ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Child malnutrition has numerous devastating consequences, including impaired synthesis of bile acids (BAs), which help absorb dietary nutrients and regulate metabolism. The goal of this proposal is to understand how malnutrition suppresses BA synthesis. Results from these studies will help us develop new therapies to restore BA levels, improve outcomes of therapeutic feeding to treat malnutrition, and increase survival among children suffering from malnutrition.

PI_NAMEs: PREIDIS, GEOFFREY A (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: absorption;Acute;Address;Albumins;Amino Acids;Anorexia Nervosa;Bile Acid Biosynthesis Pathway;Bile Acids;Blood Coagulation Disorders;Blood Coagulation Factor;Cell Line;Cessation of life;Child;Child Malnutrition;Child Mortality;Cholesterol;Citric Acid Cycle;cofactor;Complement;CYP7A1 gene;Data;Dependence;Dependovirus;Diet;dietary;dietary control;Dietary Proteins;Enteral;enzyme biosynthesis;Enzymes;Exhibits;experimental study;Fat-Restricted Diet;Fat-Soluble Vitamin;Fatty acid glycerol esters;feeding;ferrochelatase;Functional disorder;Generations;Genes;Glucose;Goals;Growth;Health;Heme;heme biosynthesis;Hepatocyte;Homeostasis;Hydroxycholesterols;Impairment;improved outcome;Intestines;intraperitoneal;Iron;iron deficiency;knock-down;Label;Life;Link;Liver;Liver Dysfunction;Malabsorption Syndromes;Malnutrition;Mass Spectrum Analysis;Measures;Metabolic;Metabolism;mouse model;Mus;neurotensin mimic 1;novel;novel therapeutics;Nuclear;Nuclear Receptors;Nutrient;nutrient absorption;Nutritional;Outcome;overexpression;Pathology;Pathway interactions;postnatal;prevent;Process;Production;Protein-Restricted Diet;Proteins;protoporphyrin IX;Publishing;receptor;Receptor Activation;Refractory;Regimen;Reporting;Research;response;Role;Signal Transduction;Small for Gestational Age Infant;Small Interfering RNA;succinyl-coenzyme A;Sulfur;Supplementation;Testing;Therapeutic;therapy outcome;transcription factor;Transcriptional Regulation;Vitamin K;Weight Gain

PROJECT_TITLE: The metabolic basis for impaired bile acid synthesis in malnutrition

STUDY_SECTION: XNDA

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


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PI_NAMEs: JEAN-LOUIS, GIRARDIN  (contact)

PROJECT_TERMS: Aging;aging brain;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Award;Basic Science;Biological Markers;Biometry;Biostatistical Methods;career;career development;Clinical;Clinical Research;Clinical Sciences;Cognitive;college;Dementia;Development Plans;Diverse Workforce;Education;education research;Effectiveness;effectiveness measure;Engineering;Epidemiologic Methods;Epidemiology;experience;Funding;Future;Goals;graduate student;Health;Heterogeneity;Immunology;Incubators;Individual;Institution;Instruction;International;Intervention;Leadership;Massachusetts;Measurement;Medical Students;meetings;Mentors;Mentorship;Methods;Mission;multidisciplinary;Names;Neurodegenerative Disorders;Neurologist;Neurology;neuropathology;Neurosciences;next generation;normal aging;novel;Ophthalmology;outreach;Physicians;Population;population health;Positioning Attribute;post-doctoral training;prevent;Productivity;professor;programs;Psychiatrist;Psychiatry;Psychosocial Assessment and Care;Public Health;Qualifying;Recording of previous events;Records;recruit;Research;Research Methodology;Research Personnel;Research Training;Resources;responsible research conduct;Role;Rotation;Scholars Program;Scientist;skills;Statistical Methods;Students;summer institute;Training;Training Programs;Translational Research;Travel;undergraduate research experience;undergraduate student;United States National Institutes of Health;Work

PROJECT_TITLE: Research Education Component


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Cognitive deficits are the main cause of disability in schizophrenia. Here we will study how specific patterns of rhythmic electrical activity in the brain contribute to aspects of cognition that are impaired in schizophrenia. This will aid in the development of new treatments for cognitive deficits.

PI_NAMEs: SOHAL, VIKAAS SINGH (contact)

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Behavior;Behavioral;behavioral outcome;Brain;Brain region;cell type;Code;Cognitive deficits;cognitive function;cognitive task;combinatorial;Communication;Computer Models;Corpus striatum structure;Cues;Development;disability;Environment;Food;Frequencies;Heart;Impaired cognition;Impairment;information processing;Inherited;inhibitory neuron;Interneurons;Laboratories;Learning;Left;Measurement;Measures;Medial;Mediating;Methods;Mus;network models;neural circuit;neural network;neuronal patterning;Neurons;novel;Odors;optogenetics;Organism;Output;Parvalbumins;Pattern;Periodicity;Phase;Play;Population Projection;Prefrontal Cortex;Process;Publishing;recruit;Rewards;Role;Schizophrenia;Signal Transduction;Specificity;Testing;Texture;Thalamic structure;transmission process;unpublished works;voltage

PROJECT_TITLE: How do parvalbumin interneuron-generated gamma oscillations organize prefrontal networks to promote behavioral adaptation?


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Diabetes;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Pediatric;Prevention

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: NARRATIVE By integrating epidemiology, epigenetics, and clinical sciences, we create new opportunity to assess cell-type specificity in the molecular control of inflammation and pediatric type 2 diabetes. This study applies specialized training in single-cell gene expression and bioinformatics to investigate single-cell molecular signatures that are found in youth with type 2 diabetes compared to healthy youth. Findings from this project will identify new markers of diabetes pathogenesis in childhood, a period in the life course whose aggressive deterioration of beta cells warrants targeted investigation to inform translational applications.

PI_NAMEs: STAIMEZ, LISA RACHEL (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: 21 year old;Adult;Advisory Committees;aged;Anti-Inflammatory Agents;Apoptosis;Artificial Intelligence;aspirate;ATAC-seq;Automobile Driving;Beta Cell;Bioinformatics;Biological Markers;Blood;Blood specimen;Cell Death;cell free DNA;cell type;Cells;Cessation of life;Childhood;Chromatin;Circulation;Classification;Clinical;Clinical Data;Clinical Research;Clinical Sciences;Complication;Cross-Sectional Studies;Data;Data Analyses;Deterioration;Development;Diabetes Mellitus;diabetes pathogenesis;Diabetic Nephropathy;Discipline;Disease;disorder control;disorder prevention;Distress;DNA Methylation;Epidemiology;Epigenetic Process;epigenetic regulation;epigenomics;experience;FOXP3 gene;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;Genetic Transcription;glycemic control;Grant;Helper-Inducer T-Lymphocyte;Immunophenotyping;improved;indexing;Individual;Inflammation;Inflammatory;Infrastructure;innovation;Insulin;Insulin Resistance;inter-individual variation;Investigation;islet;Laboratories;Leadership;Life Cycle Stages;Life Style Modification;Machine Learning;Malignant Neoplasms;Maps;Measurement;Measures;Mentors;Metabolic Diseases;Methods;Methylation;Molecular;Molecular Profiling;Molecular Target;multiple omics;Non-Insulin-Dependent Diabetes Mellitus;novel marker;Obesity;OGTT;Organ Transplantation;Parents;Participant;peripheral blood;Peripheral Nervous System Diseases;pharmacologic;Phenotype;Predisposition;prenatal testing;preservation;prevent;Prevention;recruit;Regulatory T-Lymphocyte;Reporting;Research;Research Personnel;Retinal Diseases;risk stratification;RNA;single cell ATAC-seq;single cell sequencing;single cell technology;Site;skills;sociodemographics;Source;Specificity;Structure of beta Cell of islet;success;Symptoms;systemic inflammatory response;T-Lymphocyte;Techniques;Testing;Time;Tissue-Specific Gene Expression;Training;transcription factor;transcriptome sequencing;transcriptomics;translational applications;Translations;United States National Institutes of Health;Visit;Youth

PROJECT_TITLE: Mapping Integrated Single-Cell Chromatin Accessibility with the Single-Cell Transcriptional Landscape in Pediatric Type 2 Diabetes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_DEPT: OTHER BASIC SCIENCES

PHR: THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES OVERALL NARRATIVE The HARC Center’s powerful “Systems-to-Structure” platform will uncover the mechanisms that allow HIV to inhibit host restriction factors, reveal the factors regulating HIV transcription and latency, and investigate virus- host evolution to identify new treatment strategies by targeting key cellular processes.

PI_NAMEs: KROGAN, NEVAN J (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;antagonist;Antibodies;APOCEC3G gene;arms race;Award;Biochemical;Biological Assay;Biological Sciences;career;career development;Carrier Proteins;CD4 Positive T Lymphocytes;Cell division;Cell Physiology;Cells;Chromatin;Chromatin Remodeling Factor;Collaborations;Communication;Complex;CRISPR screen;CRISPR/Cas technology;Cryoelectron Microscopy;Data;data integration;Dependence;Development;drug efficacy;Drug Targeting;Enabling Factors;Environment;Enzymes;equity, diversity, and inclusion;Event;Evolution;experience;flexibility;Fostering;Funding Opportunities;Gene Expression;Genetic;genetic regulatory protein;Genetic Transcription;genome-wide;Goals;Heterochromatin;HIV;HIV-1;HIV/AIDS;Human;Immune response;improved;Infection;innovation;Integration Host Factors;Interdisciplinary Study;Internships;Intervention;Knowledge;latent infection;Leadership;lectures;Macrophage;member;Membrane;Mentors;Mentorship;Messenger RNA;Methods;Modality;Modeling;Molecular;mRNA Export;Mutation;mutation screening;new technology;new therapeutic target;NF-kappa B;novel;novel therapeutic intervention;outreach;pathogen;Pathway interactions;Pharmaceutical Preparations;Point Mutation;preference;programs;protein complex;protein structure;Proteins;Proteomics;Regimen;Regulation;Research;Research Personnel;Research Project Grants;RNA Transport;Roentgen Rays;Role;Route;Scientist;screening;Series;Site;structural biology;structural determinants;Structure;symposium;System;Systems Biology;T-Lymphocyte;Techniques;Technology;Therapeutic;therapeutic development;therapeutic target;Training;training opportunity;transcription factor;Validation;vif Gene Products;Viral;Viral Genes;Viral Proteins;Virus;Virus Replication

PROJECT_TITLE: HARC: HIV accessory and regulatory complexes


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;AIDS prevention;Biological;Biological Sciences;Budgets;Collaborations;Communication;Communities;Complex;Dedications;Development;Educational workshop;Electronic Mail;Ensure;Environment;Equity;equity, diversity, and inclusion;Evaluation;Event;experience;Feedback;forging;Fostering;Future;Goals;Grant;HIV;HIV/AIDS;Human Resources;Infrastructure;insight;Institution;interest;International;Internships;Knowledge;Lead;Leadership;lectures;meetings;member;Mission;Monitor;National Institute of Allergy and Infectious Disease;new technology;next generation;outreach;podcast;programs;Reporting;Research;Research Personnel;Research Project Grants;Schedule;Scientist;Series;Sister;Site;structural biology;symposium;Systems Biology;therapeutic target;Underrepresented Minority;underrepresented minority student;underserved community;United States National Institutes of Health;web site

PROJECT_TITLE: Admin Core


PROJECT_TERMS: Acquired Immunodeficiency Syndrome;AIDS prevention;Area;Artificial Intelligence;Award;bioinformatics tool;Biological Sciences;Budgets;career;career development;Collaborations;Communities;community center;Complex;course development;Data;design;Development;Discipline;Education;Educational workshop;Eligibility Determination;Event;experience;Faculty;Fostering;Fred Hutchinson Cancer Research Center;Funding;Goals;Grant;high risk;HIV;HIV/AIDS;innovation;Institution;interest;Internships;Journals;Knowledge;Leadership;member;Mentors;mid-career faculty;Mission;next generation;North Carolina;Postdoctoral Fellow;programs;recruit;Research;research and development;Research Personnel;Research Project Grants;Research Support;San Francisco;Science;Scientist;senior faculty;Sister;structural biology;Students;summer internship;Systems Biology;Techniques;Training;Underrepresented Minority;Universities;Work

PROJECT_TITLE: Developmental Core


NIH_SPENDING_CATS: Biotechnology;Genetics;HIV/AIDS

PI_NAMEs: SWANEY, DANIELLE L (contact)

PROJECT_TERMS: Acetylation;Affinity Chromatography;Biological Assay;CD4 Positive T Lymphocytes;Cell Line;Cell model;Cells;Chromatin;Collaborations;Complex;Consequences of HIV;CRISPR/Cas technology;crosslink;Cryoelectron Microscopy;Data;Dependence;Deuterium;experimental study;flexibility;Gene Deletion;Genetic;Genetic Transcription;genome editing;Genomics;Goals;HIV;Hydrogen;In Vitro;Individual;innovation;Integration Host Factors;interest;Knock-out;Maps;Mass Spectrum Analysis;Measures;Membrane Proteins;Methodology;Modeling;mutant;novel;Phosphorylation;Point Mutation;Post-Translational Protein Processing;Process;protein complex;protein protein interaction;protein purification;protein structure;Protein-Protein Interaction Map;Proteins;Proteomics;Rest;RNA-Binding Proteins;Services;Signal Pathway;Solvents;stoichiometry;structural biology;Structural Models;Structure;Surface;System;Technology;technology platform;Tertiary Protein Structure;Ubiquitination;Viral;Viral Proteins;Virus;Work

PROJECT_TITLE: Core 1 Krogan


PI_NAMEs: DOUDNA, JENNIFER A (contact)

PROJECT_TERMS: Address;Affect;Affinity;Affinity Chromatography;CD4 Positive T Lymphocytes;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Collaborations;Communities;Complement;Complex;CRISPR interference;CRISPR screen;CRISPR-mediated transcriptional activation;CRISPR/Cas technology;Data;Dependence;DNA;Electroporation;Genes;Genetic;Genetic study;genetic variant;genome editing;genome-wide;genomic locus;Genomics;Goals;Guide RNA;HIV;HIV Infections;Human;Infection;innovation;Integration Host Factors;knock-down;Knock-in;Knock-out;Macromolecular Complexes;Macrophage;Maps;Mass Spectrum Analysis;Methods;Mission;mutation screening;novel;pathogen;Pathogenesis;Pathway interactions;Point Mutation;Property;protein complex;protein structure;Proteins;Proteomics;repaired;Research;Rest;Ribonucleoproteins;Role;Single-Stranded DNA;Site;Stretching;structural biology;T-Lymphocyte;Technology;Tertiary Protein Structure;Testing;Therapeutic;Time;Validation;Viral;Viral Proteins;Virus;Work

PROJECT_TITLE: Core 2


NIH_SPENDING_CATS: Bioengineering;Biotechnology;HIV/AIDS;Machine Learning and Artificial Intelligence

PI_NAMEs: CHENG, YIFAN  (contact)

PROJECT_TERMS: Address;Affinity;Antibodies;Bacteriophages;Binding;Biochemical;Biological Assay;Biology;CD4 Positive T Lymphocytes;Cell Extracts;Classification;Collaborations;Complex;convolutional neural network;crosslink;Cryoelectron Microscopy;cryogenics;Crystallography;Cysteine;Data;data integration;denoising;Dependence;design;Development;electron crystallography;Electrons;experimental study;flexibility;Genetic;Goals;graphene;HIV;HIV Antibodies;Human Cell Line;Image;image guided;Immunoglobulin Fragments;Immunosorbents;improved;innovation;Integration Host Factors;interest;Interferometry;Libraries;macromolecule;Methodology;Methods;Mining;Mission;Molecular Conformation;mutant;Network-based;novel;Oxides;particle;Property;protein complex;Protein Dynamics;protein structure;Proteomics;Recombinant Antibody;Recombinants;reconstitution;Research Personnel;Sampling;screening;Sorting;structural biology;Structural Models;Structure;Technology;technology development;tomography;Viral;Virus;virus host interaction;X-Ray Crystallography

PROJECT_TITLE: Core 3


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: DURHAM

ORG_DEPT: SURGERY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE We have recently identified the function of the adeno-associated virus (AAV) membrane-associated accessory protein (MAAP) as a novel viral egress factor that both promotes enhanced AAV secretion into the media during AAV production and increases the production of exosomes from MAAP-expressing cells. In this proposal, we aim to define the define the molecular mechanisms by which MAAP enhances AAV secretion and exosome production, and further engineer novel MAAP proteins to improve up on its endogenous functionalities. These studies not only have far reaching implications for AAV vectors by improving production processes and yield, but also, expand the exosome delivery technology platform.

PI_NAMEs: ASOKAN, ARAVIND  (contact)

PROGRAM_OFFICER_NAME: RUSSELL, LUISA MARIE

PROJECT_TERMS: adeno-associated viral vector;Adenoviruses;Adoption;arm;Biological Assay;Biology;Capsid;Cell Culture Techniques;Cell Fraction;Cell Line;Cell Physiology;Cell secretion;Cells;Chemicals;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;co-infection;Complement;Confocal Microscopy;cost;CRISPR-mediated transcriptional activation;Culture Media;Cytolysis;Data;Dependovirus;Detergents;Development;Disease;DNA Packaging;DNA Sequence;Dose;Electron Microscopy;Engineering;Ensure;Exclusion;exosome;experience;extracellular;extracellular vesicles;Family;Foundations;gene therapy;Genes;Genome;Goals;Harvest;Helper Viruses;Herpesviridae;high throughput screening;Human;improved;Integration Host Factors;Inverted Terminal Repeat;Kinetics;Knowledge;laboratory experiment;Life Cycle Stages;Ligation;Lytic;manufacture;manufacturing process;Maps;Mass Spectrum Analysis;Mediating;Membrane;Metabolic;Molecular;Molecular Virology;nanoparticle;nanopore;neuromuscular;novel;Open Reading Frames;Outcome;particle;Parvoviridae;Pathway interactions;Phylogenetic Analysis;Process;process improvement;process optimization;Production;Property;Protein Engineering;protein function;Proteins;Recombinant adeno-associated virus (rAAV);Recombinants;Risk;Role;Safety;scale up;Secretory Cell;Secretory Component;Serotyping;Signal Transduction;Single Stranded DNA Virus;stable cell line;Structural Models;Structural Protein;success;technology platform;Toxic effect;Treatment Efficacy;vector;Viral;Viral Genome;Viral Packaging;Virion;Virus Assembly;Work

PROJECT_TITLE: Engineering the biology of AAV secretion and production

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


PI_NAMEs: SALI, ANDREJ  (contact)

PROJECT_TERMS: Affinity Chromatography;Algorithms;Architecture;Biochemical;Bioinformatics;Biology;CD4 Positive T Lymphocytes;cell type;Complex;Computer software;CRISPR/Cas technology;crosslink;Cryoelectron Microscopy;Data;Data Analyses;data integration;Data Set;data tools;density;Deuterium;Development;flexibility;Genetic;Genetic Transcription;genome editing;genome-wide analysis;Goals;Heterogeneity;HIV;HIV Infections;HIV-1;Human;Hydrogen;improved;Individual;Integration Host Factors;Label;Lead;Maps;Mass Spectrum Analysis;Methods;Modeling;Molecular Conformation;multiple data types;mutation screening;network models;open source;particle;pathogen;Pathway interactions;Peptides;Post-Translational Protein Processing;protein complex;protein protein interaction;Proteins;Proteomics;Resolution;restraint;Services;Statistical Data Interpretation;structural biology;structural determinants;Structural Models;Structure;success;Systems Biology;tool;Viral;Visualization

PROJECT_TITLE: Core 4 Sali Echeverria


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

PI_NAMEs: GROSS, JOHN D (contact)

PROJECT_TERMS: 26S proteasome;Acquired Immunodeficiency Syndrome;Affect;antagonist;APOCEC3G gene;Architecture;arms race;Binding;Binding Proteins;Binding Sites;Biochemical;Biochemistry;Biological Assay;Biology;Birth;CD4 Positive T Lymphocytes;Cell Cycle Arrest;Cell Line;Cells;Cercocebus;Chromatin;Complementary DNA;Complex;CRISPR/Cas technology;cross-species transmission;Cryoelectron Microscopy;Cullin Proteins;Cytidine Deaminase;Data;Deaminase;dimer;Dimerization;Down-Regulation;Drug Design;Evolution;experimental study;Family;Family member;Genetic;genetic approach;Genetic Transcription;HIV;HIV Infections;HIV-1;Hominidae;Human;innovation;Integration Host Factors;Intercept;Knock-out;Length;Molecular;Molecular Conformation;molecular mass;Monkeys;multitask;Mutagenesis;mutation screening;novel;pandemic disease;Phosphoric Monoester Hydrolases;Polyubiquitination;prevent;Primates;Process;Protein Phosphatase 2A Regulatory Subunit PR53;Proteins;Proteomics;Proviruses;receptor;reconstruction;Resolution;Reverse Transcription;RNA;Route;Sampling;SIV;structural biology;Structure;System;Testing;Ubiquitin;Ubiquitin-mediated Proteolysis Pathway;ubiquitin-protein ligase;Ubiquitination;vif Gene Products;Viral;Viral Proteins;Virion;Virus;Virus Replication;Work

PROJECT_TITLE: Project 1


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: HOUSTON

ORG_DEPT: PATHOLOGY

ORG_STATE: TX

PHR: Project Narrative GATA2 is a transcription/pioneer factor critical for inducing prostate cancer androgen receptor (AR) expression/activation. This grant application will define the molecular mechanisms underlying how a COP1- GATA2 signaling axis works and how COP1 regulates AR signaling cascade and other regulatory systems to repress prostate cancer growth and therapy resistance.

PI_NAMEs: YANG, FENG  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: abiraterone;Address;Affect;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Applications Grants;Automobile Driving;Binding;Cancer Biology;cancer therapy;Castration;Cellular biology;Chemoresistance;chemotherapy;Clinic;Consensus;Data;Data Set;Development;Disease Progression;docetaxel;enzalutamide;GATA2 transcription factor;Genetic Transcription;Goals;Growth;Human;In Vitro;in vivo;inhibitor;inhibitor therapy;Investments;Link;Malignant neoplasm of prostate;Malignant Neoplasms;MAP Kinase Gene;MAPK4 gene;Mediating;Metastatic Prostate Cancer;Molecular;mutant;novel;novel therapeutic intervention;overexpression;patient derived xenograft model;Patients;Play;prostate cancer cell;protein degradation;Proteins;Proto-Oncogene Proteins c-akt;Receptor Activation;receptor expression;Receptor Signaling;Regulation;Repression;Resistance;RNA Splicing;Role;Signal Transduction;System;taxane;Testing;Therapeutic;therapeutic target;therapy resistant;Time;Tissues;tumor;tumor growth;ubiquitin-protein ligase;Ubiquitination;Variant;Work;Xenograft procedure

PROJECT_TITLE: COP1 REGULATION OF AR SIGNALING AND PROSTATE CANCER GROWTH AND THERAPY RESISTANCE

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


PI_NAMEs: FRANKEL, ALAN D (contact)

PROJECT_TERMS: Address;Architecture;Binding;Biochemical;Biological Assay;biophysical techniques;Carrier Proteins;CD4 Positive T Lymphocytes;Cell Line;Cell model;Cell Separation;Cells;Chromatin;Chromatin Remodeling Factor;Chronic;Clonal Expansion;Complex;CRISPR/Cas technology;Cryoelectron Microscopy;Development;dimer;Dimerization;Drug Targeting;Evolution;experimental study;Gene Expression;Genetic;genetic analysis;genetic regulatory protein;Genetic Transcription;genomic locus;Heterochromatin;Histones;HIV;HIV-1;HIV-2;HIV/AIDS;Individual;Infection;inhibitor;Integration Host Factors;integration site;Introns;latent HIV reservoir;latent infection;Link;lonely individuals;Lymphocyte;Macrophage;Maintenance;Messenger RNA;Modeling;Modification;Molecular;Molecular Conformation;monocyte;mRNA Export;mRNA Translation;mutant;mutation screening;NF-kappa B;NFKB Signaling Pathway;novel;Nuclear Export;Nuclear Pore Complex Proteins;Pathway interactions;Peptides;Phase;Play;Positive Transcriptional Elongation Factor B;Post-Translational Protein Processing;Process;promoter;Property;Protein Isoforms;Proteins;Proteomics;Provirus Integration;recruit;Regulation;Reporter;Reporting;Research Priority;Resolution;Response Elements;Rest;RNA;RNA Binding;RNA Splicing;RNA Transport;Role;Running;Shock;Signal Transduction;Site;SIV;Small Nuclear Ribonucleoproteins;stem;structural biology;Structure;synergism;tat Protein;Testing;Time;TRAF6 gene;Transcript;Transcription Elongation;transcription factor;Transcription Initiation;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;United States National Institutes of Health;Viral;Viral Genes;viral RNA;Virus;Virus Integration;Virus Replication;X-Ray Crystallography

PROJECT_TITLE: Project 2


PI_NAMEs: MARSON, ALEXANDER  (contact)

PROJECT_TERMS: arms race;Automobile Driving;Biology of HIV Infection;CD4 Positive T Lymphocytes;Cell Line;Cell model;Cell Separation;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;combinatorial;Complex;complex data;CRISPR interference;CRISPR library;CRISPR screen;CRISPR-mediated transcriptional activation;CRISPR/Cas technology;Cryoelectron Microscopy;Data;Data Set;Dependence;Evolution;flexibility;Genes;Genetic;genetic approach;genetic information;Genetic Screening;genome-wide;Goals;high throughput screening;HIV;HIV Infections;HIV-1;Human;human pathogen;human reference genome;Immune system;improved;in vivo;innovation;innovative technologies;insertion/deletion mutation;insight;Integration Host Factors;Knock-in;Knock-out;Libraries;Life Cycle Stages;Macrophage;Maps;Mass Spectrum Analysis;Membrane Proteins;Methods;Modeling;Molecular;Molecular Biology;mutant;Mutation;mutation screening;novel;Nucleic Acids;Outcome;pathogen;Pathogenesis;Phenotype;Point Mutation;Population;Positioning Attribute;Primates;protein complex;protein protein interaction;protein structure;Proteins;Proteomics;Publishing;Recording of previous events;repaired;Reporting;Research;Rest;Roentgen Rays;Role;screening;structural biology;structural determinants;Structure;System;T-Lymphocyte;Technology;therapeutic target;Time;Translating;Translations;transmission process;Viral;Viral Proteins;Virus;Virus Replication

PROJECT_TITLE: Project 3


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Eye Disease and Disorders of Vision;Genetics;Kidney Disease;Orphan Drug;Pancreatic Cancer;Precision Medicine;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Narrative This UO1 brings together a unique team of investigators in von Hippel-Lindau (VHL) mutant malignancies (e.g. clear cell Renal Cell Carcinoma (ccRCC)) to address key unanswered questions with high clinical impact. Despite the recent progress achieved by UO1 investigators and others, there remains an urgent unmet need for the development of novel combination therapeutic strategies and tissue-based biomarkers with which to optimize the clinical use of HIF2α inhibitors. The established pre-clinical and clinical research programs for the study of VHL/RCC at the NCI will continue to be a cornerstone of this renewal proposal.

PI_NAMEs: MCDERMOTT, DAVID  (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Address;Adrenal Gland Neoplasms;Advocate;Biological Markers;Brain Neoplasms;Clear cell renal cell carcinoma;Clinic;Clinical;clinical development;Clinical Research;Clinical Trials;co-clinical trial;Collaborations;Collection;Complex;Credentialing;Dana-Farber Cancer Institute;Databases;Development;Drug Targeting;Event;experience;Eye Neoplasms;Family;Future;gene product;Grant;hemangioblastoma;Hypoxia Inducible Factor;Immunocompetent;improved;in vivo;Industry;Inherited;inhibitor;Islet Cell Tumor;Kidney Neoplasms;Labyrinth;Malignant Neoplasms;meetings;mouse model;mutant;Mutate;new therapeutic target;novel;novel marker;novel therapeutic intervention;novel therapeutics;Outcome;Oxygen;pancreatic neoplasm;Pathway interactions;patient biomarkers;Patients;Pharmaceutical Preparations;pharmacodynamic biomarker;Phase I/II Clinical Trial;Pheochromocytoma;Pre-Clinical Model;pre-clinical research;precision medicine;predictive marker;programs;Regimen;Research Personnel;Resistance;resistance mechanism;Resources;response;Retinal Hemangioma;Sampling;Spinal Neoplasms;Therapeutic;Tissues;transcription factor;translational pipeline;Translational Research;tumor;tumor microenvironment;ubiquitin ligase;United States National Institutes of Health;Update;Vascular Endothelial Growth Factors;VHL gene;VHL mutation;Von Hippel-Lindau Syndrome;Work

PROJECT_TITLE: Developing a Translation Pipeline for VHL Mutant Malignancies

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-O (O1)]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Genetics;Orphan Drug;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Succinate dehydrogenase (SDH) deficient subtype of gastrointestinal stromal tumor (GIST) is (1) caused either by inherited genetic or sporadic epigenetic silencing of succinate dehydrogenase (SDH) genes; (2) characterized by variable biology that ranges from indolent growth to rapidly progressive, fatal disease; and (3) associated with limited treatment options. This proposed U01 project will (1) combine our existing National Succinate Dehydrogenase-deficient GIST Translational Research and Clinical Trial Consortium with unique NIH Clinical Center resources to evaluate the efficacy of a new combinatorial treatment strategy for SDH-deficient GIST patients; (2) create a centralized biobank of well-annotated SDH-deficient GISTs; (3) develop a network of research laboratories with novel complementary preclinical models of SDH-deficient GIST biology; and (4) develop new molecular tools to predict prognosis of SDH-deficient GIST. We anticipate that these aims will test the first efficacious combination therapy for SDH-deficient GIST, create a novel resource for researchers to improve our understanding of SDH-deficient GIST heterogeneity and biology, and molecularly define risk of disease progression/metastasis that can be used to immediately improve SDH-deficient GIST patient care and well-being.

PI_NAMEs: GLOD, JOHN WALTER;SICKLICK, JASON KEITH (contact)

PROJECT_TERMS: Address;Adolescent and Young Adult;Adult;Advocate;Agonist;Alkylating Agents;Apoptosis;avapritinib;Basic Science;Binding;biobank;Biological Assay;Biological Markers;Biology;Biopsy;Blood specimen;cancer type;Caregivers;Cell Survival;Cells;Cessation of life;Childhood;Citric Acid Cycle;Clinical;clinical center;Clinical Sciences;Clinical Trials;cohort;combinatorial;Combined Modality Therapy;Complex;Cultured Tumor Cells;cytotoxicity;Data;Data Set;Development;Disease;Disease Progression;disorder control;disorder risk;Disparate;DNA Double Strand Break;DNA Repair;DNA strand break;drug sensitivity;effective therapy;efficacy evaluation;efficacy testing;endoplasmic reticulum stress;Enrollment;epigenetic silencing;Exhibits;Extramural Activities;Family;Family member;FDA approved;Financial Support;Gastrointestinal Stromal Tumors;Generations;Genes;Genetic;Genetic Diseases;Genetic Transcription;Genomic approach;Germ-Line Mutation;Goals;Growth;Hereditary Paraganglioma;Heritability;Heterogeneity;homologous recombination;Hypermethylation;Image;Imatinib;improved;In Vitro;Indolent;Induction of Apoptosis;industry partner;Inherited;innovation;insight;Inter-tumoral heterogeneity;Laboratory Research;Lead;Life;loss of function mutation;Malignant Neoplasms;Medical;Medical Oncology;Metabolic;Modeling;Molecular;Multi-Institutional Clinical Trial;multiple omics;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;novel therapeutics;objective response rate;Outcome;Pathogenicity;Pathway interactions;patient advocacy group;Patient Care;Patients;Personal Satisfaction;Phase I/II Clinical Trial;Phase II Clinical Trials;phase II trial;Phenotype;pre-clinical;Pre-Clinical Model;Prediction of Response to Therapy;Prognosis;Prognostic Marker;prognostication;Progressive Disease;promoter;Pyruvate;receptor;Reporting;Research Personnel;Resected;Resources;response;Risk;Safety;spectroscopic imaging;Succinate Dehydrogenase;Succinates;Surgical Oncology;Syndrome;targeted treatment;temozolomide;Testing;Therapeutic;therapeutically effective;Tissues;TNF-related apoptosis-inducing ligand;TNFRSF10B gene;tool;transcriptomics;Translational Research;translational scientist;Treatment outcome;treatment strategy;tumor;Tumor Biology;tumor heterogeneity;Tumor Subtype;Tyrosine Kinase Inhibitor;United States National Institutes of Health;Validation;variant of unknown significance;Youth


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: OVERALL - NARRATIVE The Center for Environmental Exposures and Disease (CEED) at Rutgers University aims to address the environmental health concerns of NJ residents by centering efforts on the most affected communities within the state. We will accomplish this by engaging community members, organizations, and agencies as advisors and partners through all stages of research, providing critical investment and infrastructure for multidisciplinary collaborative research, and training the next generation of environmental health scientists.

PI_NAMEs: ZARBL, HELMUT  (contact)

PROGRAM_OFFICER_NAME: THOMPSON, CLAUDIA L

PROJECT_TERMS: Acceleration;Address;Affect;Area;Basic Science;career;Career Mobility;Center for Translational Science Activities;climate change;clinical practice;Collaborations;Communication;Communities;community advisory board;community engaged research;community engagement;Community Participation;community partners;community partnership;Competence;Core Facility;cost effective;Cyanotoxin;Data;data management;design;Discipline;Disease;Disparity;Education;empowerment;Ensure;Environmental and Occupational Exposure;environmental chemical;Environmental Exposure;Environmental Health;environmental justice;equity, diversity, and inclusion;evidence base;Exposure to;Fostering;Funding;Future;Grant;Hazardous Chemicals;Health;Health Policy;Home;implementation science;improved;Industrialization;Industry;Infrastructure;innovation;Intervention;Investments;K-Series Research Career Programs;Labor Unions;Lead;Linguistics;marginalized community;member;Mentors;multidisciplinary;Mycotoxins;Needs Assessment;New Jersey;next generation;novel;Patients;Pesticides;Pilot Projects;Policies;Policy Maker;Poly-fluoroalkyl substances;Population;preservation;Prevention strategy;programs;Public Health;Readiness;Recording of previous events;recruit;Regulation;Research;Research Design;Research Personnel;Research Support;Resources;Risk;Science;Scientist;Statutes and Laws;Strategic vision;stressor;superfund site;Technology;Training;Training Activity;translation to humans;translational model;translational pipeline;Translational Research;Translations;Universities;Vision;Work;Writing

PROJECT_TITLE: Rutgers Center for Environmental Exposure and Disease (CEED)

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LWJ-S (CP)]


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

PROJECT_TERMS: Address;Amplifiers;Area;Basic Science;built environment;career development;climate change;Collaborations;collaborative environment;Communication;Communities;community advisory board;community engaged research;community engagement;community partners;COVID-19 pandemic;Creativeness;data management;data sharing;Discipline;Disease;disorder prevention;efficacy evaluation;Emergency Situation;Endocrine Disruptors;Ensure;Environmental Exposure;Environmental Health;environmental health disparity;epigenomics;equity, diversity, and inclusion;Fostering;Funding;Goals;Grant;Health;health disparity;implementation science;improved;Infrastructure;innovation;Institution;Intervention;Investments;K-Series Research Career Programs;Medical;member;Mentors;Mentorship;metabolomics;microbiome research;Mission;Modeling;multidisciplinary;National Institute of Environmental Health Sciences;New Jersey;next generation;operation;Performance;Pilot Projects;Population;Populations at Risk;Postdoctoral Fellow;Prevention strategy;recruit;Research;Research Activity;Research Personnel;Research Support;Resource Allocation;Resources;Risk Assessment;Schools;Science;Scientist;Strategic vision;Structure;Students;Technology;Time;Toxicology;Training;Training Activity;Training Support;Translating;Translations;Universities;Writing

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Clinical Research;Prevention;Social Determinants of Health

PI_NAMEs: KIPEN, HOWARD M (contact)

PROJECT_TERMS: Acceleration;Address;Affect;Award;career;career development;Clinical and Translational Science Awards;clinical center;Clinical Research;Clinical Sciences;Clinical Trials;cohort;Collaborations;Collection;Communication;Communities;community engaged research;community engagement;community organizations;community partners;Consultations;Core Facility;cost effective;Data;Data Analyses;design;Disease;Disparity;E-learning;Educational workshop;Ensure;Environmental Exposure;Environmental Hazards;Environmental Health;Environmental Risk Factor;Epidemiology;Evaluation;evidence base;Exposure to;Goals;Grant;hazard;Health;Health Sciences;Health system;Healthcare;Human;implementation science;implementation strategy;improved;Individual;informatics tool;Infrastructure;innovation;Intervention;Intervention Studies;Investments;Laboratory Research;Leadership;member;Mentorship;Mission;Modality;multidisciplinary;National Center for Advancing Translational Sciences;National Institute of Environmental Health Sciences;New Jersey;next generation;novel;Observational epidemiology;Occupational Health;Participant;Patient Recruitments;Persons;Play;Population;Population Study;Program Development;Protocols documentation;Public Health;randomized trial;recruit;Research;Research Design;Research Personnel;Research Support;Resources;Risk;Sampling;Scientist;screening;Services;skills;Strategic vision;Structure;Surveys;System;Technology;Training;translational pipeline;Translational Research;United States National Institutes of Health;Universities;Wood material;Work

PROJECT_TITLE: Translational Research Support Core


NIH_SPENDING_CATS: Bioengineering;Climate-Related Exposures and Conditions;Clinical Research;Prevention;Social Determinants of Health

PI_NAMEs: CEDENO LAURENT, JOSE GUILLERMO  (contact)

PROJECT_TERMS: Address;Aerosols;Affect;Air;Amplifiers;analytical tool;Animal Model;Animals;Atmosphere;Behavioral;Biochemical;Biological;Carbon Dioxide;Cardiopulmonary;climate change;Clinical;clinical center;Cognitive;Communities;comorbidity;Complex;Core Facility;cost;Coupled;Data;Data Collection;design;Development;Diesel Exhaust;Disease;efficacy evaluation;Electronic cigarette;Ensure;Environmental and Occupational Exposure;Environmental Exposure;Environmental Health;Environmental Pollution;Environmental Risk Factor;Equipment;Evaluation;Exercise;experience;Experimental Designs;experimental study;exposed human population;Exposure to;Extramural Activities;extreme weather;field study;fine particles;Funding;Gases;Generations;Genetic;Goals;Grant;Health;high standard;Human;human model;Human Resources;Humidity;IACUC;Immunologics;Incineration;Individual;Infection;Inhalation Exposure;insight;Institutional Review Boards;instrument;instrumentation;interdisciplinary collaboration;Intervention;Investments;Laboratories;Link;Measurement;Mechanics;member;Metabolic;Monitor;nanoengineering;nanomaterials;nanoparticle;Nose;Occupational;Occupational Health;Outcome;Ozone;Participant;particle;Particulate;Pathogenesis;Performance;personal exposure monitor;Physical activity;Policies;pollutant;Population;Productivity;protocol development;Protocols documentation;Psychosocial Stress;Publications;recruit;Research;Research Personnel;Research Support;response;Rodent;Safety;Sample Size;screening;Smoke;Source;stressor;success;System;Technology;Temperature;Testing;Time;tool;toxicant;Training;Translational Research;transmission process;Treatment Efficacy;Validation;Vision;Wildfire;Work

PROJECT_TITLE: Human/Animal Exposure


NIH_SPENDING_CATS: Bioengineering;Prevention;Social Determinants of Health

PI_NAMEs: BUCKLEY, BRIAN T (contact)

PROJECT_TERMS: Ablation;Address;advanced analytics;air monitoring;air sampling;analytical method;analytical tool;Applications Grants;Biological;Biological Assay;Biological Markers;Blood;career;Chemicals;Collaborations;Communities;community engagement;community partners;Complement;Consultations;Core Facility;cost;Data Analyses;design;Detection;detection method;Development;Devices;Disasters;Disease;Doctor of Philosophy;Dust;Elements;Endocrine Disruptors;Environment;Environmental Exposure;Environmental Health;Environmental Pollutants;experience;Experimental Designs;Faculty;Goals;graduate student;Grant;Growth;Hair;Hazard Assessment;Health;Human;Individual;Inductively Coupled Plasma Mass Spectrometry;instrument;instrumentation;Interdisciplinary Study;interest;Laboratories;Lasers;Link;liquid chromatography mass spectrometry;Manuscripts;Mass Fragmentography;Mass Spectrum Analysis;Measurement;Measures;member;Metabolism;Metals;method development;Methodology;Methods;Molecular;Monitor;National Institute of Environmental Health Sciences;Needles;New Jersey;novel;organic contaminant;Paper;Pathogenesis;Performance;Phase;Poly-fluoroalkyl substances;Postdoctoral Fellow;Preparation;Procedures;Publications;Publishing;quality assurance;Quality Control;Research;Research Personnel;Research Project Grants;Research Support;response;Role;Running;sample collection;Sampling;Science;Scientist;sensor;small molecule;Soil;Solid;Sputum;Students;Supervision;Technology;Therapeutic Agents;Time;Tissue Sample;Tooth structure;toxicant;Training;Translational Research;Translations;undergraduate student;Urine;vapor;Volatilization;Water;Work;wristband

PROJECT_TITLE: Chemical Analysis & Detection


PI_NAMEs: LASKIN, DEBRA L (contact)

PROJECT_TERMS: Animal Model;Animals;Applications Grants;Basic Science;Bioenergetics;Biological;career;Cell Culture Techniques;Cell model;Cells;Chemicals;Clinical;Clinical Investigator;Clinical Sciences;Communities;Confocal Microscopy;Core Facility;Data;Data Analyses;Development;Disease;Educational workshop;Electronic Mail;Ensure;Environmental Exposure;Environmental Health;Environmental Pollutants;environmental stressor;Equipment;Experimental Designs;Exposure to;Faculty;Faculty Recruitment;Fees;Flow Cytometry;Fluorescence;Future;Genus Hippocampus;Grant;Health Promotion;Human;human model;Image;imaging system;improved;Injury;Institution;Instruction;instrument;instrumentation;K-Series Research Career Programs;Link;marginalization;Measurement;Measures;Metabolism;Metals;nanoparticle;New Jersey;new technology;Oxidative Stress;Participant;particle;Particulate Matter;Pathogenesis;Pharmaceutical Preparations;Phenotype;Pilot Projects;Population;Preparation;procedure safety;Procedures;protein expression;Protocols documentation;Publications;Research;Research Personnel;Research Project Grants;Research Support;response;Rodent;sample collection;Sampling;Scientist;Services;skills;Sorting;Specimen;Speed;Standardization;Structure;symposium;System;Technology;Tissue Model;Toxic effect;Toxic Environmental Substances;toxicant;Training;training opportunity;translational pipeline;Translational Research;United States National Institutes of Health;Universities;virtual;Vision;webinar;Western Blotting;Work;Writing

PROJECT_TITLE: Biological/Environmental Indicators & Responses


NIH_SPENDING_CATS: Bioengineering;Climate-Related Exposures and Conditions;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Social Determinants of Health

PI_NAMEs: GEORGOPOULOS, PANOS G. (contact)

PROJECT_TERMS: Accounting;Address;Air;Behavior;Biological;Biological Models;Biological Process;Cellular biology;Chemicals;Climate;climate change;Collaborations;Communities;community burden;community engagement;community organizations;community partners;community partnership;Complement;Complex;Computational Biology;computational chemistry;computer framework;Computer Models;Computer Simulation;Computer software;computerized tools;Core Facility;COVID-19;Data;Data Analytics;Data Science;Data Storage and Retrieval;Databases;Development;Diagnostic;Disease;Disease Outcome;Dose;Economic Conditions;Education;Environmental Exposure;Environmental Health;Environmental Risk Factor;environmental stressor;epigenomics;Event;explainable machine learning;exposed human population;Exposure to;field study;Genomics;Geography;Goals;Grant;Health;heterogenous data;Hybrids;Individual;Informatics;informatics tool;Inhalation;Integration Host Factors;Intervention;investigator training;Justice;Knowledge;Laboratory Study;Life Style;Link;Lung;machine learning method;mathematical model;member;metabolomics;Metagenomics;Methods;microbiome;Mining;Modeling;models and simulation;Molecular;multi-scale modeling;nanomaterials;nanoparticle;New Jersey;novel;Organ;Organism;Outcome;Oxidative Stress;Ozone;Pathogenesis;Pattern Recognition;Physiology;Policy Maker;Poly-fluoroalkyl substances;Population;Populations at Risk;Postdoctoral Fellow;posters;Prevention;Probability;Process;prognostic;Proteomics;Public Policy;Publications;Regulation;remediation;Research;research facility;Research Personnel;Research Project Grants;Research Support;response;Risk;Science;screening;Services;simulation;social factors;socioeconomics;Software Tools;Source;spatiotemporal;support tools;symposium;System;Technology;Tissues;tool;Toxic effect;Toxicant exposure;Toxicokinetics;Toxicology;Training;transcriptomics;Translating;Universities;Work;Xenobiotics

PROJECT_TITLE: Modeling Environmental Exposures & Disease


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Social Determinants of Health

PI_NAMEs: LAUMBACH, ROBERT JOHN (contact)

PROJECT_TERMS: Address;Advocate;Affect;air monitoring;Applications Grants;Benchmarking;climate change;climate impact;Communication;Communities;community advisory board;community building;community burden;community center;community engaged research;community engagement;Community Health;community organizations;Community Participation;community partners;community science;Consultations;Core Facility;Data Collection;data dashboard;Development;digital communication;Disease;drinking water;Educational workshop;Environmental Exposure;Environmental Health;environmental justice;Equity;evidence base;Evidence based intervention;exposure reduction interventions;Face;Feedback;Future;Goals;Grant;Grant Review;Health;health communication;health knowledge;Health Professional;implementation science;improved;Individual;interest;Interview;Justice;Knowledge;Leadership;Learning;Maps;meetings;member;Methods;Mission;Multimedia;Multiple Partners;New Jersey;next generation;novel strategies;people of color;Persons;Pilot Projects;Play;Policies;Policy Maker;Population;Printing;Productivity;programs;Public Health;Reduce health disparities;Regulation;Relationship-Building;Research;Research Activity;Research Personnel;Research Project Grants;Research Support;Resources;Risk;Risk Assessment;Risk Reduction;Role;Science;Scientist;skills;smartphone application;Strategic vision;symposium;traffic-related air pollution;Training;Training Activity;Translating;Translational Research;Translations;Vision;Water Pollutants;Work;working group;Writing

PROJECT_TITLE: Community Engagement Core & Science Communication


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Microbiome;Nutrition

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narra+ve The overarching goal of this proposal is to extend our on-going study to improve our understanding of how typical an9bio9c courses given to healthy young adults aﬀect their microbiome, metabolism, and immunity. Another important aspect of our proposal is to iden9fy the primary eﬀects of the an9bio9cs on par9cular microbial taxa and their metabolic pathways, and their secondary eﬀects on host metabolism and immunity.

PI_NAMEs: BLASER, MARTIN J (contact);HOLLAND, STEVEN M

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: absorption;Acute;adaptive immunity;Address;Adult;Affect;Aftercare;Amoxicillin;Animal Model;Antibiotic Therapy;Antibiotics;Azithromycin;beta-Lactams;Biological;Biological Assay;Blood;Blood Circulation;Carbohydrates;Circadian Rhythms;Clinical;clinical center;Clinical Medicine;clinically significant;Cognitive;Communities;Complex;Conduct Clinical Trials;Control Groups;COVID-19;Data;Data Analyses;Development;Diet;Diffuse;Disincentive;Electrocardiogram;Energy Metabolism;Enrollment;Evaluation;Exposure to;Extramural Activities;Fatty acid glycerol esters;Functional disorder;fungus;Gene Expression;Genes;Genetic Transcription;Goals;Health;healthy volunteer;High-Throughput Nucleotide Sequencing;Hormonal;Hour;Human;Human Microbiome;Immune;Immunity;Immunologic Markers;Immunologics;Immunology;improved;Informatics;insight;Interruption;Intramural Research Program;Leukocytes;Link;Macrolides;Measurable;Measures;Metabolic;Metabolic Marker;Metabolic Pathway;Metabolism;Metadata;metagenome;Metagenomics;microbial;microbiome;microbiome alteration;microbiome analysis;microbiota;Modeling;multiple omics;National Institute of Allergy and Infectious Disease;Natural Immunity;Nature;Oral;Outpatients;oxidation;pandemic disease;Participant;Perception;peripheral blood;pharmacologic;Physiology;Plasma;Population;Population Sizes;Procedures;programs;prospective;Radar;Random Allocation;randomized trial;randomized, clinical trials;recruit;Regimen;Research;Research Design;Research Personnel;Resistance;response;Rest;rRNA Genes;Sampling;Series;Serum Proteins;Shotgun Sequencing;side effect;Site;Skin Temperature;Sleep;Specimen;Taxonomy;Testing;Therapeutic;Time;Toxic effect;treatment group;United States;United States National Institutes of Health;Urine;Work;young adult

PROJECT_TITLE: Microbial, immune, metabolic perturbations by antibiotics (MIME study)


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetic Testing;Genetics;Human Genome;Infectious Diseases;Lung;Orphan Drug;Pediatric;Primary Immunodeficiencies;Rare Diseases;Transplantation

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Chronic suppurative respiratory tract disease is typically characterized by persistent and recurrent ear, sinus and bronchial infections and eventually bronchiectasis. Genetic causes include primary ciliary dyskinesia associated with abnormal airway clearance and inborn errors of immunity which can have very similar clinical presentations. The purpose of this application is to evaluate a stepwise process for identifying, diagnosing and managing these genetic diseases which can lead to increased possibilities for precision treatments and improved clinical outcomes.

PI_NAMEs: FREEMAN, ALEXANDRA ;OLIVIER, KENNETH N. (contact);SHAPIRO, ADAM

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: accurate diagnosis;Adult;Affect;American;Antibodies;Biological;Biological Products;Bronchiectasis;Bronchitis;Categories;Child;Chronic;chronic infection;Clinical;clinical center;clinical phenotype;Complement;congenital immunodeficiency;design;Diagnosis;Diagnostic;diagnostic value;Disease;disease diagnosis;Ear;Early Diagnosis;Evaluation;exome sequencing;experience;functional decline;Funding;gene correction;Gene Targeting;gene transplantation for gene therapy;Genes;Genetic;Genetic Diseases;genetic disorder diagnosis;genetic panel test;Genetic Predisposition to Disease;genetic variant;genome sequencing;Genotype;Hematopoietic Stem Cell Transplantation;Immune response;Immune System Diseases;Impairment;improved;Individual;Infection;Inflammation;Laboratories;Life;Mediating;medical specialties;Morbidity - disease rate;Mucociliary Clearance;National Institute of Allergy and Infectious Disease;North Carolina;novel therapeutics;Otitis Media;Outcome;participant enrollment;Pathogenicity;Pathway interactions;Patients;Persons;Phenotype;Precision therapeutics;Primary Ciliary Dyskinesias;Process;programs;Protocols documentation;Recurrence;recurrence prevention;recurrent infection;Resolution;Respiratory Disease;Respiratory System;Respiratory Tract Diseases;response;Signs and Symptoms;Sinus;Sinusitis;Site;Testing;Therapeutic;transplantation therapy;United States National Institutes of Health;Universities;Variant;whole genome

PROJECT_TITLE: Use of Tiered Genetic Sequencing and Specialty Referral for Identifying and Managing Rare Genetic Causes of Chronic Suppurative Respiratory Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-Z (O4)]


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: San Mateo

ORG_NAME: BIOAMP DIAGNOSTICS, INC.

PHR: PROJECT NARRATIVE Carbapenem-resistant organisms (CRO) are a major threat to public health worldwide, with organisms that render resistance to carbapenems through the production of degradative carbapenemase enzymes being associated with high mortality rates, as the treatment options available for them are limited. This Phase I SBIR proposal represents the first step in the development of a test – an antimicrobial susceptibility testing (AST) panel/plate with DETECT components integrated into the wells – that would be the first AST system compatible test capable of detecting carbapenemase production and classifying the enzymes present, alongside antimicrobial susceptibility. The all-in-one test would streamline existing clinical workflows, expedite care delivery to patients, and offer cost mitigation opportunities for healthcare centers by accelerating infection control de-escalation measures.

PI_NAMEs: JACKSON, NICOLE  (contact)

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Acceleration;Acinetobacter baumannii;Anti-microbial susceptibility;Antibiotic susceptibility;assay development;beta-Lactamase;beta-Lactams;Biochemical;Biological Assay;Boronic Acids;carbapenem resistance;carbapenemase;Carbapenems;care delivery;Cells;Classification;Clavulanic Acids;Clinical;Containment;cost;Cytolysis;Death Rate;design;Detection;Development;Diagnostic;Diagnostic tests;Edetic Acid;Enterobacteriaceae;Enzymes;Extended-spectrum β-lactamase;Family;Genes;Health;Health Care Costs;Healthcare;Human;Immunoassay;Incubated;Individual;Infection;Infection Control;information classification;inhibitor;interest;Kinetics;lead candidate;Measures;Mediating;Methods;Microbiology;Molecular;Molecular Structure;Multi-Drug Resistance;Organism;pathogenic bacteria;Patients;Phase;Phenotype;Plasmids;Predisposition;Probability;Production;Pseudomonas aeruginosa;Public Health;Reader;Reagent;Recombinants;Selection for Treatments;Signal Transduction;Small Business Innovation Research Grant;small molecule;small molecule libraries;standard measure;standard of care;Structure;success;Suspensions;System;Technology;Test Result;Testing;Time;transmission process;Treatment Failure;Validation;Variant

PROJECT_TITLE: Evolving the standard of care for carbapenem resistant infections, through the development of a phenotypic assay capable of DETECTing and classifying carbapenemases

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-F (14)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

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

ORG_CITY: RICHMOND

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative  This proposal is centered on the hypothesis that alcohol-induced hepatocyte injury induces biosynthesis of a group of atypical sphingolipids that promote protection and/or recovery from injury. A novel subunit of the serine palmitoyl transferase complex, Sptlc3, produces atypical sphingolipids, and we have found that its expression induces markers of autophagy which we hypothesize protect from ethanol-induced mitochondrial damage. We seek to pinpoint molecular mechanisms regulated by Sptlc3 and atypical sphingolipids, while testing the effect of Sptlc3 induction on pathways with therapeutic potential for alcoholic liver disease.

PI_NAMEs: COWART, LAUREN ASHLEY (contact);MONTEFUSCO, DAVID JOHN

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: addiction;Albumins;Alcohol consumption;alcohol exposure;alcohol response;Alcoholic liver damage;Alcoholic Liver Diseases;Alcohols;Anabolism;Area;Attenuated;Autophagocytosis;base;Beverages;Biochemical;Carbon;Cardiovascular Diseases;Cells;Ceramides;Cessation of life;Coenzyme A;cohort;Complex;constitutive expression;Data;Development;Dihydrosphingosine;Dimerization;Enzymes;Ethanol;Ethanol Metabolism;Eukaryota;Eukaryotic Cell;experimental study;Exploratory/Developmental Grant;feeding;Future;Generations;Genetic Transcription;Glycosphingolipids;Goals;Heavy Drinking;Hepatic;Hepatocyte;hepatocyte injury;In Vitro;in vivo;Injury;injury recovery;interest;Knockout Mice;Laboratories;Ligands;lipidomics;Lipids;Liver;Liver diseases;Liver Failure;liver injury;Logic;LoxP-flanked allele;Mediating;Metabolic Pathway;Metabolism;Methods;Mitochondria;Molecular;mortality;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear Receptors;Organ;Outcome;Palmitates;Palmitoyl Coenzyme A;Pathology;Pathway interactions;preference;prevent;Production;Property;Proteins;Public Health;Recovery;Regulation;Reporting;Research Project Grants;Respondent;Role;scaffold;Serine;serine palmitoyltransferase;Signal Pathway;Signal Transduction;Site;Sphingolipids;Sphingomyelins;sphingosine 1-phosphate;statistics;Surveys;Techniques;Testing;Therapeutic;Therapeutic Intervention;Tissues;tool;transcription factor;Transcription Factor 3;Transferase;Up-Regulation;Vertebral column

PROJECT_TITLE: Atypical sphingolipids in alcoholic liver disease

STUDY_SECTION: AA

STUDY_SECTION_NAME: Biomedical Research Study Section[AA-1]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: Project Narrative Heart failure is the inability of the heart to pump adequately to supply the body with sufficient oxygen to meet its needs, and heart failure is a leading cause of death in the United States, the veteran population included. Of the 50,000 individuals diagnosed with heart failure each year, 70% of these patients have heart failure due to a previous heart attack (myocardial infarction; MI). The main objective of this grant is to use a mouse MI model to understand how one of the white blood cell types, the neutrophil, influences scar formation by regulating the wound healing response, particularly the inflammatory and reparative components.

PI_NAMEs: LINDSEY, MERRY L. (contact)

PROJECT_TERMS: Affect;American;Anti-Inflammatory Agents;aptamer;Cathepsins;Cause of Death;Cell Physiology;cell type;Cells;Cicatrix;Congestive Heart Failure;Coupled;Data;Death Rate;Deposition;Development;Diagnosis;Discipline;Evaluation;Evolution;Extracellular Matrix;Fibrinogen;Fibroblasts;Fibronectins;Flow Cytometry;Funding;Galectin 3;Gelatinase B;Goals;Grant;Heart;Heart failure;Heterogeneity;In Vitro;in vitro Assay;Individual;Infarction;Infiltration;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;innovation;Interleukin-4;Intervention;Investigation;Knowledge;Left Ventricular Remodeling;Left ventricular structure;Leukocytes;Macrophage;Maps;Matrix Metalloproteinases;Mediator;military veteran;Modeling;Molecular;Monitor;Mus;Myocardial Infarction;necrotic tissue;neutrophil;new therapeutic target;novel;Outcome;Oxygen;Patients;Pattern;Peptide Hydrolases;Phase;Phenotype;prevent;Principal Component Analysis;Proteins;Proteomics;Publications;Publishing;Pump;repaired;Reporting;Resolution;response;Role;Testing;Therapeutic Intervention;thrombospondin 2;Time;Tissues;tool;United States;wound healing

PROJECT_TITLE: Neutrophil Polarization Following Myocardial Infarction


ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Viral infections have more severe chronic consequences in individuals exposed to cigarette smoke (CS) than those who are not. We show that excessive accumulation of MAVS aggregates in mice exposed to CS and influenza virus (Flu) contributes to increased lung pathology. This grant will determine the mechanism of CS- induced dysregulation of mitochondrial antiviral signaling (MAVS) during Flu and the role of PINK1 kinase in correcting this dysregulation. We will characterize the pathways leading to excessive MAVS signaling and the mechanisms by which PINK1 limits MAVS aggregation. The downstream effects of PINK1-MAVS interactions and the effects on pathological pulmonary outcomes will be studied. We will explore the therapeutic potential of PINK1 augmentation using genetic and pharmacological approaches. Lastly, we will study the MAVS aggregation pathway in patients with smoking exposure and viral infections. A clear understanding of MAVS- PINK1 interactions can provide a new target to limit Flu-mediated pathology in CS-related lung diseases.

PI_NAMEs: DELA CRUZ, CHARLES S (contact)

PROJECT_TERMS: Actins;Acute;Address;Adverse effects;aggregation pathway;Binding;Chronic;Chronic Obstructive Pulmonary Disease;cigarette smoke;cigarette smoke-induced;Disease;Event;exposure to cigarette smoke;Fibroblasts;fibrotic lung;Genetic;Grant;Growth Factor;Health;Homeostasis;improved;Individual;Inflammasome;Inflammation;Inflammatory;Influenza;influenzavirus;Injury;insight;Lung;lung injury;Macrophage;Mediating;Mitochondria;Mus;novel;null mutation;Outcome;Outer Mitochondrial Membrane;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phosphotransferases;Play;prion-like;Proliferating;PTEN gene;Pulmonary Fibrosis;pulmonary function decline;Pulmonary Inflammation;Pulmonary Pathology;Regulation;Reporting;response;response to injury;Role;Signal Transduction;Signaling Molecule;Smoke;smoke-induced lung disease;smoking exposure;Smooth Muscle;Stains;Stress Fibers;Therapeutic;Tissues;transcriptomics;Viral;Viral Respiratory Tract Infection;Virus;Virus Diseases;Zidovudine

PROJECT_TITLE: MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: The apolipoprotein E gene (APOE) is the strongest genetic risk factor for Alzheimer's disease (AD). This study aims to elucidate the effects of APOE RNA expression in AD. We have observed that not all APOE mRNA extend to their full length to produce the apoE protein. This anomaly may be caused by the presence of APOE's ε2/ε3/ε4 allele variants that alter RNA transcription through epigenetic mechanisms. We hypothesize that APOE full- length mRNA is the only functional RNA for producing apoE protein and that ε2/ε3/ε4 can differentially modulate production of functional APOE mRNA to modify AD risk. Our short-term goals are to establish an association between the expressions of APOE RNAs, ε2/ε3/ε4 alleles, and AD risk; decipher the molecular mechanisms that regulate APOE RNAs production. Our long-term goal is to understand the role of APOE expression in AD and to apply this knowledge to develop strategies for AD prevention and/or intervention.

PI_NAMEs: YU, CHANG-EN  (contact)

PROJECT_TERMS: Aging;aging population;Alleles;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease related dementia;Alzheimer's disease risk;Apolipoprotein E;Autopsy;Binding Proteins;Biogenesis;Biological;Biological Markers;Biological Process;bisulfite;Body Fluids;Brain;brain cell;cell type;Cells;Chemicals;chromatin modification;circular RNA;Complement;Complex;Consensus;Data;design;Development;DNA Methylation;Epigenetic Process;Etiology;Fluorescence-Activated Cell Sorting;Future;Gene Combinations;Gene Expression;Gene Expression Regulation;gene product;Genes;Genetic;genetic risk factor;Genetic Transcription;genetic variant;genome-wide;glucose metabolism;Goals;Healthcare Systems;Human;Human body;Human Cell Line;insight;Intervention;knock-down;Knowledge;Lead;Length;Lipids;Mainstreaming;Measurement;Measures;Messenger RNA;Methylation;Mitochondria;Modification;Molecular;mRNA Expression;Neuroglia;neuroinflammation;Neurons;neurotransmission;novel;Pathway interactions;Play;Post-Translational Protein Processing;premature;Prevention;Prevention strategy;Production;Protein Isoforms;Proteins;Publishing;pyrosequencing;Quantitative Reverse Transcriptase PCR;Reporter;Research;RNA;RNA Interference;Role;Site-Directed Mutagenesis;tool;Transcript;transcriptome;Untranslated RNA;Variant;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Redefining the Role of APOE RNA Transcripts in Alzheimer's Disease


NIH_SPENDING_CATS: Kidney Disease;Pediatric;Prevention

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Chronic kidney disease in adulthood originates in part from early life environmental exposures acting through critical windows of developmental susceptibility. Fundamental mechanistic nephrotoxicity information coupled with population-based risk assessment strategies are key to future interventions designed to prevent or treat later life chronic kidney disease. Together, the consortium will advance our understanding of the role of human- relevant metal mixtures in maladaptive kidney function using vertebrate and kidney organoid models and use experimental evidence to establish a population relevant whole-mixture risk assessment strategy applicable to diverse global populations.

PI_NAMEs: SANDERS, ALISON P (contact)

PROGRAM_OFFICER_NAME: CARLIN, DANIELLE J

PROJECT_TERMS: Address;Adolescent;Adult;adverse outcome;Affect;Age;Apoptotic;Arsenic;Benchmarking;Bioenergetics;Biological Assay;Biological Monitoring;Biomedical Engineering;Biometry;Cadmium;Cells;Chemicals;Child;Childhood;Chronic Kidney Failure;Clinical;cohort;Coupled;Data;Development;Developmental Biology;Diabetes Mellitus;Disease;Dose;Early identification;early life exposure;Environment;Environmental Exposure;epidemiologic data;Epidemiology;Ethics;Etiology;Event;Exposure to;Face;Female of child bearing age;Functional disorder;Future;Genes;glomerular function;Health;Health protection;Histology;Human;Hypertension;improved;in utero;In Vitro;in vivo;in vivo Model;indexing;innovation;Ions;Kidney;Kidney Diseases;kidney dysfunction;Label;late life;Lead;Life;Life Cycle Stages;Link;Measures;Mediating;Mercury;Metals;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;Morphology;Mus;nephrogenesis;Nephrons;nephrotoxicity;Obesity;Organoids;Outcome;oxidative damage;Oxidative Stress;Pathway interactions;Pattern;Perinatal;Physiological;Physiology;Population;population based;population health;Population Heterogeneity;Population Research;Population Study;Populations at Risk;postnatal;predicting response;Predisposition;Pregnancy;prenatal;prenatal exposure;Prevalence;prevent;Process;Public Health;Regulation;Renal Blood Flow;Renal function;Reporting;reproductive;Research;response;Risk;Risk Assessment;Risk Factors;Role;Second Pregnancy Trimester;therapy design;Third Pregnancy Trimester;Time;tool;Toxic effect;toxicant;Toxicant exposure;Tubular formation;United States National Institutes of Health;urinary;Woman;Zebrafish

PROJECT_TITLE: Metal mixture effects on mitochondrial dysfunction in kidney development and maturation: Towards a whole mixture risk assessment


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Social Determinants of Health;Violence Research

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE There is increasing evidence that men who have sex with men (MSM) experience dual epidemics of HIV and intimate partner violence (IPV), yet understanding of the synergies between these two epidemics is underdeveloped. The proposed 24 month cohort study examines associations between the experience and perpetration of IPV and bio-markers of engagement in clinical HIV care among a large diverse sample of men living with HIV.

PI_NAMEs: KAHLE, ERIN M (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: access restrictions;Address;Adherence;Affect;Alberta province;Alcohol consumption;Behavior Control;behavioral response;biological adaptation to stress;Biological Markers;Bisexual;Canada;Caring;Clinic;Clinical;clinical care;clinically relevant;cohort;Cohort Studies;comparative;condoms;Coupled;Couples;Cross-Sectional Studies;Data;design;Emotional;Epidemic;experience;Female;Frequencies;Gays;gender behavior;health care availability;Heterosexuals;HIV;HIV diagnosis;HIV Seropositivity;Hospitalization;inattention;innovation;Interruption;Intervention;intimate partner violence;Knowledge;Link;male;Measures;Mediating;Mediation;men;men who have sex with men;Meta-Analysis;Methodology;Methods;minority stress;minority stressor;Monitor;Participant;Pathway interactions;Patient Self-Report;Patients;perpetrators;Phase;population based;Prevalence;primary outcome;prospective;Psychosocial Factor;Recommendation;recruit;Reporting;Research;Research Activity;Research Design;resilience;Risk;Risk Behaviors;Role;Sample Size;Sampling;secondary outcome;Severities;sex;Sex Behavior;Sexual Partners;sexual violence;Shapes;social stigma;Social support;structural determinants;substance use;synergism;United States;Victimization;Violence;violence victimization;Viral;Viral Load result;Virginia;Woman;Work

PROJECT_TITLE: Violence and viral suppression among men living with HIV


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Biotechnology;Brain Disorders;Genetics;Human Genome;Patient Safety;Precision Medicine;Rehabilitation;Substance Misuse

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Narrative The goal of this project is to identify genetic variants associated with risk for alcohol withdrawal syndrome (AWS) and response to benzodiazepine treatment in alcohol use disorders (AUD), including sex-specific genetic effects in a large sample of subjects with AUD. Discovery of genetic variants promoting development of AWS will provide tools for the identification of at-risk patients, and selection of treatment options based on an understanding of inter-individual differences in sensitivity to this central component of AUD. This line of research may also contribute to the development of new AUD treatment approaches aimed to restore physiological dysfunctions associated with those genetic variants.

PI_NAMEs: BIERNACKA, JOANNA M;KARPYAK, VICTOR M. (contact)

PROGRAM_OFFICER_NAME: GITIK, MIRI

PROJECT_TERMS: addiction;Address;alcohol abuse therapy;Alcohol consumption;alcohol risk;alcohol use disorder;Alcohol withdrawal syndrome;Alcohols;Attention;Awareness;Benzodiazepines;Biomedical Research;Cessation of life;Clinical;Data;Development;disability;Dose;Drug Targeting;Female;Frequencies;Functional disorder;gamma-Aminobutyric Acid;Gender;Genes;Genetic;genetic analysis;Genetic Load;Genetic Markers;genetic variant;Genetic Variation;genome wide association study;genome-wide;Genomics;Glutamates;Goals;Heritability;improved;Individual Differences;insight;interest;Knowledge;male;Maps;Medical;men;Morbidity - disease rate;mortality;National Institute on Alcohol Abuse and Alcoholism;Neurobiology;Neurotransmitters;new therapeutic target;Pathway interactions;Patient Monitoring;Patients;Pharmaceutical Preparations;Pharmacogenomics;Phenotype;Physiological;Play;Policies;polygenic risk score;Prediction of Response to Therapy;predictive marker;Predisposition;Prevalence;Property;Protocols documentation;Publishing;Research;response;Risk;Risk Assessment;Risk Factors;Role;Sample Size;Sampling;Selection for Treatments;Severities;sex;Sex Differences;side effect;Substance Use Disorder;System;Testing;tool;tool development;trait;translational study;Treatment outcome;treatment response;United States;United States National Institutes of Health;Variant;Withdrawal;Woman

PROJECT_TITLE: Genomics of Alcohol Withdrawal and Treatment Response to Benzodiazepines

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Lung;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: Over 90% of breast cancer-related deaths are due to the metastatic relapse of tumors in distant vital organs such as lung and bone. Our proposed studies will provide novel insights into the poorly understood question of how a traditional cancer treatment approach, chemotherapy, triggers the wound healing responses in the lung microenvironment and subsequently fosters the metastatic relapse of breast cancer in the lung. The results from the proposed research will facilitate the development of novel strategies to prevent post-therapy metastases in breast cancer patients.

PI_NAMEs: REN, GUANGWEN  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Acceleration;acquired drug resistance;Animal Model;Biological Markers;Biological Models;Blood Vessels;bone;breast cancer metastasis;Breast Cancer Model;Breast Cancer Patient;breast cancer survival;Cancer Patient;cancer therapy;CD44 gene;Cell Proliferation;Cells;Cessation of life;Chemoresistance;chemotherapy;Cisplatin;Clinical;clinical application;clinical development;Combination Drug Therapy;cytokine;cytotoxicity;design;Development;Disease remission;Distant;Distant Metastasis;Doxorubicin;Drug resistance;Drug Utilization;Endothelial Cells;endothelial stem cell;Epithelium;experience;Failure;Fostering;Foundations;Gene Expression;Goals;Human;Immune response;improved;Inflammation;Injury;insight;Knowledge;Lung;lung metastatic;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Mediator;Mesenchymal;Mesenchymal Stem Cells;Metastatic Neoplasm to the Lung;Metastatic/Recurrent;Molecular;Mus;Myofibroblast;Natural regeneration;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Organ;osteopontin;Patient-derived xenograft models of breast cancer;Patients;Pharmaceutical Preparations;Pharmacotherapy;Plasma;Play;Population;pre-clinical;prevent;Proliferating;pulmonary function;Recurrence;Regenerative response;Relapse;repaired;Research;response;Role;Sampling;Signal Pathway;Specimen;stem cell model;Stromal Cells;Testing;Therapeutic;therapeutic target;therapeutically effective;therapy resistant;tissue injury;Tissues;TLR4 gene;translational potential;Treatment Efficacy;Treatment Failure;tumor;tumor growth;wound healing;Xenograft procedure

PROJECT_TITLE: The Role of Lung Resident Mesenchymal Stem Cells in Post-Chemotherapy Lung Metastases of Breast Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CLEVELAND

ORG_DEPT: NEUROSCIENCES

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative This study will establish basic cellular and molecular mechanisms underlying activity- dependent growth factor signaling at synapses. These pathways are evolutionarily conserved modulators of synapse structure and function, and pathway disruption is linked to devastating human brain disorders. By establishing how these pathways direct synapse function, this research will build an essential foundation for effective clinical approaches to treating neurodevelopmental and psychiatric disorders.

PI_NAMEs: BROIHIER, HEATHER  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Address;Adhesions;Adhesives;Architecture;autism spectrum disorder;autocrine;Biochemical;Bone Morphogenetic Proteins;Brain Diseases;Calcium Channel;Clinical;Coupling;Critical Pathways;Data;Defect;density;Development;Drosophila genus;extracellular;Extracellular Domain;Extracellular Matrix;Family;Foundations;Genetic study;Genetic Transcription;Glutamates;Growth Factor;Human;Impairment;in vivo;Individual;innovation;insight;Integral Membrane Protein;interest;Light;Link;Maintenance;Membrane;Mental disorders;Molecular;Motor;mutant;Mutation;Nervous System;Neurodevelopmental Disorder;Neurons;neurotransmission;Neurotransmitter Receptor;neurotransmitter release;Neurotransmitters;Nociception;novel;Pathway interactions;Phenotype;Positioning Attribute;postsynaptic;presynaptic;protein degradation;Proteins;Publishing;Regulation;Research;restraint;Role;Sensory;Side;Signal Pathway;Signal Transduction;Signaling Protein;Site;Structure;Synapses;Synaptic Cleft;synaptic function;Synaptic plasticity;Synaptic Receptors;synaptogenesis;System;Testing;Transforming Growth Factor beta;Work

PROJECT_TITLE: Linking an activity-dependent BMP pathway to synapse structure and function


ORG_CITY: Decatur

PHR: Project Narrative The average age of veterans is increasing and therefore understanding the underlying etiology of age associated disease vulnerability, as well as establishing new prevention and therapeutic strategies is of significant importance. Aging is associated with an increased susceptibility to a number of diseases including osteoporosis with its associated increased risk of fracture. Our studies aim to address improving bone health and healing by nutritional prevention strategies as well as proactive therapeutic interventions to manipulate the microbiome. We will use a comprehensive series of innovative methodologies to investigate the novel concept that the microbiome is integral to dietary Pi sensing and can alter disease pathology associated with sustained high Pi consumption including chronic inflammation and bone health. The studies proposed herein could open numerous new avenues to identify novel strategies to influence veterans' health as they age.

PI_NAMEs: BECK, GEORGE R. (contact)

PROJECT_TERMS: 16S ribosomal RNA sequencing;absorption;Address;Adult;Age;age effect;age-related disease;Aging;Agreement;American;Antibiotics;Area;beneficiary;bone;Bone Diseases;bone healing;bone health;bone loss;Bone Marrow;bone mass;bone metabolism;bone quality;Cardiovascular Diseases;CD4 Positive T Lymphocytes;Cell Count;cell growth;Cells;Cessation of life;Chronic;Clinical;clinically relevant;Community Surveys;Consumption;Cultured Cells;Data;Dementia;Diet;Diet Habits;dietary;Dietary Intervention;Dietary Phosphorus;Digestion;Disease;Disease Progression;dysbiosis;efficacy testing;Elderly;Elements;Endocrine;Enteral;Etiology;fibroblast growth factor 23;Financial Hardship;Fracture;fracture risk;Germ-Free;Goals;Gonadal Steroid Hormones;Growth;gut inflammation;gut microbes;gut microbiome;gut microbiota;Gut Mucosa;Health;High-Throughput Nucleotide Sequencing;Hip Fractures;Homeostasis;Hormones;hospital readmission;Hospitalization;Immune response;Immune system;improved;Individual;Inflammation;Inflammatory;inflammatory bone loss;Inflammatory Response;Inherited;Injections;innovation;inorganic phosphate;Intake;Intervention;Intestinal permeability;Intestines;Kidney;Kidney Diseases;Knock-out;Knowledge;Leaky Gut;Lifelong disability;Longevity;male;Malignant Neoplasms;Measures;Medicare;Metabolism;Methodology;Methods;microbiome;microbiome composition;military veteran;Minerals;Modeling;mouse model;Mus;Mutation;neutralizing antibody;Normal Range;novel;novel strategies;Nutrient;Nutritional;Operative Surgical Procedures;Osteoporosis;Parathyroid gland;Pathology;Patients;Permeability;Phenotype;Phosphorus;Physiological;Predisposition;Premature aging syndrome;Prevention;Prevention strategy;Probiotics;Process;Proteins;Publishing;Quality of life;receptor;reconstitution;Rehabilitation therapy;Renal function;Reporting;Research;response;Retrospective Studies;secondary analysis;Series;Serum;Signal Transduction;Small Intestines;Syndrome;T-Lymphocyte;Taxonomy;Testing;Therapeutic;Therapeutic Intervention;Tight Junctions;Tissues;TNF gene;Veterans;Veterans Health Administration;Woman

PROJECT_TITLE: Contribution of Phosphate to Inflammatory Bone Loss


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Fetal Tissue;Human Genome;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: NARRATIVE This project will use advanced genomic, molecular and in vivo studies to compare neural precursor cells in the brains of three primate species and the mouse. These experiments will uncover and test mechanisms of brain growth that have emerged during primate evolution.

PI_NAMEs: HAYDAR, TARIK F (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Age;Apical;Bioinformatics;Brain;Candidate Disease Gene;cell behavior;Cell division;Cell Physiology;cell type;Cells;Cerebral cortex;comparative genomics;Comparative Study;Complex;Data;Data Set;deep sequencing;Development;Elements;Embryo;Evolution;executive function;experimental study;Factor Analysis;fetal;Freezing;Gene Expression;Gene Expression Profile;Gene set enrichment analysis;Genes;Genetic Complementation Test;genomic signature;Genomics;Growth;Human;imaging modality;Imaging Techniques;Immunohistochemistry;In Situ Hybridization;in vivo;Individual;Label;Lead;Macaca;Macaca mulatta;Mammals;Maps;Molecular;Motor;Mus;Nature;Neocortex;neocortical;nerve stem cell;Nervous System Disorder;neural;neurogenesis;Neuroglia;Neurons;nonhuman primate;novel;Pan Genus;Pattern;Population;prenatal;Primates;Process;progenitor;programs;Property;Radial;Reporting;Resolution;Rodent;Role;sample archive;Sampling;Sensory;Signal Pathway;single nucleus RNA-sequencing;single-cell RNA sequencing;Specimen;stem;stem cells;subventricular zone;System;Testing;Time;tissue archive;tool;transcriptome;transcriptomics;Ventricular;Work

PROJECT_TITLE: Comparative Genomics of Precursor Diversity and Function

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Nanotechnology;Neurosciences

ORG_DEPT: ENGINEERING (ALL TYPES)

PHR: Proposed voltage imaging technology could enable high resolution mapping of network dysfunctions causing neurological disorders and can open up exciting avenues to develop therapeutic approaches based on neuromodulation. Neural circuit dysfunctions are the cause of most neurological diseases, including epilepsy, Parkinson’s disease, dystonia, depression and schizophrenia. That could greatly impact the outcome for many of the one billion people affected by neurological disorders worldwide.

PI_NAMEs: CUBUKCU, ERTUGRUL  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: 3-Dimensional;Action Potentials;Affect;Area;biomaterial compatibility;Biosensing Techniques;Brain;Calcium;Cells;Chemicals;Chronic;cognitive function;Data Collection;density;design;Detection;Development;Dimensions;Dyes;Dystonia;Electric Wiring;Electrical Engineering;electrical measurement;electrical potential;Electrodes;Electrophysiology (science);Engineering;Epilepsy;Exciton;experience;experimental study;fabrication;flexibility;fluorescence imaging;Functional disorder;Future;graphene;Human;Image;imaging capabilities;Imaging technology;improved;In Vitro;information processing;Injectable;innovation;Liquid substance;Maps;Measurement;Mental Depression;meter;Methods;Microelectrodes;Molecular Medicine;Monitor;multimodal data;multimodality;nanoengineering;nanophotonic;nanosheet;Nature;Nervous System;Nervous System Disorder;network dysfunction;neural;neural circuit;neuroimaging;Neurons;neuroregulation;Neurosciences;Noise;non-genetic;optical imaging;Optics;Organoids;Outcome;Output;Parkinson Disease;parylene C;Penetration;Persons;Phase;Photobleaching;Photons;Population;programs;quantum;Research;Resistance;Resolution;Schizophrenia;Semiconductors;Signal Transduction;Spectrum Analysis;stem cell biology;Techniques;Technology;temporal measurement;Therapeutic;Thick;Thinness;tissue phantom;Tissues;tool;two photon microscopy;two-photon;Validation;voltage

PROJECT_TITLE: Neuro-flakes: Direct Voltage Imaging of Neural Activity with Atomically-thin Optoelectronic Materials


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: STANFORD

ORG_DEPT: CHEMISTRY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE: Manipulations of RNA allow the addressing of diseases which manifest through “undruggable proteins, without the permanence and potential side effects of gene editing. The proposed research will develop RNA-based bifunctional molecules (RBMs), which can redirect endogenous Argonaute and RNA effector proteins to cause a wide range of effects in a sequence-programmable manner. This will provide modular and therapeutically- viable reagents for manipulation of human RNA.

PI_NAMEs: LUSI, ROBERT FOLLETT (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Ablation;Address;Adenosine;Affect;Base Pair Mismatch;Binding;Biological Assay;Biological Models;Biology;CCND1 gene;Cells;chemical synthesis;Chemicals;Chemistry;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complementary RNA;Complex;design;Development;Disease;Down-Regulation;Engineering;Environment;Event;experimental study;falls;Foundations;FOXM1 gene;Gel;Gene Expression;Genes;Genetic Diseases;Genetic Transcription;Goals;Guide RNA;Health;Human;Immunoprecipitation;In Vitro;in vivo;Incidence;Intervention;Laboratories;Learning;Length;Libraries;Ligands;Luciferases;Malignant Neoplasms;Mammals;Mediating;Medicine;member;Messenger RNA;Methylation;Methyltransferase;Modeling;Modification;N-terminal;Nerve Degeneration;novel;Nuclear;Oligonucleotides;Pharmaceutical Preparations;Positioning Attribute;Post-Transcriptional Regulation;posttranscriptional;prevent;Primary carcinoma of the liver cells;Proliferating;Proteins;Reagent;recruit;Reporter;Research;Resources;RNA;RNA Interference;RNA library;Scientist;side effect;Signal Transduction;skills;Small Interfering RNA;small molecule;Structure-Activity Relationship;Synthesis Chemistry;System;Therapeutic;tool;Transcript;transcriptome sequencing;Translations;Untranslated RNA;Validation;Work

PROJECT_TITLE: Modular Reagents for Programmable RNA Manipulation by Endogenous Proteins


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Children with medical complexity (CMC) are uniquely vulnerable to adverse drug events and dependent upon their under-supported family to carry out complex medication management and coordination across a network of caregivers. To improve CMC medication safety, this project will develop and test a mobile health platform, MedS@HOME, which is designed by stakeholders to support safe medication management across the child’s caregiving network. This technology has the potential to improve medication safety and chronic care outcomes across the wide range of populations that require care from caregiving networks.

PI_NAMEs: COLLER, RYAN J (contact);WERNER, NICOLE E

PROGRAM_OFFICER_NAME: GRIPIOTIS, EROFILE

PROJECT_TITLE: Improving medication safety for medically complex children with mHealth across caregiving networks

STUDY_SECTION: HSQR

STUDY_SECTION_NAME: Healthcare Patient Safety and Quality Improvement Research[HSQR]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Diabetes;Wound Healing and Care

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative: Diabetes currently afflicts 170 million people worldwide and nearly 26 million Americans (more than 8 percent of the population) and its complications have broad and devastating effects on the health and quality of life of these patients. A particularly significant and dangerous complication of diabetes is non-healing ulcerated wounds in the lower leg, which are the leading cause of amputations in the USA. In this application, we propose to study associated cell dysfunctions and improve healing by creating novel native engineered constructs capable of enhancing cell integration and evaluating their ability to improve healing in a diabetic mouse model.

PI_NAMEs: KYRIAKIDES, THEMIS R (contact)

PROGRAM_OFFICER_NAME: LI, YAN

PROJECT_TERMS: Alginates;American;Amputation;angiogenesis;Animals;Area;Attention;Behavior;Biocompatible Materials;Biomechanics;Biomedical Engineering;Blood flow;Cell Physiology;Cells;Chronic;chronic wound;Clinic;Clinical;combat;combinatorial;Complication;Complications of Diabetes Mellitus;crosslink;Dangerousness;Dermal;Development;Diabetes Mellitus;diabetic;Diabetic Foot Ulcer;Diabetic mouse;diabetic patient;diabetic ulcer;Drug Compounding;Drug Delivery Systems;Engineering;Epithelium;Excision;Extracellular Matrix;Extracellular Matrix Proteins;Family suidae;Fibroblasts;Functional disorder;Gelatinase A;Genotype;healing;Health;Histologic;Hydrogels;Hyperglycemia;Hypoxia;Immune;Impaired healing;Impaired wound healing;improved;In Vitro;in vivo;Infection;Inflammation;keratinocyte;Knockout Mice;Laboratories;Lead;Leg;limb amputation;Lower Extremity;Measurement;Microspheres;migration;Mobility decline;Molecular;Monitor;mortality;mouse model;Mus;non-healing wounds;novel;novel therapeutic intervention;Pathologic;Pathway Analysis;Patient-Focused Outcomes;Patients;Persons;Phenotype;Population;Prevention;Production;Protein-Lysine 6-Oxidase;Proteins;Quality of life;Recovery;regenerative;Role;Signal Pathway;Skin;Stains;Testing;Therapeutic;Thick;thrombospondin 2;Traction;transcriptome sequencing;Translating;United States;vessel regression;Work;wound;wound care;wound closure;wound healing

PROJECT_TITLE: ECM biomaterials for diabetic foot ulcers

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


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

ORG_CITY: Loma Linda

ORG_NAME: LOMA LINDA UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative In the blood microcirculation, endothelial cells play a key role in relaxing smooth muscle cells to produce vasodilation and increase blood flow to organs as they need, e.g. to brain or skeletal muscle during physical activity. At a catastrophic social and financial expense to societies around the world, this process is reduced with aging and the onset of neurodegenerative diseases through poorly understood mechanisms. The current research project investigates novel and controllable mechanisms to improve the function of blood vessels in the brain, thus promoting a healthier brain function to sustain the lifespan and quality of life in older humans susceptible to developing dementia such as Alzheimer’s disease.

PI_NAMEs: BEHRINGER, ERIK J. (contact);PIRES, PAULO W

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: 3xTg-AD mouse;Abbreviations;Age;Age Factors;age related;age related cognitive disorder;Aging;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Animal Model;Apolipoprotein E;Arteries;arteriole;Behavior;Behavioral;Biophysics;Blood;Blood flow;Blood Vessels;Brain;brain pathway;brain tissue;cerebral artery;Cerebral endothelium;cerebrovascular;Cerebrovascular Circulation;cerebrovascular pathology;Cerebrovascular Physiology;Cerebrovascular system;Cerebrum;Cholesterol;Cholesterol Homeostasis;Cognition;Cognitive;Coupled;Data;Dementia;Development;effective therapy;Elderly;Endothelial Cells;endothelial dysfunction;Endothelium;Excision;Experimental Designs;Functional disorder;functional improvement;gene therapy;genetic variant;gerotherapeutic;Goals;Health;Human;Human Genetics;human old age (65+);Hyperemia;Impairment;improved;in vivo;innovation;Intervention;Ion Channel;Kir2.1 channel;Knock-out;life span;Lipids;Mediator;Membrane;Memory;Metabolic;methyl-beta-cyclodextrin;Microcirculation;Molecular;mouse model;Neurodegenerative Disorders;neurovascular coupling;new therapeutic target;novel;Nutrient;Organ;Outcome;overexpression;Oxygen;Pathologic;Pathology;Pathway interactions;Patients;Perfusion;Pharmacology;Phase;Physical activity;Physiological;Physiology;Play;Potassium Channel;Predisposition;Process;Property;Publishing;Quality of life;Regulation;Relaxation;Research;Research Project Grants;Resistance;response;Risk Factors;Role;sex;Signal Pathway;Skeletal Muscle;Smooth Muscle Myocytes;social;Societies;Testing;Therapeutic Intervention;therapeutic target;Transgenic Animals;Variant;Vascular Diseases;Vasodilation;Whole Organism;Wild Type Mouse

PROJECT_TITLE: Role of Endothelial K+ Channels in Age-Related Dementia

STUDY_SECTION: BBHV

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Clinical Research;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Rheumatoid Arthritis

PHR: Project Narrative Rheumatoid arthritis (RA) affects 0.5%, of the U.S. population. The mechanisms underlying disease flare are poorly understood. Success would demonstrate a critical role for periodontal mucosal breaks in triggering RA flares, and could lead to transformative and fundamental treatment approaches focused on treating periodontitis and preventing periodontal mucosal breaks, rather than inhibiting downstream TNF, IL6, JAK signaling, or B or T cell responses.

PI_NAMEs: ORANGE, DANA ELIZABETH;ROBINSON, WILLIAM H (contact)

PROGRAM_OFFICER_NAME: MAO, SU-YAU

PROJECT_TERMS: Affect;Anti-citrullinated peptide antibody;Antibodies;Antibody Repertoire;antibody test;Antigen Targeting;Antigen-Antibody Complex;Antigens;Arthritis;Autoimmune;Autoimmune Responses;Autoimmunity;B-Lymphocytes;Bacteremia;Bacteria;Bacterial Antibodies;Bacterial DNA;Binding;Blood;cigarette smoking;citrullinated protein;Citrulline;Clinical;cohort;Collection;Cross Reactions;cross reactivity;Data Set;Dental Care;Development;Disease;DNA;DNA sequencing;Environmental Exposure;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;Exhibits;Family;Fingers;Flare;Genes;Gingival Pocket;Home;Human;Human Characteristics;IL6 gene;Immune response;Immunoglobulin A;Immunoglobulin G;Immunoglobulin Somatic Hypermutation;In Vitro;Interleukin-6;Joints;Lead;Leukocyte Elastase;Lymphocyte Subset;Lymphocytic Infiltrate;Macrophage;Measurement;Measures;Mediating;member;Monitor;Mucous Membrane;neutrophil;novel diagnostics;novel strategies;novel therapeutic intervention;Nucleotides;Oral;oral bacteria;Oral cavity;Oral mucous membrane structure;osteoclastogenesis;Osteoclasts;pathogen;Patients;Periodontal Diseases;Periodontal Pocket;Periodontitis;Plasmablast;Play;Population;pre-clinical;prevent;Production;Protein Isoforms;Protocols documentation;PRTN3 gene;Reaction;Recombinants;response;Rheumatoid Arthritis;Role;sample collection;Sampling;seropositive;Signal Transduction;single-cell RNA sequencing;Site;Specificity;Stains;Structure of germinal center of lymph node;success;Synovial Membrane;Synovitis;T cell response;T-Lymphocyte;Testing;Tissues;TNF gene;transcriptome sequencing;Venous

PROJECT_TITLE: Investigating Mucosal Breaks in the Initiation and Progression of Rheumatoid Arthritis

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]