NIH_SPENDING_CATS: Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BOSTON

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Project Narrative We seek to understand the contributions of distinct antimicrobial functions in neutrophils that are targeted by YopH and YopO from the bacterial pathogen, Yersinia pseudotuberculosis and then assess whether these functions are critical to control growth of Klebsiella pneumonia, during lung infections.

PI_NAMEs: MECSAS, JOAN C (contact)

PROJECT_TERMS: Agonist;Antibacterial Response;antimicrobial;Atherosclerosis;Autoimmune Diseases;Bacteria;bacterial genetics;bactericide;Biological Models;Cells;Chemotaxis;Communicable Diseases;Critical Pathways;Cytoplasmic Granules;Dependence;Development;Diabetes Mellitus;Disease;Event;extracellular;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Genetic;genetic manipulation;Goals;Gram-Negative Bacterial Infections;Growth;Hematopoietic stem cells;Immune;in vitro Assay;in vivo;Infection;Infection Control;insight;Integrins;Klebsiella Infections;Klebsiella pneumoniae;Learning;Location;Lung;Lung infections;Lupus;Malignant Neoplasms;MAPK3 gene;Measures;Mediating;Membrane;migration;Missense Mutation;Modeling;Molecular;Multi-Drug Resistance;Multiple Bacterial Drug Resistance;Mus;mutant;Mutation;Myeloid Progenitor Cells;neutrophil;novel;Pasteurella pseudotuberculosis;pathogen;pathogenic bacteria;Pathway interactions;Phagocytosis;phosphatidylinositol 3-kinase gamma;Phosphorylation;Phosphorylation Site;Play;PLCgamma2;Predisposition;prevent;Process;Production;protein complex;Protein Tyrosine Kinase;Protein Tyrosine Phosphatase;Protein-Serine-Threonine Kinases;Proteins;Reactive Oxygen Species;receptor;response;rhoB p20 GDI;Role;scaffold;Signal Pathway;Signal Transduction;skills;Syndrome;Testing;Therapeutic;Time;Tissues;Virulence;Visualization;Work;Yersinia

PROJECT_TITLE: Dissecting Yersinia Yop Targets in Neutrophils


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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);Antimicrobial Resistance;Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Emerging Infectious Diseases;Health Services;Infectious Diseases;Neurodegenerative;Neurosciences;Palliative Care;Prevention;Urologic Diseases

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: HEBREW REHABILITATION CENTER FOR AGED

ORG_STATE: MA

PHR: A body of research conducted by our group has demonstrated a critical need to improve the quality of care for suspected infections among nursing home residents with advanced Alzheimer’s disease and related dementias. As the next logical step, we will conduct a cluster randomized controlled trial of an intervention to optimize infection management in this population. This work addresses 3 federal research priority areas: Alzheimer’s disease, palliative care, and infection management, including initiatives to expand antibiotic stewardship activities in NHs. Thus, this work has the potential to make clinical and policy-relevant contributions by promoting patient-centered end-of-life care for millions of Americans with advanced dementia, and reducing the growing public health threat of MDROs in the nursing home setting.

PI_NAMEs: MITCHELL, SUSAN L (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Address;Advance Care Planning;advanced dementia;advanced directive;Algorithms;Alzheimer's Disease;Alzheimer's disease related dementia;American;Antibiotics;antimicrobial;Area;arm;Bacterial Infections;Bladder;Blood;Boston;Caring;case-based;Catheterization;Clinical;Communicable Diseases;Consensus;cost;Counseling;Data;Dementia;Education;end of life care;Event;Exposure to;Feedback;Foundations;Goals;Guidelines;Hospitalization;Hospitals;improved;Infection;infection management;Intervention;Intervention Trial;Lower Respiratory Tract Infection;Lower respiratory tract structure;medication administration;multi-component intervention;Multi-Drug Resistance;multi-drug resistant pathogen;Nursing Homes;Nursing Research;nursing standards;online course;Outcome;Palliative Care;Pamphlets;Parents;pathogen;patient oriented;Patients;Persons;Phase;Pilot Projects;Policies;Population;primary outcome;Procedures;programs;prospective;Prospective Studies;Provider;Proxy;Public Health;Quality of Care;Randomized, Controlled Trials;Records;Recurrence;Research;Research Infrastructure;Research Priority;Resistance;Risk;Risk Factors;secondary outcome;Thoracic Radiography;Training;treatment as usual;United States National Institutes of Health;urinary;Urinary tract;Urinary tract infection;Work

PROJECT_TITLE: Trial to Reduce Antimicrobial Use in Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD)

STUDY_SECTION: HSOD

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


ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Aging;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Liver Cancer;Liver Disease;Organ Transplantation;Rare Diseases;Transplantation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE This is a mid-career mentoring award that will expand Dr. Lai’s time and ability to mentor clinician-investigators in patient-oriented research at the intersection of aging research, hepatology, oncology, and transplantation, as well as to expand her research program to an under-studied population of older adults with hepatocellular carcinoma awaiting and undergoing liver transplantation.

PI_NAMEs: LAI, JENNIFER C. (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: abdominal CT;Acceleration;Accounting;Adipose tissue;Age;age effect;Aging;aging demography;aging related;Alzheimer's disease risk;Award;Cancer Etiology;career;career development;Caring;Categories;Cessation of life;Chronic;chronic liver disease;Chronology;Cirrhosis;Classification;Clinical;Clinical Research;cohort;Communities;comorbidity;curative treatments;Data;Data Set;Databases;Decision Making;Dedications;demographics;disability;Discipline;Disease;Dropout;Educational Curriculum;Elderly;Eligibility Determination;Endowment;Ensure;Exclusion;experience;Faculty;Financial Support;fitness;frailty;functional status;Funding;Gastroenterology;Geriatrics;Habilitation;Health;Hepatology;Hospitalization;human old age (65+);Impaired cognition;Improve Access;improved;indexing;Industry;Infrastructure;interest;Intervention;Intuition;Knowledge;Laboratories;Leadership;Liver;Liver diseases;Liver Failure;liver function;liver transplantation;Living Donor Liver Transplantation;Measurement;Medical;Medicine;Mentors;Mentorship;mid-career faculty;Modeling;mortality;MRI Scans;Muscle;muscle form;Natural History;next generation;novel;older adult;Older Population;Oncology;Operative Surgical Procedures;Organ;Organ Transplantation;Outcome;Pathway interactions;patient oriented;patient oriented research;Patients;Pattern;Perioperative;Physiological;Population;Positioning Attribute;post-transplant;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;pro-aging;prognostic;programs;Quality of life;Recurrence;Research;Research Personnel;Research Project Grants;Research Support;Resources;Risk;Risk Assessment;Risk Factors;Role;Severity of illness;Skeletal Muscle;skill acquisition;skills;Solid;Stage at Diagnosis;Standardization;Structure;Surgical Specialties;Testing;Time;Training;transplant centers;Transplant Recipients;Transplantation;tumor;Tumor Burden;tumor progression;Waiting Lists;Work;α-Fetoproteins

PROJECT_TITLE: The Impact of Frailty on Liver Transplant Outcomes in Older Adults with Hepatocellular Carcinoma

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


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

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative: In this proposal we aim to learn how abnormal biomolecular condensates contribute to the pathogenesis of tauopathy. Tauopathies, including AD/ADRD, are among the leading causes of death in the U.S. today1, and effect more than 50 million people world-wide (WHO). Through this work we will identify molecular mechanisms in early disease in order to develop targets for future pharmaceutical interventions.

PI_NAMEs: SEGAL, ROSALIND A. (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Acceleration;Affect;Alternative Splicing;Alzheimer's Disease;Alzheimer's disease related dementia;Antigens;Area;Axon;Axonal Transport;axonopathy;axoplasm;Binding;Cause of Death;Cell Nucleus;cell type;Cells;Central Nervous System;combat;Cytoplasm;Cytoplasmic Granules;cytotoxic;Data;Defect;Disease;DNA Repair;Early identification;Early Intervention;Event;Future;genetic approach;Glutamine;Human;hyperphosphorylated tau;Image;Impairment;induced pluripotent stem cell;innovation;Interruption;Intervention;Kinesin;Lead;Learning;Liquid substance;loss of function;Measures;Messenger RNA;Methods;Modeling;Molecular;Molecular Conformation;Motor;Motor Neurons;mRNA Export;mutant;Mutation;Nature;Nerve Degeneration;Neurodegenerative Disorders;neuronal cell body;Neurons;Nuclear;nucleocytoplasmic transport;Onset of illness;Pathogenesis;Pathogenicity;Pathologic;Pathology;Persons;pharmacologic;Pharmacologic Substance;Phase;Physical condensation;Play;prevent;programs;Proline;protein aggregation;protein function;Protein Splicing;Research;RNA;RNA Splicing;RNA Transport;RNA-Binding Proteins;Role;stress granule;T-Lymphocyte;tau aggregation;tau mutation;tau Proteins;tau-1;Tauopathies;Testing;Therapeutic;Time;Translations;Work

PROJECT_TITLE: Formation and function of pathologic stress granules containing RNA-Binding Protein SFPQ in tauopathy


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Hematology;Physical Injury - Accidents and Adverse Effects

ORG_CITY: PITTSBURGH

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative Severe bleeding is the most common cause of preventable death after traumatic injury, and trauma-induced coagulopathy contributes to this condition and increases the risk of mortality by 400%. Platelet dysfunction is one of the major contributors to trauma-induced coagulopathy, and therefore a biofidelic microfluidic assay will be employed to study platelet contributions to clot formation and further clarify the impact and origins of trauma- induced platelet dysfunction, and will also be used to inform on the effect of platelet transfusion approaches to resuscitate severely bleeding trauma patient samples in vitro. This microfluidic platform can provide highly physiologically-relevant hemostatic function assessment in preclinical studies, and has the potential to cause a paradigm shift in the study of hemostatic resuscitation, thereby furthering understanding of trauma-induced coagulopathy and allowing optimization of the hemostatic function of blood products that are transfused into severely bleeding patients.

PI_NAMEs: SHEA, SUSAN MARGUERITE (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Address;Admission activity;Age Years;aged;Agonist;Biological;Biological Assay;Biomedical Engineering;Bleeding time procedure;Blood Platelets;blood product;Blood specimen;Blood Vessels;Caring;Cause of Death;Cessation of life;Clinical;clinical development;clinical efficacy;Clinical Trials;Clot retraction;Coagulation Process;Data;Development;Doctor of Philosophy;Education;End Point Assay;Ensure;Etiology;experience;Five-Year Plans;Functional disorder;Funding;Goals;Hemorrhage;Hemostatic Agents;Hemostatic function;Hospitalization;Hour;In Vitro;Individual;Injury;innovation;insight;Institution;Interdisciplinary Study;Kinetics;Knowledge;Licensing;Measures;Mediator;medical schools;Mentors;Mentorship;Metabolic;Microfluidics;Microscopy;Mission;Modeling;Molecular;Morphology;mortality;mortality risk;National Heart, Lung, and Blood Institute;novel;Outcome;Patients;Perfusion;Phenotype;Physiological;Plasma;platelet function;platelet phenotype;Platelet Transfusion;point of care;Porosity;pre-clinical assessment;preclinical study;prevent;preventable death;Productivity;programs;ratiometric;receptor;Recording of previous events;Research;Research Personnel;Resources;Resuscitation;Risk;Sampling;SELP gene;Signal Transduction;Structure;success;Surface;synergism;Technical Expertise;Temperature;Testing;Therapeutic;therapy development;Time;tool;Transfusion;transfusion medicine;Translational Research;translational scientist;Trauma;trauma induced coagulopathy;Trauma patient;Traumatic Hemorrhage;Traumatic injury;Treatment Efficacy;United States;United States National Institutes of Health;Universities;Venous;Washington;Work

PROJECT_TITLE: Using Microfluidics to Identify Mechanisms of Platelet Dysfunction and Assess Therapeutic Efficacy in Traumatic Hemorrhage

STUDY_SECTION: MTI

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics;Human Genome

ORG_CITY: BURLINGTON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because proper control of chromosome segregation is necessary to prevent aneuploidy and genomic instability, which contribute to the development and progression of tumors and trisomy syndromes. Furthermore, determining the mechanisms and regulation of kinesin motor proteins is directly related to understanding how alterations in the functions of these proteins disrupt development and contribute to congenital disorders and cancer.

PI_NAMEs: STUMPFF, JASON K (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Aneuploidy;Biological;Biophysics;cell type;Cells;Chromosome Arm;chromosome missegregation;Chromosome Segregation;Chromosome Structures;Congenital Disorders;crosslink;Development;Ensure;Generations;genome integrity;Genomic Instability;interdisciplinary approach;Kinesin;Knowledge;Lead;Length;live cell imaging;Malignant Neoplasms;Mechanics;micronucleus;Microtubules;Mitosis;Mitotic Chromosome;Mitotic spindle;Molecular;Molecular Motors;Motor;Movement;Mutagenesis;neoplastic cell;Play;preservation;prevent;protein function;Proteins;Public Health;Regulation;Research;Role;single molecule;Slide;Structure;Syndrome;Tissues;Trisomy;tumor progression;Whole Organism

PROJECT_TITLE: Mechanisms of microtubule motors and chromosome segregation

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Hematology;Prevention

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Clonal hematopoiesis (CH) has recently emerged as an important new risk factor for cardiovascular disease. This application will seek to elucidate the underlying mechanisms linking CH, inflammation and atherosclerosis.

PI_NAMEs: TALL, ALAN RICHARD (contact)

PROGRAM_OFFICER_NAME: SCHOPFER, DAVID WESLEY

PROJECT_TERMS: Acceleration;Age;Anti-Inflammatory Agents;Antibodies;Antibody Therapy;Antioxidants;Apoptotic;Arterial Fatty Streak;Atherosclerosis;Automobile Driving;Binding;Blood Cell Count;Bone Marrow Cells;Breeding;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;CASP1 gene;Caspase;Cell Death;Cells;coronary event;Coronary heart disease;Defect;density;DNA;DNA Fragmentation;Elderly;Endowment;Enzymes;experimental study;extracellular;gain of function;Generations;Genetic;genetic variant;Genotype;Glycolysis;Goals;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Human;Human Genetics;IL18 gene;Impairment;in vivo;Infection;Inflammasome;Inflammation;Interleukin-1;Interleukin-1 beta;JAK2 gene;Lead;Lesion;Leukocytosis;Link;loss of function;Macrophage;Mediating;Metabolic;Mitochondria;Modeling;mouse model;Mus;Mutation;Myocardial Infarction;Necrosis;neutrophil;novel strategies;oxidation;Pathway interactions;Patients;Persons;Polycythemia;Population;premature;Proliferating;Resistance;Respiration;Risk;Risk Factors;risk variant;Role;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;Somatic Mutation;Stroke;Thrombosis;Transplantation;Variant

PROJECT_TITLE: Clonal hematopoiesis, inflammasomes and atherosclerosis

STUDY_SECTION: AICS

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


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: STANFORD

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The spatial organization of proteins within biological tissues plays a critical role in the normal functioning of the tissue and disease development. Our project aims to develop a high throughput and scalable technology for deep and unbiased spatial mapping of the proteome in tumor tissue slices. Our work is expected to accelerate mass spectrometry-based spatial proteomics, thereby advancing biomedical research and clinical diagnostics towards a better understanding of the role of tissue heterogeneity in pathophysiology, such as the role of the tumor microenvironment on cancer progression, for identifying novel biomarkers and therapeutic targets to facilitate the early detection, diagnosis, and intervention of diseases.

PI_NAMEs: TANG, SINDY KAM-YAN (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Acceleration;Address;Antibodies;Biological;biomarker identification;Biomedical Research;Cancer Biology;cancer initiation;Cell Physiology;Cells;clinical diagnostics;Couples;Data;design;Development;Devices;Diagnosis;Disease;Dissection;Early Diagnosis;Ethanol;Extracellular Protein;fabrication;Functional disorder;Goals;Heterogeneity;Human;imaging approach;Immunosuppression;innovation;innovative technologies;Intervention;Label;laser capture microdissection;Liquid Chromatography;Manuals;Maps;mass spectrometric imaging;Mass Spectrum Analysis;Measures;meter;Methods;Microdissection;Microfluidic Microchips;Microfluidics;Molecular;nano;nanoDroplet;nanofabrication;Neoplasm Metastasis;new technology;new therapeutic target;novel;novel marker;novel therapeutic intervention;Outcome;Pathology;Pathway interactions;Pharmaceutical Preparations;Play;Post-Translational Protein Processing;Preparation;preservation;Process;protein biomarkers;Proteins;Proteome;Proteomics;Publishing;Resolution;response;RNA;Role;Running;Sampling;Site;skin squamous cell carcinoma;Slice;Spatial Distribution;spatial integration;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;tandem mass spectrometry;Technology;technology platform;therapeutic target;tissue fixing;tissue mapping;Tissue Preservation;Tissues;transcriptomics;tumor;tumor heterogeneity;tumor initiation;tumor microenvironment;tumor progression;Tumor Tissue;Work

PROJECT_TITLE: An integrated microtechnology platform for spatially resolved mass spectrometry-based proteomics

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

PHR: Project Narrative This is a highly synergistic program project grant engaging multidisciplinary expertise in order to accelerate the advancement of xenotransplantation, the transplantation of organs from animals to humans, which is our best hope for overcoming the severe shortage of human organs for transplantation. We will use the most advanced genetic engineering techniques to rapidly modify miniature pigs that are close in size to humans and have been inbred for 45 years to provide a standardized, renewable source of organs for xenotransplantation. Animal models including rodents with robust human immune systems as well as non-human primates will use these genetically modified pigs in studies that will optimize immune tolerance induction to avoid graft rejection while assuring a well-functioning immune system and optimizing the function of transplanted pig organs.

PI_NAMEs: SACHS, DAVID H;SYKES, MEGAN  (contact)

PROGRAM_OFFICER_NAME: NABAVI, NASRIN N

PROJECT_TERMS: Acceleration;Animal Model;Animal Organ;Animals;B-Lymphocytes;biobank;Biological Assay;bone;Bone Marrow;Carbohydrates;CD47 gene;Cell Survival;Cells;Chimerism;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Cytokine Receptor Gene;Cytomegalovirus;data management;Databases;efficacy evaluation;enzyme linked immunospot assay;Euthanasia;Family suidae;Fluorochrome;Gene Modified;Genetic Engineering;Genotype;Goals;Graft Rejection;Graft Survival;Hematopoietic;homologous recombination;Human;humanized mouse;Hybrids;immune function;Immune response;Immune system;immune system function;Immune Tolerance;Immunity;Immunosuppression;Inbreeding;Injections;Ischemia;Kidney;Kidney Transplantation;kidney xenograft;Label;Life;Mediating;Methodology;Miniature Swine;Modeling;Monoclonal Antibodies;multidisciplinary;Mus;natural antibodies;Natural Killer Cells;nonhuman primate;novel;Office of Administrative Management;Organ;Organ Survival;Organ Transplantation;Papio;Phenotype;porcine model;Primates;Production;Program Research Project Grants;programs;Proteins;Proteinuria;Quality Control;Regimen;Regulatory T-Lymphocyte;Research Personnel;Rodent;Skin graft;Source;Standardization;synergism;T-Cell Receptor;T-Lymphocyte;Techniques;Testing;Thymectomy;Thymic epithelial cell;Thymus Gland;thymus transplantation;Tissue Sample;Tissues;tool;Transgenes;Transgenic Organisms;Transplantation;United States National Institutes of Health;Vascularization;Xenograft procedure

PROJECT_TITLE: A Tolerance Approach to Xenotransplantation


NIH_SPENDING_CATS: Biotechnology;Networking and Information Technology R&D (NITRD)

PI_NAMEs: SYKES, MEGAN  (contact)

PROJECT_TERMS: animal breeding;Animals;Authorization documentation;Communication;computer network;Computer software;Computers;Data;data access;data communication;data exchange;data management;Data Storage and Retrieval;Databases;Ensure;Expenditure;experience;Family suidae;Foundations;Genetic Engineering;genetic information;Group Meetings;Human Resources;Image;Institution;Laboratories;Laboratory Personnel;Leadership;Link;Maintenance;meetings;Methods;Monitor;National Institute of Allergy and Infectious Disease;nonhuman primate;Office of Administrative Management;Production;Productivity;programs;Records;Research;Research Personnel;scientific organization;Scientist;Secure;Services;Site;synergism;System;Training;United States National Institutes of Health;Universities;Work;Xenograft procedure

PROJECT_TITLE: Administrative and Data Management Core


PI_NAMEs: SACHS, DAVID H (contact)

PROJECT_TERMS: animal care;animal cloning;Animals;Antibodies;Backcrossings;biobank;Biological;Biological Assay;Blood specimen;boar;Breeding;Caring;Cesarean section;Clinical;clinically relevant;Collection;Communicable Diseases;computerized;Consult;Databases;design;Development;Diagnostic;diagnostic assay;Disease Management;Estrus Synchronization;Family suidae;Gene Modified;Genetic;Genetic Engineering;Immunologics;immunosuppressed;Inbreeding;Knock-out;Laboratories;Letters;Maintenance;meetings;Miniature Swine;Monitor;nonhuman primate;nuclear transfer;Organ;Papio;pathogen;Phenotype;Primates;Principal Investigator;Production;programs;Prophylactic treatment;protocol development;Protocols documentation;Quality Control;Reagent;Records;Regimen;Sampling;screening;Seminal fluid;success;Technical Expertise;Time;Tissue Sample;Training;Transgenes;Transgenic Organisms;Transportation;web platform;Xenograft procedure

PROJECT_TITLE: Large Animal Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: IOWA CITY

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE  Niemann-Pick C is an invariably fatal lysosomal disease affecting both the liver and brain. The relevance of the proposed studies to public health is that they will define tissue-specific mechanisms triggering liver and brain dysfunction in Niemann-Pick C disease. This work is expected to identify novel pathways that significantly contribute to manifestations of Niemann-Pick C, thereby setting the stage for future discovery efforts to identify and test new therapeutic strategies.

PI_NAMEs: SCHULTZ, MARK LOUIS (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Address;Affect;Age;Age Months;age related;Albumins;Autophagocytosis;autosome;Back;Biochemical;Biological Assay;Biology;Blood Chemical Analysis;Brain;brain dysfunction;career;career development;cell type;Cells;Cessation of life;Cholesterol;Cirrhosis;Data;Defect;defined contribution;Development Plans;Disease;disease model;disease-causing mutation;Endoplasmic Reticulum;Fatty Liver;Foundations;Functional disorder;Future;Genetic;Goals;Grant;Hepatocyte;Hepatomegaly;Histopathology;human induced pluripotent stem cells;in vivo evaluation;Induced Hepatocytes;Induced Neurons;induced pluripotent stem cell;Inflammation;Isoleucine;Knockout Mice;Knowledge;Kupffer Cells;Laboratories;late endosome;Length;Lipids;Liver;liver cell proliferation;liver development;Liver diseases;Liver Dysfunction;Liver Failure;liver function;loss of function;LoxP-flanked allele;Lysosomal Storage Diseases;Lysosomes;Macrophage;Mediating;Membrane Glycoproteins;Mentorship;Methods;Michigan;misfolded protein;Modeling;mouse model;Mus;mutant;Mutation;N-terminal;National Institute of Diabetes and Digestive and Kidney Diseases;Neimann-Pick's Disease Type C;Neonatal;Neurologic;Neurons;novel;novel therapeutic intervention;NPC1 gene;Pathogenesis;Pathology;Pathway interactions;Patients;Phenotype;Point Mutation;Population;Positioning Attribute;Primary carcinoma of the liver cells;Protein Export Pathway;Protein Isoforms;Proteins;proteostasis;proteostasis loss;Public Health;Research;Role;Secure;Site;symposium;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Threonine;Tissues;Training;Universities;Work;Writing

PROJECT_TITLE: Niemann-Pick C liver-specific proteostasis and pathology

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


NIH_SPENDING_CATS: Biotechnology;Genetics;Kidney Disease;Organ Transplantation;Regenerative Medicine;Transplantation

PI_NAMEs: HAWLEY, ROBERT J (contact)

PROJECT_TERMS: Address;Allogenic;animal cloning;Animal Sources;Animals;Antibodies;Binding;biobank;Biological Assay;Breeding;CD46 Antigen;CD47 gene;Cell Transplantation;Cells;Chimerism;clinical application;clinically relevant;Colony-Stimulating Factor Receptors;Complement;CRISPR/Cas technology;CSF2RA gene;Cytokine Receptors;cytotoxicity;Data;Databases;Dendritic Cells;efficacy evaluation;Engraftment;Epitopes;Euthanasia;Family suidae;gain of function;gene complementation;Gene Expression;Gene Expression Profiling;gene function;Gene Modified;Generations;Genes;Genetic;Genetic Engineering;genetic regulatory protein;Genotype;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Granulocyte-Macrophage Colony-Stimulating Factor Receptors;Hematopoietic;Heterozygote;Human;humanized mouse;IL3 Gene;IL3RA gene;Immune Tolerance;Immunoglobulin M;improved;In Vitro;Inbreeding;interest;Interleukin-3 Receptor;Kidney;kidney cell;Kidney Transplantation;Knock-out;Link;Medical;Miniature Swine;Modification;Molecular;mouse model;Myelogenous;Myeloid Progenitor Cells;nephrin;Organ Donor;Organ Survival;Organ Transplantation;Outcome;Papio;Phenotype;Play;podocyte;preclinical development;Primates;Procedures;Production;programs;promoter;protein expression;recombinase;research and development;Research Personnel;Role;Sampling;Schedule;Site;Standardization;System;Techniques;Testing;Time;Tissue Sample;Tissue Transplantation;Tissues;transgene expression;Transgenes;Transgenic Organisms;transplant model;Transplantation;Work;Xenograft procedure

PROJECT_TITLE: Miniature Swine Genetic Engineering and Characterization Core


NIH_SPENDING_CATS: Biotechnology;Kidney Disease;Organ Transplantation;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PI_NAMEs: NOWAK, GREG  (contact)

PROJECT_TERMS: Achievement;Acids;Address;Affect;Animals;Anti-CD40;Antibodies;antibody-mediated rejection;B-Cell Acute Lymphoblastic Leukemia;B-Lymphocytes;Biological Assay;bone;Bone Marrow;Bone Marrow Transplantation;CD3 Antigens;CD47 gene;CD80 gene;Cells;Chimerism;Clinical;clinical application;clinical trial protocol;Clinical Trials;Collaborations;Complement;CTLA4-Ig;Data;Development;Donor person;Down-Regulation;effective therapy;Endothelial Cells;Euthanasia;Family suidae;FDA approved;Generations;Genetic;genetic regulatory protein;Goals;Graft Rejection;Graft Survival;Growth;Health;Human;humanized mouse;Immunosuppression;In Vitro;Interleukin-3 Receptor;Ischemia;Kidney;Kidney Transplantation;kidney xenograft;Learning;Life;Macrophage;Methods;Modeling;Modification;Monoclonal Antibodies;natural antibodies;Natural Killer Cells;Organ;organ growth;Organ Harvestings;Organ Preservation;Outcome;Papio;pathogen;PECAM1 gene;peripheral blood;Phagocytosis;Pharmaceutical Preparations;Play;podocyte;post-transplant;preservation;prevent;Primates;Proteinuria;Protocols documentation;PTPNS1 gene;Regimen;Regulatory T-Lymphocyte;Renal function;Risk;rituximab;Role;side effect;Specificity;Sphingomyelinase;T-Lymphocyte;Therapeutic;thrombotic;Thymectomy;Thymus Gland;thymus xenograft;Time;TNFSF5 gene;Transgenes;Transgenic Organisms;Transplantation;Transportation;Treatment Protocols;treatment strategy;Up-Regulation;Vascularization;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Achieving Xenograft Tolerance through Thymic Programming in Primates


NIH_SPENDING_CATS: Biotechnology;Immunization;Organ Transplantation;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PROJECT_TERMS: Acute;Affect;Allogenic;Animal Model;Animals;Antibodies;Antigens;B-Lymphocytes;bone;Bone Marrow;Bone Marrow Stem Cell;CD47 gene;Cell Adhesion Molecules;Cells;Chimerism;Clinic;clinical application;Collaborations;conditioning;cytokine;Cytokine Receptors;Development;donor stem cell;Dose;Engraftment;Excision;Failure;Family suidae;Funding;Galactosyltransferases;Gene Modified;Genetic;genetic manipulation;Goals;Graft Survival;Hematopoietic;Hematopoietic Stem Cell Transplantation;Homing;Human;Immunosuppression;improved;In Vitro;in vivo;Innate Immune System;Interleukin-3 Receptor;Kidney Transplantation;kidney xenograft;Macrophage;Methodology;Methods;Miniature Swine;Modality;Modification;natural antibodies;Natural Killer Cells;Organ;Organ Transplantation;Papio;Pathway interactions;Phagocytosis;Preparation;prevent;Primates;Protocols documentation;PTPNS1 gene;receptor;Recombinants;Regulatory T-Lymphocyte;response;Skin graft;skin xenograft;Species Specificity;stem cells;success;T-Lymphocyte;Testing;Transgenes;Transgenic Mice;Transgenic Organisms;Translating;Transplantation;Treatment Protocols;Xenograft procedure

PROJECT_TITLE: Achieving Xenograft Tolerance through Mixed Chimerism


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Human Fetal Tissue;Immunotherapy;Organ Transplantation;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

PROJECT_TERMS: Animal Model;Animals;Antigen Presentation;antigen-specific T cells;Antigens;B-Lymphocytes;Biological Assay;Carbohydrates;Cells;Chimera organism;Chimerism;Clonal Deletion;Defect;Development;effector T cell;engineered T cells;enzyme linked immunospot assay;Family suidae;Fluorochrome;Future;Genetic Engineering;Grant;Growth;Hematopoietic stem cells;Heterophile Antibodies;HLA-A2 Antigen;HLA-DQ8 antigen;Human;human pluripotent stem cell;human tissue;humanized mouse;Hybrids;immune function;Immune response;Immune system;Immune Tolerance;Immunologics;Immunosuppression;improved;insight;Insulin;Label;lentivirally transduced;Life;Methods;Monitor;mouse model;Mus;natural antibodies;Natural Killer Cells;novel;Organ;Patients;Peptides;porcine model;postnatal human;prevent;Proteins;reconstitution;Regulatory T-Lymphocyte;response;Structure;T cell differentiation;T cell reconstitution;T-Cell Receptor;T-cell receptor repertoire;T-Lymphocyte;Testing;Thymectomy;Thymic epithelial cell;Thymus Gland;thymus transplantation;Tissues;tool;Toxic effect;Transgenic Organisms;Translating;Xenograft procedure

PROJECT_TITLE: Tolerance of Adaptive and Innate Human Anti-Pig Immune Responses in Humanized Mice


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Eye Disease and Disorders of Vision;Genetics;Infectious Diseases;Nanotechnology;Orphan Drug;Rare Diseases;Sexually Transmitted Infections;Topical Microbicides

ORG_CITY: Chicago

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: This application employs an integrative approach to rapid and efficient translation of our recent discovery that an already approved drug can be repurposed to treat vision loss originating from herpesvirus infection of the eye. Proposed preclinical studies will facilitate an IND application to the FDA for testing our new treatment.

PI_NAMEs: DATE, ABHIJIT A;SHUKLA, DEEPAK  (contact)

PROGRAM_OFFICER_NAME: GOVER, TONY DOUGLAS

PROJECT_TERMS: Acyclovir;Animal Model;Anti-viral Agents;anti-viral efficacy;Anti-viral Therapy;Behavioral;Binding Proteins;Biological Availability;Blindness;Cavia;Cell Death;Cells;Chemicals;Cornea;corneal epithelium;Cyclic AMP;Data;Development;DNA biosynthesis;dosage;Dose;drug development;Drug Kinetics;Drug resistance;Drug usage;efficacy study;emerging virus;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;Eye Infections;FDA approved;Film;Formulation;Frequencies;Goals;Guidelines;Health;Herpesviridae;Herpesviridae Infections;Herpesvirus 1;Herpetic Keratitis;Homologous Gene;Human;improved;in vivo;Infection;intraperitoneal;meetings;Modality;Modeling;Molecular Chaperones;mouse model;Mucous body substance;multidisciplinary;Mus;nanoformulation;novel therapeutics;nucleoside analog;ocular surface;Oral;Orphan Drugs;Oryctolagus cuniculus;Pathology;Pathway interactions;Penetration;Periodicity;Permeability;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Phase I Clinical Trials;Poloxamers;pre-clinical;preclinical study;prevent;Process;Production;Proteins;R24;response;Response Elements;RNA Interference;Safety;safety study;Scientist;Simplexvirus;Sodium;Sodium phenylbutyrate;synergism;Testing;Therapeutic;Thymidine Kinase;Time;topical antiviral;Topical application;trait;transcription factor;Translating;translational approach;Translations;United States;Urea cycle disorders;Viral;viral DNA;Viral Eye Infections;Viral Proteins;viral resistance;Virus Diseases;Virus Replication;VP 16;Work

PROJECT_TITLE: Alleviation of ER stress as a translational strategy to curb ocular viral infections


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Clinical Research;Hematology;Infectious Diseases;Patient Safety;Precision Medicine;Sepsis

ORG_CITY: ANN ARBOR

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Sepsis and other critical illnesses are a growing human health concern. In addition, adverse reactions to medications significantly contribute to our nation’s health care costs. Unfortunately, we do not fully understand how sepsis develops and what underlying causes lead to adverse drug reactions. Our research program “Translational Metabolomics in Critical Care” will study how metabolism provides important information about health, illness and drug response. The information we acquire from this work is relevant to public health because it will help us determine what signals in the blood could be used to develop new therapies for critical illnesses like sepsis and to avoid adverse drug reactions. This will improve the design of future clinical studies.

PI_NAMEs: STRINGER, KATHLEEN A (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: acylcarnitine;adverse drug reaction;Adverse reactions;Biological Assay;Blood;candidate marker;Carnitine;Clinical;clinical application;Clinical Research;Clinical Trials Design;Collaborations;Critical Care;Critical Illness;Defect;design;Detection;diagnostic biomarker;drug response prediction;effective therapy;flexibility;Future;Goals;hazard;Health;Health Care Costs;Heterogeneity;Human;improved;innovation;insight;Knowledge;Knowledge Discovery;Lead;Levocarnitine;liquid chromatography mass spectroscopy;Metabolic;metabolic abnormality assessment;Metabolic stress;Metabolism;metabolomics;Morbidity - disease rate;mortality;new therapeutic target;novel;novel therapeutics;Nuclear Magnetic Resonance;Patient Care;Pharmaceutical Preparations;Pharmacometabolomics;Pharmacotherapy;Phenotype;Point of Care Technology;porcine model;precision medicine;predictive marker;Productivity;Prognostic Marker;programs;Public Health;Research;response;Science;Sepsis;Signal Transduction;Techniques;timeline;translational research program;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-J(55)R]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

PHR: PROJECT NARRATIVE Cryptococcal meningitis is one of the most important opportunistic infections affecting people living with HIV/AIDS causes over 500,000 deaths annually. To develop improved therapies, a deeper understanding of the mechanisms by which Cryptococcus is able to replicate within the human host. We have found that the ability to survive in CO2 distinguishes virulent C. neoformans species from avirulent species and, accordingly, the goal of this project is to understand the mechanisms of CO2 tolerance with the long term goals of using this information to develop new drugs tailored to targeting Cryptococcus in the host environment.

PI_NAMEs: KRYSAN, DAMIAN J (contact);LIN, XIAORONG

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Affect;Air;Anabolism;antiretroviral therapy;Biological;burden of illness;capsule;Carbon;Carbon Dioxide;Cessation of life;Clinical;Cryptococcal Meningitis;Cryptococcus;Cryptococcus neoformans;Data;deletion library;design;differential expression;Disease;DNA Sequence Alteration;Drug Targeting;Environment;Event;Evolution;experience;experimental study;fitness;Future;Gene Expression Profile;Genes;Genetic;Genetic Polymorphism;genetic resource;Genetic Screening;Genetic Transcription;genome wide association study;Genomic approach;Genomics;Genotype;Glycolysis;Goals;Growth;High temperature of physical object;HIV anti-retroviral;HIV diagnosis;HIV therapy;HIV/AIDS;Homeostasis;Human;improved;In Vitro;Incidence;Infection;inhibitor;Lung;Maps;Meningoencephalitis;Metabolism;Minority;Modeling;Molecular;Molecular Target;mortality;mouse model;Mus;mutant;Mutation;new therapeutic target;novel anticancer drug;novel therapeutics;Opportunistic Infections;Outcome;Pathogenesis;pathogenic fungus;Pathway interactions;patient population;Patients;Persons;Phenotype;Positioning Attribute;Property;Publishing;Quantitative Trait Loci;Resource-limited setting;response;Role;Sentinel;Sphingolipids;Symptoms;Testing;trait;transmission process;Tumor Biology;Variant;Virulence;Virulent;Yeasts

PROJECT_TITLE: Genetic and mechanistic analysis of carbon dioxide tolerance in Cryptococcus pathogenesis

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Cardiovascular;Genetics

ORG_CITY: DENVER

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

ORG_STATE: CO

PHR: NARRATIVE Blood vessels carry oxygen and nutrients and are vital to organismic viability and continued homeostasis. During angiogenic development, endothelial cells create a hollow cavity called a lumen, providing a continuous conduit for blood to ﬂow. This proposal will help determine the molecular and cellular mechanisms that contribute to the creation of a lumen during embryonic blood vessel development.

PI_NAMEs: KUSHNER, ERICH J (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: 3-Dimensional;Ablation;Alleles;angiogenesis;Apical;apical membrane;Architecture;Binding;Biochemical;Biochemistry;Biogenesis;Blood;blood vessel development;Blood Vessels;Body System;Cardiovascular Diseases;Cell Culture System;Cell membrane;Cells;Chemosensitization;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR imaging;Data;density;Development;Developmental Process;Distant;Docking;Embryo;Endothelial Cells;Endothelium;Event;Excision;Generations;Genes;Genetic;Genetic Transcription;Goals;Guanine;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate Phosphohydrolases;Homeostasis;Image;Imaging Techniques;Immune response;In Vitro;in vivo;insight;Investigation;Label;Laboratories;luminal membrane;Maps;Mediating;Membrane;Microscopy;Molecular;Morphogenesis;Movement;mutant;Mutation;Names;novel;Nutrient;overexpression;Oxygen;oxygen transport;Pathway interactions;Pattern;podocalyxin;Post-Translational Protein Processing;Primary Cell Cultures;Process;programs;Protein Engineering;protein transport;Proteins;rab GTP-Binding Proteins;Reporter;Resolution;Role;Signal Transduction;Surface;synaptotagmin;Tertiary Protein Structure;Testing;Time;Tissues;trafficking;Transgenic Organisms;tumor growth;Vesicle;wasting;Work;wound healing;Zebrafish

PROJECT_TITLE: Polarized Protein Trafficking and Angiogenesis

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Hepatitis;Liver Disease;Nutrition;Prevention

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: High levels of tissue iron from excessive dietary intake are associated both with diabetes risk, fatty liver and liver damage (nonalcoholic steatohepatitis or NASH). This application proposes a clinical trial of iron reduction by simple blood donation, just as practiced at the Red Cross, to determine the effect on glucose control and the progression of liver damage in individuals with type 2 diabetes or prediabetes.

PI_NAMEs: MCCLAIN, DONALD A. (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Adoption;Adult;Aftercare;aged;Aging;Alanine Transaminase;Animal Model;beta Thalassemia;Biological Markers;Blood Banks;Blood Donations;blood glucose regulation;Cirrhosis;Clinical;Clinical Trials;cohort;Continuous Glucose Monitor;Data;Diabetes Mellitus;diabetes risk;Diabetic mouse;Diet;dietary excess;Dietary intake;Dietary Iron;Disease Progression;Dose;elastography;Epidemiology;Etiology;Evolution;fasting glucose;Fatty Acids;Fatty Liver;Ferritin;Glucose;glucose monitor;Healthcare Systems;Hereditary hemochromatosis;Homeostasis;Human;improved;improved outcome;indexing;Individual;Inflammation;Inherited;Insulin;insulin sensitivity;intravenous glucose tolerance test;Iron;Iron Overload;Link;Liver;Liver diseases;Liver Failure;Liver Fibrosis;liver inflammation;liver injury;liver stiffness;Magnetic Resonance Imaging;Measures;Metabolic Pathway;Metabolic syndrome;metabolomics;Modality;Modeling;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;Normal Range;North Carolina;nutrition;Outcome;Pain;Participant;Pathogenesis;Pathologic;Patients;Persons;Pharmaceutical Preparations;Phenotype;pilot trial;Population;Population Heterogeneity;Prediabetes syndrome;Prevalence;prevent;Prevention;Primary carcinoma of the liver cells;primary endpoint;primary outcome;Randomized;randomized placebo controlled trial;recruit;Red Cross;Research Design;Risk;Risk Factors;Rodent Model;Role;Safety;Sampling;secondary outcome;Serum;Target Populations;Testing;Time;tissue biomarkers;Tissues;Transaminases;treatment arm;ultrasound;Universities;Venous blood sampling;Work

PROJECT_TITLE: Iron Reduction for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease


NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Neurosciences;Orphan Drug;Rare Diseases;Rehabilitation

PHR: PROJECT NARRATIVE The proposed project is relevant to public health because restoring vision requires an in-depth understanding of how surviving retinal neurons respond to gene replacement therapy and how retinal plasticity affects the restoration of functional connections. The results from the proposed research are expected to have a two-fold impact: (1) further understanding of circuit-level mechanisms of functional recovery will identify the potential locations that limit therapeutic effects, and (2) knowledge essential for maximizing function after photoreceptor recovery.

PI_NAMEs: LEE, JOO YEUN  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: achromatopsia;Affect;Animal Model;Blindness;cell type;Cells;Clinical Trials;Cone;cyclic-nucleotide gated ion channels;Dendrites;Dependovirus;Development;Electrophysiology (science);Equilibrium;Excitatory Synapse;Exhibits;experimental study;Face;Functional disorder;functional restoration;ganglion cell;gene replacement therapy;gene therapy;Goals;Homeostasis;horizontal cell;Human;Image;improved;Individual;inherited retinal degeneration;Inhibitory Synapse;innovation;insight;Knowledge;Location;Measures;Mediating;Modeling;mouse model;Mus;neuronal survival;Neurons;neurotransmission;neurotransmitter release;optimal treatments;Pathway interactions;Pattern;Phase;Photoreceptors;Physiological;Presynaptic Terminals;Property;Public Health;Reaction;receptive field;Recovery;Recovery of Function;Research;Resolution;response;Retina;Retinal Diseases;retinal neuron;retinal rods;sight restoration;spatiotemporal;Structure;Synapses;Synaptic plasticity;Testing;Therapeutic;Therapeutic Effect;tool;Vertebrate Photoreceptors;Vision;Visual Acuity;voltage;Withdrawal;Work

PROJECT_TITLE: The contribution of plasticity to the recovery of retinal function following gene therapy


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Sleep Research

PHR: PROJECT NARRATIVE Vivid visual experiences in dreams during REM sleep evidently indicate that our brain holds the generative model of the world. The proposed research will investigate rapid eye movements during REM sleep as a readout of the generative model and test the superior colliculus as the central hub orchestrating it. This project will constitute the critical step to understand how we see the world through the internal model and how the abnormal expression of the model could underlie the pathogenesis of some psychiatric disorders such as schizophrenia.

PI_NAMEs: SENZAI, YUTA  (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Address;Animals;awake;Award;behavioral study;Brain;career development;Cell Nucleus;Cells;Code;Collaborations;Communities;Coupled;Data;Dreams;Electrophysiology (science);Ensure;Environment;experience;Eye;Eye Movements;gaze;generative models;Goals;Head;Head Movements;Human;insight;Laboratories;Mediating;Mental disorders;Mentors;Methods;miniaturize;Modeling;Monitor;movie;Mus;Neurons;neurophysiology;Neurosciences;optogenetics;Pathogenesis;Pattern;Perception;pharmacologic;Phase;Physiological;Pontine structure;programs;rapid eye movement;REM Sleep;Research;Research Personnel;Role;Saccades;Sampling;Schizophrenia;sensory input;Sleep;superior colliculus Corpora quadrigemina;System;Testing;Thalamic structure;Time;Training;virtual;virtual environment;Visual;visual tracking;Wakefulness

PROJECT_TITLE: Role of the Superior Colliculus in Orienting Eye Movements during REM Sleep


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative This project will address a worldwide public health issue regarding diarrhea treatment. We will investigate the safety and efficacy of a novel antidiarrheal ORS that contains calcium and activates Ca2+-sensing receptor in patients with cholera and other acute infectious diarrheal diseases in ICDDRB, Dhaka, Bangladesh. If the result is positive, this inexpensive therapy can be practically used in all the countries.

PI_NAMEs: CHENG, SAM X (contact)

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;Acute Diarrhea;Adopted;Adult;Affect;Africa;Age;Animals;Antibiotics;Antidiarrheals;Azithromycin;Back;Bangladesh;Bicarbonates;Body Weight;Calcium;Calcium-Sensing Receptors;Cause of Death;Cessation of life;Child;Childhood;Cholera;Clinical;Control Groups;Country;COVID-19;Data;Defect;Dehydration;Diarrhea;diarrheal disease;Dysentery;Ebola;Electrolytes;Emergency department visit;emerging pathogen;Enrollment;Equilibrium;Facilities and Administrative Costs;Failure;Family;Feces;Florida;Gastrointestinal tract structure;Hospital Costs;Hour;Human;Hydration status;Infant;Infection;Intestines;Intravenous;Ions;Laboratories;Laboratory Animals;Liquid substance;Malaria;Measles;Metabolic;Minerals;Morbidity - disease rate;mortality;next generation;novel;Oral;Oral Examination;Outcome;Outpatients;Output;pandemic disease;participant enrollment;Patients;pediatric patients;Policies;Public Health;Randomized;Randomized, Controlled Trials;receptor;Recommendation;Recovery;Rehydration Solutions;Rehydrations;Replacement Therapy;Reporting;restoration;Role;Safety;Severities;Symptoms;Testing;Time;treatment group;trial comparing;UNICEF;United States;Universities;Vibrio cholerae;Visit;Weight

PROJECT_TITLE: Next generation ORS: Randomized controlled trial comparing ORS with calcium vs standard ORS in reducing severity of adults with acute watery diarrhea

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MILWAUKEE

ORG_NAME: VERSITI WISCONSIN, INC.

ORG_STATE: WI

PHR: PROJECT NARRATIVE In patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, emergence of BCR-ABL1 compound mutations (two mutations in the same BCR-ABL1 molecule) confers high- level clinical resistance to tyrosine kinase inhibitors (TKIs) and leads to disease relapse. Currently, these patients lack any suitable treatment options, defining an unmet medical need. Our work will mechanistically define three complementary approaches for controlling BCR-ABL1 compound mutation-based TKI resistance and use this knowledge to develop rational strategies to improve patient outcomes.

PI_NAMEs: DEININGER, MICHAEL W. (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: ABL1 gene;Acute Myelocytic Leukemia;Address;Affinity;Alleles;Allosteric Site;American;Binding;Binding Sites;Biochemical;Biophysics;Blast Phase;Bypass;Cessation of life;Chronic Myeloid Leukemia;Chronic-Phase Myeloid Leukemia;Clinical;clinical development;Clinical Trials;Communication;Complex;Crystallography;Dasatinib;Dependence;Distant;Dose;effective therapy;Enzyme Inhibition;Event;Exhibits;FDA approved;Foundations;Gatekeeping;Imatinib;improved;inhibitor;Knowledge;Laboratory Study;leukemia;Leukemic Cell;Malignant neoplasm of lung;Malignant Neoplasms;Medical;Medicine;Melanoma;Methods;Molecular Conformation;mouse model;mutant;Mutation;Non-Small-Cell Lung Carcinoma;novel therapeutic intervention;optimal treatments;Patient-Focused Outcomes;Patients;Ph+ ALL;Pharmaceutical Preparations;Philadelphia Chromosome;Philadelphia Chromosome Positive Chronic Myelogenous Leukemia;Phosphotransferases;Physiological;Prevalence;Probability;Protac;Proto-Oncogene Proteins c-abl;Protocols documentation;Rationalization;Recurrent disease;Refractory;Regulatory Element;Reporting;research clinical testing;Residual state;Resistance;resistance mechanism;resistance mutation;Sampling;Signal Transduction;Site;Site-Directed Mutagenesis;System;targeted treatment;Technology;Testing;Therapeutic;Treatment Failure;Tyrosine Kinase Inhibitor;Work;Xenograft procedure

PROJECT_TITLE: Strategies to target BCR-ABL1 compound mutants in CML and Ph+ ALL

STUDY_SECTION: DMP

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


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

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE Alzheimer’s dementia is a large public health concern. Here we propose to investigate the link between dietary fats and genetic factors, and brain lipids and metals, which together results in downstream cognitive and motor decline in Alzheimer’s disease. Data from these studies may elucidate important mechanisms for brain degeneration in Alzheimer’s disease and provide targets for drug therapies.

PI_NAMEs: BUSH, ASHLEY I;SCHNEIDER, JULIE A. (contact)

PROGRAM_OFFICER_NAME: KWOK, RICHARD K

PROJECT_TERMS: Ablation;Acceleration;Address;Adipose tissue;aged;Aging;alpha-Linolenic Acid;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Apolipoprotein E;Biological;Biological Markers;Blood Vessels;Brain;Brain Chemistry;Brain Injuries;brain iron;Brain region;brain tissue;Cell Death;Cellular Membrane;Cerebellum;Cessation of life;Clinical;Clinical Trials;Cognitive;cohort;Complex;Data;Dementia;Deterioration;Development;Diagnosis;Diet;dietary;Dietary Fats;Disease;epidemiology study;Fatty Acids;Female;Genes;Genetic;Genotype;Goals;Human;Immune;Impaired cognition;In Situ;Inductively Coupled Plasma Mass Spectrometry;Inferior;Intake;Iron;Lasers;Lewy Bodies;Link;Lipid Peroxidation;Lipid Peroxides;lipidomics;Lipids;Maps;Measures;Mediating;Memory;Metals;Methodology;Monounsaturated Fatty Acids;Motor;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuropathology;novel;Older Population;Oleic Acids;Omega-3 Fatty Acids;oxidation;oxidized lipid;Pathologic;Pathology;Pathway interactions;peroxidation;Pharmaceutical Preparations;Phenotype;Polyunsaturated Fatty Acids;Predisposition;Proteins;Public Health;putamen;Reactive Oxygen Species;Reporting;Resources;Risk;Role;sex;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Substantia nigra structure;Synaptic Membranes;targeted treatment;Technology;Temporal Lobe;Testing;Time

PROJECT_TITLE: Neuropathologic-Epidemiological Study of Metallomics and Alzheimer's Disease

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Genetics;Major Depressive Disorder;Mental Health;Mental Illness;Prevention;Serious Mental Illness;Social Determinants of Health;Suicide;Violence Research

ORG_CITY: RICHMOND

ORG_DEPT: PSYCHIATRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative The specific aims of this project will leverage recent advances in the molecular genetics of suicidality to clarify the mechanisms by which aggregate genetic liability relates to suicidal thoughts and behaviors. We will use seven independent samples to explore how genetic liability exerts its effects across the life course via behavioral mediators and in the context of environmental exposures. This integrative approach will provide critical psychosocial context to biological findings.

PI_NAMEs: EDWARDS, ALEXIS C (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: abuse neglect;Address;Adolescence;Adult;analytical method;Area;Behavior assessment;Behavioral;behavioral disinhibition;Behavioral Mechanisms;behavioral outcome;Biological;Candidate Disease Gene;Cessation of life;Characteristics;Child Abuse;Childhood;Clinical;comorbidity;Complex;Data;data registry;depressive symptoms;Development;Disease;Divorce;Environmental Exposure;Environmental Risk Factor;Epidemiology;Etiology;Exposure to;externalizing behavior;Family;family genetics;Family Study;Feeling suicidal;Future;Genes;Genetic;Genetic Predisposition to Disease;Genetic Risk;Genetic study;genome wide association study;Heritability;ideation;improved;Impulsive Behavior;Individual;insight;Intervention;Investigation;Knowledge;Life Cycle Stages;Major Depressive Disorder;Mediating;Mediation;Mediator;Medical;Mental Depression;Mind;Modeling;Molecular;Molecular Genetics;Nature;Outcome;Pathway interactions;Phenotype;phenotypic data;Population Study;psychologic;psychosocial;Public Health;Publishing;Recording of previous events;Registries;Research;Risk;Risk Assessment;Risk Factors;Sample Size;Sampling;Signal Transduction;Single Nucleotide Polymorphism;Socioeconomic Status;Specificity;statistics;suicidal;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Testing;Time;Twin Multiple Birth;Twin Studies

PROJECT_TITLE: Harnessing advances in the genetics of suicidality to identify and dissect psychosocial pathways to risk

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative ADPKD is a common genetic disorder with limited treatment options. We will test if targeting the RNA chemical modification pathway is a new therapeutic opportunity for ADPKD. Our studies will also uncover novel mechanisms by which RNA chemical modifications regulate aberrant gene expression in ADPKD.

PI_NAMEs: PATEL, VISHAL  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Ablation;Address;Adenosine;Adult;Affect;Alleles;American;Antisense Oligonucleotides;Attenuated;Autosomal Dominant Polycystic Kidney;Biology;c-myc Genes;Cells;Chemical Dynamics;Chemicals;Chronic;clinically relevant;comparative;Cyclic AMP;Cyst;Cystic kidney;design;Disease;disease model;Disease Progression;DNA;Enzymes;Epigenetic Process;Epithelial cyst;epitranscriptomics;Event;Exhibits;fascinate;Gene Expression;Genetic;Genetic Code;Genetic Diseases;Goals;Growth;Half-Life;Human;Immunoprecipitation;inhibitor;innovation;insight;Kidney;Knockout Mice;Knowledge;loss of function;Mediating;Messenger RNA;Metabolic;Methionine;Methylation;Methyltransferase;MicroRNAs;Modeling;Modification;mouse model;mRNA Translation;Mus;new therapeutic target;Nitrogen;novel;novel drug class;novel therapeutics;Nucleotides;Oncogenes;overexpression;Pathogenicity;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Phenotype;Physiology;Polycystic Kidney Diseases;pre-clinical;Property;Proteins;Proteome;Proteomics;Proxy;Reaction;Renal tubule structure;ribosome profiling;RNA;RNA immunoprecipitation sequencing;S-Adenosylhomocysteine;S-Adenosylmethionine;Safety;Signal Transduction;Testing;therapeutic evaluation;Tissues;tolvaptan;Transcript;Translational Repression;Translations;Treatment Efficacy;Tubular formation;Up-Regulation;Vasopressin Receptor;Wild Type Mouse

PROJECT_TITLE: The impact of RNA chemical modifications on polycystic kidney disease progression

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


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

ORG_CITY: DETROIT

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: PROJECT NARRATIVE Vibrio cholerae is a major human pathogen in many developing countries, with an estimated 3-5,000,000 new cases and 100,000 deaths each year each year. The goal of this proposal is to characterize how V. cholerae has evolved to better survive in the aquatic environment, leading to cholera outbreaks. Achieving this new level of understanding will enable future research to identify new therapeutic targets and/or targets for environmental remediation.

PI_NAMEs: WITHEY, JEFFREY H (contact)

PROJECT_TERMS: adaptive immune response;adaptive immunity;Adult;Animals;biotypes;Cessation of life;Cholera;combat;Data;Developing Countries;Development;Diarrhea;Disease;Disease Outbreaks;disease transmission;Enabling Factors;Environment;Evolution;Excretory function;experimental study;Fishes;Genes;Genetic;Goals;hatching;Hour;Human;human disease;human pathogen;Infection;Innate Immune Response;Intestines;Invaded;Island;Laboratories;Larva;Life;Life Cycle Stages;Mammals;Modeling;mutant;Natural Immunity;new therapeutic target;Operon;Other Genetics;pandemic disease;pathogen;Pathogenesis;Pathogenicity;Pathogenicity Island;Phenotype;pressure;Production;remediation;response;Role;Side;Testing;timeline;transmission process;transposon sequencing;Vibrio;Vibrio cholerae;Vibrio cholerae O1;Water;Work;Zebrafish

PROJECT_TITLE: Biotype-specific evolution

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Data Science;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Social Determinants of Health

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: RELEVANCE TO PUBLIC HEALTH A diverse workforce in the biomedical sciences is key to fostering scientific innovation and to addressing health disparities in underserved populations in the United States. The post-baccalaureate training program at The Jackson Laboratory offers individuals who identify with groups currently underrepresented in biomedical research exceptional career development opportunities through the conduct of research under the mentorship of investigators who are leaders in genomics, genomic technologies, and data science. Alumni of this immersive research experience will have the foundational knowledge as well as the technical, research, communication, and professional skills needed for successful and productive careers in biomedical research.

PI_NAMEs: BECK, CHRISTINE R;BULT, CAROL J (contact)

PROGRAM_OFFICER_NAME: XIRASAGAR, SANDHYA

PROJECT_TERMS: Academy;Address;Area;Basic Science;Biomedical Research;Budgets;career;career development;Collaborations;Communication;Communities;computing resources;Connecticut;Data;Data Science;Diverse Workforce;Doctor of Medicine;Doctor of Philosophy;Economic Factors;Education;education research;Educational Curriculum;Educational Status;Environment;Equity;Evaluation;experience;Exposure to;Faculty;formal learning;Fostering;Funding;Genetic;genetic resource;Genome;genome analysis;genome resource;genome sciences;genome-wide;Genomic medicine;Genomics;Goals;health disparity;improved;Individual;informal learning;Infrastructure;innovation;Knowledge;Laboratories;Laboratory Research;Leadership;Maine;Mammalian Genetics;marginalized community;Mentors;Mentorship;Methods;Minority Groups;mouse genetics;peer;Persons;Population;Positioning Attribute;Postbaccalaureate;Productivity;Program Effectiveness;programs;Public Health;Recording of previous events;Research;Research Ethics;Research Personnel;Research Training;Resources;satisfaction;Science;science education;Science, Technology, Engineering and Mathematics;Scientific Inquiry;Scientist;skills;Students;success;synergism;Talents;Technology;The Jackson Laboratory;Training;Training Programs;Underrepresented Minority;Underrepresented Populations;Underserved Population;United States;Visit;Workplace

PROJECT_TITLE: JAX Diversity Action Plan (DAP) Post-Baccalaureate Program in Genomics (gDAP)


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Charcot-Marie-Tooth Disease;Chronic Pain;Genetics;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Prevention;Rare Diseases

ORG_CITY: ALBANY

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: PROJECT NARRATIVE We are proposing that PMP2 overexpression is necessary and sufficient to promote a positive gain of function on Schwann cell myelination in inherited demyelinating disorders. The results from this work will convert toward a better understanding the Schwann cell molecular and metabolic response in CMT disease.

PI_NAMEs: BELIN, SOPHIE  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Action Potentials;Allium cepa;analog;Axon;Binding;Biological Assay;Biopsy;burden of illness;Charcot-Marie-Tooth Disease;Coculture Techniques;Complex;Data;Defect;Demyelinating Diseases;Demyelinations;Development;Devices;Disease;Down-Regulation;Economics;effective therapy;EGR2 gene;extracellular;Fatigue;fatty acid-binding proteins;Fatty Acids;Fiber;Future;gain of function;Genes;Genetic;Genetic Recombination;Genus Hippocampus;Goals;Hereditary Motor and Sensory Neuropathy Type I;hereditary neuropathy;Hereditary, Type III, Motor and Sensory Neuropathy;Human;improved;in vivo;Inherited;insight;Intervention;Isotopes;Knowledge;Lifelong disability;lipidomics;Lipids;loss of function;Luciferases;Mediating;Mediator;Metabolic;Mitochondria;Molecular;Molecular Chaperones;Morphology;Motor;mouse model;Mus;Muscle Weakness;Mutation;Myelin;Myelin P0 Protein;Myelin Proteins;Myelinated nerve fiber;myelination;National Institute of Neurological Disorders and Stroke;Nerve;Nervous System;Neural Conduction;Neuregulin 1;neuromuscular function;Neurons;Neuropathy;neurotransmission;Nonesterified Fatty Acids;Numbness;Occupational Therapy;Orthopedics;overexpression;Pain;pain relief;palliative;Pathologic;Pathway interactions;Patient Care;Patients;Peripheral;Peripheral Nervous System Diseases;Persons;Physical therapy;Physiological;pre-clinical;Prevalence;prevent;Prevention;Prevention strategy;Preventive treatment;Production;Public Health;Quality of life;Regulation;remyelination;response;RNA Splicing;Role;Schwann Cells;Signal Transduction;Site-Directed Mutagenesis;Therapeutic;therapy development;transcription factor;Up-Regulation;uptake;Work

PROJECT_TITLE: Role of a Fatty Acid Chaperone in Schwann Cell Myelination

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Rare Diseases;Tuberous Sclerosis

ORG_CITY: WILMINGTON

ORG_NAME: NEMOURS CHILDREN'S HOSPITAL, DELAWARE

ORG_STATE: DE

PHR: Project Narrative Tuberous sclerosis complex (TSC) is a genetic disorder that presents with epilepsy and TSC- associated neuropsychiatric disorders (TANDs), but the mechanisms are unknown. We have a novel mouse panel that more faithfully recapitulates human TSC with the appropriate gene dosage and expression pattern, that also shows the genetically controlled population-level phenotypic heterogeneity seen in humans. By leveraging this heterogeneity, from spontaneous seizures to behavioral abnormalities, will deliver unprecedented mechanistic insight into the pathogenesis of TSC-associated epilepsy and TANDs.

PI_NAMEs: HERNAN, AMANDA  (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Address;Affect;Animals;Anxiety;Astrocytes;Attention;autism spectrum disorder;Behavioral;behavioral impairment;behavioral phenotyping;Benchmarking;Benign;Biological Models;Biology;Brain;clinically relevant;Cognition;Communication;Complex;Darkness;Data;Development;Disease;Disease Progression;Electrodes;Epilepsy;epileptiform;Epileptogenesis;Equilibrium;Frequencies;Gene Dosage;Gene Expression Profile;Genetic;Genetic Diseases;Germ Lines;Goals;Heterogeneity;Heterozygote;Hippocampus;Hour;Human;Impaired cognition;Implant;improved;Individual;Inherited;insight;Intellectual functioning disability;Intervention;Knock-out;Laboratory Study;Learning;Light;Mediating;Memory;Modeling;Monitor;Mus;Mutation;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neural;neural network;Neurologic;Neurons;neuropsychiatric disorder;new therapeutic target;novel;novel therapeutic intervention;Operative Surgical Procedures;Outcome;Pathogenesis;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Population;Predisposition;Process;Prognosis;Reaction Time;Refractory;repetitive behavior;Research;Role;Seizures;Severities;System;Testing;Time;TSC1 gene;TSC2 gene;Tuberous Sclerosis;tumor growth;Variant

PROJECT_TITLE: Leveraging genetically-encoded heterogeneity to understand TANDs and seizures in novel models of TSC

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ORG_CITY: KANSAS CITY

ORG_NAME: STOWERS INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: MO

PHR: Project Narrative: Meiotic drivers are selfish chromosomal loci that exploit gametogenesis to promote their own biased transmission into gametes. Meiotic drivers can directly and indirectly contribute to infertility and facilitate the spread of deleterious (e.g., disease-causing) alleles in a population. This proposal characterizes the molecular mechanisms and evolution associated with a family of meiotic drive genes to uncover how drivers work and impact genome evolution.

PI_NAMEs: ZANDERS, SARAH ELIZABETH (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TITLE: Molecular Mechanisms and Evolutionary Impacts of the wtf Meiotic Drivers

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Gene Therapy;Genetics;Muscular Dystrophy;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative The limb girdle muscular dystrophy (LGMD) gene therapy field is focused almost entirely on recessively inherited disorders, leaving dominantly inherited LGMDs far behind in the path towards a cure. This project aims to develop allele specific knockdown using siRNAs as a therapy for LGMDD1, a disabling dominantly inherited myopathy, lacking any treatments. LGMDD1 is only one of several disorders amenable to the treatment strategies described in this proposal.

PI_NAMEs: FINDLAY, ANDREW  (contact)

PROJECT_TERMS: Address;Alleles;Cells;Client;Clinical Trials;Coculture Techniques;Complex;Data;demographics;Dependovirus;Development;Disabling;Disease;disease model;disease phenotype;disorder prevention;Dose;Embryo;experience;experimental study;first-in-human;Frameshift Mutation;gain of function;gene correction;gene replacement;gene therapy;Genetic Databases;Goals;Haploidy;Hereditary Disease;Heterozygote;Histopathology;Human;Human Cell Line;human disease;improved;In Vitro;in vivo;induced pluripotent stem cell;Inherited;knock-down;Knock-in;Knockout Mice;Length;Limb-Girdle Muscular Dystrophies;loss of function;Mass Spectrum Analysis;Mediating;Methodology;MicroRNAs;Modeling;mouse model;Mus;Muscle;Muscle Fibers;Muscular Dystrophies;mutant;Mutation;Myoblasts;Myopathy;nanopore;neuromuscular;Neuromuscular Diseases;Nonsense Mutation;novel therapeutic intervention;novel therapeutics;Onset of illness;Pathologist;Patient Care;patient derived induced pluripotent stem cells;Patients;Phase;Phenotype;Physicians;pre-clinical;prevent;Proteins;proteomic signature;Proteomics;Qualifying;Research;Reverse Transcriptase Polymerase Chain Reaction;RNA;RNA Interference;RNA Sequences;routine care;Scientist;Single Nucleotide Polymorphism;Skeletal Muscle;Specificity;success;targeted treatment;Testing;Therapeutic;therapeutic development;translational therapeutics;treatment strategy;Western Blotting

PROJECT_TITLE: Allele Specific Knockdown for LGMDD1

STUDY_SECTION: SMEP

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


ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Chronic Pain;Mental Health;Neurosciences;Pain Research;Patient Safety;Prevention;Sleep Research

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE While previous studies have focused on the consequences of sleep and pain individually, the proposed research will shift the paradigm to examine the joint effects of poor sleep and pain among an at-risk group, healthcare workers (HCWs). Furthermore, the study will examine the moderating effects of job demands and resources. The findings will help inform future interventions aimed to promote health and wellness in vulnerable HCWs.

PI_NAMEs: MU, CHRISTINA XUONG (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: Address;Adult;Affect;Affective;Age;Aging;alternative treatment;associated symptom;Attention;burnout;Cessation of life;Characteristics;Chronic;Chronic Insomnia;chronic pain;Clinical;Clinical Trials;Cognitive;cognitive function;contextual factors;Coupled;COVID-19 pandemic;daily pain;Data;data harmonization;Data Set;depressive symptoms;design;Deterioration;Development;diaries;Dopamine;experience;Exposure to;Family;Feeling;Fibromyalgia;foot;Future;General Population;Health;health disparity;Health Personnel;Health Promotion;Health protection;Healthcare Systems;Hour;improved;Individual;Injury;Intervention;Joints;Knowledge;Life;Lifting;Link;Manuscripts;Medical Errors;Mental Health;middle age;Modeling;Moods;mortality;negative affect;Norepinephrine;Occupations;older adult;Opioid;Outcome;Outcomes Research;Pain;Pain management;pain sensitivity;pain symptom;Pathway interactions;Patient Care;patient safety;Patients;Personal Satisfaction;Persons;pharmacologic;physical conditioning;Policies;poor sleep;Population;Populations at Risk;Productivity;protective factors;Psyche structure;Publishing Peer Reviews;Race;Reporting;Research;research study;Resources;Risk;Risk Factors;Running;Sampling;Serotonin;sex;shift work;Site;Sleep;Sleep Deprivation;sleep health;sleep quality;Sleeplessness;sociodemographics;stressor;Surveys;symposium;Symptoms;synergism;Testing;time use;Training;United States;Work;Workplace

PROJECT_TITLE: Protecting Healthcare Workers' Health and Well-being: The Joint Effects of Sleep and Pain, and Moderations by Work Characteristics

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


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Infant Mortality;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Newark

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Aortic arch artery and its major branches are critical vessels that route the blood from the heart to the systemic circulation. Aberrant development of the aortic arch results in severe congenital heart disease. Upon completing the proposed studies, we will gain new insights into mechanisms of compensation regulating the repair of aberrantly-formed embryonic vessels.

PI_NAMEs: ASTROF, SOPHIE  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: 22q11;3-Dimensional;Alleles;aortic arch;Applications Grants;Arteries;Blood;Blood Vessels;Branchial arch structure;Breathing;Candidate Disease Gene;Cardiovascular system;Cells;Chemotactic Factors;Chromosome abnormality;Circulation;Compensation;confocal imaging;Congenital Abnormality;congenital heart abnormality;Coupled;Data;Defect;Development;Diagnosis;DiGeorge Syndrome;DNA Sequence Alteration;dosage;Eating;Embryo;Endothelial Cells;endothelial stem cell;Endothelium;Ensure;Etiology;Fibroblast Growth Factor;Fibronectins;Fluorescent in Situ Hybridization;follow-up;Future;Genes;Genetic Engineering;Goals;Growth Factor;Heart;Human;Hypoplastic Left Heart Syndrome;Hypoxia;Immunohistochemistry;Impairment;In Situ Hybridization;insight;Integrins;Interruption;KDR gene;Knock-in Mouse;Knowledge;Lead;Maps;Mediating;Modeling;Morphogenesis;mouse development;mouse model;Mouse Strains;Mus;Mutagenesis;mutant;mutant mouse model;Mutate;Neonatal;Newborn Infant;novel;Pathogenicity;Pathway interactions;Patients;prevent;Process;progenitor;prophylactic;Quality of life;recruit;repaired;response;Route;Signal Transduction;Source;Stromal Cell-Derived Factor 1;Syndrome;Testing;transcription factor;transcriptome sequencing;Trees;Vascular Endothelial Growth Factors;Veins;Venous;Work

PROJECT_TITLE: Identification of compensatory mechanisms to rescue aortic arch artery defects

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-R(02)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Genetics;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE The human body is a mixture of cells that carry different gene mutations, which may confer tissue-context- dependent advantages or disadvantages. This phenomenon of somatic mosaicism has public health relevance because the expansion of cell populations with pathological mutations, such as those in the leukemia-driver gene DNMT3A, can contribute to cancer and developmental disorders. We plan to model somatic mosaicism using both cell lines and mice that we have developed with the long-term goal of identifying tissues in which DNMT3A loss confers a selective advantage or disadvantage, as well as the mechanism of this differential tissue composition.

PI_NAMEs: WALDVOGEL, SARAH MARIE (contact)

PROGRAM_OFFICER_NAME: STEIN, KATHRYN K

PROJECT_TERMS: Address;Adipocytes;adult stem cell;Affect;Apoptosis;Biology;Blood;cancer predisposition;career;Cell Culture System;Cell Differentiation process;Cell Line;cell type;Cells;Childhood;Chimera organism;clinical care;college;constitutive expression;design;Development;developmental disease;Developmental Gene;differential expression;Disadvantaged;Disease;DNA Modification Methylases;DNMT3a;DNMT3a mutation;Drug or chemical Tissue Distribution;embryo cell;Embryonic Development;embryonic stem cell;Environment;Epigenetic Process;Epithelium;ES Cell Line;Exhibits;Failure;fitness;Flow Cytometry;Fluorescence-Activated Cell Sorting;Future;Gene Cluster;Gene Mutation;Genes;Genetic Counseling;Germ Layers;Germ Lines;Goals;Growth;Hematopoietic stem cells;Heterozygote;Human;Human body;Image Cytometry;In Vitro;in vivo;Individual;Inherited;insight;Intellectual functioning disability;intestinal epithelium;Intestines;Knock-out;Knockout Mice;Knowledge;leukemia;Location;loss of function;loss of function mutation;Loss of Heterozygosity;LoxP-flanked allele;Malignant Neoplasms;Medical center;Medicine;Mesenchymal;Messenger RNA;Methylation;Microinjections;Modeling;mosaic;Mosaicism;Mouse Embryonic Stem Cells;mouse model;mRNA Differential Displays;Mus;mutant;Mutation;neural;Neurons;novel;old mice;Organism;overexpression;Parents;Pathogenesis;Pathologic;Patient Care;Patients;Pediatric Oncologist;pediatrician scientist;Phenotype;Population;postnatal;Predisposition;Proteins;public health relevance;Rahman Syndrome;Recurrence;Reporter;Research;Risk;Role;Sampling;Seizures;self-renewal;Seminal;Shapes;Somatic Mutation;stem cell population;stem cells;success;Syndrome;System;Technology;Testing;Texas;Tissues;Training;transcriptome sequencing;trend

PROJECT_TITLE: Determining the effect of DNMT3A loss on the competitive fitness of mutant cells in somatic mosaicism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-D(21)L]


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

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Preterm birth is the leading cause of mortality in infants under age one, resulting in over one million neonatal deaths annually and increased risk of infection, neurodevelopmental disorders, and cardiovascular and pulmonary disease in surviving preterm infants. The objective of this proposal is to define the impact of maternal urinary tract infection (UTI) on preterm birth incidence and averse neonatal outcomes through comprehensive characterization of the bladder, systemic, and reproductive immune response. The success of this work will illuminate potential therapeutic opportunities to predict, reduce, or prevent UTI-associated preterm birth.

PI_NAMEs: OTTINGER, SAMANTHA  (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Address;Age;Antibiotics;Automobile Driving;Bacteria;Biological Markers;Bladder;Cardiovascular Diseases;career;Career Mobility;Cells;Cerebral Palsy;chemokine;Coupled;Couples;cytokine;Data;Diagnosis;Escherichia coli;Exhibits;experience;experimental study;fetal;Fetal health;Fetus;Flow Cytometry;Immune;immune activation;Immune response;Immunologics;Immunology;improved;Incidence;Infant Mortality;Infection;infection risk;Inflammation;Inflammatory;intrauterine infection;Knowledge;Lipopolysaccharides;Lung Diseases;Maternal Health;maternal serum;Meta-Analysis;Microbe;Modality;Modeling;Molecular;mouse model;Mus;Neonatal Mortality;neonatal outcome;Neurodevelopmental Disorder;neutrophil;Neutrophil Activation;novel;novel therapeutics;Outcome;Pathogenesis;Pathway interactions;perinatal outcomes;Phenotype;Placenta;Pregnancy;Premature Birth;Premature Infant;Premature Labor;prevent;reproductive;Reproductive Biology;Research;Research Personnel;response;Risk;skills;standard of care;success;Systemic infection;Technical Expertise;Testing;Therapeutic;Third Pregnancy Trimester;Time;Urinary tract infection;Uropathogenic E. coli;Uterus;women's reproductive health;Work

PROJECT_TITLE: Characterizing the impact of maternal immune response to urinary tract infection on preterm birth

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

PHR: PROJECT NARRATIVE This project seeks to challenge prevailing views on how electrical excitation drives the heartbeat and how the heart responds to ischemic injury. By shifting the paradigm in these two important areas of cardiology, we will provide a better understanding of the basis of cardiac arrhythmias and sudden death, generate novel anti- arrhythmic drugs, and provide a new therapeutic approach to preserve heart muscle lost during the acute phase of a heart attack.

PI_NAMEs: GOURDIE, ROBERT G (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Actins;Action Potentials;Acute;Animal Model;Anti-Arrhythmia Agents;Area;Arrhythmia;Biomedical Engineering;Brain;Cardiac;Cardiology;Clinical;Collaborations;Complex;Connexin 43;Connexins;Coupling;Data;Drug Design;Drug Targeting;exosome;Gap Junctions;Gene Modified;Goals;Heart;heart preservation;Hour;Human;human female;in silico;induced pluripotent stem cell;invention;ischemic injury;Knockout Mice;Mammals;Medicine;Mutation;Myocardial;Myocardial Infarction;Myocardium;novel;novel therapeutic intervention;peptidomimetics;pharmacologic;Phase;Phase III Clinical Trials;porcine model;Production;Protein Isoforms;Proteins;Reporting;response;Role;Severities;Signal Transduction;Skin;Sodium Channel;Sudden Death;superresolution imaging;Testing;Therapeutic;Tissues;Translating;Ventricular;Virus;voltage

PROJECT_TITLE: Connexin-based Signaling in the Heart: Cellular and Exosomal


NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Heart failure (HF) is a leading cause of death, but the prevention and treatment remain challenging. Since Rho kinase (ROCK1 and ROCK2) has recently emerged as a potential therapeutic target, the proposed research focus on the pathologic roles of ROCK1 and ROCK2 in HF by deleting both ROCKs in cardiomyocytes and/or fibroblasts. The information obtained from this study can establish the potential therapeutic effects by targeting Rho kinase activity to mitigate heart failure progression.

PI_NAMEs: SHI, JIANJIAN ;WEI, LEI  (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Actins;Adult;age related;Aging;Animal Model;Autophagocytosis;biological adaptation to stress;Cardiac;Cardiac health;Cardiac Myocytes;Cardiovascular Diseases;Cause of Death;Cell Physiology;cell type;Cerebrovascular Spasm;Cessation of life;Clinical Research;Clinical Trials;Compensation;Complex;coronary fibrosis;Cytoskeletal Modeling;Cytoskeleton;Disease;Etiology;experimental study;Extracellular Matrix Proteins;F-Actin;Family;fasudil;Fibroblasts;Fibrosis;FRAP1 gene;Functional disorder;Genes;Genetic Processes;Goals;Grant;Guanosine Triphosphate Phosphohydrolases;Heart;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Heart Injuries;Human;human disease;human model;Hypertrophy;in vivo;inducible Cre;inhibition of autophagy;inhibitor;interstitial;ischemic injury;Japan;Knock-out;Knockout Mice;Knowledge;LIM Domain Kinase 1;Mediating;member;misfolded protein;Modification;Molecular;Mus;Muscle Contraction;Myocardial Ischemia;myocardin;Myocardium;Myofibroblast;Myosin Light Chains;myosin phosphatase;Names;Nature;new therapeutic target;novel therapeutic intervention;Nuclear Translocation;Organelles;Outcome Study;Oxidative Stress;Pathogenesis;Pathologic;Pathway interactions;Phosphotransferases;pressure;Prevention;Process;Production;Protein Isoforms;Regulation;Research;response;Rho-associated kinase;ROCK1 gene;Role;senescence;Serum Response Factor;Signal Pathway;Signal Transduction;Smooth Muscle Myocytes;Stress;Stress Fibers;Subarachnoid Hemorrhage;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Time;transcription factor;treatment trial;Ventricular;Work

PROJECT_TITLE: Role of ROCK isoform-mediated actin cytoskeleton modification in the pathogenesis of heart disease

STUDY_SECTION: CCHF

STUDY_SECTION_NAME: Cardiac Contractility, Hypertrophy, and Failure Study Section[CCHF]


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Cardiovascular;Contraception/Reproduction;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE With no unequivocally effective preventative strategies available, preeclampsia is a leading cause of maternal and fetal morbidity and mortality in the US, and African American women are disproportionately affected with higher prevalence, severity and mortality than white Americans. Our limited understanding of causal relationships between risk factors for preeclampsia, its long-term consequences on cardiovascular and metabolic health and limited availability of candidates for pharmaceutical prevention hinders our ability to reduce public health burden associated with this condition. With the goal of informing effective preventative strategies for preeclampsia, our study proposes to understand causal and mechanistic [genetic, clinical and social] relationships involved in preeclampsia and to identify gene targets to accelerate the pipeline for drug discovery and repurposing.

PI_NAMEs: GIRI, AYUSH  (contact)

PROGRAM_OFFICER_NAME: SMITH, SHARON M

PROJECT_TERMS: Acceleration;Admixture;admixture mapping;Affect;African American Women;African ancestry;African Women;American;Aspirin;Benefits and Risks;biobank;Birth;Blood Pressure;Blood Vessels;Boston;cardiovascular health;Cardiovascular system;caucasian American;Child;Chromosome Mapping;Chronic Kidney Failure;Clinical;clinical risk;Cohort Studies;Collection;Data;data platform;design;Development;Diabetes Mellitus;Discrimination;disparities in morbidity;Disparity;Disproportionately impacts women;drug discovery;drug repurposing;Drug Targeting;Drug usage;early onset;effective intervention;Endothelium;epidemiologic data;Epidemiologic Methods;Epidemiology;epidemiology study;Etiology;European;experimental study;Exposure to;fetal;Fetal Death;Fetus;flexibility;Future;gene discovery;Gene Expression;Gene Proteins;Gene Targeting;Genes;Genetic;genetic architecture;Genetic Predisposition to Disease;genetic resource;Genetic study;genetic variant;genome wide association study;Genomics;Goals;Health;Health Care Costs;health management;Heritability;High Prevalence;high risk;high throughput screening;Hypertension;Incidence;Infant;innovation;insight;instrument;Intervention;Investigational Drugs;Laws;Link;Lipids;liver function;Measures;Mediating;Mendelian randomization;Meta-Analysis;Metabolic;Metabolic dysfunction;Metformin;Methods;Morbidity - disease rate;mortality;Mothers;multiple omics;Myocardial Ischemia;novel;Obesity;Outcome;Patient Self-Report;Pharmaceutical Preparations;Pharmacologic Substance;phenome;post pregnancy;Pre-Eclampsia;Pregnancy;Pregnancy Complications;Prevalence;Prevention;Prevention strategy;protein expression;Proteins;Proxy;Public Health;Race;racial disparity;racism;Renal function;Research;Retinal Diseases;Risk;Risk Factors;Risk Marker;risk stratification;Role;Sampling;segregation;Severities;side effect;Skin;skin color;Skin Pigmentation;social;Social Environment;Socioeconomic Status;Source;statistics;Stress;Stroke;Structure;theories;Thrombophilia;trait;Validation;venous thromboembolism;Woman

PROJECT_TITLE: Understanding causal mechanisms in preeclampsia through genetic instrumental variables

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(90)]


NIH_SPENDING_CATS: Cancer;Genetics;Human Genome

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Telomere shortening impedes uncontrolled cell division either by triggering replicative senescence or apoptosis or by running transformed cells into telomere crisis, in which rampant end-to-end telomere fusions and chromosome rupture restrict cell viability. This project aims to identify the molecular mechanism and physiologic repressors of telomerase-mediated DNA double-strand break repair, which may enable transformed cells to escape telomere crisis and emerge as clinical tumors. My anticipated findings will illuminate another facet of genomic instability in early tumorigenesis and may lead to novel strategies for cancer diagnosis and prevention.

PI_NAMEs: KINZIG, CHARLES GUNNAR (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: alpha-Thalassemia;Aneuploidy;Apoptosis;Award;Base Pairing;Binding;Biological Assay;cancer cell;cancer diagnosis;cancer prevention;carcinogenesis;career;Cell Aging;Cell division;Cell Survival;cell transformation;Cells;Centromere;Chromosomal Breaks;Chromosome 16;Chromosome Deletion;chromosome fusion;Chromosomes;chromothripsis;Clinical;Complex;Data;design;detection assay;Development;Dicentric chromosome;Distal;DNA Damage;DNA Double Strand Break;DNA Primase;Doctor of Philosophy;Double Strand Break Repair;Doxycycline;Ectopic Expression;Environment;Event;expectation;experimental study;Frequencies;Genes;genetic approach;Genome;Genome Stability;Genomic Instability;Genomics;Germ Cells;Goals;Gonadal structure;Haploidy;healing;Hela Cells;Human;improved;In Vitro;Institution;Length;Link;Malignant Neoplasms;Mediating;Medical;Methods;Molecular;mortality;Neoplasms;neoplastic cell;novel strategies;p53-binding protein 1;Pathologic;Pathway interactions;Patient Care;Patients;Physicians;Physiological;Polymerase;prevent;Process;programs;Proliferating;reconstitution;recruit;Regulation;repaired;Reporter;Repression;response;Role;Running;Rupture;Scientist;senescence;Signal Transduction;Somatic Cell;stem cells;Telomerase;Telomerase inhibition;Telomerase Inhibitor;Telomerase RNA Component;telomere;Telomere Maintenance;Telomere Shortening;Testing;TP53 gene;Trees;tumor;tumorigenesis

PROJECT_TITLE: Telomerase-Mediated Healing of Double-Strand Breaks in Human Cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Microbiome

ORG_CITY: CAMBRIDGE

ORG_NAME: ADA FORSYTH INSTITUTE, INC.

ORG_STATE: MA

PHR: Projective Narrative The interaction between human and its associated bacteria plays a crucial role in determining human’s heath and disease. Our research is focused on studying how human epithelial cells-produced small RNAs can be transported to oral bacteria and affect their behavior. The knowledge we gain through this study will allow us to better understand the interaction between bacteria and oral mucosa and its impact on human oral health.

PI_NAMEs: HE, XUESONG  (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: adaptive immunity;Address;Affect;antimicrobial;Bacteria;Bacterial Genes;bacterial genetics;Bacterial Proteins;Behavior;beneficial microorganism;Biochemical;Biochemistry;Biological Models;Biological Process;Carrier Proteins;cell immortalization;Cell Line;Cells;Communication Programs;Complex;Coupled;Data;Defense Mechanisms;Disease;Dissection;Encapsulated;Epithelial Cells;Exhibits;exosome;extracellular;Fluorescence Microscopy;Follow-Up Studies;Fusobacterium nucleatum;Gene Expression;Genes;genetic analysis;Goals;Growth;gut microbiome;Health;Homeostasis;Host Defense;host microbiome;host-microbe interactions;Human;human subject;Image;Infectious Agent;Intake;keratinocyte;Knowledge;Lead;Maintenance;Mediating;Membrane;Membrane Transport Proteins;Microbe;microbial;microbial homeostasis;microbial host;microbiome;Mouth Diseases;Mucous Membrane;National Institute of Dental and Craniofacial Research;Natural Immunity;novel therapeutic intervention;nucleic acid-based therapeutics;opportunistic pathogen;Oral;oral bacteria;oral commensal;Oral health;oral microbiome;Oral mucous membrane structure;pathogen;Periodontitis;periodontopathogen;Plants;Play;Porphyromonas;Predisposition;prevent;Process;Protein Binding Domain;Protocols documentation;Publishing;Regulatory Element;Regulatory Pathway;Reporting;Research;Resolution;response;RNA;RNA Recognition Motif;Role;Saliva;saliva sample;Salivary;Small RNA;social;Strategic vision;Streptococcus mitis;Surface;Testing;Therapeutic;trafficking;transcriptome sequencing;Transfer RNA;United States National Institutes of Health;Work

PROJECT_TITLE: Host tRNA-derived small RNAs (tsRNAs) mediate interactions between host and oral microbes

STUDY_SECTION: ODCS

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: NEW ORLEANS

ORG_DEPT: PATHOLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, which is characterized by chronic synovitis of peripheral joints, bone and cartilage degradation, which leads to joint disability, and there is a compelling need to explore novel therapeutic targets to develop safer and more effective therapies for RA. The proposed study will provide important insights into the negative regulation of the cells of the immune system to target inflammation and bone destruction in RA by elucidating the underlying mechanism of Gα13 signaling. Knowledge gained from this study may generate potential therapeutic means for treating RA and other inflammatory bone diseases.

PI_NAMEs: LI, YI-PING  (contact)

PROGRAM_OFFICER_NAME: MAO, SU-YAU

PROJECT_TERMS: Animal Model;Ankle;ankle joint;Arthritis;Attenuated;Autoimmune Diseases;Binding Sites;Biological;bone;Bone Diseases;cartilage degradation;Case Study;Cell Differentiation process;Cells;ChIP-seq;Chronic;Collagen Arthritis;conditional knockout;Cre lox recombination system;Data;Dendritic Cells;disability;Disease;effective therapy;Endogenous Factors;gain of function;Genes;genome-wide;Goals;Immune system;Inflammation;Inflammation Mediators;Inflammatory;insight;ITGAX gene;Joints;Knockout Mice;Knowledge;Lesion;loss of function;Macrophage;Malignant Neoplasms;Mediating;Modeling;Molecular;mouse model;Mus;new therapeutic target;NF-kappa B;overexpression;Pathologic;Pathway interactions;Patients;Peripheral;Phenotype;Phosphorylation;Pneumonia;promoter;Proto-Oncogene Proteins c-akt;Regulation;Research;Rheumatoid Arthritis;Role;Signal Pathway;Signal Transduction;STAT3 gene;Synovitis;Testing;Therapeutic;Therapeutic Effect;Tissues;TNF gene;transcriptome sequencing;Transgenic Organisms;Tuberculosis

PROJECT_TITLE: Characterizing the negative signaling in dendritic cells and macrophages to attenuate inflammation and bone destruction in rheumatoid arthritis

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]