ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Nutrition;Obesity

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it elucidates the molecular mechanisms of obesity- related changes to plasma bile acid levels and hepatic drug transport. The results could eventually guide statin dosing strategies and dosing for other drugs utilized in obese patients with comparable drug disposition pathways. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to reducing illness and disability.

PI_NAMEs: HAGENBUCH, BRUNO  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Acyltransferase;Address;Adult;Affect;Bile Acids;Binding;Biological Assay;Biological Models;Cell membrane;Cells;Child;Cholesterol;Cirrhosis;clinically significant;comorbidity;Complex;Coronary heart disease;CRISPR-mediated transcriptional activation;Cysteine;Data;Diet;disability;Disease;Dose;drug disposition;Drug Interactions;Drug Transport;Drug Utilization;Fatty acid glycerol esters;Fructose;Glycosphingolipids;Goals;Health;Healthcare;Hepatic;Hepatocyte;HepG2;Human;innovation;Knowledge;Label;Lead;Ligation;Lipids;Liver;Measures;Mediating;medication safety;Membrane;Membrane Fluidity;Membrane Microdomains;Membrane Proteins;Metabolic syndrome;Metformin;Mission;Modification;Molecular;Monounsaturated Fatty Acids;mouse model;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;Obese Mice;obese patients;Obesity;Obesity Epidemic;Outcome;Palmitic Acids;palmitoylation;Pathologic;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;Plasma;Post-Translational Protein Processing;Post-Translational Regulation;Prevalence;prevent;Proteins;Proteomics;Public Health;recruit;Research;response;Risk;Saturated Fatty Acids;Site-Directed Mutagenesis;stable cell line;Testing;trafficking;Transfection;United States;United States National Institutes of Health;uptake;Western Blotting

PROJECT_TITLE: Post-translational regulation of hepatic uptake transporters in health and disease

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Nutrition;Obesity

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE Liver dysfunction is a major driver of pathology in obesity and diabetes, and we have discovered a new metabolite-driven pathway that appears to be required for exerting these effects. This program will determine the importance of this newfound signaling pathway in preventing obesity and diabetes pathogenesis, and examine mechanisms through which this is achieved. We expect that this will lead to the development of new treatments for metabolic disease.

PI_NAMEs: CHOUCHANI, EDWARD THOMAS (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Acute;Adipocytes;Anti-Inflammatory Agents;Binding;Biochemical;Brown Fat;candidate identification;Cell membrane;cell type;Cells;Characteristics;Chronic;Data;Development;Diabetes Mellitus;diabetes pathogenesis;Disease;Distal;Endocrine;Epidemiology;Exposure to;extracellular;Fibrosis;Flow Cytometry;G-Protein-Coupled Receptors;Genetic;Grant;Health;Hepatic Stellate Cell;Hepatocyte;in vivo Model;Inflammation;Inflammatory;interest;Length;Link;Liquid substance;Liver;Liver Dysfunction;Liver Fibrosis;liver inflammation;loss of function;Macrophage;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Diseases;Metabolism;Methods;Mitochondria;Modeling;Molecular;Muscle Cells;non-alcoholic fatty liver disease;novel;Obesity;obesity prevention;obesogenic;Paper;Pathogenicity;Pathology;Pathway interactions;pharmacologic;Physiological;Physiology;Play;Profibrotic signal;programs;protonation;receptor;Regulation;Reporting;Respiration;response;Role;Series;Signal Pathway;Signal Transduction;stellate cell;Succinates;System;Testing;Tissues;uptake;western diet;Whole Organism;Work

PROJECT_TITLE: Defining mechanisms of extracellular succinate regulation over metabolic tissue function

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Klebsiella pneumoniae is a leading cause of antibiotic-resistant hospital-acquired infections and childhood mortality. In this study, we will determine what types of antibodies are associated with protection against Klebsiella pneumoniae. We will also study human antibody responses against a variety of molecules that coat the outer surface of Klebsiella pneumoniae to identify the ideal targets of a new vaccine for this bacterium.

PI_NAMEs: HARRIS, JASON B (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Address;Affect;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;Antibodies;Antibody Response;Antibody-mediated protection;Antigen Targeting;Antigens;Asia;attributable mortality;Bacteremia;Bacteria;Bacterial Antibiotic Resistance;Bangladesh;Blood;Boston;carbapenem resistance;Cephalosporin Resistance;Child;Childhood;Clinical;Complement;Data;Deposition;design;Development;Disease;effectiveness measure;Enrollment;experimental study;gut colonization;Health;Human;human monoclonal antibodies;human pathogen;Immune response;Immunity;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;improved;Individual;Infection;insight;Intestines;Klebsiella;Klebsiella pneumoniae;Knock-out;Knowledge;Longitudinal cohort;low and middle-income countries;Maps;Massachusetts;Measures;Mediating;mortality;Nasopharynx;neonatal sepsis;neutrophil;Nosocomial Infections;novel vaccines;O Antigens;Outcome;Ozone;pathogen;Patients;Phagocytes;Phagocytosis;Phase;Plasmablast;Pneumococcal Infections;Polysaccharides;Population;pre-clinical;prevent;Proxy;Rectum;Research;resistant Klebsiella pneumoniae;response;Sampling;Serology;Serotyping;Specificity;Surface;Swab;United States;United States Food and Drug Administration;Vaccine Antigen;vaccine development;vaccine efficacy;vaccine trial;Vaccines;Variant;Work;World Health Organization

PROJECT_TITLE: Antibody mediated immunity against Klebsiella pneumoniae

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Hematology

ORG_CITY: COLLEGE STATION

ORG_DEPT: PHARMACOLOGY

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PI_NAMEs: LI, ZHENYU  (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Acute;acute coronary syndrome;Adverse event;adverse outcome;Agonist;antagonist;Atrial Fibrillation;Atrial Natriuretic Factor;atrial natriuretic factor receptor A;Binding;Biological Markers;Blood Platelets;Blood Vessels;Blood Volume;Brain natriuretic peptide;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular system;Chronic;Clinical Medicine;Coronary heart disease;Cyclic GMP;Data;Development;diagnostic biomarker;Event;Guanylate Cyclase;Heart failure;Hormones;Human;Impairment;In Vitro;in vivo;Incubated;Injections;insight;Mediating;Mediator;Membrane;Modeling;Molecular;Mus;Myocardial dysfunction;Myocardial Infarction;Natriuretic Peptides;new therapeutic target;novel;Pathogenesis;Patients;Physiological;Plasma;Platelet Activation;Platelet aggregation;Platelet Aggregation Induction;platelet function;Play;pro-brain natriuretic peptide (1-76);Prognosis;receptor;Recombinants;Regulation;Risk Marker;Role;saluretic;Second Messenger Systems;Severity of illness;Signal Transduction;Soluble Guanylate Cyclase;Symptoms;Testing;Therapeutic;Thrombosis;thrombotic;Thrombus;Time;Vasodilator Agents

PROJECT_TITLE: BNP not just a biomarker of cardiovascular disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-D (02)]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: ANN ARBOR

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The basic pathogenetic mechanisms of Human papilloma virus positive head and neck squamous cell carcinoma (HPV+ OPSCC) remain incompletely understood. This proposal seeks to overcome a substantial gap in knowledge by advancing on our recent technological developments to study the molecular impact of HPV to host tumor genome integrations on the host transcriptome. Furthermore, we will also advance the general understanding of when HPV integration events drive cancer progression.

PI_NAMEs: BRENNER, JOHN CHADWICK (contact);MILLS, RYAN E;SPECTOR, MATTHEW EDWARD

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: Adoption;ATAC-seq;Biological;Biological Markers;cancer genome;Cell Line;Cells;Characteristics;Chromatin;Clinical;Clinical Trials;Clonality;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Data;Detection;Development;Disease;DNA;DNA sequencing;Elements;Engineering;Epidemic;Event;Future;gene function;Genes;Genetic;Genetic Transcription;genome sequencing;Genomics;Goals;Head and Neck Squamous Cell Carcinoma;Heterogeneity;HPV positive;Human papilloma virus infection;human papilloma virus oropharyngeal squamous cell carcinoma;Human Papillomavirus;improved;Individual;Informatics;integration site;Knowledge;Link;Location;Machine Learning;Malignant Neoplasms;Modeling;Molecular;Morbidity - disease rate;new technology;novel;oral HPV-positive head and neck cancers;Outcome;Pathogenicity;Patients;Phenotype;prognostic value;prognostication;programs;Public Health;Publishing;Recurrence;Research;Resources;Role;Sensitivity and Specificity;Specimen;Structural Models;Structure;success;Technology;technology development;Testing;Transcript;transcriptome;transcriptome sequencing;Treatment Failure;Treatment outcome;treatment risk;tumor;tumor progression;United States;Vaccines;Viral;XCL1 gene

PROJECT_TITLE: Defining the Role of HPV Integration Structures in HNSCC Molecular Heterogeneity

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Cocaine;Drug Abuse (NIDA only);Endocannabinoid System Research;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Project Narrative Cocaine use disorder (CUD) remains a vast problem in the United States due, in part, to the high economic and health costs, and, unlike other drugs of abuse, there is no FDA-approved medication for treatment. Although there are many factors that influence CUD, there is a strong interaction between stress and drug use in human cocaine users which is problematic as stress is an unavoidable and powerful contributor to CUD. The proposed research is relevant to human health sciences as understanding the neurobiological mechanisms that are responsible for the long-term consequences of stress-drug interactions on susceptibility to drug-seeking behavior remains an important and necessary area of study with the ultimate goal of developing new and more effective therapeutic strategies for managing CUD.

PI_NAMEs: MCREYNOLDS, JAYME ROSE (contact)

PROGRAM_OFFICER_NAME: VEMURI, KIRAN R V

PROJECT_TERMS: 2-arachidonylglycerol;2-arachidonylglycerol signaling;addiction;American;Animal Model;antagonist;Area;Attenuated;attenuation;Behavior;Behavioral;Brain;cell type;Cells;Cholecystokinin;Chronic stress;CNR1 gene;Cocaine;cocaine relapse;cocaine seeking;cocaine self-administration;cocaine use;Cocaine use disorder;Cocaine Users;Data;Development;Disinhibition;Drug Interactions;drug of abuse;drug seeking behavior;Drug usage;economic cost;Electrophysiology (science);endocannabinoid signaling;endogenous cannabinoid system;Enzymes;FDA approved;Fiber;Fluorescent in Situ Hybridization;Goals;Health Care Costs;Health Sciences;hippocampal pyramidal neuron;Human;in vivo;Intake;interest;Interneurons;Life;Mass Spectrum Analysis;Measurement;Measures;Mediating;Mediator;Modeling;Molecular;National Institute of Drug Abuse;neuroadaptation;neurobiological mechanism;Neurobiology;neuromechanism;neurophysiology;neurotransmission;novel;novel therapeutics;Output;patch clamp;Pharmaceutical Preparations;pharmacologic;Photometry;Population;Positioning Attribute;pre-clinical;Predisposition;Prefrontal Cortex;Prevalence;programs;Rattus;Recording of previous events;Regulation;Research;Rewards;Role;Signal Transduction;Site;Slice;socioeconomics;Stress;stressor;Synaptic plasticity;System;Techniques;Testing;Therapeutic;therapeutic target;therapeutically effective;Time;United States;Up-Regulation

PROJECT_TITLE: Role of prelimbic cortical endocannabinoid signaling in enhanced cocaine-seeking behavior following combined repeated stress and cocaine use in rats

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-M (02)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Rare Diseases

PHR: PROJECT NARRATIVE (3-sentence limit) Recent advances in hyperpolarized metabolic imaging, pioneered by our team and others, allow real-time in vivo tracking of metabolic conversions of injected hyperpolarized 13C-pyruvate to downstream metabolites in multiple metabolic pathways, resulting in new imaging biomarkers to indicate aberrant cellular metabolism, inform dis- ease progression, and guide treatment decisions. One of the major hurdles for widespread clinical translation of this novel technique is most standard clinical scanners have only proton imaging capabilities and cannot detect 13C signals. In this feasibility study, our team will develop and validate a simple, smart, cost-effective scanner “add-on module” that will enable the transfer of polarization-enhanced signals from 13C to proton and enable metabolic imaging of hyperpolarized 13C compounds on a standard clinical MRI scanner via indirect 1H detection.

PI_NAMEs: CHEKMENEV, EDUARD ;ROSEN, MATTHEW SCOT (contact)

PROGRAM_OFFICER_NAME: LIU, GUOYING

PROJECT_TERMS: Address;aerobic glycolysis;Animals;aqueous;Back;Benchmarking;Biology;Calibration;Cancer Biology;cancer therapy;cell growth;Cell Proliferation;Clinical;clinical imaging;clinical translation;Communities;Computer software;cost;cost effective;Coupled;Custom;density;design;Detection;detection sensitivity;Disease;Disease Progression;early phase clinical trial;Evaluation;Exercise;Fatty acid glycerol esters;FDA approved;Feasibility Studies;first-in-human;Frequencies;Generations;Glioblastoma;Glioma;Gluconeogenesis;Glycolysis;Goals;Hand;Heart Diseases;Human;Image;imaging biomarker;imaging capabilities;improved;in vivo;in vivo imaging;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;malignant stomach neoplasm;Metabolic;metabolic imaging;Metabolic Pathway;Metabolism;Methods;millisecond;Mitochondria;Multicenter Trials;Noise;novel;Nuclear;Oxidative Phosphorylation;Performance;Physiologic pulse;Play;Positron-Emission Tomography;Prevalence;Production;Protons;prototype;Pyruvate;Pyruvate Metabolism Pathway;radio frequency;Reproducibility;Research;Resolution;response;Role;Series;Signal Transduction;Site;Stroke;success;Surveys;System;Techniques;Technology;Testing;Thinking;Time;transmission process;Validation;Vendor;Water

PROJECT_TITLE: Plug-and-play Hyperpolarized MRI of Metabolism on Clinical Scanners

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: Rheumatoid arthritis (RA) is more prominent in women and has greater severity in the Hispanic and Black populations. One in 4 veterans has arthritis (25.6%), compared to 1 in 5 civilians. RA is a disabling autoimmune disease that is associated with depression, cardiovascular disease, and psychosocial stress as well as being more prominent in women. Our clinic at the Jesse Brown VA sees around 700-900 RA patients annually. There is no cure for RA and up to 50% of RA patients do not respond to current therapies. Therefore, we aim to find a novel therapy that can slow or reverse RA pannus formation. To resolve the critical barrier in RA treatment, we have identified a novel pathway that plays a central role in pannus formation by linking immune cell activation with joint blood vessel formation. The goal of our proposal is to understand the mechanism of the identified unique pathway and to evaluate whether the blockade of its function may be more effective than the current standard of care therapies.

PI_NAMEs: SHAHRARA, SHIVA  (contact)

PROJECT_TERMS: 3-Dimensional;Adaptor Signaling Protein;Affect;angiogenesis;Antibodies;Arthritis;arthritis therapy;Arthritogenic;Attenuated;Autoimmune Diseases;Binding;Biological Assay;Black Populations;Blood;blood vessel development;bone erosion;Carbon;Cardiovascular Diseases;Caring;CD14 gene;CD86 gene;cell motility;cell type;Cells;Cellular Metabolic Process;Chronic;Clinic;Coculture Techniques;Diagnosis;Disabling;Disease;effectiveness evaluation;Endogenous Factors;Endothelial Cells;Erythrocyte Sedimentation Rate;Exhibits;exosome;FCGR3B gene;FRAP1 gene;genetic signature;Glucose;glucose uptake;Goals;Hispanic Populations;Human Resources;Hyperplasia;Hypoxia;immune activation;immunoregulation;imprint;improved;ineffective therapies;Inflammatory;Inflammatory Arthritis;Intercept;Interferon Type II;Joints;knock-down;Label;lactate dehydrogenase A;Link;Macrophage;Mediating;Medical Care Costs;Melanoma differentiation associated gene-9;Mental Depression;Metabolic;metabolic phenotype;metabolic profile;Military Personnel;Mitochondria;Molecular;monocyte;Monokines;Myeloid Cells;neovascularization;neovasculature;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Pain;Pathology;Pathway interactions;Patients;Persons;Phenotype;Play;programs;Psychosocial Stress;Pyruvate;Quality of life;receptor;Regulation;response;Rheumatoid Arthritis;Role;Secondary to;sensor;Severities;Signal Transduction;SLC2A1 gene;standard of care;syndecan;Synovial Fluid;System;Testing;Therapeutic;Thick;Time;tissue culture;Tissues;TNF gene;transcription factor;transcriptome sequencing;Tubular formation;tumorigenic;ultrasound;Vascularization;Veterans;Woman

PROJECT_TITLE: Establishing novel therapeutic strategies to target RA pannus formation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 IMMA-G (01)]


ADMINISTERING_IC: AG

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BERKELEY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: Project Narrative This project details a study of mitochondrial regulation of neural stem cell aging and cognitive aging, and Alzheimer’s disease. This study will have profound implications in drug development for Alzheimer’s diseases.

PI_NAMEs: CHEN, DANICA  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Age;Aging;aging related disease;Alzheimer's Disease;Alzheimer's disease patient;Attenuated;Biochemical;Bioenergetics;Biogenesis;Biology;Caenorhabditis elegans;Cell Death;Cell Maintenance;Cells;Chromatin;Chronic Disease;Cognition;Cognitive aging;Data;Defect;Degenerative Disorder;Dementia;dentate gyrus;Deterioration;Development;Disease;drug development;experience;extend lifespan;feasibility testing;Functional disorder;gain of function;Genes;genetic approach;Genetic Transcription;Genomic approach;Growth;HDAC4 gene;healthspan;Hippocampus;Homeostasis;human old age (65+);Impaired cognition;improved;Intervention;knock-down;Knock-out;Knockout Mice;Knowledge;life span;Link;Mammals;Metabolism;Mitochondria;Mitochondrial Proteins;model organism;Molecular Chaperones;mouse model;Nerve Degeneration;nerve stem cell;neurogenesis;neuroregulation;normal aging;novel;Nutrient;old mice;overexpression;oxidative damage;Oxidative Stress;Parahippocampal Gyrus;Pathway interactions;Phenotype;Physiological;Predisposition;premature;programs;Proliferating;protein folding;Proteins;proteostasis;Repression;response;Risk Factors;Role;sensor;Signal Pathway;single-cell RNA sequencing;stem cell aging;stem cells;Stress;Testing;tissue degeneration;Tissues;Translations;Up-Regulation

PROJECT_TITLE: Neural Stem Cell Aging and Neurodegeneration

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-Q (55)]


ORG_DEPT: PATHOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: About 10% of Americans develop an autoimmune disease, reflecting a breakdown in the induction of T- or B-cell tolerance in the thymus, bone marrow or periphery. This study focuses on a newly discovered mechanism of T-cell tolerance induction: deletion or diversion to a regulatory-cell phenotype of self-reactive thymocytes through contact with thymic mimetic cells. Mimetic cells, via expression of appropriate lineage- defining transcription factors, take on the mantle of peripheral cell-types, while still maintaining their identity as thymic stromal cells.

PI_NAMEs: MATHIS, DIANE J (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Ablation;Address;American;Antigens;arm;Autoimmune Diseases;Autoimmunity;B-Lymphocytes;Bar Codes;Binding;Bone Marrow;Cell Line;cell type;Cells;central tolerance;Chromatin;CRISPR/Cas technology;Development;Dissection;DNA Double Strand Break;effector T cell;Freezing;Funding;gain of function;Gene Expression;Generations;Genetic;Genetic Transcription;Genetic Variation;Genomics;Goals;Grant;Health;Heterozygote;Histologic;Human;in vivo;Incidence;Insulin-Dependent Diabetes Mellitus;Lead;loss of function;Lymphocyte;Maintenance;Methodology;mimetics;Mitochondrial DNA;Molecular;Mus;Muscle;neoantigens;novel;Organ;Pathway interactions;Peripheral;pharmacologic;Phenotype;Play;Regulatory T-Lymphocyte;Reporter;Reporting;Role;Spermidine;Stromal Cells;T-Lymphocyte;Thymic epithelial cell;thymocyte;Thymus Gland;Tissues;Topoisomerase;Topotecan;transcription factor;Vitiligo;Z-Form DNA

PROJECT_TITLE: The molecular mechanism of Aire

STUDY_SECTION: CMIA

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Physical Activity

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Adults in the US spend over 50% of their waking day being sedentary, i.e., in a sitting or lying posture. Being sedentary is known to confer higher risk of diabetes and heart disease, yet sedentary time has increased greatly the 1960s given the rise of technologies that have automated jobs and incorporated screens into occupational and leisure activities. In this project, we will use advanced computation techniques to accurately quantify an individual’s sedentary behavior patterns with the ultimate goal of developing guidelines for reducing sedentary behavior and promoting healthy living, wellbeing and longevity.

PI_NAMEs: NATARAJAN, LOKI  (contact)

PROGRAM_OFFICER_NAME: ANAYA, GABRIEL

PROJECT_TERMS: Acceleration;Accelerometer;actigraphy;Address;Adult;Age;age group;Algorithms;analytical method;Architecture;Behavior assessment;behavior change;Behavioral;Body mass index;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;Child;Classification;classification algorithm;cohort;Computational Technique;Computing Methodologies;computing resources;convolutional neural network;Data;Data Set;Databases;deep learning;Development;Devices;diabetes risk;Disease Outcome;Energy Metabolism;Epidemiology;Equity;Ethnic Origin;follow-up;Fostering;Foundations;Funding;Future;Goals;Guidelines;Health;health equity;Heart Diseases;high risk;Hip region structure;Hispanic;Hour;improved;Individual;Intake;Latinx;Learning;Leisure Activities;Link;long short term memory;Longevity;Longterm Follow-up;Malignant Neoplasms;Measures;Metabolic;Methods;Modeling;Monitor;mortality;National Health and Nutrition Examination Survey;neural;Non-Insulin-Dependent Diabetes Mellitus;novel;Occupational;Occupations;older adult;Output;Participant;Patients;Pattern;Performance;Personal Satisfaction;Physical activity;Population Group;Population Heterogeneity;Populations at Risk;Postmenopause;Posture;Process;Public Health;Race;Recommendation;Reproducibility;Research;Research Personnel;research study;Risk;Sample Size;Sampling;sedentary;sedentary lifestyle;sensor;Standardization;Technology;Testing;Time;time use;tool;Training;transfer learning;wearable sensor technology;Work;Wrist;wrist worn device;Youth

PROJECT_TITLE: Leveraging deep learning to classify sitting posture and measure sedentary patterns from accelerometer data in diverse cohorts

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Anal /fecal continence (FI) is a major medical illness, as it affects many Veterans, and it affects their quality of life. Many FI patients develop symptoms after about 5 decades of life and the risk increases with advancing age, the reasons for which are not clear. Currently, there are no effective preventive strategies. The major focus of this proposal is to understand and evaluate pathophysiological changes. These studies will also evaluate the application of a novel multimodal intervention approach to prevent FI in an animal model. We believe the proposed studies will have important therapeutic implications for the treatment strategies for FI.

PI_NAMEs: MITTAL, RAVINDER K. (contact)

PROJECT_TERMS: Accidents;Adult women;Affect;Age;age effect;age related;Aging;aging population;aging related;Anatomy;Animal Model;animal old age;Animals;antagonist;Anus;Atrophic;beta catenin;Charge;child bearing;Childbirth;Clinical;clinical translation;Collagen;Complex;Connective Tissue;Cross-Sectional Studies;Defecation;Deposition;Development;Disease;Elderly;Emotional;Enrollment;Episiotomy;Evaluation;External anal sphincter structure;Extravasation;Fecal Incontinence;Feces;Fiber;fibrogenesis;Fibrosis;Functional disorder;Future;G-substrate;Gene Silencing;Genetic Transcription;Goals;GTP-Binding Proteins;Guanine Nucleotide Exchange Factors;Harvest;healing;Health;Healthcare;Histologic;Immunohistochemistry;Impaired healing;Impairment;improved;in vivo;Incontinence;injured;Injury;innovation;insight;Intervention;Investigation;Ischemia;Laboratories;Length;Life;Link;Liquid substance;Liver;Liver Fibrosis;Measurement;Mediating;Mediator;Medical;Modeling;Molecular;multi-component intervention;Muscle;Muscle function;muscle regeneration;Muscular Atrophy;novel;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Oryctolagus cuniculus;overexpression;Pathway interactions;Patients;Pattern;Pelvic Floor Disorders;Pelvic Floor Muscle;pharmacologic;Population;Postpartum Period;Pregnancy;prevent;Prevention;Prevention strategy;Proteins;Quality of life;receptor;Recovery of Function;Rectum;repaired;Reporting;Risk;Risk Factors;RNA Interference;Signal Pathway;Signal Transduction;Signaling Protein;Skeletal Muscle;Small Interfering RNA;small molecule inhibitor;Solid;Sphincter;sphincter ani muscle structure;STAT3 gene;Stat3 protein;Stenosis;Stretching;Surgical incisions;Symptoms;Therapeutic;Therapeutic Intervention;therapy development;Time;time interval;Tissues;translatable strategy;Trauma;treatment strategy;Up-Regulation;Vaginal delivery procedure;Vesicle;Veterans;Veterans Health Administration;WNT Signaling Pathway;Woman;Women's prevalence

PROJECT_TITLE: Targeting Novel Fibrogenic Signaling Pathways to Prevent Injury and Age-Related External Anal Sphincter Muscle Dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 GAST-L (01)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: CLEVELAND

ORG_DEPT: BIOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project Narrative The skull roof is an exquisite set of patterned bones that encase the brain and sensory organs of all vertebrates. In humans, calvarial defects such as craniosynostosis, which occur in 1/2500 live births, have detrimental consequences for brain and sensory organ development. The objective of this proposal is to define the role of substrate-based cell migration in regulating normal skull development as a key mechanism underlying craniofacial pathologies.

PI_NAMEs: ATIT, RADHIKA P (contact);HARRIS, MATTHEW P

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Address;Adhesions;Affect;Animal Disease Models;Animal Model;Apert syndrome;Apical;Biological Assay;bone;Bone Growth;Brain;Calvaria;cell motility;Cells;Cephalic;Chimeric Proteins;clinically relevant;Collection;Congenital abnormal Synostosis;Congenital Abnormality;coronal suture;Coupled;craniofacial;craniofacial disorder;Craniosynostosis;cranium;Cues;Data;Defect;Dependence;Development;differential expression;Differentiation and Growth;Disease;dosage;Dysmorphology;Embryo;Etiology;Exhibits;experimental study;extracellular;Extracellular Matrix;Extracellular Matrix Proteins;Fibronectins;Gene Expression Profiling;Genetic;Genetic Models;Genetic Predisposition to Disease;Growth;Human;human model;Image;improved;in vivo;Laboratories;Legal patent;Live Birth;live cell imaging;Measures;Mediating;Mesenchyme;migration;Modeling;Modification;Morphogenesis;mouse development;mouse genetics;mouse model;Mus;mutant;Mutant Strains Mice;new therapeutic target;novel;Operative Surgical Procedures;Organ;organ growth;Osteoblasts;Outcome Assessment;overexpression;Pathology;Pathway interactions;Patients;Pattern;Penetrance;Phenotype;Population;Positioning Attribute;progenitor;protein expression;Proteins;Regulation;response;Role;Sensory;stem cell expansion;Structure of fontanel of skull;Substrate Interaction;Surgical sutures;suture fusion;targeted treatment;Testing;therapy development;tool;treatment strategy;Variant;Vertebrates;Zebrafish

PROJECT_TITLE: Substrate-mediated collective cell migration incalvarial bone expansion and disease.

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: Narrative Mycobacterium tuberculosis is the causative agent of human tuberculosis, a devastating infectious disease, which infects millions of people and kills ~1.5 million annually. M. tuberculosis can replicate inside macrophages, where it becomes antibiotic tolerant and harder to kill. The aim of this proposal is to identify new anti-tubercular agents which target intracellular bacteria and to determine the mode of action of these agents.

PI_NAMEs: PARISH, TANYA  (contact)

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TERMS: Affect;analog;antagonist;antibiotic tolerance;Antibiotics;Antitubercular Agents;Bacteria;Bacterial Infections;Benzamides;Biological;Cell Death;Cell Survival;Cell Wall;Cells;Cessation of life;Chemicals;Communicable Diseases;Companions;Data;drug-sensitive;efficacy testing;Electron Transport;Ethers;Eukaryotic Cell;Evaluation;Future;Generations;Genetic Transcription;global health;Goals;Heterogeneity;HIV;Host Defense Mechanism;Human;in vivo;Infection;inhibitor;Lead;lead optimization;Location;Macrophage;Monitor;mycobacterial;Mycobacterium tuberculosis;New Agents;new therapeutic target;novel;novel therapeutics;Outcome;pathogen;Pathway interactions;Penetration;Persons;Pharmaceutical Preparations;Pharmacotherapy;Physiological;Population;Property;Recombinants;Regimen;Respiration;scaffold;Series;synergism;targeted agent;Testing;Time;Translations;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Validation;Work

PROJECT_TITLE: New anti-tubercular agents targeting intracellular bacteria

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Eye Disease and Disorders of Vision;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: GAINESVILLE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Narrative  Many psychiatric disorders are characterized by dysregulation of perception and attention, for instance, the hypervigilance seen in individuals with obsessive-compulsive or anxiety disorders when they are exposed to potentially threatening situations. The proposed research examines how novel measures of visual activity obtained with electroencephalography can be used to predict symptoms of obsessive-compulsive and anxiety disorders. Establishing reliable and valid quantitative indices of perception and attention that vary systematically with self-reported symptoms is a necessary step towards objective assessment of the brain circuits underlying emotional dysfunction in these disorders, and ultimately to inform evidence-based intervention and treatment efforts.

PI_NAMEs: KEIL, ANDREAS ;MATHEWS, CAROL A (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Address;Affect;Affective;Animal Model;Anxiety;Anxiety Disorders;anxiety spectrum disorders;Attention;Behavior;Behavioral;Biological Markers;biomarker validation;Brain;Categories;Chronic;Chronic Disease;Clinical;Clinical Data;clinical practice;clinical predictors;Cognitive Therapy;comorbidity;Complex;computer framework;Computer Models;conditioned fear;Control Groups;Cues;Data;data reduction;Diagnosis;Diagnostic;Dimensions;Disabling;Disease;Disease susceptibility;Electroencephalography;Electrophysiology (science);Emotional;epidemiology study;Etiology;Evidence based intervention;Evidence based treatment;Exposure to;Frequencies;Functional disorder;generative models;Goals;indexing;Individual;Individual Differences;individualized medicine;Intervention;Knowledge;Link;Machine Learning;Measures;men;Mental disorders;Mental Health;Methods;Modeling;Molecular;National Institute of Mental Health;neural;Neurobiology;neuromechanism;neurophysiology;novel;novel strategies;Obsessive compulsive behavior;Parameter Estimation;Participant;Patient Self-Report;Patients;Pattern;Perception;Pharmaceutical Preparations;Population;Prediction of Response to Therapy;Predictive Value;Prevalence;Process;prognostic;Psychopathology;Reporting;Research;Research Domain Criteria;Resistance;response;Role;Sampling;selective attention;Sensory;Sensory Process;Severities;Social Anxiety Disorder;societal costs;Stimulus;success;Symptoms;System;Techniques;temporal measurement;Testing;Treatment outcome;Treatment Protocols;Validity of Results;Visual;Visual attention;Visual Cortex;Visual evoked cortical potential;Visual Perception;Woman;Work

PROJECT_TITLE: Visual perception and attention in the obsessive-compulsive/anxiety spectrum: Neurophysiological characterization, predictive value, and computational modeling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-Y (02)]


ADMINISTERING_IC: HG

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: The mission of GMOD and JBrowse is to make genome data accessible using the tools of the dynamic web. The size of genomic datasets can be daunting to users, particularly as the number of sequenced species and strains proliferates. We propose to add machine learning tools to help navigate these datasets, along with user interface enhancements that exploit evolutionary similarity, and improvements to performance and usability via a series of benchmarks and outreach operations.

PI_NAMEs: HOLMES, IAN H (contact);STEIN, LINCOLN D.

PROGRAM_OFFICER_NAME: WELLINGTON, CHRISTOPHER

PROJECT_TERMS: 3-Dimensional;Address;Adoption;animation;annotation  system;Area;Base Sequence;Benchmarking;bioinformatics resource;bioinformatics tool;Biology;Color;Communities;Community Outreach;Companions;Computer software;Data;data hub;data integration;Data Set;Dedications;deep learning;Democracy;design;Diploidy;Documentation;Education and Outreach;Educational workshop;Elements;Evolution;experience;Failure;Feedback;file format;Funding;gene conservation;Gene Expression;Genes;Genome;genome annotation;genome browser;genome database;genome resource;genomic data;genomic locus;genomic variation;Genomics;Hi-C;improved;indexing;Informatics;International;Internet;Intuition;Lead;Machine Learning;Maps;Methylation;Mission;model organisms databases;Occupations;operation;outreach;pan-genome;Performance;Phase;Phylogenetic Analysis;Phylogeny;Plug-in;Proliferating;protein structure;prototype;Recommendation;Research;Resources;Sequence Analysis;Series;Signal Transduction;Speed;Structure;symposium;Synteny;System;TensorFlow;Testing;text searching;Time;tool;Training;Trees;United States Department of Agriculture;United States National Institutes of Health;usability;user-friendly;Variant;Visualization;Visualization software;web interface;web site;Writing

PROJECT_TITLE: Enhancements to the GMOD Suite of Genome Annotation and Visualization Tools

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: NEW YORK

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE Chronic pain is a major unmet medical problem that afflicts twenty percent of the population at some point of their lives and is inadequately treated by opioids, which have life-threatening side effects and abuse potential. This proposal aims to identify and characterize new receptors that mediate nerve growth factor (NGF) -induced pain and to determine how NGF and its receptors signal from subcellular compartments to cause chronic pain. A deep understanding of how NGF signals pain will provide insights into the mechanism and treatment of chronic pain, with implications for other diseases that are mediated by growth factors, including cancer.

PI_NAMEs: BUNNETT, NIGEL W (contact);SCHMIDT, BRIAN L

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Absence of pain sensation;abuse liability;adverse outcome;Affect;Anatomy;antagonist;Artificial nanoparticles;Behavior;behavioral study;Binding;Biological Assay;Bioluminescence;biophysical analysis;biophysical techniques;Biophysics;Biosensor;Calcitonin;Calcitonin Gene-Related Peptide;Cell membrane;Cell model;Cell surface;Cell Surface Receptors;chronic pain;chronic pain management;Clinical;Confocal Microscopy;design;Disease;drug discovery;Dynamin;efficacious treatment;Electrophysiology (science);Encapsulated;Endocytosis;Endocytosis Induction;Endosomes;Energy Transfer;Exhibits;extracellular;Family;Fluorescence Resonance Energy Transfer;Funding;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Glutamates;Growth Factor;Human;Image;imaging study;Immunofluorescence Immunologic;improved;In Situ Hybridization;Inflammation;inflammatory pain;inhibitor;insight;Life;Ligands;Lipids;Literature;Malignant Neoplasms;Mediating;Mediator;Medical;Membrane;Messenger RNA;metabotropic glutamate receptor 5;Molecular Chaperones;Monoclonal Antibodies;Mus;nanoparticle;Nerve Growth Factors;nerve injury;Neurons;Neuropilin-1;NGFR Protein;Nociception;Nociceptors;non-opioid analgesic;Opioid;Opioid Receptor;Pain;Pain management;pain relief;pain signal;painful neuropathy;Pathologic Processes;Pathology;Peptide Hydrolases;Persistent pain;Pharmaceutical Preparations;Phosphotransferases;Physiological Processes;Population;Process;protein protein interaction;Proteins;receptor;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Recombinant Proteins;retrograde transport;RGS19 gene;Role;scaffold;Scaffolding Protein;side effect;Signal Transduction;Spinal;Spinal Ganglia;Surface;Synaptic Transmission;Synaptic Vesicles;TACR1 gene;Testing;therapeutic target;trafficking;transmission process;Tropomyosin;Vascular Endothelial Growth Factors;Vesicle

PROJECT_TITLE: Endosomal Platforms for Signaling Pain

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


ADMINISTERING_IC: EY

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Eye Disease and Disorders of Vision;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: How coordinated neuronal activity arises in the cortex is still poorly understood, yet could be the basis of cortical function. In a past award we discovered that activating neuronal ensembles in mouse visual cortex using holographic optogenetics leads to predictable changes in visual discrimination, and we now propose to explore how these ensembles are formed and how they work. This work could help control cortical activity via activation of trigger cells in ensembles and thus provide novel strategies to ameliorate amblyopia and cortical cerebral visual impairment by reconfiguring abnormal circuits.

PI_NAMEs: YUSTE, RAFAEL  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Affect;Amblyopia;Anatomy;area striata;awake;Award;Behavioral;Biophysics;Black Box;Brain Diseases;cell type;Cells;Cerebral cortex;cerebral visual impairment;Child;Code;Computational algorithm;Data;design;developmental disease;developmental plasticity;Disease;disease model;Epidemic;excitatory neuron;Generations;Genetic Techniques;Goals;graph theory;Holography;Image;imprint;in vivo;Individual;inhibitory neuron;Interneurons;Link;Maps;Measures;Mediating;Methods;Microscopy;Modeling;mouse model;Mus;Neocortex;neural;neural circuit;Neurons;novel;novel strategies;novel therapeutic intervention;novel therapeutics;operation;Optical Methods;Optics;optogenetics;Outcome;patch clamp;Pathologic;Pattern;phenomenological models;Population;Premature Infant;Preparation;Process;Property;Publishing;Research Personnel;response;Rest;Role;Stimulus;Structure;Synapses;Synaptic plasticity;Testing;Time;Transgenic Mice;two-photon;Visual;Visual Cortex;visual discrimination;visual learning;Visual Perception;visual stimulus;Work

PROJECT_TITLE: Mechanisms of Neuronal Ensembles in Visual Cortex

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


PHR: Acute myeloid leukemia (AML) is a disease with very high morbidity and mortality and can occur as secondary to evolution of myelodysplastic syndromes (MDS), a group of diseases seen in older patients and have a high prevalence in the aging VA population. The work proposed here should have a major impact in this area by driving the development of new agents that target unique components of a novel pathway (ULK1) that we have identified in AML leukemia cells. The results of these studies could ultimately result in the development of novel therapeutic agents for refractory AML and MDS, or new strategies combining standard chemotherapy with ULK1 targeting agents and/or lead to the design of completely new anti-leukemia agents.

PI_NAMEs: PLATANIAS, LEONIDAS C. (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Aging;antileukemic agent;Area;Automobile Driving;Autophagocytosis;Biological;cancer cell;Cell Survival;Cells;cellular targeting;Characteristics;chemotherapeutic agent;chemotherapy;Clinical;clinical translation;cohort;Complex;conditional knockout;Core-Binding Factor;Cytogenetics;cytokine;Data;design;Development;Disease;Dysmyelopoietic Syndromes;Elements;Evolution;Feedback;FRAP1 gene;Functional disorder;Future;Generations;Genes;Genetic Transcription;Hematopoietic;High Prevalence;in vivo;in vivo Model;inhibitor;innovation;Interferons;Knockout Mice;Laboratories;Lead;leukemia;Leukemic Cell;leukemic stem cell;leukemogenesis;Mediating;Mitogen-Activated Protein Kinases;Modeling;Molecular;Morbidity - disease rate;mortality;mRNA Translation;Mus;Myeloproliferative disease;New Agents;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Nuclear;older patient;Outcome;Pathway interactions;patient derived xenograft model;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;Phosphorylation Site;Phosphotransferases;Play;Population;precision medicine;Program Reviews;programs;Property;Proteins;Refractory;Regulation;Research;Resistance;response;Ribosomes;Role;RUNX1 gene;Secondary to;Signal Pathway;Signal Transduction;targeted agent;Therapeutic;Therapeutic Agents;therapeutic target;transcription factor;Transcriptional Regulation;Work

PROJECT_TITLE: Signaling Pathways and Therapeutic Targeting of Leukemic Cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 HEMA-G (01)]


NIH_SPENDING_CATS: Digestive Diseases;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: MILWAUKEE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE Graft versus host disease (GVHD) of the gastrointestinal (GI) tract is one of the major complications associated with allogeneic hematopoietic stem cell transplantation (HSCT) and leads to significant morbidity and mortality. The goal of this project is to critically examine the role of an inflammatory cytokine, termed granulocyte- macrophage colony stimulating factor, in the pathophysiology of GVHD in the GI tract. The ultimate objective of this proposal is that, through these preclinical studies, we will gain new insights into this disease which will lead to the development of novel clinical approaches for the treatment of this complication after allogeneic HSCT.

PI_NAMEs: DROBYSKI, WILLIAM R. (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acute;adaptive immune response;Address;Affect;Alloantigen;Allogenic;Biology;CD4 Positive T Lymphocytes;Cells;Clinical;clinical development;clinically relevant;clinically significant;Colon;Colonic Diseases;Complication;cytokine;Cytokine Network Pathway;Dendritic Cells;Dependence;design;Development;Digestive System Disorders;Disease;experimental study;Fostering;Functional disorder;gastrointestinal;Gastrointestinal tract structure;Gene Expression Profile;Gene Modified;Generations;Genes;Goals;graft versus host disease induction;graft vs host disease;Grant;Granulocyte-Macrophage Colony-Stimulating Factor;Hematopoietic Stem Cell Transplantation;IL7 gene;Immune;in vivo;Inflammation;Inflammatory;Innate Immune Response;insight;Interferon Type II;Interleukin 7 Receptor;Interleukin-2;Interleukins;Intestinal Graft Versus Host Disease;Kinetics;Link;Mediating;mesenteric lymph node;Morbidity - disease rate;mortality;mouse model;Mus;novel;Organ;Pathogenicity;Pathologic;Pathway interactions;Phase;Play;Population;preclinical study;Production;Receptor Signaling;Regulation;Regulatory Pathway;Reporter;Role;Severity of illness;Site;Source;T-Lymphocyte;Testing;therapeutic target;Therapeutically Targetable;Tissues;transcription factor;Transcriptional Regulation;Transplant Recipients

PROJECT_TITLE: Inflammatory Cytokine Networks in Gastrointestinal Tract Graft Versus Host Disease

STUDY_SECTION: TTT

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Wound Healing and Care

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative Stem cells (SCs) are natural units of tissue repair and homeostasis, and their versatility holds promise for tissue regeneration. This research uses the skin epithelium as a model to delineate the crosstalk that SCs undergo with their local microenvironments which enable SCs to self-renew and survive long-term during normal tissue homeostasis and in response to injuries. Understanding how SCs cope with stress and with breaches in the epithelial barrier is a fundamental prerequisite to ascertaining the potential of SCs for regenerative therapies and to devise new and improved therapeutics for inflammatory disorders and cancers.

PI_NAMEs: FUCHS, ELAINE  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Acceleration;adult stem cell;Age;Aging;Algorithms;Behavior;Biology;cancer prevention;Cancerous;cell behavior;Cell Communication;Cell Lineage;cell type;Cells;Cessation of life;Chromatin;Computing Methodologies;coping;Cues;Cytoprotection;Data;Disease;Eating;Environment;Epidermis;epithelial wound;Epithelium;Event;fighting;fitness;Fluorescent in Situ Hybridization;Foundations;Genetic;genetic approach;Genomics;Goals;Growth;Hair follicle structure;Health;Homeostasis;Human;Immune;Immunofluorescence Immunologic;improved;In Vitro;in vivo;Infection;Inflammation;Inflammatory;injured;Injury;injury and repair;insight;knock-down;Knock-out;knockout gene;Knowledge;Lead;Malignant Neoplasms;Methods;Modeling;Molecular;mouse model;Mus;Mutation;Natural regeneration;Nature;Normal tissue morphology;Oncogenic;pathogen;Phagocytosis;Phase;Precancerous Conditions;Process;programs;Proliferating;Property;re-epithelialization;recruit;Regenerative Medicine;regenerative therapy;regenerative tissue;repaired;Research;Resolution;Resources;response to injury;Rest;RNA interference screen;self-renewal;Sensory Disorders;Signal Induction;Signal Transduction;single-cell RNA sequencing;Skin;skin barrier;stem cell function;stem cell niche;stem cell self renewal;stem cell survival;stem cells;Stress;Stress and Coping;System;Therapeutic;Three-Dimensional Imaging;Tissue Differentiation;tissue regeneration;tissue repair;Tissues;transcriptome;transcriptomics;tumor;tumorigenic;wound;wound bed;wound healing;wound treatment

PROJECT_TITLE: Skin Stem Cells and Their Niche Interactions

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Human Genome;Lung;Machine Learning and Artificial Intelligence;Precision Medicine

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, due to different groups of biologic processes. Genetic variants and small molecules, called metabolites, may help identify these processes and explain differences in COPD. In our study, we will classify groups of genetic variants into pathways, and examine how they relate to metabolites, as well as gene expression and proteins. We will then investigate how this information can be used to subset COPD, identify gene by environment interactions, and identify new drug targets. This work will lead to a greater understanding of disease processes in COPD and more specific treatments.

PI_NAMEs: CHO, MICHAEL H. (contact)

PROGRAM_OFFICER_NAME: GAN, WEINIU

PROJECT_TERMS: Acceleration;Affect;Airway Disease;Applied Genetics;Asthma;atopy;Automobile Driving;biobank;Biological;Biological Assay;Biological Markers;Biological Process;biomarker development;Birth;Blood;Cardiovascular Diseases;Characteristics;Chronic;Chronic Obstructive Pulmonary Disease;Classification;Clinical;cohort;Collection;Communities;comorbidity;Complement;Complex;Complex Genetic Trait;Consensus;Data;Data Set;Databases;Disease;disease heterogeneity;Disease susceptibility;disorder subtype;Drug Targeting;effective therapy;Environment;Fatty Acids;Gene Cluster;gene environment interaction;Gene Expression;Gene Proteins;Generations;Genes;Genetic;genetic analysis;genetic association;Genetic Risk;genetic variant;genome sequencing;genome wide association study;Genomic approach;Glutamine;Growth;Growth and Development function;Heterogeneity;Image;Individual;Inflammation;innovation;Investigation;Link;Lung;Lung Diseases;Machine Learning;machine learning method;Metabolic Diseases;metabolome;metabolomics;Methodology;Molecular;Molecular Profiling;mortality;new therapeutic target;novel;novel therapeutics;Obstructive Lung Diseases;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;Phenotype;Process;Proteomics;Public Health;Pulmonary Emphysema;pulmonary function;Research;Research Personnel;Resources;risk variant;small molecule;Sphingosine;statistical and machine learning;Statistical Methods;Steroids;Structure of parenchyma of lung;Therapeutic;therapeutic development;tissue resource;Tissues;trait;Trans-Omics for Precision Medicine;transcriptomics;translational genetics;Variant;web interface;whole genome;Work

PROJECT_TITLE: Identifying Subtypes of COPD Using Metabolomic and Genomic Approaches

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Burden of Illness;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Diabetes;Dissemination and Implementation Research;Health Services;Patient Safety;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: Canton

ORG_NAME: HARVARD PILGRIM HEALTH CARE, INC.

PHR: PROJECT NARRATIVE We propose a comprehensive study to evaluate the efficacy and feasibility of implementing InvesT1D, an innovative, ethically-sensitive, patient- and stakeholder-centered intervention that aims to improve management of type 1 diabetes by offering adolescents financial incentives for engagement in diabetes self- care behaviors. If this intervention is effective and cost-effective, it could have a significant impact on the health and quality of life for the over 80% of adolescents with type 1 diabetes who are struggling to meet glycemic targets. The development and evaluation of this intervention can also serve as a model for health interventions targeting other health conditions.

PI_NAMEs: WRIGHT, DAVENE RENEE (contact)

PROGRAM_OFFICER_NAME: BROADNEY, MIRANDA MARGUERITE

PROJECT_TERMS: 18 year old;Acute;Address;Adherence;Adolescence;Adolescent;Adult;Adverse event;Award;Behavior;Behavioral;behavioral health;Blindness;caregiver quality of life;Caring;Childhood;Chronic;Chronic Disease;Clinical;Complications of Diabetes Mellitus;Conflict (Psychology);Continuous Glucose Monitor;cost;Cost Analysis;cost effective;cost effectiveness;Cost Savings;cost-effectiveness ratio;dashboard;Data;design;Development;diabetes distress;diabetes management;Diabetes Mellitus;diabetes self-management;Diabetic Ketoacidosis;Economic Burden;economic evaluation;economic impact;economic outcome;Economics;effectiveness/implementation study;efficacy evaluation;Equity;Ethical Analysis;Ethics;Evaluation;experimental study;Family;financial incentive;flexibility;Future;glycemic control;Glycosylated hemoglobin A;Goals;Grant;Health;Health behavior;Health Benefit;health care delivery;health care service utilization;health economics;health plan;Health Psychology;health related quality of life;Health system;Healthcare;Healthcare Systems;high risk;improved;incentive program;incentive-based intervention;Incentives;incremental cost-effectiveness;Individual;innovation;Insulin-Dependent Diabetes Mellitus;Intervention;Interview;Investments;Kidney Failure;Laws;Length;markov model;Methodology;Methods;Modeling;models and simulation;Outcome;Paper;patient oriented;Patient Preferences;Patients;Pattern;payment;Policies;Policy Analysis;Politics;Population;Practice Management;preference;pressure;prevent;primary outcome;Privatization;programs;prospective;Protocols documentation;psychosocial development;Quality of life;Quality-Adjusted Life Years;Randomized;Randomized, Controlled Trials;Recommendation;Regimen;Research;Risk;Risk Taking;Sampling;Self Management;social;Structure;System;Technology;Time;treatment arm;treatment as usual;Treatment Protocols;willingness to pay

PROJECT_TITLE: InvesT1D: Promoting Adolescent Investment in Diabetes Care

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Research on this competitive renewal evidenced that CYP11A1-derived secosteroidal derivatives are excellent candidates to serve as radioprotectors and chemopreventive agents in UVB induced cancerogenesis, because of their high efficacy to inhibit BCC and SCC growth in vitro, and 20(OH)D3 mediated inhibition of skin carcinogenesis induced by UVB in the Ptch1+/-/SKH-1 mouse model. In addition, alternative nuclear receptors (NR), in addition to the vitamin D receptor, have been identified for (OH)nD3. This justifies continued preclinical testing of our CYP11A1-derived (OH)nD3 for inhibition of UVB-induced skin carcinogenesis and tumor growth, and to identify the specific NR pathway(s) activated by these different OH)nD3. The studies should define novel OH)nD3 s as therapeutic and chemopreventive agents against UVB-induced carcinogenesis.

PI_NAMEs: SLOMINSKI, ANDRZEJ T (contact)

PROJECT_TERMS: Chemopreventive Agent;CYP11A1 gene;Growth;In Vitro;Mediating;mouse model;novel;Nuclear Receptors;Pathway interactions;Preclinical Testing;Research;Secosteroids;Skin Cancer;Skin Neoplasms;Therapeutic;Therapeutic Agents;tumor growth;UVB carcinogenesis;UVB induced;Vitamin D3 Receptor

PROJECT_TITLE: CYP11A1-derived secosteroids as therapeutic agents in UVB induced skin cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCE-A (01)]


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

PHR: Narrative This project discovers a novel mitochondria-enriched miRNA, miR-128, is important to synchronize cellular and mitochondrial biological process during cardiac remodeling. This miRNA will be an important target to direct correct or circumvent mitochondria abnormality in dysfunctional cardiomyocytes that accompanies heart failure. This proposal incorporates epigenomic information to investigate underlying mechanism involved in aberrant miRNA activation during heart failure and provides proof of principle that enable precise engineering of transcription regulation in cardiovascular medicine.

PI_NAMEs: HUANG, WEI ;WANG, YIGANG  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Affinity;Alternative Therapies;Automobile Driving;Biological Process;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;cardiovascular disorder therapy;Cardiovascular system;Cell model;Cessation of life;Clinical;Complex;Cytosol;Data;Development;Diagnosis;DNMT3a;economic cost;Effectiveness;Engineering;Enhancers;Epigenetic Process;epigenetic silencing;epigenome editing;epigenomics;Etiology;experimental study;Failure;functional improvement;Future;Genetic Enhancer Element;Genetic Transcription;Goals;Heart;heart damage;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Homeostasis;Human;human induced pluripotent stem cells;Hypertrophy;Impairment;induced pluripotent stem cell derived cardiomyocytes;Intervention;Mass Spectrum Analysis;Mediating;Medicine;Methylation;MicroRNAs;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Morbidity - disease rate;Morphology;mortality;mouse model;Mus;Myocardial Degeneration;Myocardial dysfunction;next generation sequencing;novel;novel strategies;nucleocytoplasmic transport;overexpression;Pathologic;Pathway interactions;Patients;Phase;Pilot Projects;prevent;Prevention;Production;promoter;Proteins;Reactive Oxygen Species;recruit;response;RNA;Role;Stress;Syndrome;System;Testing;Therapeutic;therapeutic target;trafficking;transcription factor USF;Transcriptional Regulation;transcriptome;Treatment Failure;Untranslated RNA

PROJECT_TITLE: A novel strategy for heart failure therapeutics

STUDY_SECTION: MPPA

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer;Orphan Drug;Rare Diseases

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE The family of RAS oncoproteins drive tumor growth and have been widely characterized in cancer; however, non-classical RAS proteins remain poorly studied despite their relevance in this disease. We have discovered a novel cellular mechanism that results in the degradation of the non-classical RAS oncoproteins RIT1 and MRAS and it is mediated by a complex that includes the protein LZTR1. Our work into this mechanism will lead to novel insights into the regulation of non-classical RAS oncoproteins, the relevance during tumor formation, and potential innovative therapeutic approaches.

PI_NAMEs: CASTEL, PAU  (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Adaptor Signaling Protein;Alleles;Binding;Binding Proteins;Biochemical;Biological Assay;Biological Markers;Biological Process;Cancer Biology;Cancer cell line;cancer initiation;Cancer Model;cancer subtypes;cancer type;cell growth;Cell Proliferation;Cells;Chemicals;Clinic;Clinical;cofactor;Complex;Cues;cullin-3;Development;Dimerization;Disease;experimental study;Family;Future;Gene Expression Profile;Genes;genetic approach;Glioblastoma;Growth;Guanosine Diphosphate;Guanosine Triphosphate Phosphohydrolases;Hydrolase;Hydrolysis;Impairment;In Vitro;in vivo;inhibitor;innovation;insight;Knowledge;leukemia;loss of function mutation;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediating;Medicine;MEKs;Melanoma;member;Modeling;Molecular;Molecular Conformation;Molecular Profiling;mouse genetics;mouse model;Mouse Strains;Multiprotein Complexes;Mutation;Nature;novel;novel therapeutic intervention;novel therapeutics;Nucleotides;Oncogenic;Oncoproteins;Pathway interactions;pharmacologic;Pharmacological Treatment;Physiological;Play;Pre-Clinical Model;Process;Proliferating;Protac;protein degradation;Proteins;Proteolysis;Protomer;ras Proteins;Regulation;Reproducibility;Resistance;response;Role;Series;Signal Pathway;Signal Transduction;small molecule;Somatic Mutation;Specificity;Structure;Structure-Activity Relationship;Substrate Specificity;targeted treatment;Technology;Tertiary Protein Structure;Therapeutic;therapeutically effective;therapy development;therapy resistant;tumor;tumor growth;Tumor Subtype;tumorigenesis;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Regulation and tumorigenesis of non-classical RAS oncoproteins - Resubmission

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Deuterium metabolic imaging (DMI) is a novel 3D method to image metabolism of deuterium-labeled substrates in healthy or diseased human brain and has shown great clinical potential to detect aberrant metabolism in patients with high grade brain tumors. To establish the clinical value of DMI on larger patient populations and different neurological diseases, the method must migrate from dedicated (ultra)-high-field research MR scanners to the more commonly available clinical field strength of 3T. Successful development of the technical innovations in this proposal will guarantee an optimal implementation of DMI at 3T, thereby driving its further development and validation via use in larger, diverse patient populations.

PI_NAMEs: DE FEYTER, HENK ;DE GRAAF, ROBIN A (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Adoption;Alzheimer's Disease;Automobile Driving;base;Brain;Brain imaging;Brain Neoplasms;Cancer Detection;Cerebrum;Clinic;Clinical;clinical application;clinical decision-making;clinically relevant;clinically significant;Computer software;contrast imaging;Data;Dedications;denoising;Dependence;design;Detection;detection sensitivity;Deuterium;Development;Disease Progression;Elements;Excision;experience;Generations;Glucose;glucose metabolism;Goals;graphical user interface;Head;healthy volunteer;Human;human disease;Image;image processing;imaging modality;Improve Access;improved;in vivo;innovation;intravenous administration;Knowledge;Label;Length;Lipids;magnetic field;Magnetic Resonance Imaging;Maps;Measures;Metabolic;metabolic imaging;Metabolism;Methods;migration;Monitor;Nervous System Disorder;neuroimaging;novel;Oral Administration;Parkinson Disease;patient population;Patients;Performance;Play;Positioning Attribute;pre-clinical;Process;Protons;radio frequency;Relaxation;Reproducibility;Research;Resolution;Role;Sampling;Scanning;Shapes;Side;Site;soft tissue;spectroscopic imaging;System;Techniques;temporal measurement;Testing;therapeutic evaluation;Therapeutic Intervention;Time;Tissues;tool;Translations;tumor;user-friendly;Validation;Warburg Effect

PROJECT_TITLE: Deuterium metabolic imaging (DMI) of neurological disease

STUDY_SECTION: EITN

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


NIH_SPENDING_CATS: Bioengineering;Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Machine Learning and Artificial Intelligence;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: NARRATIVE Proton therapy allows superior tumor targeting and normal tissue sparing, and can potentially unleash the full potential of SBRT in liver tumor treatment. However, proton therapy delivery is greatly challenged by the intra-treatment liver tumor motion, especially for the increasingly popular and dominant pencil beam scanning (PBS) technique. This project fulfills the urgent unmet clinical needs of motion management in proton therapy, by developing the first dosimetry-guided and closed-loop system that combines simultaneous real- time imaging and on-the-fly plan adaptation, to deliver high-precision doses to moving tumors to improve liver disease care.

PI_NAMEs: LU, WEIGUO ;ZHANG, YOU  (contact)

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: 3-Dimensional;3D Print;Abdomen;Address;Affect;Algorithms;Anatomy;Artificial Intelligence;biomechanical model;Breathing;Cancer Center;Cancer Patient;Caring;Clinical;Clinical Research;Data;design;Development;Dose;dose information;dosimetry;Ensure;experimental study;Feedback;Geometry;Goals;graph neural network;Image;imaging capabilities;Impairment;improved;improved outcome;irradiation;Lead;Liver;Liver diseases;liver function;Liver neoplasms;Liver parenchyma;Malignant neoplasm of liver;Medical;Metastatic Neoplasm to the Liver;Methods;migration;millisecond;Modeling;Modernization;Monitor;Motion;Network-based;neural network;Normal tissue morphology;Paint;Patient-Focused Outcomes;Patients;Philosophy;Photons;Play;Practice Management;pre-clinical;Predisposition;prevent;Principal Component Analysis;proton beam;proton therapy;Protons;Radiation;Radiation Dose Unit;Radiation therapy;real-time images;Respiration;respiratory;response;Roentgen Rays;Role;Safety;Sampling;Scanning;Site;Source;System;Techniques;Technology;Testing;Three-Dimensional Imaging;Time;Tissues;Toxic effect;treatment planning;tumor;Uncertainty;Variant;virtual;X-Ray Computed Tomography

PROJECT_TITLE: High-Precision Proton Therapy for Liver Cancer: Developing an End-to-end Strategy with Real-time Liver Tumor Localization and On-the-fly Plan Delivery Adaptation

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ORG_CITY: LOS ANGELES

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Hypokalemic periodic paralysis (HypoPP) is a rare inherited disorder of skeletal muscle in which recurrent episodes of severe weakness, and the risk of progressive weakness with loss of ambulation, are caused by mutations of either calcium channel or sodium channel genes. Contemporary management of symptoms, with lifestyle changes or empirical usage of carbonic anhydrase inhibitors, is inadequate with diminished quality of life and no effective means to prevent late-onset permanent muscle weakness. This project builds upon the insights from our 30 years of investigating pathomechanisms of HypoPP to the rational design and preclinical testing of new pharmacologic approaches to mitigate acute attacks and of gene therapies for a more durable management that may also prevent late onset myopathic weakness.

PI_NAMEs: CANNON, STEPHEN C. (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Ablation;Acute;Address;Agonist;Alleles;antagonist;Arginine;Attenuated;base editor;Biological Assay;Biophysics;Blood;Calcium Channel;Carbohydrates;Carbonic Anhydrase Inhibitors;Clinical Management;Computer Models;CRISPR/Cas technology;Data;Defect;design;Disease;Dominant Genetic Conditions;efficacy evaluation;efficacy testing;Exercise;Extravasation;Failure;Family;Fiber;gain of function;gene editing technology;gene therapy;gene-editing approach;Genes;Glucose;Hereditary Disease;Hour;Human;Hypokalemia;Hypokalemic periodic paralysis;improved;in vivo;Infusion procedures;Ingestion;Inherited;inhibitor;insight;Insulin;Intervention;Ions;kindred;Knock-in;Knock-in Mouse;Life Style;Membrane;Missense Mutation;Mobility decline;Modification;Molecular;Monitor;mouse model;Mus;Muscle;Muscle function;Muscle Weakness;mutant;mutant mouse model;Mutation;mutation correction;Myopathy;novel strategies;Pathogenesis;Patients;pharmacologic;Pharmacotherapy;Phenotype;Point Mutation;Potassium Channel;pre-clinical;Preclinical Testing;Predisposition;preservation;prevent;Prevention;Protons;Quality of life;rational design;Recovery;Recurrence;Resources;response;Rest;Risk;sensor;Serum;side effect;simulation;Skeletal Muscle;Sodium Channel;Stress;symptom management;Testing;Therapeutic Intervention;Time;Treatment Efficacy;Validation;voltage

PROJECT_TITLE: Disease Pathogenesis and Modification for CaV1.1-Associated Hypokalemic Periodic Paralysis

STUDY_SECTION: SMEP

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


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF NURSING

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

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Every year, more than 15 million babies are born too soon, resulting in more than one million deaths. Yet, methods to predict risk for and prevent early birth are lacking. In the PROMIS study, we’ll test new ways to predict and prevent early birth using early pregnancy blood samples.

PI_NAMEs: GILLESPIE, SHANNON L. (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Address;Affect;Algorithms;Anti-Inflammatory Agents;Antibiotics;Area;Automobile Driving;Biological Markers;Birth;Blood specimen;Cell Surface Receptors;Cells;Cervical;Cessation of life;Clinical;clinical predictors;cohort;Collection;confirmatory trial;cost;cytokine;Data;design;Diagnosis;Dose;early pregnancy;efficacy testing;Enrollment;Exhibits;experimental study;extracellular;Feeds;Fetal Tissues;Future;Goals;high risk;Immune;immune function;Immune response;Immunologic Monitoring;Immunologic Receptors;immunopathology;immunoregulation;Infection;Inflammation;Inflammatory;inflammatory marker;innovation;insight;inter-individual variation;Label;Length;Ligands;Literature;Measurement;Mediating;Medical Records;Membrane;Methods;Modeling;novel;Pathogenesis;Pathologic;patient oriented;Performance;Pharmaceutical Preparations;Phenotype;Physiological;predicting response;prediction algorithm;Pregnancy;pregnancy failure;Pregnant Women;premature;Premature Birth;Premature Infant;Premature Labor;prenatal;Prenatal care;prevent;Prevention;preventive intervention;Preventive therapy;Progesterone;Public Health;Recording of previous events;Regulation;response;Risk;risk prediction;Rupture;Specificity;Testing;TLR2 gene;TLR3 gene;TLR4 gene;TLR7 gene;Toll-like receptors;Uterine Contraction;Uterine Rupture;Whole Blood;Withdrawal

PROJECT_TITLE: Prenatal Immunomonitoring in Spontaneous Preterm Birth Prevention (PROMIS)

STUDY_SECTION: RPPH

STUDY_SECTION_NAME: Reproductive, Perinatal and Pediatric Health Study Section[RPPH]


PHR: Project Narrative Harnessing the activity of natural immunoregulatory molecules to treat chronic inflammation is an attractive strategy to address the limited effectiveness and deleterious side-effects of conventional anti-inflammatory drugs. The proposed research will develop a new anti-inflammatory therapy based on synthetic multivalent nanoassemblies of galectin-1 and galectin-3, carbohydrate-binding proteins that are natural regulators of inflammation. Combining galectin-1 and galectin-3 into a synthetic nanoassembly will address the biochemical features of wild-type galectins that have limited their therapeutic effectiveness to date, thereby leading to a potent new class of anti-inflammatory therapy.

PI_NAMEs: HUDALLA, GREGORY  (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: Address;Affinity;American;Anti-Inflammatory Agents;Apoptosis;Autoimmune Diseases;Binding;Biochemical;Biological Assay;carbohydrate binding protein;carbohydrate receptor;Carbohydrates;Carrageenan;cell behavior;Cell model;Cells;Chemicals;Chemotactic Factors;Chronic;Data;Dependence;design;dimer;Dose;Drug Kinetics;Effectiveness;effectiveness evaluation;effectiveness study;Engineering;Enzyme-Linked Immunosorbent Assay;extracellular;Extracellular Space;Galactose Binding Lectin;Galectin 1;Galectin 3;Health;Histology;Human;Humoral Immunities;Imiquimod;Immune;immunoregulation;improved;In Vitro;in vivo imaging;Inflammation;Inflammatory;inhibitor;innovation;Interferons;Interleukin-6;keratinocyte;Leukocytes;Lipopolysaccharides;Macrophage;Macrophage Activation;mast cell;Measures;Membrane;Modeling;morphometry;nanoassembly;neutrophil;novel;novel therapeutics;Pathway interactions;Peptides;Pharmaceutical Preparations;Phosphatidylserines;Polysaccharides;pre-clinical;Pre-Clinical Model;programs;Proteins;Psoriasis;receptor;Recombinants;Reporting;Research;Safety;scaffold;side effect;Signal Pathway;Signal Transduction;Sterility;Structure;subcutaneous;success;T-Lymphocyte;Testing;therapeutic effectiveness;transcriptome sequencing;Translations;Variant;Work

PROJECT_TITLE: Synthetic Multivalent Galectin Assemblies as Anti-Inflammatory Therapies

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Dental, Oral, and Craniofacial Disease;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: PITTSBURGH

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Engineering full organs that can functionally integrate with the body is a major challenge in regenerative medicine. In this study, we are developing methods to tissue engineer complex dental structures and discovering mechanisms driving their integration with healthy tissues, specifically investigating innervation and anatomical bone attachment. This study will lead to new effective dental therapies and translate to improving regeneration and integration of organ systems throughout the body.

PI_NAMEs: SYED, FATIMA NAZ (contact)

PROGRAM_OFFICER_NAME: VERBRIDGE, SCOTT SPENCER

PROJECT_TERMS: 3-Dimensional;Affect;alveolar bone;Anatomy;Ankylosis;Automobile Driving;Behavior;Biochemical;Biological Models;Blood Vessels;Body System;bone;Cell Differentiation process;Cells;Clinical;Coculture Techniques;Complex;Cues;Data;Dental;Dental Pulp;dental structure;Dentistry;Development;Engineering;Ensure;Environment;Evaluation;Exhibits;Experimental Models;Fiber;functional outcomes;Goals;healing;Histologic;Implant;improved;in vivo;insight;Jaw;Knowledge;Maps;mechanical properties;Methods;mineralization;Modeling;Molecular;Molecular Profiling;Natural regeneration;Nerve Fibers;nerve supply;Neurites;neurotrophic factor;novel;Organ;organ regeneration;Organoids;osteogenic;Outcome;Pattern;Periodontal Ligament;Periodontium;Peripheral;Physiological;Population;Process;progenitor;Rattus;regenerative;Regenerative Medicine;regenerative therapy;repaired;scaffold;self assembly;Semaphorins;Sensory;Site;soft tissue;spatiotemporal;stem;stem cell biology;stem cell fate;stem cells;Structure;Structure of trigeminal ganglion;System;Time;Tissue Engineering;tissue regeneration;Tissues;tomography;Tooth Extraction;Tooth regeneration;Tooth root structure;Tooth structure;transcription factor;transcriptomics;Translating;Work

PROJECT_TITLE: Uncovering mechanisms of complex tissue assembly using dental organoids

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MSOS-A (04)]


NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Comparative Effectiveness Research;Cost Effectiveness Research;Digestive Diseases;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Primary Health Care;Social Determinants of Health

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative The proposed study is relevant to public health because expanding access to colorectal cancer screening through pharmacies located in medically underserved communities will improve prevention and early detection of cancer. Supported by preliminary work demonstrating the acceptability, feasibility, and estimated effect of the PharmFIT intervention, this is the first trial to systematically evaluate pharmacy-based CRC screening using FITs in the US. Findings related to the impact, implementation, and cost of PharmFIT will generate new knowledge about interventions delivered by community pharmacists and contribute to NCI’s mission to fund research that will reduce cancer disparities.

PI_NAMEs: BRENNER, ALISON T (contact);SHAH, PARTH D

PROGRAM_OFFICER_NAME: SARMA, ELIZABETH ANNE

PROJECT_TERMS: Address;Adopted;Adult;Affect;aged;Alaska;American Cancer Society;arm;budget impact;Cancer Control;cancer health disparity;cancer prevention;care coordination;Caring;Clinic;Colonoscopy;Colorectal Cancer;colorectal cancer screening;Communication;Communities;community collaboration;community partners;Community Pharmacy;comparison group;Complementary therapies;Consolidated Framework for Implementation Research;cost;Cost Analysis;cost estimate;Counseling;Data;Diagnostic;Disease;Effectiveness;effectiveness evaluation;effectiveness/implementation trial;Eligibility Determination;experience;experimental study;Exploration, Preparation, Implementation, and Sustainment;follow-up;Funding;Goals;health care availability;Health care facility;health care settings;health economics;Healthcare;high risk;Home;Hybrids;Idaho;implementation barriers;implementation determinants;implementation evaluation;implementation outcomes;implementation science;Improve Access;improved;Income;Individual;Inequity;informant;innovation;Insurance Coverage;Intervention;intervention cost;Interview;Knowledge;Malignant Neoplasms;Medical;medically underserved;medically underserved population;Methods;microcosting;Mission;Modeling;Montana;mortality;multidisciplinary;National Cancer Institute;North Carolina;Outcome;Patient Care;patient navigation;Patients;Pharmacists;Pharmacy facility;Population;Positioning Attribute;Prevention;Preventive service;Primary Care;primary care clinic;primary care patient;primary care provider;primary care visit;primary outcome;Process;programs;Protocols documentation;Provider;Public Health;Randomized;Randomized, Controlled Trials;Recommendation;Research;Research Personnel;Role;rurality;Scientist;screening;Screening for cancer;screening services;service intervention;Services;Site;Surveys;team-based care;Test Result;Testing;treatment as usual;underserved community;Underserved Population;United States;United States Preventative Services Task Force;Update;uptake;usual care arm;Visit;Washington;Work;Wyoming

PROJECT_TITLE: Expanding access to colorectal cancer screening through community pharmacies: The PharmFIT study

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


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

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE This competitive renewal application aims to continue our studies to unmask the mechanism of action of LukAB, a potent toxin produced by Staphylococcus aureus, which targets and kills immune cells. Information obtained from the studies proposed in this application will pave the way for the development of specific inhibitors to target and block the activity of this toxin and provide new alternatives for the treatment of infections caused by this important human pathogen.

PI_NAMEs: TORRES, VICTOR J. (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Alanine;alternative treatment;Amino Acid Sequence;Amino Acids;Antibiotic Resistance;Bacteria;Bacteriology;Binding;Biochemistry;Biological Assay;cell envelope;cell killing;Cells;Cellular biology;Cessation of life;Chronic;Clinical;Collection;combat;Communities;Complex;cost;cytotoxicity;Cytotoxin;Data;Development;Disease;Drug Metabolic Detoxication;Engineering;Environment;Exhibits;extracellular;Family member;Funding;Future;gene product;Generations;Genes;Genetic Transcription;Goals;Hospitalization;Hospitals;Human;human pathogen;humanized mouse;Immune;Immune response;Immunology;in vivo;Infection;inhibitor;insight;interdisciplinary approach;interest;Intoxication;ITGAM gene;large scale data;Leucocidin;Leukocytes;Libraries;Measures;Mediating;methicillin resistant Staphylococcus aureus;Miniature Swine;Modeling;Molecular;mouse model;Multi-Drug Resistance;multi-drug resistant pathogen;Mus;mutant;Mutation;neutrophil;novel;Organism;Output;Pathogenesis;Patients;Phagocytes;Phagosomes;Play;prevent;Process;Production;programs;Proteins;receptor;Regulation;Reporter;Research;Role;Species Specificity;Staphylococcal Infections;Staphylococcus aureus;Staphylococcus aureus infection;Surgical Wound Infection;Targeted Toxins;Techniques;Therapeutic;therapeutically effective;tissue culture;Toxin;Toxoids;transcription factor;Tropism;Vaccine Antigen;vaccine candidate;vaccine trial;Vaccines;Variant;Virulence Factors;Work

PROJECT_TITLE: Mechanistic Studies Of The Staphylococcus aureus LukAB Cytotoxin

STUDY_SECTION: BV

STUDY_SECTION_NAME: Bacterial Virulence Study Section [BV]


NIH_SPENDING_CATS: Kidney Disease;Regenerative Medicine

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: PROJECT NARRATIVE Acute kidney injury is a common cause of hospitalization, and when the kidney is unable to repair itself, this can result in chronic kidney dysfunction requiring lifelong morbidity, dialysis or even transplant. We have discovered a signaling pathway that promotes kidney repair and restores kidney function after acute kidney injury. This grant will explore how our newly discovered enzyme system regulates this signaling pathway and participates in kidney repair in mouse models, and then will correlate this with human clinical data from acute kidney injury patient samples. Finally, we will assess the efficacy of drugging this pathway in kidney repair.

PI_NAMEs: STAMLER, JONATHAN S.;ZHOU, HUALIN  (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Antioxidants;bone;Cell Cycle;Cellular Metabolic Process;Chronic;Clinical;Clinical Data;clinically significant;Coenzyme A;cofactor;Complement;Cysteine;Dialysis procedure;dimer;drug efficacy;efficacy evaluation;Enzymes;Epithelial Cells;epithelial repair;Fibrosis;G2/M Arrest;Glycolysis;Grant;Heart;Hospitalization;Human;inhibitor;Injury to Kidney;insight;Intensive Care Units;Ischemia;Kidney;kidney cell;kidney dysfunction;kidney fibrosis;kidney repair;Knock-out;Knockout Mice;Liver;macromolecule;Mediating;Mediator;Metabolic;Modification;Morbidity - disease rate;mortality;mouse model;Mus;Mutate;NADP;Nephrons;Nerve;new therapeutic target;Nitric Oxide;Nitric Oxide Synthase;novel;Nucleotides;Outcome;Oxidative Stress;Oxidoreductase;Pathway interactions;Patients;Pentosephosphate Pathway;Pharmaceutical Preparations;Phospholipids;Physiological;preclinical trial;Productivity;Proliferating;Protein S;Proteins;Pyruvate Kinase;Reactive Oxygen Species;Regulation;Renal function;repaired;Reperfusion Injury;Role;S-Nitrosothiols;Sampling;Signal Pathway;Signal Transduction;Site;Skeletal Muscle;Skin repair;small molecule;small molecule therapeutics;Sulfhydryl Compounds;Surface;Syndrome;System;Testing;Therapeutic;therapeutic target;tool;Toxin;Transplantation;Tubular formation;Ureteral obstruction

PROJECT_TITLE: Novel Regulation of Renal Function by S-Nitrosylation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-Y (05)]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Hypertension;Kidney Disease;Patient Safety;Pediatric;Prevention;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Children requiring surgery for congenital heart disease are at an increased long-term risk for hypertension, chronic kidney disease and end-stage kidney disease. The proposed study will enroll 350 children and follow them annually to characterize the natural history and clinical profiles of hypertension and chronic kidney disease. The study aims to detect modifiable risk factors and identify novel methods for clinical diagnosis that can be used to inform consensus guidelines for blood pressure and kidney function follow-up after surgical repair of congenital heart disease.

PI_NAMEs: NG, DEREK K;PARIKH, CHIRAG R (contact)

PROGRAM_OFFICER_NAME: MENDLEY, SUSAN RUTH

PROJECT_TERMS: Acceleration;Acute Renal Failure with Renal Papillary Necrosis;Adolescent;Adult;adverse outcome;Affect;Albumins;Albuminuria;Ambulatory Blood Pressure Monitoring;Ancillary Study;Area;biobank;Biological Markers;biomarker panel;Birth History;Blood Pressure;blood pressure elevation;Cardiac;Cardiac Surgery procedures;Cardiology;Cessation of life;Characteristics;Child;Childhood;Chronic Kidney Failure;Clinical;clinical care;clinical diagnosis;clinical research site;clinical risk;cohort;Cohort Studies;Common Ventricle;Congenital Abnormality;congenital heart abnormality;Congenital Heart Surgery;Consensus;Creatinine;Data;Data Collection;deprivation;Development;Diagnosis;Diagnostic;Disease;Disease Pathway;Early Diagnosis;Echocardiography;EGF gene;End stage renal failure;Enrollment;Epidemiologic Factors;Epidemiology;Event;Exclusion;Fibrosis;follow-up;Functional disorder;Future;Genetic;genetic analysis;genetic disorder diagnosis;genetic risk factor;genetic variant;Glomerular Filtration Rate;Growth;Guidelines;Health;heart defect;heart disorder diagnosis;Heart Ventricle;High Prevalence;high risk;Hypertension;Hypoplastic Left Heart Syndrome;improved;Incidence;indexing;Inflammation;Inflammatory;Injury;Injury to Kidney;insight;Intervention;Investigation;Kidney;Kidney Diseases;Lesion;Live Birth;Measurement;Measures;Medical Genetics;Methods;modifiable risk;Monitor;mortality;Natural History;Nephrology;Newborn Infant;novel;novel marker;novel therapeutics;Obesity;Operative Surgical Procedures;Outcome;Pathogenicity;Pathway interactions;Patients;Pediatric cohort;Pediatric Hospitals;Perioperative;Persons;Pharmaceutical Preparations;Phenotype;Pilot Projects;Plasma;Population;post gamma-globulins;Premature Mortality;prevent;primary outcome;prognostic tool;prospective;Proteins;Proteome;Proteomics;Quality of life;Receptors, Tumor Necrosis Factor, Type II;Recording of previous events;recruit;Registries;Renal function;repaired;Reporting;Research;Resources;Risk;Risk Factors;Sampling;Serum;Social Environment;socioenvironmental factor;Subgroup;targeted biomarker;Therapeutic;Time;TNFRSF1A gene;TNFRSF1B gene;Tubular formation;UMOD gene;Urine;Visit

PROJECT_TITLE: Kidney-Associated Diseases after Congenital Heart disease surgery In Children


ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

PHR: Mutational processes that underlie human cancer leave mutational signatures identifiable by whole genome sequencing. Precision Oncology aims to target these underlying mutational processes. Seminal work by the Sanger Institute has identified mutational patterns, including single and doublet base pair substitutions, indels, and copy number alterations, and structural variants, that are indicative of defects in DNA replication and repair, mutagen exposures, and enzymatic modification of DNA. These mutational signatures could be prognostic or predictive. Determining if these mutational signatures predict treatment response in Veterans could provide expanded therapeutic indications for larger numbers of Veterans. At a fundamental level, whether the mutational signatures identified in civilian tumors are found in tumors from United States Veterans and whether novel signatures might develop due to war-time exposures is unknown. Identification of these novel mutational signatures may reveal new therapeutic targets and inform preventative measures to reduce exposure risk.

PI_NAMEs: KELLEY, MICHAEL J;MAXWELL, KARA N (contact);PYARAJAN, SAIJU

PROJECT_TERMS: Aneuploidy;base;Base Pairing;Biological Markers;BRAF gene;brca gene;cancer genome;cancer genomics;Cancer Patient;carcinogenicity;Caring;Catalogs;Characteristics;Chromosomal Instability;chromothripsis;Clinical;clinical sequencing;clinical translation;Clinical Trials;cohort;Copy Number Polymorphism;Coupling;Data;data repository;Databases;Defect;Development;Disease;DNA;DNA biosynthesis;DNA Modification Process;DNA Repair;DNA Repair Disorder;DNA Sequence Alteration;Environmental Exposure;Epidermal Growth Factor Receptor;European;Event;exome sequencing;Fingerprint;Future;gastrointestinal;Gastrointestinal tract structure;Genetic;Genitourinary system;Genome;genome sequencing;Genomics;homologous recombination;Human;improved;Individual;insertion/deletion mutation;Knowledge;Loss of Heterozygosity;Lung;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Microsatellite Instability;military veteran;Minority;Modeling;Molecular;Mutagens;Mutation;National Cancer Institute;new therapeutic target;novel;Oncogenic;oncology program;Pathologic;Pathway interactions;Patient Selection;Patients;Pattern;Phenotype;precision oncology;Prediction of Response to Therapy;predictive marker;predictive signature;Preventive measure;Process;prognostic;prognostication;programs;Prostatic Neoplasms;Publishing;Resources;Risk;Sampling;Screening for cancer;Selection for Treatments;Seminal;Services;Single base substitution;Specimen;standard of care;success;targeted sequencing;Testing;The Cancer Genome Atlas;Therapeutic;therapeutic target;time use;Tissues;treatment response;tumor;tumor DNA;tumor growth;Tumor Markers;United Kingdom;United States;United States Department of Veterans Affairs;Urothelium;Variant;Veterans;whole genome;Work

PROJECT_TITLE: Mutational processes underlying tumor development in United States Veterans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 SPLP-Y (01)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Tobacco;Tobacco Smoke and Health

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE The proposed project will enhance our understanding of smoking and cancer-related health disparities among sexual orientation and gender identity (SOGI) minority (e.g., lesbian, gay, bisexual, and transgender) adults in the United States. The limited knowledge base regarding the prevalence and how SOGI-specific state-level policies are associated with smoking disparities among SOGI minority adults has hindered the ability to address cancer-related outcomes and design more effective lung cancer screening, prevention, and intervention efforts. The integration of multiple data sets with common smoking, gender identity, and sexual orientation measures will allow our research team to examine innovative research questions related to SOGI- specific policy factors associated with smoking behaviors, low dose computed tomography lung cancer screening eligibility and use, and smoking-related health outcomes among adults that cannot be adequately addressed with one data set alone.

PI_NAMEs: VELIZ, PHILIP T (contact)

PROGRAM_OFFICER_NAME: REYES-GUZMAN, CAROLYN

PROJECT_TERMS: 18 year old;Address;Adult;Age;aged;Awareness;Behavioral Risk Factor Surveillance System;Bisexual;cancer health disparity;Cessation of life;Cigarette Smoker;cigarette smoking;cisgender;comparison group;computed tomography screening;Data;data harmonization;data integration;Data Set;Data Sources;design;Disparity;Drug usage;Early Diagnosis;Eligibility Determination;Environment;Environmental Risk Factor;Ethnic Origin;Frequencies;Future;Gender Identity;Geographic Locations;Geography;Guidelines;Health;Health behavior;health disparity;Heterogeneity;Heterosexuals;high risk;improved;Income;Individual;innovation;Intervention;Knowledge;knowledge base;Lesbian Gay Bisexual Transgender;Lesion;Link;Literature;low dose computed tomography;Lung;lung cancer screening;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Methodology;Methods;Minority;Minority Groups;minority health;minority health disparity;Minority Health Research;mortality;Movement;multilevel analysis;multiple datasets;older adult;Outcome;Patient Self-Report;Personal Satisfaction;Policies;Population Assessment of Tobacco and Health;Populations at Risk;Prevalence;Prevalence Study;prevent;Prevention;public policy on tobacco;Race;Research;Resources;response;Risk;Risk Factors;Sample Size;Sampling;screening;Self Assessment;sex;Sex Orientation;Sexual and Gender Minorities;Smoke;Smoker;Smoking;Smoking Behavior;Smoking History;smoking prevalence;social stigma;sociodemographic factors;statistics;Subgroup;Surveys;Survival Rate;Techniques;Testing;Tobacco;Tobacco use;transgender;United States;Update;Variant;Work

PROJECT_TITLE: Smoking and Cancer-Related Health Disparities among Sexual and Gender Minority Adults

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]