NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Social Determinants of Health;Substance Misuse

ORG_NAME: PUBLIC HEALTH INSTITUTE

PI_NAMEs: SUBBARAMAN, MEENAKSHI S (contact)

PROJECT_TERMS: Address;Age;Alcohol abuse;alcohol epidemiology;alcohol research;alcohol services;Alcohols;Area;Atmosphere;Biometry;Biostatistics Core;causal model;cohort;Cohort Analysis;Collaborations;Communication;Complement;Computer software;Consultations;Data;Data Collection;data repository;Data Security;data visualization;Database Management Systems;Databases;design;detector;Development;Disparity;econometrics;Educational workshop;Ensure;Epidemiology;Equilibrium;experience;Formulation;Funding;Generations;Goals;Health Disparities Research;health disparity;high intensity drinking;Human Resources;innovation;Instruction;Learning;Machine Learning;machine learning method;machine learning model;Maintenance;Manuscripts;Maximum Likelihood Estimate;Methodology;Methods;Modeling;Monitor;Motivation;multilevel analysis;organizational structure;Participant;Positioning Attribute;Postdoctoral Fellow;pragmatic implementation;pre-doctoral;Preparation;Procedures;Process;Psychometrics;Publications;Research;Research Assistant;Research Personnel;Research Project Grants;Resources;Sampling;Secure;Series;Services;skills;Source;Statistical Methods;substance use;Survey Methodology;Surveys;System;technical writing;Techniques;theories;Training;training project;Work

PROJECT_TITLE: Statistical and Data Services Core


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Obesity

ORG_CITY: SAN FRANCISCO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Recent studies suggest that boosting number and/or activity of beige adipocyte may represent an alternative approach to tackle the obesity epidemic. In this proposal, we will determine the mechanisms of beige adipocyte plasticity. Investigations in this direction may not only reveal novel regulatory components of beige adipocyte homeostasis in vivo, but also attract clinical applications to target beige adipocyte maintenance to treat obesity.

PI_NAMEs: WANG, BIAO  (contact)

PROGRAM_OFFICER_NAME: HAFT, CAROL R

PROJECT_TERMS: Abbreviations;Ablation;Adipocytes;Adipose tissue;Adult;Affect;Age;Automobile Driving;Back;Brown Fat;Catecholamines;Cell Nucleus;Cells;Characteristics;Chromatin;clinical application;Complex;Cues;Environment;environmental change;Extracellular Matrix;Fibrosis;gene network;Genetic;genetic corepressor;Genetic Transcription;HDAC4 gene;Histone Deacetylase;Homeostasis;Human;Immune;In Vitro;in vivo;Investigation;Knowledge;Lead;lipid biosynthesis;Maintenance;Metabolic;Metabolic Diseases;metabolic fitness;Molecular;mouse model;Mus;new therapeutic target;novel;novel therapeutic intervention;Nutrient;Obesity;Obesity Epidemic;Pathway interactions;Performance;Physiological;postnatal;preservation;prevent;Process;Production;progenitor;programs;Property;receptor;Recording of previous events;Regulation;Renaissance;Repression;Research;Resolution;response;Rodent;SET Domain;Signal Transduction;Sumoylation Pathway;System;Temperature;Tissues;Transforming Growth Factor beta;uncoupling protein 1;warm temperature;Work

PROJECT_TITLE: Regulation of beige adipocyte plasticity in inguinal white adipose tissue.

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Pediatric;Prevention;Primary Health Care;Rural Health;Social Determinants of Health

ORG_CITY: BELTSVILLE

ORG_NAME: PACIFIC INSTITUTE FOR RES AND EVALUATION

ORG_STATE: MD

PHR: Project Narrative Enhancing health and healthcare for gender and sexual minority (GSM) youth in the U.S. is a national public health priority. School-based health centers (SBHCs) are well-positioned to address disparities related to health and healthcare by providing structurally competent services to GSM youth. Our community-engaged study uses replicable approaches in implementation science to enable SBHCs to adopt new practices to make services structurally competent for GSM youth impacted by inequities in healthcare and, thus, health.

PI_NAMEs: WILLGING, CATHLEEN E. (contact)

PROGRAM_OFFICER_NAME: GODETTE, DIONNE

PROJECT_TERMS: Address;Adolescent;adolescent health;Adopted;Adoption;Affect;Anxiety;Attention;Awareness;barrier to care;Behavior;behavioral health;bullying;California;Caring;cisgender;Clinical;clinical encounter;Clinical Services;Communities;community engaged research;community partnership;Competence;Data Sources;Discrimination;Disparity;Documentation;Effectiveness;Employee;Environment;Equity;Ethnography;Evaluation;experience;Foundations;Fright;Funding;Gender;gender diverse;Gender Identity;gender minority;gender minority health disparity;gender minority health research;gender minority youth;Goals;Guidelines;Health;health care delivery;health care settings;health equity;health inequalities;Healthcare;Heterosexuals;implementation outcomes;implementation process;implementation science;implementation strategy;improved;improved outcome;Individual;Inequity;innovation;Insurance Coverage;Interdisciplinary Study;Intervention;Interview;Knowledge;Language;Leadership;Lesbian Gay Bisexual Transgender Queer;Link;marginalization;Mediator;Mental Depression;Methods;minority patient;minority student;Motivation;New Mexico;Obesity;Organizational Change;organizational climate;Outcome;outcome disparities;patient population;Patients;peer;Personal Satisfaction;Physical environment;Policies;Population;Positioning Attribute;prevention service;Procedures;Process;Provider;public health priorities;Quality of Care;Readiness;Recommendation;Reproductive Health;Research;Research Institute;Resources;Risk;Role;Rural;satisfaction;scaffold;school based health center;School-Age Population;Schools;service delivery;service organization;Services;Sex Orientation;Sexual and Gender Minorities;Sexual Health;sexual minority;sexual minority status;sexual minority youth;Sexuality;Sexually Transmitted Diseases;social;social health determinants;social stigma;Solid;Staff Attitudes;Strategic Planning;Students;substance use;suicidal behavior;Surveys;Time;Training;trial design;unintended pregnancy;United States;United States National Institutes of Health;Universities;Work;Workforce Development;Youth

PROJECT_TITLE: Enhancing Structural Competency in School-Based Health Centers to Address LGBTQ+ Adolescent Health Equity

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


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Despite the longstanding dogma that premenopausal women are commonly viewed as protected from hypertension and cardiovascular disease (CVD), compelling evidence establishes that obesity abrogates the protective effects of female sex and predisposes women to obesity-associated hypertension (OAH) though, through sex specific mechanisms. The source of this sex difference in mechanisms is unknown. The proposed study aims to uncover the underlying origin of the mechanisms for sex differences in OAH by investigating role for sex chromosome complement and will test whether human female adrenals are more sensitive to leptin- mediated aldosterone production than that of males.

PI_NAMEs: BARRIS, CANDEE  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: adipokines;Adrenal Glands;Adult;Affect;Aldosterone;Anabolism;Atropine;Biology;Blood Pressure;blood pressure control;blood pressure regulation;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Cells;Clinical Data;CYP11B2 gene;Data;Dissociation;Endothelial Cells;experimental study;Female;female sex hormone;Four Core Genotypes;Funding;Gonadal Steroid Hormones;Health;Heart Rate;Human;human female;Hypertension;hypertensive;improved;In Vitro;Knowledge;Laboratories;Leptin;leptin receptor;male;Measures;Mediating;Menopause;Mentorship;Mineralocorticoid Receptor;Modeling;Molecular;mouse model;Mus;Myography;novel;Obese Mice;Obesity;obesity development;Outcome;Ovariectomy;Ovary;Phenotype;Physiology;Play;Ploidies;post-doctoral training;pre-doctoral;Premenopause;Production;Propranolol;protective effect;Receptor Inhibition;Receptor Signaling;Recording of previous events;Reporting;Research;response;Risk Factors;Role;Sampling;sex;Sex Chromosomes;Sex Differences;Signal Pathway;Signal Transduction;Source;Specificity;stem;steroidogenic acute regulatory protein;Testing;Therapeutic;therapeutically effective;Training;Universities;Vascular Diseases;Woman

PROJECT_TITLE: Origins of sex differences in the mechanisms of obesity-associated hypertension


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Diabetes;Kidney Disease;Organ Transplantation;Transplantation

ORG_CITY: NEW YORK

ORG_DEPT: SURGERY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Xenotransplantation of composite islet-kidneys (I-K) containing autologous islets, has the capacity to cure both renal failure and diabetes for patients suffering from end-stage diabetic nephropathy, which is currently an unmet medical need. If successful, our approach could provide a virtually limitless donor supply of islets and kidneys, a methodology that avoids the need for long-term immunosuppression and donor kidneys from miniature swine, which attain sizes similar to those of human recipients.

PI_NAMEs: SACHS, DAVID H (contact);YAMADA, KAZUHIKO

PROGRAM_OFFICER_NAME: NABAVI, NASRIN N

PROJECT_TERMS: Allogenic;Animal Model;Animals;Antigens;Autoimmune Responses;Autologous;Bone Marrow;Bone Marrow Transplantation;capsule;Chimerism;Chronic;Clinical;clinical application;Clinical Treatment;clinically relevant;Data;Diabetes Mellitus;diabetic;Diabetic Nephropathy;Disease;Donor person;experimental study;Family suidae;Goals;Human;Hybrids;Immune response;Immunosuppression;improved;Inbreeding;innovation;Insulin-Dependent Diabetes Mellitus;Ischemia;islet;Islets of Langerhans;Islets of Langerhans Transplantation;Kidney;Kidney Failure;Kidney Transplantation;kidney xenograft;Laboratories;Living Donors;Medical;Methodology;Methods;Miniature Swine;Modeling;Molecular;Morbidity - disease rate;mortality;natural antibodies;Nature;Nephrectomy;new technology;nonhuman primate;Organ;Pancreas;Pancreas Transplantation;Pancreatectomy;Papio;Patients;Population;pre-clinical;Predisposition;Prevalence;Protocols documentation;Regimen;Renal Glycosuria;response;Risk;Techniques;Technology;Testing;Therapeutic immunosuppression;Thymic epithelial cell;Thymus Gland;Time;Tissues;Toxic effect;Transgenic Organisms;Transplantation;Vascularization;virtual;Xenograft procedure

PROJECT_TITLE: Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: Princeton

ORG_DEPT: BIOLOGY

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative Understanding patterns of human genetic variation is critically important for the design, analysis, and interpretation of disease mapping studies. This project will develop methods to identify and study DNA sequences in humans that have been inherited from archaic ancestors, such as Neanderthals and Denisovans. These data will provide new insights into human history, characteristics of extinct humans that we exchanged genes with, and the spectrum of human genomic diversity.

PI_NAMEs: AKEY, JOSHUA MICHAEL (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Admixture;African;Anatomy;Characteristics;Communities;Complex;CRISPR/Cas technology;Data;Data Set;design;detection method;Development;Disease;DNA;DNA Sequence;Event;experimental analysis;experimental study;fitness;functional genomics;Funding;Gene Exchanges;Gene Pool;Genes;Genetic Variation;Genome;Genomics;Geography;Human;Human Genetics;Human Genome;improved;Individual;Inherited;insight;Large-Scale Sequencing;Maps;Methodology;Methods;Modeling;Modernization;Molecular;Nature;novel;Pattern;Phenotype;Population;Population Genetics;Population Heterogeneity;Population Study;Recording of previous events;reference genome;Research;segregation;Sex Bias;Shapes;Statistical Methods;Survival Analysis;System;Technology;Testing;user friendly software;Variant;whole genome;Work

PROJECT_TITLE: Identification and interpretation of introgressed hominin DNA in modern human genomes

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ADMINISTERING_IC: AG

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The proposed project will allow researchers to study behavioral and social influences on health and economic wellbeing over the life course and across generations including: how childhood experiences shape health and economic wellbeing at retirement age; the role of measured and unmeasured family background in multi- generational transmission of wealth and health; and life course and genealogic influences across the adult lifespan.

PI_NAMEs: FRIEDMAN, ESTHER M. (contact)

PROGRAM_OFFICER_NAME: BRAUDT, DAVID BRUCE

PROJECT_TERMS: Acceleration;Adult;Age;Aging;aging related;Attention;behavior influence;Behavioral;Behavioral Research;behavioral study;Book Chapters;Child;Child Development;Childhood;Collection;Complex;Contracts;Data;data centers;data enclave;Data Files;Data Set;design;disability;Disparity;distributed data;DNA;Economics;experience;Family;Family dynamics;Family member;Family Relationship;Generations;Genetic;genomic data;Genomics;Genotype;Geography;Grant;Health;health disparity;innovation;intergenerational;journal article;late life;Life;Life Cycle Stages;life span;Link;Longitudinal Studies;Longitudinal Surveys;Measures;member;Michigan;Outcome;panel study of income dynamics;Parents;Peer Review;Personal Satisfaction;Population;Positioning Attribute;Process;Publications;Qualifying;Recording of previous events;Research;Research Infrastructure;Research Personnel;Resources;Retirement;Role;Saliva;saliva sample;Sampling;Scientist;Secure;Shapes;social;social influence;social science research;Social Sciences;Social Well-Being;Socioeconomic Status;socioeconomics;Surveys;Theoretical model;time use;Training;Training Activity;transmission process;Universities;virtual;web site;Work

PROJECT_TITLE: Health and Well-being Over the Life Course and Across Multiple Generations

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetic Testing;Genetics;Human Genome;Immunotherapy;Precision Medicine

ORG_CITY: BOSTON

ORG_DEPT: MISCELLANEOUS

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Identiﬁcation of patterns in DNA mutation data can reveal the biological mechanisms that may be responsible for the alterations. We will develop computational methods to perform such analysis in DNA sequencing platforms used in the clinic. The tools we develop will aid clinicians in therapy selection in cancer and other diseases.

PI_NAMEs: PARK, PETER J (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Adopted;Algorithms;Attention;Biological;Biological Assay;Biological Markers;Biological Process;biomarker identification;brca gene;Cancer Patient;Catalogs;Cells;Characteristics;Classification;Clinic;Clinical;clinical application;clinical care;Clinical Data;clinical predictive model;cohort;Collaborations;Communities;Computing Methodologies;Cytidine Deaminase;Data;Data Set;data standards;Detection;detection method;Development;Disease;DNA;DNA Double Strand Break;DNA Sequence Alteration;DNA sequencing;Evolution;exome;exome sequencing;Formulation;gene panel;Genes;Genome;genome sequencing;Genomic Instability;Germ Lines;Goals;homologous recombination deficiency;Immune;immune checkpoint blockade;Immunotherapy;improved;insertion/deletion mutation;Malignant Neoplasms;Methodology;Methods;Mismatch Repair Deficiency;Modeling;Monitoring for Recurrence;Mutagenesis;Mutation;Mutation Detection;neoantigens;novel;patient stratification;patient subsets;Patients;Pattern;Point Mutation;Poly(ADP-ribose) Polymerase Inhibitor;predict clinical outcome;predictive modeling;Process;profiles in patients;Proliferating;Refit;repaired;replication stress;resistance mechanism;responders and non-responders;response;Sampling;Screening for cancer;Selection for Treatments;Sensitivity and Specificity;sequencing platform;simulation;Single base substitution;single-cell RNA sequencing;Somatic Mutation;Source;System;Techniques;tool;transcriptomics;tumor;tumor DNA;tumor heterogeneity;Variant;whole genome;Work

PROJECT_TITLE: Mutational signature analysis: methods and applications to the clinic

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Climate-Related Exposures and Conditions;Genetics;Human Genome;Skin Cancer

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: NARRATIVE Cancers have readily-defined characteristics often referred to as “hallmarks”; however, the question of how the sequence of cancer development progresses -- from normal tissue to carcinogen-damaged tissue to precancerous lesion and finally to malignant tumors – remains unanswered. Classically, these steps are attributed to the sequential acquisition of discrete genetic events such as driver mutations, but the clonal dynamics governing cancer development happen over years, remain largely invisible even in model systems, and have been difficult to link to specific molecular changes. Our long-term goal is to apply ecological and evolutionary principles to cancer initiation and development in order to test whether the hallmarks of cancer are acquired in three distinct phases each with distinct selective pressures and manifestations of cell competition and cooperation.

PI_NAMEs: BROWN, JOEL ;TSAI, KENNETH Y (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Actinic keratosis;Architecture;Binding;Biological Models;Cancer Center;cancer initiation;carcinogenesis;Carcinogens;Carcinoma;Cell division;Cells;Characteristics;Chronic;Clinical;Clonal Evolution;Development;driver mutation;Ecology;Environment;Epithelium;Event;experience;fitness;Genetic;Genetic Transcription;Genomics;Goals;Heritability;Heterogeneity;Human;in vivo;Individual;Investigation;Lesion;Ligands;Link;Malignant - descriptor;Malignant Neoplasms;mathematical model;Mathematics;Measures;Mediating;Modeling;Molecular;molecular dynamics;multidisciplinary;Mutation;Normal tissue morphology;novel;Oncology;Pathogenicity;permissiveness;Phase;premalignant;pressure;Proliferating;quantitative imaging;receptor;Running;single cell sequencing;single-cell RNA sequencing;Skin;Skin Cancer;Skin Carcinogenesis;Skin Carcinoma;skin squamous cell carcinoma;Stress;Testing;Time;Tissues;trait;Transplantation;tumor;tumor microenvironment;Ultraviolet Rays;UV induced;UV Radiation Exposure;Variant;Work

PROJECT_TITLE: Eco-evolutionary drivers of clonal dynamics during UV-induced skin carcinogenesis (PQ3)


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Human Genome;Lung;Precision Medicine

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative  Micro-ribonucleic acids (miRNAs) are crucial for normal lung development, lung health, and have been identified as potential therapeutic targets for Chronic Obstructive Pulmonary Disease (COPD). miRNAs interact with other biological molecules, such as transcription factors proteins and messenger RNAs (mRNAs); these interactions may be impacted by changes in the underlying DNA sequence, such as the disease-associated genetic variants identified through genome wide association studies (GWAS). In this project, we will model the regulatory roles of miRNAs in COPD using blood and lung tissue sequencing data, investigate how regulation may be altered in response to known COPD GWAS variants, and compare the results with publicly available drug response data to hypothesize potential new treatments for COPD.

PI_NAMEs: GLASS, KIMBERLY RENEE (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Address;affection;Biological;Blood;Blood specimen;Chronic Obstructive Pulmonary Disease;Clinical;clinical application;Complex;Data;data integration;Development;Disease;disease model;Disease susceptibility;DNA Sequence;Environment;Epigenetic Process;Gene Expression Regulation;Genes;genetic association;genetic variant;Genetic Variation;genome wide association study;genomic locus;Goals;Individual;insight;Link;lung development;Lung Diseases;lung health;Maps;Messenger RNA;Methodology;Methods;Modeling;Molecular;multiple omics;network models;Network-based;novel;novel therapeutic intervention;novel therapeutics;Observational Study;open source;Outcome;Pathogenesis;Pathway Analysis;Pharmaceutical Preparations;Phenotype;Play;precision medicine;preservation;programs;Proteins;Quantitative Trait Loci;Regulation;Research;response;RNA;Role;Sampling;Smoking;Software Tools;Structure;Structure of parenchyma of lung;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissue Sample;Tissues;Trans-Omics for Precision Medicine;transcription factor;transcriptome sequencing;Translating;translational impact;treatment strategy;Variant;Whole Blood

PROJECT_TITLE: Leveraging Variant-perturbed Gene Regulation to Support Precision Medicine in COPD

STUDY_SECTION: IRAP

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


NIH_SPENDING_CATS: Cardiovascular;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Pediatric;Prevention

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This randomized, double-blind, placebo-controlled, clinical trial will assess the ability of a new obesity medication to improve the durability of weight loss among adolescents with severe obesity.

PI_NAMEs: KELLY, AARON S (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: 18 year old;Address;Adolescent;Adult;adult obesity;Area;arterial stiffness;Binding;Biological;Biological Adaptation;Blood Pressure;Body fat;Body mass index;Body Weight decreased;bone health;Cardiac;cardiometabolic risk;Childhood;Clinic;Clinical;Clinical Trials;clinically relevant;Cognition;comorbidity;Controlled Clinical Trials;cost effectiveness;Data;Desire for food;Dose;Double-Blind Method;Drops;Energy Intake;Energy Metabolism;FDA approved;Formulation;Goals;Heart Rate;High Prevalence;improved;Individual;Inflammation;Life Style Modification;Maintenance;Measures;Mediating;Medical;Mental Health;metabolic rate;Morbid Obesity;Neurosecretory Systems;Obesity;Outcome;Oxidative Stress;Participant;Patients;Peripheral;Pharmaceutical Preparations;Pharmacotherapy;Phentermine;Physiological;Placebo Control;placebo group;Placebos;prevent;primary endpoint;psychosocial;Randomized;Regulatory Pathway;Relapse;Replacement Therapy;Reporting;response;Rest;Risk Factors;Role;Safety;Satiation;side effect;sobriety;Starvation;Structure;Surface;topiramate;total energy expenditure;United States National Institutes of Health;Visceral fat;Weight

PROJECT_TITLE: Role of Pharmacotherapy in Counteracting Weight Regain in Adolescents with Severe Obesity

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


NIH_SPENDING_CATS: Immunotherapy;Lymphatic Research

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Achieving tolerance remains the most important goal in transplantation. The significance of the current proposal is that it will define regulatory T cell-lymphatic interactions as an important regulatory nidus for suppression and tolerance and define the key events and structures that regulate this interaction and can be leveraged to manipulate immunity. The findings from these investigations will have general applicability to other areas of immunology such as infection, vaccination, cancer, and autoimmunity.

PI_NAMEs: BROMBERG, JONATHAN S (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adenosine;Adoptive Transfer;allograft rejection;Antigen Receptors;Antigens;Area;Autoimmunity;Binding;Blood;Blood Vessels;CCL21 gene;CD4 Positive T Lymphocytes;Cell Communication;Cell surface;conditioning;Data;Dendritic Cells;Development;draining lymph node;Endothelial Cells;Endothelium;Event;FOXP3 gene;Funding;Gatekeeping;Geography;Goals;Helper-Inducer T-Lymphocyte;Homeostasis;IL2RA gene;Immune response;Immunity;Immunology;Infection;Inflammation;Interleukin-6;Interruption;Investigation;Islets of Langerhans Transplantation;isoimmunity;Kinetics;Leukocytes;Ligands;Lymphatic;Lymphatic Endothelial Cells;Lymphatic Endothelium;Lymphocyte;Lymphoid Tissue;Malignant Neoplasms;migration;novel;pathogen;PD-1/PD-L1;Peripheral;permissiveness;Phenotype;Phosphotransferases;polarized cell;Production;programmed cell death ligand 1;programmed cell death protein 1;Publications;receptor;Receptor Cell;Receptor Signaling;Regulatory T-Lymphocyte;Resolution;response;Role;Signal Pathway;Signal Transduction;Site;Stimulus;Structure;System;Therapeutic;Thymus Gland;Time;Tissues;trafficking;transcription factor;Transplantation;Transplantation Tolerance;Tumor Necrosis Factor-Beta;Vaccination;Vascular Cell Adhesion Molecule-1;Vascular Endothelium

PROJECT_TITLE: Regulatory T Cells and Lymphatic Endothelial Cells: Regulatory Interactions for Migration and Suppression

STUDY_SECTION: TTT

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


ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Mammalian SWI/SNF ATP-dependent chromatin remodeling complexes are multi-subunit macromolecular machines that play critical roles in the regulation of chromatin architecture. However, the mechanisms by which mSWI/SNF complexes target to specific sites and engage specific features of the chromatin landscape genome- wide, and how these binding interactions impact catalytic activity remain unknown. Owing to their frequent perturbation in human disease, with genes mutated in >20% of human cancers and several intellectual disability syndromes, defining the mechanisms governing mSWI/SNF targeting and activity will enable an understanding of disease-specific biology and may provide a powerful foundation for the identification of new therapeutic strategies.

PI_NAMEs: KADOCH, CIGALL  (contact);MUIR, TOM

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: Antibodies;Architecture;ATP phosphohydrolase;Bar Codes;Bilateral;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biology;Cancer Biology;Cancer cell line;Cell Line;Cells;Chromatin;chromatin protein;chromatin remodeling;Chromatin Remodeling Factor;Complex;Consumption;Coupled;defined contribution;Development;Disease;DNA;EMSA;Enzymes;Epigenetic Process;epigenomics;Evaluation;exome sequencing;Family;Fluorescence Resonance Energy Transfer;Foundations;Gene Expression;Genes;genetic regulatory protein;genome-wide;Genomics;histone modification;Histones;Human;Human Cell Line;human disease;In Vitro;innovation;Intellectual functioning disability;Knowledge;Libraries;Maintenance;Malignant Neoplasms;Mammalian Cell;Maps;Modification;mutant;Mutate;Mutation;Neurodevelopmental Disorder;novel strategies;novel therapeutic intervention;Nucleosomes;Oncogenic;Pathology;Physiological;Play;preference;Recurrence;Regulation;Role;Series;Site;Slide;Structure;Structure-Activity Relationship;Surveys;SWI/SNF Family Complex;Syndrome;System;Tail;three dimensional structure;Variant

PROJECT_TITLE: Structure-activity relationships governing mammalian SWI/SNF chromatin remodeling activity as a function of chromatin state

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Eye Disease and Disorders of Vision;Infectious Diseases;Neurosciences

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Ocular toxoplasmosis is a relapsing disease and a major cause of visual loss. Current treatment does not affect visual outcome. We plan studies that will identify how molecular events determine whether selective autophagic targeting of Toxoplasma gondii takes place and may identify therapeutic targets against ocular toxoplasmosis.

PI_NAMEs: SUBAUSTE, CARLOS S (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Ablation;Animal Model;Antibodies;Autophagocytosis;Autophagosome;Blindness;Cells;Child;Confocal Microscopy;congenital infection;Deposition;Disease;EGF-Like Domain;EGFR inhibition;Elderly;Electron Microscopy;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Event;Galactose Binding Lectin;Genetic;immunosuppressed;Impairment;improved;in vivo;Infection;inhibitor;Invaded;Lead;live cell microscopy;Mediating;Membrane;Microbe;Molecular;Mus;novel;novel therapeutic intervention;Ocular Toxoplasmosis;Outcome;Parasites;pathogen;Pathogenesis;Pathway interactions;Patients;Penetration;pharmacologic;Phosphorylation;Phosphotransferases;prevent;Process;protective effect;protein activation;protein expression;Protein Kinase;Proteins;recruit;Recurrence;Recurrent disease;relapse prevention;Resistance;Retina;Retinitis;Role;Signal Induction;Signal Pathway;Signal Transduction;STAT3 gene;Testing;Therapeutic;therapeutic target;Toxoplasma gondii;Toxoplasmosis;Transactivation;Transgenic Mice;Ubiquitin;Vacuole;Vision;Visual;Work

PROJECT_TITLE: Autophagy and Ocular Toxoplasmosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BDCN-J(81)]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Immunotherapy;Women's Health Research

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Narrative High density of intratumoral high endothelial venules (HEVs) has been associated with Th1 immunostimulatory tumor environment, favorable response to chemotherapy, and cancer survival. It is thought that these specialized blood vessels serve as gateways for lymphocyte recruitment. We will determine the precise role of tumor HEVs in shaping immune landscape and the importance for immune checkpoint inhibition therapy.

PI_NAMEs: KOMATSU, MASANOBU  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Adoptive Transfer;Affect;anti-PD1 therapy;Antigens;Area;attenuation;B-Lymphocytes;Blood Circulation;Blood Vessels;Breast Adenocarcinoma;cancer immunotherapy;cancer infiltrating T cells;Cancer Patient;cancer survival;cancer therapy;cancer type;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Density;cell type;Cells;checkpoint inhibition;checkpoint therapy;chemotherapy;Circulation;Clinical;Clinical Research;cytokine;Dendritic Cells;density;Development;Drug Delivery Systems;effector T cell;Endothelial Cells;Environment;Enzyme-Linked Immunosorbent Assay;Exclusion;Exhibits;Favorable Clinical Outcome;gain of function;Genetic Models;High Endothelial Venule;Human;Immune;Immune checkpoint inhibitor;Immune mediated destruction;Immunofluorescence Immunologic;immunogenic;Immunotherapy;improved;Infiltration;Invaded;Laboratories;Link;loss of function;lymph nodes;Lymphocyte;Lymphocytic Infiltrate;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Melanoma;Molecular;Monomeric GTP-Binding Proteins;Mus;Natural regeneration;Nature;Neoplasms in Vascular Tissue;novel;Outcome Study;Paper;patient response;patient subsets;Patients;PD-1/PD-L1;Population;Process;Prognosis;programs;Publishing;RAS genes;recruit;Reporting;response;Role;Shapes;Specimen;Structure;success;T-Lymphocyte;tertiary lymphoid organ;Therapeutic Effect;transcriptome sequencing;treatment strategy;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Tumor Suppression;Vascular Endothelial Cell;venule

PROJECT_TITLE: Role of intratumoral high endothelial venules in tumor immunity

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Hearing Loss;Neurosciences;Prevention;Rehabilitation

ORG_CITY: CHICAGO

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative It has been shown that neural stimulation with infrared radiation is more spatially selective than electrical stimulation and could result in more independent channels to encode acoustic information in cochlear implants. Psychophysics experiments have shown that more independent channels available for encoding acoustic information will result in better music appreciation and performance of cochlear implant users in noisy listening environments, or during the use of tonal languages. While the parameters for infrared neural stimulation have been established in animal models, the proposed experiments are to translate the results into the clinic by validating the results in humans in acute tests during a translabyrinthine tumor resection surgery and to fabricate and test an first prototype of an optical cochlear implant.

PI_NAMEs: RICHTER, CLAUS-PETER  (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: Acoustic Nerve;Acoustic Stimulation;Acoustics;Action Potentials;Acute;American;Animal Model;aqueous;Auditory;Bionics;Clinic;Clinical;clinical center;Cochlea;Cochlear Implants;Collaborations;Communication;Craniotomy;Data;deaf;design;Development;Diameter;Electric Stimulation;Electric Wiring;Electrodes;Encapsulated;Environment;Equipment;Excision;experience;experimental study;fabrication;Felis catus;first-in-human;Goals;Good Manufacturing Process;Hearing;Human;human study;Hybrids;Implant;implantable device;Implanted Electrodes;improved;in vivo;Industrialization;industry partner;Infrared Rays;Institution;Intraoperative Monitoring;Language;Length;Light;manufacture;Manufacturer;Measurement;Measures;Medical Device;Methods;miniaturize;Modality;Monitor;Music;neural prosthesis;neural stimulation;Neurons;next generation;novel;Operating Rooms;Operative Surgical Procedures;optical fiber;Optics;Patients;Perception;Performance;Photons;physical property;Physiologic pulse;Polishes;pre-clinical research;Preparation;prototype;Psychophysics;Pulse Rates;Radiation;recruit;Research;response;Risk;Risk Assessment;round window;Saline;Scala Tympani;Scientist;Silicones;Site;Skull Base Neoplasms;Societies;sound;Source;Specific qualifier value;speech in noise;spiral ganglion;Stimulus;success;Surgeon;System;Technology;Temperature;Testing;Time;Tissues;tool;Translating;tumor;United States Food and Drug Administration;vestibular system;waveguide;Work;Writing

PROJECT_TITLE: Opto-Electrical Cochlear Implants

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ORG_CITY: TUCSON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE The overarching goal of this proposal is to develop immune cell engineering approaches for the monitoring and treatment of T cell-mediated autoimmune diseases such as Type-I diabetes (T1D). We will compare three functionally distinct T cell populations engineered to express 5MCARs for their ability to prevent autoimmune diabetes and ask if the 5MCAR platform can enable sensitive detection of autoimmune T cells early in the progression of diabetes. Finally, we will test additional biomimetic modifications of the 5-module design as we work towards the development of 2nd generation 5MCARs with improved function.

PI_NAMEs: KUHNS, MICHAEL S (contact);SERWOLD, THOMAS F

PROGRAM_OFFICER_NAME: BLONDEL, OLIVIER

PROJECT_TERMS: Antibodies;Antigens;Area;Autoimmune;Autoimmune Diabetes;Autoimmune Diseases;autoreactive T cell;Beta Cell;beta-2 Microglobulin;Biological Markers;biomarker driven;Biomimetics;Blood;CD3 Antigens;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD80 gene;CD8B1 gene;Cells;cellular engineering;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;Clinic;Clinical;clinical application;Complex;Cytoprotection;Cytotoxic T-Lymphocytes;Data;design;Detection;Development;Diabetes Mellitus;Disease;E protein;Elements;Engineering;Environment;Event;Evolution;Foundations;functional improvement;Generations;Goals;Health;Home;Human;Immune;immunoengineering;improved;In Vitro;in vivo;Inbred NOD Mice;Incidence;infancy;innovation;Insulin-Dependent Diabetes Mellitus;insulitis;Investigation;islet;Knowledge;Lead;Mediating;Memory;Modification;Molecular;Monitor;mouse model;Mus;new technology;novel;Pancreas;Pathogenicity;Peptides;Performance;Phenotype;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;prevent;Prevention;Process;Publishing;receptor;Regulatory T-Lymphocyte;Reporter;Reporting;research clinical testing;response;Safety;sensor;Sentinel;Signal Transduction;Solid;stem cells;Symptoms;T cell response;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;Technology;Testing;Therapeutic;Tissues;trafficking;Transmembrane Domain;treatment response;Work;α-Fetoproteins

PROJECT_TITLE: Engineering 2nd generation 5MCARs to monitor and treat Type-I Diabetes


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Data Science;Genetics;Human Genome;Pediatric;Rare Diseases

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: Project Narrative Clinical sequencing has become a frontline strategy for diagnosing rare disease, particularly in pediatrics where 10% of pediatric admissions and up to 20% of infant deaths derive from Mendelian disease. However, the capability for generating sequence data far outstrips the capability to accurately interpret these data, and over half of patients with suspected genetic disorders do not currently receive a genetic diagnosis. Our Center will share data broadly and contribute substantially to the establishment of a comprehensive catalog of the genetic causes of Mendelian diseases, thus improving diagnosis rates as well as building the biological understanding needed to develop more effective therapeutics.

PI_NAMEs: O'DONNELL-LURIA, ANNE  (contact);REHM, HEIDI L;TALKOWSKI, MICHAEL E

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: Acceleration;Admission activity;Adopted;analytical method;analytical tool;Biological;Blood;Candidate Disease Gene;Catalogs;Cell Line;Childhood;Clinical;clinical sequencing;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;Communities;Country;Data;Data Aggregation;Data Analyses;data platform;Data Set;data sharing;Development;Diagnosis;Disease;disease phenotype;Dissection;Embryo;Emerging Technologies;empowerment;epigenetic profiling;exome sequencing;Family;follow-up;gene discovery;Genes;Genetic;Genetic Diseases;genetic disorder diagnosis;genome sequencing;genomic data;Genomics;Goals;Haplotypes;improved;In Vitro;in vitro Model;in vivo;in vivo Model;induced pluripotent stem cell;Infant Mortality;insight;Investments;Joints;Kidney;large scale data;Mendelian disorder;method development;Methods;Mitochondria;Modeling;mosaic variant;Mus;Mutation;National Human Genome Research Institute;neuromuscular;novel;novel sequencing technology;parallelization;Patients;Pediatrics;Phenotype;prime editing;Process;Productivity;Rare Diseases;recruit;Research;Research Personnel;Retina;Sampling;single-cell RNA sequencing;Statistical Models;statistics;Technology;therapeutic development;therapeutic target;therapeutically effective;timeline;Tissues;tool;transcriptome sequencing;Untranslated RNA;Variant

PROJECT_TITLE: Broad Institute Mendelian Genomic Research Center


PHR: Project Narrative The proposed research is aimed at developing strategies to engineer dendritic cells so they can be safely used for induction of antigen-specific tolerance in type 1 diabetes. This work is relevant to public health and the NIH’s mission because these approaches hold the potential to prevent and to help achieve a cure for this disease.

PI_NAMEs: AGUDO CANTERO, JUDITH  (contact)

PROJECT_TERMS: anergy;Antigen Presentation;Antigen Targeting;Antigen-Presenting Cells;Antigens;Apoptosis;Autoantigens;Autoimmune Diseases;Autoimmunity;Automobile Driving;autoreactive T cell;Beta Cell;CD8-Positive T-Lymphocytes;cell type;Cells;Clinic;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Development;Diabetic mouse;Disease;Engineering;Ensure;exhaustion;expectation;Face;Gene Expression;Genetic Engineering;Genetic Transcription;Goals;Immune;Immune response;Immune system;Immune Tolerance;Immunity;immunogenic;Immunologics;Inbred NOD Mice;Inflammation;Inflammatory;innovation;Insulin-Dependent Diabetes Mellitus;Investigation;islet;Knowledge;Lentivirus Vector;Messenger RNA;MicroRNAs;Mission;mouse model;novel;Outcome;Phenotype;Play;Pre-Clinical Model;preclinical study;prevent;Prevention;Principal Investigator;Process;promoter;Proteins;Public Health;Regulatory T-Lymphocyte;Reporting;Research;response;RNA;Role;Shapes;Signal Transduction;Site;Stimulus;Surveys;T-Cell Activation;T-Lymphocyte;Testing;therapeutic candidate;Time;Tissues;transcription factor;Transgenes;Translating;Translations;Treatment Efficacy;United States National Institutes of Health;Untranslated RNA;Up-Regulation;Virus Diseases;Work;Writing

PROJECT_TITLE: Engineering dendritic cells to target islet antigen to pro-tolerogenic subsets for prevention and treatment of Type 1 Diabetes


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cardiovascular;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: EL PASO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF TEXAS EL PASO

ORG_STATE: TX

PHR: PROJECT NARRATIVE Vascular contributions to cognitive impairment and dementia (VCID) are currently considered as one of the leading causes of dementing illness. However, the underlying molecular and cellular mechanisms of VCID are not well understood, and no effective treatment strategy has been developed to date. This study will utilize a mouse model of VCID to investigate chronic cerebral hypoperfusion-induced white matter and hippocampal damage, and subsequent cognitive impairment . Understanding the VCID-related brain pathophysiology is crucial for the development of future therapeutic strategies .

PI_NAMEs: BHUIYAN, MOHAMMAD IQBAL HOSSAIN (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Alanine;Astrocytes;astrogliosis;Atherosclerosis;Attenuated;Axon;Bilateral;Biological Assay;Brain;Brain Injuries;Brain Pathology;Carotid Stenosis;Cell Death;cerebral hypoperfusion;chloride-cotransporter potassium;Chronic;Clover;Cognitive deficits;cognitive function;Complex;cytotoxic;demented;Dementia;dementia risk;Demyelinations;Development;Diffuse;Dissociation;Drug Kinetics;Edema;effective therapy;Epidemic;excitotoxicity;Family;Functional disorder;Future;Genes;Genetic Transcription;Glial Fibrillary Acidic Protein;Goals;Hippocampus;Hypertension;hypoperfusion;IL18 gene;Impaired cognition;Impairment;Inflammation;Injury;insight;interleukin-18 receptor;Ischemia;kinase inhibitor;Knowledge;Lead;Lesion;Lysine;Modeling;Molecular;mouse model;Mus;Myelin;Nerve Degeneration;Nervous System Disorder;neuron loss;Neurons;NF-kappa B;novel;Nuclear Translocation;Oligodendroglia;Pathogenesis;Phosphorylation;Phosphotransferases;Pilot Projects;Play;Proline;promoter;protein complex;Protein Isoforms;recruit;Resistance;Role;Serine;Signal Transduction;Stroke;Testing;Therapeutic;Threonine;Time;Treatment Protocols;treatment strategy;Up-Regulation;vascular cognitive impairment and dementia;white matter

PROJECT_TITLE: Astrocytic WNK-SPAK-NKCC1 Cascade in White Matter Astrogliosis and Injury

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;Infant Mortality;Infectious Diseases;Malaria;Maternal Health;Orphan Drug;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases;Vector-Borne Diseases;Women's Health Research

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative There exists a critical need in resource-limited settings to identify new strategies to reduce newborn deaths, many of which result from antenatal malaria infections with Plasmodium falciparum. We hypothesize that a strategy of screening pregnant women in malaria-endemic areas in the first trimester with a high-sensitivity rapid diagnostic test for parasites followed by treatment if positive with Artemether-Lumefantrine will reduce the risk of a negative pregnancy outcome. We will test this hypothesis in a clinical trial in Western Kenya and the Democratic Republic of the Congo, as well as study the pharmacokinetics of these antimalarials in the 1st trimester and estimate the incremental benefits of alternate approaches, in order to collectively identify a new strategy to improve pregnancy outcomes and newborn health in malaria-endemic areas.

PI_NAMEs: TAYLOR, STEVE MYER (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: adverse pregnancy outcome;Africa South of the Sahara;Aftercare;antenatal;Anti-malarials;Area;artemether;benflumetol;Birth Weight;Clinic;Clinical;Clinical Trials;cohort;Collaborations;Communicable Diseases;Complement;Country;Data;Democratic Republic of the Congo;density;design;Detection;Development;Diagnostic Sensitivity;Diagnostic tests;Discipline of obstetrics;Dose;Drug Kinetics;early pregnancy;effective therapy;efficacy testing;Enrollment;Epidemiology;experience;Fetal Growth;fetal loss;First Pregnancy Trimester;Goals;Guidelines;high risk population;improved;Infant;Infant Mortality;Infection;infection risk;innovation;Institution;Intercept;Intervention;Kenya;Left;Low Birth Weight Infant;Low Prevalence;Malaria;malaria infection;Malawi;mathematical model;Measures;Modeling;neonatal health;Neonatal Mortality;Neonatology;novel strategies;Outcome;Parasites;pharmacokinetics and pharmacodynamics;Placentation;Plasmodium falciparum;Population;Predisposition;Pregnancy;Pregnancy Outcome;Pregnant Women;Premature Birth;prenatal;prevent;Prevention strategy;Preventive therapy;primary outcome;Prophylactic treatment;Pyrimethamine;Randomized;Rapid diagnostics;Recommendation;Reporting;Resource-limited setting;Risk;Risk Reduction;Safety;Schedule;screening;Seasons;Second Pregnancy Trimester;Small for Gestational Age Infant;success;Sulfadoxine;Testing;Third Pregnancy Trimester;transmission process;treatment as usual;Treatment Efficacy;Treatment Protocols;Update;Woman;women's treatment

PROJECT_TITLE: Improving Neonatal health Through Rapid malaria testing in Early Pregnancy with high-sensitivity Diagnostics (INTREPiD)


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Human Genome;Organ Transplantation;Transplantation

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative Analysis of the complex cellular system in transplanted hearts is critical for understanding the mechanisms of chronic graft failure in heart transplant patients. This project aims to develop and apply novel single cell multi- omics methods to dissect donor and host cell chimerism and delineate the origins of pathogenic cell types. The project will deliver a powerful technology and several computational tools for studying cell lineages and cell fates and the research outcome will greatly benefit research of cellular systems of human organs and diseases.

PI_NAMEs: GAO, RULI  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Algorithms;Allografting;Biopsy;Biopsy Specimen;Biotechnology;Blood specimen;Cardiac;Cardiac Myocytes;Cause of Death;Cell Communication;cell injury;Cell Lineage;Cell Nucleus;cell type;Cells;chemokine;Chimerism;Chromatin;Chronic;Clinical;Collagen;Complex;computerized tools;Computing Methodologies;Data;Detection;Disease;DNA;DNA Markers;DNA sequencing;early onset;Endothelial Cells;Endothelium;Environment;Epigenetic Process;Etiology;Fibroblasts;Fibrosis;Freezing;Frequencies;functional outcomes;Genetic Transcription;Genets;Genome;Genotype;Goals;graft failure;heart allograft;Heart failure;Heart Transplantation;Human;human tissue;Hypertrophy;Immune;improved;Individual;Knowledge;Left Ventricular Mass;Life;Link;Measures;Mesenchymal;Metabolic Pathway;Methods;multiple omics;Mutate;Mutation;nanopore;new technology;new therapeutic target;novel;Organ;Outcome;Outcomes Research;Pathogenicity;Patients;Phenotype;Population;Process;programs;Research;RNA;Role;Sampling;Series;single nucleus RNA-sequencing;single-cell RNA sequencing;success;synergism;System;Technology;Testing;therapeutic target;Thick;Time;tool;transcriptome;Transplant Recipients;Transplantation;Variant;Vascular Diseases;vascular inflammation

PROJECT_TITLE: Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics

STUDY_SECTION: BBHV

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


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Endocrine Disruptors;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Prevention;Tobacco;Tobacco Smoke and Health

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: NARRATIVE (Public Health Relevance) Tobacco is the leading cause of preventable death in the United States. Although half of these deaths is due to cardiovascular (CV) disease, the molecular mechanism of how tobacco leads to increased CV mortality is not well understood. Studies proposed in this application will investigate how specific information in the human genome interacts with molecular actions of tobacco smoke to determine individual risk for developing CV disease.

PI_NAMEs: QUERTERMOUS, THOMAS  (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Address;Affect;Alkaline Phosphatase;Anatomy;Animal Model;Aorta;Apolipoprotein E;ARNT gene;Arterial Fatty Streak;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Atherosclerosis;Binding;Biological Assay;Biological Models;Cardiovascular Diseases;Cardiovascular system;Cell Lineage;Cell model;Cells;Cessation of life;Chondrocytes;conditional knockout;Coronary Arteriosclerosis;Coronary artery;Data;Dioxins;Disease;disease model;Disease Progression;disorder risk;Environmental Exposure;Environmental Risk Factor;Epigenetic Process;epigenomics;exposed human population;Exposure to;Functional disorder;gene environment interaction;Genes;Genetic;genetic approach;genetic association;Genetic Transcription;Goals;Heterodimerization;Histology;Human;Human Genetics;Human Genome;Hydrocarbons;In Vitro;in vitro Model;in vivo;Individual;innovation;insight;Knock-out;Knockout Mice;Lesion;Ligands;Link;loss of function;Mediating;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;novel;novel strategies;Pathway interactions;Phenotype;Physiological;Population;preventable death;promoter;protective effect;public health relevance;Receptor Signaling;Research;response;reverse genetics;Risk;Role;single cell ATAC-seq;single-cell RNA sequencing;Smooth Muscle Myocytes;Tissues;Tobacco;Tobacco smoke;Toxic Environmental Substances;Toxin;transcription factor;transcriptomics;United States;Vascular calcification;Vascular Diseases;Wild Type Mouse;Xenobiotics

PROJECT_TITLE: Identifying tobacco-genetic interactions through study of the aryl hydrocarbon receptor pathway.

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


ORG_CITY: FAIRFAX

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: GEORGE MASON UNIVERSITY

ORG_STATE: VA

PHR: Mechanisms of PSGL-1 restriction of HIV virion infectivity We propose to study the mechanisms of PSGL-1 restriction of HIV infectivity. We have recently identified PSGL-1 as a new HIV restriction factor that can inactivate the infectivity of HIV virions released from HIV producing cells.

PI_NAMEs: WU, YUNTAO  (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Amino Acids;beta-Transducin Repeat-Containing Proteins;Binding;Biological Assay;CD4 Positive T Lymphocytes;Cell membrane;Cell surface;Cells;Clathrin;dimer;Dimerization;Disabling;Disease remission;Down-Regulation;E-Selectin;Endothelium;Exclusion;extracellular;Extracellular Domain;Glycoproteins;glycosylation;HIV;HIV Infections;HIV-1;Immune;Infection;Leukocytes;Link;Lymphoid Cell;Maps;Mediating;Membrane;migration;Mucins;Mutagenesis;Myeloid Cells;N-terminal;Natural Immunity;novel therapeutic intervention;P-selectin ligand protein;particle;Pathogenesis;Pathway interactions;Phenotype;Process;Proteins;receptor;Receptor Cell;Residual state;Role;Site;Structure-Activity Relationship;Surface;Testing;Tissues;trafficking;Trefoil Motif;tyrosine O-sulfate;ubiquitin-protein ligase;Ubiquitination;Viral;Viral Physiology;Viral reservoir;Virion;Virus Assembly;virus host interaction


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Glioblastoma (GBM) is an incurable disease with current treatment including surgery, chemotherapy, and radiation. Immunotherapy has thus far failed in clinical trials for GBM. Our studies provide a novel therapeutics target, PP2A, in glioma cells to enhance GBM immunogenicity and sensitivity to immunotherapy.

PI_NAMEs: HO, SZE CHUN WINSON  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: adaptive immunity;Address;Adult;aggressive therapy;anti-tumor immune response;Brain Neoplasms;brain shape;cancer infiltrating T cells;CD8-Positive T-Lymphocytes;CD8B1 gene;cell type;Cells;checkpoint therapy;chemotherapy;Clinical;clinical efficacy;Clinical Trials;Combined Modality Therapy;Cross Presentation;CTLA4 gene;Cytoplasm;Data;Dendritic Cells;Disease;DNA;DNA Damage;ds-DNA;Effectiveness;Genetic;Glioblastoma;Glioma;Goals;Human;Immune;immune checkpoint blockade;Immune response;Immunocompetent;Immunocompromised Host;immunogenicity;Immunologics;Immunotherapy;Impairment;In Vitro;in vivo;Infiltration;Inflammatory;insight;Interferon Type I;Interferons;Knock-out;Knowledge;Link;Macrophage;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Mission;Modeling;Modification;Molecular;Mus;National Institute of Neurological Disorders and Stroke;Natural Immunity;Nature;neoplastic cell;Nervous System;Nervous System Disorder;new therapeutic target;novel;novel therapeutics;Operative Surgical Procedures;Pathway interactions;Patients;PD-1 blockade;pharmacologic;Phosphoric Monoester Hydrolases;pre-clinical;Pre-Clinical Model;Production;Protein Inhibition;Protein phosphatase;Radiation;Radiation therapy;Radiosensitization;Regulation;Reporting;Resistance;response;Role;scaffold;screening;Serine;side effect;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;small molecule inhibitor;standard of care;Stimulator of Interferon Genes;Substrate Specificity;synergism;T cell infiltration;T-Cell Activation;Therapeutic;Threonine;Treatment Efficacy;tumor;Tumor Immunity;tumor microenvironment;Tumor Promotion;tumor-immune system interactions

PROJECT_TITLE: Regulation of Tumor Immunogenicity in Glioblastoma

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Electronic Nicotine Delivery Systems;Pediatric;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE Dual use of electronic nicotine delivery systems (ENDS) and combustible cigarettes is the most common pattern of tobacco use among young adults. However, little is known about the basic behavioral processes that underlie dual use and the degree to which these processes are shared between products. The current project aims to examine behavioral underpinnings of ENDS use and tobacco dual use and craving among young adults in laboratory and naturalistic settings - focusing on cue reactivity, attentional bias, and negative affect - so that such knowledge can inform future research and intervention efforts to reduce the public health burden associated with tobacco use in the U.S.

PI_NAMEs: SOKOLOVSKY, ALEXANDER WILLIAM (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: Acute;adaptive intervention;addiction;Affect;Affective;Age;Applications Grants;Attention;attentional bias;Award;Behavior assessment;Behavioral;Cigarette;cigarette craving;cigarette smoking;Clinical Trials;cognitive process;combustible cigarette;combustible tobacco;conditioning;craving;cue reactivity;Cues;Data;data integration;Development;Devices;Drug Addiction;drug craving;Drug Exposure;Drug Modelings;Drug usage;Ecological momentary assessment;Electronic Nicotine Delivery Systems;enhancing factor;Environment;Event;Exposure to;Focus Groups;Image;in vivo;Incentives;indexing;Individual;innovation;insight;Intervention;Knowledge;Laboratories;Laboratory Finding;Laboratory Study;Longitudinal Studies;Measures;Mentors;Methodology;Methods;Modeling;Moods;Motivation;multilevel analysis;negative affect;Negative Reinforcements;Nicotine Dependence;nicotine exposure;nicotine use;novel;Participant;Patient Self-Report;Pattern;Persons;Pharmaceutical Preparations;Population;Population Assessment of Tobacco and Health;Positive Reinforcements;Predictive Factor;Preparation;preventive intervention;Process;Process Assessment;protective effect;prototype;Public Health;Relapse;Research;Research Project Grants;response;Risk;Role;Sampling;Scientific Inquiry;Series;skills;Smoking;Smoking Behavior;social;Stimulus;substance use;Surveys;theories;Time;Tobacco;tobacco products;Tobacco use;tobacco user;Training;Translating;Translation Process;Translations;uptake;vaping;Visual;young adult;Youth

PROJECT_TITLE: Dual Use of ENDS and Combustible Cigarettes: Shared, Distinct, and Cross-Conditioned Processes

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


NIH_SPENDING_CATS: Dietary Supplements;Nutrition;Obesity

ORG_CITY: HONOLULU

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF HAWAII AT MANOA

ORG_STATE: HI

PHR: The overall goal of this proposal is to determine the role of selenium (Se) and Scly-mediated Se recycling in selenoprotein synthesis and degradation in brown adipocyte adaptive thermogenesis. Because: a) the role of the antioxidant micronutrient selenium in brown adipocytes is unclear; b) the mechanism of Se recycling and selenoprotein degradation is largely understudied; and c) nutritional guidelines only consider dietary Se, neglecting its cellular recycling process as a source when Se availability is limiting; this study has the potential to impact future nutritional guidelines, clarifying the importance of Se in energy expenditure, ultimately improving our understanding of obesity development, a condition affecting millions of people worldwide.

PI_NAMEs: SEALE, LUCIA ANDREIA (contact)

PROGRAM_OFFICER_NAME: GUPTA, DHANANJAY

PROJECT_TERMS: Active Sites;Adipocytes;Adipose tissue;Adrenergic Agents;Affect;Amino Acids;Antioxidants;Binding;Brown Fat;cell growth regulation;cell immortalization;Cell Line;CRISPR/Cas technology;Diet;dietary;Dietary intake;Dietary Selenium;energy balance;Energy Metabolism;Enzymes;Exposure to;Future;Glutathione;Goals;Homeostasis;Human;Immunoprecipitation;improved;In Vitro;in vivo;in vivo Model;innovation;insight;Intake;Investigation;Iodide Peroxidase;Iodothyronine Deiodinase;Link;Lyase;Mammals;Mediating;Metabolism;metabolomics;Methods;Micronutrients;Mitochondria;Modeling;Molecular;Mus;neglect;novel;nutritional guideline;obesity development;Pathway interactions;Peroxidases;Persons;Pharmacological Treatment;Physiological;Physiology;Play;Process;Proteins;Reactive Oxygen Species;Recycling;Regulation;Research;Research Personnel;Research Proposals;response;Rodent;Role;Selenium;selenium deficiency;Selenocysteine;selenocysteine lyase;selenoprotein;Signal Transduction;Source;Stress;Thermogenesis;Thyroid Hormones;Trace Elements;transcriptomics;Transgenic Mice;Weight Gain;Wild Type Mouse

PROJECT_TITLE: Selenium metabolism in cold-induced adaptive thermogenesis


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Disability Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Physical Activity;Prevention

ORG_CITY: CHAPEL HILL

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Physical activity can positively affect aging adults, including prevention of or reduced severity of Alzheimer’s disease and related dementias and improved functional, well-being, and social outcomes. Given the increased risk for early-onset Alzheimer’s disease and related dementias, feasible and effective strategies and programs to increase physical activity levels are urgently needed for adults with intellectual disability. This project seeks to refine and test the feasibility of a multi-level physical activity program for adults with intellectual disability that utilizes self-management strategies to increase physical activity across home and community settings with a long-term goal of examining long-term effects of prevention of Alzheimer’s disease and related dementias.

PI_NAMEs: HUME, KARA ;SAVAGE, MELISSA NOEL;TOMASZEWSKI, BRIANNE  (contact)

PROGRAM_OFFICER_NAME: MCLINDEN, KRISTINA

PROJECT_TERMS: access disparities;actigraphy;Adult;Aerobic Exercise;Affect;Age of Onset;age related;Age-associated memory impairment;Aging;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease related dementia;Behavior;Behavioral;biobehavioral measurement;Biological Markers;Body Composition;Caregivers;Chronic Disease;Clinical;clinical trial protocol;Clinical Trials;Code;Communities;community setting;Control Groups;cost effective;Data;data dashboard;Dementia;design;Diabetes Mellitus;Disease;disorder prevention;early onset;Early Onset Alzheimer Disease;economic impact;efficacy study;Evidence based practice;Exercise;exercise intervention;Experimental Designs;feasibility testing;Feedback;fitness;Focus Groups;follow-up;Future;General Population;Goals;Heart Diseases;high risk population;Home;implementation barriers;improved;Individual;informal care;innovation;Intellectual functioning disability;Intervention;intervention effect;intervention program;Interview;life span;Light;Link;Long-Term Effects;Longitudinal Studies;Manuals;Measures;Medical;member;Methods;Modeling;moderate-to-vigorous physical activity;Monitor;mortality;mortality risk;Neurocognitive;North Carolina;Parents;Personal Satisfaction;Phase;Physical activity;Physiological;Pilot Projects;pilot test;Population;prevent;Prevention;Prevention trial;primary outcome;Primary Prevention;programs;protective factors;Public Health;Randomized;Randomized, Controlled Trials;recruit;Research;Risk;secondary outcome;Self Management;Services;Severities;Site;social;Social outcome;Step Tests;strength training;Strenuous Exercise;Structure;Surveys;Symptoms;Technology;Testing;Texas;Theory of Change;Time;Training Activity;Treatment Efficacy;United States National Institutes of Health;usability;Videotape;Visual;Waiting Lists;Weight;willingness;Work

PROJECT_TITLE: A Stage 1 Pilot Test for Feasibility and Efficacy of a  Multi-Level Intervention To Increase Physical Activity in Adults with Intellectual Disability: Step it Up +

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


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

ORG_STATE: CA

PHR: In this proposal, we will develop computational and experimental methods to maximize the power of high-throughput, microscopy-based phenotypic screens. Our studies will increase the power of phenotypic profiling by harnessing screens performed across the world, providing a rational approach for maximizing the chance of discovering hits for diverse pathways in future screens, and identifying novel compounds that expand our ability to perturb cancer-relevant pathways. Our proposal is designed to accelerate the pace of early drug discovery.

PI_NAMEs: WU, LANI F (contact)

PROGRAM_OFFICER_NAME: COVELL, DAVID G

PROJECT_TERMS: Acceleration;Active Learning;Address;Adoption;Affect;Biological;Biological Markers;Cancer cell line;cancer type;candidate identification;Cell Cycle Regulation;Cell Line;Chemical Structure;Chemicals;Classification;Collection;Communities;Computer Vision Systems;Computing Methodologies;Consumption;Data Set;deep learning;design;Detection;Disease;Disparate;drug discovery;Drug resistance;Drug Screening;druggable target;Epigenetic Process;Evaluation;experimental study;fighting;Funding;Future;Generations;Genetic;Grant;Image;imaging approach;improved;Individual;innovation;Knowledge;Laboratories;large-scale imaging data;Learning;learning strategy;Libraries;Machine Learning;Malignant Neoplasms;Methods;Microscopy;Modeling;Molecular Target;Mutation;new therapeutic target;novel;Pathway interactions;patient subsets;Pharmaceutical Preparations;Phenotype;Property;Proteomics;proteostasis;Research Personnel;response;screening;side effect;small molecule;Time;transcriptomics

PROJECT_TITLE: Maximizing the predictive power of high-throughput, microscopy-based phenotypic screens

STUDY_SECTION: DMP

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


NIH_SPENDING_CATS: Nutrition;Obesity

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative Adipose/fat tissue plays essential roles in maintaining whole-body metabolic homeostasis and its dysregulation causes obesity and many associated metabolic disorders. In this proposal, we will define the identity of a novel population of adipocytes that exist in various fat depots and exhibit potentially high metabolic and thermogenic properties. We will also assess overall impacts of these adipocytes on adipose tissue function, whole-body metabolic homeostasis, and protection of obesity. Results obtained will not only provide new insight into the biology of adipocytes, but also implicate these adipocytes as an important cell source and a therapeutic target in the treatment of obesity.

PI_NAMEs: CHEN, YIPING  (contact);WANG, QIONG ANNABEL

PROJECT_TERMS: Address;adipocyte biology;adipocyte differentiation;Adipocytes;Adipose tissue;Adolescent;Adult;Affect;Age;beta catenin;Biochemistry;Biological Assay;Bone Marrow;Brown Fat;Cell Line;Cell Proliferation Regulation;Cells;Child;clinical application;cold stress;Consensus;diet-induced obesity;Disease;Dyslipidemias;Embryo;Exhibits;Fatty acid glycerol esters;fetal;Foundations;FRAP1 gene;Future;Gene Modified;Genomics;Homeostasis;Hormones;Human;In Vitro;in vivo;inhibitor;insight;Knowledge;Life;Ligands;lipid biosynthesis;Mammals;Metabolic;Metabolic Diseases;Metabolism;Molecular;mouse model;Mus;Names;Neonatal;novel;Obese Mice;Obesity;obesity prevention;obesity treatment;pandemic disease;Physiological;Play;Population;PPAR gamma;precursor cell;programs;Property;Public Health;receptor;recruit;Regulation;response;Risk;Role;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Solid;Source;Testing;therapeutic target;Thermogenesis;Tissues;transdifferentiation;web site;WNT Signaling Pathway

PROJECT_TITLE: Characterization and functional assessment of a novel population of Wnt/beta-catenin driven adopocytes.

STUDY_SECTION: CADO

STUDY_SECTION_NAME: Cellular Aspects of Diabetes and Obesity Study Section[CADO]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: There is large body of evidence demonstrating that Posttraumatic Stress Disorder (PTSD) is associated with alterations in the stress hormone cortisol. There is also evidence that medications that block cortisol may be beneficial for treating PTSD and depression. The VA recently completed a study of a mifepristone, a medication that blocks cortisol and progesterone hormones, and found some benefit for veterans who did not have a history of traumatic brain injury. The proposal will test a medication from a new class of cortisol blockers which have no effect on progesterone. The proposed study will test the drug CORT108297 for treatment of PTSD and will establish a safety profile that will inform the design of future studies.

PI_NAMEs: NEYLAN, THOMAS C (contact)

PROJECT_TERMS: Abortifacient Agents;Adverse event;Affinity;Age;antagonist;anti-depressive agents;Antipsychotic Agents;Calibration;Chemistry;Chronic Post Traumatic Stress Disorder;Clinical;Clinical Trials;combat veteran;Data;design;Development;dexamethasone suppression test;Dose;Double-Blind Method;Dropout;Drops;drug testing;DSM-V;efficacy evaluation;efficacy testing;Electrocardiogram;Enrollment;FDA approved;Female;Frequencies;Functional disorder;Future;Generations;Glucocorticoid Receptor;Glucocorticoids;Goals;healthy volunteer;Hematology;Hormones;Hydrocortisone;hypnotic;Hypothalamic structure;improved;indexing;Laboratories;Major Depressive Disorder;male;Measures;Mediating;Medical;Mental Depression;Mental disorders;Mifepristone;Military Personnel;military veteran;Modeling;Mood stabilizers;Morbidity - disease rate;mortality;Outcome Measure;Participant;Patients;Peripheral;Pharmaceutical Preparations;Pharmacological Treatment;Phase;Physical Examination;Pituitary-Adrenal System;Placebo Control;Placebos;Population;Post-Traumatic Stress Disorders;pre-clinical;Progesterone;Progesterone Receptors;Quality of life;Randomized;Recording of previous events;Regimen;Regulation;Reporting;Safety;safety testing;Sample Size;screening;Secondary to;sedative;Severities;side effect;Signal Transduction;Site;Stress;Subgroup;Suicide;Sympathetic Nervous System;Symptoms;Syndrome;System;targeted treatment;Test Result;Testing;trauma exposure;Traumatic Brain Injury;Veterans;week trial;Woman;World Health Organization

PROJECT_TITLE: Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment ofVeterans with Posttraumatic Stress Disorder (PTSD)


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

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative This study is to investigate how physiological, pharmacological, and pathophysiological stimuli affect the cellular energy status of vascular endothelial cells via AMPK and ACE2, two principal molecules involved in cardiovascular health and disease. The elucidated mechanism will explain the potential long-term effects of COVID-19 on the heart disease.

PI_NAMEs: SHYY, JOHN YJ (contact);ZHANG, JIN

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: 2019-nCoV;5'-AMP-activated protein kinase;Acceleration;ACE2;Affect;angiogenesis;Angiotensin II;Angiotensins;Animal Model;arm;Arterial Lines;atheroprotective;Atherosclerosis;Binding;Biology;Cardiovascular Diseases;cardiovascular health;cell injury;Cell Physiology;cell type;Cells;Cellular biology;Cellular Metabolic Process;COVID-19;Cues;Disease;Endothelial Cells;Endothelium;energy balance;extracellular;Functional disorder;functional outcomes;Glycolysis;Goals;Health;Heart Diseases;Homeostasis;Impairment;In Vitro;in vivo;Inflammation;innovation;insight;interest;Invaded;Lead;Link;live cell imaging;long term consequences of COVID-19;Long-Term Effects;mechanotransduction;Membrane;Metformin;Molecular;mouse model;Mutant Strains Mice;novel;Organelles;Oxidation-Reduction;pharmacologic;Phosphorylation;Phosphotransferases;Physiological;Play;Post-Acute Sequelae of SARS-CoV-2 Infection;Proliferating;Protein Kinase;Proteins;Regulation;Renin-Angiotensin-Aldosterone System;Reporter;Research;Risk Factors;Role;SARS coronavirus;SARS-CoV-2 infection;SARS-CoV-2 spike protein;shear stress;Signal Transduction;spatiotemporal;Stimulus;Stress;Testing;tool;Up-Regulation;upstream kinase;Vascular Endothelial Cell;Vascular Endothelium;Vasodilation;Viral;Virus

PROJECT_TITLE: AMPK Regulation of ACE2 in Endothelial Health and Disease


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Heart Disease

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: NARRATIVE The Cardiothoracic Surgical Trials Network has conducted several clinically important randomized trials in heart valve disease, coronary artery disease, and heart failure, and has observed clinical practice related to infections following heart surgery. It is now embarking on a new paradigm whereby a well-established primary program will affiliate with a center located in an area of exceptionally high cardiovascular disease burden, with large numbers of people with diabetes, high blood pressure, obesity, and strokes. Further, it intends to expand into the area of implementation research, where it will identify strategies to bring proven therapies to clinical practice, thereby improving the treatment of patients with cardiovascular disease.

PI_NAMEs: GILLINOV, ALAN MARC (contact);PARRINO, PATRICK E

PROGRAM_OFFICER_NAME: LIU, SONGTAO

PROJECT_TERMS: Academia;Adoption;American;Area;Blood Vessels;burden of illness;Cardiac;Cardiac Surgery procedures;Cardiac Volume;Cardiovascular Diseases;Cardiovascular Surgical Procedures;Certification;Chairperson;Clinic;Clinical;Clinical and Translational Science Awards;clinical center;clinical investigation;clinical practice;Clinical Research;clinical research site;Clinical Sciences;clinical trial enrollment;Clinical Trials;Communities;Competence;Computerized Medical Record;Contracts;Coronary Arteriosclerosis;Coupled;Data;Data Coordinating Center;Development;Diabetes Mellitus;Disease;Dissemination and Implementation;Doctor of Philosophy;Education;Educational Curriculum;experience;follow-up;Fostering;Foundations;Government;Grant;gulf coast;Head;Health;Health system;Heart;Heart Diseases;Heart failure;Heart Valve Diseases;Hospitals;Hurricane;Hypertension;implementation research;implementation science;improved;Industry;Infection;Infrastructure;innovation;Journals;Knowledge;Lead;Leadership;Learning Module;Link;Louisiana;Manuscripts;Marketing;member;Mentors;Mississippi;Modeling;Monitor;Nature;next generation;novel;Obesity;Ohio;Operative Surgical Procedures;Participant;participant enrollment;Patient Recruitments;patient retention;Patients;Performance;Persons;Positioning Attribute;Process;programs;protocol development;Publications;Qualifying;randomized trial;recruit;Research;Research Institute;Research Personnel;Residencies;Resources;retention rate;Role;Scientist;secondary analysis;Site;skills;social media;Statistical Methods;Stroke;success;Surgeon;Thoracic Surgical Procedures;Tin;Training;Translating;Translational Research;United States National Institutes of Health;Universities;virtual visit;web site;Writing

PROJECT_TITLE: Cardiothoracic Surgical Trials Network


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Data Science

ORG_CITY: BOSTON

ORG_DEPT: PATHOLOGY

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: PROJECT NARRATIVE Through research resources and services, education, and clinical and translational science research, Tufts Clinical and Translational Science Institute supports the entire spectrum of translation to help meet the promise and the public’s needs of biomedical science. This includes the translation of preclinical investigation (“T.5”), into bench research into bedside care (“T1”), into effective clinical practice (“T2”), into wide care delivery and public health (“T3”), and into health policy (“T4”). By doing this, we support clinical and translational science and research that will have impact on health and health equity.

PI_NAMEs: SELKER, HARRY P. (contact)

PROGRAM_OFFICER_NAME: CURE, PABLO

PROJECT_TERMS: Abbreviations;Address;Advisory Committees;Asian population;Belief;Biometry;care delivery;Caring;Center for Translational Science Activities;clinical center;clinical practice;clinical predictive model;Clinical Research;Clinical Sciences;Clinical Trials;Clinical Trials Data Monitoring Committees;cohort;Collaborations;Communication;Communities;COVID-19;Data;data modeling;Data Science;data warehouse;Development;Discipline;Disparity;Dissemination and Implementation;Education;Electronic Health Record;Elements;Environment;Epidemiology;Equity;Evaluation;Fast Healthcare Interoperability Resources;Fostering;Good Clinical Practice;Growth;Health;Health Alliance;health data;health equity;health equity promotion;Health Policy;Health system;improved;Informatics;innovation;insight;interoperability;Investigation;language processing;Leadership;Learning;Medical;Medical center;medical schools;Mentors;Mentorship;Methods;Nature;novel;Operations Research;Outcome;patient oriented;Population Heterogeneity;pre-clinical;Process;programs;Public Health;recruit;Research;Research Design;Research Ethics;Research Methodology;Resource Sharing;Resources;Role;Science;Services;skills;System;Technology;Training;Training and Education;translational pipeline;Translational Research;Translations;Trust;Universities;Vision;Work


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Genetics;Heart Disease;Human Genome;Neurosciences;Prevention;Sleep Research

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Excessive daytime sleepiness (EDS) is common and associated with cardiovascular diseases through heterogeneous mechanisms, and our recent studies suggest two subtypes of EDS-sleep propensity and sleep fragmentation. We will use sleep metrics and multi-omics data to understand the physiology and genetic basis of each subtype of EDS, and study their associations with CVD. This study will improve our understanding of the heterogeneity of EDS and inform future interventions for both EDS and CVD.

PI_NAMEs: WANG, HEMING  (contact)

PROGRAM_OFFICER_NAME: YARDEN, RONIT I

PROJECT_TERMS: actigraphy;Affect;Behavioral;biobank;Biological;brain tissue;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Classification;Clinical;clinical risk;cohort;Communities;comorbidity;Data;Data Reporting;design;Electroencephalography;Excessive Daytime Sleepiness;Future;gene environment interaction;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Predisposition to Disease;genetic variant;genome wide association study;genome-wide;genomic locus;Genomics;Goals;Health;Heterogeneity;Hispanic Community Health Study/Study of Latinos;Hypersomnolence;Idiopathic Hypersomnolence;improved;Individual;instrument;Intervention;Jackson Heart Study;Knowledge;Laboratory Research;Link;Longitudinal Studies;Measurement;Measures;men;Mendelian randomization;metabolomics;methylomics;Modification;Molecular;Morbidity - disease rate;mortality;Multi-Ethnic Study of Atherosclerosis;Multiomic Data;Narcolepsy;National Heart, Lung, and Blood Institute;neurophysiology;novel;osteoporosis with pathological fracture;Outcome;Pathway interactions;Patient Self-Report;Phenotype;Physiological;Physiology;Polysomnography;Population;population based;Population Heterogeneity;Population Study;Process;programs;Property;Proteomics;public health intervention;Questionnaires;Reporting;Resources;Risk;Risk Factors;risk stratification;Sampling;screening;secondary analysis;sex;Sleep;Sleep Architecture;Sleep Disorders;Sleep Fragmentations;Subgroup;Testing;trait;Trans-Omics for Precision Medicine;transcriptomics;Variant;Women's Health;Work

PROJECT_TITLE: Dissecting heterogeneity of excessive daytime sleepiness and impact on cardiovascular diseases

STUDY_SECTION: CHSA

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


PHR: Project Narrative This application seeks to develop chimeric antigen receptor (CAR) T regulatory cell-based strategies for therapeutic targeting and immunomodulation of pancreatic islets and antigen presenting cells, particularly in expanding our understanding of how Treg from T1D individuals might be different from normal and what strategies might be used to make Treg more effective. Successful completion of studies here could lead to strategies to deliver targeted immunosuppressive agents to prevent type 1 (T1D) in high risk patients, to suppress autoimmunity and preserve β-cell mass in patients with recent-onset T1D, and to deliver therapeutics to the pancreas for β-cell protection, functional enhancement or regeneration in established T1D. The islet- targeting and APC-targeting approaches developed through this proposal could rapidly become a scientific foundation for clinical trials in T1D.

PI_NAMEs: MEYER, EVERETT  (contact)

PROJECT_TERMS: Adult;allograft rejection;Antigen Targeting;Antigen-Presenting Cells;Antigens;Apoptosis;Area;Autoantigens;autoimmune pathogenesis;Autoimmunity;Autologous;B-Lymphocytes;Beta Cell;biobank;biological adaptation to stress;Biology;cancer cell;Cell Death;Cell Physiology;Cell surface;Cell Survival;Cell Therapy;cell type;Cells;cellular engineering;cellular targeting;Childhood;chimeric antigen receptor;Clinical;Clinical Trials;Cytoprotection;cytotoxic;Data;Defect;Development;Diagnosis;Disease;Effectiveness;Engineering;extracellular;FDA approved;Foundations;FOXP3 gene;Gene Expression;Gene Modified;Genes;Genetic Engineering;Goals;Health;Heparin Lyase;high risk;Homing;Human;IL2RA gene;Immune;Immune mediated destruction;Immune Tolerance;immunoengineering;Immunology;immunoregulation;Immunosuppression;Immunosuppressive Agents;Immunotherapy;improved;In Vitro;in vivo;Incidence;Individual;Inflammatory;Infusion procedures;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Investigation;islet;islet allograft;Islets of Langerhans;Malignant Neoplasms;Measures;Mediating;Metabolic stress;Methods;Modeling;monocyte;Mus;Myelogenous;Myeloid Cells;Natural regeneration;Newly Diagnosed;novel;novel therapeutics;overexpression;Pathogenicity;Patients;Performance;Phase;Phenotype;Population;Pre-Clinical Model;preservation;prevent;Protein Engineering;Regulatory T-Lymphocyte;Request for Proposals;Research Personnel;response;Signal Transduction;Signaling Molecule;Specificity;stress reduction;Structure of beta Cell of islet;Surface;Surface Antigens;System;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;therapeutic target;Xenograft procedure

PROJECT_TITLE: Engineered Immune Cells for T1D


NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Pediatric;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: HADLEY

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: NARRATIVE More than six million children in the U.S. have asthma, a chronic disease that disproportionately affects lower-income, urban and racial/ethnic minority populations. Accountable care organizations are designed to support interventions that address the social and medical complexity of childhood asthma in ways traditional healthcare models are not, but the effects of the accountable care ‘experiment’ on childhood asthma clinical care, outcomes, and disparities remain largely unknown.

PI_NAMEs: GOFF, SARAH L (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: Accountability;accountable care organization;Address;Adult;Affect;Age;Agonist;Asthma;Caring;Child;Childhood;Childhood Asthma;Chronic Disease;Classification;clinical care;Complex;Contracts;COVID-19 pandemic;Data;Databases;design;Development;Diabetes Mellitus;Disease;Disparity;Emergency department visit;Enrollment;Environmental Risk Factor;Equity;ethnic disparity;ethnic health disparity;ethnic minority population;Ethnic Origin;evidence base;Evidence based treatment;experience;experimental study;Exposure to;Fee-for-Service Plans;follow-up;Health;health care model;health care quality;health inequalities;Healthcare;Healthy People 2020;high risk;high risk population;Home;Home environment;Hospitalization;hospitalization rates;Hospitals;Human Resources;improved;improved outcome;Incentives;Inequity;innovation;insurance plan;interest;Intervention;Interview;Investments;Knowledge;long-standing disparities;Low income;Massachusetts;Measures;Medicaid;Medical;Methods;Modeling;Morbidity - disease rate;Natural experiment;novel;Organizational Models;organizational structure;Outcome;outcome disparities;Outcome Measure;Outpatients;Ownership;Parents;Pattern;payment;Physicians;Policy Maker;Population;population health;Prevalence;programs;Provider;Quality Indicator;Quality of Care;Race;racial disparity;racial health disparity;racial minority population;Risk;Risk Adjustment;Risk Factors;scale up;Schools;Site Visit;social;social health determinants;Societal Factors;socioeconomic disparity;socioeconomics;Surveys;Taxonomy;Technology;Testing;Time;urban minority;Vulnerable Populations;Work

PROJECT_TITLE: The Effects of Accountable Care Organizations on Disparities in Childhood Asthma Care and Outcomes

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE The training goals for this mid-career mentoring award in patient-oriented research (POR) will focus on improving the quantity and quality of mentoring provided by Dr. Branski and increase his expertise in POR related to movement disorders affecting the upper aerodigestive tract.

PI_NAMEs: BRANSKI, RYAN COMFORT (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Acoustics;Acute;Address;Aerodigestive Tract;Affect;Aftercare;Age;Anatomy;Auditory;Award;Behavioral;Bolus Infusion;botulinum neurotoxin injection;Botulinum Toxins;career;career development;Classification;Clinical;Clinical assessments;clinical phenotype;Clinical Sciences;Communication;Communication impairment;Complex;Data;Deglutition;Deglutition Disorders;Dimensions;disability;Discipline;Disease;Dystonia;Essential Tremor;Exclusion;experience;Faculty;Family;feeding;Functional disorder;Funding;Goals;Health;Human;improved;insight;kinematics;Laboratories;Limb structure;Limb Tremors;Location;Measures;Medical;medical schools;Mentors;Mentorship;Midcareer Investigator Award in Patient-Oriented Research;Mission;Movement Disorders;multidisciplinary;National Institute on Deafness and Other Communication Disorders;Neurologic;Nomenclature;Operative Surgical Procedures;Oral;Oropharyngeal;Outcome;Parkinsonian Disorders;Patient Care;patient oriented research;patient population;Patient Self-Report;Patients;Persons;pharmacologic;Pharmacological Treatment;Pharyngeal structure;Phenotype;Population;Positioning Attribute;Postdoctoral Fellow;Primidone;Process;programs;Propranolol;Publications;Recording of previous events;Refractory;Research;Research Personnel;Severities;skills;Standardization;Structure;Students;Systemic Therapy;Therapeutic;Training;translational impact;Translational Research;treatment effect;Tremor;Update;Upper Extremity;Variant;Voice;Work

PROJECT_TITLE: Midcareer Investigator Award in Patient-Oriented Research for Dr. Ryan Branski

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


PHR: Chemokine receptors CXCR4 and ACKR3 play critical roles in cell migration during immune responses, organ development and homing of hematopoietic stem cells, through coordinated responses to a shared ligand, the chemoattractant CXCL12. Although they are promising drug targets, the structural mechanisms underlying their individual functions and their cellular crosstalk is poorly understood. The proposed studies will reveal general principles of CXCR4 and ACKR3 activation, inhibition, and functional interplay, which will inform strategies for the development of single or combination CXCR4/ACKR3 therapies.

PI_NAMEs: HANDEL, TRACY M (contact);KUFAREVA, IRINA

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Acceleration;Affect;Agonist;AMD3100;antagonist;Architecture;Autoimmune Diseases;beta-arrestin;Binding;Biochemical;Biological Assay;Biotinylation;Bone Marrow Stem Cell Transplantation;cell motility;Cells;chemokine;chemokine receptor;Chemotactic Factors;Clinical Research;complement C2a;Complex;Coupled;Coupling;Cryoelectron Microscopy;Crystallography;CXCR4 gene;CXCR4 Receptors;Development;Disease;Down-Regulation;drug discovery;Drug Targeting;Environment;experimental study;extracellular;FDA approved;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;Hematological Disease;Hematopoietic stem cells;Heterodimerization;Homing;idiopathic pulmonary fibrosis;Immune response;Immunologic Surveillance;improved;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;insight;Investigation;Knowledge;Letters;Ligands;Lymphocyte;Maps;Mass Spectrum Analysis;Mediating;migration;Modeling;Modification;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;Multiple Sclerosis;Mutagenesis;Nature;novel;organ growth;Pattern;Pharmacology;Play;preclinical study;Preparation;prevent;Property;Proteomics;receptor;Receptor Inhibition;Regulation;Resolution;response;Rest;Rheumatoid Arthritis;Roentgen Rays;Role;Signal Transduction;small molecule;small molecule therapeutics;spatiotemporal;Stromal Cell-Derived Factor 1;Structure;targeted treatment;Techniques;Therapeutic;therapeutic target;trafficking;Translating;uptake;Work;X-Ray Crystallography

PROJECT_TITLE: It's a tug of war: structure, consequences, and inhibition of CXCR4 and ACKR3 responses to lymphocyte chemoattractant CXCL12

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Colorectal Cancer;Digestive Diseases;Inflammatory Bowel Disease

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF ARIZONA

PHR: These studies will firmly establish a role for the sphingolipid enzyme acid ceramidase (AC) in colitis and colitis associated cancer (CAC), advance novel mechanisms by which AC regulates colitis and CAC, and advance AC as a therapeutic target for disease opening the door for future clinical studies.

PI_NAMEs: SNIDER, ASHLEY JONES (contact)

PROGRAM_OFFICER_NAME: GREENWEL, PATRICIA

PROJECT_TERMS: Acute;Anti-Inflammatory Agents;Apoptosis;Attenuated;Azoxymethane;Biological;Bone Marrow;cell motility;Cells;Ceramidase;Ceramides;chemically induced colitis;chemokine;Chronic;Circulation;Clinical;Clinical Research;Colitis;colitis associated cancer;Colon;Colon Carcinoma;Colonic inflammation;Complex;conditional knockout;cytokine;Data;design;Development;dextran sulfate sodium induced colitis;Disease;Enzymes;Epithelial Cells;Epithelium;Future;galactosylgalactosylglucosylceramidase;Goals;Human;Immune;immune cell infiltrate;immunoregulation;in vivo;Incidence;Inflammation;Inflammatory;Inflammatory Infiltrate;Inflammatory Response;inhibitor;Interleukin-10;Knockout Mice;Laboratories;lipid metabolism;Lipids;Macrophage;Malignant Neoplasms;Mediating;Metabolism;Modality;Modeling;Molecular;mouse model;murine colitis;Mus;Myelogenous;Myeloid Cells;new therapeutic target;novel;novel therapeutics;Pathology;Pathway interactions;pharmacokinetics and pharmacodynamics;pharmacologic;physiologic model;Play;Publishing;Rag1 Mouse;recruit;response;Role;Sodium Dextran Sulfate;Sphingolipids;Sphingosine;sphingosine 1-phosphate;Spontaneous colitis;Stimulus;targeted treatment;Testing;Therapeutic;therapeutic development;therapeutic target;Tissues;Translating;Treatment-Related Cancer;tumor;tumorigenesis;Work

PROJECT_TITLE: Role for myeloid acid ceramidase in colon inflammation and cancer

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ORG_CITY: GAINESVILLE

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Program Director/Principal Investigator : Guirgis, Faheem Wagid Lipids and lipoproteins (cholesterol and lipid metabolites) are present in sepsis and are highly biologically active regulators of inflammation, but currently the changes in lipid and lipoprotein homeostasis during sepsis are not well understood. This project will investigate the changes in lipid and lipoprotein function, oxidation, metabolites, and changes in gene expression to further our understanding of dysregulated lipid and lipoprotein metabolism in sepsis. We will analyze a bank of samples and make associations with important clinical outcomes (early death, chronic critical illness and sepsis recidivism) as supported by our published work, and will confirm our findings in a small prospective cohort of sepsis patients. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

PI_NAMEs: GUIRGIS, FAHEEM W (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Anti-Inflammatory Agents;Antioxidants;Apolipoproteins;Arylesterase;Bacterial Toxins;biobank;Biological;Cessation of life;Cholesterol;Chronic;Clinical;cohort;cost;Critical Illness;cytokine;Data;Disease;Drops;Electrospray Ionization;Endothelial Cells;Enrollment;Enzymes;evidence base;Exhibits;Failure;Fatty Acids;Foundations;Functional disorder;Gene Expression;Genes;Genomics;Grant;HDL(3) Cholesterol;Heterogeneity;High Density Lipoproteins;Homeostasis;Hospitals;Impairment;improved;Infection;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Investigation;Knowledge;Laboratories;LDL Cholesterol Lipoproteins;Leukocytes;Leukotrienes;lipid mediator;lipid metabolism;lipidomics;Lipids;Lipoproteins;liquid chromatography mass spectrometry;Low Density Lipoprotein oxidation;Low-Density Lipoproteins;Measures;Messenger RNA;Metabolic;Metabolism;Mission;monocyte;Morbidity - disease rate;mortality;National Institute of General Medical Sciences;neutrophil;novel;Organ;Organ failure;Outcome;outcome prediction;oxidation;Oxidative Stress;oxidized lipid;participant enrollment;Patient Readmission;Patient-Focused Outcomes;Patients;Pattern;Peripheral Blood Mononuclear Cell;Peroxidases;Physical Function;Play;precision medicine;predictive signature;prevent;Principal Investigator;programs;prospective;Prospective cohort;Prospective, cohort study;Prostaglandins;Proteins;Publishing;Quality of life;recidivism;Recovery;Research Personnel;response;reverse cholesterol transport;Risk;RNA;Role;Sampling;Sepsis;septic patients;Severities;Steroids;Survivors;T-Lymphocyte;Testing;Time;Toxin;Up-Regulation;Validation;Whole Blood;Work

PROJECT_TITLE: The Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis

STUDY_SECTION: SAT

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