NIH_SPENDING_CATS: Neurodegenerative

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE The directed movement of proteins and membranes between different cellular locations is a fundamental process required for the proper functioning of all eukaryotic cells. Many diseases including cancer, neurodegenerative disorders, diabetes, and immune dysfunction can be caused by intracellular protein transport defects. The proposed research will determine how membrane trafficking pathways are appropriately regulated, enhancing our fundamental understanding of this process, which should facilitate the future identification of therapeutic targets for disease intervention.

PI_NAMEs: AUDHYA, ANJON  (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Animals;Biochemistry;Biogenesis;Biological Models;Caenorhabditis elegans;Cell Differentiation process;Cell Proliferation;Cells;Cellular biology;Complex;Cytoplasm;Defect;Diabetes Mellitus;Diffusion;Disease;Endoplasmic Reticulum;Endosomes;Eukaryotic Cell;fusion gene;Future;Genetic;Goals;Golgi Apparatus;Homeostasis;Image;Immune System Diseases;insight;Intervention;Intracellular Membranes;intracellular protein transport;Laboratories;Link;Lipids;Location;Lysosomes;Malignant Neoplasms;Mediating;Membrane;Methodology;Molecular;Movement;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Organelles;Pathway interactions;Play;Process;protein degradation;Protein Sortings;protein transport;Proteins;Receptor Signaling;Regulation;Research;Resolution;Sorting;structural biology;System;therapeutic target;trafficking;Transmembrane Transport;Tumor Suppression;Vesicle;Work

PROJECT_TITLE: Molecular mechanisms that regulate vesicle formation and transport

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


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: LA JOLLA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative The following proposal seeks to illuminate the underlying cell-type specific molecular mechanisms regulating the pathogenesis of heart failure. Results from these studies will identify the affected cell-types during heart failure, reveal the molecular mechanisms directing their pathologic outcomes and provide insight into developing precise cardiac diagnostics and therapies that are tailored to affected cell-types, thus optimizing therapeutic efficacy for treating heart failure.

PI_NAMEs: CHI, NEIL C (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Address;Affect;ATAC-seq;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular Models;Cardiovascular system;cell behavior;Cell Lineage;Cell Maintenance;Cell Physiology;cell type;Cells;Chromatin;Circulation;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Data;Diagnostic;EFRAC;Endothelium;Enhancers;epigenomics;Fibroblasts;Gene Expression;Gene Expression Profile;gene function;gene regulatory network;Genetic;Genetic Transcription;genetic variant;genome editing;Genomics;Heart;Heart Diseases;Heart failure;heart function;Homeostasis;Human;human pluripotent stem cell;in vivo;individualized medicine;insight;Letters;Mediating;Modeling;Molecular;Morbidity - disease rate;mortality;multidisciplinary;Nuclear;Outcome;Pathogenesis;Pathologic;Patients;Performance;Physicians;programs;promoter;Regulator Genes;Regulatory Element;response;Scientist;single cell sequencing;Smooth Muscle Myocytes;stem cells;Technology;Tissue Sample;Tissues;transcriptome sequencing;Treatment Efficacy;Untranslated RNA;validation studies;Ventricular

PROJECT_TITLE: Cardiac Lineage-Specific Molecular Mechanisms of Heart Failure

STUDY_SECTION: CCHF

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


ADMINISTERING_IC: DA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Drug Abuse (NIDA only);Genetics;Neurosciences;Nutrition;Obesity;Opioid Misuse and Addiction;Opioids;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Precision Medicine;Preterm, Low Birth Weight and Health of the Newborn;Substance Misuse;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: TUFTS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative: Neonatal abstinence syndrome (NAS) is a public health priority that remains difficult to diagnose and manage due to the lack of understanding of biological mechanisms underlying neonatal drug withdrawal. Utilizing a non-invasive salivary platform, the current proposal seeks to understand feeding difficulty and hyperphagia often seen in neonates with severe withdrawal and identify sex-specific expression of reward and inflammatory genes that may predispose these neonates to excessive weight gain and subsequent cardiometabolic disorders. The molecular approach and objective evidence from this study may identify at-risk neonates and enable personalized strategies that supplant subjective measures in the current treatment paradigm.

PI_NAMEs: YEN, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: WU, DA-YU

PROJECT_TERMS: 1 year old;Acute;Address;Adverse effects;Age;animal data;Behavior;Behavioral;Binding;Biological;Biological Markers;Birth;Body mass index;Brain;Cardiometabolic Disease;cardiometabolic risk;Cardiovascular Diseases;career;CCL2 gene;Cells;Child;Clinical;cost;Data;Development;Diagnosis;diagnostic assay;differential expression;Dopamine;Dopamine Receptor;DRD2 gene;drug withdrawal;Energy Intake;excessive weight gain;feeding;Female;fetal opioid exposure;Funding;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Growth;Head circumference;Health;High Density Lipoprotein Cholesterol;Hospitalization;Hospitals;Hyperphagia;IL6 gene;Immune;immunoregulation;improved;Infant;Inflammation;Inflammatory;inflammatory modulation;Interdisciplinary Study;Knowledge;Laboratories;Length;Life;Lipids;low density lipoprotein triglyceride;male;Measures;Medical;Mentored Clinical Scientist Development Program;Metabolic;Metabolic Diseases;Microglia;Molecular;Molecular Analysis;Monitor;Multicenter Trials;Nature;Neonatal;Neonatal Abstinence Syndrome;neonatal brain;neonate;neurogenesis;novel diagnostics;Nutritional;Opiate Addiction;Opioid;opioid exposure;Outcome;Pathway interactions;personalized care;personalized medicine;personalized strategies;Pharmacotherapy;Phenotype;Pilot Projects;Population;precision medicine;preclinical study;prenatal;Prevention strategy;public health priorities;recruit;Regulation;Research;Rewards;Risk;risk stratification;Saliva;saliva sample;Salivary;salivary gene;Serum;sex;Sex Distribution;sexual dimorphism;Signal Transduction;Techniques;Testing;TLR4 gene;tool;transcriptomics;Translating;treatment strategy;Up-Regulation;Visit;Weight;Withdrawal;women versus men;Women's Health

PROJECT_TITLE: Sex-specific Impact of Prenatal Opioids on Brain Reward Signaling and Neonatal Feeding Regulation

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: GM

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Princeton

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: PROJECT NARRATIVE It is becoming clear that many cellular components are localized to non-membrane-bound intracellular compartments and this organization is crucial for functions including molecular processing, storage, signaling, and metabolism. Dysfunctions in the organization of non-membrane-bound compartments are implicated in human diseases including cancer and amyotrophic lateral sclerosis (ALS). Our study will reveal general principles governing the assembly, internal properties, and structural integration of non-membrane-bound compartments within cells, with impacts on our understanding of their roles in health and disease.

PI_NAMEs: JONIKAS, MARTIN CASIMIR;WINGREEN, NED S (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Activase;Algae;Amyotrophic Lateral Sclerosis;Architecture;Back;Binding;Binding Sites;Biochemical Process;Biological;biological adaptation to stress;Biological Models;Biology;biophysical model;Biophysical Process;Carbon Dioxide;carbon fixation;Cell Physiology;Cells;Cellular Structures;Chlamydomonas;Chlamydomonas reinhardtii;Chloroplasts;Collaborations;Coupling;Cryo-electron tomography;Cues;Data;Disease;Energy-Generating Resources;Engineering;Ensure;Enzymes;Equilibrium;Exclusion;Experimental Models;experimental study;flexibility;Fluorescence Recovery After Photobleaching;Free Energy;Functional disorder;Gene Expression;Gene Modified;Genetic Materials;Health;Holoenzymes;human disease;Image;In Vitro;in vivo;Individual;interdisciplinary approach;Learning;liquid dynamics;Liquid substance;Location;Magic;Malignant Neoplasms;Measurement;Mediating;Membrane;Metabolism;Microscopic;model organism;Modeling;Molecular;molecular dynamics;Multienzyme Complexes;Mutation;Nature;Organelles;Phase;Physical condensation;physical property;Physiological Processes;Positioning Attribute;Process;Property;Proteins;recruit;Regulation;repaired;response;Ribosomes;Ribulose-Bisphosphate Carboxylase;RNA;Role;sample fixation;self assembly;Signal Transduction;Source;Specificity;Starch;stoichiometry;Structure;System;theories;Thylakoids;Variant;Visualization

PROJECT_TITLE: Learning principles from the pyrenoid, a phase-separated organelle

STUDY_SECTION: MABS

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative Changes in methionine levels generate remarkable responses in cells and organisms. Methionine affects cancer cell proliferation rates as well as longevity of animals. Understanding the molecular pathways that integrate methionine metabolism with other cellular functions promises new therapeutic strategies for treatment of age-related disorders. This proposal aims to development molecular insight into a fundamental biological process with great potential for therapeutic exploitation.

PI_NAMEs: KAISER, PETER  (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Affect;age-related disease;Animals;Biochemistry;Biological Process;cancer cell;cancer therapy;Catalytic Domain;Cell Cycle;Cell Cycle Regulation;Cell Line;Cell Physiology;Cell Proliferation;Cells;Communication;Complex;Cues;demethylation;Development;Event;experimental study;F-Box Proteins;Funding;Goals;insight;Link;Longevity;Mammalian Cell;Mediating;Messenger RNA;Metabolic;Methionine;Methionine Metabolism Pathway;Methylation;Modeling;Molecular;mRNA capping;National Institute of General Medical Sciences;novel therapeutic intervention;Organism;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Physiology;preference;programs;Protein phosphatase;Proteomics;Reader;Regulation;Research;response;RNA;RNA Caps;Role;sensor;Signal Transduction;System;Therapeutic;tool;Transcript;Translating;transmission process;treatment strategy;Ubiquitin;ubiquitin ligase;Work;Yeast Model System;Yeasts

PROJECT_TITLE: Ubiquitin and Metabolite Signaling

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Brain Disorders;Genetics;Huntington's Disease;Lymphatic Research;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative Using a mouse model of Huntington’s disease (HD) that permits ~50% lowering of mutant Huntingtin, we found that pre-symptomatic lowering provided greater benefit than later Huntingtin lowering, however, for several HD model symptoms (including motor symptoms) this benefit was attenuated in older mice. In this project, we will examine if a greater level of mutant Huntingtin lowering can extend the beneficial effects of early Huntingtin lowering in older mice. We will also characterize two potential therapeutic targets, DNA damage repair and neuroinflammation, to determine if their activities correlate with either mutant Huntingtin levels or HD model phenotypes.

PI_NAMEs: ZEITLIN, SCOTT  (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: 20q;Actins;Affect;Age Months;age related;age related decline;aged;Aging;aging brain;Alleles;Antisense Oligonucleotides;Astrocytosis;Attenuated;autosome;Behavioral;behavioral phenotyping;Brain;Brain region;Cell Nucleus;Cell Physiology;Cognitive;cohort;Corpus striatum structure;cytokine;Deep Cervical Lymph Node;Disease;disease model;Disease Progression;DNA Damage;DNA Repair;efficacy testing;Elements;Encephalitis;Future;gain of function;Gene Expression;Genes;genetic signature;Gliosis;Huntington Disease;Huntington gene;Impairment;Inflammasome;insight;Introns;Isopropyl Thiogalactoside;Kinetics;knock-down;Knock-in;Lac Repressors;Ligation;Long-Term Effects;lymphatic drainage;Lymphatic function;Measures;Meningeal lymphatic system;MicroRNAs;Modeling;Monitor;Motor;motor symptom;mouse model;Mus;mutant;Mutation;Neurodegenerative Disorders;neuroinflammation;neuropathology;Nuclear Inclusion;old mice;Onset of illness;Outcome;oxidative DNA damage;Pathogenesis;Pathway interactions;Phase III Clinical Trials;Phenotype;Physiological;polyglutamine;preclinical study;promoter;Proteins;Quantitative Reverse Transcriptase PCR;repaired;Reporter;response;RNA;RNA Splicing;Safety;Single-Stranded DNA;Site;Stains;Stretching;Symptoms;System;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;Therapeutic Uses;Time;Transcript;Transcription Initiation Site;transcriptome;Transgenes;Trinucleotide Repeats;Withdrawal

PROJECT_TITLE: Understanding the mechanisms that modulate the effects of mutant Huntingtin lowering in aging Huntington's disease model mice

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: SEATTLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative While it is well-established that generation of immune responses hinges on the appropriate communication between different cells of the innate and adaptive immune system, a detailed understanding of how this crosstalk occurs in vivo is currently lacking. The proposed research will generate a better understanding of the spatial microanatomy and signaling events involved in crosstalk among innate and adaptive immune cell types involved in the development of distinct classes of adaptive immune responses to vaccines and inflammatory agonists. This will be relevant to public health because in addition to improving our fundamental grasp of the immune system, these studies will promote the development of novel vaccines and immuno-therapeutics.

PI_NAMEs: GERNER, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: 3-Dimensional;Ablation;adaptive immune response;Adaptive Immune System;adaptive immunity;Agonist;Anatomy;Antigen Presentation;Antigen-Presenting Cells;Antigens;Automobile Driving;Award;Blood;Blood Vessels;Cell Differentiation process;Cell Maturation;cell motility;cell type;Cells;Cellularity;chemokine;clinically significant;Communication;cytokine;Cytometry;Data;Dedications;Dendritic cell activation;Dendritic Cells;Dermal;Development;Drainage procedure;effector T cell;Event;follow-up;Generations;Genetic;Goals;grasp;Health;Heterogeneity;Host Defense;Human;IL2 gene;IL4 gene;imaging approach;Imaging Device;Immune;Immune response;Immune system;Immunity;Immunization;Immunotherapeutic agent;improved;in vivo;Infection;Inflammation;Inflammatory;Innate Immune System;Integrins;intercellular communication;Interleukin-12;Lead;Ligands;Location;Lymph;lymph node microenvironment;lymph nodes;Lymphatic;lymphatic drainage;Lymphoid Tissue;Mediating;Memory;Microanatomy;Modeling;Molecular;monocyte;mosaic;neutrophil;novel;novel strategies;novel vaccines;Outcome;paracrine;Peripheral;Pilot Projects;Population;Positioning Attribute;Process;Production;programs;Public Health;quantitative imaging;recruit;Regulation;Research;response;Role;Signal Transduction;Site;Skin;Source;Stimulus;T cell response;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Th2 Cells;Tissues;tool;trafficking;Vaccination;vaccine immunogenicity;Vaccines;Work

PROJECT_TITLE: The Roles of Lymphoid Tissue Microenvironments in Guiding the Immune Response

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Chronic Pain;Complementary and Integrative Health;Drug Abuse (NIDA only);Natural Products;Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative As the opioid epidemic continues to ravage across the nation with ever increasing rates due to the pandemic, we are in need more than ever of more dependable opioid substitution therapies. Mitragyna speciosa (Kratom) may be our key to developing safer opioid dependency medications through engineering the natural alkaloids within the plant, for the primary alkaloid, mitragynine, has been found to be an effective analgesic without producing an abundance of negative side effects experienced with traditional opioid substitution drugs (i.e methadone). This proposal combines methods of natural products biochemistry and protein engineering to develop mitragynine analogs that may be the answer to providing safe and effective opioid dependency medications.

PI_NAMEs: HARRIS, NATALIA  (contact)

PROGRAM_OFFICER_NAME: BABECKI, BETH

PROJECT_TERMS: Acceleration;addiction;Affect;Agonist;Alkaloids;American;Anabolism;Analgesics;analog;antagonist;Attention;Binding;Biochemical;Biochemistry;catalyst;chronic pain management;Clinical Research;Constipation;Cyclization;Dehydration;delta opioid receptor;Dependence;Derivation procedure;design;Development;Disease Management;drug discovery;Engineering;enzyme pathway;Enzyme Tests;Enzymes;Exhibits;experience;Eye;falls;flexibility;functional group;Generations;Genome;Goals;GTP-Binding Proteins;Homologous Gene;Hydroxylation;improved;Indole Alkaloids;Libraries;Life;Mammals;Medicinal Herbs;Medicinal Plants;Medicine;Mental Depression;Methadone;Methods;Methylation;Mining;Mitragyna;mitragynine pseudoindoxyl;Molecular;Monoterpenes;Morphine;mu opioid receptors;Natural Products;non-Native;novel;Opiate Addiction;Opioid;Opioid agonist;opioid epidemic;opioid overdose;Opioid Receptor;Opioid replacement therapy;Opioid Rotation;opioid use disorder;opioid withdrawal;Organism;overdose death;Pain management;pain relief;pandemic disease;Pathway interactions;Pattern;Pharmaceutical Preparations;pharmacologic;Plant alkaloid;Plants;Production;Property;Protein Engineering;Reaction;reconstitution;Recovery;Relapse;Reporting;Research;response;Route;scaffold;side effect;Signaling Protein;small molecule;Southeastern Asia;stereochemistry;Stimulant;strictosidine;structural determinants;Structure;Structure-Activity Relationship;Therapeutic;Trees;United States Food and Drug Administration;Ventilatory Depression

PROJECT_TITLE: Recovery is Achievable: Biocatalytic approaches to Diversifying Mitragynine Analogs for Opioid Substitution Therapies


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Contraception/Reproduction;Dietary Supplements;Digestive Diseases;Liver Disease;Maternal Health;Maternal Morbidity and Mortality;Nutrition;Pediatric;Pregnancy;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE This research proposal will address fundamental biological questions of iron homeostasis during pregnancy. We propose to identify the hepcidin-suppressive factor of pregnancy and define the mechanisms of adverse interaction between maternal inflammation and iron deficiency. Successful completion will transform our understanding of maternal iron regulation during pregnancy and the pathological complications of inflamed pregnancies, with important diagnostic and therapeutic implications in disorders where inflammatory conditions restrict iron and contribute to anemia.

PI_NAMEs: SANGKHAE, VEENA  (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: ACVR1 gene;Address;Adverse effects;adverse outcome;adverse pregnancy outcome;Affect;Anemia;Apoptosis;Area;Bioinformatics;Biological;Biology;Biometry;Bone Morphogenetic Proteins;California;career;career development;Cell model;Cessation of life;Clinical Sciences;Country;cytokine;Data;Developed Countries;Developing Countries;Development Plans;Developmental Biology;Diabetes Mellitus;Diagnosis;Diagnostic;Dietary Iron;Disease;Endothelial Cells;Erythrocytes;Ethics;fetal;Fetal Development;Fetal Diseases;Fetal health;Fetus;Foundations;Functional disorder;Future;global health;Goals;Grant;Health;Hepatic;Hepatocyte;hepcidin;Homeostasis;Hormones;Human;human disease;Immunology;In Vitro;in vitro Bioassay;Infection;Inflammation;Inflammatory;Institution;interest;Intervention;Intravenous;Iron;iron absorption;iron deficiency;iron metabolism;Iron Metabolism Disorders;iron supplementation;Knowledge;Liver;Los Angeles;Macrophage;malformation;Manuscripts;Maternal Health;Mediating;Mentors;Metabolism;Methodology;Mothers;mouse model;multidisciplinary;Mus;neglect;Obesity;Oral;Outcome;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peptides;Physiological;Physiology;Placenta;placental trophoblasts;Placentation;Plasma;Postdoctoral Fellow;Pregnancy;Pregnancy Complications;pregnancy disorder;Pregnant Women;Preparation;Prevalence;Process;Production;protein purification;Recycling;Regulation;Research;research and development;Research Project Grants;Research Proposals;Resources;Risk Factors;Rodent;Role;Scientist;Second Pregnancy Trimester;Signal Transduction;Signaling Protein;Source;Therapeutic;TNF gene;TNFRSF1A gene;Training;translational potential;Translational Research;trophoblast;Tumor Necrosis Factor Receptor;Ubiquitination;Universities;Virulence Factors;Writing

PROJECT_TITLE: Iron and Pregnancy: Regulatory Mechanisms and Adverse Outcomes

STUDY_SECTION: DDK

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: STONY BROOK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: PROJECT NARRATIVE The role of binding kinetics in the development of resistance to targeted drug therapy has been underexplored. This proposal will use Abl tyrosine kinase, the oncogenic driver of chronic myelogenous leukemia and target of seminal small-molecule inhibitor imatinib, as a model system to examine how mutations affect ligand association and dissociation rate. Knowledge gained from this proposal will advance our understanding of the drug dissociation process and inform the rational drug design of targeted therapeutics.

PI_NAMEs: RANGWALA, AZIZ MOHAMMEDI (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Achievement;Address;Affect;Affinity;BCR gene;bcr-abl Fusion Proteins;Binding;Binding Sites;Biochemical;Biological Assay;Biological Models;cancer cell;Cell Survival;Cellular Assay;cellular transduction;Chronic Myeloid Leukemia;Clinical;clinical efficacy;clinically relevant;combat;Crystallization;Data;Death Rate;design;Development;Disease;Dissociation;Distant;dosage;Dose;drug action;Drug Design;drug discovery;drug efficacy;Drug Kinetics;Drug Receptors;Drug resistance;Drug Targeting;effective therapy;Effectiveness;Environment;Enzymes;Equilibrium;Exhibits;experimental study;Gatekeeping;Genes;Goals;Human body;Hydrogen Bonding;Imatinib;improved;In Vitro;in vivo;Inflammatory;inhibitor;insight;interest;kinase inhibitor;Kinetics;Knowledge;leukemogenesis;Libraries;Ligand Binding;Ligands;Malignant Neoplasms;Measures;Molecular Conformation;mortality;mutant;Mutation;novel;Oncogenes;Oncogenic;Outcome;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacodynamic model;Pharmacodynamics;Pharmacologic Substance;Pharmacotherapy;Phosphotransferases;preservation;Process;Protein Family;Protein Kinase;Proteins;Proto-Oncogene Proteins c-abl;rational design;Recovery;Regimen;Relapse;Research;residence;Resistance;Resistance development;resistance mutation;Role;Schedule;Secondary to;Seminal;Series;Signal Transduction;small molecule;small molecule inhibitor;Specificity;structural determinants;success;targeted treatment;Testing;Therapeutic;therapy resistant;Time;Toxic effect;Treatment Protocols;treatment response;treatment strategy

PROJECT_TITLE: Elucidating the Role of Binding Kinetics in the Development of Abl Kinase Drug Resistance


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: This is a new application for a multidisciplinary T32 training grant in pulmonary disease which builds upon 36 years of pulmonary research training at our institution. The purpose of the program is to support the recruitment and research training of the most promising MD and PhD trainees in lung disease, establishing new pipelines of Pulmonary leaders. Our goal is to train the next generation of highly qualified, interdisciplinary research scientists able to translate new discoveries of basic science into the clinical sphere, to close health equity gaps, and to advance the prevention, diagnosis, and treatment of human lung diseases.

PI_NAMEs: INGRAM, JENNIFER L.;MURDOCH, DAVID MARTIN;PALMER, SCOTT M (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TITLE: Duke Program of Training in Pulmonary ReSearch to Promote, Engage and Retain Academic Researchers (PROSPER)


NIH_SPENDING_CATS: Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Lung;Pediatric;Primary Immunodeficiencies;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative Hermansky-Pudlak Syndrome (HPS) is a group of inherited autosomal recessive disorders caused by genetic mutations that alter the trafficking of lysosomal-related organelles/vesicles. In a subset of patients with HPS-1 and HPS-4, pulmonary fibrosis develops in the fourth or fifth decade of life, and is a major cause of morbidity and mortality. Experiments proposed in this project will define the cellular and molecular mechanisms of CHI3L1 receptor system, and whether CHI3L1 and its receptor systems are plausible targets to treat HPS-associated lung disease.

PI_NAMEs: ZHOU, YANG  (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Apoptosis;Attenuated;autosome;Biogenesis;Biology;Blood Platelets;Cell Death;cell injury;cell motility;cell type;Cells;CHI3L1 gene;Chitinase;comparison control;Complex;Cytoplasmic Granules;Defect;Deposition;Development;Disease;Disease susceptibility;DNA Sequence Alteration;Ear;effective therapy;Epithelial Cells;experimental study;Fibroblasts;Fibrosis;fMet-Leu-Phe receptor;Galectin 3;Genes;Hemorrhage;Hermanski-Pudlak Syndrome;Human;idiopathic pulmonary fibrosis;Impairment;In Vitro;in vivo;indium-bleomycin;Individual;Inherited;injury and repair;Investigation;Laboratories;Life;Lung;Lung Diseases;Lymphoid Cell;Mediating;Melanosomes;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;Myofibroblast;neutralizing antibody;Oculocutaneous Albinism;Organelles;Pathway interactions;patient subsets;Patients;Phenotype;Pigmentation physiologic function;Predisposition;Process;Production;Proliferating;protective effect;Proteins;prototype;Pulmonary Fibrosis;receptor;Regulation;repaired;response;Role;Severity of illness;Signal Transduction;System;Testing;Th2 Cells;Therapeutic;Therapeutic Effect;therapeutic target;trafficking;Vesicle

PROJECT_TITLE: Targeting CHI3L1 and its receptors in Hermansky-Pudlak Syndrome-associated lung disease

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Hearing Loss;Neurosciences;Prevention;Rehabilitation

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Project Narrative This work addresses the difficulty that many people experience when trying to understand what someone is saying in noisy social settings where other voices compete. This difficulty is most profound in people who have hearing loss, including older people, and thus the findings have the potential to impact a large section of the population. The work explores new avenues for improving the performance of hearing aids in these common, but acoustically complex, listening situations.

PI_NAMEs: BEST, VIRGINIA ANN (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TITLE: Spatial Hearing in Speech Mixtures

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Mental Health;Neurosciences

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: PROJECT NARRATIVE: The proposed research will provide critical insight into the neural basis of selective visual attention, one of the most fundamental cognitive abilities for guiding behavior. Impairments of selective attention have devastating consequences on human health and are frequently observed, for example, in visuo- spatial hemineglect associated with stroke, and in neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Progress in understanding the neural basis of visual selective attention is a necessary step toward developing effective treatments for attentional deficits.

PI_NAMEs: FIEBELKORN, IAN C. (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Anatomy;Attention;Attention deficit hyperactivity disorder;attentional control;Attentional deficit;autism spectrum disorder;Automobile Driving;Behavior;Behavioral;behavioral study;Brain;Brain region;Code;cognitive ability;Collection;Complex;Coupling;Cues;Data;Detection;Dorsal;effective therapy;electrical microstimulation;Environment;extrastriate visual cortex;Feedback;frontal eye fields;frontal lobe;gene therapy;Glycoproteins;Goals;Health;Histologic;Human;Impairment;Influentials;Injections;insight;Ion Channel;Ion Pumps;lateral intraparietal area;Lentivirus;Light;Link;Location;Macaca;Measures;Mediating;Monkeys;neural;neural circuit;Neurodevelopmental Disorder;New York;New York City;optogenetics;Parietal;Parietal Lobe;Pathway interactions;Pattern;Persons;pharmacologic;Phase;Play;Population;Process;Rabies;Research;Resources;response;Role;selective attention;Sensory;Shapes;Stroke;Testing;theories;Virus;Visual;Visual attention;Visual Cortex;Visual Fields;visual processing;Visuospatial;With laterality

PROJECT_TITLE: The functional role of frontal and parietal feedback to visual cortex in selective visual attention

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Eye Disease and Disorders of Vision;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: CHICAGO

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE For memory disorders like Alzheimer’s Disease, not all images are created equal; based on their perceptual features, some images degrade rapidly in memory while others persist (Bainbridge et al., 2019a). The primary goal of the proposed project is to determine the mechanisms that underlie changes in neural representations from perception to memory. This research will inform the mechanisms underlying memory impairments such as Alzheimer’s Disease and aphantasia, and in turn have potential to aid in the development of effective early diagnostic tools.

PI_NAMEs: BAINBRIDGE, WILMA A. (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TERMS: Address;Alzheimer's Disease;Anterior;Behavioral;Big Data;Big Data Methods;blind;Brain;Brain region;Computer Models;crowdsourcing;Development;diagnostic tool;Dissociation;experience;Eye;Functional Magnetic Resonance Imaging;Goals;Human;Image;Imagery;Impairment;Individual;innovation;Knock-out;Knowledge;Laboratories;member;Memory;Memory Disorders;Memory impairment;memory process;mental representation;Methods;Mind;Nature;neural;neural patterning;Neurodegenerative Disorders;neuroimaging;neuromechanism;Neurons;Participant;Patients;Pattern;Perception;Population;Prevalence;Process;Psyche structure;regional difference;Research;Risk;Role;Running;Semantic memory;Semantics;Sensory;Steel;Structure;Temporal Lobe;Testing;Vision;Vision Disorders;Visual;visual imagery;visual information;visual memory;Visual Perception;Visualization;Work

PROJECT_TITLE: The neural and behavioral causes underlying differences between visual perception and memory

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Cerebrovascular;Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Digestive Diseases;Health Services;Heart Disease;Hematology;Liver Disease;Patient Safety;Prevention;Stroke

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: NARRATIVE Atrial fibrillation disproportionately impacts patients with cirrhosis, yet little is known about the comparative effectiveness and safety of oral anticoagulants (OAC), in this high-risk population. The proposed study will provide robust and timely evidence regarding the effects of specific OAC strategies in patients with cirrhosis and atrial fibrillation, to better inform clinical care and optimize OAC prescribing and stroke prevention. This work will also yield a highly flexible and generalizable infrastructure for assessing therapeutic drug effects in vulnerable patients with cirrhosis.

PI_NAMEs: SIMON, TRACEY  (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Address;Adult;Adverse event;Affect;aged;Algorithms;Anticoagulants;Anticoagulation;Ascites;Atrial Fibrillation;Benefits and Risks;Blood Coagulation Disorders;Calibration;Cause of Death;chronic liver disease;Cirrhosis;Clinical;clinical care;Clinical Trials;cohort;comparative effectiveness;comparative safety;cost;Data;Data Set;Databases;Diabetes Mellitus;Diagnosis;Dose;drug metabolism;drug testing;Effectiveness;effectiveness outcome;electronic health data;Electronic Health Record;end stage liver disease;Ensure;Epidemic;Equilibrium;Esophagus;Event;evidence base;Exclusion;fall risk;falls;flexibility;frailty;General Population;head-to-head comparison;Health Benefit;Healthcare;Healthcare Systems;Hemorrhage;Hepatic;Hepatic Encephalopathy;high dimensionality;high risk;high risk population;Impaired cognition;improved;Individual;Infrastructure;innovation;Intracranial Hemorrhages;Knowledge;Laboratories;Link;Liver;liver metabolism;Medicaid;Medicare;Methods;Microcirculation;Modeling;Morbidity - disease rate;mortality;novel;Obesity;Odds Ratio;Oral;Outcome;patient population;Patients;Peritonitis;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;phenotyping algorithm;Polypharmacy;population based;Portal Hypertension;predictive tools;Predictive Value;Prevalence;Prevention;Probability;Provider;Public Health;Randomized, Controlled Trials;recruit;Regimen;Risk;routine care;Safety;safety outcomes;Sample Size;selective prevention;Severities;Stroke;Stroke prevention;stroke risk;Subgroup;Sum;Testing;Therapeutic;Thrombocytopenia;Thrombosis;Time;Uncertainty;Vulnerable Populations;Warfarin;Work

PROJECT_TITLE: The Comparative Effectiveness and Safety of Oral Anticoagulants in Patients with Cirrhosis and Atrial Fibrillation

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Neurosciences;Pediatric

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE  This project will be the first to longitudinally examine the brain basis of preschool language development in typical children and late talkers. Children with language delay are at risk for a host of later academic and socio- emotional problems, but we do not have good predictive models of who will have negative outcomes. Elucidating the drivers of development has implications for the screening of language delay with objective biomarkers to mechanistically inform early intervention.

PI_NAMEs: BOOTH, JAMES R (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: 4 year old;6 year old;8 year old;Age;age difference;behavior measurement;Behavioral;Biological Markers;Brain;Child;Code;cohort;Data;Development;Diffusion Magnetic Resonance Imaging;Dimensions;Dorsal;dorsal visual stream;Early Intervention;elementary school;Emotional;Experimental Designs;Formulation;Future;Individual Differences;Inferior;innovation;interest;Intervention;Judgment;Language;Language Delays;Language Development;Language Development Disorders;Lead;Learning;Magnetic Resonance Imaging;Measures;Modeling;Morphology;multimodal neuroimaging;neural;Neurocognitive;neuroimaging;novel;Nursery Schools;open data;Outcome;Pathway interactions;phonology;power analysis;predictive marker;predictive modeling;Publishing;Research;Research Support;Rest;Retrospective Studies;Risk;Role;Sampling;screening;semantic processing;Semantics;skills;Speech;Standardization;Steam;Stream;structural imaging;Structure;Testing;theories;Time;tractography;ventral visual stream;Vocabulary;white matter;Work

PROJECT_TITLE: Neurolinguistic development in 4 to 8 year-old late talkers with language delay


NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Secretory diarrhea remains a leading cause of mortality and morbidity among children worldwide with limited treatment options. This proposal employs rotavirus, the most common cause of fatal infectious diarrhea, to investigate the role of the volume-regulated anion channel in mediating secretory activity in the intestinal epithelium. This will unveil novel signaling pathways in the epithelium and identify potential targets for anti- diarrheal therapeutics, contributing to the NIH’s mission to develop fundamental knowledge and apply it to reduce the burden of disease.

PI_NAMEs: GEBERT, JOHN THOMAS (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Ablation;Adenosine Diphosphate;Age;Anions;Antidiarrheals;Biological Assay;Biosensor;burden of illness;Calcium;Calcium Oscillations;Calcium Signaling;Cells;Child;clinically relevant;CRISPR/Cas technology;Data;Diarrhea;Discipline;Dysentery;Enterocytes;Epithelial Cells;Epithelium;Equilibrium;Event;Fluids and Secretions;Frequencies;Gastrointestinal tract structure;Genes;Genetic;Health;Homeostasis;Human;Image;in vivo;Infection;insight;intercellular communication;intestinal epithelium;Intestines;Ions;knock-down;Knock-out;Knowledge;Life;Mediating;Mission;Morbidity - disease rate;mortality;mouse model;Mus;new therapeutic target;Nonstructural Protein;novel;optogenetics;Organoids;Paracrine Communication;Pathogenesis;pathogenic virus;Pathologic Processes;Pathway interactions;pharmacologic;Phenotype;Physiologic pulse;Play;Protein Kinase;Proteins;purinoceptor P2Y1;Recombinants;Regulation;Research;rho;Rho-associated kinase;Role;Rotavirus;Rotavirus Infections;Severities;Signal Pathway;Signal Transduction;Signaling Molecule;small hairpin RNA;stressor;Swelling;targeted treatment;Testing;Therapeutic;tool;United States National Institutes of Health;Variant;Viral;Work

PROJECT_TITLE: The volume-regulated anion channel as a regulator of secretory activity in the intestinal epithelium


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Genetics

ORG_NAME: ALTIUS INSTITUTE FOR BIOMEDICAL SCIENCES

PHR: Project Narrative: Cells in the same tissue can express the exact same gene at different levels, and these deviant differences increase with age. Increased cell-to-cell variation in gene expression is a conserved age-related phenomenon with unknown causes. In this project I will determine what causes gene expression variation to increase with age using C. elegans and human tissue cultures.

PI_NAMEs: BURNAEVSKIY, NIKOLAY  (contact)

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: Address;Adult;Age;age difference;age related;Aging;aging related;Alleles;Animals;autosome;Biological Models;Caenorhabditis elegans;Cell Communication;Cell Culture Techniques;cell type;Cells;Chromosomes;Coculture Techniques;cohort;Communication;Controlled Environment;Deterioration;deviant;Diploidy;dosage;Event;experimental study;Fibroblasts;Gene Expression;gene expression variation;Gene Proteins;Genes;Genetic Transcription;Genome;Genome engineering;Gerontology;Global Change;Health;Homeostasis;Human;human tissue;in vivo;Individual;individual response;Intestines;juvenile animal;Knowledge;large datasets;Lead;Learning;life span;Mammalian Cell;Mammals;Measures;Messenger RNA;Methods;Muscle;Organ;Organism;Pathway interactions;Pattern;Phase;Physiological;Polyploidy;Population;Prevalence;Production;promoter;Proteins;Quantitative Microscopy;Reporter;Reporter Genes;Reproducibility;Resistance;response;RNA;senescence;senescent cell;single cell analysis;single-cell RNA sequencing;Sister;skills;Somatic Mutation;stoichiometry;Stress;Techniques;Testing;tissue culture;Tissues;Training;Variant;young adult

PROJECT_TITLE: Discriminating between causes of age-related variegated gene expression

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE This project will advance understanding of the biological mechanisms by which the specific microRNA, miR- 219a-5p, functions as a novel anabolic (e.g. bone forming) agent in bone metabolism. This knowledge could potentially lead to novel clinical treatments using miR-219a-5p mimics as a molecular tool to enhance bone formation in vivo, during both aging or following a fracture.

PI_NAMEs: MONROE, DAVID G (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: 3' Untranslated Regions;Acceleration;Adult;Affect;Age;Aging;aging process;antagonist;Biological;Biology;bone;bone cell;Bone Formation Stimulation;bone fracture repair;bone loss;bone mass;bone metabolism;bone preservation;Bone remodeling;Cell Lineage;Cell Physiology;Cells;Clinical;clinical development;Clinical Treatment;combat;Data;dentin matrix protein 1;Development;effective intervention;Elderly;Exhibits;experimental study;Fracture;fragility fracture;Genes;Goals;Health;Homeostasis;Impairment;improved;In Vitro;in vivo;inhibitor;insight;Knowledge;Mesenchymal Stem Cells;microRNA delivery;MicroRNAs;Molecular;mouse model;Mus;Mutation;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Orphan;osteoblast differentiation;Osteoblasts;Osteocytes;Osteogenesis;osteogenic;Osteoporosis;Osteoporotic;Pathway Analysis;Pathway interactions;Patients;Pattern;Physiological;Play;Population;prevent;Process;Publications;receptor;Receptor Down-Regulation;receptor downregulation;Receptor Inhibition;Regulation;Retinoic Acid Receptor;Risk;Role;skeletal;societal costs;Tissues;tool;transcription factor;Transfection;Work

PROJECT_TITLE: The Role of miR-219a-5p in Bone Metabolism

STUDY_SECTION: SBSR

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


ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: We have discovered that an innate immune signaling pathway, mediated by the cGAS and STING proteins, is necessary to elicit natural killer cells to reject tumors, and that the two proteins act in different cells: cGAS in the tumor cells and STING in non-tumor cells. Our results suggest that cGAMP, an intermediary molecule that is made by cGAS and activates STING, is made in the tumor cells and transferred to other cells to induce the response, and we have identified transporter molecules that may be responsible for transfer of cGAMP from cell to cell. We propose to investigate the role of the cGAS-STING pathway, cGAMP transfer and the transporters we have discovered, in T and NK cell responses to cancer and viral infections in vivo. 1

PI_NAMEs: RAULET, DAVID H (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Alleles;anti-tumor immune response;Anti-viral Response;Antigen-Presenting Cells;Antitumor Response;Binding;Bone Marrow;cancer cell;cancer immunotherapy;Cancer Model;cell transformation;Cells;Chimera organism;conditional knockout;Cre driver;CRISPR interference;Critical Pathways;cytokine;Data;Data Analyses;Defect;Dendritic Cells;Dinucleoside Phosphates;DNA;DNA biosynthesis;DNA Viruses;Enzymes;Event;Failure;genetic approach;Genetic Engineering;Genetic Transcription;Genetically Engineered Mouse;genome-wide;Graft Rejection;Herpesviridae;Immune;immune activation;Immune response;Immune signaling;In Vitro;in vivo;Infection;inhibitor;Injections;intercellular communication;Interferon Type I;Interferons;Investigation;Knockout Mice;Macrophage;Malignant Neoplasms;Mammalian Cell;Mediating;Mediator;Membrane Transport Proteins;Modeling;Mus;Natural Killer Cells;Neoplasm Transplantation;neoplastic cell;neutrophil;NK Cell Activation;novel;novel strategies;pathogen;Pathway interactions;Periodicity;prevent;Process;Production;Productivity;Proteins;receptor;Research;response;Role;Series;Shapes;Signal Pathway;Signal Transduction;Site;SLC19A1 gene;small molecule;Stimulator of Interferon Genes;T cell response;T-Lymphocyte;Testing;treatment response;tumor;tumor DNA;tumor microenvironment;Viral;Viral Cancer;viral DNA;Virus;Virus Diseases

PROJECT_TITLE: STING-dependent activation of Natural Killer cells by viral and tumor DNA


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: PORTLAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Narrative This project aims to unravel the mechanisms of impaired walking automaticity in PD in order to develop, in the long term, more effective rehabilitation interventions or pharmacological trials to restore gait automaticity during normal daily activities. Gait automaticity, or the ability to multitask while walking, is a critical functional skill that may be improved with the addition of appropriate rehabilitation, such as cueing on top of the standard pharmacological treatment with levodopa. Our outcomes, mobile imaging (fNIRS) and inertial gait measures in the laboratory will elucidate the mechanisms underlying walking automaticity deficits in people with PD.

PI_NAMEs: MANCINI, MARTINA  (contact)

PROGRAM_OFFICER_NAME: MARDEN, SUSAN F

PROJECT_TERMS: active control group;Affect;Age;Area;Attention;Basal Ganglia;Brain;Cerebral cortex;Characteristics;chronic neurologic disease;Clinical Trials;cognitive ability;cognitive function;cognitive reserve;Compensation;Complex;Cues;Dependence;Development;Devices;Dopamine;Elderly;Equilibrium;Executive Dysfunction;executive function;falls;Feedback;Floor;frontal lobe;functional near infrared spectroscopy;Future;Gait;Gait abnormality;Gait speed;Goals;Healthcare Systems;Home;Image;Impaired cognition;Impairment;improved;innovation;Intake;Intervention;Laboratories;Learning;Levodopa;Life;locomotor control;Malignant Neoplasms;Measures;Memory;Methods;Mobility disability;Monitor;Motor;Motor Cortex;motor learning;Movement;Multiple Sclerosis;multitask;Nervous System;novel;Occipital lobe;Outcome;Parkinson Disease;Participant;Pattern;Peripheral Nervous System Diseases;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Physiological;Population;Prefrontal Cortex;Quality of life;Randomized;Rehabilitation therapy;Resources;Risk;Route;secondary analysis;sensor;Sensory;sensory cortex;skills;Speed;Survivors;System;Tactile;tactile stimulation;Techniques;Technology;Testing;Time;Translating;Traumatic Brain Injury;user-friendly;Visuospatial;Walking;walking performance;walking speed;wearable device;wearable sensor technology;wireless;Wireless Technology;Wrist

PROJECT_TITLE: Cortical correlates of gait in Parkinson's disease: impact of medication and cueing

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Natural Products

ORG_CITY: WACO

ORG_NAME: BAYLOR UNIVERSITY

PHR: Public Relevance Statement The proposed novel strategy for how the synthesis of natural products is approached will accelerate their exploration as new avenues for small molecule intervention against cancers of the brain and breast, Alzheimer’s, inflammation, and both cardiovascular and infectious disease. The structure-activity relationships derived from biological studies of simplified derivatives identified in route to the targeted natural products through our approach, along with derived cellular probes, will lead to identification of novel therapeutic targets impacting the treatment of human disease. The identification of novel small molecule-protein interactions is critical for the development of the next generation of human therapeutics and the proposed research will contribute significantly to this arena.

PI_NAMEs: ROMO, DANIEL  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acceleration;Alzheimer's Disease;analog;Bacterial Infections;bioactive natural products;Biological;Biology;Cardiovascular Diseases;Cardiovascular system;Cells;Cellular biology;cellular targeting;chemical genetics;Chemicals;Communicable Diseases;Data Collection;design;Development;Goals;Harvest;Health;Human;human disease;Inflammation;innovation;Intervention;Lead;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant Neoplasms;Medicine;Molecular;Natural Products;new therapeutic target;next generation;novel;novel strategies;novel therapeutics;Oxidation-Reduction;pharmacophore;Proteins;Research;Route;small molecule;Structure-Activity Relationship;Therapeutic;Therapeutic Intervention;therapeutic lead compound

PROJECT_TITLE: Pharmacophore-Directed  Retrosynthesis Applied to Bioactive Natural Products Informing Mechanism of Action Studies

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


NIH_SPENDING_CATS: Cancer;Genetics

ORG_DEPT: PATHOLOGY

PHR: Project Narrative One of the most frequently mutated genes in human cancer is the TP53 gene. We have found that the mutant form of p53 promotes tumor development by suppressing the innate immune response pathway. We seek to understand how this occurs and to try various strategies to reactivate this pathway.

PI_NAMEs: MARTINEZ, LUIS ALFONSO (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Alleles;Apoptosis;Binding;cancer cell;Cells;Chromosomal Instability;Chromosomal Loss;Chronic;Complex;Cytoplasm;daughter cell;Development;DNA;DNA Binding Domain;DNA Damage;Genes;Genetic;Genetic Transcription;Genome;Genomic Instability;Human;Immune;Immune Evasion;Immune signaling;Immune system;Innate Immune Response;IRF3 gene;Lesion;Malignant Neoplasms;Missense Mutation;mutant;Mutate;Mutation;Neoplasm Metastasis;novel;Oncogenes;Oncogenic;paracrine;Paracrine Communication;Pathway interactions;Play;Point Mutation;prevent;Proteins;Reporting;response;Role;Signal Pathway;Signal Transduction;Stimulator of Interferon Genes;TBK1 gene;Therapeutic;therapeutic target;TP53 gene;triple-negative invasive breast carcinoma;tumor;Tumor Promotion;Tumor Suppression;Tumor Suppressor Genes

PROJECT_TITLE: Oncogenic functions of mutant p53

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Cost Effectiveness Research;Digestive Diseases;Pediatric;Pediatric Cancer;Prevention;Radiation Oncology;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Subsequent malignant neoplasms are the leading cause of mortality in childhood, adolescent and young adult (AYA) cancer survivors. In particular, the risk of colorectal cancer is elevated in this population, and it is critical to identify risk factors associated with colorectal cancer development in order to identify high-risk survivors for screening and prevention. The proposed study pools individual participant data on 51,309 survivors from 8 international childhood and AYA cohorts in order to comprehensively examine risk factors of, and mortality after, subsequent colorectal cancer.

PI_NAMEs: HENDERSON, TARA OLIVE;MOSKOWITZ, CHAYA  (contact)

PROGRAM_OFFICER_NAME: BURNETT, ANDREA NICOLE

PROJECT_TERMS: Abdomen;Address;Adolescent and Young Adult;Aftercare;Age;Alkylating Agents;Anthracycline;Attention;Biology;Body mass index;cancer diagnosis;Cancer Survivor;cancer therapy;chemotherapy;Chemotherapy and/or radiation;Childhood;childhood cancer survivor;Cisplatin;Clinical;cohort;Cohort Studies;Colonoscopy;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;common treatment;cost effectiveness;Cost Effectiveness Analysis;Country;Data;Development;Dose;Ensure;evidence base;Exposure to;follow-up;Future;General Population;Genetic;Guidelines;high risk;Incidence;Individual;International;Investigator-Initiated Research;Knowledge;Life Style;Long-Term Survivors;Malignant Childhood Neoplasm;Malignant Neoplasms;Morbidity - disease rate;mortality;Neoplasms;novel;Outcome;Participant;Pediatric Oncology Group;Pelvis;Physical activity;Population;Premature Mortality;prevent;Prevention;Procarbazine;Prognosis;Radiation;Radiation Dose Unit;Radiation exposure;Radiation therapy;Resources;Risk;Risk Factors;Role;screening;screening guidelines;sex;Standardization;Survivors;Time;Work;young adult

PROJECT_TITLE: International Study of Subsequent Colorectal Cancer Among Survivors of Childhood, Adolescent, and Young Adult Cancers (I-SCRY)

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


NIH_SPENDING_CATS: Cardiovascular;Hypertension

ORG_CITY: MEMPHIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF TENNESSEE HEALTH SCI CTR

PHR: Project Narrative Endothelial cells regulate arterial contractility. Dysfunctional control of contractility by endothelial cells is a hallmark of several cardiovascular diseases, including hypertension, but pathological mechanisms involved are poorly understood. We will investigate the novel hypothesis that TMEM16A channels regulate arterial contractility, investigate signaling mechanisms involved and test the concept that vasodilation mediated by these proteins is dysfunctional during hypertension.

PI_NAMEs: JAGGAR, JONATHAN H (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Acetylcholine;Animal Model;Anions;Arteries;Attenuated;Biochemistry;Biosensor;Blood flow;Blood Pressure;blood pressure reduction;Blood Vessels;Calcium;Calcium Signaling;Calcium-Activated Potassium Channel;Cardiovascular Diseases;Cations;Cell Line;Cell membrane;cell type;Cell Wall;Chloride Channels;Cholinergic Agonists;Confocal Microscopy;Coupled;Coupling;Data;Electrophysiology (science);Endothelial Cells;Genetic;Genetic Models;Hypertension;Immunofluorescence Microscopy;Impairment;Ion Channel;Knock-out;Knockout Mice;Lighting;Lysine;Measures;Mediating;Membrane Potentials;Methods;Microscopy;Molecular Biology;Mus;Muscle Cells;Myography;nanoscale;Nitric Oxide;novel;Organ;patch clamp;Pathologic;Phosphotransferases;Physiological;pressure;Property;Proteins;ratiometric;Regulation;Resistance;Signal Pathway;Signal Transduction;Smooth Muscle Myocytes;Speed;Stimulus;Study models;superresolution microscopy;Surface;Systemic blood pressure;Tamoxifen;Techniques;Testing;TRP channel;two photon microscopy;two-photon;ultra high resolution;Vascular Diseases;Vasodilation;Vasodilator Agents;virtual;Western Blotting

PROJECT_TITLE: Chloride channels in endothelial cells

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Data Science;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Modern studies collect complex patient level information over serially administered tasks of a biobehavioral modality, across multiple modalities and at potentially multiple longitudinal visits. Our proposal characterizes recorded data as high-dimensional highly structured functional objects, and develops a principled statistical framework for its joint analysis. The proposed methodological framework will provide interpretation and rigorous inference from these data structures, which will help guide medical and health care decisions.

PI_NAMEs: SENTURK, DAMLA  (contact);TELESCA, DONATELLO

PROGRAM_OFFICER_NAME: WOUHIB, ABERA

PROJECT_TERMS: Age;autism biomarker;autism spectrum disorder;Behavior Therapy;Behavioral;behavioral impairment;biobehavior;Biological;Biological Markers;biomarker identification;Brain;Brain imaging;Brain region;Child;Clinical Trials;Cognitive;cognitive development;cognitive process;Communication;Communities;Complex;complex data;Data;Data Analyses;data fusion;data modalities;data modeling;Data Science;Development;Diagnosis;dimension reduction;Dimensions;Effectiveness;Electroencephalography;Exhibits;Experimental Designs;flexibility;Funding;Goals;Grant;Healthcare;Heterogeneity;high dimensionality;high risk;High-dimensional Modeling;imaging modality;Imaging technology;Impaired cognition;Impairment;individuals with autism spectrum disorder;Infant;insight;instrument;interest;Intervention Trial;Investigation;Joints;Learning;Life;Literature;longitudinal design;Longitudinal Studies;Longitudinal trends;Measures;Medical;Methodology;Modality;Modeling;Modernization;Movement;multimodal data;multimodality;Nature;Neurodevelopmental Deficit;Neurodevelopmental Disorder;novel;Patients;Performance;pharmacologic;Population;predictive marker;Process;Public Health;repetitive behavior;Research;Siblings;social;social attention;Social Behavior;social communication;Social Interaction;Statistical Data Interpretation;Statistical Methods;Structure;Techniques;Time;trend;United States National Institutes of Health;user friendly software;Visit;visual tracking

PROJECT_TITLE: Functional Data Analysis for High-Dimensional Biobehavioral Data

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Epilepsy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE A growing number of mutations in the voltage-gated sodium channel SCN8A are being identified in patients with severe epilepsy and other neurological disorders such as autism. However, the mechanisms by which these mutations lead to the observed clinical features are poorly understood, and current therapies are often inadequate. To address these gaps, we will study disease mechanisms and explore new treatment strategies using mice expressing human SCN8A mutations.

PI_NAMEs: ESCAYG, ANDREW P (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Address;anti-epileptic agents;autism spectrum disorder;Basic Science;Behavior;Behavioral;Behavioral Assay;behavioral phenotyping;Biological Assay;Biological Markers;Biophysics;Brain;Brain region;cell type;Cells;Central Nervous System;childhood epilepsy;Clinical;clinical heterogeneity;clinical phenotype;Complex;Development;Developmental Delay Disorders;Disease;disease mechanisms study;drug candidate;effective therapy;Electrophysiology (science);Epilepsy;epileptic encephalopathies;Etiology;excitatory neuron;experimental study;Face;Frequencies;Functional disorder;Future;gain of function;Gene Family;Generations;Genes;genetic approach;genetic inhibitor;Heterozygote;Hippocampus;Human;improved;In Vitro;in vivo;Individual;inhibitory neuron;Intellectual functioning disability;Interneurons;Intractable Epilepsy;Knock-in;Knock-in Mouse;Lead;loss of function;mammalian genome;Modeling;mouse model;Mus;mutant;Mutation;Nervous System Disorder;novel therapeutic intervention;Parvalbumins;Pathogenicity;Pathologic;Pathology;Patients;personalized medicine;Pharmaceutical Preparations;pharmacologic;Phenotype;Physiology;Play;preclinical study;Predisposition;premature;Preparation;Recurrence;Resistance;respiratory;response;Risk;Role;SCN8A encephalopathy;SCN8A gene;Seizures;selective expression;Severities;Slice;social deficits;Sodium Channel;Somatostatin;sudden unexpected death in epilepsy;Testing;Thalamic structure;Therapeutic;therapeutic development;therapy development;Translational Research;treatment optimization;treatment strategy;Variant;Vasoactive Intestinal Peptide;voltage

PROJECT_TITLE: SCN8A encephalopathy: disease mechanisms and treatment

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Cancer

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Centrioles are core components of centrosomes, which organise the dynamic microtubule cytoskeleton, and primary cilia, which enable many signalling pathways. Plk4-mediated centriole amplification results in tissue hyperplasia and increased susceptibility to tumorigenesis in the mouse providing a model for the supernumerary or defective centrosomes found in a high proportion of human tumors. This research will advance our understanding of cellular responses to supernumerary centrosomes and identify pathways that can be targeted for restoring centriole numbers or cell cycle regulation or for directing such cells to cell death, thereby finding translational application in the development of multiple drug strategies for cancer treatment.

PI_NAMEs: GLOVER, DAVID M (contact)

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Actins;Affect;Apoptosis;base;Brain;cancer therapy;Cell Cycle;Cell Cycle Arrest;Cell Cycle Regulation;Cell Death;cell motility;Cell Proliferation;Cell Proliferation Regulation;Cell surface;Cells;Centrioles;Centrosome;Cerebral cortex;Cilia;ciliopathy;cilium biogenesis;cohesion;Coupling;Cytokinesis;Cytoplasm;Cytoskeleton;Defect;Development;Developmental Process;Disease;Ensure;Excision;Functional disorder;Generations;Genes;genome wide screen;GTPase-Activating Proteins;Guanine Nucleotide Exchange Factors;Human;Hyperplasia;Inherited;kinetosome;knock-down;Knock-out;Lead;Length;Liquid substance;Malignant Neoplasms;Mediating;Microcephaly;Microtubule-Organizing Center;Microtubules;Mitosis;Mitotic spindle;Modeling;Mus;neoplastic cell;novel;Organelles;overexpression;p53-binding protein 1;PAK-1 kinase;Pathway interactions;permissiveness;Pharmaceutical Preparations;Phosphorylation;Physiological Processes;Pilot Projects;PLK1 gene;Predisposition;Procentriole;Prognosis;Proliferating;protein complex;Protein Kinase;Proteins;receptor;Regulation;Research;response;Role;S phase;Signal Pathway;Signal Transduction;Signaling Protein;Site;stem cell proliferation;System;Testing;Tissues;TP53 gene;translational applications;tumor;tumorigenesis;ubiquitin isopeptidase

PROJECT_TITLE: Supernumerary Centrosomes and Cell Proliferation

STUDY_SECTION: CSRS

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


NIH_SPENDING_CATS: Aging;Climate-Related Exposures and Conditions;Clinical Research;Clinical Trials and Supportive Activities;Prevention;Women's Health Research

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Men and women over the age of 65 are the most vulnerable population during severe environmental heat events, experiencing significantly worse health outcomes than any other age cohort. The global population of aged individuals is growing rapidly, resulting in an increasingly larger vulnerable population as the frequency and severity of heat waves continue to increase. While there is a vast literature detailing age-related declines in physiological responses to environmental heat stress, the significant question remains: In what specific environments does this age disparity begin to occur? Our laboratory originally developed, and has a long history of using, a unique, rigorous, and reproducible approach to identify critical environmental limits to prolonged heat exposure specific to older men and women. This research approach combines physiological and biophysical approaches to delineate safe from potentially unsafe environmental conditions for older adults from a human heat balance standpoint.

PI_NAMEs: KENNEY, W. LARRY (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Acceleration;Address;Adult;Age;Age disparity;age related;age related decline;aged;Aging;aging population;Air Movements;Aspirin;Australia;biophysical techniques;Biophysics;Blood flow;Blood Platelets;Cardiac;cardiovascular disorder prevention;climate adaptation;climate change;climate-related health;clinically relevant;clopidogrel;cohort;Communication;Cross-Sectional Studies;Data;Dose;Dryness;Environment;environmental change;Environmental Hazards;Environmental Wind;Equilibrium;European Union;Event;evidence base;experience;extreme weather;Frequencies;Goals;Health;Heat Losses;Heat Stress;Heat Waves;Human;human old age (65+);Humidity;Hydration status;Impairment;Industry;innovation;Intervention;Laboratories;Literature;men;Military Personnel;Modeling;older adult;older men;Older Population;older women;Pharmaceutical Preparations;Physiologic Thermoregulation;Physiological;Physiology;Platelet Inhibitors;Plavix;Policies;poor health outcome;Population;predicting response;Primary Prevention;Psychometrics;Recording of previous events;Reproducibility;Research;response;Risk;Safety;Secondary Prevention;Series;Severities;Skin;solar radiation;Sports;success;Sweating;Temperature;Testing;Triage;Vulnerable Populations;Woman

PROJECT_TITLE: Identification of Critical Thermal Environments for Aged Adults

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


NIH_SPENDING_CATS: Diabetes;Genetics

PHR: RELEVANCE TO PUBLIC HEALTH STATEMENT The incidence of metabolic dysfunction is rising dramatically in the US and is associated with elevated morbidity and mortality secondary to obesity, type 2 diabetes, cardiovascular disease, and certain forms of cancer. In the proposed studies we will determine the expression impact of the mitochondrial fission protein Drp1 in the regulation of metabolism and skeletal muscle mass in mice. We intend for our research to uncover novel therapeutic targets to combat metabolic dysfunction and type 2 diabetes mellitus-associated myopathy.

PI_NAMEs: ZHOU, ZHENQI  (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Adult;Aging;Animals;Architecture;Binding;Cardiovascular Diseases;Cell Respiration;Cells;Citric Acid Cycle;Clinical;combat;Complex;Confocal Microscopy;Data;Dominant-Negative Mutation;Dynamin;Electron Transport;Energy Metabolism;Enzymes;exercise training;Fatty acid glycerol esters;fatty acid metabolism;fatty acid oxidation;Functional disorder;gain of function;Gene Expression;genetic regulatory protein;glucose disposal;Glucose Intolerance;Health;Heterozygote;Impairment;In Vitro;in vivo;Incidence;Insulin;Insulin Resistance;insulin sensitivity;interest;knock-down;Knock-out;Knockout Mice;Laboratories;life span;Link;Lipids;Maintenance;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;Metabolism;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial genome;Molecular;Molecular Chaperones;Morbidity - disease rate;mortality;mouse model;Mus;Muscle;Muscle Fibers;muscle form;muscle metabolism;Muscle Mitochondria;Muscular Atrophy;Myopathy;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Organelles;Outcome;oxidation;Oxidative Phosphorylation;Phenotype;Play;Process;Proteins;Public Health;Recombinant Proteins;Regulation;Research;Research Proposals;Rodent Model;Role;Secondary to;Signal Transduction;Skeletal Muscle;Spirometry;Succinate Dehydrogenase;Tamoxifen;Testing;Time;Tissues

PROJECT_TITLE: Role of dynamin-related protein 1 in the regulation of metabolism and skeletal muscle mass

STUDY_SECTION: IPOD

STUDY_SECTION_NAME: Integrative Physiology of Obesity and Diabetes Study Section[IPOD]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Neurosciences;Nutrition;Prevention

ORG_CITY: DALLAS

ORG_DEPT: PEDIATRICS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Inflammatory bowel disease is a chronic debilitating condition affecting 3 million Americans. Its cause is not known but genetics are a risk factor, and my prior work has uncovered that cells with endocrine and neuronal properties that inhabit the gut wall play an important role in this condition. This proposal aims to characterize the role of these cell populations in chronic intestinal inflammation, which ultimately may open the door for novel therapeutic strategies.

PI_NAMEs: SIFUENTES-DOMINGUEZ, LUIS  (contact)

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: Ablation;ACTL6B gene;Advisory Committees;Affect;American;Anti-Inflammatory Agents;Attention;Basic Science;Biological Models;Calcium;Candidate Disease Gene;career;career development;CDX2 gene;Cell Compartmentation;Cell Lineage;Cells;Childhood;Chronic;Clinical Sciences;Colitis;Colon;Complex;Data;Data Analyses;Development Plans;dextran sulfate sodium induced colitis;Disease;drug development;early onset;Endocrine;Enteral;Enteric Nervous System;Enteroendocrine Cell;Environment;Environmental Exposure;Epithelium;experience;experimental study;Foundations;Functional disorder;Gastroenterology;Gene Mutation;Genes;Genetic;Genetic Diseases;Genetic Predisposition to Disease;Genetic study;genetic variant;Goals;gut inflammation;Hepatology;Homeostasis;Hormone secretion;Human;Human Genetics;Immune;immunoregulation;Impairment;In Vitro;in vivo;in vivo Model;Individual;Inflammation Mediators;Inflammatory Bowel Diseases;Innate Immune Response;interest;Interferon Activation;Interferon Type I;Interferons;Interleukin-10;intestinal epithelium;Intestines;K-Series Research Career Programs;knockout animal;LoxP-flanked allele;Mediating;Medical center;Mentors;Mentorship;Missense Mutation;Modeling;mouse model;Mus;Mutation;Nervous System;Neuroendocrine Cell;Neurons;Neurosecretory Systems;new therapeutic target;next generation sequencing;novel therapeutic intervention;nutrition;Pathogenesis;Pathogenicity;Phenotype;Play;Population;Predisposition;professor;Property;Proteins;Regulation;Reporting;Research;Research Personnel;response;Ribosomes;Risk Factors;Role;Secretory Vesicles;sensor;Signal Transduction;skill acquisition;SNAP receptor;Syndrome;Technology;Texas;Tissues;transcriptome sequencing;type I interferon receptor;Ulcerative Colitis;Universities;vesicular release;villin;Work

PROJECT_TITLE: Role of SCGN in Intestinal Immune Homeostasis

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Lung;Lung Cancer;Mental Health;Prevention;Substance Misuse;Telehealth;Tobacco;Tobacco Smoke and Health

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: PROJECT NARRATIVE Continued tobacco use among cancer survivors is a cause of second primary cancers and increased overall mortality, thus, there is an urgent need to develop novel smoking cessation interventions that particularly target cancer-specific risk factors of smoking relapse in real-time given chronic levels of high stress and unique cessation barriers in this population. We propose to develop a mindfulness-based intervention for smoking cessation tailored for cancer survivors, that delivers intervention content via smartphone application in real-time when risk of smoking relapse is high. This project will result in a highly scalable and cost-effective intervention for cancer survivors ready to be tested in a large-scale clinical trial.

PI_NAMEs: YANG, MIN-JEONG  (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: acceptability and feasibility;Acceptance Process;Acute;Address;Affect;Affective;anti-cancer research;arm;Attention;Awareness;barrier to care;Benchmarking;Breathing;Cancer Center;cancer diagnosis;Cancer Prevention Intervention;cancer recurrence;Cancer Survivor;Cancer Survivorship;cancer therapy;career;Cellular Phone;Chronic;Client satisfaction;Clinical;Clinical Trials;Cognitive;cost effective intervention;craving;Data;Development;Distress;Ecological momentary assessment;Effectiveness;efficacy testing;Elements;experience;Fatigue;Feasibility Studies;feasibility testing;Feedback;follow-up;Fright;Future;General Population;Goals;Guilt;handheld mobile device;Health;Hour;improved;Individual;innovation;Intervention;Interview;Knowledge;Link;Literature;Malignant Neoplasms;Measures;Meditation;Methodology;mHealth;mindfulness;mindfulness intervention;Mission;mortality;Nature;negative affect;novel;Outcome;Pain;Participant;Patient Self-Report;patient-level barriers;Patients;Perception;Persons;Phase;Population;portability;Preparation;primary outcome;Procedures;Process;prototype;Psychometrics;Qualitative Methods;Quality of life;Randomized;Randomized, Controlled Trials;Recording of previous events;Relapse;relapse risk;Risk;Risk Factors;Role;satisfaction;Second Primary Cancers;secondary analysis;Self-Examination;Shame;smartphone application;Smoke;Smoker;Smoking;smoking abstinence;smoking cessation;Smoking Cessation Intervention;smoking prevalence;smoking relapse;sound;standard care;Stress;Structure;Survivors;temporal measurement;Testing;Therapeutic;Time;Tobacco;tobacco abstinence;Tobacco use;Tobacco Use Cessation;Training;Treatment Cost;Work

PROJECT_TITLE: Mindfulness-based ecological momentary intervention for smoking cessation among cancer survivors

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Genetics;Human Genome;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Dysregulation of epigenetic gene regulatory mechanisms, including DNA methylation, has been linked to human neurodevelopmental disorders, intellectual disability, and craniofacial abnormalities. The TET family of DNA demethylases have also been implicated in these disorders. This proposal investigates how TET enzymes regulate neural stem cell biology and embryonic neurodevelopment. Findings from this study will enhance our understanding of the epigenetic regulation of neurodevelopment and could facilitate the identification of new therapeutic targets to improve treatment of neurodevelopmental disorders.

PI_NAMEs: MACARTHUR, IAN CAMPBELL (contact)

PROGRAM_OFFICER_NAME: KOSTER, MARANKE IRENE

PROJECT_TERMS: 4-Hydroxy-Tamoxifen;Apoptosis;Astrocytes;Biology;bisulfite sequencing;Brain;brain tissue;candidate identification;Carbon;Cell Line;Cell Maintenance;Cell Survival;Cerebral cortex;Compensation;craniofacial;Craniofacial Abnormalities;Cytosine;Data;Defect;demethylation;Development;differential expression;Dioxygenases;Disease;DNA;DNA biosynthesis;DNA Methylation;DNA Modification Process;DNMT3a;Down-Regulation;Embryo;Embryonic Development;embryonic stem cell;Enterobacteria phage P1 Cre recombinase;Enzymes;Epigenetic Process;epigenetic regulation;Etiology;Excision;Exhibits;Failure;Family;Family member;gastrulation;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genome Mappings;genome-wide;Goals;Histones;Human;improved;in vivo;inducible Cre;insight;Intellectual functioning disability;interest;Joints;Knock-out;Knowledge;Link;LoxP-flanked allele;Maintenance;Maps;Mediating;member;Mentorship;Methylation;Methyltransferase;Modeling;Modification;mouse model;Mus;Nerve Degeneration;nerve stem cell;Nervous System;nervous system development;nestin protein;neural;Neuroanatomy;neurodevelopment;Neurodevelopmental Disorder;Neurons;neuroregulation;new therapeutic target;novel;Oligodendroglia;Phenotype;Physicians;Play;Positioning Attribute;programs;Proliferating;promoter;Prosencephalon;Proteins;Recurrence;Regulator Genes;Regulatory Element;Reporting;Research;response;Role;Scientist;self-renewal;skills;stem cell biology;stem cell biomarkers;stem cell function;stem cell proliferation;Syndrome;Tamoxifen;targeted treatment;Testing;Tetanus Helper Peptide;Tissues;Training;transcriptome sequencing;transcriptomics;Transgenes;whole genome

PROJECT_TITLE: Epigenetic regulation of neural stem cell biology by Tet DNA dioxygenases

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Social Determinants of Health

ORG_CITY: COLLEGE PARK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: PROJECT NARRATIVE Little is known about the lifetime effect of Medicare on individual longevity and whether it varies across socioeconomic groups. The impact of Medicare’s introduction on completed longevity will be evaluated using new data and a novel empirical approach. Results from this study will contribute to scientific knowledge that will inform the design of health insurance programs in the US.

PI_NAMEs: YUE, DAHAI  (contact)

PROGRAM_OFFICER_NAME: CHATTERJI, MINKI

PROJECT_TERMS: Affect;Age;age group;Area;Big Data;Birth;Censuses;Characteristics;Chronic;cohort;Coronary Artery Bypass;Data;Data Aggregation;Data Set;Death Rate;Death Records;design;disabled;Education;Elderly;Eligibility Determination;Ethnic Origin;Evaluation;Gender;Genealogical Tree;Generations;geographic difference;Geographic Locations;Geography;Goals;Health;health care availability;health care service utilization;Health Insurance;Health Policy;Heterogeneity;Hospitalization;Hospitals;human old age (65+);improved;Income;Individual;individual variation;Insurance;Insurance Coverage;Interruption;Investigation;Investments;Knowledge;Life Expectancy;Link;Long-Term Effects;Longevity;Measurable;Measures;Medical;Medicare;Modeling;mortality;Mortality Decline;novel;Occupations;older adult;Operative Surgical Procedures;Outcome;Participant;Patients;Pattern;Physicians;Policies;Policy Maker;Population;population health;Preventive care;Price;Privatization;programs;Publishing;Race;Records;Reduce health disparities;Religion;Reporting;Research;Running;Series;Services;simulation;sociodemographic factors;Socioeconomic Status;socioeconomics;Subgroup;Surveys;Time;Time Series Analysis;trend;Variant;Work

PROJECT_TITLE: The Impact of Medicare on Individual Longevity: Evidence from Medicare Introduction Using Big Data

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


NIH_SPENDING_CATS: Autoimmune Disease;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Inflammatory Bowel Disease;Microbiome

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Over 3 million people in the United States have been diagnosed with inflammatory bowel disease (IBD), a chronic and incurable condition of unknown cause that carries with it significant morbidity and healthcare costs. It has been recognized that the composition of the intestinal bacteria is abnormal in IBD and this contributes to the development of disease, but the specific mechanisms by which the intestinal bacteria become abnormal and how this causes IBD are not fully known. The proposed research will explore how adenosine produced in the gastrointestinal lumen regulates intestinal inflammation through its action on the intestinal microbiota and how these host-microbe interactions can be targeted therapeutically to treat IBD.

PI_NAMEs: KAO, DANIEL JOSEPH (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: 5'-Nucleotidase;Adenosine;Amino Acids;Animals;Anti-Inflammatory Agents;Area;auxotrophy;Bacteria;bacterial metabolism;Chronic;Clinical;clinical application;Colitis;Colon;colon bacteria;Colorado;commensal microbes;Communicable Diseases;conditional knockout;Data;Development;Diagnosis;Disease;dysbiosis;Enteral;Enterobacteriaceae;Epithelial Cells;Escherichia coli;experience;extracellular;Gastroenterologist;gastrointestinal;Gastrointestinal tract structure;Genes;Germ-Free;Goals;Growth;gut inflammation;gut microbiota;Health;Health Care Costs;Homeostasis;host-microbe interactions;Human;Infection;Inflammation;Inflammatory Bowel Diseases;insight;interest;intestinal epithelium;intestinal homeostasis;Intestinal Mucosa;Intestines;Investigation;Mediating;medication administration;member;Mentors;Mentorship;Metabolic Pathway;Metabolism;metabolomics;Methods;microbial;Microbiology;microbiome;microbiome analysis;microbiota;Molecular;Morbidity - disease rate;mouse model;Mucous Membrane;Mus;mutant;next generation sequencing;novel;nucleotide metabolism;Nutrient;Nutritional;Oral Administration;Oxidative Stress;pathogen;Pathogenesis;Pattern;Persons;Physicians;pressure;Property;Publishing;purine metabolism;Purines;Research;Research Personnel;Resolution;response;Role;Salmonella;Salmonella enterica;Salmonella typhimurium;Scientist;Shapes;Signal Transduction;Stress;Symbiosis;targeted treatment;Testing;Therapeutic;Therapeutic Uses;thiopurine;Tissues;Training;transcriptomics;Translating;translational applications;treatment strategy;United States;Universities;Virulence;Work

PROJECT_TITLE: Modulation of Host-Microbe Interactions by Extracellular Purines in the Gastrointestinal Lumen


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative Opioid overdose remains one of the biggest challenges we face in public health, with over 70% of nearly 71,000 drug overdose deaths in 2019 linked to opioids and it continues to surge. To address this crisis, we need a better understanding of the fundamental reaction and adaptation of the brain in response to opioids. Our goal is to develop genetically encoded, fluorescent sensor proteins that detect opioid receptor activation downstream by monitoring secondary increases of reactive oxygen species levels that could reveal adaptation of opioid signaling in real time.

PI_NAMEs: LEE, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Acute;addiction;Addictive Behavior;Address;Analgesics;animal tissue;Animals;antinociception;Anxiety;Arrestins;Behavior;Binding Proteins;Brain;brain tissue;cell type;Cells;Chronic;Clinic;clinically relevant;Codeine;Complex;Coupling;Dependence;desensitization;design;Detection;Directed Molecular Evolution;Disease;disease phenotype;Dose;Drug Addiction;drug development;Drug Exposure;Drug Tolerance;drug withdrawal;Drug Withdrawal Symptoms;Embryo;Emotions;Engineering;Enhancers;Enterobacteria phage P1 Cre recombinase;Epidemic;Equipment;Exhibits;Face;Fentanyl;fluorescence imaging;Funding;Future;G Protein-Coupled Receptor Signaling;Goals;Green Fluorescent Proteins;GTP-Binding Proteins;Health;high throughput screening;Homologous Gene;Human;Hydrogen Peroxide;improved;In Vitro;in vivo;Injections;innovation;insight;kappa opioid receptors;kidney cell;Kinetics;Ligands;Link;Machine Learning;MAPK8 gene;Measures;Mediating;Molecular;Molecular Target;Monitor;Morphine;motivated behavior;mu opioid receptors;Mus;NADPH Oxidase;National Institute of Drug Abuse;Neurobiology;Neurodegenerative Disorders;Neuronal Plasticity;Neurons;neurotransmission;novel;Opioid;Opioid agonist;Opioid Analgesics;opioid epidemic;opioid exposure;opioid overdose;Opioid Receptor;opioid use;optogenetics;Output;overdose death;Pain;Pain management;Pathologic;Pathway interactions;Performance;peroxiredoxin;Persons;Pharmaceutical Preparations;pharmacologic;Physiological Adaptation;prevent;Production;Property;Protein Activation Pathway;Protein Engineering;Proteins;prototype;Public Health;quantum;Reaction;Reaction Time;Reactive Oxygen Species;receptor;Receptor Activation;Reporter;Research;response;Rodent Model;sensor;side effect;Signal Pathway;Signal Transduction;Site;Slice;Source;spatiotemporal;Specificity;Stress;Structure;System;targeted imaging;Technology;Time;Tissues;tool;Toxic effect;United States Dept. of Health and Human Services;Universities;Validation;Ventilatory Depression;Ventral Tegmental Area;Virus;Washington

PROJECT_TITLE: Deciphering biased agonistic activation of mu-opioid receptor by novel optogenetic hydrogen peroxide sensor


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Genetics;Human Genome;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_NAME: JOSLIN DIABETES CENTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE We have performed a genome-wide screen for gene modifications that protect beta cells against immune- mediated killing in a mouse model for type 1 diabetes. This powerful and stringent screen identified the type 1 diabetes-associated gene RNLS that we have now extensively validated for its effect on beta cell resistance in both mouse islet cells and human stem cell-derived beta cells. This research aims to further understand how RNLS deletion protects beta cells against autoimmunity and whether targeting this gene pharmacologically could provide a new avenue for the prevention of type 1 diabetes.

PI_NAMEs: YI, PENG  (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: Achievement;Age of Onset;Antigen Presentation Pathway;Autoimmune Diabetes;autoimmune pathogenesis;Autoimmune Responses;Autoimmunity;autoreactivity;Award;Beta Cell;beta cell replacement;Biological Assay;CD8-Positive T-Lymphocytes;Cell Transplantation;Cells;Cellular biology;Cellular Stress;chemokine;clinical application;CRISPR screen;Data;Development;Diabetes Mellitus;diabetes pathogenesis;Diabetes prevention;Diabetic mouse;Disease;endoplasmic reticulum stress;Enzymes;Equilibrium;FDA approved;Funding;Gene Modified;Genes;Genetic;genome editing;genome wide association study;genome wide screen;genome-wide;genome-wide analysis;glycemic control;Glycolysis;Grant;Human;human disease;Human Genome;human pluripotent stem cell;human stem cell-derived;human stem cells;Immune;immune cell infiltrate;Immune mediated destruction;immunogenicity;Immunologic Tests;Immunology;Immunosuppression;improved;In Vitro;in vivo;Inbred NOD Mice;Individual;Infiltration;inhibitor;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Investigation;islet;Islet Cell;Laboratories;Lead;loss of function;Measures;Mediating;Metabolic;Metabolism;Methods;Mitochondria;molecular modeling;mouse model;Mus;Mutation;NADH;Nature;novel;novel therapeutics;Oral;Pancreas;Pargyline;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;Pluripotent Stem Cells;Positioning Attribute;prevent;Prevention;Preventive;Preventive treatment;Production;protective effect;Protocols documentation;Publications;recruit;Research;Resistance;Respiration;Risk;Role;Shapes;small molecule inhibitor;stem cell differentiation;stem cells;Stress;Structure;Structure of beta Cell of islet;Surveys;systemic autoimmunity;T-Cell Activation;Testing;Therapeutic;therapeutic evaluation;Translations;Validation

PROJECT_TITLE: Functional Validation of Gene Modifications that Protect Beta Cells against Autoimmunity Identified by Genome-Wide CRISPR Cas9 Screening

STUDY_SECTION: CADO

STUDY_SECTION_NAME: Cellular Aspects of Diabetes and Obesity Study Section[CADO]


ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: NARRATIVE This NIA Leadership Award is to support Dr. Thompson’s efforts to create a robust, highly visible, innovative, and sustainable “interdisciplinary translational rehabilitation Geroscience-based research and education program” as a cornerstone of research excellence at Boston University.

PI_NAMEs: THOMPSON, LADORA V (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Acceleration;Address;Affect;Age;Aging;aging mechanism;aging process;Area;Arthritis;Assessment tool;authority;Award;Basic Science;bench to bedside;Biological;Biological Models;Biology of Aging;Boston;career development;Chronic Disease;Clinical;clinical investigation;Clinical Research;Clinical Sciences;clinical training;Collaborations;Communities;design;Development;disability;disability risk;Disease;Education;education resources;educational atmosphere;Educational Curriculum;Educational process of instructing;Educational workshop;Endowment;Ensure;Environment;Etiology;experience;Faculty;Fostering;Foundations;frailty;Funding;Geroscience;Grant;Human;human old age (65+);improved;Infrastructure;injury recovery;innovation;Institution;Interdisciplinary Education;Interdisciplinary Study;International;Intervention;Knowledge;knowledge integration;Laboratories;Leadership;meetings;Mentors;Methodology;Molecular;mouse model;Movement;multidisciplinary;Mus;Muscle;muscle physiology;new technology;Older Population;Phase I Clinical Trials;Phenotype;Physical therapy;Pilot Projects;Population;Positioning Attribute;pre-clinical;Predisposition;Process;professor;Prognosis;Program Research Project Grants;programs;Publications;recruit;Recruitment Activity;rehabilitation research;rehabilitation science;Rehabilitation therapy;Research;Research Design;Research Personnel;Research Training;Resources;sarcopenia;Science;Scientist;Seminal;skills;skills training;Stroke;Students;synergism;Testing;Tissues;Training;Transcend;Translational Research;translational scientist;Translations;Universities;Work

PROJECT_TITLE: Academic Leadership Award - The Translational Rehabilitation in Geroscience Initiative

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Biological Aging Study Section[NIA-B]


NIH_SPENDING_CATS: Brain Disorders;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: BLOOMINGTON

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative Sport-related concussion (SRC) is a significant public health problem resulting in over 200,000 annual trips to the Emergency Department (ED) in the United States. Mounting evidence from human studies has demonstrated that repetitive head impact exposure (HIE) may contribute to decreased SRC tolerance in contact sport athletes. The goal of this project is to utilize modern machine learning and statistical methods and use head impact characteristics, player and team information to determine the SRC risk factors and factors influencing post-SRC recovery.

PI_NAMEs: HAREZLAK, JAROSLAW  (contact);STEMPER, BRIAN D

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Acceleration;Accident and Emergency department;Accounting;Acute;Athletic;base;Biomechanics;Brain;Brain Concussion;Characteristics;Clinical;cognitive function;college;Computers;contact sports;Data;Data Set;demographics;Education;Enrollment;Equilibrium;Excision;Exposure to;Frequencies;Goals;Head;head impact;Health;high school;Human;improved;Incidence;Individual;Injury;injury prevention;innovation;Intervention;Literature;machine learning method;Manufactured football;Measurement;Measures;Medical;Medical Staff;mild traumatic brain injury;Modeling;Modernization;Outcome;Personality Traits;Play;Policies;Positioning Attribute;prediction algorithm;Protective Devices;prototype;Public Health;Recording of previous events;Recovery;Reporting;Research;Risk;Risk Factors;Safety;Seasons;Series;Severities;Sports;Statistical Methods;Statistical Models;Symptoms;System;Techniques;Testing;Time;tool;Training;United States;Visualization

PROJECT_TITLE: Influence of the College Football Athletes' Cumulative Head Impact Exposure (HIE) on the mTBI incidence and post-mTBI health outcomes

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


NIH_SPENDING_CATS: Aging;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Prevention

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it supports the National Institute of Aging mission to accelerate the translation of treatments for human aging. This project seeks to further determine if a population that is not already burdened by chronic disease can benefit from metformin treatment. Successful completion of the study will help inform which subjects could benefit from metformin treatment to slow aging.

PI_NAMEs: MILLER, BENJAMIN FRANCIS (contact)

PROGRAM_OFFICER_NAME: NELLISSERY, MAGGIE JACOB

PROJECT_TERMS: 5'-AMP-activated protein kinase;Acceleration;Aerobic Exercise;Affect;Age;age acceleration;Aging;aging biomarker;aging process;blood glucose regulation;blood-based biomarker;burden of chronic illness;Chronic;Chronic Disease;Clinical effectiveness;clinical translation;Clinical Trials;clinically relevant;Complex;Complication;Continuous Glucose Monitor;cost;Data;design;Disease;Dose;Double-Blind Method;Enrollment;Epidemiology;Exercise;exercise training;experimental study;Fasting;FRAP1 gene;Glucose Clamp;Goals;Health;Health Benefit;Hepatic;Human;human subject;Hyperinsulinism;Hypoglycemic Agents;improved;Individual;inhibitor;Insulin;Insulin Resistance;insulin sensitivity;Knowledge;Lead;life span;Measures;Metabolic;Metformin;Methods;Mission;Mitochondria;Mitochondrial Proteins;Muscle Mitochondria;National Institute on Aging;Non-Insulin-Dependent Diabetes Mellitus;novel;Outcome;patient population;Peripheral;Pharmaceutical Preparations;Pharmacological Treatment;pill;placebo group;Placebos;Population;Post-Translational Protein Processing;prevent;Prevention;protective effect;Protein Analysis;protein degradation;Proteomics;Public Health;Randomized;Research;Research Design;Respiration;response;Risk Factors;Secondary to;sedentary;Skeletal Muscle;Specific qualifier value;Stable Isotope Labeling;Testing;Training;Training Programs;translational potential;Translations

PROJECT_TITLE: Does insulin sensitivity impact the potential of metformin to slow aging?