ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Caregiving Research;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dementia;Depression;Health Services;Mental Health;Neurodegenerative;Neurosciences;Pain Research;Palliative Care;Physical Rehabilitation;Rehabilitation;Social Determinants of Health

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative The proposed research study explores the delivery a supportive intervention for caregivers of patients with dementia in order to improve pain management. Thus, the study is highly relevant to public health as it affects the health of a continuously growing segment of our population, namely these who are called to assume the essential role of family caregiving, and the study aims to demonstrate the value of a feasible and sustainable behavioral intervention for caregivers.

PI_NAMEs: DEMIRIS, GEORGE  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Absence of pain sensation;Activities of Daily Living;Address;Adoption;advanced dementia;Affect;Agitation;Alzheimer's disease caregiver;Alzheimer's disease diagnosis;Alzheimer's disease patient;Alzheimer's disease related dementia;American;Anxiety;anxiety reduction;Area;attentional control;behavior observation;Behavior Therapy;caregiver education;caregiver interventions;caregiver quality of life;Caregiver support;Caregivers;caregiving;Caring;Cessation of life;Chronic stress;Cognitive Therapy;Communication;Confusion;Control Groups;cost;Cost Analysis;cost comparison;Dementia;dementia care;Dementia caregivers;design;Deterioration;empowerment;Etiology;experience;Family;Family Caregiver;family caregiving;Family member;family support;Feeling;Friends;General Population;Goals;Grief reaction;group intervention;Health;Health Professional;Healthcare;high risk;Hospice Care;hospice environment;hospice utilization;Hour;Household;Hygiene;improved;informal caregiver;Intervention;Longitudinal Studies;Medication Management;Mental Depression;Modeling;National Institute on Aging;older adult;Outcome;Pain;Pain management;Pain quality;Palliative Care;Patient Care;patient population;Patient Self-Report;Patients;Perception;Pharmacologic Substance;Philosophy;physical conditioning;Pilot Projects;Placebo Effect;Population;post intervention;premature;Prevalence;primary outcome;Public Health;Publishing;Quality of Care;Quality of life;Randomized;randomized, clinical trials;Reporting;research study;Role;satisfaction;secondary outcome;Services;Social support;Spouses;standard care;Stress;success;Symptoms;therapy development;Training;Translations;Transportation;United States;United States National Institutes of Health;video chat;Work

PROJECT_TITLE: Supporting Family Caregivers of Persons with Dementia

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: ANN ARBOR

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Sensing microbe-associated molecular patterns and host endogenous immunomodulatory phytocytokines by cell surface-resident pattern recognition receptors (PRRs) constitutes a core process in launching an effective immune response against pathogen infections. This project will elucidate the mechanisms underlying PRR complex activation and attenuation by protein post-translational modifications, the elaborate and specific PRR signaling relay, and the feedback loops mediated by phytocytokines. Given the considerable similarities of innate immunity among multicellular eukaryotes, we anticipate that our research will have a broad impact on the study of innate immunity and signal transduction in general.

PI_NAMEs: SHAN, LIBO  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Animals;attenuation;BAK1 gene;Cell membrane;Cell surface;Cell Surface Receptors;Cells;Complex;Cytoplasm;environmental adaptation;Eukaryota;Event;Feedback;Fortification;Gene Expression;Goals;graduate student;Growth;Homeostasis;Immune;Immune response;Immune signaling;Immunity;immunoregulation;Infection;Interdisciplinary Study;Ligands;Mediating;Microbe;microbial;Modification;Molecular;Natural Immunity;novel;pathogen;Pathway interactions;Pattern;Pattern recognition receptor;Peptides;Perception;Phosphorylation;Phosphotransferases;Plants;Post-Translational Protein Processing;Postdoctoral Fellow;Process;receptor;Receptor Signaling;Reproduction;Research;Research Personnel;Resolution;Signal Pathway;Signal Transduction;spatiotemporal;Specificity;training opportunity;Ubiquitination;undergraduate student

PROJECT_TITLE: Immune signal perception and integration by cell surface receptors and peptide liga

STUDY_SECTION: MRAC

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


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Hypertension

ORG_CITY: COLUMBIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE WENCESLAU, CAMILLA F.  One of the major pathophysiological characteristic of hypertension is the presence of vascular remodeling. However, the exact trigger that leads to vascular remodeling is still unknown. Here we observed for the first time that the increase in circulating levels of cell death-derived mitochondria and gut-derived bacteria fragments activates immune danger sensors leading to vascular remodeling and hypertension.

PI_NAMEs: WENCESLAU, CAMILLA FERREIRA (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Actins;Adult;Advanced Development;Affect;Animal Model;Animals;antagonist;Aorta;Arteries;Attention;Bacteria;Binding;Biological Markers;Blood Pressure;blood pressure elevation;blood pressure reduction;Blood Vessels;Cell Death;cell injury;cell motility;Cells;Characteristics;Chronic;Circulation;cofilin;Data;Dependence;driving force;Female;fMet-Leu-Phe receptor;formyl peptide;FPR1 gene;Functional disorder;G-Protein-Coupled Receptors;Genetic Engineering;Germ-Free;Goals;high salt diet;Human;Hypertension;hypertensive;Immune;Immune system;Immunobiology;Inflammation;Infusion procedures;innate immune function;Innate Immune System;innovation;Interdisciplinary Study;Intrinsic factor;juvenile animal;Knockout Mice;Lead;Leaky Gut;Leukocytes;Link;Lipopolysaccharides;Literature;Maintenance;male;mature animal;Mediating;Mesentery;microbiota;Mitochondria;Modeling;Molecular;Motility;Movement;Mus;National Heart, Lung, and Blood Institute;network dysfunction;neutrophil;normotensive;novel;novel therapeutic intervention;pathogen;Patients;Pattern recognition receptor;Peptide Initiation Factors;Peptides;Play;polymerization;Polymers;pressure;prevent;Rattus;receptor;Receptor Activation;Research;Research Personnel;Research Project Grants;Resistance;Role;sensor;Sentinel;sex;Signal Pathway;Source;Technology;Testing;Therapeutic;Time;Tissues;Vascular Diseases;vascular injury;Vascular remodeling;zonulin

PROJECT_TITLE: Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertension

STUDY_SECTION: HM

STUDY_SECTION_NAME: Hypertension and Microcirculation Study Section[HM]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza

ORG_CITY: ATHENS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project narrative The proposed research is relevant to public health because the discovery and mechanistic understanding of novel innate immune mechanisms protective against a wide range of influenza strains is expected to advance our knowledge of pathogenesis in influenza infections and lay down the ground work for future design of novel therapies aimed at improving the antiviral effect of the airway epithelium. Thus, the proposed research is important to the mission of the NIH by developing fundamental knowledge that will help to fight human diseases.

PI_NAMEs: RADA, BALAZS  (contact);TRIPP, RALPH A

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: adaptive immune response;adaptive immunity;Affect;airway epithelium;airway surface liquid;Animal Model;Anions;anti-influenza;Anti-viral Agents;Antibody titer measurement;antimicrobial;apical membrane;Attenuated;attenuation;Biological Models;Biology;Birds;bronchial epithelium;Cell-Free System;Cells;Cysteine;cytokine;Data;design;Economic Burden;Enzymes;Epithelial Cells;extracellular;fighting;Future;Goals;Hemagglutinin;Human;human disease;Hydrogen Peroxide;hypothiocyanite;Immune;Immune system;Impairment;improved;In Vitro;in vitro testing;in vivo;Influenza;Influenza A virus;Influenza B Virus;influenza infection;Influenza prevention;influenza virus strain;influenza virus vaccine;influenzavirus;innate immune mechanisms;Innate Immune Response;innovation;Intervention;Knowledge;Leukocytes;Link;Lung;Lung infections;lung injury;Measures;Mission;Molecular;Molecular Mechanisms of Action;Morbidity - disease rate;mortality;mouse model;Mouse Strains;Mus;NADPH Oxidase;Natural Immunity;Neuraminidase inhibitor;novel;novel therapeutics;Outcome;Oxidases;Participant;Pathogenesis;Pathogenicity;Patients;Persons;Proteins;Public Health;Pulmonary Inflammation;Pulmonary Pathology;recruit;Research;Resistance;response;Role;Route;Source;System;Testing;Therapeutic;Thiocyanates;United States National Institutes of Health;Vaccination;Viral;Viral Drug Resistance;Virion;virucide;Virus;Virus Diseases;Virus Inactivation;Virus Replication;weapons;Work

PROJECT_TITLE: Dual oxidase and lactoperoxidase in influenza infection

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Human Genome;Immunization;Immunotherapy;Precision Medicine;Prevention;Vaccine Related

ORG_CITY: BIRMINGHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Host Factors in Response to Therapeutic Monoclonal Antibodies and Vaccination PROJECT NARRATIVE The lack of effective clinical responses in many patients receiving ablative monoclonal antibody therapy challenges clinical and translational investigators to delineate the mechanistic basis for such differences. Genetic inquiry can identify the contributions that the recipient brings to these differences, especially in terms of variant structures of the antibody receptors mediating the responses. Delineation of these variants will inform advances in antibody engineering and will guide, in advance of antibody administration, individual therapeutic choices for effective implementation of precision medicine.

PI_NAMEs: KIMBERLY, ROBERT P. (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Ablation;Affect;Affinity;African;Antibodies;antibody engineering;Antibody Therapy;antibody-dependent cell cytotoxicity;Biological;Biological Process;Cell membrane;cell type;Cells;Clinical;Clinical Investigator;cohort;Consensus;Coupled;CRISPR/Cas technology;cytokine;Data;Effectiveness;European;Excision;Fc Receptor;FCGR2C gene;FCGR3A gene;Genes;Genetic;genetic variant;genomic locus;Genomics;Human;Immune response;Individual;innovation;Integration Host Factors;Laboratories;Ligand Binding;Link;Lymphoid Cell;Macrophage;Mediating;Modeling;Monoclonal Antibody Therapy;monocyte;Myeloid Cells;nanopore;novel;Patients;Persons;Phagocytosis;Population Heterogeneity;precision medicine;predicting response;premature;Productivity;protein structure;Proteins;Reagent;receptor;receptor expression;Resolution;response;Series;Signal Transduction;Single Nucleotide Polymorphism;SNP genotyping;Stratification;Structure;Terminator Codon;Therapeutic;Therapeutic antibodies;Therapeutic Monoclonal Antibodies;translational scientist;Vaccination;vaccination protocol;Variant


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Infectious Diseases;Liver Disease;Prevention;Vaccine Related

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Chronic infection by hepatitis viruses often results in dysregulation of the immune system and diminished responses to standard vaccination. The inability of the immune system to control the virus and chronic inflammation gradually destroy the liver. A better understanding of how chronic liver infection impact adaptive immunity and the production of anti-viral antibodies will be essential for restoring normal immune function of the affected subjects.

PI_NAMEs: LAW, MANSUN  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: 2019-nCoV;Achievement;adaptive immunity;Affect;Anti-viral Agents;Antibodies;Antibody Response;Antigens;Awareness;B-Cell Activation;B-Lymphocytes;Caring;Cell Lineage;Cells;Chronic;Chronic Hepatitis B;Chronic Hepatitis C;chronic infection;Complement 3d Receptors;Data Set;Diagnosis;Endowment;Epitopes;experience;Face;Functional impairment;Generations;Genes;Genetic;genetic signature;Genetic Transcription;Germ Lines;Glycoproteins;Goals;Hepatitis;Hepatitis B;Hepatitis C;Hepatitis C Acquisition;Hepatitis C virus;high risk population;HIV;Human;Immune;immune function;Immune response;Immune system;Immunogenetics;Immunologic Memory;Individual;Infection;Inflammation;influenza virus vaccine;influenzavirus;Information Protection;Learning;Liver;Liver Cirrhosis;liver infection;Longitudinal Studies;Lymphocyte;Malignant neoplasm of liver;Mediating;Memory;Memory B-Lymphocyte;Modeling;Molecular;neutralizing antibody;Patients;Persons;Phenotype;Population;prevent;Production;Property;Public Health;receptor;Recovery;Reporting;response;Risk;Sampling;Shapes;Surface;T-Lymphocyte;Time;transmission process;Vaccination;vaccine development;Vaccines;Viral;Viral Antibodies;Viral hepatitis;Virus;Virus Diseases;virus envelope

PROJECT_TITLE: Understanding human antibody responses to chronic viral hepatitis C


NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: VETERINARY SCIENCES

ORG_STATE: PA

PHR: Project Narrative Leishmaniasis is a serious neglected tropical disease where destructive cutaneous lesions develop and treatment is often ineffective. The studies in this proposal seek to define the role of host factors that promote pathology in leishmaniasis and identify new targets for host-directed immunotherapy.

PI_NAMEs: SCOTT, PHILLIP  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Antiparasitic Agents;Automobile Driving;Benign;Binding;Bioinformatics;CCL3 gene;CCL4 gene;CCR5 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;cell type;Cells;chemokine;Chronic;chronic infection;Clinical;Cultured Cells;Cutaneous;Cutaneous Leishmaniasis;CXCL3 gene;CXCL9 gene;CXCR3 gene;Cytolysis;Cytotoxic T-Lymphocytes;Data;design;Disease;Disease Progression;disorder control;Equilibrium;ex vivo imaging;Experimental Models;experimental study;Future;Generations;Genetic Transcription;imaging approach;Immune response;Immunologics;immunopathology;Immunotherapy;improved;In Vitro;in vitro Model;in vivo;Individual;Infection;Inflammasome;Inflammation;Inflammatory;insight;Integration Host Factors;Knowledge;Leishmania;Leishmaniasis;Lesion;Link;Lymphocyte;Mediating;Modeling;Molecular;mouse model;Mus;neglected tropical diseases;Outcome;Parasites;Pathologic;Pathology;Pathway interactions;Patients;Pattern;perforin;Pharmaceutical Preparations;Pharmacotherapy;Physiological;Play;Production;Publications;recruit;Regulatory T-Lymphocyte;Reporter;response;Role;Series;Severities;Signal Transduction;Sterility;Testing;Treatment Failure

PROJECT_TITLE: CD8 T cell-dependent pathways leading to immunopathology in cutaneous leishmaniasis

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity

ORG_CITY: CHICAGO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE During obesity, adipose tissue macrophages (ATMs) adopt a metabolically activated phenotype that contributes to low-grade chronic inflammation in adipose tissue and insulin resistance. Although studies in humans and experimental animal models support targeting the inflammatory phenotype of ATMs to improve insulin sensitivity, the molecular mechanisms underlying this inflammation are incompletely understood. We have identified a novel proinflammatory signaling pathway in macrophages triggered by metabolic stimuli and distinct from infectious stimuli – and, our overall goal is to delineate the contribution this pathway to obesity- associated insulin resistance.

PI_NAMEs: BECKER, LEV  (contact)

PROGRAM_OFFICER_NAME: BASU, RAJATAVA

PROJECT_TERMS: Adipocytes;Adipose tissue;Adopted;Agammaglobulinaemia tyrosine kinase;Anti-Inflammatory Agents;atherosclerosis risk;Attenuated;Automobile Driving;Bacteria;Bacterial Infections;Cardiovascular Diseases;Cell surface;Central obesity;Chronic;Clinic;Clinical;Complex;cytokine;Data;Diabetes Mellitus;Disease;drug action;Drug Targeting;Event;Experimental Animal Model;Exposure to;Fatty acid glycerol esters;Fatty Acids;Fatty Liver;fighting;Funding;gene therapy;Genetic;genetic approach;Glucose Intolerance;glucose tolerance;Goals;Host Defense;Human;human tissue;improved;in vivo;Infection;Inflammation;Inflammation Mediators;Inflammatory;innovation;Insulin Resistance;insulin sensitivity;insulin signaling;Knockout Mice;Leukocytes;Link;Lipids;Macrophage;Macrophage Activation;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;Modeling;Molecular;mouse model;Mus;Myeloid Cells;Natural Immunity;NF-kappa B;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obese Mice;obese patients;Obesity;Pathway interactions;Patients;Peptide Signal Sequences;Peritonitis;Pharmacotherapy;Phenotype;Phosphotransferases;Play;Positioning Attribute;Post-Translational Protein Processing;Protein Tyrosine Kinase;Publishing;Reporting;Risk Factors;Role;Signal Pathway;Signal Transduction;Source;Spleen;Stimulus;SYK gene;Testing;Therapeutic;Therapeutic Intervention;Treatment Efficacy;Tyrosine Kinase Inhibitor;Visceral fat;Work

PROJECT_TITLE: 'Metabolically Activated' Macrophages in Obesity and Insulin Resistance

STUDY_SECTION: IPOD

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: LAWRENCE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: NARRATIVE This project addresses a novel mechanism of microglial activation and the associated brain pathology in Alzheimer's disease (AD) by aiming to determine the role of Stimulator of interferon genes (STING) activated via cytosolic mitochondrial DNA (mtDNA) sensing by cGMP-AMP (cGAMP) synthase (cGAS) in shaping microglial phenotype in an AD animal model. Our studies will elucidate how STING activation contributes to the development of microglial activation and the associated brain pathology in AD as well as how mtDNA is released into the cytosol in AD-related conditions. The results will provide a novel strategy for the treatment of AD, and will impact our understanding of brain pathology in other neurodegenerative diseases such as Diffuse lewy body disease (DLBD) and the Down's syndrome that show hippocampal amyloidopathy.

PI_NAMEs: DU, HENG  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta accumulation;abeta deposition;Adaptor Signaling Protein;Address;Affect;aging population;Alzheimer's Disease;Amyloid beta-Protein;Animal Disease Models;antiviral immunity;Apoptotic;Attenuated;BAX gene;behavior test;Biological Assay;Brain;Brain Injuries;Brain Pathology;Cells;Cognitive deficits;Critical Pathways;Cyclic GMP;Cytosol;Data;Dementia;Development;Diffuse Lewy Body Disease;Disease;DNA;Down's Syndrome;Extravasation;Gene Activation;Gene Expression Profile;glial activation;Golgi Apparatus;Hippocampus;Immune;Impaired cognition;Inflammation Mediators;Inflammatory;Innate Immune Response;Interferons;Learning;Light;Link;Mediating;Memory;Messenger RNA;Microglia;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial permeability transition pore;Morphology;Mus;Myelogenous;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurons;novel;novel strategies;Oxidative Stress;Pathologic;Pathway interactions;Patients;Phagocytosis;Phenotype;Phosphorylation;Pilot Projects;Preventive;Production;Regulation;Reporting;Role;Senile Plaques;sensor;Shapes;Signal Transduction;Source;Sterility;Stimulator of Interferon Genes;Stress;Synapses;Testing;transcriptomics;treatment strategy;Voltage-Dependent Anion Channel;Western Blotting

PROJECT_TITLE: mtDNA leakage and STING-dependent microglial innate immune response in Alzheimer's disease

STUDY_SECTION: NOMD

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Genetics

ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: Bacteria acquire immunity to their viruses by capturing viral DNA fragments, storing them in their own genomes, and then using these “memories” to recognize the invaders during subsequent infections and destroy them. We propose to study the molecular details of “CRISPR adaptation” - the poorly understood process by which fragments of foreign DNA become part of bacterial genome.

PI_NAMEs: SEMENOVA, EKATERINA  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: acquired immunity;Address;Antibiotic Resistance;Archaea;Autoimmune;Automobile Driving;Bacteria;Bacterial Genome;Biological Models;Cell Physiology;Cells;Cessation of life;Clustered Regularly Interspaced Short Palindromic Repeats;comparative;Complex;Cytoprotection;Devices;Discrimination;DNA;DNA Sequence;Ensure;Enzymes;Escherichia coli;Eubacterium;Eukaryotic Cell;falls;Funding;Future;Generations;Genes;Genetic;genetic element;Genetic Recombination;Genetic Transcription;Genome;genome editing;Goals;helicase;Horizontal Gene Transfer;Immune system;Immunity;in vivo;Infection;innovation;Laboratories;Link;Memory;Methods;Mobile Genetic Elements;Molecular;nuclease;Nucleic Acids;Parasites;Pattern;Population;prevent;Process;Production;Prokaryotic Cells;Proteins;Reaction;repaired;Resistance;resistance gene;response;RNA;Selection Bias;Small RNA;Spacer DNA;Structure;suicidal;System;Viral;viral DNA;Virus;Work

PROJECT_TITLE: The Function of Small RNA-Based viral Defense System in E. coli - Renewal 1

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


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

ORG_CITY: CLEVELAND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder, for which there is no effective treatment. The proposed study seeks to better understand the molecular mechanisms by which signals induce AD-associated neuropathology via regulation of oligodendrocyte metabolism and to reveal novel targets for developing therapeutics to treat AD.

PI_NAMEs: QI, XIN  (contact)

PROJECT_TERMS: Adult;age related neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Animal Model;Animals;Astrocytes;astrogliosis;Axon;axonal degeneration;Behavioral;beta-Galactosidase;Binding;Bioenergetics;Biological Assay;Brain;Cell Aging;cell population study;cell type;Cells;Cessation of life;Cognitive;Cognitive deficits;cognitive function;Compensation;Data;Demyelinations;density;Development;Disease;Disease Progression;Dissociation;driving force;Dynamin;effective therapy;enzyme activity;Enzymes;Event;Exhibits;Exposure to;Functional disorder;Genetic Suppression;genome wide association study;Glucose;Glycolysis;Glycolysis Induction;Glycolysis Inhibition;Glycolysis Pathway;Heterozygote;hexokinase;Human;Impaired cognition;Impairment;improved;in vivo;Inflammasome;Inflammation;Inflammatory;Injury;Interleukin-1 beta;Knock-in;Knock-in Mouse;Knock-out;Maintenance;Measures;Mediating;Metabolic;Metabolism;Mitochondria;Molecular;Mus;Myelin;myelin degeneration;myelination;Nerve Degeneration;Neuroglia;neuroinflammation;Neurons;neuropathology;novel;oligodendrocyte progenitor;Oligodendroglia;Outer Mitochondrial Membrane;Oxygen;Pathologic;Pathologic Processes;Pathology;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;precursor cell;Production;Protein Dephosphorylation;Protein Isoforms;Proteins;Proteomics;Regulation;remyelination;Reporting;Role;senescence;senescence associated secretory phenotype;Signal Induction;stressor;Symptoms;Therapeutic;Time;transcriptomics;upstream kinase;white matter;Work

PROJECT_TITLE: Mechanism of white matter pathology in Alzheimer's disease

STUDY_SECTION: CMBG

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


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: NARRATIVE Muscularization of distal microvessels is a major pathological feature of pulmonary arterial hypertension (PAH), but sources of smooth muscle cells (SMCs) found within lesions remain unclear. We show for the first time that lung pericytes act as progenitors for SMCs in both PAH and experimental chronic hypoxia. Through a combination of established cellular assays, novel transgenic mouse models and cutting edge CRISPR gene editing, we will demonstrate that activation of a novel HIF2a/SDF1 signaling pathway is essential for differentiation of pericytes into SMCs and that its manipulation has the potential to facilitate the discovery of novel therapeutic approaches capable of reversing muscularization and restoring pulmonary vascular homeostasis.

PI_NAMEs: YUAN, KE  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: AMD3100;Animal Model;antagonist;arteriole;Bioinformatics;Biology;Blood capillaries;Blood Vessels;Cell Culture Techniques;Cell Differentiation process;Cell Hypoxia;Cell Lineage;Cell Proliferation;cell type;Cells;Cellular Assay;Cessation of life;Chronic;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CSPG4 gene;CXCR4 gene;CXCR4 Receptors;Data;directed differentiation;Disease;Disease Progression;Dissociation;Distal;Endothelium;Exhibits;Functional disorder;Genes;Genetic Transcription;Homeostasis;Human;Hypoxia;Impairment;improved outcome;insight;Knock-out;Label;Lead;Lesion;Life;Lung;lung pressure;Lung Transplantation;maladaptive behavior;Maps;Medical;Mesenchymal;Molecular;Morphology;mouse model;Mus;Muscle;novel;novel therapeutic intervention;overexpression;Pathogenesis;Pathogenicity;Pathologic;Patients;Pericytes;Pharmaceutical Preparations;Phenotype;Plasma;Play;Population;premature;prevent;Production;progenitor;Proliferating;Property;pulmonary arterial hypertension;pulmonary vascular remodeling;Pulmonary vessels;Reporting;response;right ventricular failure;Role;Severities;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Smooth Muscle;Smooth Muscle Myocytes;Source;Stains;stem cell differentiation;Stress;Stromal Cell-Derived Factor 1;Testing;therapeutic target;Time;Tissues;transcriptome sequencing;transdifferentiation;Transgenic Mice;Vascular remodeling;Vasodilation

PROJECT_TITLE: Pericytes differentiate into smooth muscle cells through HIF2a/SDF1 activation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-G(03)]


NIH_SPENDING_CATS: Biotechnology;Diabetes;Digestive Diseases;Genetics;Human Genome;Liver Disease;Nutrition;Obesity

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Our preliminary published and unpublished studies support a role for the SET-domain containing protein, SETDB2, in glucocorticoid receptor (GR)-dependent gene expression essential to liver metabolism during metabolic stress. We hypothesize liver SETDB2 deficiency will be protective to the metabolic adverse effects of excess endogenous or exogenous glucocorticoids. Successful execution of this proposal will result in mechanistic insight into the genomic regulation behind glucocorticoid- induced diabetes through a potential unique SETDB2-GR regulatory node, which may open new therapeutic strategies for multiple glucocorticoid associated diseases in humans.

PI_NAMEs: OSBORNE, TIMOTHY F (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Acute;Adverse effects;Affect;Anti-Inflammatory Agents;Area;Binding;Cardiovascular Diseases;Cell Nucleus;cell type;ChIP-seq;Chromatin;Chromatin Loop;chromatin modification;Chronic;Clinical;clinically relevant;Code;Collaborations;CREB1 gene;Cytoplasm;Data;Development;Dexamethasone;Diabetes Mellitus;diet-induced obesity;Disease;Dissociation;DNA receptor;Enhancers;Enzymes;Epigenetic Process;epigenomics;Equilibrium;experimental study;Exposure to;Fasting;Fatty acid glycerol esters;Fatty Liver;feeding;Gene Activation;Gene Expression;Gene Expression Regulation;gene repression;Gene Targeting;Genes;Genome;genome-wide;Genomics;Glucagon;Glucocorticoid Receptor;Glucocorticoids;Gluconeogenesis;Glucose;Glucose Intolerance;glucose production;Hepatic;Homeostasis;Hormonal;hormone response element;Hormones;Human;human disease;hypercholesterolemia;Hyperglycemia;Hyperlipidemia;immunoregulation;insight;Insulin Resistance;Knock-out;Knowledge;Lipids;Liver;liver metabolism;Longitudinal Studies;Measures;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic stress;Metabolic syndrome;Metabolism;Molecular;mouse genome;mouse model;Mus;Muscular Atrophy;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Nutritional;Obesity;Pathway interactions;Patients;Physiological;Play;Postabsorptive Hypoglycemia;prevent;programs;promoter;Proteins;Publishing;receptor function;recruit;Regulation;Research;response;Risk Factors;Role;SET Domain;side effect;Site;Stress;Study models;synergism;Transactivation;transcription factor;transcriptome sequencing;Untranslated RNA;Visceral fat;Weight Gain;Work

PROJECT_TITLE: A Glucocorticoid Receptor-SETDB2 Co-Regulated Liver Metabolic Gene Program

STUDY_SECTION: MCE

STUDY_SECTION_NAME: Molecular and Cellular Endocrinology Study Section[MCE]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: PROJECT NARRATIVE  The objective of this proposal is to determine the role of voltage-gated calcium channels in oligodendrocyte development and myelination of the central nervous system. This work is relevant to developing means to induce remyelination in myelin degenerative diseases and for myelin repair in damaged nervous tissue.

PI_NAMEs: PAEZ, PABLO MARTIN (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Adult;Affect;Animals;Brain;Calcium Channel;Cell Communication;Cell Fractionation;Cell Maturation;Cell membrane;cell type;Cells;Central Nervous System;Communication;Complex;Cre lox recombination system;Data;Degenerative Disorder;Dendritic Spines;Designer Drugs;designer receptors exclusively activated by designer drugs;Development;electrical property;Electrophysiology (science);experimental study;Foundations;Future;G-Protein-Coupled Receptors;gain of function;Gene Expression;Genes;Genetic Recombination;genetic technology;Goals;Human;Image;Immunohistochemistry;improved;In Vitro;in vivo;in vivo imaging;insight;Investigation;inward rectifier potassium channel;Ion Channel;Ions;knock-down;Long-Term Potentiation;Mediating;Membrane Potentials;migration;Molecular;Morphology;mouse development;mouse model;Mus;Muscarinic Acetylcholine Receptor;Mutation;Myelin;myelin degeneration;myelination;nerve stem cell;Nerve Tissue;Neurons;oligodendrocyte progenitor;Oligodendroglia;Pathway interactions;Point Mutation;postnatal;postnatal development;postsynaptic;Potassium Channel;Process;Proliferating;Proteins;Proteomics;remyelination;repaired;Research;Rest;Role;Signal Transduction;Stem Cell Development;stem cells;Structure;Synapses;System;Techniques;Technology;Testing;Time;Timothy syndrome;transcription factor;transcriptome sequencing;voltage;white matter damage;Work

PROJECT_TITLE: Modulation of Oligodendrocyte Development by Voltage-Operated Calcium Channels

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Bioengineering;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_NAME: DANA-FARBER CANCER INST

PHR: PUBLIC HEALTH RELEVANCE: Pathological evidence suggests a potential link between neurodegeneration and aberrant intracranial mechanical stress. The project proposed here will (1) identify the sources of such stress and quantify its magnitude in health and disease, (2) measure the effect of these stressors on neuron function, and (3) identify classes of molecules involved in sensing and transducing these stresses from the tissue to the cellular level. Achieving these aims will open new avenues of research for identifying therapeutic targets for neurodegeneration.

PI_NAMEs: FRANCO, JOY ANN (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: 3-Dimensional;Address;Age;Award;Blood flow;Brain;Caenorhabditis elegans;career;Cerebrovascular Disorders;clinically relevant;dementia risk;Disease;disease model;doctoral student;Engineering;Environment;environmental change;executive function;extracellular;Fluorescence Microscopy;Goals;Health;Human;Impaired cognition;interest;Invertebrates;Knowledge;Link;Measures;Mechanical Stress;Mechanics;Mechanoreceptors;mechanotransduction;Memory impairment;Modeling;Molecular;Nerve Degeneration;neural;Neurobiology;Neurodegenerative Disorders;Neurons;Neurophysiology - biologic function;Neurosciences;novel;Pathologic;Pathology;Peripheral Nervous System;Phase;Postdoctoral Fellow;programs;Proteins;public health relevance;receptor;Research;research study;Role;Scholarship;sensor;Signal Pathway;Source;Spectrum Analysis;Stress;stressor;Structure;Tauopathies;therapeutic target;tissue stress;Touch sensation;Training Support;Traumatic Brain Injury;viscoelasticity;Work

PROJECT_TITLE: Effects of Extracellular Mechanics on Mechanosensory and Central Neuron Function


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Hearing Loss;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: DAVIS

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The most common complaint with respect to sensory processing among the aged is the reduced ability to understand speech in noisy environments. We currently have only a limited understanding of how changes in the central nervous system reflect these perceptual deficits, which can be devastating as they can leave aged individuals socially isolated, depressed, suicidal and has been correlated with Alzheimer's Disease. The experiments of this proposal will investigate the central mechanisms of hearing complex auditory stimuli in young and aged individuals in order to provide insights into remediation of age-related hearing deficits.

PI_NAMEs: MALONE, BRIAN J.;RECANZONE, GREGG HOWARD (contact)

PROJECT_TERMS: Acoustics;Address;Affect;age effect;age related;age related changes;age related decline;Age-associated memory impairment;aged;Aging;aging population;Alzheimer's Disease;animal old age;Animals;Area;Attention;attentional modulation;Attenuated;Auditory;Auditory area;auditory pathway;auditory processing;auditory stimulus;Auditory system;Brain;Central Nervous System;Code;Cognitive deficits;comorbidity;Complex;Data;Depressed mood;directed attention;Elderly;Environment;Equilibrium;Event;experimental study;Female;Foundations;Geriatrics;Goals;hard of hearing;Hearing;Hearing Aids;Human;Individual;insight;Intervention;Investigation;juvenile animal;Knowledge;Lateral;Lead;male;Measures;Medial;Mental disorders;Mental Health;Modeling;Monkeys;Nervous System;neural;neural correlate;Neurons;Noise;nonhuman primate;normal aging;normal hearing;Perception;Peripheral;Persons;Population;Presbycusis;Primates;Process;programs;Property;reconstitution;remediation;Research;response;Rodent;Self-Help Devices;Sensory;Series;Signal Transduction;Social isolation;sound;Source;Speech;Speech Perception;Stimulus;suicidal;Text;Visual

PROJECT_TITLE: Effects of aging on signal in noise processing

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Lung;Neurosciences;Sleep Research

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative This proposal will quantify the effects of a new approach for treating patients with obstructive sleep apnea, a disease with substantial cardiovascular morbidity and mortality. It leverages a combination of proven analytical methods to evaluate the impact of ansa cervicalis neurostimulation, a highly novel treatment that has recently demonstrated promise for relieving pharyngeal obstruction in apneic patients by harnessing the substantive effects of caudal traction on the upper airway. Unlocking caudal pharyngeal traction as a therapeutic mechanism for the treatment of obstructive sleep apnea has the potential to generate new medical and surgical approaches for the management of this common disease.

PI_NAMEs: KENT, DAVID T. (contact)

PROGRAM_OFFICER_NAME: BAIZER, LAWRENCE

PROJECT_TERMS: Address;Air Movements;airway muscle;airway obstruction;American;analytical method;Anatomy;Area;Attenuated;Bilateral;Breathing;Cardiovascular system;Cervical;Characteristics;Contracts;Data;Defect;Development;Dilator;Disease;Distal;Eligibility Determination;Endoscopy;genioglossus muscle;Health;Human;Hypoglossal nerve structure;hypopharynx;insight;Knowledge;Lateral;Legal patent;Literature;lung volume;Maintenance;Mediating;Medical;Methods;Morbidity - disease rate;mortality;Muscle;Neck;neuromuscular;neurophysiology;non rapid eye movement;novel;novel strategies;novel therapeutics;Obstruction;Obstructive Sleep Apnea;Operative Surgical Procedures;Oropharyngeal;Patient Compliance;Patients;personalized strategies;Pharmaceutical Preparations;Pharyngeal structure;Physiological;Physiology;Polysomnography;positive airway pressure;pressure;Publishing;REM Sleep;Research;response;Rest;Sedation procedure;Site;Sleep;Soft Palate;soft tissue;Source;Stretching;Structure;success;Techniques;Testing;Therapeutic;therapeutically effective;Thyroid cartilage structure;Tissues;tongue root;Trachea;Traction

PROJECT_TITLE: The Effect of Ansa Cervicalis Neurostimulation on Airway Patency in Obstructive Sleep Apnea

STUDY_SECTION: RIBT

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


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics

ORG_CITY: BERKELEY

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: This study aims to investigate the molecular and cellular bases of the heterogeneity of lens  epithelium that consists of distinct cell clusters with different functions. Moreover, we will explore novel regulatory mechanisms of distinct epithelial cell clusters in lens  growth control, lens homeostasis maintenance and various lens pathological outcomes. We will gain  insights into fundamental mechanisms about how distinct epithelial cell clusters selectively  response to various external stimuli to regulate the lens size and homeostasis over the course of  postnatal lens development and aging.

PI_NAMEs: GONG, XIAOHUA  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: 1 year old;Age;age related;Aging;Anterior;Antibodies;AQP1 gene;base;Candidate Disease Gene;Cataract;Cell Physiology;cell type;Cells;Development;Disease;Epithelial Cells;Epithelium;Exhibits;experimental study;Eye;Fiber;Gene Expression Profile;Gene Mutation;Genes;Genetic Transcription;Goals;Growth;Heterogeneity;high resolution imaging;Homeostasis;Image;Impairment;insight;Knock-out;Knockout Mice;Knowledge;lens;Lens development;Lens Fiber;Light;Literature;Maintenance;MAP2K1 gene;Mediating;Microphthalmos;Molecular;monolayer;Mus;novel;Outcome;Pathologic;Phase;Phenotype;Physiological;postnatal;postnatal development;Proliferating;Property;Proteins;rapid growth;Regulation;Resolution;response;Retina;Shapes;Signal Pathway;Signal Transduction;Signal Transduction Pathway;single cell analysis;single-cell RNA sequencing;Stimulus;Testing;Tissues;transcription factor;transcriptomics;Transgenic Animals;Transgenic Mice;transmission process;Up-Regulation;Water

PROJECT_TITLE: Lens epithelial cell heterogeneity during development

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative The experiments in this proposal are designed to uncover the mechanisms used by Clostridium difficile to form an infectious spore. The project is relevant to the NIH's mission of understanding and preventing bacterial infections and digestive diseases.

PI_NAMEs: MCBRIDE, SHONNA M. (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Anaerobic Bacteria;Antibiotic Resistance;Antibiotic Therapy;Award;Bacteria;Bacterial Infections;Biochemical;Biological Process;Cells;Cessation of life;Clostridium;Clostridium difficile;Complex;Data;design;Development;diarrheal disease;Digestive System Disorders;Disease;Disinfectants;DNA Binding;Environment;Excretory function;experience;experimental study;Exposure to;Feces;Gastrointestinal tract structure;Gene Expression Regulation;Genes;Genetic;genetic approach;Genetic Transcription;Genome;Germination;Goals;Health Care Costs;in vivo;individual responsibility;Infection;innovation;Intestinal Diseases;Intestines;Mission;Molecular;Molecular Genetics;Oral;Orthologous Gene;particle;pathogen;Pathogenesis;Pathway interactions;Peptide Initiation Factors;Phosphorylation;Phosphotransferases;Positioning Attribute;prevent;Process;Protein Analysis;protein function;Proteins;Publishing;Recurrence;Refractory;Regulation;Regulatory Pathway;Relapse;Reproduction spores;Research;Resistance;Role;Route;Toxin;transmission process;United States;United States National Institutes of Health;Work

PROJECT_TITLE: Genetic Mechanisms of Sporulation Induction in C. difficile

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Natural Products

ORG_CITY: ANN ARBOR

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative  The continuing advancement of molecular medicine requires a constant access to more diverse subsets of small-molecules, which are not well represented among the known drug candidates. Chemical synthesis is one of the most important means used to gain access to such compounds. The development of conceptually novel approaches that will aid the synthesis of bioactive molecules and new therapeutic agents is the subject of these studies.

PI_NAMEs: NAGORNY, PAVEL  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Area;Bacteria;Biological;Biological Process;cancer therapy;Cardenolides;Cardiac Glycosides;catalyst;chemical synthesis;Complex;Contraceptive methods;Derivation procedure;Development;Disease;Diterpenes;drug candidate;Family;glycosylation;Health;Heart;hormone regulation;Human body;Immune System Diseases;improved;Inflammation;member;Metabolic Diseases;Methods;Molecular Medicine;Natural Products;novel strategies;novel therapeutics;oxidation;Pattern;Pharmaceutical Chemistry;Pharmacotherapy;Plants;Reaction;Recording of previous events;rhodotoxin;scaffold;small molecule;Stereoisomer;Steroids;Study Subject;Techniques;Terpenes;Therapeutic;Therapeutic Agents

PROJECT_TITLE: New Methods and Strategies for the Synthesis and Selective Derivatization of Natural Products

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Strabismus (misaligned eyes) can be both visually and socially debilitating. We recently identified three genetic duplications (areas with an extra copy of the DNA) that increase the risk of strabismus, and this project aims to understand the mechanism by which those duplications increase risk. In the long term, this work will provide fundamental knowledge about how and why strabismus develops and pave the way for the development of new treatments that address its underlying cause.

PI_NAMEs: WHITMAN, MARY CATHERINE (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affect;Area;Binding;Binocular Vision;Bioinformatics;Biological Assay;Blindness;Cells;Cephalic;Child;Chromatin;chromatin remodeling;Chromatin Structure;Chromosome 10;Chromosome 2;Chromosome 4;Code;cohort;Copy Number Polymorphism;cost effective;CRISPR/Cas technology;Defect;design;Development;DNA;Enhancers;Enrollment;Environmental Risk Factor;Epigenetic Process;epigenetic regulation;Esotropia;Exotropia;Eye;Family;Family Study;First Degree Relative;Frequencies;Functional disorder;Gene Cluster;Gene Dosage;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene function;Genes;Genetic;genetic pedigree;Genetic study;Genetic Transcription;genome sequencing;genome wide association study;genomic locus;Goals;Heritability;Human;imprint;In Vitro;Individual;induced pluripotent stem cell;Inherited;insertion/deletion mutation;insight;Introns;Knowledge;Location;Low Birth Weight Infant;Luciferases;Maps;maternal cigarette smoking;member;Methylation;MicroRNAs;Molecular;Molecular Conformation;Morphology;Motor Neurons;Muscle;nerve stem cell;neuron development;Neuronal Differentiation;Neurons;next generation sequencing;Nucleic Acid Regulatory Sequences;Occupational;Operative Surgical Procedures;Paralysed;Pathogenesis;Pathology;Patients;Penetrance;Population;Population Study;premature;Premature Birth;preventive intervention;proband;Proteins;Recurrence;Refractive Errors;Regulation;Regulatory Element;Relative Risks;Reporting;Risk;Risk Factors;Running;screening;Signal Pathway;Single Nucleotide Polymorphism;social;stem cells;Strabismus;Syndrome;Testing;Twin Studies;Untranslated RNA;Variant;Vision;Visual;whole genome;Work

PROJECT_TITLE: Molecular mechanisms underlying strabismus risk

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Biotechnology;Genetics

PHR: Project Narrative  The proposed work seeks to elucidate the mechanisms and functions of fatty acid oxidation in T cell differentiation, the dysregulation of which could lead to a variety of immune-related diseases, such as cancer, infections, and autoimmune and inflammatory diseases. The completion of the proposed research will lay a solid foundation for the development of new metabolic-based therapeutic approaches for a wide range of immune-related diseases, which pose substantial and costly threats to public health.

PI_NAMEs: XIONG, JIANHUA  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: academic preparation;Acetates;Acetyl Coenzyme A;Acetylation;Acids;Advisory Committees;Affect;Applications Grants;ATP Citrate (pro-S)-Lyase;Autoimmune Diseases;Biochemical;Bioenergetics;Biological Assay;Candidate Disease Gene;career development;Carnitine Palmitoyltransferase I;Catabolic Process;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;Cellular biology;Cellular Immunity;Central Nervous System;Chemicals;ChIP-seq;citrate carrier;Citrates;Citric Acid Cycle;Collaborations;Communication;conditional knockout;Core Facility;cost;cytokine;Cytosol;Data;Development;Development Plans;Disease;disease model;Endothelial Cells;Endothelium;Ensure;Environment;Enzyme-Linked Immunosorbent Assay;etomoxir;experience;Experimental Autoimmune Encephalomyelitis;extracellular;Extramural Activities;fatty acid oxidation;Fatty Acids;Fellowship;Flow Cytometry;Foundations;Gene Expression;Gene Expression Regulation;Gene Proteins;Genes;Genetic;Genetic Transcription;Genomics;Genus Hippocampus;Goals;Grant;Histone Acetylation;Histone H3;Histopathology;Homeostasis;Immune;Immunology;In Vitro;in vivo;Infection;Inflammatory;inhibitor;insight;Institution;interest;Intraperitoneal Injections;Job Application;K-Series Research Career Programs;Knockout Mice;Knowledge;Learning;Lesion;long chain fatty acid;Lysine;Malignant Neoplasms;Measures;Mediation;Meninges;Mentors;Mentorship;Metabolic;metabolic abnormality assessment;metabolic phenotype;Metabolism;Methods;Mitochondria;Mitochondrial Matrix;Mitochondrial Proteins;Modeling;Molecular;mouse model;Mus;National Heart, Lung, and Blood Institute;next generation sequencing;non-histone protein;novel;Oral;oxidation;Oxygen Consumption;Pathway interactions;pharmacologic;Positioning Attribute;Postdoctoral Fellow;Process;Professional Competence;Protein Acetylation;Protein Isoforms;Proteins;Proteomics;Public Health;Publications;Research;Research Training;Role;Scientist;Secure;Signal Transduction;Site;skills;Solid;T cell differentiation;T cell infiltration;T cell regulation;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;tenure track;Therapeutic;Training;transcriptome sequencing;Transducers;translational applications;translational potential;Tricarboxylic Acids;United States National Institutes of Health;Work;Writing

PROJECT_TITLE: Mechanisms and functions of fatty acid oxidation in T cell differentiation

STUDY_SECTION: MTI

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Dietary Supplements;Hematology;Nutrition;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: PROJECT NARRATIVE AML is a lethal blood cancer that needs to develop improved therapeutic approaches. Our proposed research focusing on abnormal vitamin B6 pathway will provide an innovative aspect to understand mechanisms essential to support AML cell proliferation. Functional characterization of abnormal vitamin B6 pathway in AML and detailed understanding of mechanisms underlying its selectivity and synergy will provide novel therapeutic targets and approaches to improve current therapeutic strategies for AML.

PI_NAMEs: ZHANG, LINGBO  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;acute toxicity;Affect;BCL1 Oncogene;Blast Cell;Blood Cells;Bone Marrow;cancer cell;cancer therapy;Candidate Disease Gene;Cell Line;Cell Proliferation;Cells;Cessation of life;chemotherapy;Combined Modality Therapy;CRISPR screen;Data;Dependence;druggable target;Environmental Risk Factor;Enzymes;Exhibits;extracellular;functional genomics;Genetic Engineering;Genomics;Goals;Growth;Hematologic Neoplasms;Hematopoietic Neoplasms;Hematopoietic stem cells;Immune;Impairment;improved;In Vitro;in vivo;in vivo Model;inhibitor;innovation;Investigation;leukemia;leukemia treatment;Leukemic Cell;Malignant - descriptor;Malignant Neoplasms;Medical;Metabolic;Metabolic Pathway;Metabolism;Molecular;mouse model;Myelogenous;new therapeutic target;Normal Cell;novel;novel therapeutic intervention;older patient;Pathway interactions;patient derived xenograft model;Patients;Pattern;peripheral blood;Persons;pharmacologic;Pharmacology;Process;Production;Proliferating;Proteins;rapid growth;Reaction;Regulation;Research;Sampling;single-cell RNA sequencing;Specificity;synergism;Technology;Therapeutic;Therapeutic Effect;therapeutic target;Toxic effect;Treatment Efficacy;tumorigenesis;Vitamin B6;Vitamins;Work

PROJECT_TITLE: Characterizing vitamin B6 pathway dependency in acute myeloid leukemia

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Narrative We have recently found that spontaneous variations in the waking state account for a substantial fraction of the variations in responsiveness of cortical neurons to sensory stimuli. We also found that sorting the animal's cortical sensory responses and behavioral choices by arousal state (as measured by pupil diameter) revealed an inverted U, with optimal responses and performance occurring at intermediate levels of arousal. Here we will address the cellular, network, and neuromodulatory mechanisms underlying the determination of optimal state for neural and behavioral performance. We hypothesize that neuromodulatory transmitter systems are in constant flux and that these fluctuations in release cause ongoing and influential changes in the operating properties of the cerebral cortex. We will use a variety of state-of-the-art techniques, including whole cell recording, two-photon imaging, and optogenetics, to reveal the precise cellular, network, and neuromodulatory mechanisms underlying rapid state control in awake, behaving mice. Dyscontrol of neuromodulatory transmitter release may underlie several different disease disorders. Understanding their mechanisms of function is critical to understanding both the ordered and disordered brain.

PI_NAMEs: MCCORMICK, DAVID  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Action Potentials;Animals;Arousal;Attention deficit hyperactivity disorder;Auditory;Auditory area;autism spectrum disorder;awake;Behavior;Behavior monitoring;Behavioral;behavioral response;Brain;Brain Diseases;Cerebral cortex;Detection;Diameter;Disease;Funding;Goals;Image;Influentials;Investigation;Laboratories;Measures;Membrane Potentials;Mus;Nature;neural;Neurons;neuroregulation;operation;optogenetics;Pathway interactions;Performance;Property;Pupil;Pyramidal Cells;Research Personnel;response;Schizophrenia;Sensory;sensory cortex;sensory stimulus;Shapes;Sorting;Synapses;System;Techniques;two-photon;Variant;Whole-Cell Recordings

PROJECT_TITLE: Cortical Dynamics and Neural/Behavioral Performance


NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Herpes Simplex Virus-1 (HSV-1) causes ocular (eye) herpes that affects ~500,000 people in the United States. HSV-1 encoded microRNAs (miRNA) facilitate virus to evade defense responses. We propose to identify viral miRNA species during disease progression, identify their targets and design strategy for inhibiting HSV-1 miRNAs in the eye.

PI_NAMEs: NAQVI, AFSAR RAZA;SHUKLA, DEEPAK  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Acyclovir;Affect;Aftercare;analog;Animals;Anti-viral Agents;Anti-viral Response;Antigen Presentation Pathway;Antigen-Presenting Cells;Antigens;Attenuated;Autologous;B-Lymphocytes;Biological Process;Blindness;Blood;CD4 Positive T Lymphocytes;CD8B1 gene;Cell Line;Cell Physiology;Cells;Code;Cornea;cytokine;cytotoxic;Data;defense response;Dendritic Cells;design;Development;Disease;disease model;Disease Progression;Double Stranded DNA Virus;Drug resistance;Exhibits;Experimental Designs;Eye;Eye diseases;Eye Infections;Family;Flow Cytometry;Functional impairment;Gene Expression;Genes;Genome;Goals;Herpes Labialis;Herpesviridae;Herpesviridae Infections;Herpesvirus 1;Herpetic Keratitis;Host Defense;Human;Immune;immune cell infiltrate;Immune Evasion;immune function;Immune response;Immune system;immunoregulation;Impairment;in vitro Assay;in vivo;Infection;Infiltration;Inflammation;inhibitor;insight;Interferon Activation;Interferons;Keratitis;Kinetics;Knowledge;latent infection;Lytic;lytic gene expression;Lytic Virus;Macrophage;Measures;Mediating;member;Messenger RNA;MicroRNAs;Morbidity - disease rate;mouse model;Mus;Myeloid Cells;Natural Killer Cells;neutrophil;new therapeutic target;novel;Oligonucleotides;Outcome;Pathogenesis;pathogenic virus;Pathology;Pathway interactions;Pattern;Persons;prevent;Production;Productivity;Proteins;Regulation;Reporting;Resolution;response;RNA;Role;seropositive;Severities;Severity of illness;single-cell RNA sequencing;Sorting;Supporting Cell;Suspensions;Swab;T cell response;T-Cell Activation;T-Lymphocyte;Therapeutic;therapeutic target;Tissues;Topical application;Transcript;Transfection;translational study;Tropism;United States;Untranslated RNA;uptake;Vaccines;Viral;Viral Antigens;Viral Genes;Viral Genome;Viral Load result;Viral Physiology;Virion;Virus;Virus Activation;virus host interaction;Virus Replication;Work

PROJECT_TITLE: HSV-1 Encoded MicroRNAs in the Pathogenesis and Treatment of Ocular Herpes


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: COLUMBIA

ORG_NAME: DOTY SCIENTIFIC, INC.

PHR: A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets Narrative Thousands of researchers are regularly using Nuclear Magnetic Resonance (NMR) techniques, with a majority of the applications driven by the need for structure and function determination in biological macromolecules. The advances developed under this project, in combination with several other advances under separate pro-jects, will allow NMR laboratories to dramatically improve their sensitivity on solids, on a budget they will be able to afford, equipping biomedical researchers with superb new tools for structure-function studies of mem-brane proteins and cellular membrane systems. The components developed under this project will also have major applications in ultra-broadband 6G communications equipment and THz medical imaging methods.

PI_NAMEs: DOTY, FRANCIS DAVID (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: 2019-nCoV;6G Wi-Fi;Alzheimer's Disease;Amyloid beta-42;Amyloid Fibrils;Area;astrophysics;attenuation;Awareness;Binding;Biological;Biomedical Research;Budgets;Cellular Membrane;cold temperature;Communication;Confined Spaces;cost;Country;Cryoelectron Microscopy;Data;design;Development;Diameter;Engineering;Equipment;Frequencies;Funding;Future;High temperature of physical object;HIV;imaging modality;imaging system;improved;invention;Laboratories;macromolecule;Magic;Malignant Neoplasms;manufacture;manufacturing cost;Medical Imaging;Membrane Proteins;meter;Methods;next generation;novel;Nuclear;Nuclear Magnetic Resonance;operation;Optics;Pharmaceutical Preparations;Phase;photonics;Physiologic pulse;Play;Price;Proteins;Publishing;Research;Research Personnel;Resolution;restraint;Role;Satellite Communications;Scanning Tunneling Microscopy;Shapes;Signal Transduction;Small Business Innovation Research Grant;Solid;solid state;solid state nuclear magnetic resonance;Source;Spectrum Analysis;structural biology;Structure;System;Techniques;Technology;Temperature;Testing;Time;tool;transmission process;waveguide;Work


ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Narrative The fungus Candida albicans is responsible for significant morbidity and mortality in hospitalized patients, causing deep-seated invasive infections. Other manifestations of candidiasis include mucosal infections in the oral and vaginal cavities. C. albicans is nearly unique amongst fungi in its ability to thrive in and on human hosts; there are few other fungal species that can do so effectively. This ability must be rooted in specialized adaptations of C. albicans to the host environment but, to date, only a few of these are known. In this proposal a validated set of C. albicans genes will be assessed genetically, all of which are uncharacterized, yet upregulated in response to mammalian innate immune cells. We present compelling data that these genes are excellent candidates to mediate the unique commensal-pathogen life style of C. albicans.

PI_NAMEs: LORENZ, MICHAEL C (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Adhesions;Affect;Age;Amaze;Amino Acids;amyloid formation;Animal Model;Antioxidants;Bacterial Adhesins;Binding;biological adaptation to stress;Biological Assay;Biology;Candida;Candida albicans;Candidiasis;Catheters;Cell Culture Techniques;Cell surface;Cell Wall;Cells;Cessation of life;chemotherapy;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Codon Nucleotides;Complex;Data;Defect;deletion library;Diagnosis;Disseminated candidiasis;Eligibility Determination;Environment;fitness;flexibility;Fungal Genes;fungus;Gastrointestinal tract structure;gene conservation;Gene Expression Profiling;Gene Library;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Transcription;genome annotation;Goals;Hospitalization;Human;Human Microbiome;Hydrolase;Iatrogenesis;Immune;immunological status;implantable device;In Vitro;in vivo;Infection;innovation;Laboratories;Libraries;Life;Life Style;Lipase;Lysine;Macrophage;Malignant Neoplasms;Mediating;Mediator;Metabolism;Methods;microbiome components;microbiota;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;mouse model;Mucous Membrane;Mus;mutant;Mutate;Natural Immunity;neutrophil;novel;novel therapeutics;Nutritional;Open Reading Frames;Operative Surgical Procedures;Oral;Oral candidiasis;oral infection;Organism;Outcome;oxidation;oxidative damage;Oxidative Stress;pathogen;pathogenic fungus;Pathogenicity;Patients;Peptide Hydrolases;Peptides;Phagocytes;Phagocytosis;Phenotype;Physiological;Property;Proteins;Quinones;Reactive Oxygen Species;Resistance;response;Risk Factors;Role;Saccharomyces cerevisiae;Series;Skin;success;Surface;Symbiosis;System;Testing;transcriptome sequencing;Trauma;United States;Vagina;Veins;Virulence;Virulence Factors;Vulvovaginal Candidiasis

PROJECT_TITLE: Characterization of novel virulence factors in Candida

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


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

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE The U.S. health care system is poorly equipped to deal with the growing number of persons living with Alzheimer’s disease and related dementias (PLWD) and their complex medical and psychosocial needs, which may help explain the high rate of potentially inappropriate psychotropic and opioid polypharmacy these PLWD experience. We will use national Medicare data to characterize patient characteristics associated with such central nervous system-active polypharmacy, followed by a national survey of their treating clinicians to understand the clinical decision-making that underlies such potentially inappropriate prescribing. Finally, with input from a multidisciplinary Expert Panel, we will identify possible intervention targets and critical remaining knowledge gaps to reduce psychotropic and opioid polypharmacy.

PI_NAMEs: MAUST, DONOVAN T (contact);VORDENBERG, SARAH ELIZABETH

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Accounting;Address;Agitation;Agonist;Alzheimer's disease related dementia;American;anti-depressive agents;anti-epileptic agents;Antipsychotic Agents;Attitude;Behavior Control;Behavioral Symptoms;Belief;beneficiary;Benzodiazepine Receptor;Benzodiazepines;Caregivers;Caring;Central Nervous System;Cessation of life;Characteristics;Clinical;clinical decision-making;cohort;Combination Medication;Communities;Complex;Data;Data Set;Decision Making;Delusions;Dementia;Dementia caregivers;Distress;Drug Prescriptions;evidence base;experience;Exposure to;fall injury;follow-up;Funding;Future;Geriatrics;Goals;Healthcare;Healthcare Systems;hypnotic;Impaired cognition;improved;insight;Intervention;Interview;Knowledge;Life;Link;Medical;Medicare;Memory impairment;Methods;multidisciplinary;older adult;Opioid;Pain;Patients;Persons;Pharmaceutical Preparations;Pharmacological Treatment;Policies;Polypharmacy;Population;prevent;Process;provider factors;psychological symptom;psychosocial;Regimen;Research;Resources;respiratory;Risk;Sampling;Sleeplessness;Societies;Structure;Surveys;symposium;Symptoms;therapy design;Time;Vacuum;Work

PROJECT_TITLE: Prescribing without a guide: A national study of psychotropic and opioid polypharmacy among persons living with dementia

STUDY_SECTION: HSQE

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


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Confluent vascular endothelial cells respond to fluid shear stress from blood flow by activating three distinct signaling pathways at cell-cell contacts, but our molecular understanding of these events is limited. This project will test the role of adhesion GPCRs of the latrophilin family in these events, and will use a new DNA origami nanodevice to visualize effects of mechanical tension on conformation of potential mechanosensing proteins. Together, this work will provide a molecular foundation for understanding at unprecedented depth the mechanotransduction processes that are critical in vascular physiology and disease.

PI_NAMEs: LIN, CHENXIANG ;SCHWARTZ, MARTIN A (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Address;Adhesions;Adult;alpha-latrotoxin receptor;Area;Arterial Fatty Streak;Arteries;Atherosclerosis;Biochemical;Biology;Blood flow;Blood Vessels;bone morphogenetic protein receptors;cadherin 5;Cardiac;Cell Line;Cells;Collaborations;conformational conversion;Cryoelectron Microscopy;Cytoskeleton;Data;Development;Devices;Diameter;Disease;DNA;Elements;Embryonic Development;Endoglin;Endothelial Cells;Endothelium;Event;experimental study;Extracellular Domain;Family;Foundations;G-Protein-Coupled Receptors;Genes;Heart Valves;In Vitro;in vivo;Inflammation;Intercellular Junctions;KDR gene;Knock-out;Lead;Learning;Liquid substance;lymphatic valve;malformation;Mammals;mechanical force;mechanical load;Mechanics;Mechanoreceptors;mechanotransduction;Mediating;Mediator;Medicine;member;Modeling;Molecular;Molecular Conformation;Mus;Myosin ATPase;nanodevice;Nanotechnology;notch protein;novel;Pathway interactions;Pattern;PECAM1 gene;Physiological;Physiology;Play;postnatal;Predisposition;Process;protein complex;Protein Conformation;Proteins;Publishing;response;Role;shear stress;Signal Pathway;Signal Transduction;Specific qualifier value;Testing;Trees;Vascular Endothelial Cell;Visualization;Work

PROJECT_TITLE: Fluid shear stress mechanotransduction at endothelial cell-cell junctions

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Cancer;Liver Disease;Nanotechnology;Nutrition;Rare Diseases

ORG_CITY: RICHMOND

ORG_DEPT: GENETICS

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Narrative The proposal aims at analyzing the role of macrophage AEG-1 in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), interrogate cysteine palmitoylation as a regulatory mechanism for AEG-1 function, and evaluate inhibition of AEG-1 in hepatocytes and macrophages as a therapeutic strategy for NASH and NASH-HCC. These studies will provide novel mechanistic insights into AEG-1 function and facilitate development of a novel therapeutic strategy for NASH.

PI_NAMEs: SARKAR, DEVANAND  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Address;Adipocytes;Adipose tissue;Astrocytes;Biochemical;Biological Assay;Biology;Cells;chronic liver disease;Cirrhosis;Clinic;Clinical Trials;Cysteine;cytokine;Development;Diet;Diethylnitrosamine;Disease;Enzymes;Event;experimental study;Failure;Fatty acid glycerol esters;Fatty Acids;Gene Expression;Genes;global health;Hepatocyte;High Fat Diet;Human;Impairment;Inflammation;Inflammatory;insight;Interleukin-1 beta;Intervention;knock-down;Knock-in Mouse;Knockout Mice;lipid biosynthesis;Lipolysis;Liver;loss of function;Macrophage;Macrophage Activation;Molecular;Monitor;mouse model;Mus;Mutate;Myeloid Cells;nanoparticle;nanoparticle delivery;nonalcoholic steatohepatitis;Nonesterified Fatty Acids;novel;novel therapeutic intervention;Oncogenes;oxidation;palmitoylation;Pathogenesis;Play;Post-Translational Protein Processing;PPAR alpha;Preventive;Primary carcinoma of the liver cells;Process;Proteins;Publishing;Resistance;RNA Interference;Role;Seminal;Serine;single-cell RNA sequencing;Small Interfering RNA;sugar;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;TNF gene;Transgenic Mice;Translations;Treatment Efficacy;Triglycerides;tumorigenic;Western World

PROJECT_TITLE: The role of AEG-1 in NASH and NASH-HCC

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Noncoding RNAs are major players in the programming of gene expression in development and disease. Our research program uncovers how this programming is initiated at the molecular level and develops fundamental models to study other similar mechanisms that are dysregulated in disease. We dissect key interactions in these pathways to determine how to correct aberrant gene programming.

PI_NAMEs: JOHNSON, AARON M. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Base Pairing;Biochemical;Biological;Cell Nucleus;Cells;Centromere;Chromatin;Development;Disease;Epigenetic Process;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene repression;Genes;Genome;Genome Stability;Genomic approach;Goals;Heritability;Heterochromatin;Histones;Human;human disease;Human Genome;insight;Intervention;Junk DNA;Link;Malignant Neoplasms;Mediating;Messenger RNA;Modeling;Molecular;Molecular Mechanisms of Action;Nuclear;Pathway interactions;pharmacologic;piRNA;programs;Public Health;Reader;Regulation;Research;RNA;RNA-Binding Proteins;Study models;System;Transcript;Untranslated RNA;Work

PROJECT_TITLE: Mechanisms of heterochromatin targeting and epigenetic genome regulation

STUDY_SECTION: MRAA

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


ORG_CITY: BOZEMAN

ORG_NAME: MONTANA STATE UNIVERSITY - BOZEMAN

ORG_STATE: MT

PHR: Public Health Relevance: RNA-guided nucleases that protect bacteria and archaea from infection by viruses are now being routinely repurposed for genome engineering in a wide variety of cell types and multicellular organisms. However, creative and safe application of these new tools requires a fundamental understanding of how these systems function. This proposal aims to elucidate the mechanisms of two nucleic acid guided defense systems in bacteria (Argonaute proteins and CRISPR-Cas systems), with an eye toward the development of new tools for molecular biology and medicine.

PI_NAMEs: WIEDENHEFT, BLAKE A (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Adaptive Immune System;Antibiotic Resistance;Archaea;Bacteria;Bacteriophages;cell community;cell type;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Creativeness;Development;Disease;DNA;Ecology;Equilibrium;Evolution;Genes;Genetic;genetic element;Genetic Variation;Genome engineering;Goals;Guide RNA;human microbiota;Immune system;Infection;innovation;insight;interest;Invaded;Mediating;Molecular Biology;Molecular Medicine;mortality;nuclease;Nucleic Acids;Organism;Pathogenesis;Phylogenetic Analysis;Planets;Play;preservation;Process;Proteins;public health relevance;Research;Role;Sampling;Small RNA;Source;System;tool;trait;Viral;Virulence;Virus;Virus Diseases;Work

PROJECT_TITLE: Structural and functional understanding of bacterial defense and viral counter defense

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Complementary and Integrative Health;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative The intestinal pathogen Clostridiodies difficile is most common hospital-acquired infection in the United States, and the inefficacy of current antibiotic treatment regimens highlight the need to develop alternative treatment strategies. Transplantation of fecal bacteria from a healthy donor into an infected patient’s intestinal tract has emerged as a remarkably effective and promising therapy, however, the mechanism through which beneficial bacteria act to clear C. difficile is not well understood. This proposal seeks to understand how the body’s own immune system works with the fecal transplant to support resolution of C. difficile infection. 1

PI_NAMEs: ABT, MICHAEL C. (contact)

PROJECT_TERMS: Ablation;Adoptive Transfer;alternative treatment;Antibiotic Therapy;Bacteria;Bile Acids;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Shape;Cells;Cessation of life;Clinical;Clostridium difficile;cohort;Complex;cost estimate;cytokine;Data;Diarrhea;Disease;disorder control;Economic Burden;Engraftment;enteric pathogen;Environment;Exhibits;experience;Failure;fecal transplantation;FOXP3 gene;gain of function;Genotype;gut colonization;gut inflammation;gut microbiome;Health Care Costs;Healthcare Systems;Heterozygote;Hospitalization;Human;Immune;immune activation;Immune system;Immune Targeting;immunological status;immunoregulation;impaired capacity;Impairment;Incidence;Infection;Inflammation;Inflammation Mediators;Inflammatory;insight;Interleukin-10;Intestines;Longitudinal Studies;loss of function;Mediating;Medical;metabolome;metabolomics;microbial;microbial community;microbiome;microbiota;monocyte;mouse model;Mus;neutrophil;new therapeutic target;Nitrogen;Nosocomial Infections;novel therapeutics;opportunistic pathogen;Oxygen;Pathway interactions;Patients;pharmacologic;Population;prevent;Production;Rag1 Mouse;Recombinants;Recurrence;Regulatory T-Lymphocyte;Reporter;Resolution;Role;Severities;Shapes;Signal Transduction;Source;success;Testing;Therapeutic;Toxic Megacolon;Transplantation;transplantation therapy;Treatment Protocols;treatment strategy;United States;Work

PROJECT_TITLE: Investigating Immune-Microbiome interactions during treatment of Clostridioides difficile with fecal microbiome transplantation

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


NIH_SPENDING_CATS: Aging;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Patient Safety;Social Determinants of Health

PHR: Project narrative/public health relevance statement This project will examine the effects of the Skilled Nursing Facility Value-Based Purchasing program on outcomes for older adults leaving the hospital and entering skilled nursing facilities for post-acute care. This is important because one in five Medicare beneficiaries currently receives post-acute care in a skilled nursing facility, and this care is expensive and frequently associated with adverse outcomes. Understanding how this program achieves intended results, and what unintended consequences may come from the program particularly given the effects of the COVID-19 pandemic, will help shape payment programs intended to improve outcomes in post-acute care.

PI_NAMEs: BURKE, ROBERT EDWARD (contact)

PROJECT_TERMS: acute care;Admission activity;adverse outcome;beneficiary;care outcomes;Caring;cost;COVID-19;COVID-19 impact;COVID-19 mortality;COVID-19 pandemic;COVID-19 pandemic effects;COVID-19 prevalence;COVID-19 susceptibility;Data;Death Rate;design;Development;Disparity;Elements;ethnic minority;ethnic minority population;evidence base;Face;Fee-for-Service Plans;Future;Goals;Health;Health care facility;Health system;Home;hospital readmission;Hospitalization;Hospitals;Impaired cognition;improved;improved outcome;Incentives;Individual;insight;Interview;Length of Stay;low socioeconomic status;Medicare;Methods;mortality;older adult;Outcome;patient population;Patient-Focused Outcomes;Patients;payment;Performance;personal protective equipment;Policies;Policy Maker;pressure;Process;programs;public health relevance;racial minority;racial minority population;Readiness;readmission rates;resilience;response;Schedule;Shapes;Skilled Nursing Facilities;Stress;stressor;Structure;success;Testing;Time;Vulnerable Populations

PROJECT_TITLE: Effect of post-acute care pay for performance in skilled nursing facilities on outcomes and disparities

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: NARRATIVE A vaccine against group A Streptococcus (GAS) is a major global health priority, but this quest must provide efficacy while avoiding autoimmune sequelae linked to the pathogen. We recently made the critical discovery that choice of adjuvant is key for GAS vaccine efficacy. We will undertake head-to-head comparison of M protein and non-M protein GAS vaccines, adjuvanted with both alum and selected emulsion and liposome-based adjuvants, in humanized and outbred murine models and the non-human primate model of GAS pharyngitis. This work will serve as a valuable resource to the entire vaccine research field and facilitate progression of a GAS vaccine into commercial use.

PI_NAMEs: NIZET, VICTOR  (contact);WALKER, MARK JOSEPH

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: 3-Dimensional;Acute;Adjuvant;Adjuvant Study;Adult;aluminum sulfate;animal efficacy;Animal Model;Antigens;Autoimmune;brain tissue;Carbohydrates;Cessation of life;Child;Clinical;Collaborations;Communities;Conjugate Vaccines;cross reactivity;data modeling;Disease;disease model;efficacy study;Emulsions;experience;experimental group;Formulation;global health;Goals;head-to-head comparison;Health Priorities;healthcare burden;Heart;Human;Immune;Immune response;Immunity;Immunization;immunogenic;Infection;intraperitoneal;Investigation;Link;Liposomes;manufacture;Mission;Modeling;mortality;mouse model;multiple myeloma M Protein;Mus;N-terminal;nonhuman primate;pathogen;pathogenic bacteria;Pharyngeal structure;Pharyngitis;Phase;Plasminogen;Play;pre-clinical;preclinical development;preclinical study;prevent;Primary Infection;Productivity;Program Development;protective efficacy;Proteins;Public Health;Pyoderma;Queensland;reduce symptoms;Resources;response;Rheumatic Fever;Rheumatic Heart Disease;Role;Safety;Scientist;Series;Skin;Streptococcal Vaccines;Streptococcus pyogenes;Subunit Vaccines;Switzerland;technology training;Technology Transfer;Tennessee;Tissues;Tonsillitis;Transgenic Organisms;Universities;Vaccinated;Vaccination;Vaccine Antigen;vaccine candidate;vaccine development;vaccine efficacy;vaccine formulation;Vaccine Research;vaccine safety;Vaccines;Work

PROJECT_TITLE: Identifying the Most Effective Adjuvant(s) for Leading Group A Streptococcal Vaccine Antigens in Preclinical Mouse and Nonhuman Primate Models


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

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: This application will investigate major regulatory signaling of APOE variants in peripheral immunity (neutrophils) and brain (microglia) as targets to treat Alzheimer’s disease (AD). We identified a critical role for APOE4 in the induction of inflammatory neutrophils and their recruitment to the diseased brain, which promotes a neurodegenerative phenotype in microglia associated with disease progression. We will implement our new tools to specifically modulate the crosstalk between APOE4-neutrophils and microglia to ameliorate disease progression using novel mouse models and human samples, including microglia and neutrophils from AD patients. These strategies and new tools will allow us to investigate the role of APOE variants in neutrophil- microglia interactions in AD.

PI_NAMEs: BUTOVSKY, OLEG  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Acceleration;Acute;Affect;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Alzheimer's disease risk;Apolipoprotein E;apolipoprotein E-4;APP-PS1;Area;Astrocytes;Basic Science;Blood;Brain;brain cell;Brain Diseases;Cells;cerebral atrophy;Chronic;Clinic;cognitive function;Data;Dementia;Disease;Disease associated microglia;Disease Progression;Female;Gender;Genetic;genetic risk factor;genome-wide;Genotype;Gliosis;Goals;Human;Immune response;Immunity;immunoregulation;Impaired cognition;improved;In Vitro;in vivo Model;induced pluripotent stem cell;Infiltration;Inflammatory;Inflammatory Response;innate immune function;innate immune pathways;insight;Investigation;Late Onset Alzheimer Disease;Macrophage;male;Mediating;Memory impairment;Meta-Analysis;Microglia;Modeling;mouse model;Mus;Natural Immunity;Nerve Degeneration;Neurodegenerative Disorders;neurodegenerative phenotype;neuroinflammation;neuroprotection;neutrophil;Neutrophil Infiltration;novel;novel therapeutic intervention;Onset of illness;Outcome;Peripheral;Phenotype;Play;Protein Isoforms;recruit;Regulation;Research;Resolution;Risk;risk variant;Role;Sampling;Senile Plaques;sex;Signal Transduction;Spatial Distribution;tau Proteins;tool;Transgenic Mice;Translating;trend;Variant

PROJECT_TITLE: Gender-dependent APOE4 regulation of neutrophil-microglia crosstalk in Alzheimer's disease

STUDY_SECTION: CMND

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


NIH_SPENDING_CATS: Autoimmune Disease;Eye Disease and Disorders of Vision;Immunotherapy;Neurosciences

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Inflammatory diseases of the eye pose a serious threat of visual impairment or even blindness, especially if they affect the tissues comprising the visual axis. The eye has developed strategies to maintain essential immune competence, while limiting opportunities for inflammatory damage. Our proposed studies focus on important components of these strategies, particularly antigen presentation and the balance between effector T cells, regulatory T cells, and anergic T cells within the retina, and how local manipulations of these components can be used therapeutically to treat inflammatory eye disease.

PI_NAMEs: MCPHERSON, SCOTT W (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Acceleration;Affect;anergy;Antigen Presentation;Antigen Targeting;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Arrestins;Autoantigens;Autoimmune;autoimmune pathogenesis;Autoimmunity;Blindness;CD4 Positive T Lymphocytes;Cell Communication;Cells;Central Nervous System;Chronic;Complex;cytokine;Dendritic Cells;Disease;effector T cell;Equilibrium;Eye;Eye diseases;Generations;Graves' Disease;Homeostasis;Immune;immune function;Immune response;Immune Tolerance;Immunocompetence;Inflammatory;Injury;Insulin-Dependent Diabetes Mellitus;ITGAX gene;Knowledge;Learning;Local Therapy;Mediating;Microglia;Modeling;mouse model;Mus;Myeloid Cells;Nature;Organ;Peptides;Phenotype;Play;Population;prevent;Process;Production;Property;Regulation;Regulatory T-Lymphocyte;response;Retina;Rheumatoid Arthritis;Role;Sarcoidosis;Severities;side effect;Signal Transduction;Systemic Lupus Erythematosus;Systemic Therapy;T cell anergy;T-Lymphocyte;Testing;Therapeutic;Therapeutic Uses;Thymus Gland;Tissue Grafts;Tissues;Transgenic Mice;translational study;uveoretinitis;Visual;Visual impairment

PROJECT_TITLE: Local Control and Regulation of Retinal Autoimmunity

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

ORG_CITY: ROCHESTER

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative: Understanding HIV infection status is an important component of reducing spread of the disease and ensuring infected patients receive lasting and effective care. Unfortunately, current HIV self-tests do not detect the virus directly, and therefore aren’t useful at the earliest stages of infection or as a way to monitor if therapy is effective. We will address this gap by developing the first easy to use HIV self-test that directly detects the genetic material of the virus.

PI_NAMEs: MILLER, BENJAMIN L (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Acceleration;Accident and Emergency department;Address;amplification detection;antibody detection;antiretroviral therapy;Biological Assay;Blood capillaries;Blood Volume;Caring;Catalytic DNA;Cellular Phone;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Complex;Contracts;Coupled;Cytolysis;Data;Data Set;design;Detection;detection assay;detection limit;Development;Devices;Diagnostic;Disease;DNA;Emergency department visit;Ensure;Enzymes;Feedback;Fingers;Fluorescence;Genetic Materials;genomic RNA;Guidelines;HIV;HIV Antibodies;HIV Infections;Human immunodeficiency virus test;Humidity;Infection;innovation;instrumentation;Interview;Laboratories;manufacture;Manufacturer;manufacturing test;Masks;Medical center;Methods;Molecular;Monitor;Nanotechnology;novel strategies;Nucleic Acids;operation;Paper;pathogenic virus;Patient Recruitments;Patients;Performance;performance tests;Phase;pilot test;Plasma;Plasma Cells;Porosity;Preparation;Process;Production;prototype;Reaction;Reader;Research;Risk;RNA;RNA amplification;Sampling;self testing;Sensitivity and Specificity;Source;Specificity;stability testing;Structure;success;Temperature;Testing;Universities;usability;Validation;Viral;viral detection;Viral Load result;viral rebound;viral RNA;Virion;Virus;Whole Blood;whole genome;Work

PROJECT_TITLE: Paper-based HIV self test


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Myelodysplastic syndrome and myeloproliferative disorders currently affect over 400,000 individuals in the United States alone; they affect blood production and predispose to leukemia. Their onset is age-dependent but the genetic factors that determine their risk with aging is not understood. This proposal examines the role of acquired mutations in the blood with aging that promote and protect against the acquisition of these blood disorders with the goal of identifying new approaches to their early identification and prevention.

PI_NAMEs: SCHRATZ, KRISTEN E (contact)

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Adult;Affect;African American;Age;age related;Aging;Applications Grants;Automobile Driving;autosome;Baltimore;biobank;Biological Markers;Blood;Chromosomes;Clinical;Clonal Evolution;Clonality;cohort;Communities;Computational Biology;Data;Development;Disease;Disease Outcome;Disease Progression;disorder risk;DNA Damage;Dysmyelopoietic Syndromes;Early identification;Environment;Erythrocytes;Etiology;Event;gain of function mutation;Gene Mutation;Genes;Genetic;genetic epidemiology;Germ Lines;Germ-Line Mutation;Goals;Hematologic Neoplasms;Hematological Disease;Hematopoiesis;Hematopoietic;Heritability;Individual;Inherited;JAK2 gene;Knowledge;Lead;Length;leukemia;Life;Link;Longterm Follow-up;loss of function;loss of function mutation;Malignant Neoplasms;Measures;medical schools;Mendelian disorder;Mentors;Mentorship;mutant;Mutation;Myelodysplastic/Myeloproliferative Disease;Myelogenous;Myeloproliferative disease;novel;novel marker;novel strategies;Participant;Patients;Pattern;Phenotype;Phylogenetic Analysis;Polycythemia Vera;Population;population based;Population Control;predictive marker;premature;Prevalence;Prevention;pro-aging;Production;promoter;Publications;reconstruction;Reporting;response;Risk;Risk Factors;RNA-Directed DNA Polymerase;Role;Sampling;sequencing platform;skills;Solid;specific biomarkers;stem cells;Syndrome;Telomerase;Telomerase RNA Component;telomere;Testing;Training;trait;United States;Universities;Untranslated RNA;Woman;Women's Health;Work

PROJECT_TITLE: Determinants of Myeloid Clonal Evolution

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Regenerative Medicine

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative The proposed research will provide important new information about the functioning of cones under daylight conditions. Preliminary studies suggest that the regeneration of cone pigments is driven by light through a novel biochemical mechanism in Müller cells. Given the importance of cones to human vision, the proposed research is highly relevant to the NEI mission. The gene for one of the proteins to be studied (RGR) is a susceptibility locus for retinitis pigmentosa, hence the project is also relevant to the broad NIH mission that pertains to reducing illness and disability.

PI_NAMEs: TRAVIS, GABRIEL H (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 11-cis-Retinol;absorption;Address;All-Trans-Retinol;Binding;Biochemical;cDNA Expression;Cells;chromophore;Cone;Consumption;disability;disorder of macula of retina;Dissociation;Exhibits;Exposure to;Family;Funding;G-Protein-Coupled Receptors;Genes;Genetic;Goals;Human;Inherited;Insecta;Invertebrates;Isomerism;Knowledge;Light;Mammals;member;Metabolic Pathway;Methodology;Mission;Muller's cell;Mutation;NADP;Natural regeneration;Neural Retina;novel;Opsin;Outcome Study;Oxidation-Reduction;Oxidoreductase;Pathway interactions;Photobleaching;Photons;Photophobia;Photoreceptors;Phototransduction;Physiological;Pigments;Process;Proteins;Publishing;Reaction;Reporting;Research;Retina;Retinal Cone;Retinal Diseases;Retinal Pigments;retinal regeneration;Retinaldehyde;Retinitis Pigmentosa;Retinol dehydrogenase;Rhodopsin;Rod;Role;Source;Specificity;Substrate Specificity;Susceptibility Gene;Testing;United States National Institutes of Health;Vertebrate Photoreceptors;Vertebrates;Visible Radiation;Vision;Visual;visual cycle;Visual Perception;Visual System

PROJECT_TITLE: Mechanisms for Light-driven Chromophore Synthesis by Müller Cells to Regenerate Cone Opsin and Maintain Cone Sensitivity

STUDY_SECTION: BVS

STUDY_SECTION_NAME: Biology of the Visual System Study Section[BVS]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Patient Safety;Pediatric;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

PHR: PROJECT NARRATIVE As some children who have obstructive sleep-disordered breathing (snoring or sleep apnea) benefit from tonsillectomy surgery and some do not, the decision for tonsillectomy relies on good communication so that treatment decisions align with the patient and family values. Black and Hispanic children have poorer sleep and surgery outcomes which may in part be attributed to negative clinician attitudes and deficient communication with families. We evaluate how patient race/ethnicity and surgeon bias influence communication and care outcomes, learn how parents and clinicians perceive communication during surgical visits, and ultimately direct interventions to promote respectful communication, reduce disparities, and improve outcomes for children with obstructive sleep-disordered breathing.

PI_NAMEs: BOSS, EMILY FRANCES (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: Address;Adenoidectomy;Affect;alternative treatment;Attitude;Audiotape;Behavior;Black race;care delivery;care outcomes;Caring;Child;Child Care;Child Rearing;Childhood;Clinical;clinical encounter;Code;cohort;Collaborations;Communication;communication behavior;Communication Research;Complex;Consultations;Coupled;cultural competence;Decision Making;Disparate;Disparity;disparity reduction;Educational Intervention;Elements;Emotional;Emotions;Environmental Risk Factor;Equity;ethnic bias;ethnic diversity;ethnic minority population;Ethnic Origin;experience;Family;Goals;health care quality;Hispanic;implicit bias;improved;improved outcome;innovation;insight;Institution;Intervention;Interview;Language;Learning;Low income;Maps;Mediating;Mediator;Minority;minority children;Operative Surgical Procedures;Outcome;Parents;Participant;patient oriented;Patient-Focused Outcomes;Patients;Perception;Persons;physical conditioning;Play;poor sleep;Population;Postoperative Period;preference;Prevalence;Procedures;Published Comment;Quality of Care;Race;racial bias;racial diversity;racial minority population;Reaction;Recording of previous events;recruit;Reduce health disparities;Regrets;Reporting;repository;Research;response;Role;shared decision making;Sleep;Sleep Apnea Syndromes;Sleep disturbances;Snoring;social;Sum;Surgeon;surgery outcome;Surgical complication;Testing;therapy development;Time;Tonsillectomy;Trust;Visit;Vulnerable Populations;Work

PROJECT_TITLE: Project CONNECTS (Communication and Outcomes that eNhaNce Equity in Childhood Tonsillectomy and Sleep)

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Hearing Loss;Neurodegenerative;Neurosciences

ORG_CITY: SPRINGFIELD

ORG_NAME: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED

PHR: Project Narrative The proposed studies are designed to better understand how age-related hearing loss negatively impacts acoustic information processing in auditory brain centers. Brain substances/neurotransmitters involved in hearing and attention show age-related changes, but those specifically involved in attention seem resistant to aging. Neurotransmitter systems in the older brain may provide unique receptor targets for the development of drugs designed to ameliorate certain aspects of age-related loss of speech understanding.

PI_NAMEs: CASPARY, DONALD M. (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acetylcholine;acetylcholine receptor agonist;Acoustics;Affect;age effect;age related;age related changes;aged;Aging;Amino Acids;Anesthesia procedures;antagonist;Attention;attentional modulation;Auditory;Auditory area;auditory pathway;Auditory system;auditory thalamus;awake;Award;Behavioral;Binding;Brain;Cell Nucleus;cell type;Cells;cholinergic;Cholinergic Receptors;Code;Cognition;Cognitive;Complex;Data;design;Development;Disease;Dorsal;Drug Design;drug development;Drug Targeting;Elderly;Electrophysiology (science);Exposure to;Female;Fluorescent in Situ Hybridization;Future;Glutamates;Grant;Hearing;human old age (65+);Impaired cognition;improved;In Vitro;in vivo;Individual;Industrialization;Inferior Colliculus;information processing;juvenile animal;Knowledge;Location;male;Medial geniculate body;Mediating;Mental Depression;Modeling;Neurons;Neurotransmitters;Nicotinic Receptors;novel;Older Population;optogenetics;patch clamp;Pharmaceutical Preparations;pharmacologic;Pharmacology;Pontine structure;Population;postsynaptic;preference;Presbycusis;presynaptic;Property;radioligand;Rattus;Rattus norvegicus;receptor;Receptor Activation;receptor function;Resistance;Resources;response;Sensory;Sex Differences;Signal Transduction;Slice;social;Social isolation;Speech;Stimulus;Structure;synaptic function;System;Tegmentum Mesencephali;Thalamic structure;Transcript;United States;Withdrawal;young adult

PROJECT_TITLE: Coding in Auditory Neurons: Effects of Amino Acids

STUDY_SECTION_NAME: Auditory System Study Section[AUD]