NIH_SPENDING_CATS: Data Science;Eye Disease and Disorders of Vision;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Patient Safety

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: NARRATIVE For researchers to take full advantage of the large amount of clinical data that is captured in electronic health records and incorporate this information into machine learning and artificial intelligence applications, outcomes research, genotype-phenotype association studies, and other areas, it is critically important to be able to accurately identify diseases and outcomes of interest; the existing approach relies exclusively on administrative billing codes to identify these entities. In this study we will develop and test novel approaches to identifying and characterizing sight-threatening eye diseases and their outcomes in electronic health record data. By fulfilling the aims of this grant, we will make it easier for researchers throughout the country and the world to make use of electronic health record and clinical registry data to study patients with chronic diseases, which is essential to the mission of the National Institutes of Health.

PI_NAMEs: STEIN, JOSHUA D (contact)

PROGRAM_OFFICER_NAME: EVERETT, DONALD F

PROJECT_TERMS: Acceleration;Adverse event;Algorithms;Area;Artificial Intelligence;Big Data;Bioinformatics;Biometry;Blindness;care providers;Categories;Chronic Disease;Classification;Clinical;Clinical Data;clinical decision-making;Clinical Research;clinical trial recruitment;Clinical Trials;clinically relevant;Cluster Analysis;Code;cost;Country;Data;Data Element;data registry;Data Set;Databases;Deterioration;Development;Diabetic Retinopathy;Diagnostic tests;Disease;Disease Progression;electronic health data;Electronic Health Record;Evolution;experience;Eye;Eye diseases;flexibility;Foundations;Future;Genotype;Glaucoma;Grant;Health Services Research;Healthcare;improved;innovation;interest;Intervention;Machine Learning;machine learning algorithm;Macular degeneration;Manuals;Methodology;Methods;Mission;Nature;novel;novel strategies;Ophthalmology;Outcome;Outcomes Research;Paper;Patient Recruitments;Patients;Phenotype;Planning Techniques;Positioning Attribute;Precision Medicine Initiative;Probability;Process;Registries;Research;Research Personnel;Research Project Grants;Running;segregation;Sensitivity and Specificity;Severity of illness;Sorting;Source;Stable Disease;Structure;structured data;Techniques;Testing;Text;Time;tool;Translational Research;United States National Institutes of Health;unstructured data;Vision;Work

PROJECT_TITLE: Enhanced Identification of Ocular Phenotypes and Outcomes in Electronic Health Record Data

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-T(02)]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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);Bioengineering;Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_FIPS: US

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) represents one of the most significant healthcare problems in the aging population of the United States, but the contribution of the blood-brain barrier and meningeal lymphatics impairment in AD is yet to be fully elucidated. This is partly due to the lack of an effective and reliable model to capture the complex interactions between the various cellular components in the brain. Drawing upon our considerable experience in 3D modeling of AD in a dish, the BBB, and neurovascular units in vitro, we propose to create a comprehensive model of AD focusing on key interactions and the role of the BBB and meningeal lymphatics impairment in Aβ clearance to gain a deeper understanding of underlying mechanisms.

PI_NAMEs: CHOI, SE HOON ;JORFI, MEHDI ;KAMM, ROGER D (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: 3-Dimensional;Abeta clearance;Acceleration;AD transgenic mice;Address;Affect;age related;aging population;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Antibodies;Astrocytes;Biological Markers;Biological Models;Blood;Blood - brain barrier anatomy;Blood Cells;Blood Vessels;Brain;Brain Chemistry;brain parenchyma;Brain Pathology;candidate marker;cell behavior;Cell Culture Techniques;cell type;Cells;Central Nervous System;Cerebral Amyloid Angiopathy;Cerebrospinal Fluid;Clinical;Complex;Deep Cervical Lymph Node;Dementia;Deposition;design;Development;disease model;Disease Progression;disease-in-a-dish;drug discovery;Elderly;Endothelial Cells;Environment;Event;experience;Extracellular Matrix;Genetic Transcription;Goals;Healthcare;Human;human disease;hyperphosphorylated tau;Immune;Impaired cognition;Impairment;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Intercellular Fluid;interest;interstitial;Intervention;Liquid substance;Lymphatic;lymphatic circulation;Lymphatic clearance;lymphatic dysfunction;Lymphatic function;Lymphatic System;lymphatic vessel;Lymphocyte;Meningeal lymphatic system;Meninges;Microfluidic Microchips;microfluidic technology;Microfluidics;Microglia;Modeling;Molecular;Monitor;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurons;neurovascular;neurovascular unit;new therapeutic target;Organoids;Pathogenicity;Pathologic;Pathology;Pathway interactions;Peptides;Pericytes;Persons;Phagocytosis;Pharmaceutical Preparations;Physiological;Population;Process;Property;Role;Senile Plaques;spheroids;stem cells;Structure;System;tau Proteins;Technology;Testing;Therapeutic Intervention;three-dimensional modeling;tool;transcriptome sequencing;United States

PROJECT_TITLE: Human 3D Neuro-Vascular Interaction and Meningeal Lymphatic Models with Application to Alzheimer’s Disease

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: CHAPEL HILL

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative The Infectious Disease Pathogenesis Research Training Program seeks to train postdoctoral trainees to conduct outstanding research in the fields of bacterial pathogenesis, immunology, virology and epidemiology of infectious disease pathogenesis, to foster the development of skills necessary to conduct productive interdisciplinary research, and to facilitate professional growth and development to ensure academic and research success.

PI_NAMEs: JULIANO, JONATHAN J (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: Communicable Diseases;Pathogenesis;Research Training;Training Programs

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: HOUSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative My proposal aims to use cryo-electron tomography and correlative fluorescence microscopy to elucidate the high-resolution structural changes that lead to excitotoxic loss in dendritic spines (DS). I hypothesize following glutamate excitotoxicity dually innervated DS that contain both an inhibitory and excitatory synapse have a more stable DS structure than single innervated DS containing only an excitatory synapse. If successful, this project would determine the high-resolution actin network differences between dually and singly innervated DS and provide evidence for the protective effect of inhibitory synapses on DS structure ensuing excitotoxicity.

PI_NAMEs: ANDERSON, ERIK DAVID (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: 3-Dimensional;Actins;Action Potentials;Affect;age related;age related neurodegeneration;Alzheimer's Disease;Axon;Calcium;Cells;chemical fixation;Cryo-electron tomography;Cryoelectron Microscopy;Cytoskeleton;Dendrites;Dendritic Spines;Diffusion;Dose;Excitatory Postsynaptic Potentials;Excitatory Synapse;excitotoxicity;Fluorescence;Fluorescence Microscopy;Glutamates;Head and neck structure;Image;Inhibitory Synapse;Injury;interest;Ions;Learning;Macromolecular Complexes;Membrane;Memory;Microscopy;Modeling;Molecular;Morphology;nanometer resolution;Neck;Necrosis;Nerve Degeneration;neural circuit;Neurologic;neuron apoptosis;Neuronal Injury;Neurons;prevent;Process;protective effect;Rattus;Research;Research Personnel;Resolution;Resources;Role;Secondary Protein Structure;Shock;Spatial Distribution;Stroke;Structure;Synapses;Techniques;therapeutic target;Training;Transfection;Vertebral column;Visualization

PROJECT_TITLE: Determining the ultrastructural differences between dually and singly innervated dendritic spines and their changes following glutamate excitotoxicity using Cryo-Electron Tomography


ADMINISTERING_IC: AG

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);Bioengineering;Biotechnology;Brain Disorders;Data Science;Dementia;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_CITY: SEATTLE

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Improvements to mass spectrometry will better enable the study of aging, neurodegenerative diseases such as Alzheimer's, and age-related cancers. This project addresses the missingness endemic to virtually every quantita- tive mass spectrometry proteomics experiment and offers a robust analytical solution that will signiﬁcantly improve the utility of mass spectrometry experiments. The computational methods developed by this project will enable additional discoveries within Alzheimer's disease proteomics data, leading to better understanding of Alzheimer's disease biology, identiﬁcation of brain region-speciﬁc biomarkers, and selection of potential therapeutic targets.

PI_NAMEs: HARRIS, LINCOLN JEFFERY (contact)

PROGRAM_OFFICER_NAME: CHAKROBORTY, SHREAYA

PROJECT_TERMS: Address;age related;Aging;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloid beta-Protein;asymptomatic Alzheimer's disease;Benchmarking;Biological;Biology;biomarker discovery;biomarker identification;Brain region;Cells;Cerebrospinal Fluid;comorbidity;Computer software;computerized data processing;Computing Methodologies;Data;Data Discovery;data imputation;Data Set;deep neural network;differential expression;Dimensions;Disease;experimental study;FASTK Gene;Funding;Future;Genetic;global health;hyperphosphorylated tau;improved;ionization;Joints;Knowledge;Label;laser capture microdissection;Learning;learning strategy;Left;light weight;Link;Machine Learning;machine learning method;malformation;Malignant Neoplasms;mass spectrometer;Mass Spectrum Analysis;Measurement;Measures;Messenger RNA;Methods;Molecular;Molecular and Cellular Biology;Network-based;Neural Network Simulation;Neurodegenerative Disorders;Noise;novel;open source;Pathogenesis;patient biomarkers;Patients;Pattern;Peptides;Performance;Persons;phosphoproteomics;Prevalence;Procedures;Process;Prognosis;Proteins;Proteome;Proteomics;Public Health;Publishing;Reproducibility;Research Personnel;Running;Sampling;Software Tools;specific biomarkers;statistical learning;Therapeutic Intervention;therapeutic target;Training;United States National Institutes of Health;virtual;Work

PROJECT_TITLE: Imputing quantitative mass spectrometry proteomics data using non-negative matrix factorization

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


NIH_SPENDING_CATS: Aging;Nutrition;Obesity;Prevention

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Aging is the greatest risk factor for many age-related diseases that impair quality of life and is a growing public health concern in the United States. One hallmark of aging is cellular senescence, which has been shown to promote age-related pathologies. This proposal will examine how dietary protein and branched-chain amino acids regulate healthy aging by affecting cellular senescence, with the goal of gaining mechanistic insight into cellular senescence and aging that will aid in developing geroprotective interventions.

PI_NAMEs: CALUBAG, MARIAH  (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Adipose tissue;Affect;Age;Age related pathologies;age-related disease;aged;Aging;aging related;Apoptotic;Automobile Driving;Biology of Aging;Branched-Chain Amino Acids;Cardiovascular Diseases;Cell Aging;Cell Culture Techniques;Cell Cycle Arrest;cell growth regulation;Cells;Complex;Consumption;Cultured Cells;Dasatinib;Development;Diabetes Mellitus;Diet;diet-induced obesity;dietary;Dietary Intervention;dietary manipulation;Dietary Proteins;DNA Damage;Eating;experimental study;extend lifespan;Faculty;family burden;Fellowship;Female;fibroblast growth factor 21;Fibroblasts;frailty;FRAP1 gene;Gene Expression;Genetic;geroprotector;Goals;hallmarks of aging;Health;Healthcare Systems;healthspan;healthy aging;Homeostasis;Hormone Responsive;Human;human old age (65+);Impairment;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;insight;Intervention;Isoleucine;Leucine;Life;life span;Liver;Longevity;Macronutrients Nutrition;male;Malignant Neoplasms;Mediating;member;Mentorship;Metabolic;Metabolic dysfunction;Metabolism;Methods;middle age;Mitochondria;Molecular;mortality;mTOR Inhibitor;Mus;Muscle;Nature;Obese Mice;old mice;Pathology;Pathway interactions;Persons;Pharmaceutical Preparations;pharmacologic;Population;Predisposition;premature;prevent;pro-aging;Process;protein intake;Protein Kinase;Proteins;Public Health;Quality of life;Quercetin;Regimen;Research Personnel;Resistance;response;Risk Factors;Rodent;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Signal Transduction;Sirolimus;skills;Stimulus;Stress;stressor;Supplementation;tenure track;Testing;Tissues;Training;transcriptome;United States;Valine

PROJECT_TITLE: Regulation of cellular senescence and metabolic health by dietary protein

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Duchenne/ Becker Muscular Dystrophy;Muscular Dystrophy;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: SAN ANTONIO

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE The cerebellum improves behavior using implicit learning encoded by climbing-fiber-induced LTD, a type of plasticity subject to regulation because without gating, its induction would occur promiscuously potentially corrupting the capacity for accurate new learning. Because GABAA receptor-mediated inhibition opposes climbing-fiber-mediated plasticity and learning, we seek to test the hypothesis that in a mouse model of dystrophinopathy (Duchenne muscular dystrophy, DMD), loss of dystrophin-dependent GABAA receptor clustering in Purkinje cells explains plasticity deficits that affect implicit learning in these animals. Furthermore, we will test whether increasing inhibition in these cells provides symptomatic relief by increasing the threshold for plasticity induction; in this way, completion of this project will help determine pathology related to impaired plasticity gating, the etiology of brain deficits in DMD, and provide insight into therapeutic strategies to recover cerebellar function in this disorder.

PI_NAMEs: CHRISTIE, JASON M;PUGH, JASON RICHARD (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Affect;Agreement;Animals;Attention deficit hyperactivity disorder;autism spectrum disorder;Automobile Driving;Behavior;Behavioral;behavioral phenotyping;Brain;Brain Diseases;Calcium;Calcium Signaling;cell type;Cells;Cerebellar Diseases;Cerebellum;Chronic;cognitive disability;comorbidity;Conflict (Psychology);Custom;Data;Dendrites;Disease;Disinhibition;Duchenne muscular dystrophy;Dystrophin;dystrophinopathy;Engineering;Etiology;Exhibits;expectation;Fiber;Fire - disasters;Functional disorder;genetic technology;Goals;Health;Human;Impairment;improved;in vivo;Inferior;Inhibitory Synapse;insight;interdisciplinary approach;Interneurons;Learning;Link;Long-Term Depression;Mediating;Molecular;Molecular Genetics;mouse model;Mus;Muscular Atrophy;Nervous System Disorder;neural;neural circuit;Neurobiology;Neurologic;Neurologic Symptoms;novel;Olives - dietary;Outcome;Pathologic;Pathology;Patients;Performance;Pharmaceutical Preparations;pharmacologic;prevent;Process;Purkinje Cells;receptor;Regulation;response;Role;Symptoms;Synapses;synaptic function;Testing;Therapeutic;therapeutic target;therapy development;Transgenic Mice;treatment strategy;Wild Type Mouse;Work

PROJECT_TITLE: Cerebellar pathology in the absence of plasticity gating


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BUFFALO

ORG_NAME: VA WESTERN NEW YORK HEALTHCARE SYSTEM

ORG_STATE: NY

PHR: Cardiovascular disease is the leading cause of death among Veterans and congestive heart failure, in particular, is among the most common conditions resulting in death, disability, and hospitalization. Heart failure with preserved ejection fraction (HFpEF) has emerged as the most common form of heart failure, but our poor understanding of how it develops has made it difficult to devise effective treatments. The research proposed in this application will address this problem by examining how repetitive stretch-induced remodeling of the non- cellular components of heart muscle (i.e., the cardiac extracellular matrix) leads to persistent fibrotic collagen deposition and a sustained reduction in cardiac compliance that promotes the development of HFpEF in patients with chronic coronary artery disease (CAD). Improved understanding of this process is anticipated to reveal new targets for therapies designed to prevent or reverse heart muscle stiffening in CAD patients at-risk of developing HFpEF and significantly improve the quality of life and survival of Veterans with this common condition.

PI_NAMEs: WEIL, BRIAN RAYMOND (contact)

PROJECT_TERMS: Address;Adhesives;Aging;Angiography;Angioplasty;Area;Autopsy;Biochemical;Biological;Blood capillaries;Cardiac;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cessation of life;Chronic;Classification;Clinical;clinically relevant;cohort;Collagen;comorbidity;Congestive Heart Failure;Coronary;Coronary Arteriosclerosis;coronary fibrosis;Coronary Vessels;Data;Deposition;Development;disability;Disease;Dyspnea;effective therapy;EFRAC;Evidence based treatment;Exertion;Exhibits;experience;experimental study;Exposure to;Extracellular Matrix;Family suidae;Feedback;Fibrillar Collagen;Fibroblasts;Fibrosis;Frequencies;Functional disorder;Glycoproteins;Glycosaminoglycans;Goals;Healthcare Systems;Heart Diseases;Heart failure;heart failure with reduced ejection fraction;hemodynamics;Heterogeneity;Hospitalization;Hypertension;Implant;improved;interstitial;Investigation;Ischemia;Left;Left Ventricular Mass;Left ventricular structure;Link;Mechanics;Medicine;military veteran;Modeling;Monitor;Morbidity - disease rate;mortality;multidisciplinary;Myocardial;Myocardial tissue;Myocardium;new therapeutic target;novel;novel therapeutic intervention;Obesity;Outcome;Patients;Phenotype;Phenylephrine;Population;porcine model;preservation;pressure;Prevalence;prevent;Process;Prognosis;Property;Quality of life;Research;revascularization;Risk;Risk Factors;Role;Stenosis;Stretching;Symptoms;Telemetry;Testing;therapy design;treatment strategy;Ventricular;Veterans

PROJECT_TITLE: Repetitive Stretch-Induced Myocardial Stiffening in Chronic Coronary Artery Disease


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: MONTCLAIR

ORG_DEPT: CHEMISTRY

ORG_NAME: MONTCLAIR STATE UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative  This research aims to evaluate the hypothesis that phosphodiesterase 11A, an enzyme expressed in a brain region closely associated with memory, and increasingly expressed as humans age, can be inhibited by small molecules and improve performance in animal models of memory without mechanism-based adverse events.

PI_NAMEs: HOFFMAN, CHARLES S.;KELLY, MICHY PATRICE;ROTELLA, DAVID  (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: Acute;Address;Adverse event;Age;age related;age related decline;Age-associated memory impairment;age-related disease;Age-Related Memory Disorders;aged;Aging;analog;Animal Model;Animals;Anterior;Anxiety;Area;Attention;Behavior;Behavioral;behavioral study;Biological Assay;Biological Availability;Brain;Brain region;candidate validation;Cells;cohort;Controlled Study;Cyclic AMP;Cyclic GMP;Data;demented;Dementia;Disease;disease model;Dose;Drug Kinetics;Drug Targeting;effective therapy;enzyme substrate;Enzymes;Evaluation;experimental study;Family;Genes;Genetic;Health;Hippocampal Formation;Hippocampus;Human;Impaired cognition;improved;In Vitro;in vivo;in vivo Model;inhibitor;innovation;Investigation;Knock-out;Lead;Libraries;Literature;long term memory;Mammalian Cell;Measures;Mediating;Memory;Memory impairment;Memory Loss;memory retrieval;Mental Depression;Mental disorders;Methods;Motor;Motor Activity;mouse model;Mus;Mutant Strains Mice;Neurodegenerative Disorders;Neurons;novel;novel therapeutic intervention;old mice;Oral;Performance;Permeability;pharmacologic;phosphodiesterase 11a;Phosphorylation;Physiological;prevent;Primates;Protein Isoforms;Proteins;Research;Rodent;screening;Sensory;side effect;Signal Transduction;Signaling Molecule;small molecule;small molecule inhibitor;Social Behavior;Social Interaction;System;therapeutic target;Viral;Yeasts

PROJECT_TITLE: Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS]


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: TN

PHR: Service-related diseases including post-traumatic stress disorder (PTSD) are a major problem in Veterans. There is also an increased prevalence of inflammatory bowel disease (IBD; ulcerative colitis and Crohn’s disease) in VA patients. IBD and PTSD appear to be linked. It has been speculated that this is related to altered gut bacteria (microbiome), but this potential explanation, and the cellular/molecular features of IBD in Veterans have not been determined. We will utilize our long experience in IBD research, our robust clinical and research infrastructure, and the synergy of the Collaborative Merit Award to address knowledge gaps. Using powerful molecular techniques, we will study stool bacterial composition and function, as well as genes and proteins expressed, and metabolites in gut tissues from VA IBD and PTSD patients. We will use novel models involving intestinal cells from patients, and mice infected with patient microbiota and tested in experimental colitis, to uncover causes of these diseases and develop a Roadmap for new treatments in Veterans.

PI_NAMEs: WILSON, KEITH T. (contact)

PROJECT_TERMS: Address;Attenuated;Award;bench to bedside;Biological;Biological Assay;Biology;Cells;Cellular biology;Chronic stress;Clinical;clinical infrastructure;Clinical Management;Clinical Research;Colitis;Collaborations;Colon;Crohn's disease;Data;Diagnosis;diarrheal disease;Disease;dysbiosis;Early Diagnosis;Epithelium;experience;Feces;Functional disorder;Gastroenterologist;Gastrointestinal Diseases;gastrointestinal epithelium;Gene Expression;Genes;Germ-Free;Grant;gut bacteria;gut inflammation;gut microbiome;gut-brain axis;Human;human disease;human microbiota;humanized mouse;Immune;Immune System Diseases;Immunofluorescence Immunologic;improved;in vivo Model;Incidence;Inflammatory Bowel Diseases;inflammatory marker;Inflammatory Response;Intervention;intestinal epithelium;Intestines;Knowledge;Link;Liver diseases;Messenger RNA;metabolomics;Metagenomics;microbiome;microbiome alteration;microbiota;military service;Modality;Modeling;Molecular;Morbidity - disease rate;mouse model;Mus;novel;novel therapeutics;Organoids;Outcome;Pathogenesis;Patients;Persian Gulf Syndrome;Physicians;Post-Traumatic Stress Disorders;Predisposition;Prevalence;Prevention;programs;Proteins;Psychological Stress;Recording of previous events;Research;Research Infrastructure;response;Role;Sampling;Scientist;Services;Source;Spermidine;stool sample;Structure;synergism;systemic autoimmunity;systemic inflammatory response;Techniques;Technology;Testing;Tissues;translational goal;translational impact;Ulcerative Colitis;Veterans;Work

PROJECT_TITLE: BCCMA: Targeting Gut-Microbiome in Veterans Deployment Related Gastrointestinal and Liver Diseases: Dysbiosis, PTSD, and Epithelial and Immune Biology in Inflammatory Bowel Disease in Veterans


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Cardiovascular;Contraception/Reproduction;Genetics;Human Genome;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Preeclampsia affects millions of pregnancies worldwide, and there are limited therapeutics for patients. Senescent cells have been implicated in the pathogenesis of preeclampsia, and designing drugs targeting senescent cells holds great promise. The histone variant H2AJ has been shown to control the senescent- associated secretory phenotype, and we have knocked down this protein in a model of trophoblast development to uncover its function.

PI_NAMEs: JENSEN, TYLER BARRY (contact)

PROGRAM_OFFICER_NAME: WEINBERG, DAVID H

PROJECT_TERMS: 3-Dimensional;Affect;Architecture;BRCA1 gene;BRCT Domain;Cell Aging;Cell Cycle Arrest;cell type;Cells;Characteristics;Chromatin;chromosome conformation capture;Cleavage Under Targets and Release Using Nuclease;cohesin;Complex;Data Set;Deposition;Development;Disease;DNA Damage;DNA Repair;Down-Regulation;Drug Design;drug development;Drug Targeting;Eclampsia;embryonic stem cell;Endometrium;Enhancers;Euchromatin;experience;fetal;Fibroblasts;First Pregnancy Trimester;Fluorescent in Situ Hybridization;Foundations;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;Genome;Genome Mappings;Genome Stability;Goals;Heterochromatin;Hi-C;Histone H2A;Histones;Hormones;Human;Human Development;human disease;human embryonic stem cell;Immunoprecipitation;Inflammatory;insight;Invaded;knock-down;Knowledge;learning strategy;Life;Link;Maintenance;Mass Spectrum Analysis;Mentorship;Modality;Modeling;Molecular Conformation;Morbidity - disease rate;mortality;normotensive;novel therapeutics;Nuclear;Organ;Outcome;Pathogenesis;Patients;Pattern;Phenotype;Physicians;Placenta;placental mammal;Placentation;Pre-Eclampsia;Pregnancy;pregnancy disorder;pregnant;Pregnant Women;Production;promoter;Proteins;Research;response;Role;Sampling;Scientist;segregation;senescence;senescence associated secretory phenotype;senescent cell;senolytics;senomorphic;Signal Pathway;skills;Specific qualifier value;Stains;Syncytiotrophoblast;System;Tail;Techniques;Tertiary Protein Structure;Therapeutic;Therapeutic Intervention;therapeutic target;Third Pregnancy Trimester;Time;Training Activity;Transcriptional Regulation;transcriptome sequencing;transcriptomics;trophoblast;trophoblast stem cell;Up-Regulation;Variant;Villous

PROJECT_TITLE: H2AJ as a regulator of placental senescence and genome organization


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Infectious Diseases;Malaria;Orphan Drug;Pediatric;Prevention;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative Malaria remains one of the biggest infectious disease problems in the world, and drugs are of critical importance to treat episodes of malaria, prevent disease in high risk groups, and limit transmission. In this context, antimalarial drug resistance is a major threat. We will study the pharmacology of key drugs in studies evaluating the treatment of malaria in Ugandan children, prevention of malaria in Ugandan pregnant women, and prevention of malaria in children in Burkina Faso. These studies will help us to optimize regimens for the treatment and prevention of malaria.

PI_NAMEs: AWEEKA, FRANCESCA T.;ROSENTHAL, PHILIP JON (contact)

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: adverse birth outcomes;Africa;African;African Women;Age;Amodiaquine;Anti-malarial drug resistance;Anti-malarials;artemether;Artemisinins;artesunate;benflumetol;Birth;Burkina Faso;Chemoprevention;Chemopreventive Agent;Child;Clinical;Clinical Trials;Collaborations;Combined Modality Therapy;Communicable Diseases;Communities;Data;Disease;Drug Exposure;Drug Kinetics;Drug resistance;drug sensitivity;Drug usage;drug-sensitive;Exposure to;Funding;Goals;high risk population;improved;Incidence;Infant Mortality;insight;Malaria;Malaria prevention;Malnutrition;Measures;New Agents;Nutritional status;optimal treatments;Outcome;Parasite resistance;Parasitemia;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology;Pharmacology Study;Pharmacotherapy;Populations at Risk;Pregnancy;pregnancy prevention;pregnant;Pregnant Women;Prevalence;prevent;Prevention approach;Preventive;Preventive therapy;Prospective cohort;Pyrimethamine;Randomized;Recurrence;Regimen;Research;Resistance;Risk;Sampling;Schedule;Seasons;Southeastern Asia;Sulfadoxine;Testing;transmission process;Treatment Protocols;trial comparing;Uganda;uptake;Vaccines;vector control;Woman

PROJECT_TITLE: Pharmacological insights into antimalarial exposure, clinical outcomes, and drug resistance in Africa

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Prevention;Substance Misuse;Substance Misuse Prevention

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative This program offers postdoctoral research training in substance abuse prevention to generate knowledge about the translation of research into real-world settings in order to impact prevention practice and policy, and ultimately, public health. The training provided aligns very well with NIDA strategic research objectives and priorities. Also, since the program's inception, it has been very successful in training fellows from diverse backgrounds as prevention scientists.

PI_NAMEs: TEBES, JACOB K (contact)

PROGRAM_OFFICER_NAME: GOLDSTEIN, AMY B

PROJECT_TERMS: Research Training;substance abuse prevention;Training Programs

PROJECT_TITLE: Research Training Program in Substance Abuse Prevention


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: BALTIMORE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE COUNTY

ORG_STATE: MD

PHR: PROJECT NARRATIVE The overall goal of this multi-PI G-RISE at UMBC proposal is to increase the number and enhance the preparation of underrepresented, biomedical, and behavioral sciences students who earn PhD degrees and advance to leadership positions in a range of STEM careers.

PI_NAMEs: BREWSTER, RACHEL MELISSA (contact);CRESISKI, ROBIN HERLANDS;GREEN, ERIN ;JOHNSON, JUSTINE MARIE;LACOURSE, WILLIAM RICHARD;SUMMERS, MICHAEL FINLEY

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TITLE: G-RISE at UMBC

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - D[TWD-D]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

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

ORG_CITY: Fort Lauderdale-Davie

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: NOVA SOUTHEASTERN UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative Periodontitis can cause jaw bone destruction, tooth loss. and increased risk of developing systemic conditions. This application is relevant to public health because it will provide us new knowledge about balancing host immune and inflammatory responses in periodontitis by promoting functions of immune regulatory cells. The proposed research is relevant to the part of NIH's mission that it will contribute to the future development of local therapeutic strategies that are effective in treating periodontitis.

PI_NAMEs: HAN, XIAOZHE  (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: Adoptive Transfer;Alveolar Bone Loss;Animal Model;Anti-Inflammatory Agents;Antiinflammatory Effect;Autoimmune Diseases;B-Lymphocytes;bone;bone loss;Cell Communication;Cell Differentiation process;Cell Line;Cells;clinically relevant;Coculture Techniques;cytokine;Data;Development;Disease;Future;Gingiva;Gingivitis;Grant;Homeostasis;Human;human disease;Immune;immune checkpoint;immune function;Immune response;Immunoglobulin G;Immunoglobulin-Secreting Cells;immunoregulation;In Vitro;in vivo;in vivo imaging system;Infiltration;Inflammation;Inflammatory;inflammatory bone resorption;Inflammatory Response;Injections;insight;Interleukin-10;intravital microscopy;Jaw;Knowledge;Ligation;lipid mediator;Macrophage;Mediating;Mediator;Mission;Modeling;monocyte;multi-photon;Mus;neutrophil;Neutrophil Infiltration;Osteolytic;Osteoporosis;pathogen;PD-1/PD-L1;Periodontal Diseases;Periodontitis;Peripheral Blood Mononuclear Cell;Phagocytosis;Phase;Phenotype;Play;Process;Production;programmed cell death ligand 1;programmed cell death protein 1;Public Health;Publishing;receptor;receptor expression;Regulation;Research;Resolution;Rheumatoid Arthritis;Risk;Role;Signal Transduction;Testing;Therapeutic;Time;Tissues;TNFSF11 gene;Tooth Loss;United States National Institutes of Health;Up-Regulation

PROJECT_TITLE: Regulatory B Cell in the Amelioration of Immune-Mediated Periodontal Disease

STUDY_SECTION: ODCS

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Narrative  Parkinson’s disease (PD) is an incurable neurodegenerative disorder (ND) affecting over a million Americans but no effective treatment options are available to slow down the progression of the disease mainly due to the lack of an in-depth mechanistic understanding of the complex neurodegenerative processes underlying the disease. The research proposed here will identify a novel protective mitochondrial and nuclear subcellular signaling network mediated by protein kinase D1 activation, which is inherent in dopaminergic neurons during the early stages of neuronal oxidative stress (OS). The outcome of this research program will help devise a new treatment strategy that can intervene early in the progression of this debilitating disease.

PI_NAMEs: KANTHASAMY, ANUMANTHA GOUNDER (contact);KANTHASAMY, ARTHI

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Affect;American;Animal Model;Biogenesis;Biological Models;Brain-Derived Neurotrophic Factor;Cell Culture Techniques;Cell model;Cell Nucleus;Cell Survival;Cells;Chemicals;Cognitive deficits;Complex;conditional knockout;constitutive expression;CREB1 gene;Disease;disease model;Disease Progression;dopaminergic neuron;effective therapy;Exhibits;Genetic Transcription;Goals;Histologic;Histone Deacetylase;Human;improved;Inflammatory Response;innovation;Mediating;Mitochondria;mitochondrial dysfunction;mitopark mouse;Modeling;Molecular;motor deficit;mouse model;mtTF1 transcription factor;Mus;Nature;Nerve Degeneration;neural;neurochemistry;Neurodegenerative Disorders;neuroinflammation;neuronal survival;Neurons;neuroprotection;Neurotoxins;nigrostriatal system;novel;novel therapeutic intervention;Nuclear;Nuclear Accidents;Nuclear Protein;Nuclear Translocation;Outcomes Research;oxidative damage;Oxidative Stress;Parkinson Disease;Pathologic;Pathway interactions;Peptides;Phosphotransferases;preclinical efficacy;Predisposition;prevent;Process;programs;protein activation;Protein Kinase;Protein translocation;Protein-Serine-Threonine Kinases;Quality Control;Reporting;Research;response;Role;Signal Pathway;Signal Transduction;stem;Stress;System;Testing;therapeutic target;Time;Transcriptional Regulation;translational approach;translational potential;Up-Regulation

PROJECT_TITLE: Compensatory Mitochondrial Protective Mechanisms Against Oxidative Stress in PD

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Social Determinants of Health

ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE This study aims to understand characteristics that relate to higher or lower electric vehicle adoption levels in a neighborhood, through talking with community members and examining large datasets for the state of California. We also examine how having a higher number of electric vehicles in a neighborhood relates to air pollution levels and emergency department visits and hospitalizations due to asthma or chronic obstructive pulmonary disease in the local community, and if these relationships might be different in different communities.

PI_NAMEs: GARCIA, ERIKA  (contact)

PROGRAM_OFFICER_NAME: QUINN, ASHLINN KO

PROJECT_TERMS: Address;Adoption;Adult asthma;Air;air monitoring;Air Pollutants;Air Pollution;Asthma;asthma exacerbation;Back;California;Cardiopulmonary;Case Study;catalyst;Cessation of life;Characteristics;Charge;Childhood Asthma;Chronic Obstructive Pulmonary Disease;climate change;Collaborations;Communities;community empowerment;community engaged approach;community engaged research;community engagement;community partners;contextual factors;Data;Data Analyses;Data Set;Databases;design;Disease;Emergency department visit;Ensure;Environment;epidemiologic data;Equity;Evaluation;Exposure to;fine particles;Focus Groups;Foundations;Future;Health;Health Benefit;health disparity;health equity;Hospitalization;Housing;housing instability;improved;Incentives;Inequity;Infrastructure;innovation;insight;Knowledge;large datasets;Left;Light;Los Angeles;Measures;meetings;member;Methods;Modification;Motor;Neighborhoods;Nitrogen Dioxide;Nitrogen Oxides;Outcome;Participant;Particulate Matter;Pattern;Policy Maker;Population;Predictive Factor;premature;Public Health;Reporting;Research;respiratory health;social health determinants;social structure;sociodemographics;Socioeconomic Status;Source;Structure;Testing;traffic-related air pollution;Transportation;trend;underserved community;United States;Vehicle Emissions;Work

PROJECT_TITLE: Electric Vehicle Adoption in California: Predictors, Impacts on Local Air Quality and Respiratory Health, and Inequities

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Breast Cancer;Cancer;Neurosciences;Nutrition;Orphan Drug;Rare Diseases;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE The current treatment options for breast cancer brain metastases with human epidermal growth factor receptor 2 (HER2+) are limited, leading to a poor prognosis for these patients. The proposed study aims to demonstrate that (a) de novo lipid synthesis as a novel therapeutic target for HER2+ breast cancer brain metastases and (b) targeting lipid metabolism improves the treatment outcome. Our findings will directly inform the design and interpretation of future clinical trials using agents that target lipid metabolism to improve treatment of patients with HER2+ breast cancer brain metastases.

PI_NAMEs: JAIN, RAKESH K. (contact);VANDER HEIDEN, MATTHEW G.

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Animal Model;barrier to care;Biology;Biomass;Blood;Blood - brain barrier anatomy;blood-brain tumor barrier;Brain;Brain Neoplasms;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;Cells;Central Nervous System;Cephalic;Clinic;Clinical;clinical translation;Clinical Trials;clinically relevant;CRISPR/Cas technology;Data;Dependence;design;Development;Disease;disorder control;Disseminated Malignant Neoplasm;Dose;Drug Delivery Systems;Drug resistance;Drug Targeting;Drug usage;effective therapy;environmental change;Enzymes;Epidermal Growth Factor Receptor;ERBB2 gene;Exhibits;Family;Fatty acid glycerol esters;Fatty Acids;Fatty-acid synthase;Focused Ultrasound;Future;Genes;Genetic Transcription;Growth;high risk;Human;Implant;improved;In Vitro;in vivo;inhibitor;innovation;insight;Intercellular Fluid;Lesion;lipid biosynthesis;lipid metabolism;Lipids;Liver;Liver neoplasms;Liver X Receptor;lymph nodes;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;Metabolic;Metastatic malignant neoplasm to brain;Methods;Molecular;mortality;multidisciplinary;Mus;Neoplasm Metastasis;new therapeutic target;novel;novel strategies;Nutrient;Nutrient availability;Oncogenic;Pathway interactions;patient prognosis;Patients;Pharmaceutical Preparations;Pre-Clinical Model;Proliferating;Protocols documentation;Refractory;Refractory Disease;response;Signal Transduction;Site;targeted agent;targeted treatment;Technology;Therapeutic;Therapeutic Index;Tissues;translatable strategy;Treatment Efficacy;Treatment outcome;treatment response;tumor;tumor growth;tumor metabolism;tumor microenvironment;tumor progression;uptake

PROJECT_TITLE: Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolism

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

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

ORG_CITY: STONY BROOK

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Public health relevance statement: The disruption of numerous human genes and their isoforms driven by non-coding genetic variants is implicated in cancer and several neuropsychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder and autism. This project will contribute novel pre-trained deep-learning tools to decipher the language of non- coding DNA and facilitate integration of gene regulatory information from rapidly accumulating sequence data with NLM’s genetic databases (for example, dbSNP, dbGaP and ClinVar), which serve both scientists and the public health by helping identify the genetic components of disease.

PI_NAMEs: DAVULURI, RAMANA V (contact)

PROGRAM_OFFICER_NAME: WANG, YANLI

PROJECT_TERMS: Address;autism spectrum disorder;Benchmarking;Binding;Bioinformatics;Biological Assay;Bipolar Disorder;candidate validation;cell type;ChIP-seq;ClinVar;Code;Communities;Complex;Computer Vision Systems;Consumption;CRISPR/Cas technology;Data;Data Set;database of Genotypes and Phenotypes;Databases;dbSNP;deep learning;deep neural network;Development;Disease;Distant;DNA;DNA Sequence;DNA Sequence Analysis;Family member;Future;Gene Expression Regulation;Genes;Genetic;Genetic Code;Genetic Databases;genetic variant;Genome;genome editing;Goals;Human;Human Cell Line;human DNA;Human Genome;insight;Label;Language;Luciferases;Malignant Neoplasms;Methods;Modeling;Mus;Natural Language Processing;Neural Network Simulation;neuropsychiatric disorder;novel;Organism;Parkinson Disease;Performance;pre-trained model;pre-trained transformer;prediction algorithm;predictive modeling;promoter;Protein Isoforms;Proteins;Public Health;public health relevance;Regulatory Element;Reporter;Research;Research Personnel;Resources;RNA Splicing;Schizophrenia;Scientist;Semantics;Site;Source Code;Specificity;Techniques;Time;Tissues;tool;Training;transcriptome;transfer learning;Translating;United States National Library of Medicine;Untranslated RNA;Variant;Visualization;web server

PROJECT_TITLE: Developing novel deep-learning based methods for deciphering non-coding gene regulatory code


ED_INST_TYPE: OVERALL MEDICAL

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE The proposed research program is relevant to public health because it encompasses the development and characterization of the highly specific monoclonal antibody inhibitors for disease-related proteases. These proteases are pivotal in the pathogenesis of many disorders including cancer, neuropathic pain, obesity, stroke, and viral infections. Highly specific monoclonal antibody inhibitors will accelerate research directed to a better understanding of basic pathology of these diseases and lead to the development of therapeutic interventions targeting these diseases.

PI_NAMEs: GE, XIN  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Acceleration;Achievement;Antibodies;Antibody Binding Sites;antibody inhibitor;antibody libraries;Antibody-Dependent Enhancement;Binding;blood-brain barrier crossing;Cancer Model;Development;Disease;drug discovery;Drug Kinetics;Drug Targeting;Engineering;Enzyme Inhibition;Epitopes;Family;Generations;Half-Life;Health;high throughput screening;Human;Hybridomas;inhibiting antibody;inhibitor therapy;invention;Laboratories;Malignant Neoplasms;Membrane;Methodology;Methods;Monoclonal Antibodies;mouse model;new technology;Obesity;painful neuropathy;Pathogenesis;Pathology;Peptide Hydrolases;Pharmacologic Substance;Physiological Processes;Prodrugs;programs;Property;Protease Inhibitor;Public Health;rational design;Research;SARS-CoV-2 inhibitor;screening;Series;Serine Protease;Serum;Signaling Molecule;small molecule inhibitor;Specificity;Stroke;success;Technology;Therapeutic;therapeutic development;Therapeutic Intervention;Therapeutic Monoclonal Antibodies;TMPRSS2 gene;Treatment Efficacy;Virus Diseases

PROJECT_TITLE: Therapeutic Monoclonal Antibodies Inhibiting Proteases of Biomedical Importance

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


ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Each year, approximately 795,000 people suffer a stroke and more than 140,000 people die from stroke in the United States. However, there is only one FDA-approved drug for ischemic stroke, the tissue plasminogen activator (tPA), which is beneficial to patients only within 4.5 hours of having a stroke. Therefore, there is an urgent need to identify novel therapeutic targets for treatment of this devastating disease. This study aims to reveal the pathological role of the cell swelling-activated chloride channel and evaluate the effectiveness of targeting this membrane protein in ischemic stroke.

PI_NAMEs: QIU, ZHAOZHU  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Abnormal Cell;Acute;Alteplase;Animals;Anions;Area;Astrocytes;Behavioral;Biological Assay;Blood;Blood Vessels;Brain;brain cell;Brain Injuries;Cause of Death;Cell Death;cell type;Cell Volumes;Cells;Cessation of life;Chemicals;Chloride Channels;Chlorides;Chronic;Chronic Phase;Classification;cytotoxic;Data;Dicumarol;Disease;effectiveness evaluation;efficacy evaluation;Electrophysiology (science);excitotoxicity;FDA approved;Female;functional outcomes;Gene Expression;genome-wide;Glutamates;Goals;high throughput screening;hippocampal pyramidal neuron;Hour;improved;in vitro activity;in vivo;Induced Neurons;Infarction;inhibitor;innovation;Ion Channel;Ischemia;Ischemic Brain Injury;Ischemic Stroke;Knockout Mice;live cell imaging;Long term disability;male;Measures;Mediating;Mediator;Medical;Membrane Proteins;meter;Middle Cerebral Artery Occlusion;Molecular;mouse model;Mus;N-Methyl-D-Aspartate Receptors;Nervous System Disorder;neuroinflammation;Neurologic;neuronal excitability;Neurons;neuroprotection;new therapeutic target;novel;Obstruction;Operative Surgical Procedures;Osmosis;Outcome;Oxygen;patch clamp;Pathogenesis;Pathologic;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Physiology;post stroke;programs;Proteins;Research;Research Personnel;RNA interference screen;Role;Safety;screening;Slice;Specificity;Stroke;stroke model;stroke therapy;Swelling;targeted treatment;Testing;therapeutic target;Thrombectomy;thrombolysis;Time;tool;Traumatic Brain Injury;United States;Water;Work

PROJECT_TITLE: Cell Swelling-Activated Chloride Channel in Ischemic Stroke

STUDY_SECTION: BINP

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


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

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE For last two decades, Alzheimer’s Disease (AD) research has been focusing on a neuron-centric biochemical process that leads to synaptic deficits and neuronal degeneration. However, recent failures in clinical trials call for studies that lead to unbiased and holistic understanding of disease pathways in different types of brain cells. This project aims to unbiasedly explore and validate neuron-glia and glia-glia interaction in the AD brain by combining a computational systems biology platform, novel 3D Alzheimer’s-in-a-dish models, and the enriched multiple-omics AD databases. The completion of this study will provide a validated integrated bioinformatics tool to unbiasedly identify altered neuron-glia and glia-glia crosstalk pathways in AD and will provide novel therapeutic targets and repositioned drug candidates for translating into clinical studies for AD patients.

PI_NAMEs: KIM, DOO YEON ;WONG, STEPHEN TC (contact)

PROGRAM_OFFICER_NAME: ARUNKUMAR, NANDINI

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Address;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's Disease Pathway;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Astrocytes;Biochemical Process;bioinformatics tool;Brain;brain cell;brain tissue;candidate validation;Cell Communication;Cell Culture Techniques;Cell model;cell type;Cells;Cellular biology;chemokine;Clinical Research;Clinical Trials;Computational algorithm;cytokine;Data;Data Set;Databases;Development;Disease;Disease Pathway;disease-in-a-dish;drug candidate;drug repurposing;Failure;FDA approved;Funding;General Hospitals;genetic regulatory protein;Human;human induced pluripotent stem cells;inhibitor;innate immune pathways;insight;Interferons;knock-down;Knowledge;knowledge base;Ligands;Massachusetts;Mediating;Methodist Church;Microglia;Modeling;multiple omics;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;Neuroglia;neuroinflammation;neuron loss;Neurons;neurovascular;new therapeutic target;novel;Oligodendroglia;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway Analysis;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Phase I Clinical Trials;Play;Proteomics;receptor;Research;Resolution;Role;Senile Plaques;sex;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;spatiotemporal;Subgroup;Synapses;Systems Biology;tau Proteins;Technology;Testing;text searching;Therapeutic;therapeutic target;Transcriptional Activation;transcriptomics;Translating;United States National Institutes of Health

PROJECT_TITLE: Systematic modeling and prediction of cell-type-specific and spatiotemporal crosstalk pathways in Alzheimer's Disease


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Contraception/Reproduction;Dietary Supplements;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infertility;Nutrition;Prevention;Social Determinants of Health

ORG_CITY: HADLEY

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: PROJECT NARRATIVE Men’s reproductive health is a critically understudied area of research, and ambient exposures including air pollution and temperature may have important adverse impacts on male fertility. Together, findings from this study will provide a comprehensive understanding of the impact of exposure to ambient air pollution and both high and low ambient temperatures during developmentally-relevant windows of spermatogenesis on men’s reproductive health and infertility treatment outcomes. Findings will add to the evidence base identifying optimal timing of infertility treatment to male partner environmental risk factors and suggesting future research directions for potential benefits of behavioral or pharmacologic interventions in the weeks leading up to fertility treatment.

PI_NAMEs: NOBLES, CARRIE  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Acceleration;Accounting;Address;Air;Air Pollution;ambient air pollution;Ancillary Study;Antioxidants;Area;Behavioral;Cities;Clinical;clinical translation;coarse particles;cold temperature;Communities;cost;Country;Couples;Data;Development;DNA Fragmentation;DNA Methylation;Embryonic Development;Endocrine disruption;Environmental Epidemiology;Environmental Risk Factor;Epidemiology;epigenetic aging;Epigenetic Process;Evaluation;evidence base;experience;Exposure to;extreme temperature;Fertility;Fertilization in Vitro;Financial Hardship;fine particles;folic acid supplementation;Foundations;Future;Grant;Health;High temperature of physical object;Household Air Pollution;Impairment;implantation;Individual;Infertility;infertility treatment;Intervention;intrauterine insemination;K-Series Research Career Programs;Link;Literature;Live Birth;male;male fertility;Measures;Meiosis;member;men;Mentored Research Scientist Development Award;Mentors;Mentorship;Mitosis;Modeling;novel;Observational Study;offspring;Outcome;Oxidative Stress;Oxidative Stress Induction;Ozone;Participant;pharmacologic;Placebos;Predisposition;Pregnancy;Pregnancy Outcome;Probability;Process;Productivity;programs;Randomized;Records;Reporting;Reproduction;reproductive epidemiology;Reproductive Health;reproductive outcome;Research;Risk Factors;Sampling;Seminal fluid;Site;Sodium Chloride;sperm cell;Spermatogenesis;Spermiogenesis;stressor;success;Supplementation;systemic inflammatory response;Temperature;Training;Treatment outcome;Treatment Side Effects;United States;Utah;Zinc supplementation

PROJECT_TITLE: Exposure to Ambient Air Pollution and Temperature During Spermatogenesis: Impact on Men's Reproductive Health and Infertility Treatment Outcomes


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Narrative Molecular mechanisms of BPH initiation and progression remain incompletely understood. The lack of understanding of these mechanisms is a barrier to improved treatment. Our study will reveal novel molecular mechanism regulating BPH initiation and progression and inspire novel therapeutic avenues for BPH.

PI_NAMEs: XIN, LI  (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Acute;Affect;Age;Aging;Anatomy;Attenuated;autocrine;AXIN2 gene;Bacterial Infections;Benign Prostatic Hypertrophy;beta catenin;Biological;Cells;cohort;Development;Disease;Embryo;Epithelial Cell Proliferation;Epithelial Cells;epithelial stem cell;Epithelial-Stromal Communication;Epithelium;Etiology;fetal;Fibroblast Growth Factor;Gene Expression Profile;Genetically Engineered Mouse;Goals;Growth;Heterogeneity;Histologic;Homeostasis;Human;improved;In Situ;In Vitro;in vitro Assay;in vivo;Inflammation;insight;laser capture microdissection;Left;Life;Ligands;lower urinary tract symptoms;men;Mesenchymal;Mitotic;Molecular;mouse model;Mus;Muscle;Nodule;Non-Malignant;novel;novel therapeutics;paracrine;Pathogenesis;Peptide Initiation Factors;Phenotype;Play;Process;Proliferating;Prostate;Prostatic;Prostatic duct;Prostatic Epithelium;Quantitative Reverse Transcriptase PCR;Regional Anatomy;RNA;Role;Signal Transduction;single-cell RNA sequencing;Specimen;stem cells;Stromal Cells;Stromal Hyperplasia;Techniques;theories;Tissues;transcriptome sequencing;Transforming Growth Factor beta;Urethra;Urinary Retention;WNT Signaling Pathway;Work

PROJECT_TITLE: Molecular mechanisms of initiation of benign prostatic hyperplasia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-B(90)]


ORG_CITY: MINNEAPOLIS

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Kidney transplantation is the preferred treatment for end stage renal disease yet many transplant recipients still suffer from rejection and the side effects of immunosuppressive medications. Transplantation tolerance has the potential to eliminate the need for chronic immunosuppression and avoid their attendant side effects thereby improving the health and well-being of transplant recipients. Developing successful approaches to induce transplant tolerance has the potential to improve countless patients’ lives along with significantly decreasing the societal burden of end-stage organ disease.

PI_NAMEs: ADAMS, ANDREW B (contact);HERING, BERNHARD JOSEF;LARSEN, CHRISTIAN P.

PROGRAM_OFFICER_NAME: SHAW, JULIA M

PROJECT_TERMS: Acceleration;adaptive immune response;adaptive immunity;Address;Antibodies;antigen-specific T cells;Apoptotic;Autoimmune Diseases;Bone Marrow;Bone Marrow Stem Cell Transplantation;Cardiovascular Diseases;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Therapy;Cells;Chronic;clinical application;clinically relevant;Collaborations;Data;design;Development;Diabetes Mellitus;digital;Disease;Effector Cell;Elements;End stage renal failure;Environment;Fertilization;Fingerprint;Goals;Health;Heart Diseases;Human;Immune;Immune response;Immune Tolerance;immunoregulation;Immunosuppression;improved;industry partner;Infection;Inflammasome;Inflammation;Inflammatory Response;Innate Immune Response;innovation;insight;interest;Interleukin-1;isoimmunity;ITGAM gene;Kidney Transplantation;Leukocytes;Maintenance;Malignant Neoplasms;Mediating;Memory;migration;Modeling;monocyte;Morbidity - disease rate;mortality;Myeloid Cells;Myeloid-derived suppressor cells;nanoparticle delivery;Nanotechnology;Natural Immunity;neutrophil;next generation;nonhuman primate;novel;novel strategies;novel therapeutics;Organ;Organ Transplantation;Outcome;OX40;Pathway interactions;Patients;Personal Satisfaction;Pharmaceutical Preparations;Phase;prevent;programs;Property;prospective;Publications;Publishing;Reagent;receptor;Regenerative Medicine;Regimen;Regulatory T-Lymphocyte;Reperfusion Injury;Research;Research Personnel;response;Role;side effect;Signal Transduction;single cell ATAC-seq;Solid;synergism;System;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;Techniques;Testing;Therapeutic;therapeutic target;Tissues;TNFRSF5 gene;TNFSF4 gene;TNFSF5 gene;transcriptome sequencing;Transplant Recipients;Transplantation;Transplantation Tolerance

PROJECT_TITLE: Advancing Transplantation Tolerance in Nonhuman Primates


NIH_SPENDING_CATS: Transplantation

PI_NAMEs: ADAMS, ANDREW B (contact)

PROJECT_TERMS: Agreement;Animals;Biological;Budgets;Clinical Research;cloud based;Collaborations;Communication;Complex;Data;Data Analyses;Data Collection;data standards;Data Storage and Retrieval;data visualization;Elements;Ensure;experience;Goals;Human Resources;IACUC;Industry;Infrastructure;innovation;Institution;Leadership;Maintenance;meetings;Minnesota;Modeling;Monitor;nonhuman primate;Outcome;Persons;Preparation;Principal Investigator;Procedures;programs;Progress Reports;Protocols documentation;Publications;Reporting;Research;Research Personnel;Resource Allocation;Role;Sampling;Schedule;shared database;Structure;symposium;System;Teleconferences;Translating;Translational Research;Transplantation Tolerance;United States National Institutes of Health;Universities


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);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: NEUROLOGY

PHR: Project Narrative The aim of this research is to develop biomarkers to predict who will develop post-stroke cognitive decline and to understand the pathogenesis of this disease. Specifically, the role of blood-brain barrier disruption will be studied. The potential impact of this research on public health is to develop strategies for mitigating the impact of Alzheimer's disease and related dementias (ADRD) on society.

PI_NAMEs: LEIGH, RICHARD  (contact)

PROJECT_TERMS: Acceleration;Acute;acute stroke;Affect;aging population;Alzheimer's disease related dementia;arterial spin labeling;Biological Markers;biomarker development;Blood;Blood - brain barrier anatomy;Blood flow;Blood Tests;blood-brain barrier crossing;blood-brain barrier disruption;blood-brain barrier permeabilization;Brain;Brain scan;brain tissue;cardiovascular risk factor;Caregivers;Cerebrum;Chronic;Clinical;clinical imaging;cognitive testing;cohort;Contrast Media;Dementia;Development;Disease;Epidemiology;epidemiology study;Evaluation;Event;Functional disorder;Gadolinium;Goals;Health system;Healthcare Systems;Homeostasis;Hospitals;Hypoxia;Image;imaging study;Impaired cognition;Impairment;improved;Incidence;Individual;Inflammatory;Inflammatory Response;Injury;Ischemia;Ischemic Stroke;Link;Longitudinal Studies;Magnetic Resonance Imaging;Maps;Measurement;Measures;Mediating;Methods;Microvascular Dysfunction;Monitor;MRI Scans;novel;novel marker;Pathogenesis;Pathology;patient subsets;Patients;Perfusion;perfusion imaging;Permeability;Persons;post stroke;post stroke cognitive impairment;predictive marker;Prevalence;Process;Public Health;recruit;recurrence prevention;Research;Resolution;response;Risk;Role;Secondary Prevention;serial imaging;Serial Magnetic Resonance Imaging;Signal Transduction;Societies;Sterility;Stroke;stroke patient;targeted biomarker;Techniques;Testing;Therapeutic;Therapeutic Trials;Time;time use;tissue injury;Translating;vascular cognitive impairment and dementia;Vascular Dementia;Vascular Diseases;vascular factor;vascular risk factor;Water;white matter;White Matter Hyperintensity

PROJECT_TITLE: Global Blood-Brain Barrier Disruption and Post-Stroke Cognitive Decline

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Genetics;Human Genome;Immunotherapy;Kidney Disease;Organ Transplantation;Transplantation

PI_NAMEs: RAMACHANDRAN, SABARINATHAN  (contact)

PROJECT_TERMS: Adopted;Antigens;Architecture;Bioinformatics;bioinformatics pipeline;Biological Assay;Blood capillaries;Blood specimen;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Circulation;clinical application;Clonality;complex data;Data Analyses;data analysis pipeline;Data Set;design;Development;digital;Discrimination;exhaustion;experience;Fingerprint;Genetic Transcription;Heterogeneity;high dimensionality;Immune;Immune response;Immune Tolerance;Immunologic Surveillance;Immunologics;immunopathology;Immunosuppression;Immunotherapy;Infiltration;insight;Kidney;kidney allograft;Kidney Transplantation;Knowledge;Laboratories;Lateral;Leadership;Locales;lymph nodes;Macaca fascicularis;Maintenance;Metabolic Diseases;Methodology;MHC Class II Genes;Mission;Modeling;Molecular Profiling;multiple omics;nonhuman primate;novel;Organ Transplantation;Performance;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Positioning Attribute;Pre-Clinical Model;Procedures;programs;Proliferating;Proteins;Regimen;Regional Anatomy;Regulation;Regulatory T-Lymphocyte;Research Personnel;Resources;Rhesus;Role;Sampling;Series;single cell ATAC-seq;Sorting;spatiotemporal;Specificity;Spleen;System;T cell infiltration;T cell receptor repertoire sequencing;T-cell receptor repertoire;T-Lymphocyte;Technology;Testing;Tissues;transcriptome;transcriptome sequencing;Transplant Recipients;Transplant-Related Disorder;Transplantation Immunology;Transplantation Tolerance;Tubular formation;Variant;Withdrawal

PROJECT_TITLE: Immunosurveillance and Immunopathology Core


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Bioengineering;Chronic Pain;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lupus;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Patient Safety;Social Determinants of Health;Substance Misuse

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Despite treatment advances in rheumatology, pain remains the most prominent, unaddressed patient complaint in systemic lupus erythematosus (SLE), a condition that disproportionately affects women and racial minorities. The proposed research uses electronic health records to characterize chronic pain and its biopsychosocial mechanisms in SLE. The information learned from the study is relevant to public health efforts to understand the burden and natural history of pain; and it is also relevant to NIAM’s mission of improving the understanding of biopsychosocial components of pain in rheumatology.

PI_NAMEs: FALASINNU, TITILOLA  (contact)

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: addiction;Algorithms;American;Analgesics;Award;Behavioral;biomedical informatics;biopsychosocial;body map;career;Chronic;Chronic Disease;chronic pain;chronic pain management;Clinic;Clinical;clinical decision support;Clinical Decision Support Systems;Clinical Management;Clinical Research;clinically significant;Code;Communication;comorbidity;Computational algorithm;Computing Methodologies;cost;Data;data registry;Deterioration;Development;Diagnostic;diagnostic accuracy;Dimensions;Disease;Disproportionately impacts women;Educational workshop;effective therapy;Electronic Health Record;Epidemic;Epidemiologist;experience;Future;General Population;Geography;Goals;Grant;Health;Healthcare Systems;Hospitalization;improved;Individual;Inflammatory;Investments;K-Series Research Career Programs;Knowledge;knowledge integration;Knowledge Management;Learning;Lupus;Machine Learning;Measures;Medicine;Mentors;Mentorship;Methods;Mission;Modeling;Moods;mortality;multidisciplinary;Natural History;Natural Language Processing;opioid misuse;opioid overdose;opioid use;Organ;Outcome;Pain;pain catastrophizing;Pain Clinics;Pain management;pain reduction;Pain Research;pain score;Patient Self-Report;patient stratification;Patients;Persistent pain;Persons;Pharmaceutical Preparations;Phenotype;phenotyping algorithm;Population-Based Registry;post-doctoral training;prescription opioid;Prevalence;Principal Investigator;profiles in patients;psychologic;psychosocial;Public Health;Publishing;racial minority;Registries;Research;Research Personnel;Rheumatism;Rheumatology;Risk Factors;risk stratification;Science;Sensitivity and Specificity;skills;Sleep;social;sociodemographic variables;socioeconomics;Structure;structured data;Subgroup;support tools;symposium;Symptoms;Systemic Lupus Erythematosus;targeted treatment;Techniques;tenure track;Testing;text searching;Time;Training;Translating;treatment stratification;United States;United States National Institutes of Health;unstructured data;Writing

PROJECT_TITLE: Characterization of Chronic Pain and its Biopsychosocial Mechanisms in Lupus using Electronic Health Records

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Endocrine Disruptors;Genetics;Human Genome;Liver Disease;Nutrition

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: 8. Project Narrative This project investigates the underlying biological mechanisms whereby environmental chemicals alter the expression of genes that control physiological processes that affect human health and liver-based disease. This research is centered on the effects of foreign chemicals on gene transcription events whose dysregulation leads to non-alcoholic fatty liver disease, which affects an estimated 25% of all US adults and is a major cause of advanced disease and liver failure. Overall, the findings obtained are expected to increase our understanding of the effects of environmental chemical exposures on hepatic metabolism and the development of liver disease.

PI_NAMEs: WAXMAN, DAVID J (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Abbreviations;Address;Adult;advanced disease;Affect;Agonist;Architecture;Automobile Driving;Benzene;Biological;blood glucose regulation;carbohydrate metabolism;cell type;Cells;Chemical Exposure;Chemicals;Chromatin;Chromatin Loop;Cirrhosis;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Complex;constitutive androstane receptor;CRISPR interference;Deoxyribonucleases;Dependovirus;Development;Diagnosis;Diet;Disease;Disease Progression;endonuclease;Environment;environmental chemical;environmental chemical exposure;Environmental Pollutants;Enzymes;Epigenetic Process;Etiology;Evaluation;Event;Exposure to;Fatty Liver;fatty liver disease;Gene Expression;Gene Expression Profile;gene network;gene regulatory network;gene repression;Gene Targeting;Genes;Genetic Transcription;Genome;Genomics;Guide RNA;Health;Hepatic;Hepatic lobule;Hepatocyte;High Fat Diet;Human;in vivo;Industrialization;Inflammation;insight;interest;Knock-out;Ligands;Link;lipid biosynthesis;lipid metabolism;Liver;Liver Cirrhosis;liver development;Liver diseases;Liver Failure;liver metabolism;Lobule;Mediator;Metabolic Pathway;Metabolism;Mitochondria;Modeling;mouse model;Mus;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel marker;Nuclear;Nuclear Pore Complex;Nuclear Receptors;Orthologous Gene;Pathologic;Pathology;Pathway Analysis;Pathway interactions;Physiological Processes;Positioning Attribute;PPAR alpha;pregnane X receptor;prevent;Primary carcinoma of the liver cells;Process;programs;promoter;Proteins;prototype;receptor;Receptor Activation;Research;Role;Serotyping;single nucleus RNA-sequencing;Site;Specificity;Testing;therapeutic target;Time;Tissues;transcription factor;transcription termination;transcriptome;transcriptomic profiling;Untranslated RNA;Work;Xenobiotic Metabolism;Xenobiotics

PROJECT_TITLE: Xenobiotic-responsive hepatic long non-coding RNAs

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ORG_CITY: PITTSBURGH

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: PA

PHR: The objective of this study is to address the gap in knowledge of best practices for remote insulin pump management to mitigate adverse effects the ongoing pandemic has on high-risk Veterans on insulin pumps (VIPs). The long-term goal of this research is to establish an evidence-based telehealth program for safe and effective remote insulin pump management to improve access to remote care for VIPs and meet the growing demand for insulin pump therapy. An established telehealth program for VIPs will: (1) benefit vulnerable Veterans living in rural communities and other Veterans who face access challenges unrelated to distance from their closest VA, (2) expand care options for Veterans with diabetes who may be candidates for insulin pump therapy but are unable to access VA specialty care, and (3) enhance VIPs ability to connect with their care team for critical real-time troubleshooting of unexpected device failures. Expanding Veteran access to remote insulin pump management assures continued quality care and connection for VIPs.

PI_NAMEs: ESTOCK, JAMIE  (contact)

PROJECT_TERMS: Accounting;Address;Adverse effects;Adverse event;adverse event risk;Appointment;care delivery;Caring;Clinic;Clinical;clinical development;connected care;COVID-19 pandemic;Data;design;Devices;Diabetes Mellitus;Education;Endocrinology;Enrollment;Equipment Malfunction;evidence base;Exclusion;experience;Glycosylated hemoglobin A;Goals;Health care facility;Health Services Accessibility;high risk;Improve Access;improved;Injury;Insulin Infusion Systems;interest;Interview;Joints;Knowledge;medical complication;Medical Device;medical specialties;Methodology;Methods;Modeling;operation;Outcome;pandemic disease;pandemic disruption;pandemic impact;pandemic response;Patients;post-pandemic;Prevention;Process;programs;Provider;Quality of Care;Recommendation;Recovery;remote delivery;remote health care;Remote management;Reporting;Research;research and development;Research Priority;Risk;Rural Community;Rural Health;Sampling;satisfaction;Service delivery model;Specific qualifier value;Structure;Technology;telehealth;Time;tool;United States Food and Drug Administration;Veterans;virtual healthcare

PROJECT_TITLE: Pandemic-Related Disruptions in care for Veterans on Insulin Pumps (PD-VIP): A Mixed Methods Analysis

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Gene Therapy;Genetics;Heart Disease;Lung;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Pediatric Cardiomyopathy;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Project Narrative: Pompe disease results from mutations in the gene for acid α-glucosidase (GAA). Current therapeutic strategies delay disease progression but many patients eventually suffer respiratory failure. Supported by preliminary data, this renewal application uses rat models of Pompe disease to test the hypothesis that adeno- associated virus (AAV) gene therapy is capable of restoring life-long GAA expression throughout the nervous system, skeletal and cardiac muscle, thereby preserving cardiorespiratory function and prolonging life.

PI_NAMEs: BYRNE, BARRY J (contact);FULLER, DAVID D

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Address;adenovirus mediated delivery;Adult;Age;Animal Model;Antibodies;autosome;Brain;Breathing;Cardiac;Central Nervous System;Cerebrospinal Fluid;Cessation of life;Child;Creatine Kinase;CRISPR/Cas technology;Data;Dependovirus;Desmin;Disease;Disease Progression;Dose;early onset;Early treatment;enzyme replacement therapy;enzyme therapy;Enzymes;extend lifespan;Failure;gallium arsenide;Gene Mutation;gene product;gene therapy;Genes;Glucan 1,4-alpha-Glucosidase;Glycogen;Glycogen storage disease type II;Goals;Grant;Heart failure;heart function;heart preservation;Human;Immune;Immune response;Immunosuppression;Impairment;Injections;Intravenous;Laboratories;Late-Onset Disorder;Life;life span;life-sustaining therapy;male;Mediating;Modeling;mortality;Mus;Muscle;Mutation;Myocardium;Neonatal;Nerve Degeneration;Nervous System;neural;Neuromuscular Diseases;neuron loss;Neurons;neuropathology;Onset of illness;Pathology;Patients;pediatric cardiologist;Phase I/II Clinical Trial;Phenotype;postnatal;pre-clinical;preclinical development;preservation;prevent;promoter;Proteins;rat genome;Rattus;Recombinants;Residual state;Respiration;respiratory;Respiratory Diaphragm;Respiratory Failure;Respiratory Insufficiency;response;Serotyping;Skeletal Muscle;Spinal Cord;standard of care;Symptoms;Synapsins;Testing;Therapeutic;Tissues;Transgenes;Treatment Efficacy;vector;Work

PROJECT_TITLE: Control of Breathing and Pompe Disease

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


PHR: PROJECT 2 NARRATIVE The objective of Project 2 is to develop a safe, effective, and clinically translatable protocol in nonhuman primates for inducing stable tolerance in living donor kidney transplants. To work toward this end, we will investigate the efficacy and mechanism of peritransplant infusions of apoptotic donor leukocytes and tailored immunotherapy in a preclinical model of living donor kidney transplantation in nonhuman primates.

PI_NAMEs: HERING, BERNHARD JOSEF (contact)

PROJECT_TERMS: Acute;Alleles;Allografting;antagonist;Antigens;Apoptosis;Apoptotic;Blood;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Chronic;clinical translation;Data;efficacy evaluation;efficacy study;exhaust;exhaustion;Frequencies;Generations;Graft Survival;high dimensionality;Immune;immunoregulation;Immunosuppression;Immunotherapy;improved;Inflammasome;Infusion procedures;Interleukin-10;islet;islet allograft;Islets of Langerhans Transplantation;Kidney;kidney allograft;Kidney Transplantation;Leukocytes;living kidney donor;Lymphoid Cell;Macaca;Macaca fascicularis;Macaca mulatta;Memory;migration;Modeling;Modification;Monoclonal Antibodies;Morbidity - disease rate;Myeloid Cells;nonhuman primate;Organ;Organ Transplantation;Pathogenicity;peptide I;Peptides;Phenotype;Pre-Clinical Model;prevent;Process;programmed cell death ligand 1;programs;Protocols documentation;recruit;Regimen;Regulatory T-Lymphocyte;Reperfusion Injury;Rodent;single cell sequencing;Sirolimus;Solid;Sorting;Specificity;Spleen;Study models;synergism;System;T-Lymphocyte;Testing;Thymus Gland;TNFRSF5 gene;Translations;transplant model;Transplantation;Transplantation Tolerance;Urine;Work

PROJECT_TITLE: Apoptotic Donor Leukocytes to Promote Kidney Transplant Tolerance


ORG_CITY: GRAND FORKS

ORG_NAME: UNIVERSITY OF NORTH DAKOTA

ORG_STATE: ND

PHR: The objective of this application is to define cellular and molecular mechanism by which brain angiogenesis (formation of new blood vessels) is regulated under low energy conditions. Our project is relevant to and has implications for public health because, if successful, it will identify a novel drug target to regulate a novel innate mechanism for brain angiogenesis under pathological conditions such as traumatic brain injury, stroke, hypoxia, metabolic and nutritional disorders, and tumors.

PI_NAMEs: GOLOVKO, MIKHAIL Y (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Ablation;Address;adeno-associated viral vector;Adult;Aging;angiogenesis;Angiogenic Factor;Animals;Attenuated;attenuation;Behavioral;behavioral outcome;Biochemical;Biological Assay;Blood Vessels;Brain;brain endothelial cell;Brain Hypoxia-Ischemia;Brain Injuries;Brain Ischemia;Calcium;Cell Proliferation;cell type;cerebrovascular;Cerebrum;Chronic;Clinical;Compensation;Core-Binding Factor;Cytoplasm;Data;design;Disease;Drug Targeting;Endothelial Cells;FGF2 gene;Genetic Models;Glioblastoma;Glycolysis Inhibition;Hypoxia;In Vitro;in vivo;in vivo imaging;Injections;innovation;Intranasal Administration;Intraventricular Injections;Ischemia;knock-down;Laboratories;Link;Mediating;Metabolic;Metabolic Brain Diseases;Metabolic Diseases;minimally invasive;Modeling;Molecular;mouse model;Mus;Nerve Degeneration;neuronal survival;Neurons;Neurosciences;neurotoxicity;new therapeutic target;normoxia;novel;Nutrition Disorders;Outcome;overexpression;Oxygen;Pathologic;Pathology;Phenotype;Phospholipase C;Phospholipases A;Production;Public Health;Pump;receptor;Recovery;Regulation;Research;response;Role;Signal Transduction;Stroke;Techniques;Testing;Therapeutic;therapeutic target;Time;Traumatic Brain Injury;tumor;tumorigenesis;two photon microscopy;Validation;Vascular Endothelial Growth Factors;Vascular Endothelium;Work

PROJECT_TITLE: Validation of Adenylosuccinate as a Novel Endogenous Pro-Angiogenic Factor in the Brain


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;Genetics;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE Epidemiological data link the history of traumatic brain injury (TBI) to increased likelihood of development of Alzheimer’s disease (AD) and AD-related dementias (ADRD) later in life. While recent analyses estimate the overall risk of dementia attributable to TBI at 5-15%, it is still poorly understood how history of brain trauma may contribute to neurodegeneration years or even decades later. Here we propose to determine whether TBI may speed up detrimental cellular changes occurring during normal brain ageing, thus leading to AD/ADRD.

PI_NAMEs: LIPINSKI, MARTA M (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Acceleration;Affect;age related;Aging;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Anti-Inflammatory Agents;Apolipoprotein E;apolipoprotein E-4;Autophagocytosis;Biochemical;Brain;cell type;Cholesterol;Cholesterol Homeostasis;Cognitive;Coronary heart disease;Data;Defect;Dementia;dementia risk;Demyelinations;Development;Disease;epidemiologic data;Feedback;fly;Functional disorder;functional outcomes;Genes;Genetic;Genetic Polymorphism;genetic risk factor;Genetic Screening;High Density Lipoprotein Cholesterol;Homeostasis;Homologous Gene;hypercholesterolemia;Image;in vitro Model;Inflammation;Inflammatory Response;inhibition of autophagy;Injury;Late Onset Alzheimer Disease;Lead;Life;Link;lipid metabolism;lipidomics;Lipids;Lipofuscin;Long-Term Effects;Lysosomes;Mediating;Meta-Analysis;misfolded protein;Modeling;Mus;Mutant Strains Mice;Mutation;Myelin;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;normal aging;old mice;Organelles;Outcome;Pathologic;Pathology;Pathway interactions;Pharmaceutical Preparations;Phenotype;Predisposition;protein aggregation;proteostasis;Recording of previous events;Spatial Distribution;spatiotemporal;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Speed;SR-BI receptor;Testing;Time;Traumatic Brain Injury

PROJECT_TITLE: Dysregulation of autophagy-lysosomal function links TBI to late-onset neurodegeneration


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

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Narrative Toxoplasma gondii is an obligate intracellular pathogen that can cause serious disease in immunosuppressed people (such as AIDS patients) and fetuses and is also a major cause of blindness in otherwise healthy individuals. In this proposal, we will determine the mechanisms by which Toxoplasma uses the secreted effector protein TgWIP to modulate the host leukocyte migration machinery, thereby hijacking these cells as Trojan Horses to mediate its in vivo dissemination. By advancing our understanding of the molecular mechanisms by which Toxoplasma disseminates through co-opting host leukocytes, the proposed work can provide novel insights into cell motility, which is likely shared by various types of metastatic cancer cells and immune cells, and will also lay the foundation for the development of safe, non-transmissible vaccines or novel therapeutics to block Toxoplasma dissemination.

PI_NAMEs: CHEN, BAOYU ;SAEIJ, JEROEN  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: 2-tyrosine;Acquired Immunodeficiency Syndrome;Actins;acute infection;Adaptor Signaling Protein;Adhesives;Affect;Animal Model;Animals;Attenuated Vaccines;Bar Codes;Behavior;Binding;Biochemical;Biochemistry;Biological Assay;Bioluminescence;Blindness;Brain;cancer cell;cell motility;Cell-Matrix Junction;Cells;Cellular biology;Cessation of life;Co-Immunoprecipitations;Complex;CRISPR/Cas technology;Cytoskeleton;Cytosol;Data;Defect;Dendritic Cells;Development;Disease;Disseminated Malignant Neoplasm;Distant;Equus caballus;Exhibits;Fetus;foodborne;Foundations;Genes;HIV;Human body;Image;Immune;Immune system;Immunocompromised Host;immunosuppressed;In Vitro;in vivo;Individual;Infant;Infection;innovation;insight;Intervention;Knowledge;Leukocytes;Life;loss of function;Luciferases;Measures;Mediating;Mesenchymal;migration;Molecular;Mothers;Motility;Mus;mutant;Names;NCK adaptor protein 1;novel;novel therapeutics;NR0B2 gene;Organ;parasite invasion;Parasites;pathogen;Pathology;Pathway interactions;Patients;Peptides;Persons;Phosphoric Monoester Hydrolases;polymerization;Polymers;Population;prevent;Process;Proline-Rich Domain;Protein Kinase;protein protein interaction;protein purification;Protein Tyrosine Phosphatase;Proteins;PTPN11 gene;PTPN6 gene;receptor;Recombinants;Regulation;Research;response;rho;Route;Shuttle Vectors;Site;Structure;Testing;Therapeutic Intervention;Time;Tissues;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;transmission process;Transplant Recipients;Tyrosine Phosphorylation;Vaccines;Work

PROJECT_TITLE: Mechanisms of host leukocyte-mediated Toxoplasma dissemination in its host

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ADMINISTERING_IC: OD

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: HIV/AIDS

ORG_CITY: SAN ANTONIO

ORG_NAME: TEXAS BIOMEDICAL RESEARCH INSTITUTE

PHR: OVERALL NARRATIVE The Southwest National Primate Research Center (SNPRC) is hosted by Texas Biomedical Research Institute in San Antonio, Texas. It is one of seven National Primate Research Centers, and the only one hosted by a private, non-profit organization. The Center has more than 60 years of nonhuman primate research experience and through constant improvement and innovation it continues to be a leader in biomedical research.

PI_NAMEs: SCHLESINGER, LARRY S. (contact)

PROGRAM_OFFICER_NAME: BUHRING, BETTINA D

PROJECT_TERMS: 2019-nCoV;Aging;Area;Back;Biomedical Research;Breeding;Callithrix;Caring;Communicable Diseases;Communities;comparative;Data;Education and Outreach;experience;Funding;Future;Goals;Health;human disease;human model;Immunology;improved;Infrastructure;innovation;Institution;Leadership;Macaca;Medicine;Metabolic Diseases;Mission;Neurosciences;nonhuman primate;Nonprofit Organizations;Outcome;Papio;Positioning Attribute;Primates;Privatization;Productivity;programs;Publications;Recording of previous events;Research;Research Institute;Research Personnel;Research Project Grants;Resources;response;Science;Scientist;Services;stem;Structure;Students;success;Technology;Texas;Training;translational medicine;United States National Institutes of Health;Work


ORG_CITY: PHILADELPHIA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE DNA deaminase enzymes can generate purposeful genomic mutations and play important immune defense roles, but are naturally constrained in various manners that make them suboptimal as biotechnological tools. This proposal aims to leverage knowledge of DNA deaminase structure and function to engineer CRISPR/Cas- coupled base editors that are capable of generating targeted genomic changes in an efficient and controllable manner. The outcome of this work will be an enhanced understanding of the base editing mechanism and a suite of editing tools with properties necessary to study, diagnose, or treat diseases involving precise genomic changes.

PI_NAMEs: KOHLI, RAHUL MANU (contact)

PROJECT_TERMS: activation-induced cytidine deaminase;Address;Adenosine;anti-cancer;Antibodies;Antibody Response;anticancer activity;apoB mRNA editing catalytic subunit;Attenuated;B-Lymphocytes;base;base editing;base editor;Basic Science;BCAR1 gene;Biochemical;Biological;Biological Models;Biology;Biotechnology;chemotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;Chromosomal translocation;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;cost;Coupled;Cytosine;Cytosine deaminase;Deaminase;Deamination;Diagnosis;Disease;disease-causing mutation;Distant;DNA;ds-DNA;Endonuclease I;Engineering;Enzymes;Epigenetic Process;Event;Family;Family member;frontier;Generations;Genes;Genetic Engineering;Genome;genome editing;genome editor;Genome engineering;Genome Stability;Genomic Instability;genomic locus;Genomics;Guide RNA;Hyperactivity;Immune;Immunoglobulin Somatic Hypermutation;Immunoglobulins;Impairment;improved;innovation;insertion/deletion mutation;insight;Knock-out;Knowledge;Laboratories;Limes;Link;Malignant Neoplasms;Medicine;member;Molecular;Mutagenesis;Mutate;Mutation;Nature;next generation;Nucleic Acids;Nucleosides;Oncogenic;Outcome;Pathway interactions;Patients;Physiological;Play;Positioning Attribute;precise genome editing;programs;Property;Rattus;Reaction;reconstitution;repaired;Resistance;Retroviridae;Risk;risk minimization;RNA;RNA Binding;Role;Single-Stranded DNA;Site;small molecule;spatiotemporal;Structure;System;T-Lymphocyte;Terminator Codon;Therapeutic;tool;Transfer RNA;transition mutation;Translating;Translational Research;Uracil;Variant;Work;Zinc

PROJECT_TITLE: Engineering Efficient and Controllable Base Editors

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


PHR: Kidney transplantation is the preferred treatment for end stage renal disease yet many transplant recipients still suffer from rejection and the side effects of immunosuppressive medications. Transplantation tolerance holds the promise of long-term transplant survival without immunosuppression. Developing successful approaches to induce transplant tolerance has the potential to improve countless patients’ lives along with significantly decreasing the societal burden of end-stage organ disease.

PROJECT_TERMS: Acceleration;adaptive immunity;Affinity;Age;Allografting;Anti-Inflammatory Agents;Anti-viral Therapy;Antibodies;antigen-specific T cells;Autoimmunity;Biological Products;Biological Response Modifiers;Bone Marrow;Calcineurin inhibitor;Cardiovascular Diseases;Cell Physiology;Cell Therapy;Cessation of life;chemokine;Chimeric Proteins;clinical translation;Clinical Trials;clinically relevant;cost comparison;cytokine;Development;Diabetes Mellitus;Dialysis procedure;Disease;donor-specific antibody;Effector Cell;End stage renal failure;Environment;experience;graft failure;Health Care Costs;Heart Diseases;high risk;Human;Immune;immune checkpoint;immune function;Immune response;Immune Tolerance;Immunity;immunomodulatory therapies;immunoregulation;Immunosuppression;improved;Industry;Infection;Inflammatory;Inflammatory Response;Infusion procedures;Innate Immune Response;innovation;isoimmunity;Kidney Transplantation;life span;Maintenance;Malignant Neoplasms;member;Memory;mesenchymal stromal cell;migration;Minority;Modeling;monocyte;Morbidity - disease rate;mortality risk;Myeloid Cells;Myeloid-derived suppressor cells;Natural Immunity;neutrophil;non-compliance;nonhuman primate;novel;novel therapeutics;Organ;Organ Transplantation;Outcome;OX40;Pathway interactions;Patient-Centered Care;Patients;Pharmaceutical Preparations;premature;preservation;prevent;Production;Property;Protocols documentation;Quality of life;Reagent;Regimen;Regulatory T-Lymphocyte;Reperfusion Injury;Research Personnel;response;restraint;Role;safety assessment;Scaffolding Protein;Self Tolerance;side effect;Signal Transduction;Solid;T cell response;T-Cell Activation;T-Lymphocyte;Testing;Thinking;TNF gene;TNFRSF5 gene;TNFSF4 gene;TNFSF5 gene;Toxic effect;transplant model;Transplant Recipients;Transplantation;Transplantation Tolerance;Tumor Necrosis Factor Receptor

PROJECT_TITLE: Promoting Kidney Transplantation Tolerance Through Novel Immunomodulation and Cellular Therapy


NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Precision Medicine

ORG_CITY: ATLANTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: EMORY UNIVERSITY

PHR: Narrative Genetic variations of NMDAR GRIN genes have been identified in children with profound neurodevelopmental problems, including intractable seizures, autism, and intellectual disability. We will compare the functional effects of disease-associated variants with the missense variants present in the general population in the GRIN2A gene to evaluate the idea that variation of intolerant genes can act as risk factors for neurological disorders. We will elucidate how the loss and gain of NMDAR activity promote network hyperexcitability and induce epileptic phenotypes in mice engineered to harbor the variant, which will allow us to suggest novel strategy of potential personalized therapies.

PI_NAMEs: YUAN, HONGJIE  (contact)

PROJECT_TERMS: Address;Animal Model;autism spectrum disorder;Brain;Child;Data;de novo mutation;defined contribution;Dendritic Spines;density;Development;Disease;Drug Receptors;early onset;Economics;Electroencephalography;Engineering;Epilepsy;epileptic encephalopathies;Evaluation;experimental study;extracellular;Family;FDA approved;Funding;gain of function;Gene Frequency;General Population;Genes;Genetic Variation;Genome;Glutamate Receptor;Hippocampus;Histopathology;Human;human disease;in vivo;Individual;Intellectual functioning disability;Ion Channel Gating;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Ligands;Link;loss of function;Measures;Mediating;Memantine;Modeling;Morphology;mouse model;Mus;Mutation;N-Methyl-D-Aspartate Receptors;neocortical;Nervous System Disorder;Neurodevelopmental Disorder;Neurodevelopmental Problem;Neurologic;neuronal circuitry;Neurons;NMDA receptor A1;novel strategies;novel therapeutic intervention;Patients;pediatric patients;Permeability;personalized medicine;Pharmaceutical Preparations;pharmacologic;Phenotype;Play;postsynaptic;precision medicine;Prognosis;Property;protein function;Psyche structure;Publishing;Pyramidal Cells;rare variant;receptor;receptor function;Reporting;Resolution;response;Risk Factors;Role;Seizures;Signal Transduction;Slice;Societies;Survival Rate;Symptoms;Synapses;synaptic inhibition;Synaptic Transmission;targeted treatment;Testing;Thick;Time;Transgenic Mice;Variant;Work

PROJECT_TITLE: NMDAR Mutations & Neurodevelopmental Disorder: from Mechanism to Targeted Therapy

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative Ovarian cancer is a leading cause of cancer deaths among women with a five-year survival below 50% despite recent advances in therapy. These studies will determine the mechanisms by which a key signaling molecule (FAK) coordinately promotes tumor recurrence and acquired chemotherapy resistance. Knowledge gained from these studies will provide a blueprint for understanding FAK-driven disease, and will identify women whose disease will benefit from FAK-targeted drugs.

PI_NAMEs: SCHLAEPFER, DAVID D (contact);STUPACK, DWAYNE G.

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: 3-Dimensional;Adhesions;ATAC-seq;Automobile Driving;Back;bench to bedside;beta catenin;Bioinformatics;Biological Assay;Biological Markers;biomarker identification;Biopsy;Cancer Etiology;Cancer Model;Cancer Patient;Cancer Relapse;Cause of Death;Cell Adhesion;Cell Culture Techniques;Cell Reprogramming;Cell Separation;Cell Survival;Cells;Cellular biology;Chemoresistance;chemotherapy;Chromosomes;clinical trial analysis;clinical trial protocol;Clinical Trials;Cluster Analysis;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;combinatorial;Complement;Complex;Databases;Defect;Dependence;Disease;DNA Repair;DNA Repair Gene;Drug Targeting;Environment;epigenome;Exhibits;Focal Adhesion Kinase 1;Fostering;FOXM1 gene;Genes;Genetic;Genetic Markers;genetic signature;Genomics;Goals;Growth;Human;Hypoxia;Implant;In Vitro;in vivo;insight;Integrins;Knock-out;Knowledge;KRAS2 gene;Link;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Maps;mechanotransduction;model development;Modeling;Molecular;Molecular Conformation;Motility;Mus;mutant;Neoadjuvant Therapy;neoplastic cell;novel;Nuclear;Oncogenes;Oncogenic;Organoids;Ovarian;ovarian neoplasm;Paclitaxel;Patient-Focused Outcomes;Patients;Peritoneal;pharmacologic;Phenotype;Phosphotransferases;Platinum;Pre-Clinical Model;prognostic;programs;Proliferating;Protein Tyrosine Kinase;PTK2 gene;reconstitution;Recurrence;Recurrent tumor;research clinical testing;Resistance;response;RNA;Role;Sampling;Serous;Signal Pathway;Signal Transduction;Signaling Molecule;single cell sequencing;single-cell RNA sequencing;Sleeping Beauty;standard of care;stem;stemness;Stress;Supporting Cell;System;Testing;The Cancer Genome Atlas;three dimensional cell culture;Time;TP53 gene;transcription factor;transcriptome sequencing;transcriptomics;Transplantation;treatment response;tumor;tumor growth;tumor heterogeneity;tumor microenvironment;Tumor Promotion;Tyrosine Phosphorylation;Validation;Woman;Women's mortality

PROJECT_TITLE: Dissecting FAK-regulated oncogenic signaling programs in ovarian cancer

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