ORG_CITY: LEEDS

ORG_NAME: NORTHAMPTON VA MEDICAL CENTER

PHR: After a right brain stroke, >50% of veterans experience problems with dressing, eating, self-care or steering their wheelchairs because their ability to move, orient, and respond toward the left side is limited: spatial neglect. Spatial neglect prevents them from functioning independently, and their needs in the hospital and at home are greatly increased. An effective treatment for spatial neglect is 10 days of visuomotor training while wearing optical prisms (PAT), however many clinicians [fail to diagnose spatial neglect and use this approach. In this study, we will develop a brain scanning test that could objectively identify the veterans with spatial neglect after stroke who are the best candidates to receive PAT and recover their ability to function. When the research is complete, we expect that brain scans done in the hospital can guide the team to refer veterans to PAT rehabilitation: improving daily life function] and quality of life.

PI_NAMEs: BARRETT, A. M. (contact)

PROJECT_TERMS: Address;Algorithms;Attention;Basal Ganglia;behavior prediction;Behavioral;Biological;Biological Markers;biomarker identification;biomarker validation;Brain;Brain imaging;Brain scan;candidate identification;candidate marker;care systems;Caregivers;Caring;Characteristics;Classification;Clinical;Clinical Data;Clinical Treatment;Clinical Trials;Cognition Disorders;Cognitive;cognitive rehabilitation;Communities;Data;Development;Diagnosis;Eating;effective therapy;Elements;Enrollment;evidence base;expectation;experience;fall risk;frontal lobe;frontal lobe cortex;functional disability;functional improvement;functional independence;functional outcomes;Home;hospital readmission;Hospitalization;Hospitals;imaging biomarker;improved;innovation;Lateral;Left;Lesion;Life;Maps;Measures;Medical center;Modeling;Motor;motor recovery;Movement;Neurobiology;neuroimaging;neuroimaging marker;Neurology;Optics;Outcome;Paralysed;Parietal;Parietal Lobe;Pathologic;Pathway interactions;Patients;Perception;personalized approach;personalized health care;post stroke;precision medicine;predicting response;Prediction of Response to Therapy;predictive marker;prevent;Process;prognostic model;Prospective Studies;Quality of life;Recovery;Recovery of Function;recruit;rehabilitation research;Rehabilitation therapy;Reporting;Research;Research Personnel;Scientist;Self Care;Series;Side;spatial neglect;Specificity;Sterile coverings;Stroke;stroke rehabilitation;stroke survivor;Supervision;Symptoms;System;targeted treatment;Techniques;Testing;Training;Treatment outcome;treatment responders;treatment response;Uncertainty;Veterans;Visual;visual motor;Wheelchairs;white matter;Work

PROJECT_TITLE: Prism adaptation treatment (PAT) for right brain stroke rehabilitation

STUDY_SECTION_NAME: Sensory Systems & Communication Disorders[RRD3]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: Aurora

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE The studies in this proposal will test a novel role of systemic upregulation of the signaling molecule, PTEN, by the pharmacological agent, 5-azacytindine, in suppressing vascular disease progression. Studies using cultured smooth muscle cells and macrophages will define the role of 5-azacytidine on PTEN expression and cell phenotypic changes, studies using mouse models of vascular disease and pharmacological approaches will establish the importance of PTEN upregulation on inhibition of vascular disease, and studies using normal and diseased human arteries will add translational significance. As SMC phenotype and recruitment of macrophages are critical to the progression of vascular diseases, our findings will be highly relevant with the potential to develop novel therapeutics aimed at preserving the mature SMC phenotype for purposes such as stabilization of atherosclerotic lesions and inhibition of in-stent restenosis.

PI_NAMEs: WEISER-EVANS, MARY CM (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acute;Angiotensin II;Arterial Fatty Streak;Arteries;Atherosclerosis;Azacitidine;Biological Assay;bisulfite;Blood Vessels;cell dedifferentiation;Cells;Chromatin;Chronic;cofactor;Complex;Coronary artery;CRISPR/Cas technology;Data;design;Disease Progression;DNA;DNA Methylation;DNA Modification Methylases;Down-Regulation;Etiology;Event;Fibrosis;Genes;Genetic Transcription;Genomics;high throughput screening;Human;human disease;Hypermethylation;In Situ;In Situ Hybridization;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory milieu;inhibitor;Injury;Knockout Mice;Ligation;Macrophage;Manuscripts;Mediating;Methylation;Modeling;Molecular;mouse model;Mus;Muscle;Myelogenous;myocardin;neointima formation;novel;novel therapeutics;Nuclear;Pathogenicity;Pathologic;pharmacologic;Phenotype;Phosphoric Monoester Hydrolases;PIK3CG gene;Platelet-Derived Growth Factor;Play;preservation;prevent;promoter;protective effect;PTEN gene;public health relevance;Publishing;pyrosequencing;recruit;Regulation;Reporter;Repression;restenosis;Role;Signaling Molecule;Site;small molecule;Smooth Muscle Myocytes;Stents;Stimulus;Testing;Therapeutic;therapeutic target;transcription factor;Transcriptional Regulation;Up-Regulation;Vascular Diseases;Vascular remodeling;Vascular Smooth Muscle

PROJECT_TITLE: PTEN promoter hypermethylation underlies vascular disease progression

STUDY_SECTION: AICS

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Climate-Related Exposures and Conditions;Intellectual and Developmental Disabilities (IDD);Maternal Health;Mental Health;Microbiome;Neurosciences;Pediatric;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: DURHAM

ORG_DEPT: PSYCHOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Air pollution exposure early in life is linked to disorders like autism spectrum which show high co-morbidity with gastrointestinal issues. This project will characterize microbiome, gut, and behavioral changes in the offspring of pregnant mice exposed to air pollution. It will determine causality among the microbiome composition changes, gut permeability changes, and behavioral abnormalities and thereby enhance our understanding of this devastating disorder.

PI_NAMEs: BILBO, STACI D (contact)

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Ablation;Address;Adult;Age;Air Pollution;Anxiety;Atopobium vaginae;Attention;autism spectrum disorder;Bacteria;Behavior;Behavioral;behavioral outcome;Birth;Brain;brain dysfunction;Brain region;Characteristics;Cognitive deficits;Communication;comorbidity;comparison control;Data;Deglutition;Development;Diesel Exhaust;Disease;disorder risk;Environmental Exposure;Environmental Impact;Environmental Pollutants;environmental stressor;Etiology;Excitatory Synapse;exposed human population;Exposure to;Female;Fostering;Functional disorder;gastrointestinal;gastrointestinal epithelium;Goals;gut bacteria;gut dysbiosis;gut microbiome;gut microbiota;immune activation;Immune response;Impairment;in vivo;Inflammation;Inhalation;Intervention;intestinal epithelium;Intestinal permeability;Life;Link;male;maternal microbiome;maternal stress;Metagenomics;microbial;microbiome;microbiome composition;microbiome therapeutics;microbiota;Microglia;model of autism spectrum disorder;Modeling;Morphology;Mus;Neurodevelopmental Disorder;Newborn Infant;novel;offspring;Outcome;particle;particle exposure;Particulate Matter;Patients;Phagocytes;Phagocytosis;Phenocopy;Phenotype;Population;Pregnancy;pregnant;prenatal;prenatal exposure;prevent;pup;receptor;Reporting;Rodent;Role;sex;single cell sequencing;social deficits;Stimulus;stressor;Structure;Supplementation;Synapses;Testing;Therapeutic;Third Pregnancy Trimester;Time;Toxic Environmental Substances;Toxicant exposure;transmission process;Vaginal delivery procedure;virtual;Virus Diseases;Volatile Fatty Acids;Weaning

PROJECT_TITLE: Gut-brain dysfunction following combined prenatal stressors: relevance for autism

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: LA JOLLA

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative. This program establishes a high-throughput system for targeted biosynthetic gene cluster discovery, engineering, and heterologous production. Our team evaluates and implements a new synthase- guided single cell genomics approach for the discovery of natural products from marine animal-associated microbes. This unique fusion between chemical biology, targeted single-cell genomics and synthetic biology suggest an innovative new approach to antibiotic discovery.

PI_NAMEs: BURKART, MICHAEL D. (contact);STEPANAUSKAS, RAMUNAS ;WOYKE, TANJA

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Anabolism;Animals;Antibiotics;Bioinformatics;Biology;Carrier Proteins;Cells;Chemicals;Color;Communicable Diseases;Communication;Complex;Data;Development;Ecosystem;Engineering;Ensure;Environment;ESKAPE pathogens;Fatty Acids;Flow Cytometry;functional genomics;Gene Cluster;genetic makeup;Genome;genome database;Genomic approach;genomic data;Genomics;Goals;human disease;Hybrids;Hydro-Lyases;innovation;insight;Label;Laboratories;marine;marine natural product;Metabolic;Metabolism;Metagenomics;Methodology;Methods;Microbe;microbial;Microbial natural product;microbiome;Modeling;Molecular Probes;natural product derivative;Natural product discovery;Natural Products;Natural Source;Needles;novel;novel strategies;nudibranch;Organism;pathogenic microbe;Peptides;Planets;Play;polyketide synthase;polyketides;Porifera;Preparation;Production;programs;reconstruction;Research;Role;sample collection;single cell genomics;Sorting;Source;synthetic biology;System;Urochordata

PROJECT_TITLE: Enabling synthetic biology through single cell functional genomics

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Infectious Diseases;Racial and Ethnic Minority Health Research

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: During the course of the pandemic and over the last 35 years despite much effort we have only cured a single individual of human immunodeficiency virus or HIV. There is, however, a small group of individuals, termed elite controllers or ECs, who are able to control HIV all on their own, and during our prior studies of these people we have seen that they down-regulate a key human gene that the virus relies upon. This grant is focused on how, at a molecular level, these individuals are capable of doing so.

PI_NAMEs: SUTTON, RICHARD  (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Africa;African;African American population;American;antiretroviral therapy;Asian Americans;ATAC-seq;Authorization documentation;autosome;Bioinformatics;Biological Assay;causal variant;CCR5 gene;CD4 Positive T Lymphocytes;Cell surface;chromosome conformation capture;Cis-Acting Sequence;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;Collaborations;Complementary DNA;Coupled;CRISPR/Cas technology;Data;Defect;Disease remission;Distal;DNA sequencing;Down-Regulation;Enhancers;Enterochromaffin Cells;Ethnic Origin;European;exome sequencing;Family member;Freezing;Genes;Genetic;genetic pedigree;Genetic study;Genetic Transcription;genome wide association study;Genomics;Grant;Guide RNA;Health;Hispanic Americans;HIV;HIV Infections;HIV Long Terminal Repeat;HLA-B Antigens;Homologous Gene;Household;Human;immune function;In Vitro;indexing;Individual;Inheritance Patterns;interest;Kinetics;Laboratories;Lentivirus Vector;Link;Macrophage;Master of Science;Medical;Messenger RNA;Methods;Molecular;Nature;novel;overexpression;pandemic disease;Paper;Patients;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Phenotype;Population;Production;Protein Isoforms;Proteins;Publishing;Race;receptor;Recording of previous events;recruit;Reporter;Reproducibility;Resistance;RNA;Sampling;Slave;T memory cell;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;Technology;Testing;Training;transcription factor;Transcriptional Regulation;transcriptome sequencing;Transfection;Uganda;Universities;Variant;vector;Vesicular stomatitis Indiana virus;viral resistance;Virus;Virus Replication

PROJECT_TITLE: Mechanisms of transcriptional regulation of ccr5 and host genetic control of HIV

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative: Aging, a strong risk factor for Alzheimer's disease, causes detrimental changes in the hippocampus, which is a key brain region responsible for learning and memory function. This proposal investigates how TIMP2, a protein revealed to be elevated in young blood, acts within the central nervous system to facilitate hippocampal synaptic function on a gene expression, cellular, and cognitive level in the context of Alzheimer's disease pathology. Creating insight into this mechanism will inform therapies targeting facets of Alzheimer's disease, while also providing insights into how other secreted proteins within the hippocampus influence cognitive function.

PI_NAMEs: CASTELLANO, JOSEPH MICHAEL (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Ablation;Age;aged;Aging;aging brain;aging process;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapy;Amyloid;Amyloid beta-Protein;Award;Behavioral;Blood;Blood Vessels;Body System;Brain;Brain region;Cause of Death;Cells;Central Nervous System;Cognitive;cognitive function;cognitive performance;cohort;Data;Dementia;dementia risk;Dendritic Spines;dentate gyrus;Dependence;Development;Elderly;Endothelium;Environment;Exhibits;Exposure to;Gene Expression;Genes;granule cell;Heart;Hilar;Hippocampus;Human;Impaired cognition;Impairment;improved;in vivo;Infusion procedures;Injections;insight;Intercellular Fluid;Investigation;Knock-in;Knock-in Mouse;Learning;Left;Link;Liver;Long-Term Potentiation;Mediating;Memory;Metabolism;Microdialysis;MMP2 gene;Modeling;mouse model;Mus;Muscle;neuroblast;Neurons;new therapeutic target;novel;old mice;overexpression;Pancreas;Parabiosis;Pathway interactions;Perforant Pathway;Performance;Phenocopy;Plasma;Play;Population;Positioning Attribute;Protein Secretion;Proteins;Publishing;Regulation;Rejuvenation;Reporting;response;Risk Factors;Role;Signal Pathway;Slice;Source;Synapses;synaptic function;Synaptic plasticity;targeted treatment;Tissue Inhibitor of Metalloproteinases;Tissues;tool;transcriptome sequencing;Viral;Wild Type Mouse;Work

PROJECT_TITLE: Mechanisms of TIMP2-mediated hippocampal revitalization in Alzheimer's disease

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: GM

ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Princeton

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative Cell division is a key process in biology; it is the process by which cells separate their genetic material (chromosomes) into two identical daughter cells and coordinated by a microtubule-based machinery called the mitotic spindle. Although spindles are essential to the life of a healthy cell, and spindle malfunction can result in cancers and other disease states, we still do not know how microtubules are made at the correct location and time to build the mitotic spindle. Our work seeks to uncover exactly how microtubules make mitotic spindles, which will help explain not only how a cell divides, but can help us understand the origins of diseases that begin in improper cell division and cell regeneration.

PI_NAMEs: PETRY, SABINE  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Binding;Biochemistry;Biological Assay;Biology;Biophysics;Cell Cycle Regulation;Cell division;Cell Physiology;cell regeneration;Cells;Cellular biology;Centrosome;Chromosome Segregation;Chromosomes;Complex;Cryoelectron Microscopy;Cytokinesis;Data;daughter cell;defined contribution;Disease;egg;Event;Failure;Fiber;Foundations;Generations;Genetic Materials;Importins;In Vitro;insight;Kinetochores;Laboratories;Life;light microscopy;Liquid substance;Location;Macromolecular Complexes;Malignant Neoplasms;Mechanics;Mediating;Membrane;Metaphase;Microscopy;Microtubule Bundle;Microtubules;Mitosis;Mitotic spindle;Modeling;Molecular Machines;monomer;novel;Organelles;particle;Pathway interactions;Phase;Physical condensation;Positioning Attribute;Process;protein complex;Proteins;Reaction;reconstitution;Regulation;Research;Research Personnel;Role;Scientist;Shapes;Side;single molecule;Sister Chromatid;Source;structural biology;Structure;System;Time;Tubulin;Visualization;Work;Xenopus

PROJECT_TITLE: Role and Mechanisms of Microtubule Nucleation in Spindle Assembly

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


NIH_SPENDING_CATS: Biotechnology;Cystic Fibrosis;Gene Therapy;Genetics;Lung;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: STANFORD

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Given our success with functional correction of CFTR mutations in airway stem cells from cystic fibrosis (CF) patients, herein we test gene corrected human airway stem cell behavior in vitro and in pre-clinical animal models of surgical transplantation, to advance the first stem cell-based therapy for CF.

PI_NAMEs: NAYAK, JAYAKAR V (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Air;Airway Disease;airway epithelium;Animal Model;Anion Transport Proteins;Anions;Architecture;Autologous;autosome;Basal Cell;Behavior assessment;behavior in vitro;Bicarbonates;Biocompatible Materials;Biological Assay;Biological Models;bioluminescence imaging;cell behavior;Cell Count;Cell Differentiation process;Cell Fraction;Cell Proliferation;cell replacement therapy;Cell Survival;Cell Therapy;Cell Transplantation;Cells;Chimerism;Chlorides;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Collagen;Collagen Type I;constitutive expression;CRISPR correction;CRISPR/Cas technology;Cystic Fibrosis;cystic fibrosis airway;cystic fibrosis airway epithelia;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Delta F508 mutation;Development;Differentiated Gene;Discrimination;Dissociation;Electrolytes;Engineering;Engraftment;Epidermal Growth Factor;Epithelial Cells;Epithelium;experimental study;Family suidae;FDA approved;Functional disorder;gene correction;genome editing;Green Fluorescent Proteins;Growth Factor;Heparin Binding;Human;human stem cells;Immune;Immunohistochemistry;immunosuppressed;improved;In Vitro;in vivo;in vivo engraftment;Infiltration;Inflammation;innovation;Life Expectancy;Liquid substance;Luciferases;Lung;Maxillary Sinus;Measures;Mediating;Medical;Membrane;Mendelian disorder;Methods;Microsurgery;migration;Modality;Modeling;mouse model;Mucous body substance;Mus;Mutation;novel;Operative Surgical Procedures;Outcome;Pathologic;Patients;Pattern;personalized strategies;Physicians;pre-clinical;Proliferating;protein expression;Proteins;Publishing;recruit;recurrent infection;Regulator Genes;replacement tissue;Respiratory Failure;Respiratory System;Respiratory Tract Infections;restoration;Rodent;Rodent Model;scaffold;Scientist;Sinus;Site;Small Intestinal Submucosa;Sorting;stem;stem cell expansion;stem cell proliferation;stem cell replacement;stem cell therapy;Stem cell transplant;stem cells;Stromal Cells;success;Surgical Models;symptom treatment;System;Technology;Testing;Time;Tissues;Translating;Translations;Transplantation;Transplantation Surgery;treatment strategy;VX-770;Water

PROJECT_TITLE: Optimizing Surgical Transplant of CFTR Gene-Corrected Human Basal Stem Cells to the Upper Airway

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


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

ORG_CITY: CLEVELAND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Brain cholesterol metabolism impairment is an early prominent event in the brains of patients with Alzheimer’s disease (AD). The proposed study seeks to better understand the molecular mechanisms by which signals induce AD-associated neuropathology via regulating brain cholesterol metabolism, and to reveal novel targets for developing therapeutics to treat AD.

PI_NAMEs: QI, XIN  (contact)

PROJECT_TERMS: abeta accumulation;Abeta synthesis;AD transgenic mice;Affect;Age;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;amyloid pathology;amyloid precursor protein processing;Amyloidosis;Animal Model;Animals;Area;ATP phosphohydrolase;Attenuated;Autopsy;Behavioral;Binding;Biochemical;Biogenesis;Biological Assay;Brain;brain control;brain dysfunction;Cell Culture Techniques;cell injury;Cells;Cholesterol;cholesterol control;Cholesterol Homeostasis;cholesterol trafficking;Cognitive deficits;Data;density;Development;dimer;Dimerization;Disease Progression;Embryo;Enzymes;Event;Exposure to;Family;gain of function;Gene Mutation;Genes;Genetic;Goals;Heterozygote;Hippocampus;Huntington Disease;Impairment;improved;inhibitor;Injury;insight;knock-down;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Link;lipid metabolism;Lipids;Measures;Mediating;Membrane;Membrane Microdomains;Metabolic Pathway;Mitochondria;Molecular;Mus;mutant;mutant mouse model;Mutant Strains Mice;Nerve Degeneration;neuroinflammation;Neurological status;neuron development;neuronal survival;Neurons;neuropathology;new therapeutic target;novel;overexpression;Oxidative Stress;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peptides;Phospholipids;Proteomics;Risk Factors;Role;Signal Induction;Signal Pathway;spatial memory;Sphingomyelins;Sterols;Symptoms;Synapses;Synaptic plasticity;tau Proteins;Testing;Therapeutic;Transgenic Mice;Transgenic Organisms;Wild Type Mouse;Work

PROJECT_TITLE: Role of brain lipid metabolism in Alzheimer's disease

STUDY_SECTION: CMND

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The global burden of sepsis is concentrated in sub-Saharan Africa where epidemic HIV, broad pathogen diversity, and limited health system capacity challenge effective management of life-threatening infections. This research will stratify sepsis patients in Uganda into meaningful subtypes to enhance diagnosis, clinical trial design, and management of sepsis in sub-Saharan Africa.

PI_NAMEs: CUMMINGS, MATTHEW JOHN (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Address;Adult;Affect;Africa South of the Sahara;Bioinformatics;Biological;biological heterogeneity;Biological Markers;biomarker driven;Biometry;Blood specimen;career;career development;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell type;Cells;Cessation of life;Clinical;Clinical Data;clinical epidemiology;clinical heterogeneity;Clinical Investigator;Clinical Management;Clinical Research;clinical translation;Clinical Trials;Clinical Trials Design;clinically relevant;cohort;Collaborations;Communicable Diseases;comorbidity;Complement;Complex;Country;Critical Care;Critical Illness;cytokine;Data;Derivation procedure;Development;Development Plans;Diagnosis;Emerging infection;endothelial dysfunction;Environment;Epidemic;Epidemiology;Ethics;exhaustion;experience;Fibrinolysis;Foundations;functional genomics;Funding;genetic signature;Genomics;global health;Goals;Health system;high risk;High-Throughput RNA Sequencing;HIV;Hospitals;Immune;immune activation;immune modulating agents;Immune response;Immune System Diseases;Immunologist;Immunology;immunomodulatory therapies;improved;Income;Infection;Inflammatory;Knowledge;Laboratories;Life;Machine Learning;Malnutrition;Measurement;Mediating;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;Modeling;Molecular;Molecular Epidemiology;mortality;National Institute of Allergy and Infectious Disease;Natural Killer Cells;novel;Organ failure;Outcome;pathogen;pathogen genomics;Pathway interactions;patient oriented;patient oriented research;patient stratification;Patient-Focused Outcomes;Phenotype;Pilot Projects;prospective;Prospective, cohort study;Qualifying;Research;research data dissemination;Research Design;Research Institute;Research Personnel;Resolution;Resource-limited setting;response;RNA;RNA analysis;Sampling;Scientist;Sepsis;septic;septic patients;T-Lymphocyte;Techniques;Testing;tool;Training;transcriptome;transcriptome sequencing;transcriptomics;Translational Research;translational scientist;Treatment Efficacy;Treatment Protocols;treatment response;treatment strategy;Uganda;Universities;unsupervised learning;Virus;Whole Blood

PROJECT_TITLE: Subtyping sepsis in Uganda using clinical, pathogen, and host response profiling

STUDY_SECTION: MID

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: This project evaluates mismatch in life history data collected retrospectively versus prospectively, using the American's Changing Lives (ACL) Study - a nationally-representative, three-decade panel of adults. The study contributes to two overarching goals of the Public Health Service: increasing healthy active life expectancy and reducing social disparities in health.

PI_NAMEs: BURGARD, SARAH A. (contact)

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: Address;Adult;Age;Aging;aging related;American;Behavior;Birth;Calendar;Caregivers;Characteristics;Child Rearing;Code;cohort;Cohort Studies;Collection;Communities;Complex;cost;cost effective;Data;data quality;Dedications;Dimensions;Disparity;disparity elimination;Disparity population;Education;Employment;Environment;Environmental Exposure;Ethnic Origin;Europe;Event;Evolution;expectation;experience;Fostering;Funding;Gender;gender disparity;Goals;Health;Health and Retirement Study;health care service utilization;health disparity;Health Sciences;Health Surveys;healthy aging;improved;Individual;Inequality;innovation;instrument;Interview;investigator training;late life;Life;Life Cycle Stages;Life Expectancy;life history;life span;Longitudinal Studies;Measurement;Measures;Mediation;Methodology;middle age;Morbidity - disease rate;multi-racial;National Institute on Minority Health and Health Disparities;novel;Occupations;Parents;Persons;Policy Maker;Prevalence;Process;prospective;Protocols documentation;psychosocial;Race;Recommendation;Recording of previous events;Reporting;Research;Research Personnel;Resources;Respondent;Retrospective Studies;Risk;Role;Schools;Severities;Shapes;Shock;social;social disparities;social health determinants;Social Network;Social Sciences;sociodemographic predictors;sociodemographics;Socioeconomic Status;socioeconomics;Subgroup;Survey Methodology;Surveys;Survivors;Testing;theories;therapy design;Time;Tobacco use;United States;United States Public Health Service;Validation

PROJECT_TITLE: ACL-LIFE Life History Interview and Validation

STUDY_SECTION: SSPB

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Genetics

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROBING ALLOSTERY IN METHYL-LYSINE READER DOMAINS Project Narrative: Chromatin is the complex of histone proteins, RNA, and DNA that dynamically packages the genome within each eukaryotic cell. Allosteric interactions in chromatin regulatory complexes are critically important phenomena that create unique opportunities for pharmacologic intervention. This research will aim to create high-quality allosteric chemical probes for methyl-lysine reader domains to explore chromatin biology and the therapeutic potential of allosterically modulating these domains.

PI_NAMEs: FRYE, STEPHEN VERNON (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: academic program;Address;Area;assay development;Binding;Biological Assay;Biology;Biophysics;Catalytic Domain;Cell Lineage;Cells;Chemicals;Chromatin;Complement;Complex;Disease;DNA;drug discovery;Eukaryotic Cell;experience;Family;flexibility;frontier;Future;Gene Expression;Genome;histone modification;Histones;in vitro Assay;in vivo;Intellectual Property;interest;Intervention;Knowledge;Lysine;Molecular;Nucleotides;Outcome;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Play;Post-Translational Protein Processing;Productivity;Proteins;Reader;Regulation;Research;Resources;Risk;RNA;Role;Scientific Advances and Accomplishments;small molecule;Talents;temporal measurement;Therapeutic;Therapeutic Intervention;Time;Training;transcription factor;Validation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-B(07)R]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Non-Human

ORG_CITY: ROCHESTER

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Anemia, defined as an insufficient number of red blood cells, affects roughly one third of the world’s population and can be caused by a variety of factors that impair red blood cell production. The process by which functional red blood cells are produced from committed progenitor cells is incompletely understood. The studies outlined in this proposal will significantly enhance our understanding of how essential steps in red blood cell production are coordinated, providing much needed insights into a process fundamental to human health and disease.

PI_NAMEs: STEINER, LAURIE A. (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Acetylation;Affect;Anemia;Cell Cycle;Cell division;cell type;Chromatin;Chromatin Structure;Complex;condensin;Data;Defect;design;Disease;Dysmyelopoietic Syndromes;Enhancers;Enzymes;Epigenetic Process;Erythroblasts;Erythrocytes;Erythroid;Erythroid Cells;Erythropoiesis;Failure;Funding;Gene Expression;Gene Expression Profile;gene repression;Gene Silencing;Goals;Health;Hematopoietic;Higher Order Chromatin Structure;Histone H4;histone methyltransferase;Histones;Human;Impairment;Inherited;insight;Laboratories;Link;Lysine;Mass Spectrum Analysis;Mediating;Methylation;Modeling;novel;Nuclear;Nucleosomes;Output;Pathway interactions;Physical condensation;Play;Population;Post-Translational Protein Processing;Preparation;Process;Production;progenitor;Proteins;Reader;recruit;Red Blood Cell Count;Regulation;Role;stem cells;Tail;Testing;Time;Transcriptional Regulation;transcriptome

PROJECT_TITLE: Elucidation of the Role of Setd8 and H4K20me1 in Erythropoiesis

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Digestive Diseases;Hematology;Infant Mortality;Infectious Diseases;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Sepsis

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Neonatal infections are a global health concern, but why neonates are highly susceptible to infections is not well understood. We have shown that neonatal mice have increased iron available for bacterial growth and that decreasing this iron improves neonatal survival during sepsis. The success of the studies outlined in this proposal may lead to the identification of therapeutic targets that can improve outcomes during neonatal infections.

PI_NAMEs: BERMICK, JENNIFER  (contact)

PROJECT_TERMS: absorption;Adult;Allergic Disease;Antibiotic Therapy;Antibiotics;antimicrobial;Asthma;Autoimmune Diseases;Bacteria;Biological Markers;Birth;Blood Volume;Brain;Breast Feeding;Cattle;Cells;Cessation of life;Childhood;clinically relevant;combat;Consumption;Critical Illness;Data;Death Rate;Defect;Deferoxamine;Developing Countries;Development;Diagnosis;Diet;dietary excess;Dietary Iron;Disease;early onset sepsis;Enteral;Erythrocytes;Escherichia coli;Escherichia coli Infections;experimental study;fitness;Fostering;Gallium;global health;Glutamine;Goals;Gram-Negative Bacteria;Greater sac of peritoneum;Growth;Human Milk;Immune;Immune response;Immune system;improved;improved outcome;Incidence;infancy;Infection;Infection prevention;Intake;intestinal barrier;Intestines;intraperitoneal;Iron;iron absorption;iron deficiency;Iron Isotopes;iron metabolism;Iron Uptake Inhibition;Lactation;Lactoferrin;Life;Measurement;Measures;Metabolic;microbiome;Morbidity - disease rate;mortality;mouse model;Mus;Necrotizing Enterocolitis;Neonatal;neonatal infection;neonatal mice;Neonatal Mortality;neonatal period;neonatal sepsis;neonate;Nutritional Requirements;Organism;Outcome;Passive Immunization;pathogen;pathogenic Escherichia coli;Peritoneal;Play;Predisposition;Pregnancy;Premature Infant;prevent;pup;rapid growth;receptor;Recycling;Research;response;Risk;Role;senescence;Sepsis;Serum;Siderophores;Signs and Symptoms;SLC11A2 gene;Source;success;Supplementation;System;therapeutic target;Tissues;Trace Elements Nutrition;Transferrin;United States;uptake;Virulent;Wheezing;Work

PROJECT_TITLE: Targeting iron to improve outcomes in neonatal Escherichia coli sepsis

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Nanotechnology

ORG_CITY: SAN ANTONIO

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Delayed diagnosis of fungal infections is a proven risk factor for increased morbidity and mortality. There currently is no FDA approved, benchtop, pan fungal diagnostic assay that is fast, has inexpensive equipment, can be used directly on pure cultures or clinical specimens, or on mixed cultures. This proposal will use a new, inexpensive sequencing technology called nanopore sequencing, and a little used region in the fungal ribosomal repeat called the intergenic space region to yield a rapid diagnostic assay using a single sequence.

PI_NAMEs: WICKES, BRIAN  (contact)

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Aspergillus;Bacteria;Base Sequence;Biological Assay;C10;Candida;Capital;Case Study;Cessation of life;Clinical;Computers;Contracts;cost;Cryptococcus;data management;Death Rate;Dedications;Deposition;Development;Diagnosis;Diagnostic;diagnostic assay;Diagnostic Procedure;diagnostic strategy;Dideoxy Chain Termination DNA Sequencing;Disease Outbreaks;Drug resistance;emerging pathogen;Epidural Injections;Equipment;Etiology;Face;Failure;FDA approved;Foundations;Frequencies;fungus;Future;Genbank;Generations;Goals;health care settings;Healthcare;Hour;Human;Immune system;Immunocompromised Host;immunosuppressed;Infection;innovation;instrument;Laboratories;Literature;Maintenance;Malaria;Microbiology;Missouri;Molds;Molecular;Molecular Diagnostic Testing;molecular diagnostics;molecular sequence database;Morbidity - disease rate;mortality;Multi-Drug Resistance;Mycoses;Names;nanopore;new technology;novel;novel sequencing technology;novel strategies;Pathogenesis;pathogenic fungus;Pathogenicity;Patients;Pattern;Persons;portability;Preparation;programs;Protocols documentation;Rapid diagnostics;rapid test;resistance in Candida auris;Rhizomucor;Ribosomal DNA;Ribosomes;Risk Factors;Running;Sampling;Severities;Specificity;Specimen;Sporothrix;Standardization;Steroids;Technical Degree;Technical Expertise;Technology;Testing;The science of Mycology;Thumb structure;Time;Tornadoes;Trichosporon;Tuberculosis;virtual;Virus;Walking;Yeasts

PROJECT_TITLE: Development of a rapid, pan fungal diagnostic assay

STUDY_SECTION: CRFS

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: BALTIMORE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE COUNTY

ORG_STATE: MD

PHR: PROJECT NARRATIVE This multidisciplinary research will explore the interaction between solid surfaces and microorganisms to improve quantitative understanding of microbial dechlorination kinetics. The new knowledge will be used in mathematical models to optimize bioamendment materials to enhance bioremediation. Collaboration with environmental consulting professionals will integrate the novel technology through advanced site models for evaluation of effectiveness at Superfund sites.

PI_NAMEs: GHOSH, UPAL  (contact)

PROGRAM_OFFICER_NAME: HENRY, HEATHER F

PROJECT_TERMS: Adsorption;anthropogenesis;Area;Attenuated;Bacteria;Behavior;Biodegradation;Bioremediations;Carbon;Carbon Black;Characteristics;chemical property;Chemicals;Coal;Collaborations;contaminated sediment;Coupled;Data;dechlorination;dehalogenation;design;Development;Diffusion;effectiveness evaluation;Electric Conductivity;Electrons;Engineering;engineering design;Environment;Environmental Engineering technology;experimental study;field study;geochemistry;ground water;Growth;halogenation;Hydrophobicity;improved;Individual;Injections;innovation;Interdisciplinary Study;Investigation;Kinetics;Knowledge;Laboratories;laboratory experiment;Laboratory Study;Learning;Life Cycle Stages;mass flux;materials science;mathematical model;Medial;Metabolic Biotransformation;microbial;microbial community;microorganism;microorganism interaction;Microscopy;Modeling;models and simulation;multidisciplinary;Natural graphite;new technology;Organism;particle;Partition Coefficient;Performance;physical property;Plants;pollutant;Polychlorinated Biphenyls;Population;Process;Property;Reaction;remediation;Research;Role;Silicon Dioxide;Site;Solid;Sorting;Source;superfund site;Surface;synergism;Technology;Testing

PROJECT_TITLE: Leveraging the chemo-physical interaction of halorespiring bacteria with solid surfaces to enhance halogenated organic compounds bioremediation


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE Our proposed research is related to public health because our study provides a novel therapeutic target for brain aneurysm disease, a condition that leads to a high rate of disability and death in stroke patients upon rupture. In particular, we propose that inhibiting the activity of a special compartment called “podosome” in the cells that locate at the innermost of the blood vessels has a beneficial effect on the formation and growth of brain aneurysms. Therefore, our work is related to the part of the NIH's mission that pertains to reducing the burdens of illness and disability.

PI_NAMEs: XU, ZHEN  (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Aneurysm;Aneurysmal Subarachnoid Hemorrhages;Animal Model;Area;Arteries;Blood flow;Blood Vessels;Brain;Brain Aneurysms;brain endothelial cell;burden of illness;Cause of Death;Cells;cerebrovascular;Cerebrovascular system;Cessation of life;Circle of Willis;clinical risk;Data;Development;Dilatation - action;disability;Disease;Endothelial Cells;Endothelium;Event;experimental study;Extracellular Matrix;Extracellular Matrix Degradation;FDA approved;Friction;Functional disorder;FYN gene;gain of function;Goals;Growth;Growth and Development function;Health Care Costs;Hospitalization;Hospitals;Human;Impairment;in vivo;Independent Living;inhibitor;innovation;Intervention;Intracranial Aneurysm;kinase inhibitor;Knowledge;Link;loss of function;Lytic;Mechanics;Mission;Molecular;Monomeric GTP-Binding Proteins;mouse model;Mus;new therapeutic target;novel;novel therapeutics;Operative Surgical Procedures;Organelles;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Peptide Hydrolases;Persons;Pharmaceutical Preparations;pharmacologic;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;prevent;Protein Tyrosine Kinase;Protein Tyrosine Phosphatase;PTPN12 gene;Public Health;Research;Resolution;response;Risk Factors;Role;Rupture;Ruptured Aneurysm;scaffold;Scaffolding Protein;SH3 Domains;shear stress;Signal Pathway;Signal Transduction;single molecule;Site;src-Family Kinases;Stroke;stroke patient;Subarachnoid Hemorrhage;Survivors;Testing;therapeutic target;translational potential;United States;United States National Institutes of Health;Vascular Endothelium;Vascular Permeabilities;Work;Zebrafish

PROJECT_TITLE: The Role of Podosomes in Cerebrovascular Integrity and Intracranial Aneurysm

STUDY_SECTION: BINP

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


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

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Cerebral blood vessels are completely covered by astrocytic processes called endfeet. Recent research shows endfeet releasing vasoactive molecules that regulate blood flow and tropic molecules that induce and maintain the blood brain barrier. It is unknown whether these functions change with aging and may be worsened by the presence of amyloid in Alzheimer disease.

PI_NAMEs: SONTHEIMER, HARALD W (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Ablation;Acceleration;Address;Age;age-related disease;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Amyloid;Amyloid deposition;amyloid pathology;Amyloidosis;Animals;Arteries;arteriole;Astrocytes;Biological;Blood;Blood - brain barrier anatomy;Blood capillaries;Blood flow;Blood Vessels;Cell Separation;cell type;Cerebral Amyloid Angiopathy;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular system;Cerebrum;Chronic;clinically relevant;Control Animal;Data;Deposition;Dinoprostone;Disease;Endothelium;experimental study;familial Alzheimer disease;functional decline;Functional disorder;Functional impairment;gender difference;Gene Expression;Genes;Genetic;Genomics;Gliosis;Health;healthy aging;Hippocampus;Hyperemia;Impairment;improved;in vivo;innovation;Lasers;life span;Magnetism;Maintenance;Matrix Metalloproteinases;Modeling;mouse model;multiphoton imaging;Mus;neurotoxic;neurovascular coupling;neurovascular unit;normal aging;novel;Pathogenesis;Pathologic;pathological aging;Peptide Hydrolases;Pericytes;Positioning Attribute;Process;protein expression;Protein Overexpression;Proteins;Proteome;Proteomics;Research;Role;Secondary to;Senile Plaques;sex;Sex Differences;Signal Induction;Signal Transduction;Smooth Muscle;Specific qualifier value;Structure;Surface;Tight Junctions;Time;Toxic effect;Tracer;transcriptome;transcriptome sequencing;Transgenic Mice;Trees;Vibrissae

PROJECT_TITLE: Changes in Cerebrovascular Function with Aging in Normal and AD Brain


NIH_SPENDING_CATS: Aging;Clinical Research;Lung;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Endoplasmic reticulum (ER) stress in epithelial cells lining the distal lung airspaces (alveolar epithelial cells (AECs)) plays a key role in the development of an age-associated disease called idiopathic pulmonary fibrosis (IPF). However, what causes ER stress during aging and how ER stress damages AEC is not clear. Here we propose to link chaperone protein GRP78 loss-induced ER stress to AEC dysfunction and IPF by studying how GRP78-loss promotes dysregulated mitochondrial function and metabolism via crosstalk between UPRER and mTOR signaling, leading to an aging phenotype in AECs and subsequent lung fibrosis.

PI_NAMEs: ANN, DAVID K.;ZHOU, BEIYUN  (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Abnormal Epithelial Cell;Address;age related;age-related disease;aged;Aging;aging related;alveolar epithelium;Anabolism;Apoptosis;Bioenergetics;biological adaptation to stress;Bleomycin;cell age;Cell Aging;Cell Death;Cell Line;Cells;Characteristics;Charge;Chronic;Cicatrix;Data;Development;Diagnosis;Disease;Distal;Down-Regulation;effective therapy;Endoplasmic Reticulum;endoplasmic reticulum stress;Epithelial Cells;fibrogenesis;fibrosing agent;Fibrosis;fibrotic lung;fitness;FRAP1 gene;Functional disorder;Gene Expression;glucose metabolism;glucose-regulated proteins;Glutamine;Goals;GRP78 gene;Homeostasis;Human;idiopathic pulmonary fibrosis;Impairment;In Vitro;in vivo;Individual;ineffective therapies;Inherited;Knock-out;Knockout Mice;Link;Lung;male;Mediating;Metabolic;metabolic fitness;Metabolic Pathway;Metabolism;misfolded protein;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;Molecular Chaperones;Morbidity - disease rate;Morphology;mouse model;Mus;Mutate;old mice;older adult;overexpression;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;Pathway interactions;Patients;Phenotype;Pilot Projects;Play;protein folding;Proteins;proteostasis;proteostasis loss;Publishing;Pulmonary Fibrosis;pulmonary function;Pulmonary Surfactant-Associated Protein C;Reactive Oxygen Species;Reporting;response;Role;senescence;Signal Transduction;Specificity;Stress Response Signaling;Therapeutic;therapeutic target;Tissues;Type II Epithelial Receptor Cell

PROJECT_TITLE: Role of Chaperone GRP78 and Mitochondrial Dysfunction in ER Stress-Mediated Pulmonary Fibrosis

STUDY_SECTION: LIRR

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

ORG_STATE: MA

PHR: Project Narrative Appropriate feeding behaviors rely on accurate estimation of future energy balance, which in turn relies on gastrointestinal signals related to stomach stretch and nutrient content. How these visceral signals are integrated to assess internal state and guide feeding behaviors is poorly understood. This proposal will define how interoceptive signals from the gastrointestinal tract lead to satiety-related sensations, drive feeding termination, and ultimately regulate energy balance at the level of the lateral parabrachial nucleus, thereby identifying new therapeutic targets for metabolic diseases such as obesity.

PI_NAMEs: RUDA, KIERSTEN  (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Address;Affect;Anatomy;Anesthesia procedures;Architecture;Area;awake;Axon;Behavior;Behavioral;Body Weight;Brain;Brain Stem;Calcitonin Gene-Related Peptide;Calcitonin Receptor;Calcium;cell type;Chronic;Consumption;Data;dimensional analysis;Eating;energy balance;Environment;Esophagus;Esthesia;Exhibits;experimental study;Fasting;feeding;Feeding behaviors;Food;food consumption;Future;gastrointestinal;Gastrointestinal tract structure;Genes;hindbrain;Homeostasis;Image;imaging approach;in vivo;in vivo imaging;Individual;Ingestion;Interoception;Knowledge;Lateral;Lead;Link;Liquid substance;Malaise;Maps;Measurement;Measures;Mechanical Stimulation;Mediating;Metabolic Diseases;Methods;multimodality;Mus;Nature;neural;Neurons;new therapeutic target;novel;Nucleus solitarius;Nutrient;Obesity;optogenetics;Oral cavity;Organ;parabrachial nucleus;Pathway interactions;Pattern;Physiological;Population;preference;Presynaptic Terminals;prodynorphin;Protocols documentation;Research;response;Role;Satiation;Sensory;Signal Transduction;Site;Small Intestines;spinal pathway;Stimulus;Stomach;Stretching;Testing;Thalamic structure;therapeutic target;Time;Training;transcriptomics;two-photon;Upper digestive tract structure;Visceral;Visceral pain;Work

PROJECT_TITLE: Functional mapping of the parabrachial nucleus: from gastrointestinal topography to satiety


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Diabetes;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Prevention;Social Determinants of Health

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Diabetes distress is common affecting over one-third of people with type 2 diabetes, negatively impacting self- management and outcomes, and disproportionately affecting low-income individuals. The proposed project will pilot test a Mindfulness-Based Diabetes Education intervention, specifically adapted for adults with type 2 diabetes and elevated diabetes distress, to assess feasibility and acceptability. Utilizing mixed-methods, this study will also characterize key contextual factors that relevant to intervention delivery and implementation setting the stage for a future, larger study in safety-net healthcare settings.

PI_NAMEs: PRESLEY, CAROLINE A (contact)

PROGRAM_OFFICER_NAME: JEAN-FRANCOIS, BEDA

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adult;Affect;Alabama;Award;Behavior;behavior change;Behavior Therapy;Behavioral;Behavioral trial;Blood Glucose;Blood Pressure;cardiovascular disorder risk;career development;Certification;Characteristics;Clinic;Clinical;clinical application;comparison intervention;Complex;Complications of Diabetes Mellitus;contextual factors;County;Data;Development;Development Plans;diabetes distress;diabetes education;diabetes educator;diabetes management;Diabetes Mellitus;diabetes self-management;Diet;Diet Modification;Disease;Distress;Education;Educational Intervention;efficacy study;efficacy trial;emotional distress;Evaluation;Evidence based intervention;experience;Face;feasibility testing;Focus Groups;follow-up;Future;glucose monitor;glycemic control;Goals;Grant;Health behavior;health care settings;Healthcare;Healthcare Systems;high risk;Hypertension;implementation design;implementation science;improved;Infrastructure;Intervention;intervention delivery;Intervention Studies;Knowledge;Link;Low income;Low Income Population;medication compliance;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;mindfulness;mindfulness intervention;mindfulness-based stress reduction;Non-Insulin-Dependent Diabetes Mellitus;Outcome;Participant;patient engagement;patient oriented research;Patients;perceived stress;Persons;Physical activity;pilot test;Population;Practical Robust Implementation and Sustainability Model;primary care setting;Process Measure;programs;Provider;psychological outcomes;Randomized, Controlled Trials;recruit;Research;Research Methodology;Research Personnel;Risk Factors;safety net;satisfaction;Self Management;Series;Site;skills;Stress;stress reduction;symposium;Testing;Tobacco Use Disorder;Training;Vulnerable Populations;Work

PROJECT_TITLE: Mindfulness-Based Diabetes Education for adults with elevated diabetes distress


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Despite advancements in antiretroviral therapy, cryptococcal meningitis continues to be the most common cause of meningitis in persons living with HIV and carries a high mortality rate in low-income countries. The proposed research focuses on quantifying human natural killer cell cytotoxicity against Cryptococcus neoformans and the identification of differentially expressed genes involved in exhaustion, cytokine production, and cytotoxicity. This research could lead to the identification of pathways that can be targeted by immunotherapies to enhance natural killer cell cytotoxicity with the overall goal to increase fungal clearance, reduce morbidity, and reduce mortality from cryptococcal meningitis.

PI_NAMEs: OKAFOR, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Activated Natural Killer Cell;Acute;adaptive immune response;Adult;Affect;Africa;Africa South of the Sahara;Antibodies;antibody-dependent cell cytotoxicity;Antifungal Therapy;Antigens;antiretroviral therapy;arm;brain parenchyma;burden of illness;CD4 Positive T Lymphocytes;Cell Physiology;Cell Separation;Cell surface;Cell-Mediated Cytolysis;Cells;Central Nervous System Infections;Chronic;Clinical;Cryptococcal Meningitis;Cryptococcosis;Cryptococcus;Cryptococcus neoformans;CXCL10 gene;CXCR3 gene;cytokine;Cytokine Receptor Gene;cytotoxic;cytotoxicity;Data;Death Rate;Defect;Diagnosis;differential expression;Disease;Disease Progression;exhaustion;extracellular;Functional disorder;Future;Gene Expression;Genes;Goals;Granzyme;HIV;HIV Infections;Human;IL2RB gene;Immune;immune modulating agents;Immune response;Immune signaling;Immunocompromised Host;Immunotherapy;Impairment;improved;In Vitro;Individual;Infection;Inflammation;Inflammation Mediators;innovation;Interferon Type II;Life;lonely individuals;low income country;Lymphoid;Meninges;Meningitis;Molecular;Morbidity - disease rate;mortality;Mycoses;Natural Killer Cells;Ontology;pathogen;pathogenic fungus;Pathway Analysis;Pathway interactions;Patients;Pattern;Persons;Phenotype;Physiological;Predisposition;Production;receptor;receptor expression;Receptor Signaling;Research;Resolution;Risk;Role;Signal Pathway;Signal Transduction;Solid;Sterility;Symptoms;targeted treatment;Technology;Testing;Therapeutic;TNFSF10 gene;transcriptome;transcriptome sequencing;Translating;Virus Diseases

PROJECT_TITLE: NK Cell Cytotoxicity Against Cryptococcus neoformans in Persons with Advanced HIV and Cryptococcal Meningitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F17-M(20)L]


NIH_SPENDING_CATS: Kidney Disease

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Project Narrative: The kidneys are frequent targets of both environmental contaminants and several classes of therapeutic agents that exhibit dose-limiting nephrotoxicity. We will use primary cultures of proximal tubular cells from fresh human kidneys in targeted studies to identify protein, lipid, and low-molecular- weight metabolite patterns that are associated with exposure to a diverse array of nephrotoxic chemicals. We anticipate validating biomarkers that are linked to chemical mechanism of action, are specific and highly sensitive, and correspond to exposure prior to or after onset of only minimal renal injury.

PI_NAMEs: LASH, LAWRENCE H. (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;adduct;anti-cancer;Anti-viral Agents;Antibiotics;Antimycin A;Aromatic Polycyclic Hydrocarbons;Benchmarking;Biological Markers;Biological Models;biomarker validation;Cardiolipins;Cell Physiology;Cell Survival;Cells;Chemical Exposure;Chemicals;chemotherapeutic agent;Chronic Kidney Failure;Cisplatin;Cysteine;Cytoplasm;Cytoskeleton;cytotoxicity;Data;Dependence;Dialysis procedure;Disease;Dose Limiting;Environment;environmental agent;Environmental and Occupational Exposure;Environmental Pollutants;Exhibits;exosome;Experimental Models;exposed human population;Exposure to;extracellular;Fumarates;halogenation;Heat-Shock Proteins 90;Heavy Metals;High Pressure Liquid Chromatography;Human;improved;in vivo;Incubated;Injury;Injury to Kidney;Keratin;Kidney;kidney cell;Kidney Diseases;Label;Link;lipidomics;Lipids;Mass Spectrum Analysis;Measures;Mercuric chloride;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Modification;Molecular Weight;multiple reaction monitoring;nephrotoxicity;Non-Steroidal Anti-Inflammatory Agents;novel;novel marker;Organ Transplantation;Patients;Pattern;Pharmaceutical Preparations;Phenotype;Plasma;Polymyxin B;potential biomarker;protein biomarkers;Proteins;Proteomics;Public Health;Rattus;Recovery;renal damage;Renal Replacement Therapy;Resolution;Shotguns;side effect;Solvents;Source;Spectrometry, Mass, Electrospray Ionization;sulfite oxidase;Supporting Cell;tandem mass spectrometry;Tenofovir;Testing;Therapeutic;Therapeutic Agents;Therapeutic Uses;Time;Toxic effect;toxicant;Trichloroethylene;Tubular formation;Urine;Validation

PROJECT_TITLE: Mitochondrial and Cellular Biomarkers of Renal Injury from Environmental and Therapeutic Agents

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Prevention;Rare Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: Columbus

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative Importance to public health: The purpose of this project is to understand infection mechanisms of leukocytes with Ehrlichia chaffeensis, which causes an emerging infectious disease, human monocytic ehrlichiosis. Ultimately, our findings are expected to reveal novel molecules and signaling pathways that could serve as relevant targets for future therapeutic discovery; however, what is learned will contribute to a broader understanding of how cellular organelles and intracellular infection are regulated in human cells. Relevance to NIH’s mission: our work pertains to developing fundamental knowledge that will reduce the burden of human disability.

PI_NAMEs: RIKIHISA, YASUKO  (contact)

PROGRAM_OFFICER_NAME: PERDUE, SAMUEL S

PROJECT_TERMS: Aerobic Bacteria;Amino Acids;Animal Diseases;Autophagocytosis;Autophagosome;Back;Bacteria;Binding;cell injury;Cells;Communicable Diseases;Complementary DNA;Cytoplasm;Deferoxamine;Development;disability;Doxycycline;Drug Metabolic Detoxication;Ehrlichia;Ehrlichia chaffeensis;Ehrlichiosis;Emerging Communicable Diseases;Ferritin;Future;Goals;Growth;Homeostasis;Host Defense Mechanism;Human;human disease;Hybrids;Immunologics;Infection;innovation;Intervention;Iron;Iron Chelating Agents;Iron Chelation;iron metabolism;Kinetics;knock-down;Knock-in;Knowledge;Learning;Leukocytes;Libraries;Light;Link;Macrophage;Maps;Mediating;Membrane;Metabolism;Mission;Mitochondria;Molecular;monocyte;mutant;nanobodies;novel;novel strategies;Nuclear Receptor Coactivator 4;Organelles;pathogen;Pathogenesis;Pattern;Peptide Nucleic Acids;pharmacologic;Prevalence;prevent;Preventive measure;Process;Productivity;Proliferating;Proteins;Public Health;Reactive Oxygen Species;response;Rickettsia;Risk;Role;screening;Signal Pathway;Small Interfering RNA;SOD2 gene;Superoxide Dismutase;Superoxides;Surface;Surface Plasmon Resonance;Testing;Therapeutic;tick-borne;Ticks;Time;Tissues;Transfection;Type IV Secretion System Pathway;United States National Institutes of Health;Work;Yeasts

PROJECT_TITLE: Keys to prevent iron hijacking and infection by intracellular bacteria


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Climate-Related Exposures and Conditions;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE Depression and anxiety are common mental health disorders in adolescents, but factors that contribute to these outcomes are poorly understood. We will study how air pollution, which can affect brain development and function, may contribute to these disorders in adolescence by changing the structure, organization, metabolism, or function of the brain. We will combine two existing study populations with repeated measures of air pollution exposure and mental health outcomes from birth through adolescence to provide important information to guide future public health interventions.

PI_NAMEs: CECIL, KIM M;RYAN, PATRICK H;YOLTON, KIMBERLY  (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: 12 year old;18 year old;Acute;Address;Adolescence;Adolescent;adolescent mental health;Adult;Affect;Age;age group;Air Pollutants;Air Pollution;American;Aminobutyric Acids;Anatomy;Anxiety;Attention deficit hyperactivity disorder;autism spectrum disorder;Biological;Birth;Brain;brain volume;Cause of Death;Child;child depression;Childhood;cognitive ability;cohort;Conceptions;critical period;Data;Development;diagnostic criteria;Diameter;Diesel Exhaust;Disease;disorder risk;early adolescence;Early identification;Early treatment;Emergency department visit;Environment;epidemiology study;experience;Exposure to;externalizing behavior;fine particles;follow-up;Functional Magnetic Resonance Imaging;Future;gamma-Aminobutyric Acid;Genetic;Genetic Predisposition to Disease;Glutathione;Health;Hormonal;hospitalization rates;Hypersensitivity;Incidence;Intervention;Justice;Life;Link;Longitudinal cohort;Measures;Mediating;Mental Depression;Mental disorders;Mental Health;Metabolism;meter;Modeling;modifiable risk;Motor Skills;neuroimaging;neuroinflammation;Neuropsychology;neurotoxic;novel;Ohio;Outcome;Oxidative Stress Induction;Particulate Matter;Pathway interactions;Policies;pollutant;Population;prenatal;Prevalence;prevent;Prevention;Preventive;Primary Prevention;prospective;Prospective cohort;public health intervention;Recurrence;Research;Risk;Risk Factors;Role;School Drop-Outs;Schools;screening;social;social determinants;Structure;Student Dropouts;study population;substance use;suicidal risk;Suicide attempt;System;Teenagers;Testing;Time;Toxicology;traffic-related air pollution;ultrafine particle;Unemployment;Well in self;young adult

PROJECT_TITLE: Longitudinal Impact of Air Pollution on Mental Health and Neuroimaging Outcomes during Adolescence in the Cincinnati Combined Childhood Cohorts (C4)

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


ORG_CITY: Nashville

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative  Ubiquitin is a post-translational modification that regulates diverse cellular processes and its dysregulation is associated with many human diseases ranging from neurodegeneration to cancer. Here, we propose research directions that will result in a deeper understanding of how ubiquitin networks are regulated during conditions of stress to facilitate the cellular adaptive response. Dissecting these mechanisms will provide a platform for long-term exploration of ubiquitin networks as potential therapeutic targets in the treatment of human diseases.

PI_NAMEs: MACGURN, JASON A (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Amino Acids;Binding Proteins;Biochemical;biological adaptation to stress;Biology;blood glucose regulation;cancer type;Cell Physiology;Cells;Cellular Stress;Code;Elements;Enzymes;Eukaryotic Cell;Family;Genetic;Glucose Transporter;Human;human disease;insight;Investigation;Length;Malignant Neoplasms;Membrane;Modification;Nerve Degeneration;Pathway interactions;Peptides;Phosphorylation;Phosphotransferases;Polymers;Positioning Attribute;Post-Translational Protein Processing;protein degradation;protein protein interaction;Proteins;Proteomics;proteostasis;Quality Control;Regulation;Research;response;Signal Transduction;SLC2A1 gene;Stress;Syndrome;therapeutic target;trafficking;Ubiquitin;Work;Writing;Yeasts

PROJECT_TITLE: Deciphering the ubiquitin code in stress signaling and membrane trafficking

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Clinical Research;Diabetes;Digestive Diseases;Genetics;Human Genome;Neurodegenerative;Neurosciences;Peripheral Neuropathy

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: Gastroparesis in patients with diabetes mellitus lacks curative therapy and represents a significant health care burden. Reduced expression of the enzyme producing the inhibitory neurotransmitter nitric oxide in gastric neurons is a pathogenetically significant alteration in gastroparesis, but pharmacological modulation of nitric oxide signaling has not been beneficial due to side effects. This project will determine how impaired mitochondrial metabolism in diabetes and consequent dysregulation of gene transcription can be reversed to restore nitric oxide-dependent gastric functions using drugs already approved for use in humans.

PI_NAMEs: ORDOG, TAMAS  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: alpha ketoglutarate;Anxiety;ATP Synthesis Pathway;Binding;Biological Assay;blood glucose regulation;Cells;ChIP-seq;Chromatin;Chromatin Loop;chromosome conformation capture;Citric Acid Cycle;Clinical Trials;cohesin;Confocal Microscopy;CRISPR/Cas technology;Cultured Cells;curative treatments;Data;Diabetes Mellitus;diabetic;diabetic gastroparesis;DNA;DNA-Directed RNA Polymerase;Drug usage;Dyspepsia;effective therapy;Enhancers;Enteral;enteric neuropathy;Enzymes;Epigenetic Process;epigenetic regulation;epigenome editing;epigenomics;Gastric Emptying;Gastroparesis;Gene Deletion;gene repression;Genes;Genetic Transcription;genome editing;genome-wide;healthcare burden;HIF1A gene;histone demethylase;histone methylation;Histones;Human;human tissue;Hypoxia;hypoxia inducible factor 1;Impairment;In Vitro;in vivo;in vivo evaluation;inhibitor;Label;Link;Mediating;Mental Depression;metabolomics;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Molecular;Molecular Target;motor disorder;mouse model;Mus;Neurons;Neuropathy;Neurotransmitters;Nitrergic Neurons;Nitric Oxide;Nitric Oxide Synthase;Nitric Oxide Synthase Type I;non-invasive monitor;NOS1 gene;NOS2A gene;Nuclear Translocation;Nutritional;Oxygen;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology Study;Physiological;Procollagen-Proline Dioxygenase;promoter;Quality of life;recruit;Regulatory Element;Research;restoration;RNA Interference;Role;Sampling;sensor;side effect;Signal Transduction;Stomach;Succinates;Symptoms;Techniques;Tissues;Transactivation;transcription factor;Transcriptional Regulation;transcriptome sequencing;Translations;Transplantation;Upstream Enhancer;Western Blotting

PROJECT_TITLE: Epigenetic dysregulation in diabetic enteric neuropathy

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


NIH_SPENDING_CATS: Biomedical Imaging

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: Project Narrative Our program has assembled outstanding multidisciplinary teams devoted to understanding the roles played by transition metals in catalytic transformations central to human health and disease. The approaches to these problems incorporate a suite of advanced paramagnetic resonance techniques, many of which we have developed, augmented by kinetic and photophysical measurements. The essential biological and biochemical challenges we address include: radical reactions catalyzed by `Radical-SAM' enzymes, the most widespread metalloenzyme superfamily; enzymatic formation of bio-available nitrogen, on which over half the world's population depends; the role of Mn2+ in radiation resistance, including the resistance of human tumors, in aging, and in oocyte fertilization.

PI_NAMEs: HOFFMAN, BRIAN M (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Biological Transition Metals

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


NIH_SPENDING_CATS: Childhood Obesity;Lung;Nutrition;Obesity;Pediatric;Women's Health Research

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE (RELEVANCE)  Obesity is an uncontrolled global epidemic. Maternal exposure to ambient fine particulate matter (PM2.5) correlates with offspring obesity. We and others have shown the adverse programming of offspring adiposity by maternal PM2.5 exposure, explaining this association. Using unique knockout and transgenic mouse models, this project will determine the unexplored maternal pathogenesis for this programming, aiming to develop effective intervention strategies that target the maternal pathogenesis and thus may benefit the health of both the mother and child.

PI_NAMEs: YING, ZHEKANG  (contact);YU, LIQING

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Adipocytes;air filter;Animal Model;Chemicals;Child;Closure by clamp;Conceptions;constitutive expression;Data;demethylation;Dependence;DNA;Dose;effective intervention;Embryo Transfer;Epidemic;epidemiology study;Exposure to;Female;fine particles;Gene Expression;Genes;Genetically Modified Animals;Germ Cells;Health Benefit;Hypermethylation;Inflammation;Inflammation Mediators;inhibitor;Intervention;Knock-out;Laws;Leptin;Lesion;Link;lipid biosynthesis;Location;Lung;male;Mammalian Oviducts;Maternal Exposure;maternal obesity;Mediating;Messenger RNA;Modeling;Mothers;mouse model;Mus;Obesity;obesity risk;offspring;offspring obesity;Oocytes;Ovarian;overexpression;Partner in relationship;Pathogenesis;Phosphotransferases;Policies;Prevention;programs;Publishing;Pulmonary Inflammation;Role;Techniques;Testing;transcriptome sequencing;Transgenic Mice

PROJECT_TITLE: Mechanism for Programming of Offspring Adiposity by Maternal PM2.5 Exposure


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: DAVIS

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative Evaluation of fibrosis and tubular atrophy from chemically stained kidney biopsies are essential for diagnosis and disease-severity assessment, but current techniques are time-consuming, non-specific and contribute to interobserver variability and imprecision, affecting care. We propose to optimize and test a new kind of microscope (“DUET”) that can visualize fibrosis (scarring) and other tissue abnormalities directly from standard H&E slides to enable high-quality reproducible and accurate fibrosis scoring and evaluation. This multi-site project will also provide a unique opportunity to perform a retrospective study from hundreds of existing H&E slides with associated months to years of clinical follow-up data, and to create a method with demonstrated utility in more than one institution.

PI_NAMEs: FEREIDOUNI, FARZAD  (contact)

PROGRAM_OFFICER_NAME: GOSSETT, DANIEL ROBERT

PROJECT_TERMS: Acute;Adoption;Affect;Agreement;Algorithms;Artificial Intelligence;Atrophic;Basement membrane;Biomedical Engineering;Biopsy;Body System;Caring;Cessation of life;Chemicals;Chronic Kidney Failure;Cicatrix;Clinical;clinical care;clinical practice;clinically significant;Collagen;Color;computer scientist;Computer software;Consumption;cost;Creativeness;Data;Data Science;deep learning;design;Detection;Development;Diagnosis;diagnosis standard;Diagnostic;diagnostic value;digital;Disease;Disease Management;disease prognosis;End stage renal failure;Etiology;Evaluation;Fibrillar Collagen;Fibrosis;fluorescence imaging;follow-up;Formalin;Goals;Hematoxylin and Eosin Staining Method;Histologic;histological stains;Histology;Image;Image Analysis;Injury;Institution;instrument;instrumentation;Interobserver Variability;Kidney;kidney allograft;kidney biopsy;Kidney Diseases;Kidney Failure;kidney fibrosis;Laboratories;Machine Learning;macromolecule;Manuals;Measures;Methods;Microscope;Microscopy;Morphology;Nature;novel;Optics;Organ;Outcome;Paraffin Embedding;Pathologist;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Performance;personalized diagnostics;predict clinical outcome;Preparation;Procedures;Process;prognostic model;prognostic value;Recurrence;Renal function;Renal Replacement Therapy;Reproducibility;Research;Retrospective Studies;Running;Scientist;Severity of illness;Signal Transduction;Sirius Red F3B;Site;Slide;Specimen;Speed;Staging;Stains;stem;System;Techniques;Technology;Testing;Time;Tissue Embedding;Tissues;tool;Translations;transmission process;Trichrome stain;Trichrome stain method;Tubular formation;Universities;Validation;virtual;Visual;Visualization

PROJECT_TITLE: Rapid quantitative renal fibrosis evaluation with dual-mode microscopy

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: The central nervous system comprises numerous neuronal subtypes that form specific connections, allowing for complex computations, such as the detection of various visual features by the retina. Using the retina as a model system, we intend to utilize innovative genetic techniques to investigate the role of the cadherin family of cell-recognition molecules in the process of retinal direction-selective circuit wiring. Our ultimate goal is to understand the principles underlying cadherin-mediated connectivity in the retina as a gateway to understand neuronal patterning in the central nervous system, and to offer new cures for various diseases in the eye and the brain.

PI_NAMEs: DUAN, XIN  (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Address;Adopted;Anatomy;Atlases;Axon;axon guidance;Biological Assay;Biological Models;Bipolar Neuron;Brain;Brain region;Cadherins;Cell Adhesion Molecules;Cell Communication;Cells;Central Nervous System;Chimeric Proteins;Clustered Regularly Interspaced Short Palindromic Repeats;Code;combinatorial;Complex;CRISPR/Cas technology;Defect;Detection;Development;differential expression;Disease;Ensure;Etiology;experimental study;extracellular;Eye;Eye diseases;Family;gain of function;ganglion cell;gene interaction;Genes;Genetic;genetic approach;Genetic Techniques;Goals;in utero;in vivo;Individual;Injections;innovation;insight;Interneurons;Knowledge;Location;Logic;Mediating;Methods;Molecular;Molecular Profiling;mutant;Nervous System;Nervous System Disorder;neural;neural circuit;Neurites;neurodevelopment;neuronal patterning;Neurons;Nose;novel;Pattern;Physiological;Positioning Attribute;postsynaptic;Process;Proteins;Retina;Retinal Ganglion Cells;retinal neuron;Role;segregation;Series;Signal Transduction;Specific qualifier value;Specificity;starburst amacrine cell;Study models;Synapses;synaptogenesis;System;Testing;tool;Translating;Vision;Visual;visual information

PROJECT_TITLE: Mechanisms Underlying Type II Cadherin Guided Assembly of Retinal Circuits

STUDY_SECTION: NDPR

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


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: The goal of this R01 is to explore and define the specificity/functionality of IgG3+ B cell responses and the mechanism by which the immune system programs such potent antiviral humoral immunity.

PI_NAMEs: JUELG, BORIS DOMINIK (contact)

PROGRAM_OFFICER_NAME: PALIN, AMY COLLEEN

PROJECT_TERMS: Adjuvant;Antibodies;Antibody Response;Antigens;B-Lymphocytes;cytokine;Cytotoxic T-Lymphocytes;Development;Disease Progression;Epitopes;Evolution;Exposure to;Funding;Goals;HIV;HIV vaccine;Humoral Immunities;IgG3;Immune;Immune system;Immunity;Infection;Learning;Link;Mediating;neutralizing antibody;Patients;programs;recruit;Research;response;Role;Specificity;T cell response;T-Lymphocyte;Vaccination;vaccine trial;vaccine-induced immunity;Viral;Viral Physiology;Virus

PROJECT_TITLE: Demystifying the antiviral activity of the IgG3+ antibody response

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Diabetes;Neurosciences

ORG_CITY: GAINESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Gamma-aminobutyric acid (GABA) is a potent neurotransmitter that is strongly and selectively synthesized in neurons and pancreatic islet beta cells. Our long-term goal is to understand the role of GABA in human islet biology for healthy and disease states such as type 1 and type 2 diabetes. The objectives of this project are to characterize the mechanism of islet GABA release and to bring clarity to the regulatory role of GABA in islet function and blood glucose homeostasis.

PI_NAMEs: PHELPS, EDWARD  (contact)

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Acceleration;Affect;Anabolism;Anions;Beta Cell;Biology;Biosensor;Blood Glucose;blood glucose regulation;Brain;Catabolism;cell type;Cell Volumes;Cells;conditional knockout;Coupled;Cre-LoxP;Cytosol;Dependence;Development;Devices;diabetes management;diabetes pathogenesis;Diabetes prevention;Disease;Enteroendocrine Cell;enzyme biosynthesis;Enzymes;Event;extracellular;Feedback;Fluorescence Resonance Energy Transfer;gamma-Aminobutyric Acid;Genetic;Genetic Models;Glucose;glucose tolerance;Glutamine;glycemic control;Glycine;Goals;Health;Heterozygote;High Pressure Liquid Chromatography;Hormone secretion;Human;Immune;Immunomodulators;Impairment;insulin secretion;Insulin-Dependent Diabetes Mellitus;Intervention;islet;Islet Cell;Islets of Langerhans;Knock-out;Knockout Mice;Knowledge;Link;LoxP-flanked allele;Measurement;Measures;Mediating;Membrane Potentials;Metabolic;Metabolism;Microfluidic Microchips;Modeling;Mus;Nervous System;neural;Neuroglia;Neurons;neurotransmitter release;Neurotransmitters;Non-Insulin-Dependent Diabetes Mellitus;novel;Optics;Pancreas;paracrine;Paracrine Communication;Pathway interactions;Periodicals;Periodicity;Permeability;pharmacologic;Pharmacologic Substance;Pharmacology Study;Phenotype;Physiologic pulse;Physiological;Physiology;Production;Protein Isoforms;Reporting;Research;restoration;Role;Secretory Vesicles;Shunt Device;Signal Transduction;Slice;small hairpin RNA;Synapses;System;Taurine;Technical Expertise;technological innovation;Time;tool;type I and type II diabetes;Vesicle;Whole Organism;Work

PROJECT_TITLE: Mechanism and dynamics of islet GABA signaling


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases;West Nile Virus

ORG_CITY: MENANDS

ORG_NAME: WADSWORTH CENTER

PHR: PROJECT NARRATIVE Studies are proposed to comprehensively assess thermal responses of Culex mosquitoes with and without West Nile virus infection and create more informed transmission models under variable temperatures. Given the strong effects of temperature on viral replication rates, the variability of vector species and population responses to temperature, and the documented role of interactions among viral genotype and environment in governing transmission, studies which aim to model temperature need to consider the evolution of dynamic vector-virus interactions. We will address this gap in infectious disease modeling by simulating evolution under higher temperatures in the lab and utilize these data to inform novel predictive transmission models.

PI_NAMEs: CIOTA, ALEXANDER TIMOTHY (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Acceleration;Affect;Arboviruses;biological systems;Biology;Cessation of life;Climate;Culex (Genus);Culex pipiens;Culicidae;Data;Development;dynamical evolution;emerging pathogen;Environment;enzootic;Evolution;fitness;Flaviviridae;Flavivirus;future climate scenario;Genotype;Geography;High temperature of physical object;Human;in vivo;Infection;infectious disease model;Invertebrate Biology;Laboratories;life history;Location;Modeling;novel;pathogen;Population;predictive modeling;Prevalence;response;Role;System;Temperature;Testing;theories;trait;transmission process;Update;Variant;vector;vector competence;vector-borne pathogen;Vectorial capacity;Viral;viral fitness;viral transmission;Virus;Virus Replication;West Nile viral infection;West Nile virus

PROJECT_TITLE: Modeling the influence of temperature on the evolution of vector-virus interactions

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


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

ORG_CITY: LITTLE ROCK

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Narrative This project focuses on links between circulating glucose metabolism and age-related processes occurring in the cells in the brain that support the neurons. These studies will test the idea that these support cells lose some of their ability to move glucose from the circulation to the neurons, which contributes to the cognitive problems associated with aging and further exaggerated in Alzheimer’s disease. Ultimately, it is anticipated that this study will help us understand changes that occur during aging that make the elderly more vulnerable to disorders such as Alzheimer’s disease, and perhaps even the mental deterioration that sometimes occurs in diabetes.

PI_NAMEs: BARGER, STEVEN W (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta accumulation;age effect;age related;age related decline;Age-associated memory impairment;age-related disease;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;amyloid pathology;Astrocytes;Attenuated;behavior test;Biological Assay;Blood Circulation;blood glucose regulation;Blood Vessels;Brain;brain parenchyma;brain tissue;Cell membrane;cell type;Cells;Cerebral cortex;Cerebrum;Chickens;Chronic;Circulation;Cognition;Cognitive;Compensation;conditional knockout;Defect;Dependence;Desire for food;Deterioration;Diabetes Mellitus;Disease;egg;Elderly;Elements;Endothelium;Energy Metabolism;Exhibits;Gene Modified;Genetic;Glucose;glucose metabolism;glucose tolerance;Glucose tolerance test;glucose transport;Glucose Transporter;GLUT-3 protein;Hippocampus;Human;Hyperglycemia;hyperphosphorylated tau;impaired glucose tolerance;Impairment;innovation;Insulin;Insulin Resistance;Interruption;Link;Memory;Memory impairment;Memory Loss;metabolic rate;Modification;Mus;Nerve Degeneration;Nervous System Physiology;Neurologic;Neurons;neurophysiology;Non-Insulin-Dependent Diabetes Mellitus;normal aging;novel;Obesity;overexpression;Overweight;Pancreas;Performance;Peripheral;Phenotype;Physical activity;Play;Process;Protein Isoforms;Proteins;Psyche structure;Resolution;Role;SLC2A1 gene;spatial memory;Specimen;Supporting Cell;Surveys;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;trafficking;trait;uptake;Work

PROJECT_TITLE: Compromised function of a glial glucose transporter in aging and Alzheimer's disease


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: Project Narrative: Dr Madabhushi's pioneering work on artificial intelligence (AI) has enabled the development of decision support tools to aid clinicians in treating patients suffering from a variety of cancers (breast, prostate, lung, head and neck), but also cardiovascular, kidney and eye disease. Most recently his group adapted AI and radiomics technologies developed for their VA merit project on lung cancer screening for Veterans to digitally analyze CT scans to identify the severity of COVID19 disease. His work has recently focused on the use of AI to help eliminate racial disparities in medicine by identifying disease patterns that might be specific to certain populations, in turn enabling development of population-specific personalized risk calculators. He is applying this AI approach to disease diagnosis, risk stratification, outcome and treatment response prediction in Veterans, where their unique exposure to wartime environments and particular lifestyle choices, engenders different disease phenotypes compared to the civilian population.

PI_NAMEs: MADABHUSHI, ANANT  (contact)

PROJECT_TERMS: Address;Adjuvant Chemotherapy;aggressive therapy;Algorithms;Artificial Intelligence;artificial intelligence algorithm;Award;Benign;Bioinformatics;Biopsy;Breast;cancer diagnosis;cancer immunotherapy;Cancer Patient;cancer type;Cardiovascular Diseases;career;Chemotherapy and/or radiation;Clinical;clinical decision support;clinical investigation;cohort;Collaborations;Communities;companion diagnostics;computer infrastructure;Computer Vision Systems;Computer-Assisted Diagnosis;computerized;computerized tools;COVID-19 severity;Data;Development;Diagnosis;Diagnostic;diagnostic tool;digital;digital pathology;Disease;disease diagnosis;disease phenotype;Environment;experience;explainable artificial intelligence;Exposure to;Eye diseases;Funding;Genomics;head and neck cancer patient;Head and neck structure;Health;high risk;Image;Image Analysis;imaging biomarker;Immunotherapy;Journals;Kidney;Kidney Diseases;Legal patent;Life Style;Lung;lung basal segment;lung cancer screening;Machine Learning;Magnetic Resonance Imaging;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;malignant oropharynx neoplasm;Manuscripts;Marketing;Medicine;military veteran;Modernization;molecular phenotype;Multimodal Imaging;multimodality;National Cancer Institute;Nodule;novel;Oncologist;oncology program;Ophthalmology;oral HPV-positive head and neck cancers;Oropharyngeal;Outcome;Paper;Pathologic;Pathology;pathology imaging;patient subsets;Patients;Pattern;Pattern Recognition;Peer Review;Population;Populations at Risk;precision medicine;precision oncology;predicting response;Prediction of Response to Therapy;Prognosis;prognostication;Prostate;prostate cancer risk;Proteomics;Publications;Publishing;racial disparity;Radiation therapy;Radiogenomics;radiological imaging;radiologist;Radiology Specialty;radiomics;Recurrence;Research;Research Personnel;Resources;Risk;Risk Assessment;Risk Marker;risk prediction;risk stratification;San Francisco;Scanning;Scientist;Series;service programs;Site;standard of care;support tools;symposium;Technology;Tissues;tool;Toxic effect;Translating;treatment response;Tumor-Infiltrating Lymphocytes;Urologist;Validation;Veterans;Work;X-Ray Computed Tomography

PROJECT_TITLE: BLRD Research Career Scientist Award Application


NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Mental Health;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Improving glycemic control and psychosocial well-being in adolescents is essential to preventing complications and mortality associated with type 1 diabetes. In this project, we will develop an ecological momentary intervention to optimize adolescents’ use of advanced diabetes technology for self-management. The knowledge generated through this project will contribute to the advancement of self-management behaviors and improve health outcomes for individuals with type 1 diabetes.

PI_NAMEs: DEJONCKHEERE, MELISSA  (contact)

PROGRAM_OFFICER_NAME: THORNTON, PAMELA L

PROJECT_TERMS: 18 year old;acceptability and feasibility;Acute;Adherence;Adolescence;Adolescent;Adolescent Development;adolescent health;adolescent health outcomes;Adolescent Health Services;Affect;Age;age group;arm;Award;Behavior;behavior change;Behavioral;Biological Process;Blood Glucose Self-Monitoring;Cardiovascular Diseases;career;career development;Caring;Child;Childhood;Chronic;Clinical Trials;Collection;Communities;Complex;Continuous Glucose Monitor;critical period;Data;Data Collection;data integration;data streams;Dedications;design;Development;Development Plans;Devices;diabetes distress;Diabetes Mellitus;Diabetic Ketoacidosis;Ecological momentary assessment;education research;efficacy outcomes;Environment;Environmental Risk Factor;Evaluation;executive function;experience;Family Practice;feasibility testing;Feedback;Glucose;glycemic control;Glycosylated hemoglobin A;Goals;hands-on learning;Health;high risk population;Hormonal Change;Hypoglycemia;implementation strategy;improved;Incidence;Individual;insight;Institution;Insulin;Insulin Infusion Systems;Insulin Resistance;Insulin-Dependent Diabetes Mellitus;Intervention;intervention mapping;Intervention Trial;K-Series Research Career Programs;Kidney Diseases;Knowledge;Knowledge acquisition;Learning;Life;Life Expectancy;longitudinal analysis;macrovascular disease;medical schools;Mentored Research Scientist Development Award;Mentors;Mentorship;Methods;Michigan;mobile application;Morbidity - disease rate;mortality;Natural Language Processing;Neuropathy;Outcome;Patients;Pilot Projects;pilot test;prevent;primary outcome;Problem Solving;Process;Psychosocial Factor;psychosocial outcome;psychosocial wellbeing;Pump;Quality of life;Recommendation;Regimen;Regulation;Research;Research Personnel;Retinal Diseases;Risk;Self Management;Short-Term Memory;skills;Structure;Techniques;Technology;Testing;theories;Theory of Change;Time;Training;Translating;Treatment Protocols;United States;Universities;Well in self

PROJECT_TITLE: Optimizing Use of Advanced Diabetes Technology for Self-Management in Adolescents with Type 1 Diabetes: Integration of Real-Time Glucose and Narrative Data

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: CORVALLIS

ORG_NAME: OREGON STATE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The goal of this project is to investigate the structure-activity relationships of lipid nanoparticle components to improve the efficacy of RNA therapeutics. A greater understanding of nanomaterials and their biological interactions will allow for advanced engineering of this emerging class of therapeutics in numerous biomedical applications, including oncology.

PI_NAMEs: SAHAY, GAURAV ;SUN, CONROY GHIN CHEE (contact)

PROGRAM_OFFICER_NAME: AVULA, LEELA RANI

PROJECT_TERMS: 3-Dimensional;Address;Bar Codes;Basic Science;Biodistribution;Biological;Biological Assay;Biological Process;biological systems;bioluminescence imaging;Biophysics;Breast Cancer therapy;calreticulin;cancer cell;Cancer Model;cell killing;Cells;Characteristics;Chemical Structure;Chemicals;chemotherapy;Clinical;clinical translation;clinically relevant;Combined Modality Therapy;complex biological systems;Data;design;Development;Diffusion;Disease;DNA;dosage;Dose;effectiveness evaluation;Endosomes;Engineering;expectation;experience;Formulation;Future;Gene Delivery;gene therapy;Goals;Healthcare;Heel;Histopathology;hydrophilicity;Immunohistochemistry;Immunologics;immunoregulation;improved;In Vitro;in vivo;individualized medicine;insight;Knowledge;Label;Libraries;lipid nanoparticle;Luciferases;Malignant Neoplasms;Measurement;Messenger RNA;Methodology;Migration Assay;Modification;Molecular;Molecular Target;mouse model;multidisciplinary;multimodality;mutant;nanoengineering;nanomaterials;nanomedicine;nanoparticle;Nanotechnology;novel;novel strategies;Oncologist;Oncology;Organ;Outcomes Research;Periodicity;Population;preclinical study;Process;Property;Proteins;Protocols documentation;radiation effect;Radiation therapy;Radiosensitization;Rare Diseases;RNA;RNA delivery;RNA Interference;Role;Route;Scheme;Series;Solid Neoplasm;Structure;Structure-Activity Relationship;System;Technology;Testing;Therapeutic;therapeutic RNA;Tissues;tool;trafficking;Transfection;Treatment Efficacy;Treatment Protocols;tumor;tumor microenvironment;Tumor Volume;uptake;vaccine development;vaccine distribution;Vaccines;Viscosity

PROJECT_TITLE: Mechanistic insights on structure, topology and radiation effects on RNA nanomedicines

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: The Type 1 diabetes (T1D) epidemic remains a major health problem worldwide. Immune therapeutics (ITs) hold great promise for the treatment of T1D. However, their inadequacy and toxicity have plagued our progress toward their full utilization. Our main goal here is to develop a method for the targeted delivery of ITs in T1D.

PI_NAMEs: ABDI, REZA  (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Address;Affinity;Anti-diabetic Drugs;Antibodies;Antibody Therapy;Autoantigens;Autoimmune;Autoimmune Diabetes;autoreactive T cell;Binding;Biodistribution;CD3 Antigens;Cell Communication;Clathrin;clinical application;clinical efficacy;collaborative approach;cytokine;Data;Dendritic Cells;density;design;Diabetes Mellitus;diabetic;Disease;Dose;Drug Delivery Systems;effective therapy;efficacy evaluation;Encapsulated;Endocytosis;Endothelial Cells;Engineering;Epidemic;Equilibrium;experimental study;Family;Formulation;Glycoproteins;Goals;Health;High Endothelial Venule;Home;Human;human data;Immune;immune modulating agents;Immunosuppression;Immunotherapeutic agent;improved;Inbred NOD Mice;Inflammation;Inflammatory;Injections;innovation;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;insulitis;intravenous injection;lymph nodes;Lymphatic;Mediating;Methods;Monoclonal Antibodies;Morbidity - disease rate;multidisciplinary;Nanodelivery;nanomedicine;nanoparticle;nanoparticle delivery;nanopolymer;novel;Pancreas;Pathogenicity;Pathway interactions;Patients;Peripheral;Play;pre-clinical;preservation;prevent;Process;Property;Public Health;Regulatory T-Lymphocyte;Research;Research Personnel;Role;side effect;Site;Specificity;surface coating;T cell response;T-Cell Activation;T-Lymphocyte;targeted delivery;Testing;Therapeutic;Time;Tissues;Toxic effect;trafficking;Venous;virtual

PROJECT_TITLE: New way in delivering immunomodulatory drugs in T1D


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

ORG_CITY: NEW HAVEN

ORG_DEPT: GENETICS

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: The  collective  burden  of  various  neurodegenerative  diseases  is  large,  yet  no  active  therapeutics  exist  to  effectively  slow  disease  onset  or  progression.  The  studies  proposed  in  this  application  will  allow  us  to  determine  the  molecular  and  cellular  mechanisms  through  which  ataxin- 1  regulates  oligodendroglial  differentiation  and  function,  and  will  elucidate  the  non- neuronal  contributions  to  neurodegenerative  diseases,  revealing  novel  potential  entry  points  for  therapeutic  intervention  in  disorders  associated  with  ataxin- 1  mutations  such  as  spinocerebellar  ataxia  type  1,  frontotemporal  dementia,  amyotrophic  lateral  sclerosis,  and  Alzheimer’s disease.

PI_NAMEs: LIM, JANGHOO  (contact)

PROJECT_TERMS: Alleles;Alzheimer's Disease;Alzheimer's disease risk;Amyotrophic Lateral Sclerosis;ataxin-1;Autopsy;Behavioral;behavioral impairment;Biochemical;Biological Assay;CAG repeat;Cell Line;Cell Lineage;cell type;Cells;Central Nervous System;Cerebellar Ataxia;Cerebellum;Code;Codon Nucleotides;cohort;Complex;Data;Dependence;Disease;Disease Progression;DNA Sequence Alteration;Event;Exons;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Gene Expression;genetic approach;Goals;high standard;Histologic;Human;human induced pluripotent stem cells;human tissue;Impairment;In Vitro;in vivo;insight;Interruption;Investigation;Knock-in Mouse;Knockout Mice;Length;loss of function;Modeling;Molecular;mouse genetics;Multiple Sclerosis;Mus;mutant;Mutation;Myelin;myelination;Nerve Degeneration;Nervous System;Neurodegenerative Disorders;neuron loss;Neuronal Dysfunction;Neurons;novel;oligodendrocyte lineage;oligodendrocyte progenitor;Oligodendroglia;Onset of illness;Pathogenesis;Pathologic;Phenotype;polyglutamine;Population;Process;Progressive Nonfluent Aphasias;Proteins;Purkinje Cells;Research;Risk;Role;Sampling;selective expression;Single Nucleotide Polymorphism;single nucleus RNA-sequencing;sporadic amyotrophic lateral sclerosis;stem cell differentiation;stem cells;Therapeutic;Therapeutic Intervention;Time;Tissues;transcription factor;Trinucleotide Repeat Expansion;Type 1 Spinocerebellar Ataxia

PROJECT_TITLE: Investigation of the role of ATXN1 in oligodendroglia and neurodegenerative diseases

STUDY_SECTION: CMBG

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