ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: With constant advances in our understanding of cellular repair processes, the questions asked by the radiation biology community are increasing in complexity, creating a dire need for a multi-disciplinary computational tool to help a) interpret existing experimental results and b) design promising new ex- periments. TOPAS-nBio is a Monte Carlo platform specifically developed to connect research disci- plines, to simulate the initial energy deposition events (physics), followed by the diffusion and reaction of chemical species (chemistry) to infer biological observables at the cell and organelle scale (biolo- gy). The TOPAS-nBio features developed in the previous funding cycle have already been well re- ceived by the research community. The new developments of TOPAS-nBio will offer mechanistic out- come predictions from the initial radiation track structure for various cell types for in vitro and in vivo experiments, and thereby drive hypothesis generation at the forefront of bio-physical research.

PI_NAMEs: SCHUEMANN, JAN PATRICK OSCAR (contact)

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: Animal Model;Animals;Area;Biochemical;Biological;biological effect of radiation;Biological Models;Biology;Biophysics;cell injury;Cell Line;Cell model;cell type;Cells;Cellular Structures;Chemical Models;chemical reaction;Chemistry;Communities;computerized tools;Data;Deposition;design;Development;Diffusion;Discipline;DNA;DNA Damage;DNA Repair;DNA Repair Pathway;DNA strand break;dosimetry;Environment;Event;Experimental Designs;experimental study;Foundations;Funding;Generations;genetic information;Goals;Heterogeneity;Human;improved;In Vitro;in vivo;in vivo Model;interdisciplinary approach;Interdisciplinary Study;interest;Link;Linux;Lung;Methods;Mission;Modality;Modeling;Monte Carlo Method;multidisciplinary;Mus;neoplastic cell;Neurons;open source;Organelles;Outcome;outcome prediction;Performance;Physics;pre-clinical;preclinical study;predictive modeling;Process;Publishing;Radiation;radiation effect;Radiation induced damage;radiation response;Radiation therapy;Radiobiology;Reaction Time;Relative Biological Effectiveness;repaired;repository;Research;response;simulation;Speed;Structure;Systems Biology;Testing;Tissues;tool;tumor;tumor growth;Tumor Volume;Update;Work

PROJECT_TITLE: TOPAS - nBio, a Monte Carlo tool for radiation biology research

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-K(04)M]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Cardiovascular;Clinical Research;Coronaviruses;Emerging Infectious Diseases;Hematology;Infectious Diseases

ORG_CITY: MILWAUKEE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VERSITI WISCONSIN, INC.

ORG_STATE: WI

PHR: Project Narrative Thrombotic complications are associated with increased severity and mortality in coronavirus disease 2019 (COVID-19). The proposed studies aim to understand the molecular mechanism underlying these thrombotic complications and may help to identify novel approaches to control severity and mortality associated with COVID- 19.

PI_NAMEs: WEN, RENREN  (contact)

PROGRAM_OFFICER_NAME: ZOU, SHIMIAN

PROJECT_TERMS: 2019-nCoV;Affinity;Antibodies;Antibody Formation;Autoantibodies;Automobile Driving;autoreactivity;B-Lymphocytes;Binding;Blood Platelets;C-reactive protein;Cells;Cloning;Coagulation Process;Complement 3d Receptors;Complex;COVID-19;COVID-19 patient;COVID-19 severity;cross reactivity;CXCR3 gene;Development;Disease;Endothelium;enhancing factor;experience;Fibrin fragment D;Hemostatic function;Heparin;heparin-induced thrombocytopenia;Hospitalization;IgG1;Immune response;Immunoglobulin G;Immunoglobulins;Impairment;Incidence;Inflammatory;inflammatory marker;inhibiting antibody;Interleukin-6;ITGAX gene;Link;Literature;Memory;Methods;Molecular;monocyte;Morbidity - disease rate;mortality;neutrophil;novel;novel strategies;Pathogenesis;Pathogenicity;Pathway interactions;Patients;PF4 Gene;Plasma;Plasmablast;Platelet Activation;Polysaccharides;protein expression;receptor;receptor binding;response;SARS-CoV-2 infection;SARS-CoV-2 spike protein;severe COVID-19;Severities;single-cell RNA sequencing;Structure of germinal center of lymph node;Surface;Symptoms;Testing;Thromboembolism;Thrombosis;thrombotic;thrombotic complications;Thrombus;Time;Tissues;TNF gene;transcriptome;Venous;venous thromboembolism;Virus

PROJECT_TITLE: B-cell response and thrombotic complications in COVID-19

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Networking and Information Technology R&D (NITRD);Skin Cancer

ORG_CITY: NEW HAVEN

ORG_DEPT: PHARMACOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Using next-generation multi-scale modeling approaches that integrate structural and systems considerations, we propose new frameworks for identifying optimal combinations of clinically available RAF, MEK and ERK kinase inhibitors in melanoma and colorectal cancer. We combine modeling and experimental approaches (in vitro and in vivo) to define rules for predicting how to apply these drugs in specific cancers for more durable inhibition of oncogenic ERK signaling in RAF- and/or RAS-driven cancers – thereby limiting or delaying treatment resistance.

PI_NAMEs: HLAVACEK, WILLIAM S;KHOLODENKO, BORIS N;LEMMON, MARK A (contact);RADHAKRISHNAN, RAVI

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Accounting;Affect;BAY 54-9085;Behavior;Binding;Biochemical;Biological Models;BRAF gene;Caco-2 Cells;Cancer cell line;Cell Line;Cell model;Cell Proliferation;cell transformation;Cells;Clinic;Clinical;clinical efficacy;Colorectal Cancer;Compensation;Complex;Computer Models;Coupled;Data;Dimerization;Disabling;Drug Combinations;Drug Controls;drug efficacy;Drug resistance;drug sensitivity;Drug Targeting;Dryness;Effectiveness;experimental study;Feedback;Foundations;Free Energy;Genetic;Genetically Engineered Mouse;Goals;Growth;In Vitro;in vivo;inhibitor;kinase inhibitor;Kinetics;knock-down;Knock-out;KSR gene;Link;Malignant Neoplasms;MAP Kinase Gene;mathematical model;MEKs;Melanoma;Melanoma Cell;Modeling;Molecular;Molecular Biology;Molecular Conformation;molecular dynamics;multi-scale modeling;Mutate;Mutation;next generation;novel;novel strategies;Oncogenic;overexpression;Pathway interactions;patient derived xenograft model;Pharmaceutical Preparations;Phosphotransferases;Positioning Attribute;precision medicine;predictive modeling;Predisposition;prevent;Property;protein expression;Protein Isoforms;Protein Kinase;Proteins;RAS driven cancer;Recovery;Regulation;Resistance;response;scaffold;Scaffolding Protein;Signal Pathway;Signal Transduction;Signaling Protein;small molecule inhibitor;Specificity;standard of care;success;synergism;System;Systems Biology;targeted treatment;Testing;Therapeutic;therapy resistant;Thermodynamics;tool;tumor;Validation;Work;Xenograft procedure

PROJECT_TITLE: Multiscale Modeling to Optimize Inhibition of Oncogenic ERK Pathway Signaling

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: CHICAGO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: The field of biophysical chemistry has learned an enormous amount about the relationships between the function and dynamics of biological molecules, which has assisted in the development of drugs and other treatments. The next stage in biological science involves addressing more complex systems using increasingly sophisticated approaches augmented by computational methods. Our studies will shed light on biological phenomena including how bacteria “steal” our iron or other trace compounds, thereby counteracting our innate immune response.

PI_NAMEs: SOSNICK, TOBIN R (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Address;Amides;Area;Bacteria;Biological;Biological Phenomena;Biological Sciences;Biology;biophysical chemistry;biophysical properties;Cells;Complex;computerized tools;Computing Methodologies;Deuterium;deuteron;Disease;drug development;experience;Exposure to;Hydrogen;Hydrogen Bonding;improved;in vivo;Individual;Innate Immune Response;interest;Iron;Kinetics;Knowledge;Label;Learning;Mass Spectrum Analysis;Membrane;Membrane Proteins;Methods;Molecular Chaperones;Molecular Conformation;Nutrient;Pattern;Phase;Physical condensation;Physical Function;physical property;Physiologic pulse;Potassium Channel;Process;Property;Protein Chemistry;Protein Dynamics;protein folding;Proteins;Protons;Research;Resolution;Sampling;Science;skills;Stress;Structure;System;Techniques;Theft;water channel

PROJECT_TITLE: Studies of the function of membrane and soluble proteins and their biophysical properties.


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: The proposed research is relevant to public health because it focuses on identifying how the exposures of different protein-rich foods affect gut microbiota and infant growth during early complementary feeding. Findings are expected to have significant scientific and clinical implications for identifying beneficial gut microbial changes and dietary patterns and for informing dietary interventions to prevent the risk of overweight and later obesity.

PI_NAMEs: TANG, MINGHUA  (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Address;Adult;Affect;Age;age group;Age Months;Amino Acids;Bacteria;Biological Markers;Biometry;Blood;Body Composition;Body Weight;Breast;Butyrates;Child Nutrition;Clinical;Clinical Trials;Collaborations;Complementary Feeding;Consumption;critical period;Dairying;Data;Development;developmental plasticity;Diet;dietary;Dietary intake;Dietary Intervention;Dietary Practices;disorder risk;Evaluation;evidence base;feeding;Food;food consumption;Genes;Goals;Growth;Growth and Development function;gut microbiota;Health;Human;Human Milk;IGFBP3 gene;infancy;Infant;Inflammation;Insulin;Insulin-Like Growth Factor I;Intake;Intervention;Knowledge;Length;Life;Lipids;Marketing;Measures;Meat;Mediating;Mediation;Metabolism;Metagenomics;microbial;microbiome;microbiota;microbiota composition;Modeling;multidisciplinary;novel;Obesity;obesity in children;Overweight;Pathway interactions;Pattern;Pilot Projects;Plants;Positioning Attribute;prevent;Production;programs;protein intake;Proteins;Public Health;Race;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Research;Risk;Ruminococcus;sex;standard of care;total energy expenditure;United States Department of Agriculture;United States National Institutes of Health;Volatile Fatty Acids;Weight;Weight Gain

PROJECT_TITLE: Dietary influence on infant growth and the gut microbiota

STUDY_SECTION: INMP

STUDY_SECTION_NAME: Integrative Nutrition and Metabolic Processes Study Section[INMP]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: PROJECT NARRATIVE Frequency and severity of Traumatic Brain Injury (TBI) are higher among Veterans, creating needs for TBI rehabilitation that could last a lifetime. Clinical study is hindered by small sample sizes, high variability, low data output, and a lack of experimental control. We utilize a swine model that can uniquely recreate the mechanisms and manifestations of human TBI, but moderate-to-severe injuries have not been studied beyond the acute time period – too short to represent the challenges inherent in brain injury rehabilitation in our Veterans. In the proposed project, I will extend studies of moderate TBI into long-term, Veteran-relevant recovery and rehabilitation phases, establishing the first translational model of moderate TBI Rehabilitation and Recovery. I will christen this model with studies testing the efficacy and mechanisms of regular exercise or dietary branched-chain amino acids during brain injury rehabilitation. This project will advance our understanding of neurorehabilitation and facilitate my transition to an independent VA investigator.

PI_NAMEs: O'DONNELL, JOHN CHARLES (contact)

PROJECT_TERMS: Acceleration;actigraphy;Acute;amino acid therapy;Animal Model;Animals;Anisotropy;Autopsy;Blinded;Blood;Brain;Brain Injuries;Brain Mass;brain size;Brain-Derived Neurotrophic Factor;Branched-Chain Amino Acids;career;Caring;Chronic;Clinical;Clinical Management;Clinical Research;clinically relevant;Cognition;Cognitive deficits;cognitive enhancement;cognitive recovery;cognitive testing;Coma;Communities;Data;Data Collection;Data Correlations;Dedications;Development;Diagnostic;Diet;dietary;Dietary Supplementation;Diffuse;Diffuse Axonal Injury;Diffusion Magnetic Resonance Imaging;Doctor of Philosophy;driving force;effective therapy;efficacy testing;Electrophysiology (science);empowerment;Enrollment;Environment;Etiology;Evaluation;Exercise;exercise rehabilitation;experience;Family suidae;Fatigue;Frequencies;Future;Gait;General Population;Goals;Head;Histopathology;Human;Immunohistochemistry;improved;improvement on sleep;in vivo;Individual;Injury;interest;Intervention;Investigation;Investments;K-Series Research Career Programs;Knowledge;Life;long term recovery;long-term rehabilitation;Longitudinal Studies;Medical;Medical center;member;Mentors;Mentorship;military veteran;Mission;Modeling;Monitor;multimodality;Nerve Degeneration;Nervous System Trauma;neurobehavioral;neuroimaging;Neurologic;neurological rehabilitation;neuropathology;neuroprotection;novel therapeutics;Outcome;Output;Pathology;Pathway interactions;patient variability;Patients;Pennsylvania;Phase;Philadelphia;Physical Exercise;Placebos;porcine model;pre-clinical;Pre-Clinical Model;Productivity;prognostic;Protocols documentation;Qualifying;Randomized;Recovery;Recovery of Function;rehabilitation research;rehabilitation strategy;Rehabilitation therapy;Research;research and development;Research Personnel;Resolution;Resources;restoration;Rodent Model;Sample Size;Serum;Services;severe injury;Severities;Signal Transduction;Sleep;Sleep Deprivation;Sleep disturbances;sleep quality;Slice;Structure;System;Testing;Therapeutic;therapeutic target;Time;tractography;translational model;Translations;Traumatic Brain Injury;Traumatic Brain Injury recovery;treadmill;treatment group;Unconscious State;Unit of Measure;Universities;Veterans

PROJECT_TITLE: Translational Modeling of Brain Injury Rehabilitation to Maximize Recovery.

STUDY_SECTION_NAME: Career Development Program - Panel I[RRD8]


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Repetitive mild traumatic brain injury (mTBI) caused by blast effects of explosive devices is the “signature injury” of Soldiers, Marines, and other Servicemembers who served in the Iraq and Afghanistan conflicts and may have devastating personal, professional and domestic consequences. The proposed project will use sophisticated brain imaging techniques and measurement of chemicals in spinal fluid (the fluid surrounding the brain) and in blood plasma to identify objective markers of mTBI. These markers will help to improve the diagnosis of mTBI in Veterans of the Iraq and Afghanistan wars and improve Veterans' health care. A long- term goal is to determine the risks of repetitive blast trauma mTBI for progressing to such fatal dementing disorders as Alzheimer's disease or the mid-life dementia that has been found in professional boxers and football players, and the role that neuroinflammation and vascular disturbance may play in such outcomes.

PI_NAMEs: PESKIND, ELAINE R. (contact)

PROJECT_TERMS: actigraphy;Address;Afghanistan;Alzheimer's Disease;Apolipoprotein E;Behavioral;Biological Markers;blast trauma;Blood Vessels;Brain;Brain Concussion;brain dysfunction;Brain imaging;Brain region;Brain Stem;Central Nervous System;Cerebrospinal Fluid;Characteristics;Chemicals;Chemotactic Factors;Chronic;Clinical;Clinical assessments;clinical phenotype;Clinical Trials Design;Cognitive;cognitive function;cognitive performance;cognitive task;combat zone;comorbidity;demented;Dementia;Development;Devices;Diagnosis;diagnostic criteria;Diffusion Magnetic Resonance Imaging;Disabling;Disease;evidence base;Exhibits;exosome;Fiber;fluorodeoxyglucose positron emission tomography;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Genetic Polymorphism;genetic risk factor;Goals;Haplotypes;Healthcare;Imaging Techniques;Impaired cognition;Impairment;improved;Iraq;K-Series Research Career Programs;Liquid substance;Magnetic Resonance;Manufactured football;MAPT gene;Marines;Measurement;Memory impairment;middle age;Migraine;mild traumatic brain injury;Modality;Modeling;Monitor;Moods;Nerve Degeneration;Nervous System Trauma;Neurocognitive;neurodegenerative dementia;neuroimaging;neuroimaging marker;Neuroimmune;neuroinflammation;Neurologic;Neuropsychology;neurovascular;Outcome;Performance;Plasma;Play;Post-Concussion Syndrome;Post-Traumatic Stress Disorders;potential biomarker;prevent;Process;prospective memory;protein biomarkers;Proteins;rational design;Recording of previous events;Research;response;Rest;Risk;Role;service member;Short-Term Memory;Signs and Symptoms;Sleep;Sleep disturbances;Symptoms;Thalamic structure;tool;tractography;Veterans;War;wounded service member;wounded soldier

PROJECT_TITLE: Mild TBI and Biomarkers of Neurodegeneration

STUDY_SECTION_NAME: Brain Health and Injury[RRD1]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Comparative Effectiveness Research;Dental, Oral, and Craniofacial Disease;Primary Health Care

ORG_CITY: BIRMINGHAM

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: We propose to create an Implant Registry capturing implant therapy that is provided by practitioners within the NDPBRN. The aim is to determine the therapies associated with the greatest amount of success and the least amount of complications. With the data generated through this registry, we will add to the generalizable knowledge about implant therapy, the complications and therapies associated with implant success at the fixture level and the patient level.

PI_NAMEs: CUNHA-CRUZ, JOANA  (contact)

PROGRAM_OFFICER_NAME: FISCHER, DENA

PROJECT_TERMS: adjudication;Biological;Biological Factors;Biometry;bone;Budgets;Client satisfaction;Clinical;clinical practice;Complication;Data;Data Collection;data registry;Decision Trees;Dental General Practice;Dental Implants;Dentistry;design;Diagnosis;disease classification;Enrollment;Esthetics;evidence base;Goals;Health;health related quality of life;Image;Implant;Incidence;Inflammation;Knowledge;Literature;Measures;medical specialties;Modeling;Mucositis;Mucous Membrane;National Institute of Dental and Craniofacial Research;Online Systems;Operative Surgical Procedures;Oral health;Patients;peri-implant bone loss;peri-implantitis;personalized therapeutic;Phase;practice setting;practice-based research network;Predictive Factor;Prevalence;Private Practice;Prosthesis;Protocols documentation;Quality of Care;radiological imaging;recruit;Registries;Resources;restoration;Risk Factors;success;System;Tissues;tool;Training;Treatment outcome

PROJECT_TITLE: A Dental implant registry of treatment outcomes of implant therapy by practitioners in the National Dental Practice Based Research Network


ADMINISTERING_IC: ES

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

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

ORG_CITY: SALT LAKE CITY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE Many western U.S. cities have poor air quality during colder months; we will improve existing air quality models to better identify the origin of these pollutants. We will estimate associations between these pollutants and acute cardiorespiratory health events in 12 cities. We aim to inform public health interventions, develop new methods for air quality modeling, and better understand the heath impacts of air pollution during colder months in the western U.S.

PI_NAMEs: HOLMES, HEATHER A (contact)

PROGRAM_OFFICER_NAME: QUINN, ASHLINN KO

PROJECT_TERMS: Acute;Address;Aerosols;Air;Air Pollutants;Air Pollution;Altitude;Atmosphere;atmospheric chemistry;atmospheric processes;Back;Biomass;Carbon;cardiorespiratory fitness;Categories;Cities;Communities;Complex;Data;data fusion;data integration;density;Emergency department visit;Emergency Situation;epidemiological model;Epidemiology;epidemiology study;Event;experience;fine particles;Health;Hour;Human;improved;Industrialization;innovation;interest;Literature;Location;London;meteorological data;Meteorology;Methodology;Methods;Modeling;Nitrates;novel;novel strategies;Physics;Play;Policy Developments;pollutant;Pollution;Public Health;public health intervention;Reaction;Regulation;Role;Seasons;sensor;Smog;Sodium Chloride;Source;Temperature;Time;Time Series Analysis;Uncertainty;United States;Visit;Work

PROJECT_TITLE: A multicity study of wintertime inversions and acute cardiorespiratory health events in the western U.S.

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CORAL GABLES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: A growing number of inherited mutations have been found in the IKM (KCNQ2/KCNQ3) channels that cause epilepsy in patients. We recently determined that lipophilic compounds act on IKM channels with potential antiepileptic effects. We will here test more variants of these compounds on heterologously expressed channels and on human neurons derived from induced pluripotent stem cells (iPSC) expressing wild type and mutated KCNQ2 and KCNQ3 channels to establish which variants of these compounds can become new antiepileptic drugs.

PI_NAMEs: BARRO-SORIA, RENE  (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Affect;Alternative Therapies;anti-epileptic agents;Brain;Cessation of life;CRISPR/Cas technology;Cysteine;Data;Defect;Dependence;Development;Disease;Drug Design;early onset;Epilepsy;Functional disorder;functional restoration;Gene Delivery;Genes;genetic variant;genome editing;Goals;Homeostasis;Human;improved;Induced Mutation;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;Inherited;Intellectual functioning disability;Intervention;Ion Channel;Lead;Length;Link;lipophilicity;Maintenance;Maps;Measures;Molecular;Movement;Mutagenesis;mutant;Mutate;Mutation;neuronal excitability;Neurons;patch clamp;Pathogenesis;Patients;Persons;pi bond;Polyunsaturated Fatty Acids;Potassium Channel;programs;Proteins;reduce symptoms;Research;Seizures;sensor;Site;structural determinants;Technology;Testing;unnatural amino acids;Variant;Viral;voltage;Work;Xenopus oocyte

PROJECT_TITLE: Molecular Mechanisms of Epilepsy-Causing Mutations in IKM channels: anti-epileptic effect of Lipophilic compounds.

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cancer;Genetics;Rare Diseases

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE: Soft Tissue Sarcomas (STSs) are a rare group of mesenchymal tumors in adults that are resistant to conventional treatments such as chemotherapy, due to their extensive heterogeneity. A common feature in many soft tissue sarcomas is altered cellular metabolism due to downregulation of the rate limiting enzyme in the formation of glucose. The proposed research will explore the mechanisms of how re-expression of this enzyme effects STS progression, providing more mechanistic insight for novel sarcoma therapies.

PI_NAMEs: NANCE, BAILEY  (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Ablation;Adult;Affect;Alanine;Alleles;analytical ultracentrifugation;Attenuated;aurora kinase A;Binding;Binding Sites;Biogenesis;Biological Assay;c-myc Genes;Cartilage;cdc Genes;CDK4 gene;Cell Cycle;Cell Cycle Regulation;Cell Fractionation;Cell Nucleus;Cells;chemotherapy;Co-Immunoprecipitations;combat;Complement;Complex;confocal imaging;Connective Tissue;conventional therapy;Cytoplasm;Data;Dependence;dimer;Disease;Dissociation;Down-Regulation;effective therapy;Enzymes;Epigenetic Process;Excision;Exhibits;experimental study;Exposure to;Fatty acid glycerol esters;Fructose;Fructose-1,6-Bisphosphatase;functional outcomes;Gene Expression;Genetic;genetic signature;Genetic Transcription;Gluconeogenesis;Glucose;glucose metabolism;glucose uptake;Growth;Heterogeneity;Histologic;Hypoxia;improved;In Vitro;in vivo;inhibitor;insight;Malignant Neoplasms;Maps;Measures;Mediating;Mesenchymal Cell Neoplasm;Metabolic;Metabolism;Methods;Mitochondria;Modeling;Molecular;Molecular Conformation;mouse model;Mus;Muscle;mutant;N-terminal;novel;novel therapeutics;Nuclear;Nuclear Export;Nuclear Translocation;Operative Surgical Procedures;Oxidative Phosphorylation;Patients;Play;prediction algorithm;promoter;Protein Isoforms;protein protein interaction;Proteins;Recurrence;Repression;Research;Resistance;restoration;Role;Sarcoma;Scanning;sedimentation velocity;Signal Transduction;Site;Site-Directed Mutagenesis;small molecule inhibitor;Soft tissue sarcoma;Stimulus;Structure;Therapeutic;transcriptome sequencing;Transfection;treatment response;tumor;tumor growth

PROJECT_TITLE: The Role of the Fructose-1,6-Bisphoshatase 2 and c-Myc Interaction in Sarcoma Progression


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome

ORG_CITY: CHAPEL HILL

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE The majority of muscle cells in the heart, unlike most other cells in the body, contain more than the standard two copies of DNA, with these extra copies frequently located within additional nuclei within the cell. Research on this phenomenon has typically focused on its relevance to the low rate of cell division see in this type of cell and its implications for heart health, but exciting, recently published results suggest that the separate nuclei within these muscle cells may be combining together in a nuclear ‘code’ that informs the nature of the resulting cell and its resistance to stressors such as heart attacks. This Steven I. Katz proposal will result in the identification of the elements of this code and its implications with regards to genetic variation and heart attack severity using state-of-the-art experimental approaches and novel computational algorithms.

PI_NAMEs: RAU, CHRISTOPH DANIEL (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Adult;Affect;Age;Algorithms;Apoptosis;Bioinformatics;Blood;Cardiac;Cardiac health;Cardiac Myocytes;Cardiac Volume;Cell division;Cell Nucleus;cell type;Cells;Code;Collaborations;combat;comparative;Computational algorithm;Data;Development;Diagnostics Research;Disease;DNA;effective therapy;Elements;Gene Expression;Genes;Genetic;Genetic Transcription;Genetic Variation;Genomics;Goals;Grant;Heart;heart cell;Heart failure;heart function;Heart Injuries;Hypertrophy;image reconstruction;Incidence;Infarction;Laboratory Research;Link;Literature;Mononuclear;mortality;Mus;Muscle Cells;Myocardial Infarction;Nature;new technology;next generation sequencing;novel;novel strategies;novel therapeutics;Nuclear;overexpression;Phenotype;Polyploidy;Population;Population Heterogeneity;Predisposition;Proliferating;Publishing;Regenerative capacity;Research;Research Personnel;Resistance;response;Role;Severities;single nucleus RNA-sequencing;single-cell RNA sequencing;Site;skills;Spatial Distribution;Split-Pool Ligation Transcriptome sequencing;Stress;stressor;Technology;Therapeutic;three dimensional structure;Transcript;transcriptome;transcriptome sequencing;transcriptomics;trend;Variant;Visual;Work

PROJECT_TITLE: Elucidating the Role of Multinuclearity in Healthy and Diseased Mammalian Cardiomyocytes

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE The current proposal “NRF2-dependent redox signaling in pancreatic cancer” will use genetic and biochemical tools to explore the mechanisms by which Nrf2 regulates redox signaling in pancreatic ductal adenocarcinoma through regulating cysteine and methionine oxidative modifications. We anticipate that our results will explain fundamental aspects of redox homeostasis in PDA and will inform the development of more effective therapies for PDA and potentially other KRAS driven malignancies.

PI_NAMEs: CHIO, CHRISTINE IOK IN (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: Ablation;advanced disease;Amino Acids;Biochemical;biochemical tools;Biological Assay;Biology;cancer cell;ChIP-seq;Cysteine;Cytoprotection;Cytostatics;cytotoxic;cytotoxicity;Development;DNA;DNA Damage;effective therapy;Elongation Factor;Enzymes;fitness;Genes;Genetic;genetic approach;Genetic Transcription;Genetically Engineered Mouse;Glycolysis;Growth;Homeostasis;Human;Impairment;In Vitro;in vivo;interest;KRAS oncogenesis;KRAS2 gene;Lipids;macromolecule;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metabolic;Methionine;Modification;mouse model;Mus;Mutagens;mutant;Mutate;Mutation;Natural Killer Cells;neoplastic cell;Oncogenes;Organoids;oxidation;Oxidation-Reduction;oxidative DNA damage;pancreatic cancer cells;Pancreatic duct;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic tumorigenesis;Pathogenesis;Post-Translational Protein Processing;Process;Prognosis;Protein Biosynthesis;Proteins;Proteome;Reactive Oxygen Species;Resistance;ribosome profiling;Ribosomes;Role;Signal Transduction;Stage at Diagnosis;Sulfur;Testing;therapeutic target;Transcript;transcription factor;transcriptome sequencing;Translational Regulation;Translations;Transplantation;tumor;tumor progression;tumorigenesis;Up-Regulation;Western Blotting

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

PHR: PUBLIC HEALTH RELEVANCE Heart disease prematurely ends African American lives in the rural southeast. New ways to prevent heart disease are needed that help people access resources to live a healthy life using a “whole person” approach to CVD and social needs, especially in high-need communities.

PI_NAMEs: DAVE, GAURAV J (contact);LINDAU, STACY TESSLER

PROGRAM_OFFICER_NAME: BRUNO, FERNANDO PEREIRA

PROJECT_TERMS: Accountability;Address;Adult;African American;African American population;Behavior Therapy;Behavioral Model;burden of illness;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;care costs;Caring;Characteristics;Child;Clinic;Clinical;clinical encounter;Clinical Services;Communities;community academic partnership;community clinic;Community Health;Community Services;comparison control;Computerized Medical Record;Consolidated Framework for Implementation Research;contextual factors;cost;Cost Effectiveness Analysis;cost estimate;County;Data;data resource;density;Diabetes Mellitus;digital solutions;disease disparity;effectiveness evaluation;effectiveness/implementation design;effectiveness/implementation study;family management;Federally Qualified Health Center;geographic disparity;Glycosylated hemoglobin A;Goals;Health;health assessment;Health Care Costs;Health care facility;health inequalities;health management;Health Promotion;health service use;heart disease prevention;Heart Diseases;high risk;Hybrids;Hypertension;implementation evaluation;implementation facilitators;implementation science;implementation strategy;improved;Individual;innovation;Intervention;Knowledge;Life;Link;Lipids;Literature;Maps;Methods;minority communities;Modeling;Morbidity - disease rate;mortality;National Heart, Lung, and Blood Institute;North Carolina;Obesity;organizational readiness;Outcome;Participant;Patients;Persons;pragmatic intervention;pragmatic trial;premature;preventive intervention;Process;public health relevance;racial disparity;Research;Resources;Risk;Risk Factors;Rural;rural African American;Rural Community;rural health network;rural healthcare;Rural Minority;rural setting;screening;Self Efficacy;Self Management;service providers;Services;social;social health determinants;standard of care;Stress;System;theories;Translations;United States;Weight

PROJECT_TITLE: Implementation of EMR-Integrated Referrals to Link Clinical and Community Services to Reduce Health Inequity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DIRH-K(07)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Cancer;Complementary and Integrative Health;Eczema / Atopic Dermatitis;Genetics;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in the skin and implicated in cutaneous sensation, including thermo-sensation, nociception, and itch, in addition to maintenance of the skin barrier, wound healing, and hair growth. The dysfunction of TRPV3 channels, often a result of genetic mutations, is associated with numerous human skin diseases, including a genodermatosis known as Olmsted syndrome, atopic dermatitis, and rosacea. Our goal is to study TRPV3 channels using a combination of biophysical and biochemical techniques and to obtain detailed information about their structure and function that will help develop new drug design strategies.

PI_NAMEs: SOBOLEVSKY, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: Acne Vulgaris;Affinity;Agonist;Alkaloids;analog;Anhydrides;antagonist;Atopic Dermatitis;base;Binding;Binding Sites;Biochemical;Biological Assay;Biophysics;Borates;Calcium;Calmodulin;Camphor;Cells;Chemicals;citral;Collaborations;colorectal cancer progression;Combined Modality Therapy;Complex;Coumarins;Cryoelectron Microscopy;Cutaneous;Data;Dermatitis;design;Detection;Development;Disease;disease-causing mutation;DNA Sequence Alteration;Drug Design;Electrophysiology (science);Endogenous Factors;Esthesia;Eugenol;farnesyl pyrophosphate;Fluorescence;Fluorescent Dyes;Functional disorder;Fura-2;gain of function;Goals;Growth;Guanine;Hair;Heating;High temperature of physical object;Human;Individual;inhibitor;inorganic phosphate;Ion Channel;Ion Channel Gating;isopentenyl pyrophosphate;keratinocyte;Kinetics;Knowledge;Ligands;Lipid Bilayers;Lipids;Maintenance;Malignant neoplasm of lung;Measurement;Mediating;Membrane Lipids;Methodology;Methods;Molecular;Molecular Conformation;Molecular Sieve Chromatography;Mutagenesis;mutant;Mutation;natural product inspired;Nociception;novel therapeutic intervention;novel therapeutics;Olmsted syndrome;overexpression;Pain;patch clamp;Periodicity;Pharmaceutical Preparations;Phase Transition;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Physiological;Physiological Processes;Plant Extracts;Play;Positioning Attribute;Process;Proteins;Pruritus;Psoriasis;ratiometric;Regulation;Reporting;Research;Role;Rosacea;sensor;Signal Transduction;Site-Directed Mutagenesis;Skin;skin barrier;skin disorder;Skin Neoplasms;Skin Physiology;small molecule;Stimulus;Structural Models;Structure;Techniques;Temperature;Testing;Thermodynamics;thermostability;Transmembrane Domain;TRP channel;Vanilloid;wound healing

PROJECT_TITLE: Structural and functional principles of activation and regulation of the transient receptor potential channel TRPV3.

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


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

ORG_CITY: Chicago

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: We expect our proposed work to establish the concept that combination treatments that target both endocrine- therapy sensitive and tolerant populations, prior to recurrence and the development of resistance, will be highly effective in preventing relapse and disease progression. Overall, the studies we propose have tremendous potential to impact outcome for women diagnosed with ER+ breast cancer by identifying new combination therapies with that can lower their risk of disease relapse.

PI_NAMEs: COLOFF, JONATHAN L. (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Address;adjuvant endocrine therapy;Aromatase Inhibitors;biological adaptation to stress;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;cancer stem cell;cell growth;Cell Survival;Cells;Cellular Stress;Combined Modality Therapy;Data;Development;Diagnosis;Disease;Disease Progression;disorder risk;Drug resistance;Drug Tolerance;ESR1 gene;Estrogen Receptors;Event;Funding;Genetic;genetic signature;Growth;hormone therapy;Human;Immunocompetent;Immunocompromised Host;In Vitro;in vivo;inhibitor;insight;Link;Malignant Breast Neoplasm;Mammary Neoplasms;Mediating;mouse model;Mus;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;new combination therapies;NF-kappa B;novel;novel strategies;Organoids;Pathway interactions;Patients;Phenotype;Population;Pre-Clinical Model;pressure;prevent;Primary Neoplasm;Proliferating;Property;Recurrence;Recurrent disease;Recurrent tumor;Regulation;Relapse;relapse prevention;relapse risk;Resistance;Resistance development;resistance mechanism;response;Risk;Role;single-cell RNA sequencing;small molecule inhibitor;Stress;Survival Rate;Tamoxifen;Target Populations;Testing;Therapeutic;therapy resistant;Time;tumor;tumor xenograft;Withdrawal;Woman;women's diagnosis;women's outcomes;Work;Xenograft procedure

PROJECT_TITLE: Estrogen Receptor and NFkB Crosstalk in Breast Cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Biotechnology;Hematology;Immunotherapy;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public Health Relevance Our team will gain biological insights into immune system control of graft-versus-host disease (GVHD) providing an exciting new approach for GVHD prevention and therapy. Our findings have broad implications for the use of agonist VISTA antibody for hematopoietic stem cell and solid transplantation as well as autoimmunity settings.

PI_NAMEs: BLAZAR, BRUCE R (contact);NOELLE, RANDOLPH J.

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Acute Graft Versus Host Disease;Affect;Affinity;Agonist;Allogenic;anergy;Anti-Inflammatory Agents;Antibody Activation;Antigens;Antitumor Response;Autoimmunity;Binding;Biological;Biology;Calcineurin inhibitor;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Chemotaxis;Clinical Trials;conditioning;Cyclic GMP;cytokine;Data;disease model;disorder prevention;Disparate;Dose;Down-Regulation;Exclusion;Frequencies;Functional disorder;Generations;graft vs host disease;graft vs leukemia effect;Grant;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;Immune;Immune system;Immunoglobulins;In complete remission;in vivo;Infiltration;Inflammation;Inflammatory;inflammatory milieu;Inflammatory Response;inhibiting antibody;insight;Interleukin-10;leukemia;Ligands;Link;Macrophage;Maintenance;Mediating;Memory;Minor;Modeling;Monoclonal Antibodies;monocyte;Mus;Myelogenous;Myeloid Cells;Myeloid Leukemia;novel strategies;operation;Organ;P-selectin ligand protein;Pathogenesis;Patients;Peer Review;Peripheral;Pharmaceutical Preparations;prevent;programs;Prophylactic treatment;public health relevance;Publications;Receptor Signaling;Refractory;Refractory Disease;Regulatory T-Lymphocyte;response;Rest;Role;Severities;Side;side effect;Solid;Steroids;Suppressor-Effector T-Lymphocytes;Survival Rate;T cell response;T memory cell;T-Cell Activation;T-Cell Activation Pathway;T-Cell Depletion;T-Cell Receptor;T-Lymphocyte;Testing;Transgenic Organisms;Translating;Translations;Transplant Recipients;Transplantation

PROJECT_TITLE: Exploiting the VISTA Pathway to Prevent Acute GVHD and Control Steroid Refractory Disease

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


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);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative  Our strong preliminary data suggest that there is a subpopulation of wild-type neurons strikingly recapitulating several key phenotypes of familial Alzheimer’s disease (FAD) neurons. This proposal aims further to conduct a set of mechanistic studies to characterize this newly discovered selectively vulnerable cell population and explore the therapeutic potential of the US FDA-approved compounds. The completion of the proposed study will enable the development of novel therapeutic strategies for AD.

PI_NAMEs: MAESAKO, MASATO  (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Age of Onset;Alzheimer's Disease;Alzheimer's disease brain;Amyloid beta-Protein;Autopsy;Binding;Biological Assay;Biological Models;Biosensor;Brain;brain tissue;Cell Separation;Cells;Characteristics;Clinical;Cyclic AMP-Dependent Protein Kinases;Data;Data Set;Databases;Development;Disease;early onset;enzyme substrate;familial Alzheimer disease;FDA approved;Fluorescence Resonance Energy Transfer;gamma secretase;Genetic;Genetic Transcription;Goals;Grant;Heterogeneity;Human;human induced pluripotent stem cells;Impairment;In Vitro;in vivo;Individual;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;Knock-in;Knowledge Portal;Link;Mediating;Molecular;Molecular Conformation;mouse model;Mus;mutant;Mutation;Nerve Degeneration;Neurons;non-demented;novel;novel therapeutic intervention;novel therapeutics;Pathologic;Pathology;Pathway interactions;Persons;pharmacologic;Pharmacologic Substance;Phenotype;Phosphorylation;Physiological;PKA inhibitor;Play;Population;Post-Translational Protein Processing;presenilin;presenilin-1;Production;Proteomics;resilience;response;Role;sensor;Site;tau Proteins;Tg2576;Therapeutic;Time;Tissues;transcriptomics;Transgenic Mice;Transgenic Organisms;Vulnerable Populations

PROJECT_TITLE: A unique subpopulation of wild-type neurons recapitulating FAD phenotypes

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative Regulation of gene transcription is fundamental to developmental processes and preventing disease. While enhancers, functional DNA elements that increase gene transcription, little attention has been devoted to silencers, the inverse elements that reduce transcription. The proposed research seeks to uncover DNA- binding proteins and chemical modifications that will allow investigators to easily identify new silencers and better understand how they lead to decreased transcription.

PI_NAMEs: SEGERT, JULIAN ANDREW (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: 3-Dimensional;Address;Affinity;Architecture;Attention;Binding;Binding Proteins;Biological Assay;Biology;career;Cell Separation;cell type;Cellular Assay;Characteristics;Chemicals;ChIP-seq;Chromatin;chromatin modification;cofactor;Collection;combinatorial;Complex;Data;design;Development;Developmental Process;Disease;DNA;DNA Binding;DNA-Binding Proteins;Drosophila genus;Elements;Embryo;Enhancers;Ensure;Epigenetic Process;experience;experimental analysis;Experimental Designs;falls;Fluorescent in Situ Hybridization;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;Genome;genome wide association study;Genomics;high throughput screening;Histone Code;histone modification;Histones;human disease;improved;insight;Investigation;Label;Maps;Mass Spectrum Analysis;Mesoderm;Methods;Modeling;Modification;Molecular Conformation;morphogens;mutant;Nature;Pathway interactions;Positioning Attribute;Post-Translational Protein Processing;prevent;Process;promoter;protein protein interaction;Proteomics;recruit;Regulation;Regulatory Element;Reporter;Repressor Proteins;Research;Research Personnel;Research Project Grants;Role;Snails;spatiotemporal;Statistical Models;Surveys;System;Techniques;Testing;tool;transcription factor;Transcriptional Silencer Elements;Validation;Variant;Visualization;Western Blotting

PROJECT_TITLE: Characterization of silencer element-associated chromatin

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


ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

ORG_STATE: MI

PHR: It has increasingly become evident that obstructive sleep apnea (OSA) is negatively associated with adverse neurocognitive consequences. The negative neurocognitive consequences of OSA in the elderly may be compounded by the co-existence of another disorder, chronic obstructive lung disease (COPD). The combined effect of these two highly prevalent diseases, OSA and COPD, also known as Overlap Syndrome, may put the elderly Veteran at increased risk for developing early dementia, poor functional health and poor quality of life. Our goal is to advance the rehabilitative health care of elderly Veterans at increased risk for cognitive impairment and sleep disturbances by evaluating effective treatment pathways, with the aim of improving overall health and quality of life.

PI_NAMEs: CHOWDHURI, SUSMITA  (contact)

PROJECT_TERMS: Aging;airway obstruction;Alzheimer's Disease;Arousal;Award;Brain;Cardiovascular system;Caring;Catchment Area;Chronic;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Clinical;Cognitive;Cognitive deficits;cognitive enhancement;cognitive function;cognitive testing;comorbidity;Complex;Continuous Positive Airway Pressure;Data;Dementia;disability;Disease;Drowsiness;Early treatment;Education;effective therapy;effectiveness evaluation;Elderly;experience;falls;Feasibility Studies;Functional disorder;Future;General Population;Goals;Health;Healthcare;Hospitalization;Hypercapnia;Hypoventilation;Hypoxia;Impaired cognition;Impairment;improved;improvement on sleep;Individual;Injury;innovation;Long-Term Care for Elderly;Medical;Memory;Mental Depression;mild cognitive impairment;military veteran;mortality;Neurocognitive;Neurocognitive Deficit;Neurodegenerative Disorders;novel;Obstructive Sleep Apnea;older adult;Outcome;Oxygen;Pathway interactions;Patients;pharmacologic;Pilot Projects;poor sleep;Population;positive airway pressure;pressure;Prevalence;Probability;prospective;Quality of life;Questionnaires;randomized, controlled study;Rehabilitation therapy;Research;Research Design;Research Priority;Risk;Short-Term Memory;Sleep;Sleep Disorders;Sleep disturbances;Sleep Fragmentations;sleep health;sleep quality;Stroke;Symptoms;Syndrome;Time;ventilation;verbal;Veterans

PROJECT_TITLE: Impact of Positive Airway Pressure Therapy on Clinical Outcomes in Older Veterans with Chronic Obstructive Pulmonary Disease and Comorbid Obstructive Sleep Apnea (Overlap Syndrome)

STUDY_SECTION_NAME: Chronic Medical Conditions & Aging[RRD6]


ADMINISTERING_IC: HD

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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Infertility affects 1 in 6 couples worldwide. Known genetic factors account for ~10-15% of male factor infertility cases, whereas, the remaining ~35-40% of the male factor cases have an unknown etiology. Therefore, a comprehensive understanding is sperm chromatin in development is required for better diagnoses or developing effective male infertility therapies.

PI_NAMEs: HAMMOUD, SAHER SUE (contact)

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: Acetylation;Affect;Antibodies;Back;Binding;Biochemical;Biological;Biological Assay;Biological Process;Cell Nucleus;Cells;Chromatin;Code;Complex;Couples;Custom;Data;Deposition;Development;Diagnosis;DNA;DNA Packaging;egg;Elements;Embryo;Embryonic Development;Epigenetic Process;Epitopes;Etiology;Evolution;Excision;Fertility;Fertilization;Future;Genetic;genetic approach;Genetic Models;Genetic Transcription;Genome;Genomic Segment;Genomics;Hand;Histone Code;Histones;Immunofluorescence Immunologic;Infertility;insight;Intracytoplasmic Sperm Injections;Investigation;Link;Lysine;male;male fertility;Male Infertility;Mammals;Maps;Mass Spectrum Analysis;Methylation;Modification;Molecular;mouse model;Mutant Strains Mice;Mutation;novel;offspring;Oocytes;Outcome;Parents;Partner in relationship;Pattern;Phosphorylation;Post-Translational Protein Processing;protamine 1;Protamines;protein function;Proteins;Reagent;reproductive;Role;Series;Serine/Threonine Phosphorylation;Site;Somatic Cell;Specificity;sperm cell;sperm quality;Spermatids;Spermatogenesis;System;Testing;Testis;transgenerational epigenetic inheritance;Transgenic Mice;Transgenic Organisms;transmission process;Variant;Visit;zygote

PROJECT_TITLE: Sperm Chromatin:  Implications on organismal development and fertility


NIH_SPENDING_CATS: Genetics;Infertility;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Retrotransposons can seriously damage the genome of the nascent embryo and cause sporadic diseases and infertility. Here we will explore a new sensing mechanism that involves early embryonic cells “sniffing” one another for endogenous retroviruses and the removal of cells that failed to silence their genetic parasites. Our line of investigation will provide new targets for genetic diagnosis and interventions targeting pregnancy loss, birth defects and childlessness.

PI_NAMEs: ZWAKA, THOMAS P. (contact)

PROJECT_TERMS: Address;Apoptosis;arms race;Attention;Cell Communication;Cell Cycle Arrest;Cells;Chromatin;Code;Congenital Abnormality;Data;Defect;defense response;Development;Disease;DNA;DNA Damage;DNA Methylation;Double-Stranded RNA;early pregnancy;early pregnancy loss;Elements;Embryo;embryo cell;Embryonic Development;embryonic stem cell;Endogenous Retroviruses;Epiblast;Excision;Exogenous Factors;experimental study;Fossils;gene therapy;Genetic;genetic disorder diagnosis;Genome;Goals;Grant;Growth;Health;Immune;Immune system;immunoregulation;Infertility;Investigation;Length;Monitor;Mus;Normal tissue morphology;novel;Nucleic Acids;Outcome;Parasites;peer;Phagocytosis;Physiology;Play;Pluripotent Stem Cells;Police;Pregnancy loss;Process;Proteins;Repetitive Sequence;replicator;Research Proposals;response;Retrotransposon;Risk Factors;Role;sensor;Specific qualifier value;Stimulator of Interferon Genes;Stress;stress granule;System;Testing;tissue culture;TP53 gene;transposon/insertion element;Untranslated RNA;Viral load measurement;viral RNA;Virion;Virus;Work;Zinc Fingers

PROJECT_TITLE: Protection of early embryogenesis and pluripotent stem cells against genetic parasites through a primitive immune system

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative There are currently limited treatment options for improving endothelial dysfunction in vascular diseases, a leading cause of morbidity and mortality. Activated Protein C (APC) is a promising therapeutic that promotes multiple cytoprotective effects including stabilization of endothelial barriers, anti-inflammatory responses and anti-apoptotic activities. The proposed research is important because it will advance the status of APC by understanding the mechanism by which APC activation of protease-activated receptor-1 promotes endothelial cytoprotection.

PI_NAMEs: TREJO, JOANN  (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: activated Protein C;Agonist;Anti-Inflammatory Agents;Anticoagulants;Apoptosis;Apoptotic;Arginine;ARRB1 gene;ARRB2;beta-arrestin;Binding;Caveolae;caveolin 1;Cell membrane;Cells;CRISPR/Cas technology;Cytoprotection;desensitization;Endothelial Cells;endothelial dysfunction;Endothelium;Exhibits;Future;G-Protein-Coupled Receptors;Goals;GRK5 gene;GTP-Binding Proteins;Heterotrimeric GTP-Binding Proteins;Human;improved;In Vitro;in vivo;Inflammation;Inflammatory Response;Injury;innovation;insight;Knock-out;Ligands;Mediating;Mediator;Membrane;Membrane Microdomains;Morbidity - disease rate;mortality;N-terminal;new therapeutic target;novel;PAR-1 Receptor;Pathogenesis;Pathologic;Pathway interactions;Peptide Hydrolases;pharmacologic;Phosphorylation;Phosphotransferases;Physiological;preclinical study;receptor;Research;resilience;response;Sepsis;Signal Induction;Signal Pathway;Signal Transduction;Site;Specificity;Sphingosine-1-Phosphate Receptor;SPHK1 enzyme;System;Testing;Therapeutic;therapeutic development;Thrombin;Transducers;Vascular Diseases

PROJECT_TITLE: Endothelial Cytoprotective Signaling by Activated Protein C/Protease-activated Receptor-1

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases

ORG_DEPT: PATHOLOGY

PHR: Narrative Currently, we know T cell responses become exhausted due to persistent antigen availability; however, how chronic infections impact antigen recognition by T cells is currently unknown. Our work will address this unmet need by determining the kinetics of antigen recognition and the associated phenotypic responses.

PI_NAMEs: EVAVOLD, BRIAN D (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: acute infection;adaptive immune response;Affinity;Antigen-Presenting Cells;Antigens;Area;base;Binding;Biology;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Characteristics;Chronic;chronic infection;Complex;Data;DNA;effector T cell;Environment;Equilibrium;Event;exhaust;Exhibits;functional outcomes;Goals;immune checkpoint blockade;Immunity;Infection;innovation;insight;Intervention;Kinetics;Length;Ligands;Lymphocytic choriomeningitis virus;Measures;Membrane;Memory;MHC antigen;Mus;novel;Outcome;Parasitic infection;pathogen;Peptide/MHC Complex;Phenotype;Plasmodium;Polyomavirus;Process;Proteins;Publishing;receptor;recruit;Reporter;Research;response;Role;sensor technology;Signal Transduction;Surface;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;TCR Activation;Testing;Time;two-dimensional;Virus Diseases;Work

PROJECT_TITLE: CD8 T cell antigen recognition during chronic infection

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


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Biotechnology;Genetics;Hematology;Human Genome;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE This project is tightly aligned with the research objectives supported by “Stimulating Hematology Investigation: New Endeavors (SHINE)” program by unveiling Biology and Pathophysiology of Myelodysplastic Syndromes (MDS) and identifying regulatory factors governing function of aged hematopoietic stem and progenitor cells. Our studies will furnish novel insights about how transcription factors and somatic mutations mutually reinforced to shape the genome during aging and results clonal hematopoiesis (CH) and MDS. Our discoveries may establish the rationale for targeting therapeutic vulnerability in the elderly with CH and MDS.

PI_NAMEs: CHENG, XIAODONG ;HUANG, YUN  (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Affinity;aged;Aging;Ascorbic Acid;base editing;Base Excision Repairs;Binding;Biochemical;Bioinformatics;Biological Models;Biology;Bone Marrow;Bone Marrow Transplantation;CD34 gene;Cell Separation;Cells;clinically relevant;Clonal Expansion;CRISPR/Cas technology;Cytosine;Deamination;Defect;demethylation;Disease;DNA;DNA Binding;DNA Methylation;DNA Repair Enzymes;DNA Sequence Alteration;DNMT3a;Dysmyelopoietic Syndromes;Elderly;Enzymes;Epigenetic Process;epigenetic regulation;epigenome editing;epigenomic profiling;Etiology;Exhibits;exome sequencing;Family member;fitness;Frequencies;Functional disorder;Gene Modified;Genetic Transcription;Genome;genome editing;genome-wide;Genomics;Guanine;Hematology;Hematopoiesis;Hematopoietic stem cells;Human;Impairment;In Vitro;Individual;inhibitor;innovation;insight;Intervention;Investigation;Knowledge;Maintenance;Mediating;Methods;Methylation;Mismatch Repair;mouse model;Mus;mutant;Mutation;Mutation Detection;Myeloproliferative disease;novel;novel therapeutics;Output;Pathogenesis;Pathologic;Patients;pharmacologic;Positioning Attribute;programs;Psychological reinforcement;Publishing;Recording of previous events;repair enzyme;Reporting;Research;response;Rodent Model;Role;Sampling;Scheme;Shapes;Somatic Mutation;Systems Biology;targeted treatment;Testing;Therapeutic;Thymine DNA Glycosylase;tool;transcription factor;Transcriptional Regulation;Untranslated RNA

PROJECT_TITLE: Mutual reinforcement between somatic mutations and transcription factors in clonal hematopoiesis

STUDY_SECTION: BBHV

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Immunotherapy;Patient Safety

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE This grant provides the continued opportunity for Vanderbilt-Ingram Cancer Center (VICC) to participate in the National Clinical Trials Network (NCTN). It supports the infrastructure at VICC for the conduct of NCTN trials, thus allowing our investigators to collaborate with others around the country, to serve in leadership roles within the NCTN, to bring scientific discoveries from VICC into NCTN trials and to mentor the next generation of clinical investigators in the NCTN system.

PI_NAMEs: CIOMBOR, KRISTEN KEON (contact)

PROGRAM_OFFICER_NAME: MOONEY, MARGARET M

PROJECT_TERMS: Academic Medical Centers;Advanced Malignant Neoplasm;Advisory Committees;Alabama;Antineoplastic Agents;Appointment;Area;Authorship;Automobile Driving;Award;Basic Science;Berlin;Biology;Breast;Budgets;cancer care;Cancer Center;cancer clinical trial;cancer genomics;Cancer Patient;cancer therapy;Catchment Area;Cessation of life;Clinical Cancer Center;Clinical Investigator;Clinical Research;Clinical Sciences;Clinical Trials;Clinical Trials Network;Collaborations;Collection;Communities;Compassion;Comprehensive Cancer Center;Conduct Clinical Trials;Country;Data;data submission;Death Rate;Dedications;Department chair;design;Development;Diagnosis;Discipline;Discipline of obstetrics;Disease;drug discovery;Early Detection Research Network;early phase trial;Early Therapeutic-Clinical Trials Network;Eastern Cooperative Oncology Group;Education;Education and Outreach;Ensure;evidence base;Faculty;Funding;gastrointestinal;Goals;Grant;Growth;Gynecology;Health;Human;Image;imaging science;Immunology;Immunotherapy;improved;improved outcome;Incidence;Infection;Inflammation;Informatics;Infrastructure;innovation;Institution;Institutional Review Boards;inter-institutional;interest;investigator-initiated trial;Jordan;Kentucky;Knowledge;Lead;Leadership;Malignant neoplasm of pancreas;Malignant Neoplasms;Manuscripts;Medical;medical specialties;Medicine;meetings;member;Mentors;Mentorship;Mission;multidisciplinary;Mutation;National Cancer Institute;National Clinical Trials Network;NCI Center for Cancer Research;next generation;novel;Obesity;participant enrollment;patient oriented;Patient-Centered Care;Patients;PD-1/PD-L1;PDL1 inhibitors;Phase;Physicians;Prevention;Principal Investigator;Process;programs;Protocols documentation;radiological imaging;Radiology Specialty;recruit;Research;Research Activity;Research Personnel;Research Priority;resistance mechanism;Resource Sharing;Resources;Role;Science;Scientist;Services;Site;success;System;targeted treatment;Technology;Tennessee;Tobacco use;Training;Translational Research;Translations;tumor;United States;Universities;web site;Work

PROJECT_TITLE: Vanderbilt Network Lead Academic Participating Site for the NCTN


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative  The work in this proposal is aimed at elucidating the basic pathogenic mechanisms and the regulatory pathways involved in proteotoxicity and quality control underlying neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although these diseases are becoming an increasingly relevant public health challenge in our aging society, the mechanisms underlying most of these neurodegenerative conditions remain poorly understood. The biochemical, molecular, and genetic studies outlined in this proposal could lead to novel therapeutic interventions for those neurodegenerative diseases, for which effective treatments are still lacking.

PI_NAMEs: WANG, JIOU  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Address;Affect;Aging;aging population;Alzheimer's Disease;amino acid metabolism;Amyotrophic Lateral Sclerosis;Biochemical;Biological;Branched-Chain Amino Acids;C9ORF72;Caenorhabditis elegans;Cells;Creutzfeldt-Jakob Syndrome;CRISPR screen;Defense Mechanisms;design;Disease;effective therapy;Enzymes;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Future;Genetic;Genetic Screening;Genetic study;Genetic Transcription;genome-wide;Heat-Shock Response;Huntington Disease;innovation;insight;interest;Invertebrates;Investigation;KDM1A gene;Knowledge;L3MBTL1 gene;MADH2 gene;Mammalian Cell;Mammals;Mediating;misfolded protein;Modeling;Molecular;Molecular Target;Monitor;mutant;Nerve Degeneration;Neurodegenerative Disorders;neurotoxicity;novel;novel therapeutic intervention;Parkinson Disease;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phenotype;Post-Translational Protein Processing;prevent;programs;protein aggregation;protein misfolding;protein TDP-43;Proteins;proteotoxicity;Public Health;Quality Control;Regulation;Regulatory Pathway;Reporter;Research;response;screening;Signal Pathway;Signal Transduction;Societies;Stress;success;superoxide dismutase 1;Suppressor Genes;System;Therapeutic Intervention;tool;Toxic effect;Transacylase;transcription factor;ubiquilin;ubiquitin isopeptidase;Work

PROJECT_TITLE: Mechanisms of Novel Regulators of Proteotoxicity and Quality Control Associated with ALS/FTD

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND-M]


NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Endocrine Disruptors;Infertility;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: NARRATIVE Per- and polyfluoroalkyl substances (PFAS) are environmental toxicants of urgent scientific, governmental, and public concern over their near-universal human exposure and adverse health effects. Understanding the effect of PFAS exposure on a couple’s ability to conceive and carry a pregnancy to term is a critical research gap and an important public health goal. The proposed study is designed to determine the effects of paternal and maternal preconception exposure to PFAS on reproductive, pregnancy, and birth outcomes.

PI_NAMEs: MAHALINGAIAH, SHRUTHI  (contact)

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: adverse outcome;Affect;Air;Amniotic Fluid;Animal Model;Biochemical;biological specimen archives;Biometry;Birth;Birth Rate;Birth Weight;Blood;Breathing;chemical property;Chemicals;Clinic;Clinical;Clinical Data;cohort;Conceptions;consumer product;cost efficient;Couples;Data;design;Eating;Environment;Environmental Epidemiology;Environmental Exposure;Environmental Pollution;Epidemiology;Epigenetic Process;evidence base;exposed human population;Exposure to;failure Implantation;Family;Female;Fertility;Fertilization;Food;Food Packaging;General Population;Germ Lines;Gestational Age;Health;health goals;Home;Human;Human body;Impairment;implantation;Individual;Infertility;innovation;Investigation;Knowledge;Label;Life Style;Live Birth;Low Birth Weight Infant;male;Malignant Neoplasms;Manufacturer;Maternal Exposure;Measures;men;Methods;Neonatal;Nulliparity;offspring;Outcome;Outcome Study;perfluorooctane sulfonate;perfluorooctanoic acid;perinatal health;perinatal outcomes;Phase;Physiological;Plasma;Policies;Poly-fluoroalkyl substances;Population;Pregnancy;Pregnancy loss;Pregnancy Outcome;Premature Birth;Production;prospective;Public Health;recruit;Reproduction;reproductive;reproductive epidemiology;Reproductive Health;reproductive outcome;reproductive success;Research;Research Design;Resistance;Risk;Sample Size;Schools;Seminal fluid;Serum;sperm cell;Stains;substance use;Textiles;Thyroid Diseases;Time;Toxic Environmental Substances;United States;Water;Weights and Measures;Woman;Workplace

PROJECT_TITLE: The Impact of Maternal and Paternal Preconception Perfluoroalkyl Substance (PFAS) Exposure on Reproductive and Perinatal Outcomes

STUDY_SECTION: IRAP

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


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

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE  Apicomplexan parasites are the causative agents of a number of important human diseases including malaria, cryptosporidiosis, and toxoplasmosis. Our immediate goal is to determine the mechanism by which a parasite-specific molecule regulates the biogenesis and development of the vacuole in which the parasite Toxoplasma gondii survives and replicates. Our long-term goal is to produce fundamental knowledge with the potential to uncover new therapeutic targets for the future treatment of multiple parasitic diseases.

PI_NAMEs: REESE, MICHAEL LLOYD (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Address;Animal Model;Animals;Antigen Presentation;Biochemical;biochemical model;Biogenesis;Biophysical Process;biophysical techniques;candidate validation;cell type;Cells;Cessation of life;Chemicals;Collaborations;Complex;Complication;crosslink;Cryptosporidiosis;Cytoplasmic Granules;Cytosol;Data;Development;Diameter;Disease;Electron Microscopy;experimental study;Foundations;Future;Genetic;Goals;Human;human disease;Immune;Immunocompromised Host;immunosuppressed;In Vitro;Individual;Infection;Ingestion;innovation;intermolecular interaction;Invaded;Knowledge;Life;Malaria;Mass Spectrum Analysis;Mediating;Membrane;Membrane Proteins;Methods;Molecular;Molecular Chaperones;Molecular Genetics;Molecular Weight;Morphology;Mutagenesis;mutant;Mutate;Negative Staining;new therapeutic target;Nutrient;Organelles;Parasites;Parasitic Diseases;pathogen;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiology;Planet Earth;Protein Analysis;protein complex;Protein Kinase;protein protein interaction;Protein Secretion;Proteins;Recombinants;reconstitution;Regulation;Role;Site;Structural Models;Structure;System;Techniques;Testing;three dimensional structure;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;trafficking;unilamellar vesicle;uptake;Vacuole;Vesicle;virtual;Virulence

PROJECT_TITLE: Kinase regulation of trafficking at the Toxoplasma intravacuolar network

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Patient Safety

ORG_CITY: CLEVELAND

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The Case Comprehensive Cancer Center Lead Academic Performance Site Program aims to advance the mission of the National Clinical Trials Network (NCTN) in bettering quality of life, treatments, and cures for patients with cancer through prospective clinical trials. We strive to lead this effort by developing the treatments of the future, collaborating nationally, and making these cutting-edge therapies available to improve the lives of cancer patients we serve in Northeast Ohio.

PI_NAMEs: GERDS, AARON THOMAS (contact);SPRATT, DANIEL EIDELBERG

PROJECT_TERMS: Address;Advisory Committees;American College of Radiology Imaging Network;biobank;Biological Markers;Brain;Breast;cancer care;Cancer Center;Cancer Patient;cancer therapy;cancer type;Clinic;Clinical;Clinical Data;clinical infrastructure;Clinical Research;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;Collaborations;Communication;Communities;Community Clinical Oncology Program;Component of the National Cancer Institute;Comprehensive Cancer Center;County;Data;Data Analyses;data management;data submission;design;Development;Developmental Therapeutics Program;Diagnosis;Diagnostic;Disease;Early Therapeutic-Clinical Trials Network;Eastern Cooperative Oncology Group;Education;Educational process of instructing;Ensure;experience;Faculty;Funding;Future;gastrointestinal;Generations;Genitourinary system;Goals;Gynecologic;Hematology;hospital organization;Hospitals;Image;improved;improved outcome;Individual;Industry;industry partner;Infrastructure;innovation;Institution;interest;Investigation;Lead;Leadership;Lung;Malignant Neoplasms;Medical;medical schools;medical specialties;meetings;Melanoma;member;Mentors;Meta-Analysis;Minority;Mission;Multi-Institutional Clinical Trial;National Cancer Institute;National Clinical Trials Network;Ohio;Oncology;operation;Operative Surgical Procedures;Orphan;Patient Care;Patients;performance site;Phase;Physicians;Pilot Projects;Population Heterogeneity;Positioning Attribute;Procedures;programs;prospective;protocol development;Protocols documentation;quality assurance;Quality Control;Quality of life;Radiation;rare cancer;recruit;Research;Research Personnel;Role;secondary analysis;Services;Site;Southwest Oncology Group;success;System;Time;Tissue Sample;Translational Research;trial planning;Underrepresented Populations;Universities;University Hospitals;Vision

PROJECT_TITLE: Case Comprehensive Cancer Center NCTN Lead Academic Participating Site


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Neurosciences;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Regenerative Medicine;Rehabilitation;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: NARRATIVE Skeletal muscle injuries, in particular irrecoverable volumetric muscle loss (VML) traumas that often damage surrounding nervous and connective tissue, are devastating to a range of civilian and military patients. New tissue engineering approaches are needed to promote both muscle innervation to enable force generation and connective tissue integration at the muscle-tendon junction to allow efficient force transfer and locomotion. This proposal will apply a collagen scaffold mimicking the alignment and electrical excitability of muscle to drive innervated regeneration of complex VML injuries occurring near muscle-tendon junctions.

PI_NAMEs: CALIARI, STEVEN  (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: 3-Dimensional;Ablation;Address;Animals;Antibodies;beta Tubulin;Biocompatible Materials;Biological;Biomechanics;Biomimetics;biophysical properties;Bioreactors;Cell Maturation;Cell Survival;Cells;Cholinergic Receptors;Cicatrix;Clinical;clinically relevant;Coculture Techniques;Collagen;collagen scaffold;Complex;conditioning;Confocal Microscopy;Connective Tissue;Cues;Cytoskeletal Modeling;Defect;Denervation;Dermis;design;Development;Electric Conductivity;Electric Stimulation;electrical potential;Engineering;experience;Extracellular Matrix;Fibrosis;functional improvement;Functional Regeneration;Gait;gait examination;Generations;Glycosaminoglycans;Histologic;Image;immunocytochemistry;Immunohistochemistry;Implant;improved;In Vitro;in vivo;Injury;innovation;Locomotion;Measurement;Measures;Mechanical Stimulation;Mechanics;military patient;Modeling;Movement;Muscle;Muscle Fibers;Muscle function;muscle progenitor cell;muscle regeneration;muscle repair;Muscular Atrophy;myogenesis;Myosin Heavy Chains;Natural regeneration;neglect;Nerve;nerve stem cell;nerve supply;Nerve Tissue;Nervous System Trauma;Neuromuscular Junction;Neuronal Differentiation;Neurons;Operative Surgical Procedures;osteochondral tissue;patient population;Patients;Peripheral Nerves;Peripheral Nervous System;preconditioning;Process;Proliferating;Rattus;Recovery of Function;Repair Complex;repair strategy;repaired;restoration;scaffold;Signal Transduction;Skeletal Muscle;Skeletal muscle injury;Skeletal system;stem cell differentiation;Structure;success;Technology;Tendon structure;Testing;Therapeutic;tibialis anterior muscle;Tissue Engineering;tissue regeneration;tissue repair;Tissues;transmission process;Trauma;Vascularization;volumetric muscle loss;Work

PROJECT_TITLE: Aligned and electrically conductive collagen scaffolds for guiding innervated muscle-tendon junction repair of volumetric muscle loss injuries

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: SAN ANTONIO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Narrative Glioblastomas (GBM) are lethal brain tumors for which ionizing radiation (IR) remains the mainstay of therapy; however, these tumors inevitably recur, and the recurrent tumors are highly therapy resistant. Using PDX and syngeneic mouse models and human GBM specimens we aim to mechanistically understand how IR promotes GBM recurrence and radioresistance via genetic changes to the tumor cells and senescence-associated changes to the brain microenvironment. We propose to test elimination of senescent cells with “senolytics” as a novel strategy to improve GBM therapy.

PI_NAMEs: BURMA, SANDEEP  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Adjuvant Chemotherapy;Astrocytes;Brain;brain cell;Brain Neoplasms;cancer stem cell;Cells;Development;DNA Repair;DNA Sequence Alteration;efficacy testing;Genetic Induction;genetic signature;Glioblastoma;Glioma;Growth;Growth Factor;Human;improved;improved outcome;Ionizing radiation;Ligands;Malignant neoplasm of brain;Modality;Modeling;mouse model;Mutation;neoplastic cell;novel;novel strategies;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;pre-clinical;Publishing;Radiation;Radiation exposure;radiation resistance;Radiation therapy;radioresistant;Radiosensitization;Recurrence;Recurrent tumor;Refractory;Research;Resistance;resistance mechanism;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Senotherapeutic;Senotherapy;Specimen;temozolomide;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;therapy resistant;transcription factor;transcriptional reprogramming;Transgenic Mice;translational approach;tumor;Tumor Promotion;tumorigenic

PROJECT_TITLE: Radiation-induced senescence in the brain microenvironment: Implications for glioblastoma recurrence and therapy

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Neurosciences;Physical Activity

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

PHR: PUBLIC HEALTH RELEVANCE: Heart failure with preserved ejection fraction (HFpEF) accounts for greater than 50% of all heart failure (HF) cases nationwide, and the prevalence of this form of HF relative to heart failure with reduced ejection fraction (HFrEF) is growing by approximately 10% per decade. The proposed project seeks to determine the regulation and functional consequences of sympathetic nervous system (SNS) overactivity in patients with HFpEF. Findings from this study may provide new information that translates directly into an improved ability to perform activities of daily living, which is likely to lead to improved quality of life and a better prognosis in this patient group.

PI_NAMEs: AMANN, MARKUS ;WRAY, D. WALTER (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Acceleration;Activities of Daily Living;Address;Adrenergic Agents;Affect;alpha-adrenergic receptor;American;antagonist;Autonomic Dysfunction;Baroreflex;Blood;Blood flow;Blood Pressure;Blood Vessels;Brain;Buffers;Cardiopulmonary;cardiovascular risk factor;Cardiovascular system;Characteristics;Circulation;Clinical;clinical care;design;Development;Disease;Dissociation;Dyspnea;EFRAC;Exercise;exercise intolerance;Exercise Tolerance;Exertion;Fatigue;Feedback;Functional disorder;Heart failure;heart failure with reduced ejection fraction;heart function;hemodynamics;Impairment;improved;Infusion procedures;innovation;insight;Knowledge;Limb structure;Mediating;Methodology;mortality;Muscle;neuromuscular;neurovascular;Organ;Pathologic;Pathway interactions;Patients;Peripheral;pharmacologic;Phenotype;Phentolamine;Physical activity;Play;premature;preservation;Prevalence;Prognosis;public health relevance;Quality of life;Reflex action;Regulation;Regulatory Pathway;Research;Resistance;response;Rest;Signal Transduction;Skeletal Muscle;success;Sympathetic Nervous System;Symptoms;Translating;Treatment Failure;treatment strategy;vasoconstriction;Vasomotor;Work

PROJECT_TITLE: Autonomic Dysfunction in Patients with HFpEF

STUDY_SECTION: CCHS

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Clinical Research;Gene Therapy;Genetics;Immunization;Immunotherapy;Orphan Drug;Ovarian Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

PHR: Project narrative. Ovarian cancer is the most lethal gynecologic malignancy and the survival rate of women with epithelial ovarian cancer has changed little in the last 30 years. There is an urgent need for new innovative therapeutic strategies. Studies described in our proposal will investigate engineered natural killer cells used in combination with antibody therapies for universal tumor antigen targeting to treat ovarian cancer and other malignancies.

PI_NAMEs: WALCHECK, BRUCE K (contact);WU, JIANMING

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Affinity;Animal Model;Antibodies;Antibody Therapy;antibody-dependent cell cytotoxicity;Antibody-Dependent Enhancement;Antigen Targeting;Area;arm;Basic Science;Binding;Biometry;Board Certification;cancer cell;cancer immunotherapy;Cancer Model;cell killing;Cell Proliferation;Cell-Mediated Cytolysis;Cells;Cellular biology;Cetuximab;Chemoresistance;Clinic;Clinical;Clinical Research;Clinical Trials;Clonal Expansion;Cryopreservation;Cytoplasm;cytotoxic;Data;Docking;Dose;Down-Regulation;Elements;Engineered Gene;engineered NK cell;engineered stem cells;Engineering;Epithelial ovarian cancer;ERBB2 gene;Evaluation;Exhibits;experience;extracellular;Fc Receptor;FCGR3A gene;FCGR3B gene;Generations;Goals;Grant;Gynecologic Oncologist;Human;Immunoglobulin G;Immunotherapy;improved;In Vitro;in vivo;induced pluripotent stem cell;Ink;Innate Immune System;innovation;interdisciplinary approach;ITAM;Killer Cells;leukemia/lymphoma;Leukocytes;Lymphocyte;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Membrane;Metalloproteases;Monoclonal Antibodies;Monoclonal Antibody Therapy;mouse model;Myelogenous;Natural Killer Cell Immunotherapy;Natural Killer Cells;neoplastic cell;NK Cell Activation;NK cell therapy;novel;ovarian neoplasm;patient derived xenograft model;Patients;Physicians;pre-clinical;prevent;receptor;receptor function;Recombinants;Regulation;Resistance;response;Scientist;Serous;Signal Transduction;Solid Neoplasm;Specificity;Survival Rate;Technology;Testing;Therapeutic;Therapeutic Monoclonal Antibodies;Transmembrane Domain;Trastuzumab;tumor;Tumor Antibodies;Tumor Antigens;tumor microenvironment;tumor xenograft;Woman;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Expression of recombinant Fc receptors by engineered NK cells to enhance cancer cell killing

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Aging;Diabetes;Estrogen;Genetics;Human Genome;Nutrition;Obesity;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE A number of differences exist between men and women in adipose tissue development and function, which leads to sex differences in risk, prevalence, and treatment of metabolic diseases. My studies will determine the role of genetic differences between female (XX) and male (XY) animals and cells as a contributor to sex differences in adipose tissue accumulation and function. The physiological impact of these genetic mechanisms will be further investigated to understand how adipose tissue differences drive increased metabolic disease risk in postmenopausal women.

PI_NAMEs: WIESE, CARRIE BETH (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Acceleration;adipocyte biology;Adipocytes;adiponectin;Adipose tissue;Alleles;Animals;ATAC-seq;Automobile Driving;Biology;blood glucose regulation;Blood Vessels;Body fat;Body Weight;Body Weight decreased;Calorimetry;career;Cell Physiology;Cells;Chemicals;ChIP-seq;Chromatin Structure;Complement;Development;disorder risk;dosage;Eating;energy balance;Environment;Enzymes;Epigenetic Process;experience;Fatty acid glycerol esters;Female;Foundations;Gene Deletion;Gene Dosage;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genome;Genomics;Goals;Gonadal Hormones;histone demethylase;histone methylation;Histones;Hormonal;Hormones;Human;improved;In Vitro;in vivo;Laboratories;lipid biosynthesis;Lipids;Lipolysis;Liver;Lysine;male;men;Menopause;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Mitochondria;Modeling;Molecular;mouse model;Mus;Obesity;ovarian failure;Ovarian hormone;Ovariectomy;Physiological;Physiology;Ploidies;Positioning Attribute;Postmenopause;Prevalence;Proliferating;Property;Research;Research Personnel;Resources;Risk;Role;Scientist;sex;Sex Chromosomes;Sex Differences;single-cell RNA sequencing;Skeletal Muscle;Tissues;Training;Weight Gain;Woman;X Chromosome;X Inactivation

PROJECT_TITLE: Epigenetic mechanisms underlying sex differences in obesity


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Pediatric;Prevention;Sleep Research;Substance Misuse;Underage Drinking

ORG_CITY: EUGENE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: 8. PROJECT NARRATIVE Young adults experience a confluence of major risk factors for alcohol use disorder, including exposure to stressful life events, insufficient sleep, and late sleep timing. This research will use biobehavioral approaches to generate understanding about the linkages between stressful life events, sleep duration and timing, and alcohol use in young adults, with a long-term aim of developing effective preventative interventions for alcohol use disorders.

PI_NAMEs: CASEMENT, MELYNDA D (contact)

PROGRAM_OFFICER_NAME: KUMAR, SHAILESH

PROJECT_TERMS: Acute;Adolescent and Young Adult;Affect;Age;Age Years;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;Alcohol dependence;alcohol misuse;alcohol use disorder;Alcoholism;biobehavior;Brain;Cessation of life;Characteristics;Chronic;circadian;Communities;comorbidity;Consumption;cost;deter alcohol use;Development;disability;Disease;disorder prevention;Equipment and supply inventories;Etiology;experience;Experimental Designs;experimental study;Exposure to;follow-up;Frequencies;Future;Goals;Health;high risk;high risk drinking;Hour;improved;improvement on sleep;Injury;Intervention;Laboratories;Licensing;Link;Measurement;Measures;Medial;Mediating;men;Mental Health;Mental health promotion;Modeling;modifiable risk;Monitor;Morbidity - disease rate;mortality;Neurosecretory Systems;Observational Study;Patient Self-Report;physical assault;Prefrontal Cortex;Prevention;preventive intervention;prospective;Psychologist;Psychopathology;Randomized;Recommendation;Recording of previous events;recruit;Reporting;Research;Research Design;Research Personnel;response;Rewards;Risk;Risk Factors;Sampling;Series;sexual assault;Sleep;sleep behavior;Sleep Deprivation;Sleep disturbances;sleep regulation;Stress;Stressful Event;stressor;Suicide attempt;Symptoms;System;Testing;time use;Translating;Woman;young adult

PROJECT_TITLE: Mechanisms of Risky Alcohol Use in Young Adults: Linking Sleep Duration and Timing to Reward- and Stress-Related Brain Function

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


NIH_SPENDING_CATS: Aging;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dietary Supplements;Natural Products;Nutrition;Physical Activity;Physical Injury - Accidents and Adverse Effects;Prevention;Women's Health Research

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Cocoa products, containing high concentrations of flavanols, are widely used and their health benefits have received increasing attention in the medical literature. Promising results from preclinical and clinical studies show beneficial effects of flavanols on muscle and physical performance, but no large, randomized controlled trials have tested effects of supplemental cocoa flavanols on clinically meaningful outcomes among aging adults. This study will determine whether supplemental cocoa flavanols slow age-related declines in physical performance and decrease falls and fall-related fractures (broken bones) that are major public health problems in older women and men in the U.S.

PI_NAMEs: CRANDALL, CAROLYN JANET;LEBOFF, MERYL SUSAN (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: adjudication;Adult;adverse outcome;Age;age related decline;aged;Aging;Ancillary Study;Attention;Beverages;Biogenesis;Biological Markers;Blood specimen;Body Composition;Body mass index;bone;Bone Density;Boston;cancer risk;Cardiovascular Diseases;cardiovascular disorder prevention;Center for Translational Science Activities;Cessation of life;Clinic;Clinical;Clinical Research;Clinical Sciences;Cocoa Powder;cohort;Cohort Studies;cost;cost effective;Cost efficiency;cost efficient;Data;design;Double-Blind Method;Elderly;epicatechin;Equilibrium;Ethnic Origin;Exercise;fall injury;Fall prevention;falls;Flavanol;follow-up;Forearm Fracture;Fracture;Growth;Hand Strength;Health;Health Benefit;health care service utilization;Health Personnel;Hip Fractures;Hospitalization;Hospitals;human old age (65+);improved;Injury;Intervention;Knowledge;Literature;Location;Malignant Neoplasms;Measurement;Measures;Mediating;Medical;Medical Records;men;meter;Mitochondria;Modification;Multivitamin;Muscle;Muscle function;muscle strength;Musculoskeletal;Nutrient;older adult;older men;older women;Outcome;Outcome Study;Oxidative Stress;Participant;Performance;Peripheral arterial disease;Phenotype;Physical assessment;Physical Function;Physical Performance;Physicians;Placebo Control;Placebos;Population;preclinical study;Prevention strategy;primary outcome;Primary Prevention;Prospective Studies;Public Health;Questionnaires;Race;Randomized;Randomized, Controlled Trials;Recovery;Recurrence;Reporting;Resources;Risk;Risk Reduction;sex variable;Source;Spinal Fractures;Supplementation;Testing;Thinness;translational study;United States National Institutes of Health;Visit;walking speed;Water;Woman;Women's trial;wrist fracture;young adult

PROJECT_TITLE: COcoa Supplement and Multivitamins Outcomes Study (COSMOS): Effects on Falls and Physical Performance

STUDY_SECTION: NAME

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


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Clinical Research;Health Effects of Indoor Air Pollution;Lymphatic Research;Neurosciences

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: NARRATIVE This project will examine the role of circulating microparticles and glymphatic functional changes seen associated with carbon monoxide neuropathology. Studies involve a murine model and a survey of blood samples obtained from patients who are suffering acute carbon monoxide poisoning.

PI_NAMEs: THOM, STEPHEN RAYMOND (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute;adaptive immune response;Adherence;adverse outcome;Animal Model;Animals;Antioxidants;aquaporin 4;Astrocytes;Biochemical;biological adaptation to stress;Blood;Blood Circulation;Blood specimen;Blood Vessels;Brain;Brain Injuries;Carbon Monoxide;Carbon Monoxide Poisoning;Carboxyhemoglobin;Cells;cerebral microvasculature;Cerebrospinal Fluid;Cerebrovascular system;Cerebrum;Cessation of life;Data;Demyelinations;Diameter;Dose;Event;Excision;Exhibits;Fluorescence Microscopy;Functional disorder;Glial Fibrillary Acidic Protein;glymphatic dysfunction;glymphatic flow;glymphatic function;glymphatic system;Goals;Hospitals;Hypoxia;Image;Immune Tolerance;Impaired cognition;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Infusion procedures;Injections;Injury;Knockout Mice;Lead;Liquid substance;Lymphatic;Magnetic Resonance Imaging;Mediating;meter;Methods;minimally invasive;mitochondrial dysfunction;Modification;Morbidity - disease rate;motor impairment;mouse model;Mus;Myelin Basic Proteins;Neuroglia;neuroinflammation;Neurologic;Neurologic Deficit;neuropathology;Neutropenia;neutrophil;Neutrophil Activation;nitrosative stress;novel;Oxidative Stress;p65;particle;Pathologic;Pathway interactions;Patients;Peptide Hydrolases;Periodicity;Peroxidases;Play;Poison;Poisoning;Process;Production;Resistance;response;Role;Stream;Stress;Surveys;Survivors;System;Thrombospondin 1;transmission process;Vesicle;Vestibular dysfunction;Visit;wasting;water channel;white matter change

PROJECT_TITLE: Inflammatory changes and glymphatic dysfunction in carbon monoxide neuropathology

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_NAME: COALITION FOR NATIONAL TRAUMA RESEARCH

PHR: Program Director/Principal Investigator: LaGrone, Lacey N. Project Narrative The Design for Implementation: The Future of Trauma Research and Clinical Guidance conference series will facilitate alignment of stakeholders in the definition, and early execution, of next steps toward an ideal future state for the evidence-based care of the injured patient. The burden of injury is high, and the current variability in outcomes unacceptable: 47% of deaths among Americans ages 1-46 are due to injury, and a patient is twice as likely to die at the worst performing U.S. trauma center as compared to the best. This dissemination and implementation science initiative, in collaboration with the Coalition for National Trauma Research (CNTR), will increase the rapidity, equity, and effectiveness with which healthcare interventions and guidance inform excellence without exception in the care of the injured patient. Page Continuation Format Page

PI_NAMEs: LAGRONE, LACEY  (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Genetics;Hematology;Infectious Diseases;Lung;Rare Diseases;Sepsis

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Acute lung injury (ALI) has high mortality because of edema resulting from pulmonary vascular endothelium dysfunction and currently there is no specific treatment for this disease. Healthy endothelial cells prevent edema formation through expression of receptor tyrosine kinase Tie2 and vascular endothelial (VE)-cadherin (VE-cad) to maintain blood vessel barrier integrity. The present investigation will determine how expression of the transcription factor Elf2 in endothelial cells induces the expression of Tie2 and VE-cad needed to repair the injured blood vessel endothelial barrier.

PI_NAMEs: TIRUPPATHI, CHINNASWAMY  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Acute Lung Injury;Agonist;Azacitidine;Binding;Binding Proteins;Biochemical;Blood Vessels;cadherin 5;Calcium;Calcium Signaling;Calmodulin;Cell Nucleus;Complex;CpG dinucleotide;Data;demethylation;derepression;Disease;Dissociation;DNA;DNA Methyltransferase Inhibitor;DNA Modification Methylases;DNMT3B gene;Edema;Endothelial Cells;endothelial repair;Endothelium;Epigenetic Process;G-Protein-Coupled Receptors;Gene Expression;gene repression;Genes;Genetic Transcription;genome wide methylation;Goals;Homeostasis;Hypermethylation;imaging approach;Inflammatory;injury and repair;Investigation;Knock-out;Knockout Mice;Lung;lung injury;lung microvascular endothelial cells;lung repair;Mediating;Methyl-CpG-Binding Protein 2;Methylation;Modeling;Molecular;mortality;mouse model;Mus;novel;Nucleic Acid Regulatory Sequences;Oranges;PAR-1 Receptor;Phosphorylation;Phosphotransferases;Predisposition;prevent;programs;promoter;Promoter Regions;receptor expression;Receptor Protein-Tyrosine Kinases;Regulation;repaired;Repression;Resolution;response;restoration;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Seminal;Sepsis;septic patients;Signal Induction;Signal Transduction;Testing;therapeutic target;Thrombin;TIE-2 Receptor;TLR4 gene;transcription factor;Transferase;vascular endothelial cadherin-2;vascular endothelial dysfunction;Vascular Permeabilities

PROJECT_TITLE: Transcription Factor Elf2 Signals Resolution of Lung Injury

STUDY_SECTION: RIBT

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