rate;mortality;mouse model;Mucous Membrane;Mus;new therapeutic target;Nutrient;nutrient absorption;Operative Surgical Procedures;Organoids;Osmosis;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Patients;Physicians;Positioning Attribute;Predisposition;prevent;Prognosis;Proteins;Recurrent disease;Refractory Disease;Relapse;relapse risk;Research Personnel;response;Risk;Risk Factors;Role;Sampling;Scanning Electron Microscopy;Scientist;Site;skills;Small Intestines;stem;stem cells;Structural defect;Structural Protein;Structure;Surface;Survival Rate;Testing;Therapeutic Intervention;Tissues;translational study;Transmission Electron Microscopy;Ulcerative Colitis;Veterans;villin;Villus

PROJECT_TITLE: The role of enterocyte apical structure in inflammatory bowel disease pathogenesis


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Diabetes is a major cause of morbidity and mortality in Veterans; it remains the main cause of lower limb amputations, blindness, and kidney failure. The proposed research is relevant to Veterans health because it represents a novel approach to understanding the relationship between the gut microbiome, bile acid signaling, and type 2 diabetes. The investigators will determine whether microbial bile acid biotransformations affect blood sugars. Moreover, they will determine if the gut microbiome can be manipulated to treat type 2 diabetes. Thus, the proposed research is relevant to the part of Veteran Affairs Office of Research and Development mission to better understand how the gut microbiome affects health and to find new treatments for type 2 diabetes.

PI_NAMEs: ZARRINPAR, AMIR  (contact)

PROJECT_TERMS: absorption;Address;Adult;Affect;Agonist;antagonist;Back;Bacteria;Bile Acids;bile salts;Blindness;Blood Glucose;blood glucose regulation;Cholesterol Homeostasis;Data;Diabetes Mellitus;Diabetic mouse;Diet;diet-induced obesity;Dietary Fats;Dietary intake;Disease;Ecology;Energy Metabolism;Engineering;Engraftment;Environment;Enzymes;Escherichia coli;General Population;Genes;Gluconeogenesis;Glucose;glucose metabolism;glucose tolerance;glycogenesis;Goals;gut microbiome;gut microbiota;Health;Hepatic;hepatic gluconeogenesis;High Fat Diet;Homeostasis;Hormones;Hydrolase;Immune response;improved;innovation;Insulin;insulin sensitivity;Intake;interest;Kidney Failure;Knock-in;Knockout Mice;limb amputation;Link;Lower Extremity;Mediating;Metabolic;metabolic abnormality assessment;Metabolic Biotransformation;Metabolic syndrome;Metabolism;Metagenomics;microbial;microbiome;microbiome research;microorganism;Mission;Modeling;Modification;Morbidity - disease rate;mortality;muricholic acid;Mus;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Nutrient;Obese Mice;Outcome;Outcome Study;Performance;Physiological;Physiology;Play;Population;Prevalence;Production;receptor;Research;research and development;Research Personnel;response;Ribosomal RNA;Role;Serum;Signal Pathway;Signal Transduction;Source;Testing;theories;tool;Transcript;transcriptome sequencing;translational impact;United States Department of Veterans Affairs;vector;Veterans;Wild Type Mouse

PROJECT_TITLE: The Role of Bile Salt Hydrolase in Glucose Metabolism


ORG_NAME: RLR VA MEDICAL CENTER

PHR: NARRATIVE A link between dementia and bone loss, often occurring with aging, has been suggested, although never con- clusively demonstrated. Using TREM2 mutant mice as a model of increased risk for Alzheimer's disease (AD), we will investigate the cellular and molecular mechanisms responsible for the deterioration of the skeletal system in this condition. Successful completion of these studies will widen our understanding of the cellular and molec- ular basis of the skeletal defects in mice with increased susceptibility to develop AD, and may set the basis for treatments that will improve both the cognitive and skeletal deficits in patients with AD.

PI_NAMEs: PLOTKIN, LILIAN IRENE (contact)

PROJECT_TERMS: Adult women;Age Months;aged;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Arginine;Axon;bcl-1 Genes;beta catenin;Biomechanics;bone;bone cell;Bone Density;bone fragility;bone loss;Bone Marrow Cells;bone mass;Bone Matrix;bone quality;Bone Resorption;bone strength;Brain;cathepsin K;Cell Count;Cell Separation;Cells;Cognitive;Connexin 43;cortical bone;Cyclin D1;Data;Defect;Dementia;dementia risk;Dendrites;Deterioration;Diagnosis;DNA Sequence Alteration;Elderly;Excision;Exhibits;Female;Fracture;Gene Expression;Genes;genetic manipulation;Geometry;Goals;Gonadal Steroid Hormones;Health;Heterozygote;High Prevalence;high risk;Hip region structure;Histidine;Impairment;improved;In Vitro;in vivo;Individual;insight;LDL-Receptor Related Protein 1;Life;Ligand Binding;Link;lipoprotein receptor related protein 5;male;Measures;men;Mental disorders;Microglia;Modeling;Modulus;Molecular;Morphology;mortality;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Myeloid Cells;Nervous System Disorder;Neurologic;old mice;Orchiectomy;Osteoblasts;Osteoclasts;Osteocytes;Osteoporosis;Ovariectomy;Patients;Phenotype;Post-Traumatic Stress Disorders;Predisposition;prevent;Prisoner;Property;protein expression;Publishing;Quality of life;Reporting;Risk;Risk Factors;Role;sex;Signal Transduction;skeletal;Skeletal system;Skeleton;Stress;substantia spongiosa;Testing;tibia;Tissues;TREM2 gene;Variant;Veterans;War;WNT Signaling Pathway;Woman;Work

PROJECT_TITLE: Skeletal complications to a TREM2 variant associated with Alzheimer's Disease


ORG_CITY: MATHER

ORG_NAME: VA NORTHERN CALIFORNIA HEALTH CARE SYS

PHR: We aim to characterize the essential roles of two proteins GRK5 and SAP97 in reduction (desensitization) of adrenaline stimulation of a signaling molecule nitric oxide to enhance cardiac output. We will find how this regulation goes wrong in heart diseases and thus offers novel strategies to treat heart diseases.

PI_NAMEs: XIANG, YANG K (contact)

PROJECT_TERMS: Address;Adrenergic Agents;Adrenergic Receptor;adrenergic stress;Agonist;aorta constriction;Attenuated;Binding;Biochemistry;Biological Assay;Biosensor;C-terminal;Calcium;Cardiac;Cardiac Output;Cardiomyopathies;Chronic;Co-Immunoprecipitations;Complex;Coupling;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cyclic GMP;Cyclic GMP-Dependent Protein Kinases;Data;desensitization;Disease;Dissociation;Electrophysiology (science);Enzyme-Linked Immunosorbent Assay;Epinephrine;Fluorescence Resonance Energy Transfer;Fluorescent Dyes;Functional disorder;G-substrate;GTP-Binding Proteins;Health;Heart;Heart Diseases;Heart failure;heart function;heart preservation;Human;Impairment;in vivo;Individual;inhibitor;innovation;Knock-in;Knock-out;Knockout Mice;Knowledge;Muscle Cells;Myocardial;Myocardial dysfunction;Myocardial Infarction;Nitric Oxide;Nitric Oxide Synthase;NOS1 gene;NOS3 gene;novel;novel strategies;Optics;Pathway interactions;phosphodiesterase 4D;phospholamban;Phosphorylation;Phosphotransferases;Physiological;Play;preservation;Proteins;receptor;Receptor Signaling;Recovery;Regulation;Research;restoration;Role;Ryanodine Receptor Calcium Release Channel;Scaffolding Protein;Serine;Signal Transduction;Signaling Molecule;Soluble Guanylate Cyclase;Stress;Synapses;Synaptic Receptors;Techniques;Testing;Transgenic Mice;Transgenic Organisms

PROJECT_TITLE: Desensitization of beta1 adrenergic receptor-nitric oxide signaling in cardiac diseases


ORG_CITY: NORTH LITTLE ROCK

ORG_NAME: CENTRAL ARKANSAS VETERANS HLTHCARE SYS

ORG_STATE: AR

PHR: Veterans, particularly the elderly, have a higher incidence of heart diseases than the general population including hardening of the valves of the heart which is a debilitating condition with no effective non-surgical treatment options. This disease involves the aortic valves becoming “bone like” and rigid which prevents the valve from opening properly and stresses the heart as it tries to pump blood out the valve. This research will study the processes underlying these changes in the heart valve and evaluate the potential efficacy of drugs as inhibitors of hardening of the valves. These drugs might have benefit to protect Veterans from developing this condition or potentially reverse the condition in Veterans with established aortic valve disease.

PI_NAMEs: MORRIS, ANDREW J (contact);SMYTH, SUSAN S.

PROJECT_TERMS: Acceleration;Adipose tissue;Aging;antagonist;aortic valve;aortic valve disorder;Aortic Valve Stenosis;Apolipoproteins;Atherosclerosis;Behavioral;Binding;blood pump;bone;calcification;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Models;Cell Culture System;Cell Differentiation process;Cell surface;Cell Surface Receptors;cell type;Cells;Coronary Arteriosclerosis;Data;Development;Diagnosis;Diet;Disease;disorder risk;Down-Regulation;drug efficacy;Elderly;Endothelial Cells;Endothelium;Environmental Risk Factor;Enzymes;Exhibits;Experimental Models;experimental study;extracellular;Fibrosis;Funding;Gene Knock-Out Model;Gene Silencing;General Population;Generations;Genes;Genetic;genetic risk factor;Genetic Transcription;Heart;heart cell;Heart Diseases;Heart Valves;Heritability;Human;immune cell infiltrate;improved;Incidence;Inflammation;Inflammatory;inhibitor;Injury;interest;interstitial cell;Intervention;Investigational Therapies;Link;lipid phosphate phosphatase;Lipids;Lipoprotein (a);Literature;Low-Density Lipoproteins;LPAR4 gene;lysophosphatidic acid;Lysophosphatidic Acid Receptors;Mediating;Medical;Metabolic Diseases;military veteran;mineralization;Modeling;Molecular;mortality;mouse model;Mus;NF-kappa B;Normal tissue morphology;novel strategies;osteogenic;particle;Pathologic;permissiveness;Pharmaceutical Preparations;pharmacologic;Phenotype;Post-Translational Protein Processing;prevent;Process;promoter;Reagent;receptor;Receptor Activation;Recombinants;Reporting;Research;response;Risk;Role;Serum;Signal Pathway;Signal Transduction;small molecule;small molecule therapeutics;Source;Stenosis;Stress;Testing;Therapeutic Intervention;tissue culture;Tissues;transcription factor;valve replacement;Variant;Vascular calcification;vascular inflammation;Veterans

PROJECT_TITLE: Lysophosphatidic Acid and Cardiovascular Disease Risk


ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: Inherited DNA mutations in the SDHA or SDHB genes can cause defects in the essential metabolic enzyme, succinate dehydrogenase (SDH) and are common in the general population (greater than 1.5% of individuals). Some of these mutations have no medical consequence, but others increase the risk of developing cancer and this risk can also be passed on to children. Individuals who have inherited harmful SDH mutations should undergo screening tests to detect any cancer at an early, curable stage. Genetic counseling and DNA testing should be done for family members of individuals who inherited a harmful mutation. Of the many thousand SDH mutations already discovered from DNA testing, less than 50 have been definitively categorized as harmful or having no medical consequences. We will test SDHA or SDHB mutations to determine which increase the risk of cancer. These results will inform the counseling and medical care of the more than 300,000 US Veterans estimated to have inherited an SDHA or SDHB gene mutation.

PI_NAMEs: HEINRICH, MICHAEL C (contact)

PROJECT_TERMS: Address;Amino Acids;Benign;Biological Assay;Budgets;Cancer Etiology;cancer risk;Carbon;Caring;Categories;Cell Line;Child;Classification;Clinical;clinical decision-making;clinically relevant;clinically significant;Codon Nucleotides;Complement;complement deficiency;Counseling;Coupled;CRISPR/Cas technology;Data Set;deep sequencing;Defect;Development;Diagnosis;DNA;DNA Sequence Alteration;Early Diagnosis;Ensure;Enzymes;Family member;Foundations;functional loss;Gene Mutation;General Population;Generations;Genes;Genetic;Genetic Counseling;Genetic Enhancement;genetic testing;genetic variant;Germ Lines;Germ-Line Mutation;Glucose;Glycerol;Goals;Growth;Guidelines;Healthcare;Hereditary Disease;Heritability;Heterozygote;Homologous Gene;Human;Human Cell Line;human model;Impairment;improved;Individual;Inherited;Intervention;Knock-out;Knowledge;Lead;Libraries;Life;lifetime risk;loss of function;loss of function mutation;Malignant Breast Neoplasm;Malignant Neoplasms;Medical;Medical Genetics;Medicine;Metabolic;Methods;Missense Mutation;Modeling;Multienzyme Complexes;Mutagenesis;mutant;Mutation;mutation screening;novel;Paraganglioma;Pathogenicity;Patient Care;Patients;Pheochromocytoma;Population;Predisposition;Procedures;Proteins;Publishing;Recommendation;Regimen;Renal Cell Carcinoma;Reporting;Risk;screening;Screening for cancer;Screening procedure;Source;Statistical Models;Stromal Neoplasm;Succinate Dehydrogenase;Technology;Testing;testing services;tumor;Variant;variant of unknown significance;Veterans;Veterans Health Administration;Work;Yeast Model System;yeast protein;Yeasts

PROJECT_TITLE: Functional profiling of germline SDH variants associated with cancer susceptibility


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Obesity is prevalent among US military veterans and linked to an increased incidence of cardiovascular disease, diabetes, pulmonary disorders and certain forms of cancer. As the veteran population ages, diminished produc- tion of the primary sex hormone, estrogen, promote fat accumulation in menopausal women. We discovered a subpopulation of adipocytes in humans and mice termed bone marrow-derived adipocytes (BMDAs) that exhibit an inflammatory character. These unique adipocytes are more abundant in female than male mice, and are increased by loss of estrogen in female mice. These observations led us to hypothesize that BMDAs provide a link between sex hormone-related changes in adiposity and body-wide inflammation. This project will test this hypothesis in mice in which estrogen signaling is suppressed, and in which BMDAs and their progenitors are specifically ablated. Understanding the mechanisms by which sex hormones regulate BMDA and progenitor production holds the potential for therapies to prevent menopausal diseases in aging female veterans.

PI_NAMEs: KLEMM, DWIGHT J (contact)

PROJECT_TERMS: Abdomen;abdominal fat;Ablation;Adipocytes;Adipose tissue;Age;Aging;Antibody Therapy;Area;Attenuated;Biogenesis;Body Composition;Body fat;Bone Development;Bone Marrow;Buttocks;Cardiovascular Diseases;Cells;Cellularity;Characteristics;combat;Communities;comorbidity;cytokine;Data;Diabetes Mellitus;Disease;energy balance;Energy Metabolism;ESR1 gene;Estradiol;Estrogen deficiency;Estrogens;Exhibits;Fatty acid glycerol esters;Female;Follicle Stimulating Hormone;Follicle Stimulating Hormone Receptor;Gene Expression;Genes;Gonadal Hormones;Gonadal Steroid Hormones;Health;Healthcare Systems;Hematopoietic stem cells;Heterogeneity;Hip region structure;hormonal signals;Hormone Receptor;Human;hypothalamic pituitary ovarian axis;Incidence;Individual;Inflammation;Inflammatory;Integrins;interest;ITGAM gene;Knock-out;Leptin;Life;Link;Lung Diseases;Macrophage;male;Malignant Neoplasms;Measures;Medical;Menopause;Mesenchymal;Metabolic;Metabolism;military veteran;Mitochondria;mouse model;Muramidase;Mus;Myelogenous;novel strategies;Obesity;Operative Surgical Procedures;Ovarian Ablation;Ovarian hormone;Ovariectomy;patient population;Patients;Phenotype;Platelet-Derived Growth Factor alpha Receptor;prevent;Process;Production;progenitor;Proliferating;Protein Isoforms;receptor;Reporting;Research;Role;Scientific Inquiry;Signal Transduction;stem cell population;Stromal Cells;Testing;Tissues;uncoupling protein 1;Veterans;Veterans Health Administration;Weight Gain;Woman

PROJECT_TITLE: Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes


ORG_CITY: DALLAS

ORG_NAME: VA NORTH TEXAS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: PROJECT NARRATIVE Myocardial infarction is the major cause of heart failure that is projected to increase 46% by the year of 2030. My proposed studies aim to understand how macrophages, the key immune cells recruited to carry out tissue repair after ischemic injury, control this crucial process through sensing and responding to DNA presented in the cytosol. My studies will also delineate if two immune modulators that have the potential to disrupt the DNA sensing and responding and are readily available clinically, modulate the behavior of macrophages and promote repair. This research will have the potential to reveal novel therapeutic targets to limit remodeling and heart failure after myocardial infarction.

PI_NAMEs: CAO, DIAN  (contact)

PROJECT_TERMS: Acute;Address;Affect;AIM2 gene;amlexanox;Award;Behavior;Binding Proteins;Biology;Bone Marrow Cells;Cardiac;Cardiac Myocytes;cardioprotection;Cardiovascular system;Caring;CASP1 gene;cell type;Cells;Chronic Phase;Clinical;Cytosol;cytosolic receptor;Data;Development;Disease;DNA;DNA receptor;Drug usage;ds-DNA;Effectiveness;Engineering;Event;experimental study;Fibroblasts;gain of function;Goals;guanylate;Heart failure;IL18 gene;Immune;Immune response;Immunity;Immunologics;Immunology;Immunomodulators;improved;In Vitro;in vivo Model;Incidence;Infarction;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;Interferon Type I;Interferon-beta;Interferons;Interleukin-1 beta;Intervention;Ischemia;ischemic injury;Knock-out;Knowledge;Knowledge acquisition;Laboratories;Link;Longevity;Macrophage;Mediating;Mitochondria;Modeling;mortality;Mus;Muscle Cells;Myelogenous;Myocardial;myocardial damage;Myocardial Infarction;Myocardial Ischemia;Myocardium;Nature;new therapeutic target;novel;novel strategies;novel therapeutics;Nuclear;Oligonucleotides;Outcome;overexpression;pathogen;Pathologic;Pathway interactions;Patients;Periodicity;Phagocytes;Phagosomes;Pharmaceutical Preparations;Phosphotransferases;Play;prevent;Process;Production;Publishing;Quinacrine;Records;recruit;repaired;Reporter;Reporting;Research;Resources;response;Role;Safety;sensor;Signal Transduction;Sterility;System;targeted treatment;TBK1 gene;Testing;therapeutic target;Time;tissue injury;tissue repair;Translating;translational impact;United States National Institutes of Health;Vacuole;Veterans;Viral;Work

PROJECT_TITLE: Intracellular immunity, cytosolic DNA sensing by cyclic GAMP synthase, and macrophages in ischemic injury and cardiac remodeling


ORG_CITY: JACKSON

ORG_NAME: G V SONNY MONTGOMERY VA MEDCIAL CENTER

ORG_STATE: MS

PHR: With aging along with prevalent risk factors such as diabetes, COPD, obesity, hypertension, and heart failure. While we have made great advances in the drugs and devices available to treat heart failure in adults, they do not work in elderly patients with this condition. The research proposed in this application will attempt to fill this critical gap by studying age-related impairment in the adaptive response that occurs during heart failure. The proposed research will highlight new therapeutic targets and further our understanding about how alterations in glucose and fatty acid metabolism occurred with aging in a preclinical model of heart failure. The outcome of the studies could provide a basis for improving contractile function and have a major impact on symptoms, disability, and survival of Veterans with heart failure.

PI_NAMEs: LI, JI  (contact)

PROJECT_TERMS: Address;Adult;Adverse effects;age related;age-related disease;Aging;aging related;Agonist;AMP-activated protein kinase kinase;antagonist;Antioxidants;Basic Science;Binding;Cardiac;Cardiac Myocytes;Caring;Cause of Death;Chronic Obstructive Pulmonary Disease;Clinical;comorbidity;Compensation;Complex;Congestive Heart Failure;Coronary;cost;Data;Dependovirus;Development;Devices;Diabetes Mellitus;Diagnosis;disability;experimental study;fatty acid metabolism;FRAP1 gene;Glucose;Goals;Healthcare Systems;Heart;Heart failure;heart function;Heart Hypertrophy;Homeostasis;Hospitalization;Hypertension;hypertensive;Hypertrophy;Impairment;improved;Inflammatory;Knock-out;Knockout Mice;Laboratories;Left Ventricular Hypertrophy;Mediating;Mediator;Medical center;Metabolic;Metabolism;Microvascular Dysfunction;military veteran;Molecular;Mus;new therapeutic target;novel;Obesity;older patient;Outcome Study;overexpression;Pathologic;Patients;Pharmaceutical Preparations;pharmacologic;Physiological;Play;Population;Pre-Clinical Model;pressure;Prevalence;prevent;Prevention;Promoter Regions;Proteins;Provider;provider networks;Publishing;Regulation;Reporting;Research;Resources;response;Response Elements;Rest;Risk Factors;Role;Scaffolding Protein;sensor;Signal Pathway;Signal Transduction;Sirolimus;Stress;Symptoms;synergism;Testing;Tetanus Helper Peptide;Time;transcription factor;Transgenic Mice;Translational Research;Treatment Failure;Ventricular Remodeling;Veterans;Work

PROJECT_TITLE: A Stress Inducible Protein Sestrin2 in Heart Failure


PHR: As Veterans age, they can lose the ability to perform activities of daily living because they are susceptible to poor or inadequate repair of musculoskeletal tissues such as muscle, ligaments, and bone. A major contributor to this poor repair is a severe, traumatic injury that affects multiple limbs. Despite known consequences of compromised healing of musculoskeletal tissues, a pre-clinical model of polytrauma has not been validated to recapitulate the multiple factors limiting activities of daily living, namely delayed fracture healing, soft tissue fibrosis and calcification, bone weakness, metabolic dysfunction, and cognitive impairment. If successful, this project will validate such a murine model that combines skin burn injury, soft tissue injury of the lower hindlimb, and a fracture of one femur midshaft to produce a hyper-inflammatory response. All injuries are well controlled favoring reproducibility. If validated, the mouse model can be used to study mechanisms by which severe injury causes common clinical complications among Veterans.

PI_NAMEs: NYMAN, JEFFRY STEPHEN (contact)

PROJECT_TERMS: Activities of Daily Living;Adult;Affect;Age;Aging;allodynia;Architecture;Area;Assisted Living Facilities;Bioluminescence;biomechanical test;Blood;Blood specimen;Body Weight;bone;Bone callus;Bone Density;bone fracture repair;bone fragility;bone loss;bone mass;bone quality;bone strength;Bone Tissue;Burn injury;calcification;Cartilage;CCL2 gene;chronic pain;Clinical;Cognition;Cognitive;cognitive function;Collagen;Contralateral;density;Deposition;Direct Lytic Factors;Dual-Energy X-Ray Absorptiometry;Euthanasia;Evaluation;ex vivo imaging;experience;Failure;Femoral Fractures;Femur;Fibrin;Fibrosis;Finite Element Analysis;Fluorescent Probes;Foundations;Fracture;functional decline;Functional impairment;Future;gait examination;Goals;healing;Hindlimb;Histology;Homeostasis;Hyperalgesia;Hypersensitivity;Image;Impaired cognition;Impairment;improved;in vivo;in vivo imaging;Individual;Inflammation;Inflammatory Response;Injections;injured;Injury;Interleukin-10;Interleukin-13;Interleukin-6;Intervention;Life;Ligaments;Limb structure;Literature;Luciferases;Measurement;Measures;mechanical stimulus;Memory;Memory impairment;Metabolic dysfunction;microCT;military service;Minerals;Mobility decline;Modeling;Monitor;mouse model;Movement;Multiple Fractures;Multiple Trauma;multiplex assay;Mus;Muscle;muscle regeneration;Musculoskeletal;Musculoskeletal Diseases;musculoskeletal injury;Natural regeneration;NF-kappa B;novel;object recognition;Organ;Osteoporosis;Outcome;Pain;pain perception;pain sensitivity;Pathologic Processes;pharmacologic;Phenocopy;placebo group;Plasma;pre-clinical;Pre-Clinical Model;Predisposition;productivity loss;prognostic indicator;Quality of life;Regulatory Element;repaired;Reporter;Reproducibility;Resistance;response;response to injury;Running;severe injury;Severities;sex;Short-Term Memory;Site;skin burn;Skin injury;Sleep;Sleep Wake Cycle;soft tissue;Soft Tissue Injuries;spine bone structure;Structure;Testing;Therapeutic;therapeutic target;Thick;Time;Tissue imaging;tissue repair;Tissues;TNF gene;Transgenic Mice;Trauma;Traumatic injury;Validation;vehicular accident;vertebra body;Veterans

PROJECT_TITLE: Validation of pre-clinical models of musculoskeletal healing following trauma


ORG_CITY: BROOKLYN

ORG_NAME: VA NEW YORK HARBOR HLTHCARE/SYS/BROOKLYN

PHR: L-type calcium channel (Cav1.3) contributes to cardiac function and contractility. Cav1.3 is normally absent in the healthy adult ventricles but recently our group demonstrated that Cav1.3 gene is re-expressed in the ventricles of patients with heart failure. Preliminary studies from our laboratory demonstrated that Cav1.3 is truncated at its C-terminus portion which moves to the nucleus and causes an increase in its own gene expression thereby allowing more calcium entry into the heart. In this research, we aim at leveraging this C-terminus mobile property to enhance cardiac function and improve heart contractility in heart failure. The findings from this work will have important therapeutic implications for Veterans suffering from heart failure.

PI_NAMEs: BOUTJDIR, MOHAMED  (contact)

PROJECT_TERMS: Action Potentials;Adult;Aging;Anterior Descending Coronary Artery;atrioventricular node;Biochemical;Calcium;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cause of Death;Cell membrane;Cell Nucleus;Cell Physiology;ChIP-seq;Coupling;Data;design;design and construction;Developed Countries;Development;differential expression;Echocardiography;Electrophysiology (science);Elements;Enhancers;Environment;FDA approved;fetal;functional restoration;Gene Expression;Gene Expression Regulation;gene therapy;Genes;Genetic Transcription;Health;Heart;Heart Atrium;Heart Contractilities;Heart failure;heart function;Histology;improved;in vivo;innovation;Ions;Knockout Mice;L-Type Calcium Channels;Laboratories;Left;Left Ventricular Ejection Fraction;Left Ventricular Function;Ligation;Light;Maps;Mediating;Messenger RNA;mouse model;Mus;Muscle Cells;Neonatal;Neurosecretory Systems;novel;novel therapeutic intervention;Optics;patch clamp;Patients;Peptides;Play;Population;promoter;Promoter Regions;Property;Proteins;Public Health;Publishing;rational design;Regulation;Reporting;Research;Role;Signal Transduction;Sinoatrial Node;Testing;Therapeutic;Time;Tissues;transcription factor;transcriptome sequencing;Transfection;translational impact;vector;Ventricular;Veterans;voltage;Western Blotting;Work

PROJECT_TITLE: Mechanisms and Therapeutic Role of C-terminus of Cav1.3 L-type Calcium Channel in the Heart


ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: This work will benefit both Veterans and civilians who have osteoarthritis (OA), by identifying novel approaches to target the control of inflammation and pain. The number of patients in the US estimated to have symptomatic osteoarthritis approaches 27 million. Incidence rate is 26% higher than the general population in active duty service members 20-24 years old, and >100% higher for those >40 years old, largely due to increased incidence of acute and chronic joint injury in the military. This project will identify a novel method of treatment to inhibit inflammation and chronic pain that results from arthritis development after joint injury. Expanding medical approaches for OA will improve quality of life, enhance rehabilitative efforts, and diminish the need for joint replacement in Veterans.

PI_NAMEs: SCANZELLO, CARLA ROSE (contact)

PROJECT_TERMS: Ablation;Acceleration;active duty;Acute;Address;Animal Disease Models;Animals;Anti-Inflammatory Agents;Antibodies;Arthralgia;arthritic pain;Arthritis;Behavior;Bone remodeling;Bone Resorption;Caring;Cartilage;cartilage repair;CD14 Antigen;CD14 gene;Cell Culture Techniques;Chronic;chronic pain;Clinical;clinical care;Clinical Trials;Cumulative Trauma Disorders;Data;Degenerative polyarthritis;Development;Disease;Dose;Drug Delivery Systems;economic impact;Ensure;functional improvement;Future;General Population;Genetic;Goals;Human;Image;improved;In Vitro;Incidence;Individual;Inflammation;Inflammatory;Injury;Innate Immune Response;innovation;insight;joint function;joint injury;Joints;Link;loss of function;Macrophage;Measures;Medial meniscus structure;Mediating;Medical;meniscus injury;Mesenchymal Stem Cells;Methods;Military Personnel;military service;Miniature Swine;Modeling;Molecular;monocyte;mouse model;Mus;Mutant Strains Mice;Myeloid Cells;Natural Immunity;Neutralization Tests;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Osteitis;osteoarthritis pain;osteoclastogenesis;Osteoclasts;Pain;pain behavior;pain inhibition;Pain Measurement;pain reduction;pain relief;Pathology;Pathway interactions;Patient Selection;Patients;Pattern;Pattern Recognition;Pattern recognition receptor;Pharmaceutical Preparations;pharmacologic;Phase;phase change;pilot test;porcine model;Positioning Attribute;Pre-Clinical Model;prevent;programs;Quality of life;Reagent;receptor;Receptor Activation;Receptor Inhibition;Receptor Signaling;reconstruction;Rehabilitation therapy;repair strategy;repaired;Replacement Arthroplasty;Reproducibility;Research Personnel;response;service member;socioeconomics;Source;spontaneous pain;stem cell therapy;subchondral bone;Surgical Models;Synovitis;Techniques;Testing;Therapeutic;tissue culture;tissue injury;Tissues;Toll-like receptors;tool;translational approach;Translations;Traumatic Arthropathy;Veterans;Work

PROJECT_TITLE: BCCMA: Cartilage Repair Strategies to Alleviate Arthritis Pain (Care AP): Targeting Pattern-Recognition to Reduce Pain-Related Pathology in Osteoarthritis


ORG_CITY: MILWAUKEE

ORG_NAME: CLEMENT J. ZABLOCKI VA MEDICAL CENTER

ORG_STATE: WI

PHR: The proposed research is relevant to public health as triple-negative breast cancer (TNBC) is very progressive and lacks molecular targets for therapeutic intervention. This application will test the hypothesis that p38 MAPK activation promotes TNBC oncogenesis by activating a metabolic pathway. By demonstrating the role of p38 in TNBC oncogenesis and the therapeutic target activity of the p38-activated metabolic pathways, the proposed research will contribute significantly to improve health care of TNBC patients and female Veterans.

PI_NAMEs: CHEN, GUAN  (contact)

PROJECT_TERMS: 6-Phosphofructo-2-kinase;aerobic glycolysis;Binding;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Cells;Clinic;Clinical;Collaborations;Combined Modality Therapy;Complex;Data;Dose;Enzymes;Estrogen Receptors;Family member;Female;Fructose-2,6-bisphosphatase;functional group;Gene Expression;Genes;Genetic;Genetic Transcription;glucose uptake;Glycolysis;Growth;Healthcare;improved;Individual;inhibitor;Knock-out;Link;Malignant Breast Neoplasm;Malignant Neoplasms;MAP Kinase Gene;MAPK12 gene;Mass Spectrum Analysis;Metabolic;Metabolic Pathway;molecular targeted therapies;mouse genetics;Mus;new therapeutic target;novel;novel therapeutic intervention;Oncogenes;Outcome;overexpression;Pathogenesis;Pathologic;Pathway interactions;pharmacologic;Phosphorylation;Phosphotransferases;Pirfenidone;polyoma middle tumor antigen;Progesterone Receptors;Prognosis;Protein Family;Proteins;Proteomics;public database;Public Health;Regulation;Research;RNA;Role;screening;Signal Transduction;Signal Transduction Pathway;SLC2A1 gene;Specimen;Subgroup;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissues;triple-negative invasive breast carcinoma;tumorigenesis;Veterans;Warburg Effect

PROJECT_TITLE: Glycolytic signaling of p38gamma in breast cancer


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Membrane proteins are critical drug targets for a wide range of human diseases, but existing methods are poorly suited to understanding interactions between membrane proteins and the surrounding lipid environment. We will develop new technologies combining lipid nanodiscs and mass spectrometry to understand the structure, biophysics, and function of these interactions and their relevance to biology and disease.

PI_NAMEs: MARTY, MICHAEL T (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: advanced disease;Affect;Age;Automobile Driving;Binding;Binding Sites;Biological Assay;Biological Process;Biology;Biomedical Research;Biophysics;Cell Physiology;Complex;Complex Mixtures;Disease;drug discovery;Drug Targeting;Environment;Foundations;functional outcomes;Global Change;Goals;Human;human disease;improved;Ion Channel;Lipid Bilayers;Lipid Binding;lipidome;lipidomics;Lipids;Lipoproteins;Mass Spectrum Analysis;Membrane Proteins;Methods;Molecular;mutant;nanodisk;new technology;novel;novel strategies;novel therapeutic intervention;particle;Physiological;Physiology;protein function;protein structure;Proteins;response;Site;Specificity;structural biology;Structure;tool;Viral

PROJECT_TITLE: Unravelling Membrane Protein-Lipid Interactions using Nanodiscs and Mass Spectrometry


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease;Prevention

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Fatty liver disease (FLD) is a burgeoning health problem with few therapeutic options. We have used human genetics to identify genetic variants in a gene called PNPLA3. One variant confers increased susceptibility and the other increased resistance to FLD. In this application we will build on these discoveries to glean new insights into the pathogenesis of FLD with a goal of developing new strategies and targets for the treatment of chronic liver disease.

PI_NAMEs: COHEN, JONATHAN CHARLES;HOBBS, HELEN HASKELL (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Address;Adipose tissue;African;African ancestry;Alcoholic Fatty Liver;Animal Model;Autophagocytosis;Binding;Biochemical;Biological Assay;Body mass index;Cells;chronic liver disease;Clinical;cofactor;combat;Complex;CRISPR/Cas technology;Development;Diagnosis;Disease;Disputes;Etiology;European;Fasting;Fatty Liver;fatty liver disease;feeding;Future;gain of function;gene discovery;Genes;genetic approach;genetic risk factor;Genetic Transcription;genetic variant;Glean;Goals;Grant;Health;Heart;Hepatic;High Prevalence;Hispanic Populations;Homeostasis;Human;Human Genetics;Hydrolysis;Impairment;in vivo;Individual;insight;Insulin Signaling Pathway;Laboratories;Lipase;Lipids;Liver;Liver diseases;Luciferases;Maps;Mediating;Messenger RNA;Metabolic;Methods;Molecular;Monitor;mouse model;multicatalytic endopeptidase complex;Mus;mutant;Mutation;non-alcoholic fatty liver disease;novel therapeutic intervention;Nutritional;Obesity;Pathogenesis;Pathogenicity;Pathway interactions;Phospholipase;Physiological;population based;Population Genetics;Post-Transcriptional Regulation;posttranscriptional;Predisposition;Prevalence;prevent;Prevention;Prevention strategy;problem drinker;Process;protein expression;protein protein interaction;Proteins;Public Health;reconstitution;recruit;Resistance;Role;Sampling;Site;Surveys;System;Technology;Testing;Therapeutic;Tissues;Translations;Triglycerides;ubiquitin-protein ligase;Variant

PROJECT_TITLE: PNPLA3 in Susceptibility and Resistance to Fatty Liver Disease

STUDY_SECTION: NMHD

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


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: GALVESTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: Narrative HIV continues to cause a global pandemic with more than 36 million infections worldwide. In this project, we aim to understand the molecular mechanisms for the modulation of BRD4 to induce HIV epigenetic suppression and to test as a proof of concept if the two novel small molecules identified in our laboratory can induce repression and/or silencing of latent HIV in vivo by modulating this pathway.

PI_NAMEs: HU, HAITAO  (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, GERARD

PROJECT_TERMS: Aftercare;analog;Binding;Binding Sites;Biotinylation;Bromodomain;Bromodomains and extra-terminal domain inhibitor;CD4 Positive T Lymphocytes;Cell model;Cells;Chemicals;Chromatin;Chromatin Structure;Complex;design;Docking;Epigenetic Process;epigenetic regulation;Future;Genetic Transcription;Genome;Goals;Histones;HIV;Human;humanized mouse;In Vitro;in vivo;Infection;innovation;Investigation;Knock-out;Laboratories;latent infection;Lead;Lysine;Mediating;Microglia;Molecular;Molecular Probes;mouse model;multidisciplinary;Mus;Myeloid Cells;novel;novel strategies;overexpression analysis;pandemic disease;Pathway interactions;Peripheral Blood Mononuclear Cell;prevent;Protein Family;Protein Isoforms;protein protein interaction;Proteins;Reader;recruit;Regulation;Repression;Research;Residual state;Role;scaffold;Site;small molecule;Structure;T-Lymphocyte;Tertiary Protein Structure;Testing;Toxic effect;Transactivation;Transcription Elongation;transcriptome sequencing;transcriptomics;viral DNA;Withholding Treatment

PROJECT_TITLE: Modulation of BRD4 to epigenetically suppress HIV

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Genetics;Heart Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Cardiac fibrosis is a major cause of morbidity and mortality worldwide, affecting almost all forms of cardiovascular disease, but no effective therapies are currently available. This study will investigate the molecular mechanisms that regulate the long-term fate and persistence of myofibroblasts, the key driver and mediator of fibrosis. The proposed studies will likely provide new fundamental insights into cardiac stromal biology, and open potential avenues for the development of novel therapeutic strategies against fibrosis.

PI_NAMEs: CHO, SANGKYUN  (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Advisory Committees;Affect;Animal Model;antifibrotic treatment;Attenuated;Back;Biocompatible Materials;Biology;Biomedical Engineering;Cardiac;cardiac tissue engineering;Cardiology;Cardiovascular Diseases;Cardiovascular system;career;cell type;Cells;Cellular Assay;Characteristics;Child;Chromatin;Committee Members;coronary fibrosis;Custom;Development;drug candidate;druggable target;effective therapy;Effector Cell;efficacy testing;Engineering;Environment;Epigenetic Process;epigenomics;Etiology;Event;Extracellular Matrix;Feedback;Fibroblasts;fibrogenesis;Fibrosis;Genetic;Genetic Markers;Goals;Heart;Heart failure;human induced pluripotent stem cells;Hydrogels;Hypertrophy;Immunoprecipitation;in vitro Assay;in vivo;induced pluripotent stem cell;inherited cardiomyopathy;insight;live cell imaging;Mass Spectrum Analysis;mechanical properties;mechanical signal;Mechanics;Mediating;Mediator;Medicine;Mentors;Mentorship;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multiple omics;Mus;Myocardial;Myocardial Ischemia;Myofibroblast;novel;novel therapeutic intervention;Pathologic;Pathway interactions;Patient-Focused Outcomes;Play;Population;pressure;programs;Proteins;Proteomics;Protocols documentation;Regenerative Medicine;Regulation;Regulatory Element;Reporter;Research;Research Training;response;Role;Series;Signal Transduction;single cell analysis;single cell genomics;synergism;System;Testing;Therapeutic;Time;Tissues;Training;training opportunity;transcription factor;transdifferentiation;Transforming Growth Factor beta;Transposase;Universities;virtual

PROJECT_TITLE: Elucidating the Role of Microenvironment Mechanics in Regulating Cardiac Myofibroblast Plasticity

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(OA)]