NIH_SPENDING_CATS: Cancer;Genetics

PHR: Project Narrative Currently, there is a gap in understanding how transcription is utilized to aid in DNA repair and maintain genomic integrity. The Integrator complex is known to associate with RNA Polymerase II and utilize its RNA endonuclease activity to regulate transcription at nearly all RNAPII loci. My research has uncovered a surprising interaction between a critical DNA repair protein and Integrator, and this proposal will elucidate the mechanistic underpinnings between these two important nuclear processes.

PI_NAMEs: JENSEN, MADELINE K (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Active Sites;Address;Amino Acids;Auxins;Binding;Biochemical;Biological Assay;BRCA1 gene;C-terminal;Cancerous;career;Cell Line;Cell Nucleus;Cell Physiology;Cells;Cellular Stress;ChIP-seq;Co-Immunoprecipitations;Code;Complex;Cryoelectron Microscopy;Cytoplasmic Protein;Data;Disease;DNA Damage;DNA lesion;DNA Probes;DNA Repair;DNA Repair Gene;endonuclease;Endoribonucleases;Etoposide;experimental study;Fellowship;Foundations;Gel Chromatography;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic Transcription;genome integrity;Goals;Growth;Human;Hydrogen Peroxide;Hyperthermia;inhibitor;insight;Ionizing radiation;Knock-out;Knowledge;knowledge base;Licensing Factor;loss of function;member;Modeling;Mutagenesis;mutant;Mutation;Nuclear;Null Lymphocytes;p53-binding protein 1;Patients;Phenotype;prevent;Process;promoter;Proteins;Publishing;Reactive Oxygen Species;recruit;Regulation;repaired;Research;Resolution;response;Ribosomal RNA;RNA;RNA Polymerase II;Role;scaffold;Scientist;Site;skills;Stress;Structure;success;System;Testing;Training;Transcriptional Regulation;transcriptome;transcriptome sequencing;Untranslated RNA;Up-Regulation;Western Blotting

PROJECT_TITLE: Identification and structural basis of a potential licensing factor of the Integrator cleavage module

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease

ORG_CITY: STONY BROOK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: Narrative Podocytes are highly specialized cells that are critical for the filtration of blood into urine. Podocytes are unable to regenerate after injury, therefore podocyte loss is a critical component in the development of kidney diseases. I observed novel intercellular bridges forming between injured podocytes and neighboring parietal epithelial cells in injured mouse kidneys, therefore, I will investigate the role of intercellular bridges as a method of direct communication between injured podocytes and parietal epithelial cells in kidney diseases.

PI_NAMEs: CINTRON PREGOSIN, NINA  (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: Actins;Adult;Affect;American;Area;Attenuated;Awareness;axon guidance;Binding Sites;BIR Domain;BIRC3 gene;blood filtration;Bowman's space;Cell Communication;Cell Differentiation process;cell type;Cells;Characteristics;ChIP-seq;Chronic Kidney Failure;Coculture Techniques;Communication;Cytoplasm;Cytoskeletal Modeling;Data;Data Set;Diabetic mouse;Diabetic Nephropathy;Dialysis procedure;differential expression;Disease;End stage renal failure;Epithelial Cell Proliferation;Epithelial Cells;Epithelium;Family member;Focal Adhesions;Focal and Segmental Glomerulosclerosis;Gene Expression;Genes;GKLF protein;Glomerular capsule structure;glomerular filtration;Goals;high risk;Immune;immunocytochemistry;Immunofluorescence Immunologic;In Vitro;Inhibition of Apoptosis;inhibitor;injured;Injury;Invaded;Kidney;Kidney Diseases;Kidney Transplantation;knock-down;Knock-out;Kruppel-like transcription factors;Laboratories;Left;Ligands;Maintenance;Mediating;Membrane;Methods;Modeling;Mus;Natural regeneration;Neoplasm Metastasis;nephrogenesis;nephrotoxicity;Neurons;novel;Nuclear RNA;Organelles;Parietal;Pathologic;Periodic acid Schiff stain method;Persons;pharmacologic;Physiological;Physiology;podocyte;polymerization;Polymers;Prevalence;prevent;Prions;Process;progression risk;Proliferating;Promoter Regions;protein transport;Proteins;Rapidly Progressive Glomerulonephritis;receptor;Recovery;Renal glomerular disease;response;Role;Serum;Severities;Stains;Stress;Structure;Testing;Therapeutic;therapeutic target;Thinness;trafficking;transcription factor;transcriptome sequencing;Transmission Electron Microscopy;United States;Urine;Vesicle;vesicle transport;Virus;Waiting Lists;Zinc Fingers

PROJECT_TITLE: Investigating podocyte-parietal epithelial cell communication through intercellular bridges in kidney disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-G (O1)]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Narrative Chromatin modifying enzymes are frequently mutated in cancers that lead to dysregulation of important cellular functions. Among them, the histone methyltransferase MLL1 has both loss of function mutations and copy number gains in cancer. Elucidating how MLL1 contributes to tumorigenesis highlights its multifaceted roles in tumorigenesis and facilitates development of new therapeutic strategies.

PI_NAMEs: DOU, YALI  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Affect;Alleles;borealin;Cancer Cell Growth;cancer recurrence;Cell Cycle;Cell division;Cell Physiology;Cells;Centromere;Chimeric Proteins;Chromatin;Chromosomes;cofactor;Complex;Defect;Deposition;Development;Enzymes;epigenetic drug;Epigenetic Process;Etiology;Family;gain of function;Genes;Genetic Transcription;Genome;Haspin;Hematologic Neoplasms;Histone H3;histone methyltransferase;Histones;Human;human disease;Hyperactivity;In Vitro;insight;interdisciplinary approach;Liquid substance;loss of function mutation;Malignant Neoplasms;Mediating;Metaphase;Methylation;Methyltransferase;Missense Mutation;Mitosis;Mitotic;Mixed-Lineage Leukemia;MLL gene;Mutate;Mutation;Neoplasm Metastasis;novel;novel therapeutic intervention;Oncogenic;overexpression;Pathway interactions;pediatric acute leukemia;Phase;Physical condensation;Play;Primary carcinoma of the liver cells;Prognosis;Proteins;proteogenomics;Reader;Regulation;Role;SET Domain;therapeutic target;Transcriptional Regulation;Tumor Suppressor Proteins;tumorigenesis

PROJECT_TITLE: Non-canonical function of transcription cofactor MLL1 in cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-H (02)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biomedical Imaging

ORG_CITY: LA JOLLA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative: The cell membrane tension dictates the shape and many downstream properties of cells and the organs made of cells; thus, membrane tension is important in disease but difficult to measure. Here, we propose to build a contrast agent that can map and measure the cell membrane tension using an optical or ultrasound signal. This contrast agent will help guide the detection and treatment of important diseases and be a tool for in vivo research.

PI_NAMEs: JOKERST, JESSE VINCENT (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: 3-Dimensional;Address;Animal Model;Binding;Biological Phenomena;Biomedical Research;Carbon;Cell Culture Techniques;Cell division;Cell membrane;Cell model;cell motility;Cells;cellular imaging;Chemicals;Chemistry;Clinical;Contrast Media;Cultured Cells;Data;Detection;Development;Disease;disease diagnosis;Dyes;Electrons;Endocytosis;Exocytosis;experience;experimental study;fascinate;feasibility testing;Fluorescence;fluorescence imaging;fluorescence lifetime imaging;fluorophore;Funding;Goals;Head;Hela Cells;Human Resources;Image;imaging agent;imaging modality;imaging probe;in vivo;in vivo imaging;innovation;Isotonic Exercise;Knowledge;Label;life span;Link;Lipids;Longitudinal Studies;Maps;Mass Spectrum Analysis;Measures;Meiosis;Membrane;Methods;Microscope;Microscopy;Mitosis;Modality;Molecular;Molecular Conformation;Motility;National Institute of General Medical Sciences;Nature;NMR Spectroscopy;novel;Optics;Organ;Organic Chemistry;Osmolalities;Osmotic Pressure;Outcome;Penetration;photoacoustic imaging;Photons;Population;Prevention;Process;Property;redshift;Research;Resolution;response;Rest;Role;Shapes;Signal Transduction;small molecule;Spectrum Analysis;stressor;Structure;System;Techniques;technology development;Testing;Therapeutic;Thick;Time;Tissues;tool;Toxicity Tests;Transportation;Ultrasonic wave;ultrasound;unilamellar vesicle;Vesicle;Work

PROJECT_TITLE: New Chemical Tools to Measure Cell Membrane Tension in Vivo

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-C (03)]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: PROJECT NARRATIVE Metastasis is the major cause of mortality in cancer patients today, with over 90% of cancer deaths being due to metastasis, and there are very few treatment options available for treating metastatic cancer. In my preliminary work, I discovered a novel mediator of metastasis: the human INAFM2 protein, which may present a future druggable target. The aims of this grant are to fully confirm INAFM2’s role in cancer metastasis by using mouse models and to determine INAFM2’s biological function and molecular mechanism.

PI_NAMEs: MOLOTKOVA, ANNA  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Address;Amino Acid Sequence;Binding;Binding Proteins;Biochemical;Biological Assay;Biological Process;Biotinylation;Bone Tissue;Cancer cell line;Cancer Patient;cancer type;capsule;Cell Fractionation;Cell Line;Cell membrane;cell motility;Cells;Cellular Assay;Cessation of life;Chemotaxis;Clear cell renal cell carcinoma;Co-Immunoprecipitations;CRISPR/Cas technology;Data;design;Diagnosis;Disease;Disseminated Malignant Neoplasm;druggable target;Embryo;Ewings sarcoma;experimental study;expression vector;Future;Gastric Adenocarcinoma;gene discovery;Genes;genome-wide;glycosylation;Grant;Growth;Guide RNA;Human;In Situ Hybridization;In Vitro;in vivo;in vivo Model;Individual;inhibitor;Injections;Integral Membrane Protein;Intercept;Kidney;knock-down;Knowledge;Libraries;Localized Disease;Malignant Childhood Neoplasm;Malignant Neoplasms;MAP Kinase Gene;Mass Spectrum Analysis;Mediating;Mediator;Metastatic Ewing's Sarcoma;Metastatic Neoplasm to the Lung;Methods;migration;Modeling;Molecular;mortality;Motility;mouse model;Mus;Neoplasm Metastasis;new therapeutic target;novel;overexpression;p38 Mitogen Activated Protein Kinase;Pathway interactions;Patients;Periosteum;Pharmacotherapy;Phenotype;Phosphorylation;Phosphorylation Site;Population;Post-Translational Protein Processing;Primary carcinoma of the liver cells;Proteins;Publishing;Regulation;Role;SCID Beige Mouse;Serum;Signal Transduction;Site-Directed Mutagenesis;soft tissue;Study models;Surface Plasmon Resonance;Survival Rate;Tail;tandem mass spectrometry;Testing;Therapeutic;tibia;Transcriptional Activation;transcriptome sequencing;tumor;Validation;vector control;Veins;Western Blotting;Work;Xenograft Model;Xenograft procedure;Zebrafish

PROJECT_TITLE: Molecular mechanism of INAFM2 in metastasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Human Genome;Pediatric;Rare Diseases;Rehabilitation

ORG_CITY: CHARLESTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative Hypermobile Ehlers Danlos Syndrome (hEDS) is a genetic disorder that causes symptoms affecting multiple body systems including the joints, skin, gastrointestinal tract, and heart. Despite its prevalence of 1 in 500 individuals, there are currently no reliable tests or treatments available for hEDS. The completion of this proposal will provide new understanding of the disease, opening new avenues for future studies and the potential for therapeutic approaches that will make a significant impact on the lives of those affected by hEDS and their families.

PI_NAMEs: GENSEMER, CORTNEY ANNE (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Acceleration;Affect;Animal Model;Biochemical;Biology;Body System;Cardiovascular system;Caring;Cell Degranulation;Cells;Chromatin;chronic pain;Clinical;clinical diagnosis;Co-Immunoprecipitations;cohort;Collagen;Collagen Fibril;comorbidity;Complex;Connective Tissue;connective tissue development;Connective Tissue Diseases;Data;Defect;Development;Diagnosis;diagnostic development;diagnostic tool;Diameter;Disease;disease phenotype;DNA;Ehlers-Danlos Syndrome;Ensure;Environment;Etiology;Exhibits;exome sequencing;experience;Extracellular Matrix;Faculty;Family;fibrillogenesis;follow-up;Future;gastrointestinal;Gastrointestinal tract structure;Gene Family;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Markers;genetic registry;genome wide association study;genome-wide;Genotype;Goals;Hand;healthcare burden;Healthcare Systems;Heart;Heritability;heritable connective tissue disorder;Heterozygote;Histologic;Homeostasis;Hospitalization;Immunologics;in vitro testing;in vivo;Individual;insight;Joint Laxity;Joints;Kininogenase;KLK15 Gene;Knock-in Mouse;Legal patent;mast cell;mechanical properties;Mechanics;Mediator;Medical Genetics;medical specialist;Modeling;Molecular;molecular diagnostics;mouse model;Mus;Musculoskeletal;Mutation;Neurologic;novel;Occupational Therapy;Operative Surgical Procedures;Outcome;Pathogenesis;Pathogenicity;Patients;Phenotype;Physical therapy;Play;Population;Positioning Attribute;Prevalence;Process;Property;Protein-Lysine 6-Oxidase;Proteins;Proteomics;Quality of life;Registries;risk variant;Role;Serum;Single Nucleotide Polymorphism;Skin;Skin Manifestations;Statistical Data Interpretation;Stomach;symptom management;Symptoms;Syndrome;targeted treatment;Testing;Therapeutic;Tissues;Training;trypsin-like serine protease;Variant

PROJECT_TITLE: Genetic and Molecular Mechanisms of hypermobile Ehlers Danlos Syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-C (20)]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Disability Research;Hearing Loss;Mental Health;Neurosciences;Pediatric;Prevention;Rehabilitation;Social Determinants of Health

ORG_CITY: INDIANAPOLIS

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Psychosocial adjustment following cochlear implantation represents a critical outcome that includes social (e.g., adaptability), emotional (e.g., depression), and behavioral (e.g., aggression) competence and functioning in daily living. The overall objective of the research project is to predict variability in psychosocial adjustment in prelingually deaf, early-implanted cochlear implant users by identifying underlying mechanisms of risk and resilience. Findings will have direct clinical implications for the early identification, diagnosis, and treatment of at-risk psychosocial outcomes in pediatric cochlear implant users by identifying specific assessment and intervention targets to promote effective coping responses to stress in order to enhance psychosocial adjustment.

PI_NAMEs: CASTELLANOS, IRINA  (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Address;Aggressive behavior;Area;Auditory;auditory deprivation;Behavior;Behavioral;Characteristics;Child;Child Behavior;Child Development;Childhood;childhood hearing loss;Clinical;clinically significant;Cochlear implant procedure;Cochlear Implants;Cognitive;Communication;Competence;coping;deaf;deafness;design;Development;Diagnosis;Distal;Early identification;Emotional;Emotions;executive function;Exposure to;Future;Hearing;hearing impairment;Implant;Individual;Individual Differences;Informal Social Control;Intervention;Knowledge;Language;longitudinal design;Mediating;Mental Depression;Modeling;Neurocognitive;normal hearing;novel;Outcome;Parents;Pathway interactions;Process;programs;prospective;psychosocial;psychosocial adjustment;psychosocial outcome;Questionnaires;Recording of previous events;Reporting;Research;Research Project Grants;resilience;Resources;response;Risk;Risk Reduction;Science;skills;social;Stress;stressor;Taxes;Testing;Work

PROJECT_TITLE: Predicting psychosocial adjustment in pediatric cochlear implant users

STUDY_SECTION_NAME: Special Emphasis Panel[ZDC1 SRB-Z (44)]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Mental Health;Neurosciences;Substance Misuse

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE The research proposed under this F31 fellowship will assess the role of KCC2-mediated synaptic plasticity in the VTA during naturalistic reward learning and will characterize the circuitry involved in this process. This will allow for the establishment of KCC2 modulation as a novel form of synaptic plasticity during reward learning and will demonstrate the potential of KCC2 as a target for intervention to treat neuropsychiatric disorders that are characterized by aberrant reward learning such as obsessive compulsive disorder and schizophrenia, among many others.

PI_NAMEs: WOO, JOYCE  (contact)

PROGRAM_OFFICER_NAME: BABECKI, BETH

PROJECT_TERMS: Acceleration;addiction;Address;Alcohols;Animals;Anions;Association Learning;Aversive Stimulus;Behavior;Behavioral;Binding;Brain;Brain region;Butyric Acids;Cannulas;Cells;chloride-cotransporter potassium;Chlorides;Collection;Coupled;Cues;Data;Desire for food;dopaminergic neuron;Down-Regulation;drug of abuse;Electrophysiology (science);Environment;Equilibrium;Event;experience;experimental study;Exposure to;Fellowship;genetic approach;Homeostasis;Infusion procedures;inhibitory neuron;interest;Intervention;Label;Lateral;Learning;Link;Mediating;Mediator;Memory;Mental Depression;Midbrain structure;Modeling;Modification;Molecular;multidisciplinary;neural network;neuronal circuitry;Neurons;neuropsychiatric disorder;Neurotransmitters;Nicotine;nicotine exposure;novel;novel therapeutics;Nucleus Accumbens;Obsessive-Compulsive Disorder;Organism;Outcome;Output;patch clamp;Pathology;Pathway interactions;Periodicity;Permeability;Pharmaceutical Preparations;pharmacologic;Play;prevent;Process;Rattus;receptor;receptor function;Research;Research Personnel;reward dysfunction;Rewards;Role;Schizophrenia;Scientist;Stimulus;Stress;Synapses;Synaptic plasticity;therapeutic target;Theta Rhythm;Time;Translating;Ventral Tegmental Area

PROJECT_TITLE: Dynamic Changes in Chloride Homeostasis Coordinates Midbrain Inhibitory Network Activity during Reward Learning

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Neurosciences;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE The acute cardiovascular care of spinal cord injury, including blood pressure regulation, is not backed by sufficient evidence to form hard guidelines. This research seeks to use ultrasound to understand how spinal cord injury affects vessels in the spinal cord and their ability to compensate for variation in blood pressure. This study will also attempt to use blood pressure maintenance to optimize the distribution of blood flow around the injury and maximize healing, with the potential for eventual translation into human spinal cord injury patients.

PI_NAMEs: ROUTKEVITCH, DENIS  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Acute;acute care;Address;Affect;Algorithms;Area;blind;Blood;Blood flow;Blood Pressure;blood pressure regulation;Blood Vessels;Brain;Cardiovascular system;Caring;Clinic;Clinical;Clinical Markers;Compensation;Contusions;Data;detection limit;Development;diagnostic tool;Doppler Ultrasound;Equilibrium;Excision;Feedback;Filament;first-in-human;functional outcomes;Goals;Guidelines;healing;Hemorrhage;Heterogeneity;Homeostasis;Hour;Human;hypoperfusion;Image;Imaging Techniques;Impairment;Implant;improved;Infusion procedures;Injury;innovation;insight;Intervention;Intravenous;Laminectomy;Link;Maintenance;Measurement;Measures;Modeling;Monitor;novel;Organ;Outcome;outcome prediction;Patients;Perfusion;pharmacologic;Physicians;precision medicine;pressure;Procedures;Prognostic Marker;Proxy;Rattus;Recommendation;Research;Resolution;response;Saline;Severities;Site;Spatial Distribution;spatiotemporal;Spinal;Spinal Cord;Spinal cord injury;Spinal cord injury patients;Spinal Cord Ischemia;spinal cord mapping;spine bone structure;Stroke;Techniques;Therapeutic;therapeutic target;Time;Tissues;tool;Translations;treatment effect;ultrasound;Umbra;Variant;Vascular Diseases;vascular injury;Withdrawal

PROJECT_TITLE: Spinal Cord Injury: A Cardiovascular Perspective using Ultrasound

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE This project aims to better understand how our sense of smell works by studying odorant receptors (ORs) in humans. We will investigate how ORs bind to different odor molecules and how they are activated to send signals to our brain. By uncovering the fundamental properties of OR function, we hope to gain insights that could lead to new therapies for smell-related disorders.

PI_NAMEs: MANGLIK, AASHISH  (contact);MATSUNAMI, HIROAKI ;VAIDEHI, NAGARAJAN

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Adopted;Binding;Biological Models;Biology;Brain;Characteristics;chemical binding;Chemicals;Chimeric Proteins;combinatorial;Cryoelectron Microscopy;Disease;Event;Experimental Models;Family;Fatty Acids;Fishes;G-Protein-Coupled Receptors;Gene Duplication;Goals;Hand;Homology Modeling;Human;Human Genome;Hydrophobicity;innovation;insight;Ligands;Logic;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;molecular recognition;Mutagenesis;nanobodies;novel therapeutics;Odorant Receptors;Odors;Olfactory Pathways;olfactory sensory neurons;OR51E2 gene;paralogous gene;preference;Process;Property;Propionates;receptor;Receptor Activation;receptor binding;receptor function;Signal Transduction;Smell Perception;Structure;Vertebrates;Volatile Fatty Acids;Volatilization;Work

PROJECT_TITLE: Structural dynamics of human odorant receptors in olfaction

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


ADMINISTERING_IC: NS

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: BOSTON

ORG_NAME: IRIS KINETICS INC

ORG_STATE: MA

PHR: Project Narrative We aim to demonstrate a new multi-spectral light source with remarkable illumination uniformity we call Efficient Uniform Color-Light Integration Device (EUCLID) and its potential impact in a broad range of biological microscopic and mesoscopic imaging applications. EUCLID employs a diffuse-reflective, adjustable hollow cavity for uniform mixing of light from discrete sources with high efficiency and provides a simple method to compensate for spatial non-uniformity introduced by optical components in the imaging system. We propose to apply EUCLID to multispectral mesoscale imaging of neuronal and hemodynamic activity and neuromodulation in the cortex of awake mice implanted with crystal skull windows.

PI_NAMEs: SEYMOUR, ELIF  (contact)

PROGRAM_OFFICER_NAME: AUBRECHT, TARYN GRACE

PROJECT_TITLE: A Spatially Uniform Illumination Source for Widefield Multi-Spectral Optical Imaging

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-S (12)]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Human Genome;Orphan Drug;Pediatric;Pediatric Cardiomyopathy;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Recent studies have identified an association between genetic variants in a new set of genes and the development of hypertrophic cardiomyopathy (HCM), a common genetic heart condition that causes sudden cardiac death and congestive heart failure. This application will focus on a subset of these genetic variants that are involved in controlling the folding and degradation of proteins in the cardiac muscle cells. We will determine the impact of these new genetic variants on the clinical outcomes of patients with HCM and also perform experiments to understand the mechanisms behind how they cause or exacerbate disease.

PI_NAMEs: DAY, SHARLENE M (contact)

PROGRAM_OFFICER_NAME: SHANBHAG, SUJATA MADHUKAR

PROJECT_TERMS: Affect;Alternative Splicing;Arrhythmia;BAG3 gene;biobank;Bioinformatics;Biological;Biological Models;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiomyopathies;Cardiovascular system;Case/Control Studies;Chaperone Gene;Client;Clinical;clinical diagnosis;clinical risk;Code;Congestive Heart Failure;Data;data modeling;Development;Dilated Cardiomyopathy;Disease;disease heterogeneity;Disease Pathway;Etiology;experience;Experimental Models;experimental study;Genes;Genetic;genetic architecture;genetic association;Genetic Epistasis;Genetic Models;genetic testing;genetic variant;genome editing;genome wide association study;genomic locus;Genotype;Goals;Heart;Heart failure;heart function;Heat shock proteins;Heat-Shock Proteins 70;Human;Human Genetics;human induced pluripotent stem cells;human model;human stem cell-derived;Hypertrophic Cardiomyopathy;improved;insight;Kinetics;knock-down;Knowledge;Label;Link;Maintenance;Measures;Medicine;Modeling;Molecular;Molecular Chaperones;Muscle;Myofibrils;novel;novel therapeutics;Outcome;overexpression;Patient-Focused Outcomes;Patients;Phenotype;Population Study;protective allele;protein degradation;Protein Dynamics;Protein Isoforms;protein protein interaction;Proteins;Quality Control;Registries;Regulation;Research Personnel;risk prediction;risk stratification;risk variant;RNA Splicing;Role;Sampling;Sarcomeres;Severity of illness;Source;sudden cardiac death;System;Testing;Therapeutic;therapeutic target;Tissue Banks;Transcript;Variant

PROJECT_TITLE: Risk Alleles in Protein Quality Control Genes as Modifiers of Hypertrophic Cardiomyopathy

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Membrane proteins represent ~30% of the mammalian proteome and over half of all drug targets, but are nearly always studied in physical contexts that do not model their relevant membrane environments – and this is limiting understanding. We seek to understand the role of the native membrane environment on epidermal growth factor receptor, a membrane protein that plays crucial roles in cellular and lipid metabolism, differentiation, motility, and proliferation in cancer.

PI_NAMEs: HUTCHISON, JAMES M (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: acrylic acid;Address;Adopted;Affect;anti-depressive agents;Automobile Driving;Behavior;Binding;Biochemical;Biological Assay;Bulla;Cell membrane;cofactor;Complex;Cryoelectron Microscopy;Data;Detergents;Deuterium;Development;dimer;Drug Targeting;EGF gene;Environment;Epidermal Growth Factor Receptor;experience;extracellular;Family;G-Protein-Coupled Receptors;Glioblastoma;Hydrogen;In Vitro;in vivo;Individual;Integral Membrane Protein;Ion Channel;Kinetics;Knowledge;Length;Ligand Binding;Ligand Binding Domain;Link;lipid metabolism;lipidome;lipidomics;Lipids;Literature;Malignant Neoplasms;Mass Spectrum Analysis;member;Membrane;Membrane Lipids;membrane model;Membrane Proteins;Metabolism;Methods;monomer;Motility;nanodisk;non-Native;Osmosis;Peripheral;Phosphotransferases;Physiological;Play;Probability;Proliferating;Property;protein structure;Protein Tyrosine Kinase;Proteins;Proteome;receptor;receptor function;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regulation;Role;Signal Transduction;Solvents;Sphingolipids;Structure;styrofoam;System;Technology;Time;Training;Transmembrane Domain;transmission process;Tropomyosin;Tyrosine Kinase Domain;Uncertainty;Vertebral column;Vesicle;Visualization;Water

PROJECT_TITLE: Studying EGFR where it lives: How membrane lipids define receptor properties


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Huntington's Disease;Mental Health;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: Nashville

ORG_DEPT: PSYCHOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Huntington’s disease (HD) is a chronic, fatal neurodegenerative disease associated with vast impairments in executive functioning; however, the presentation of executive dysfunction in HD is highly variable across disease progression and the underlying mechanisms driving these declines are poorly understood. Building on seminal findings of key contributors to executive dysfunction in other disease populations, the proposed study aims to extend these findings by examining the association of chronic stress, inflammatory cytokines, and a standardized marker of disease burden with executive functioning in a sample of adults with HD. This study will improve the field’s understanding of the specific processes driving one of the cardinal features of HD, executive dysfunction, and has the potential to inform treatment targets for supportive care.

PI_NAMEs: CIRIEGIO, ABAGAIL ELIZABETH (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Acute;acute stress;Adenine;Adult;Affect;Age;Automobile Driving;Autopsy;autosome;Biological;Biological Assay;blind;burden of illness;cancer type;Central Nervous System;Cerebrospinal Fluid;Characteristics;Chromosome 4;Chronic;Chronic Kidney Failure;Chronic stress;Communities;comparison control;congenital heart abnormality;cytokine;Cytosine;Data Analyses;data management;Development;Disease;Disease Marker;Disease Progression;Executive Dysfunction;executive function;Exhibits;Family;Fellowship;follow-up;Functional disorder;Funding;Genes;Glass;Goals;Grant;Guanine;Health;Health behavior;human model;Huntington Disease;IL8 gene;Impairment;improved;Individual;Inflammation;Inflammatory;inflammatory marker;Interleukin-10;Interleukin-4;Interleukin-6;Intervention;Interview;Knowledge;Literature;Measurement;Measures;Methodology;Methods;mouse model;Nature;Neurocognitive;Neurodegenerative Disorders;Participant;Patient Self-Report;Patients;Peripheral;Phenotype;Plasma;Play;Population;Positron-Emission Tomography;Process;prospective;Research;response;Role;Sampling;Seminal;sex;Short-Term Memory;skills;social;Social support;Source;standard measure;Standardization;Stress;stress state;Stressful Event;stressor;Supportive care;Symptoms;Testing;TNF gene;Training;Training and Education;United States National Institutes of Health

PROJECT_TITLE: Stress, Inflammation, and Neurocognitive Functioning in Adults with Huntington’s Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


NIH_SPENDING_CATS: Diabetes

ORG_CITY: BIRMINGHAM

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative (3 sentences) Diabetes mellitus results from insufficient or ineffective insulin production by the pancreatic β-cell and affects millions of people worldwide. In recent years, the importance of macrophages for β-cell expansion in pathological conditions, such as obesity, has been highlighted; pregnancy has also been identified as a period of robust β- cell expansion, despite β-cell proliferation under steady-state conditions being low. Therefore, this proposal aims to characterize islet macrophages throughout gestation and investigate their requirement in β-cell expansion during late gestation providing insight into potential targets to increase insulin production. 1

PI_NAMEs: BURNETTE , KALIA  (contact)

PROJECT_TERMS: Adoptive Transfer;Adult;Affect;Anti-Inflammatory Agents;Beta Cell;Biological Assay;Blood Glucose;Bromodeoxyuridine;Cell Communication;cell growth;Cell Lineage;Cell Maturation;Cell Physiology;Cell Proliferation;Cells;CSF1R gene;cytokine;Diabetes Mellitus;diabetic patient;Diagnosis;Event;experimental study;fetal;Flow Cytometry;Frequencies;Gene Expression;Genetic Transcription;Glucose tolerance test;Growth;Heart Diseases;High Fat Diet;Hyperglycemia;Immunofluorescence Immunologic;Immunologics;Impairment;Inflammatory;Injury;insight;Insulin;insulin sensitivity;islet;Kidney Failure;Macrophage;Measures;Modeling;Monitor;monocyte;Mus;Myelogenous;Obesity;Pancreas;Pathologic;Persons;Phenotype;Physiological;Population;Pregnancy;Production;Proliferating;recruit;Reporter;Reporting;response;Role;Signal Transduction;single-cell RNA sequencing;Source;Stroke;Structure of beta Cell of islet;Testing;Tissues;transcriptomics;Transforming Growth Factor beta;Transgenic Mice;Visualization

PROJECT_TITLE: Identifying Gestational-induced Changes in Islet Macrophages as a Potential Target for Beta-cell Expansion

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F06-L (20)]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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);American Indian or Alaska Native;Brain Disorders;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research

ORG_CITY: MINNEAPOLIS

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Projective Narrative The first ever International Indigenous Dementia Research Network Annual Conference series addresses a critical need to advance knowledge, discovery and scientific collaboration in Alzheimer’s Disease and Related Dementias (ADRD) in Indigenous populations. There is currently no equitable venue for academics and communities studying dementia in Indigenous populations to come together and share scientific and Indigenous knowledge in a way that is comparable to other disciplines or disease-focused research areas. To remedy this situation, we will implement a 5-year annual conference series with the long-term goal of creating a sustainable, supportive, worldwide network of scholars committed to knowledge exchange and collaboration to advance research, knowledge, and mentorship in community-based, culturally appropriate ADRD research with Indigenous populations.

PI_NAMEs: JACKLIN, KRISTEN  (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Address;Aging;Alaska Native;Alaska Native population;Alzheimer's disease related dementia;American Indian Population;American Indians;Area;Attention;Australia;Biological Markers;Canada;career;caregiving;Caring;cohort;Collaborations;Communities;community organizations;Country;Dementia;Development;Diagnosis;Discipline;Disease;disparity gap;Elderly;Epidemiology;Equity;Evaluation;experience;Goals;Group Meetings;health disparity;health equity;Health Promotion and Education;Healthcare;Indigenous;indigenous community;Inequity;International;Knowledge;Lead;Mainstreaming;member;Mentors;Mentorship;Methodology;Minority;National Institute on Aging;Native Hawaiian or Other Pacific Islander;Native-Born;outreach;Paper;Pathway interactions;Persons;Policies;Policy Maker;Population;Positioning Attribute;Postdoctoral Fellow;posters;Preparation;Prevalence;Process;racial disparity;Research;Research Methodology;Research Personnel;Research Support;Science;Scientific Advances and Accomplishments;Scientist;screening;Series;special interest group;Structure;Students;success;symposium;volunteer

PROJECT_TITLE: The International Indigenous Dementia Research Network Annual Conference

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Established Investigators and Conference Grants Study Section[AGCD-4]


NIH_SPENDING_CATS: Biotechnology;Genetics;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: BERKELEY

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Most genetic variants associated with disease are single point mutations which are potentially correctable via systems that exchange a single DNA base (base editors). However, the capacity of this approach is limited by editing promiscuity at neighboring bases which constrains target selection to a narrow range of mutations where nearby off-target edits would not negate the effect of the edit or induce additional pathogenic mutations. This proposal addresses an unmet clinical need for the advent of precision editors using a two-pronged approach that extends existing technology and creates an entirely new kind of editing enzyme with intrinsic properties that prevent off-target edits.

PI_NAMEs: DOHERTY, ERIN E (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Address;Adenine;Amino Acid Substitution;Autologous Transplantation;base;base editor;Biology;Catalytic Domain;Cell Therapy;Cells;Chemicals;Clinic;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Data;Deaminase;Deamination;Dependence;design;Disease;DNA;DNA-Binding Proteins;donor stem cell;DRADA2b protein;dsRNA adenosine deaminase;Enzymes;genetic variant;Genome;genome editing;Goals;graft vs host disease;Guide RNA;Hematopoietic stem cells;Homologous Transplantation;Human;human stem cells;Hybrids;Immune;immunodeficiency;insight;large scale data;Link;Mediating;Methods;Modification;Mucopolysaccharidosis I H;Mutation;mutation screening;Neurodegenerative Disorders;novel;Nucleotides;Pathogenicity;Patients;Point Mutation;prevent;Property;Regulation;Reporting;response;RNA;Severe Combined Immunodeficiency;Single-Stranded DNA;Site;Specificity;stem cells;success;System;Technology;Testing;therapeutic target;Variant;Work

PROJECT_TITLE: Precision Deaminases to Expand the Scope of Diseases Amenable to CRISPR-mediated Correction


ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE OVERALL Age is a major risk factor for increased susceptibility to infectious diseases, including respiratory virus infection such as influenza and SARS-CoV-2. This Center will define the contribution of airway epithelial cells to age- related dysfunction of the tissue-resident immune system, particularly in the context of lung responses to viral infections. These discoveries could form the basis for next-generation therapeutics to treat lung diseases, an outcome of great public health importance given the range of infectious and other age-related immune diseases that originate in, or secondarily impact, the lung.

PI_NAMEs: GARCIA-SASTRE, ADOLFO ;PALUCKA, ANNA KAROLINA  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 2019-nCoV;3-Dimensional;adaptive immune response;adaptive immunity;Affect;Age;age effect;age related;age related changes;Age Years;aged;Aging;aging related;Air;airway epithelium;Alternative Splicing;Alveolar;Anti-viral Response;Antigen Presentation;Biological Assay;Biological Models;Biology;Biomedical Engineering;bioprinting;Breathing;CD8-Positive T-Lymphocytes;Cell Aging;Cell model;cell type;Cells;Chronic;Communicable Diseases;Communication;Computational Biology;COVID-19 pandemic;data dissemination;Data Science Core;Dedications;defined contribution;Development;Disease;dysbiosis;Epigenetic Process;epigenetic regulation;Epithelial Cells;epithelial stem cell;Epithelium;frontier;Functional disorder;gene editing technology;Genes;Genetic Transcription;Genome;Genomic medicine;Genomics;Goals;Human;human model;human old age (65+);human tissue;Immune;immune function;Immune response;Immune system;Immune System Diseases;Immunity;immunological status;Immunology;immunoregulation;improved;in vivo;Individual;Infection;Inflammation;Inflammatory;Inflammatory Response;Influenza;influenza infection;Innate Immune Response;innovative technologies;Interferon Type I;Intervention;Kinetics;Knowledge;Lead;Liquid substance;Lung;Lung Diseases;Lung immune response;Maps;Measures;medical schools;Memory;Messenger RNA;microbiome;Modeling;Molecular;Myelogenous;Natural Immunity;novel;novel therapeutics;older adult;Older Population;Outcome;pathogen;pathogenic virus;Pathway interactions;posttranscriptional;Predisposition;prevent;preventive intervention;programs;Protein Isoforms;Public Health;Research;Research Personnel;Research Project Grants;Research Support;resident commensals;Resistance;respiratory infection virus;respiratory microbiome;Respiratory Tract Infections;respiratory virus;response;Risk;Risk Factors;RNA Splicing;role model;Sampling;seasonal influenza;senescence;Services;Shapes;Site;Slice;Structure;Structure of parenchyma of lung;System;T-Lymphocyte;technology development;The Jackson Laboratory;Time;Tissues;Training;Transcription Process;transcriptome;Viral;Viral Antigens;Viral Respiratory Tract Infection;virology;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Modulation of Lung Immune Responses to Viral Infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 AM-I (J1)]


NIH_SPENDING_CATS: Infectious Diseases;Lung

PI_NAMEs: PALUCKA, ANNA KAROLINA  (contact)

PROJECT_TERMS: Accountability;Adherence;Budgets;Clinical;Clinical Data;Clinical Research;Collaborations;collaborative environment;Communication;conflict resolution;Consultations;Data;data dissemination;data management;Data Science Core;Data Set;data sharing;Dedications;emerging pathogen;Ensure;Equipment;Exercise;experience;Fostering;Funding;Genomics;Geography;global health;Goals;Grant;Group Meetings;Home;Human;human data;Immunologist;Immunology;improved;Influenza;Institution;Laboratories;Lead;Leadership;Logistics;Lung immune response;medical schools;meetings;member;Monitor;National Institute of Allergy and Infectious Disease;outreach;Pathogenesis;Pilot Projects;Policies;Policy Compliance;Procedures;Productivity;Program Development;programs;Recommendation;Recording of previous events;Regulation;Reporting;Research;research and development;Research Personnel;Research Support;Resolution;Resource Allocation;Resource Development;Resource Sharing;Resources;RNA Viruses;Role;scientific organization;Secure;Services;Site;Specialist;Structure;success;synergism;Technology;technology development;timeline;Translational Research;United States National Institutes of Health;virtual;Virus Diseases;Work

PROJECT_TITLE: Administrative Core


PROJECT_TERMS: Air;Blood;Bone Marrow;cancer care;Clinical;Code;Collaborations;Collection;Consent;Data;data management;Disease;Doctor of Medicine;Doctor of Philosophy;Ensure;experimental study;Follow-Up Studies;Future;Genomic medicine;Healthcare;Hospitals;Human;Human Resources;human subject;human tissue;Infrastructure;Life;Liquid substance;Lung;Lung immune response;microbiome;Nasopharynx;Ohio;Oral;Pediatric Hospitals;programs;Regulation;Research;Research Institute;Research Personnel;Research Project Grants;Resources;sample collection;Sampling;Specimen;stem cells;Structure of parenchyma of lung;technology development;The Jackson Laboratory;Tissue Sample;Training;Universities;Virus Diseases

PROJECT_TITLE: Sample Core


NIH_SPENDING_CATS: Aging;Clinical Research;Data Science;Infectious Diseases;Lung;Networking and Information Technology R&D (NITRD)

PI_NAMEs: CHAUSSABEL, DAMIEN  (contact)

PROJECT_TERMS: Affect;Age;age related;age related changes;Aging;aging process;Air;airway epithelium;Automobile Driving;Back;Bioinformatics;Biological;Candidate Disease Gene;candidate selection;Collaborations;Communicable Diseases;Communities;Complex;Computational Science;COVID-19 pandemic;Data;data access;Data Analyses;data dissemination;data harmonization;data integration;data interoperability;data management;data mining;data modalities;data repository;data reuse;Data Science Core;Data Set;data sharing;data submission;data visualization;Dedications;defined contribution;Doctor of Philosophy;Educational workshop;empowerment;Ensure;Epithelial Cells;Exhibits;experience;experimental study;FAIR principles;Functional disorder;Future;Generations;Genes;Geographic Locations;Goals;Human;Immune;Immune system;Immune System Diseases;Immunity;Immunologist;Immunology;Individual;Infrastructure;injured airway;insight;interoperability;Liquid substance;Lung;Lung immune response;medical schools;meetings;Meta-Analysis;Metadata;Mining;Modeling;Molecular;molecular phenotype;Molecular Profiling;multimodal data;multimodality;older adult;Older Population;Outcome;Pathway interactions;Policies;Predisposition;preventive intervention;Proteins;Publications;Research;Research Personnel;Research Project Grants;response;Risk Factors;Running;Sampling;Scientist;secondary analysis;Source;Source Code;Structure of parenchyma of lung;System;Systems Analysis;technology development;The Jackson Laboratory;Tissues;tool;transcriptome sequencing;United States National Institutes of Health;Validation;Virus Diseases;web app;Work

PROJECT_TITLE: Data Science Core


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Genetics;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PROJECT_TERMS: 2019-nCoV;3-Dimensional;adaptive immunity;Address;Affect;Age;age effect;age related;age related changes;aged;Aging;Air;airway epithelium;Alternative Splicing;Antigen Presentation;Antigen-Presenting Cells;antiviral immunity;Biological Assay;Breathing;CD8-Positive T-Lymphocytes;Cells;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Communicable Diseases;Coupled;COVID-19 pandemic;Data Analyses;Data Science Core;defined contribution;Dendritic Cells;Disease;E-Cadherin;Epigenetic Process;epigenetic regulation;Epithelial Cells;epithelial stem cell;Epithelium;experimental study;Exposure to;Functional disorder;Future;Gene Targeting;Generations;Genes;Genetic Transcription;Genome;Goals;Human;Immune;Immune response;Immune system;Immune System Diseases;Immunity;Immunofluorescence Immunologic;immunological status;Immunology;in vivo;Individual;induced pluripotent stem cell;Infection;Inflammation;Inflammatory;Inflammatory Response;Influenza;influenza infection;influenzavirus;innovative technologies;Interferon Type I;Interferons;Kinetics;Label;Link;Liquid substance;Lung;Lung immune response;Macrophage;Malignant neoplasm of lung;Measures;Messenger RNA;microbiome;Modeling;Molecular;multimodal data;Myelogenous;Natural Immunity;novel;older adult;Older Population;Operative Surgical Procedures;Outcome;pathogen;Pathway interactions;Patients;Polyadenylation;Predisposition;preventive intervention;Production;progenitor;programs;protein expression;Protein Isoforms;Proteins;Proteomics;Research;respiratory infection virus;respiratory virus;response;Risk Factors;RNA;RNA Splicing;sequencing platform;Shapes;Slice;stem cells;Structure of parenchyma of lung;System;T-Lymphocyte;Testing;Time;tissue resident memory T cell;Tissues;transcriptome sequencing;transcriptomics;Validation;Viral;Viral Antigens;Viral Proteins;Virus;Virus Diseases;young adult

PROJECT_TITLE: Modulation of lung immunity by epithelial cells from older individuals


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Lung;Microbiome;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PI_NAMEs: OH, JULIA  (contact)

PROJECT_TERMS: adverse outcome;Affect;Age;age related;age related decline;Aging;aging related;aging related disease;Air;Alveolar Macrophages;Anti-viral Response;antiviral immunity;ATAC-seq;Biological Assay;cell type;Cells;Chromatin;Chronic;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;commensal microbes;CRISPR interference;cytokine;Data;Data Science Core;differential expression;Disease;Electrical Resistance;Epigenetic Process;epigenome;Epithelium;Exposure to;flu;Genes;Genetic Transcription;genome-wide;Goals;Growth;Hour;IFNAR1 gene;Immune;Immune response;Immunity;Immunofluorescence Immunologic;Immunologic Memory;Individual;Inflammation;inflammatory milieu;Influenza;influenza infection;Interferons;knock-down;Knock-out;Link;Liquid substance;Lung;Lung immune response;Maintenance;Measures;Mediating;Memory;Metabolism;metabolomics;Methods;Microbe;microbial;microbial colonization;microbiome;Modeling;Modification;Morphogenesis;multiple omics;Natural Immunity;older adult;Outcome;pathogenic microbe;Pathway interactions;Patients;Phenotype;Play;Predisposition;Production;progenitor;resident commensals;respiratory;respiratory microbiome;respiratory microbiota;response;Role;Sampling;senescence;single-cell RNA sequencing;Specificity;Stimulus;technology development;therapeutic target;Tissues;transcriptome;transcriptome sequencing;transcriptomics;Viral;virulence gene;Virus Diseases

PROJECT_TITLE: Modulation of epithelial memory by the microbiome


PI_NAMEs: WILLIAMS, ADAM  (contact)

PROJECT_TERMS: 3-Dimensional;Address;age related;age related changes;Aging;aging related;Air;airway epithelium;Alleles;alveolar epithelium;Alveolar Macrophages;Alveolar sac;Alveolus;Animals;Back;Bacteria;Beds;Benchmarking;Biological Assay;bioprinting;bronchial epithelium;Bronchoalveolar Lavage;Cell Communication;Cell Shape;cell type;Cells;Coculture Techniques;commensal bacteria;Communities;CRISPR interference;Data;Dendritic Cells;Development;Engineering;Enterobacteria phage P1 Cre recombinase;Environment;Epigenetic Process;Epithelial Cells;Epithelium;experience;Exposure to;Flow Cytometry;Functional disorder;Funding;Genes;Genetic;Genetic Techniques;Genetic Transcription;Goals;Histologic;Homeostasis;Human;human tissue;Immune;immune function;Immune response;Immunity;Immunology;immunoregulation;improved;induced pluripotent stem cell;Infection;Inflammation;influenza infection;influenzavirus;Innate Immune Response;innovation;knockout gene;Liquid substance;Lung;Lung Diseases;Lung immune response;Macrophage;medical schools;Metabolic Pathway;Methodology;Methods;microbiome;microbiota;Microscopy;Modeling;Modification;Molecular;monocyte;Morphology;novel;Organ;overexpression;Pathway interactions;Physiological;Production;programs;Protein Isoforms;Recombinants;Recording of previous events;Reporter;Reporter Genes;Research;Resources;respiratory;respiratory virus;response;reverse genetics;RNA Splicing;Sampling;Shapes;Structure of parenchyma of lung;Study models;System;T-Lymphocyte;Technology;technology development;The Jackson Laboratory;Tissue Model;Tissues;tool;tool development;transcriptome sequencing;Vascularization;ventilation;Viral;viral detection;Viral Pathogenesis;Virus;Virus Diseases;Virus Integration;Work

PROJECT_TITLE: Technology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infection


NIH_SPENDING_CATS: Autism;Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative:  Epigenetic regulation through the post-translation modification of histones is critical for normal neuronal function and epigenetic regulators have been implicated in neurodevelopmental disorders including autism spectrum disorder (ASD). This project will study an uncharacterized epigenetic regulator, Setd2, in the context of neurons to determine its role in regulating neuronal function and explore how loss of Setd2 can lead to circuit dysfunction in a novel mouse model. Results are expected to aid the understanding how epigenetic dysregulation can lead to ASD, identify convergent pathways of different causes of ASD, and identify therapeutic targets for SETD2-related neurodevelopmental disorders.

PI_NAMEs: POPE, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Acute;Address;Affect;Agonist;Alternative Splicing;antagonist;autism spectrum disorder;Bacterial Artificial Chromosomes;Brain;cell type;Cells;ChIP-seq;Classification;Complex;Data;Databases;de novo mutation;Deposition;Development;differential expression;DNA Repair;Embryo;Epigenetic Process;epigenetic regulation;Epilepsy;Equilibrium;Etiology;excitatory neuron;Fragile X Syndrome;Functional disorder;Gene Expression;Genes;Genetic Transcription;Growth;Heterozygote;Histone H3;histone methylation;histone methyltransferase;histone modification;Histone-Lysine N-Methyltransferase;Histones;Homeostasis;Human;inhibitor;Intellectual functioning disability;Knowledge;loss of function;Lysine;Macrocephaly;Malignant Neoplasms;Measures;medical schools;Messenger RNA;metabotropic glutamate receptor 5;Methylation;Methyltransferase;Molecular;mouse model;mRNA Expression;mRNA Translation;Mus;Neocortex;Neurodevelopmental Disorder;Neurons;novel;Obesity;Ontology;patch clamp;Pathway interactions;Patients;Phenotype;Post-Translational Protein Processing;postnatal;Prosencephalon;Protein Biosynthesis;Protein Synthesis Inhibitors;Proteins;Research;Ribonucleoproteins;Ribosomal Proteins;Risk;risk variant;RNA;RNA Binding;RNA Splicing;RNA-Binding Proteins;Role;scaffold;SET Domain;Signal Pathway;Signal Transduction;Slice;somatosensory;Spliced Genes;Synapses;synaptic function;Synaptic Transmission;Syndrome;Testing;therapeutic target;Transcriptional Regulation;transcriptome sequencing;translation factor;Translations

PROJECT_TITLE: Mechanisms of Setd2 in cortical circuit function: Convergence with Fragile X Syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurosciences

ORG_DEPT: NEUROSURGERY

PHR: Brain oscillations and the genes associated with them are promising but poorly understood targets for future neuromodulatory therapies for cognitive disorders like Alzheimer’s disease. SMAD3 expression is associated with memory-enhanced oscillations and gene expression, but it is unknown exactly how SMAD3 influences cognitive processes in the brain. By silencing SMAD3 in human brain tissue in vitro, then characterizing how SMAD3-controlled gene networks influence synchronized neural activity in the same tissue, this project will make major progress toward the ultimate goal of developing neurotherapeutics for cognitive dysfunction.

PI_NAMEs: MOORE, HALEY D (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Action Potentials;Affect;Alzheimer's Disease;Animal Model;Animals;Autopsy;Binding;Binding Sites;Biological Markers;Brain;brain tissue;cell type;Cells;clinically relevant;Cognition Disorders;Cognitive;cognitive function;cognitive process;Cognitive Therapy;Collaborations;Complex;Culture Techniques;Data;Data Set;density;dentate gyrus;Development;Disease;effective therapy;Electrophysiology (science);Epilepsy;excitatory neuron;experience;experimental study;Fellowship;Frequencies;Functional disorder;Future;GABA Receptor;Gene Expression;Gene Expression Profile;gene network;Gene Targeting;gene-editing approach;Generations;Genes;Genetic;Genetic Transcription;Genomic approach;Glutamate Receptor;Goals;Human;Human Characteristics;Impaired cognition;Impairment;improved;In Vitro;innovation;insight;Investigation;Ion Channel;knock-down;Knockout Mice;Knowledge;Lead;Learning;Link;Long-Term Potentiation;MADH3 gene;Mediating;member;Memory;memory process;Mentors;Mentorship;Methods;Microelectrodes;Molecular;Molecular Biology;multiple omics;Mutation;Nervous System Disorder;neural;Neurodegenerative Disorders;neurogenesis;Neuroglia;Neurologic Dysfunctions;Neurons;neuropsychiatric disorder;neuroregulation;Neurosciences;neurosurgery;novel;novel therapeutics;Nucleic Acid Regulatory Sequences;Pathway Analysis;Pathway interactions;Patients;Peripheral;Phase;Physicians;Process;programs;Proteins;Publishing;Regulation;Regulator Genes;Regulatory Element;Reporting;Resources;Retrieval;Rodent;Role;Scientist;Signal Transduction;single nucleus RNA-sequencing;Slice;small hairpin RNA;Study Skills;support network;Synapses;System;Techniques;Temporal Lobe;Tissues;tool;Training;transcription factor;transcriptomics;Transforming Growth Factor beta;Viral;Work

PROJECT_TITLE: The role of SMAD3 in gene networks underlying human brain activity


PHR: Project Narrative The human nuclear pore complex is a !110 MDa protein complex that controls macromolecular transport between the nucleus and cytoplasm. We propose to develop a spatiotemporal integrative model that describes the assem- bly pathway of the human nuclear pore complex. We believe our work will elucidate the molecular mechanism that drives the formation of the nuclear pore complex, and will provide a computational framework to study the dynamics of other large macromolecules in the cell.

PI_NAMEs: LATHAM, ANDREW  (contact)

PROJECT_TERMS: Agreement;Autoimmune;Auxins;Cardiovascular Diseases;Cell Nucleus;Cells;Collaborations;Complex;computer framework;Cytoplasm;Data;density;Electron Microscopy;Electrons;Eukaryota;European;Evolution;Experimental Models;experimental study;Feedback;Fluorescence;Functional disorder;Future;Grain;Hour;Human;human disease;human model;improved;Individual;insight;Interphase;Laboratories;Light;light microscopy;Likelihood Functions;Link;macromolecule;Malignant Neoplasms;Membrane;Methodology;Microbiology;Modeling;Molecular;molecular modeling;Monte Carlo Method;Mutation;Nervous System Disorder;Nuclear Envelope;Nuclear Physics;Nuclear Pore Complex;Nuclear Proteins;Nuclear Structure;open source;Pathway interactions;Play;Pore Proteins;postmitotic;predictive modeling;Probability;Process;protein complex;Proteins;Research;Role;Sampling;simulation;spatiotemporal;Structure;Testing;theories;Time;Tomogram;Work

PROJECT_TITLE: Uncovering the molecular mechanism of interphase nuclear pore complex assembly with spatiotemporal integrative modeling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Bioengineering;Biotechnology;Gene Therapy;Genetics;Immunotherapy;Lung;Rare Diseases;Regenerative Medicine

PHR: Project Narrative Acute respiratory distress syndrome (ARDS) occurs when the lung is injured severely after, among other conditions, respiratory infections, trauma, or sepsis. 40% of patients with ARDS do not survive, and there are no current treatments, though they are urgently needed in preparation for the next respiratory pandemic. We plan to engineer cells that can deliver treatments predicted to help lung cells regenerate directly to the injured lung in hopes that these cells can someday be used to treat patients with ARDS.

PI_NAMEs: JACOB, ANJALI  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Adoptive Transfer;Adult;AGTR2 gene;Alveolar;alveolar epithelium;Alveolus;Area;Binding;cancer cell;Cell Differentiation process;Cell Line;Cell membrane;cell regeneration;Cell surface;Cell Surface Receptors;Cell Therapy;cell type;Cells;Cessation of life;chimeric antigen receptor T cells;Chronic lung disease;Clinical Trials;Coculture Techniques;COVID-19 pandemic;Cuboidal Cell;Cytoprotection;Data;design;engineered T cells;Engineering;Epithelial Cell Proliferation;Epithelial Cells;epithelial injury;Epithelium;epithelium regeneration;experimental study;Functional disorder;Future;Gases;Genes;Genetic Transcription;Goals;Growth Factor;Hepatocyte;HGF gene;Histologic;Human;improved;In Vitro;in vivo;in vivo Model;Inflammatory;injured;Injury;interest;Intravenous;keratinocyte growth factor;keratinocyte growth factor receptor;Knowledge;Label;Life;Ligands;Lung;lung injury;Malignant Neoplasms;Measures;Membrane;Membrane Proteins;mesenchymal stromal cell;MET gene;Modeling;mortality;mouse model;Mus;Natural regeneration;notch protein;Output;pandemic disease;Pathway Analysis;Patients;Permeability;Physiological;pre-clinical;Prediction of Response to Therapy;Predisposition;Preparation;prevent;Proliferating;Pulmonary Surfactant-Associated Protein C;Recombinant Growth Factor;Recombinant Hepatocyte Growth Factor;Recombinants;Regenerative response;Regulatory T-Lymphocyte;Reporter;respiratory;Respiratory Failure;Respiratory Tract Infections;response;response to injury;Sepsis;severe injury;Signal Pathway;Signal Transduction;stem cells;Structure of parenchyma of lung;Surface;surfactant;System;T cell therapy;T-Lymphocyte;Therapeutic;Therapeutic Uses;Tissues;transcription factor;Trauma;Type II Epithelial Receptor Cell

PROJECT_TITLE: Modulating signaling pathways in alveolar epithelial cells with engineered T cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Aging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Physical Activity

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE This project will determine the disease altering properties of high intensity aerobic exercise through the systematic examination of 250 individuals with Parkinson’s disease (PD) who participate in a 12-month community-based cycling program compared to a historical control group of 125 individuals with PD with identical outcome metrics. The role of genetics in exercise and disease progression will be examined by developing a prognostic model in which genetic burden, determined through the calculation of a PD polygenic risk score, is a key factor. Identifying the potential role genetics may have in modulating the disease altering potential of exercise will advance PD understanding and accelerate development of a personalized medicine approach to PD exercise prescription.

PI_NAMEs: ALBERTS, JAY L. (contact)

PROGRAM_OFFICER_NAME: CHO, HYUN JOO

PROJECT_TERMS: Acceleration;Address;Aerobic Exercise;Age;American Physical Therapy Association;Area;Behavioral;Biological;Biomechanics;Characteristics;Cities;Clinical;Communities;community setting;Control Groups;cost;Coupled;Data;demographics;Development;Disease;Disease Progression;disorder control;effective intervention;Effectiveness;Enrollment;executive function;Exercise;exercise prescription;exercise program;Gait speed;Genes;Genetic;Genome;Genotype;Healthcare;Heart Rate;illness length;improved;Individual;insight;Intervention;Laboratories;Latino Population;Location;Lower Extremity;Measures;Modeling;Motor;motor control;Movement Disorders;Nervous System Disorder;novel;Ohio;Operative Surgical Procedures;Outcome;Parkinson Disease;Participant;Patients;Performance;personalized medicine;Persons;Pharmaceutical Preparations;Pharmacologic Substance;Phenotype;physical therapist;Policies;Politics;polygenic risk score;Population;Posture;primary outcome;Process;processing speed;prognostic model;programs;Property;Protocols documentation;Randomized, Controlled Trials;Recommendation;recruit;Risk;risk variant;Role;sex;Short-Term Memory;Site;Societies;Sodium Chloride;Symptoms;Testing;Time;Trail Making Test;Translations;United States National Institutes of Health;Upper Extremity;Vertebral column

PROJECT_TITLE: The Interplay between Genetics and Aerobic Exercise to Slow Parkinson's disease (GEARS) Trial

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 SMEP-C (05)]


NIH_SPENDING_CATS: Cancer;Immunotherapy;Lymphatic Research

ORG_CITY: STANFORD

ORG_DEPT: PATHOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative: This fellowship application seeks to discover the immune cell population that is responsible for initiating the biological process that allows tumors to spread into distant organs, with the ultimate goal of developing a therapeutic strategy to treat metastatic disease. I will utilize state-of-the-art technology and computational analysis to identify these immune cells, and develop a therapy that reprograms them away from undertaking this undesirable role. Advances from the proposed study will broadly impact cancer patients since metastatic disease is a major cause of cancer-related deaths worldwide.

PI_NAMEs: HAYASHI, KAZUKUNI  (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Abbreviations;Activities of Daily Living;adaptive immunity;Address;Adjuvant;Adoptive Cell Transfers;Advanced Development;Antibodies;antibody conjugate;Antigen Presentation Pathway;Antigen Targeting;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Biological Assay;Biological Process;cancer cell;Cancer Etiology;Cancer Patient;Cell Communication;Cells;Cessation of life;Coculture Techniques;Computer Analysis;Detection;Development;Disease;Distal;Distant;Distant Metastasis;Education;Effector Cell;effector T cell;experimental study;Fellowship;Goals;high dimensionality;Human;Image;imaging system;Immune;Immune system;Immune Tolerance;Immunotherapeutic agent;In Vitro;in vivo;indexing;Infiltration;Innate Immune System;Invaded;Investigation;Knowledge;Ligands;Liver;Location;Lung;Lymph Node Involvement;Lymph Node Tissue;lymph nodes;Malignant Neoplasms;Mediating;Mediator;Melanoma;Metastasis Induction;Metastatic Neoplasm to Lymph Nodes;Modeling;Monoclonal Antibodies;mouse model;multiplexed imaging;Mus;Neoplasm Metastasis;neoplastic cell;novel;Organ;Organism;Pancreatic Ductal Adenocarcinoma;Phase;Phenotype;Population;programmed cell death ligand 1;programs;Publications;Publishing;Regulatory T-Lymphocyte;Role;single-cell RNA sequencing;spatiotemporal;T-Cell Development;T-Lymphocyte;Technology;Testing;Therapeutic;Time;transcriptomics;tumor;Tumor Antigens;Tumor Cell Invasion;Tumor Promotion;Work

PROJECT_TITLE: Reprogramming Antigen Presenting Cells in Lymph Nodes to Overcome Tumor Immune Tolerance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Duchenne/ Becker Muscular Dystrophy;Muscular Dystrophy;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DAVIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Many musculoskeletal diseases including Duchenne Muscular Dystrophy are characterized by the accumulation of extracellular matrix (ECM) components, termed fibrosis, which is widely viewed as irreversible. The proposed research aims to elucidate the mechanism by which fibrotic ECM organization affects mechanical properties and regenerative capacity of skeletal muscle, as well as the efficacy of Collagenase Clostridium histolyticum in treating muscle fibrosis. The results of these experiments will provide a greater understanding of the interaction between fibrotic ECM architecture and deficits in muscle function, as well as provide a potential therapeutic for reversing fibrosis in DMD and other musculoskeletal diseases.

PI_NAMEs: WOHLGEMUTH, ROSS PAUL (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Ablation;Affect;Anterior;Architecture;Articular Range of Motion;Biological Assay;boys;cell behavior;Cell Differentiation process;Chronic;Clinical Trials;Collagen;Collagen Fiber;Collagen Fibril;collagenase;Connective Tissue;Contracture;crosslink;Data;Dependence;Development;Digestion;Disease;Duchenne muscular dystrophy;Dystrophin;efficacy evaluation;Exhibits;experimental study;Extracellular Matrix;Fibrosis;Gel;Generations;Genes;Health;Hindlimb;imaging modality;Impairment;improved;in vivo;in vivo regeneration;Injections;insight;Intramuscular;Intramuscular Injections;Label;Lateral;Lead;Lower Extremity;mdx mouse;Measures;mechanical properties;Mechanics;Microbial Collagenase;Microscopy;Modeling;mortality;multiphoton microscopy;Muscle;Muscle Fibers;Muscle function;muscle progenitor cell;muscle regeneration;muscle stiffness;muscle strength;Muscle Weakness;Muscular Atrophy;Muscular Dystrophies;Musculoskeletal Diseases;Mutation;Myoblasts;Myopathy;Natural regeneration;patient mobility;Patients;prevent;Proliferating;Proteins;Quality of life;Recovery;reduced muscle strength;regeneration function;regeneration potential;regenerative;Regenerative capacity;Research;Running;second harmonic;Signal Transduction;Skeletal Muscle;stem cell function;stem cell proliferation;Stretching;Testing;Therapeutic;tissue regeneration;Tissues;transmission process;X Chromosome

PROJECT_TITLE: Using collagenase to target collagen architecture in fibrotic skeletal muscle to reduce stiffness and promote tissue regeneration.


NIH_SPENDING_CATS: Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Opioids;Pain Research;Pediatric;Prevention;Substance Misuse

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Identifying risk factors for prescription opioid use and cannabis use in emerging adults is key to preventing substance abuse disorders. Emerging adults who use cannabis are frequently prescribed opioids in medical settings, but the potential harms and benefits of co-use in the context of acute pain are unknown. The long-term goal of this research program is to identify malleable risk and protective factors that impact opioid and cannabis co-use in emerging adults receiving opioid prescriptions in the outpatient setting, which will directly inform preventative interventions.

PI_NAMEs: FELDSTEIN EWING, SARAH W.;WILSON, ANNA CAMILLE (contact)

PROGRAM_OFFICER_NAME: COLLIER KIDEMU, KEVA WONTORIA

PROJECT_TERMS: 21 year old;Acute Pain;Acute pain management;Adolescence;Adolescent;Adult;Affect;Age;age group;Ambulatory Care;Apical;Attenuated;biobehavior;Biological Assay;Biological Testing;Cannabis;Caring;Characteristics;chronic pain;Cohort Studies;community advisory board;Data;Databases;Development;diaries;Disease;Drug Monitoring;Drug Prescriptions;early onset;early onset substance use;Education;emerging adult;emerging adulthood;Employment;Enrollment;experience;Family history of;Frequencies;Funding;Future;Goals;Healthcare;improved;Individual;Intention;Intervention;Knowledge;marijuana legalization;marijuana use;marijuana use disorder;Measures;Medical;Medical Records;Mental Depression;Methods;Modeling;modifiable risk;Motivation;Nature;negative affect;Opioid;opioid exposure;opioid use;opioid use disorder;Outcome;Outpatients;Overdose;Pain;pain catastrophizing;Pain management;Pain Measurement;pain relief;Participant;Patient Self-Report;Pattern;Persons;Pharmaceutical Preparations;polysubstance use;prescription opioid;Prevention;preventive intervention;Preventive medical care;programs;prospective;Prospective, cohort study;protective factors;Provider;psychosocial;Recording of previous events;Recreation;reduced substance use;Reporting;Research;resilience factor;Risk;Risk Factors;Role;Sampling;Self Efficacy;Severities;substance abuse prevention;substance use;Substance Use Disorder;Surveys;Teenagers;THC concentration;therapy design;Time;transition to adulthood;young adult

PROJECT_TITLE: Co-use of cannabis and prescription opioids in emerging adults in medical settings

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Cancer;Genetic Testing;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety;Prevention;Prostate Cancer;Racial and Ethnic Minority Health Research;Urologic Diseases

ORG_CITY: LOS ANGELES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Accurate prediction of a highly variable clinical course is the key to effective management of localized prostate cancer, a disease that annually affects millions of lives. The germline genome has been shown to play a critical role in prostate cancer clinical outcomes, suggesting enormous potential for risk stratification applications. I will establish the utility of germline genomic biomarkers to enhance standard of care management for this disease.

PI_NAMEs: ZELTSER, NICOLE  (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Address;Adjuvant;Affect;African;African American population;African ancestry;Age;American;Androgens;Behavior;Biochemical;Bioinformatics;Biological Markers;Biopsy;BRCA2 gene;cancer diagnosis;Cancer Etiology;Cancer Patient;cancer type;Caring;Categories;Cessation of life;Chinese;Clinic;Clinical;clinical prognostic;clinical risk;cohort;Data;deprivation;Diagnosis;Disease;Disease Management;Disseminated Malignant Neoplasm;DNA;DNA Repair;Early Diagnosis;Financial cost;follow-up;gene repair;Genes;Genetic;Genome;genomic biomarker;Genomics;Germ Lines;Germ-Line Mutation;Goals;hazard;Health;Heritability;high risk;Histologic;Human;Impairment;improved;Incidence;Indolent;Inherited;lifetime risk;Local Therapy;Localized Disease;Longterm Follow-up;Malignant neoplasm of prostate;Malignant Neoplasms;men;men's group;Methods;Mexican;Modeling;Molecular;mortality;Multivariate Analysis;Mutate;Not Hispanic or Latino;Operative Surgical Procedures;Outcome;Pathogenicity;Patients;Performance;Play;polygenic risk score;predictive modeling;Prognosis;prostate cancer metastasis;prostate cancer progression;prostate cancer risk;Prostate Cancer therapy;Prostate-Specific Antigen;psychologic;Puerto Rican;Quality of Care;Quality of life;Radiation;rare variant;Recurrence;Regression Analysis;Relapse;relapse prediction;Risk;Risk Assessment;risk stratification;Role;Sampling;Scheme;Serum;Somatic Mutation;standard of care;Statistical Data Interpretation;Subgroup;Systemic Therapy;targeted sequencing;Testing;Training;tumor;Validation;Variant

PROJECT_TITLE: Predicting prostate cancer clinical outcomes with germline genomic biomarkers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: Hazardous drinking is a large and growing problem for Veterans across age groups. Many Veterans with hazardous drinking and other mental health problems seek care in the Emergency Department (ED). This study is a randomized controlled trial (N=450) of an alcohol intervention starting in the VHA ED with peer support personnel delivering brief alcohol advice, combined with a continuing 6-session program of post-ED strengths-based peer mentorship to facilitate reductions in alcohol use and to link Veterans with alcohol problems to needed primary and specialty care including other needed services such as homeless outreach and case management where needed. If successful, the proposed study will provide key data on the effectiveness of using peer support specialists in the VHA to help Veterans with hazardous drinking who may have difficulty engaging in needed care that potentially improve their mental and physical health outcomes.

PI_NAMEs: BLOW, FREDERIC C;PFEIFFER, PAUL NELSON (contact)

PROJECT_TERMS: Accident and Emergency department;Acute;addiction;Affect;Age;age group;Alcohol abuse;alcohol abuse therapy;alcohol consequences;Alcohol consumption;alcohol intervention;alcohol related consequences;alcohol risk;alcohol screening;alcohol seeking behavior;alcohol use disorder;Alcohols;Area;Back;behavior change;binge drinking;brief advice;brief alcohol intervention;brief intervention;care outcomes;care seeking;care systems;Caring;Case Management;Clinical;cohort;Communities;comparison intervention;coping;Data;design;drinking;drinking behavior;Educational Intervention;efficacy evaluation;Emergency Care;Emergency Department patient;Emergency department visit;Emotional;Enrollment;Environment;evidence base;experience;Frequencies;hazardous drinking;Health;Health Services Accessibility;Health Services Administration;Healthcare Systems;high risk drinking;Homelessness;Human Resources;Hybrids;implementation facilitators;improved;improved outcome;Individual;Intervention;intervention effect;Interview;Link;Managed Care;Measures;Mediator;Medical;Medical Care Team;Medical center;medical specialties;Mental Health;Mental Health Services;Mentorship;Meta-Analysis;Methods;Morbidity - disease rate;Motivation;Outcome;outreach;Participant;Patients;peer;peer coaching;peer support;physical conditioning;Post-Traumatic Stress Disorders;Primary Care;primary care setting;programs;Provider;psychiatric symptom;Public Health;Randomized;Randomized, Controlled Trials;Reporting;Research;Research Priority;Resources;Role;role model;screening;Self Efficacy;service delivery;Services;Social support;Specialist;Standardization;Structure;substance abuse treatment;suicidal;Symptoms;Time;Training;Treatment Efficacy;United States Health Resources Administration;Use Effectiveness;Veterans;Veterans Health Administration;Vulnerable Populations;War;Writing

PROJECT_TITLE: Improving Outcomes for Emergency Department Patients with Alcohol Problems

STUDY_SECTION_NAME: HSR-4  Mental and Behavioral Health[HSR4]


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Childhood Injury;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stroke;Unintentional Childhood Injury

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Despite progress in reducing the extent of injury after perinatal hypoxic-ischemic brain injury, there are presently no approved therapeutics to both reduce the extent of secondary injury and promote regeneration. The goal of this proposal is to use a mouse model of perinatal hypoxic-ischemic brain injury to test the therapeutic efficacy of a cytokine that we hypothesize will both preserve injured neurons and stimulate the replacement of damaged neurons and glia from the resident neural stem cells of the subventricular and subgranular zones.

PI_NAMEs: LEVISON, STEVEN W (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Action Potentials;Animals;antenatal;Anxiety;Apoptotic;Astrocytes;astrogliosis;Axon;axon injury;axon regeneration;Behavior;Behavior Disorders;behavioral impairment;Biological Assay;Brain Hypoxia-Ischemia;Brain Injuries;Brain region;Cell Death;cell injury;cell regeneration;Cells;Cerebral Palsy;Cerebrum;Cognition Disorders;Cognitive;Corpus Callosum;cytokine;Data;Development;Diffusion Magnetic Resonance Imaging;Discipline of obstetrics;Electrophysiology (science);Emotional;endogenous stem cells;Epilepsy;experimental study;Flow Cytometry;Genetic;gliogenesis;Gliosis;Goals;gray matter;Histologic;Hypoxic-Ischemic Brain Injury;imaging study;improved;in vivo;Incidence;Infant;Inflammation;Inflammatory Response;Injury;insight;Intranasal Administration;Knowledge;Learning;LIF gene;Life;loss of function;Maps;Memory;Microglia;Modeling;Molecular;Monitor;mortality;Motor;motor disorder;mouse model;Mus;Myelin;myelination;Natural regeneration;neonatal care;nerve stem cell;Nervous System Physiology;neural;neural initiation;neurogenesis;Neuroglia;Neurologic;Neurologic Deficit;Neurological disability;neurological recovery;neuron loss;Neuronal Injury;neuronal survival;Neurons;neurophysiology;neuroprotection;Oligodendroglia;Oxidative Stress;Perinatal;Perinatal Hypoxia;perinatal injury;perinatal ischemic stroke;Premature Birth;preservation;Production;progenitor;Proliferating;Publishing;Recovery;regenerative;Regenerative response;repaired;response;stem;stem cell niche;stem cell proliferation;stem cells;subventricular zone;Testing;Therapeutic;therapeutic evaluation;Treatment Efficacy;white matter;Wild Type Mouse

PROJECT_TITLE: Intranasal LIF to improve neurological recovery from perinatal hypoxia-ischema

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative This is a long-standing program to train scientists and physician/scientists in arteriosclerosis-related research. M.D.'s, Ph.D.'s, and others with professional degrees participate in an integrated clinical and laboratory research training program with a focus on heart disease and related disorders such as diabetes and hypertension. The program will also focus on mentoring the next generation of healthcare researchers.

PI_NAMEs: GINSBERG, HENRY N (contact);REILLY, MUREDACH P;TAYLOR, JACQUELYN Y

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TITLE: Postdoctoral Training in Arteriosclerosis Research

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Lung;Lung Cancer;Nutrition;Orphan Drug;Prevention;Rare Diseases;Tobacco;Tobacco Smoke and Health

ORG_CITY: HERSHEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative/Public Health Relevance Statement Tobacco smoking is a major etiological agent in the development of oral squamous cell carcinoma (OSCC) which is a disfiguring disease that can strip away the patient’s voice and certain basic needs such as eating and drinking. Although smoking cessation is the only intervention proven to reduce tobacco-related cancers, the results of this application will provide critical mechanistic insights toward the design of future chemoprevention trials targeting addicted smokers who are unable to quit as well as non- or former smokers who are exposed to carcinogens through environmental exposures (food-borne carcinogens, second-hand smoke).

PI_NAMEs: EL-BAYOUMY, KARAM E (contact)

PROGRAM_OFFICER_NAME: RISCUTA, GABRIELA

PROJECT_TERMS: adduct;Allelic Imbalance;Anthocyanins;Antioxidants;Aromatic Polycyclic Hydrocarbons;Base Excision Repairs;Benzo(a)pyrene;Biological Assay;Black Raspberry;carcinogenesis;Carcinogens;Cells;Chemoprevention;Chemopreventive Agent;Clinical Trials;cofactor;Cohort Studies;Cytoprotection;Data;Deoxyribonucleotides;design;Development;Dietary Intervention;Disease;disorder control;DNA Adducts;DNA Damage;DNA lesion;DNA Repair;DNA Repair Enzymes;DNA Repair Inhibition;DNA Structure;drinking;Drug Metabolic Detoxication;Eating;Enteral;Environment;Environmental Carcinogens;Environmental Exposure;environmental tobacco smoke;Enzymes;Epithelium;Epoxy Compounds;Etiology;Event;Excision;Exposure to;foodborne;former smoker;Freeze Drying;Future;Gel;Gene Mutation;genomic locus;Glutathione Disulfide;Glycols;Head and Neck Cancer;Heterogeneity;high risk;Human;In Vitro;insight;Intervention;keratinocyte;Knock-out;Literature;Loss of Heterozygosity;Malignant Epithelial Cell;malignant mouth neoplasm;Minerals;Molecular;mouse model;mouth squamous cell carcinoma;multimodality;Mus;Mutagenesis;Mutation;N'-nitrosonornicotine;NADP;neoplastic;Nitrosamines;novel;Nucleotide Excision Repair;OGG1 gene;Oral;Oral cavity;Oral Leukoplakia;Oral mucous membrane structure;Oxidation-Reduction;oxidative damage;oxidative DNA damage;Participant;Patients;Phase;Physical condensation;Powder dose form;preservation;prevent;Prevention;Prevention approach;Prevention strategy;Prevention trial;public health relevance;Pyrenes;Reaction;Recycling;Reduced Glutathione;repair enzyme;repair function;repaired;Ribonucleotides;Risk Factors;Role;Scheme;Skin Carcinoma;Smoker;smoking cessation;Structure;Surface;targeted treatment;Time;Tissues;Tobacco;Tobacco smoke;Tobacco smoking behavior;Tobacco use;Tobacco-Associated Carcinogen;Tobacco-Related Carcinoma;Topical application;TP53 gene;Transfection;translational study;Tumor Suppressor Genes;Voice;Xenobiotic Metabolism

PROJECT_TITLE: Chemoprevention by Black Raspberry of Oral Cancer Induced by Tobacco Carcinogens: Translational Studies

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Bioengineering;Kidney Disease

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE  We are proposing to create a new educational initiative titled MERRIT: Multidisciplinary Engineering and Renal Research for Innovation of Technology. The joint program between Mount Sinai and Cooper Union aims to bring together nephrology and engineering mentors from the two institutions to supervise patient-centered design teams and individual research projects on kidney disease.

PI_NAMEs: AZELOGLU, EVREN U. (contact);LIMA, ERIC GEVORK

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: 3D Print;Accounting;Achievement;Acute;Award;Awareness;Biomedical Engineering;Budgets;career;Chemical Engineering;Chronic Kidney Failure;Clinical;Collaborations;collaborative environment;Communities;cost;design;Development;drug development;drug discovery;Education;education research;Engineering;Equipment;Evaluation;Expenditure;experience;Faculty;Future;graduate student;Hour;Human;Individual;innovation;Institution;Internal Medicine;Internet;Interview;invention;Joint Ventures;Joints;Journals;Kidney;Kidney Diseases;Libraries;Life Style;manufacture;Manuscripts;materials science;Mechanics;medical schools;Medicare;member;Mentors;Mentorship;Modernization;multidisciplinary;Nephrology;new technology;novel therapeutics;Outcome;patient oriented;Patients;Peer Review;Physicians;Physiology;Postdoctoral Fellow;programs;prototype;Publishing;recruit;Research;Research Personnel;Research Project Grants;Resources;Schools;Scientist;Series;skills;Solid;Structure;Students;summer research;symposium;technological innovation;Technology;technology development;Therapeutic;Training;Transplantation;Treatment Cost;undergraduate research experience;undergraduate student;web site;Work

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


ORG_CITY: LA JOLLA

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative The goal of this training program is to develop the next generation of clinician-scientist in the field of Anesthesiology. We propose to continue a unique training experience that addresses core clinical problems in anesthesiology and utilize collaborative research experiences across the campus. Fellows with their mentoring team have the ability to work beyond, within, and in larger collaboratives to undertake research at the broadest level to involve as many disciplines necessary to adequately address the questions asked to solve unique problems.

PI_NAMEs: PATEL, HEMAL H (contact);ROTH, DAVID M

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TITLE: Interdisciplinary Anesthesiology Research Training Program


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Narrative Rapid evolution of influenza and other viruses, such as SARS-CoV-2, to escape immunity prevalent in the population challenges development of vaccines with long-term protective efficacy. This Project seeks to resolve key questions concerning immune-response mechanisms and to apply them to immunogen-design approaches. It will study human responses to vaccination and conduct immunization experiments in non-human primates and mice.

PI_NAMEs: HARRISON, STEPHEN COPLAN (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: 2019-nCoV;Affect;Affinity;Age;age group;Anatomy;Antibodies;Antibody Affinity;Antigenic Variation;Antigens;B cell repertoire;B-Lymphocyte Epitopes;B-Lymphocytes;Binding Sites;Blood;Cell Compartmentation;Cells;cohort;Coupling;design;Directed Molecular Evolution;Distant;Epitopes;Evolution;exhaustion;experimental study;Face;Foundations;future pandemic;Goals;Grant;Hemagglutinin;Herd Immunity;Human;Humoral Immunities;Immune;Immune response;Immunity;Immunization;imprint;In Vitro;Individual;Infant;Infection;Influenza;influenzavirus;Laboratories;Location;lymph nodes;Memory;Memory B-Lymphocyte;Modeling;Molecular;movie;Mus;Neuraminidase;nonhuman primate;novel;novel vaccines;pandemic virus;Plasma Cells;Plasmablast;Population;pressure;programs;Property;protective efficacy;Proteins;receptor binding;Recording of previous events;response;Role;Sampling;Secure;Serum;Specificity;Structure;T-Lymphocyte Epitopes;Testing;Update;Vaccination;vaccination strategy;Vaccine Antigen;vaccine development;vaccine efficacy;vaccine response;Vaccines;Variant;Viral;viral resistance;Virus;Zoonoses

PROJECT_TITLE: Structure-function analysis of infection- and vaccine-induced B-cell repertoires


PROJECT_TERMS: Administrator;Agreement;Animals;Area;Authorship;B cell repertoire;Boston;Communication;Decision Making;Disclosure;Ensure;experience;Grant;human subject protection;Individual;Infection;Institution;Laboratory Research;Leadership;Manuscripts;meetings;Monitor;Occupational activity of managing finances;Office of Administrative Management;organizational structure;Pediatric Hospitals;Periodicals;Preparation;Principal Investigator;programs;Progress Reports;Publications;Quality Control;Radiation;Regulation;Reporting;Research;Research Personnel;Schedule;Structure;symposium;Technology Transfer;United States National Institutes of Health;Vaccines;web site;Writing

PROJECT_TITLE: Core A: Administrative Core


ORG_NAME: DANA-FARBER CANCER INST

PHR: Relevance to Public Health One of the major drawbacks in using currently available epigenetic perturbants, such as histone deacetylase (HDAC) inhibitors, is that they often affect the transcriptional levels of thousands of genes at once, which greatly hinders their use in treating most human pathologies, at the exception of a few blood cancers. We hypothesize that to widen the use of epigenetic perturbants as potential therapeutics, a new generation of inhibitors needs to be developed with much more specific effects on the transcriptome, corresponding to a paradigm shift from “multigenic” to “oligogenic” HDAC inhibitors. In this application, we propose to develop a novel strategy to identify “oligogenic” HDAC complex inhibitors, investigate how these new compounds affect the transcriptome, and understand the molecular mechanisms underlying these activities, which might in turn help developing a second generation of epigenetic perturbants with improved therapeutic properties.

PI_NAMEs: VIDAL, MARC  (contact)

PROGRAM_OFFICER_NAME: AMIN, ANOWARUL

PROJECT_TERMS: Address;Affect;anti-cancer;Binding;Biological;Biological Availability;Biological Models;Cancer Death Rates;cancer immunotherapy;cancer type;Cell Line;Cell Physiology;Cells;Complex;Data;Deacetylase;Development;drug discovery;Enzymes;Epigenetic Process;experimental study;FDA approved;Future;gene repression;Generations;Genes;Genetic Transcription;Goals;Hematopoietic Neoplasms;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;Human Pathology;immune checkpoint blockade;Immunotherapy;improved;In Vitro;in vivo;inhibitor;Invaded;Investments;Learning;Malignant Neoplasms;Mammalian Cell;Modeling;Molecular;Multiple Myeloma;neoplastic cell;neuroblastoma cell;novel;novel strategies;novel therapeutics;paralogous gene;Pathway interactions;Pharmaceutical Preparations;Phenotype;Phosphotransferases;promoter;Property;protein complex;Proteins;Public Health;Regulation;Reporter;Reporter Genes;Repression;small molecule;small molecule libraries;Specificity;Substrate Specificity;T-Cell Lymphoma;targeted cancer therapy;targeted treatment;Testing;Therapeutic;Tissues;Transcriptional Regulation;transcriptome;transcriptomics;tumorigenesis;tumorigenic;Work;Yeasts

PROJECT_TITLE: Selective disruption of histone deacetylase complexes using protein interaction modulators

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

PI_NAMEs: VALENCIA, SARAH M (contact)

PROJECT_TERMS: Animal Model;Animals;Antibodies;Antigens;Avian Influenza;B cell repertoire;biocontainment facility;biodefense;Biological Assay;Biomedical Research;Collaborations;Collection;Consultations;Development;experience;Ferrets;Funding;Goals;Grant;Hamsters;Human;Immune response;Immunology;in vitro Assay;Infection;Influenza;influenza virus strain;influenzavirus;Laboratory Animal Models;laboratory facility;Lead;Libraries;Microbiology;Modeling;Monitor;Mus;National Institute of Allergy and Infectious Disease;Pathogenicity;Plasma;Procedures;Productivity;programs;Qualifying;Quality Control;Reagent;repository;Research;Research Activity;Research Support;response;Risk;Sampling;Secure;Serum;Services;Specimen;ST14 gene;Structure;Vaccines;virology;Virus;Work

PROJECT_TITLE: Core B: Virology Core


ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative Since cardiovascular and respiratory diseases including heart attack, high blood pressure, obesity, metabolic disease, stroke, asthma, and emphysema are major health problems in the USA and world-wide, it is necessary to train scientists as integrative thinkers capable of pushing the frontiers of mechanistic, organismal physiology knowledge to better understand disease processes. For nearly 25 years of continuous T32 funding, we have had a strong track record of training predoctoral students in multidisciplinary didactic instruction and modern physiological research in order to prepare students to conduct physiological research using novel techniques and methods and teach future generations of physicians and scientists how the human body works in health and disease. For these and other reasons, we request funds to support eight predoctoral students each year for the next five years.

PI_NAMEs: HODGES, MATTHEW ROBERT (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Organism;Physiology;Training

PROJECT_TITLE: Integrated Physiology Training: Molecule to Organism


PI_NAMEs: LEE, JIWON  (contact)

PROJECT_TERMS: age group;analytical tool;Antibodies;Antibody Repertoire;Antibody Response;Antigens;Attention;B cell repertoire;B-cell receptor repertoire sequencing;B-Lymphocytes;college;Data;Data Analyses;data repository;database query;design;Development;DNA Sequencing Facility;Elderly;Engineering;Exposure to;Funding;Goals;Hemagglutinin;Human;Humoral Immunities;Immune;imprint;Individual;Infant;Infection;Influenza;Influenza Hemagglutinin;Influenza vaccination;influenza virus vaccine;Infrastructure;Investigation;Length;Liquid Chromatography;Mediating;Memory B-Lymphocyte;Molecular;Monitor;Monoclonal Antibodies;Neuraminidase;next generation sequencing;Online Systems;Plasmablast;Play;Population;professor;programs;Proteomics;Recombinants;Research Personnel;Research Support;Resolution;Resources;response;Role;Sampling;seasonal influenza;Seasons;Sequence Analysis;Series;Serum;Services;Shapes;Structure;success;tandem mass spectrometry;Technology;Time;tool;Transcript;transcriptomics;Vaccination;vaccination strategy;Vaccines;Viral;Virus Diseases;Work;young adult

PROJECT_TITLE: Core C: IgSeq and NGS Core


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

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Tumor-initiating cells are a rare subpopulation of tumor cells that have intrinsic resistance to standard cancer therapeutics. This proposal seeks to clarify the relationship between tumor initiating cells (TIC) in the primary tumor and metastasis-initiating cells (MIC) at metastatic sites capable of forming macrometastases, and to identify TIC vulnerabilities that can be exploited to prevent tumor progression. We anticipate the findings from this work will reveal a transcriptional program that is unique to tumor-initiating cells, which can be leveraged to eliminate cells that escape the effects of cancer therapeutics.

PI_NAMEs: SOUTO, ERIC PHILIP (contact)

PROJECT_TERMS: Address;Behavior;cancer stem cell;candidate identification;Cell Line;Cell Physiology;Cell Proliferation;Cell surface;Cells;Cellular biology;chemotherapy;Classification;Clinical;Confocal Microscopy;CRISPR/Cas technology;Critical Pathways;Development;Disease;Distant;Drug resistance;DsRed;Enterobacteria phage P1 Cre recombinase;Epithelium;ERBB2 gene;ESR1 gene;Excision;Fatty acid glycerol esters;Flow Cytometry;Fluorescence-Activated Cell Sorting;Gene Expression Profile;Generations;Genes;Genetic;genetic manipulation;Genetic Predisposition to Disease;Genetic Transcription;Harvest;Histologic;Hormonal;Human;improved;Intraperitoneal Injections;Knock-out;Label;Lesion;Malignant Breast Neoplasm;Malignant Neoplasms;Mammospheres;Mediating;Metastatic/Recurrent;Methods;Modeling;Molecular;mortality;Mus;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Outcome;overexpression;Palpable;Pathway interactions;patient derived xenograft model;Patients;Phenotype;Play;Population;predicting response;pressure;prevent;Primary Neoplasm;Prognosis;prognostic;programs;Property;rare cancer;Recurrence;Reporter;Resistance;response;Role;self-renewal;Signal Transduction;single-cell RNA sequencing;Site;STAT3 gene;stem cell biology;System;Tamoxifen;targeted treatment;Testing;Therapeutic;Transplantation;treatment response;triple-negative invasive breast carcinoma;tumor;tumor heterogeneity;tumor initiation;tumor progression;Tumor Promotion;tumor xenograft;Work

PROJECT_TITLE: Identifying and Targeting STAT3 Tumor-Initiating Cells in Triple-Negative Breast Cancer


PHR: Project Narrative The goal of our T32 training program is to train the next generation of academic anesthesiologists to become independent physician-scientists in the field of anesthesiology and perioperative medicine. Our T32 research training program has four main research themes: 1) Perioperative Organ Protection, 2) Cardiovascular, 3) Neurosciences and Brain Health, and 4) Biocomputing/Bioengineering and Health Informatics.

PI_NAMEs: CANNESSON, MAXIME ;EGHBALI, MANSOUREH  (contact)

PROJECT_TITLE: Multidisciplinary Anesthesiology and Perioperative Medicine Research Training Program