NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases;Prevention

PI_NAMEs: ALPERT, MICHAEL DAVID (contact)

PROJECT_TERMS: Anti-Retroviral Agents;Antibodies;antiretroviral therapy;Biological Products;CCR5 gene;CD8-Positive T-Lymphocytes;Cells;Chronic;Collaborations;cost;Data;Diagnosis;Disease remission;Equilibrium;Evolution;exhaustion;fitness;Formulation;Goals;Healthcare;HIV;HIV Infections;HIV Receptors;immune activation;Immune response;Immunity;Immunologics;improved;Injections;insight;Intramuscular Injections;Kinetics;Macaca;Mediating;neutralizing antibody;Outcome;Patients;Persons;Pharmaceutical Preparations;prevent;Probability;programs;Resistance;Resolution;Response Latencies;Signal Transduction;simian human immunodeficiency virus;synergism;Tail;Testing;Therapeutic;Time;tool;treatment group;Vaccines;Viral;Viral reservoir;viral RNA;Virus;Virus Latency;Virus Replication;Vision;Withdrawal;Work

PROJECT_TITLE: Project 3:Optimal use of ART in establishing functional cures


ADMINISTERING_IC: DA

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Opioid Misuse and Addiction;Opioids;Patient Safety;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: DANVILLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: GEISINGER CLINIC

ORG_STATE: PA

PHR: PROJECT NARRATIVE  The proposed research will elucidate how community contextual factors related to economic, social, and physical conditions work in conjunction with individual-level genetic risk factors, healthcare factors, and comorbid medical conditions in generating or mitigating risk for opioid use disorder. It will also identify program implementation factors at the individual, interpersonal, and organizational levels that influence adherence to medication-assisted treatment among patients with opioid use disorder. The research results will inform investment in preventive interventions where community conditions may increase risk for opioid use disorder as well as how health systems can increase retention in treatment programs for opioid use disorder.

PI_NAMEs: POULSEN, MELISSA  (contact)

PROGRAM_OFFICER_NAME: WILEY, TISHA R  A

PROJECT_TERMS: Abate;addiction;Adherence;Administrator;Adult;biobank;Buprenorphine;buprenorphine treatment;case control;Categories;Characteristics;Chronic;Clinic;Clinical;Communities;community intervention;community-level factor;comorbidity;contextual factors;County;Coupled;Data;Death Rate;deprivation;design;disorder risk;Doctor of Philosophy;Dropout;Economics;Electronic Health Record;Environment;Epidemiologist;epidemiology study;exome sequencing;experience;gene environment interaction;Genetic;Genetic Risk;genetic risk factor;Genotype;geographic disparity;Geography;Goals;Grant;Health;health data;Health system;Healthcare;illicit opioid;implementation determinants;implementation science;improved;Individual;informant;innovation;Integrated Health Care Systems;Interview;Investments;Knowledge acquisition;Link;Measurement;Mediating;Mediation;Medical;medication-assisted treatment;Medicine;Mental disorders;Mentored Research Scientist Development Award;Mentors;Mentorship;Methods;Modeling;multilevel analysis;Natural Language Processing;Nested Case-Control Study;novel;Opioid;opioid agonist therapy;opioid epidemic;opioid mortality;opioid overdose;opioid treatment program;opioid use;opioid use disorder;Outpatients;Overdose;overdose death;Patient Compliance;Patient Participation;Patients;Pattern;Pennsylvania;Pharmacogenetics;Pharmacotherapy;Phase;Play;prevent;preventive intervention;Program Effectiveness;programs;Qualitative Research;Relapse;Research;Research Personnel;Research Project Grants;response;Risk;Risk Factors;risk mitigation;Role;rural counties;scale up;skills;social;social cohesion;social determinants;social health determinants;socioeconomics;Statistical Data Interpretation;Substance Use Disorder;success;Surveys;Training;Training Activity;treatment adherence;Treatment outcome;treatment program;Work

PROJECT_TITLE: Understanding the role of community determinants in opioid use disorder and program implementation factors influencing patient adherence to opioid agonist therapy

STUDY_SECTION: CIHB

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


ADMINISTERING_IC: AI

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;HIV/AIDS

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PI_NAMEs: FARZAN, MICHAEL R. (contact)

PROJECT_TERMS: adaptive immune response;adeno-associated viral vector;adenovirus mediated delivery;Adverse event;Antibodies;antibody engineering;antibody mimetics;antiretroviral therapy;Base Pairing;Binding;Capsid;Catalytic RNA;Cells;Cellular Immunity;cellular transduction;Clinical;Collaborations;Data;Dependovirus;Disease remission;DNA;Dose;Duchenne muscular dystrophy;Enterobacteria phage P1 Cre recombinase;FDA approved;HIV-1;Human;immune clearance;improved;in vivo;Individual;Infection;inhibitor;Innate Immune Response;Intramuscular;Luciferases;Macaca;Macaca mulatta;Measurement;Measures;Mediating;Modeling;Mus;neutralizing antibody;Pathway interactions;Pharmaceutical Preparations;Prophylactic treatment;protein expression;Proteins;Reporter;Safety;simian human immunodeficiency virus;Site;System;Testing;Therapeutic;Time;Trans-Activators;transgene expression;Transgenes;Vaccines;vector;vector genome;viral rebound;Virus;Work

PROJECT_TITLE: Project 4: A permanent off-switch for AAV


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Genetics;Lung;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PHR: Project Narrative Cystic Fibrosis (CF) remains the most lethal genetic disease in the Caucasian population, caused by mutation in the CFTR gene, with a wide range of disease severity. Using cutting-edge techniques of stem cell culturing, differentiation into airway epithelium, and gene-editing, this proposal seeks to establish the role of alternative ion channels in patients with extreme disease manifestations. The findings will clarify disease mechanisms in CF, facilitate individualized treatments for patients, and advance use of stem cell- derived airway epithelium to model lung diseases.

PI_NAMEs: WANG, RUOBING  (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: 3-Dimensional;Agonist;Air;airway epithelium;Archives;Award;Basal Cell;Biological Assay;Biological Models;Biology;Boston;candidate validation;career;career development;Caring;Caucasians;Cells;Childhood;Chloride Channels;Chlorides;Clinical;CRISPR/Cas technology;Cystic Fibrosis;cystic fibrosis airway epithelia;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Defect;Delta F508 mutation;Derivation procedure;Disease;disease model;disease phenotype;drug discovery;Drug Modelings;Electrophysiology (science);Environment;Epithelial Cells;epithelial Na+ channel;Epithelium;Evaluation;Exhibits;exome sequencing;Freezing;Functional disorder;Future;gene editing technology;Genes;Genetic;Genetic Diseases;Genetic Polymorphism;genetic variant;Genotype;Goals;Human;improved;In Vitro;in vitro Model;Individual;individual patient;individual response;individualized medicine;induced pluripotent stem cell;inhibitor;Ion Channel;Ions;Liquid substance;Lung Diseases;lung preservation;Manuscripts;Measures;Medicine;meetings;member;Mendelian disorder;Mentors;Mentorship;Modeling;molecular phenotype;Mucociliary Clearance;Mucous body substance;Mutation;novel;Organoids;Patients;Pediatric Hospitals;Pharmaceutical Preparations;pharmacologic;Phenotype;Physicians;Population;Positioning Attribute;precision drugs;Preparation;Protocols documentation;pulmonary function;pulmonary function decline;Regenerative Medicine;Research;Research Personnel;Respiratory Disease;response;Role;Scientist;Severity of illness;single-cell RNA sequencing;Sodium Channel;stem cells;System;Techniques;Testing;therapeutic candidate;therapeutic evaluation;Time;timeline;Training;Universities;Variant;Vertebral column;Viscosity

PROJECT_TITLE: Using Induced Pluripotent Stem Cells to Characterize Cystic Fibrosis

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

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: CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE We have developed a brain-penetrant, small molecule drug candidate, called MW189, that targets dysregulated inflammation and attenuates brain dysfunction. The proposed project will fill the remaining gaps necessary to bring MW189 to a future clinical study in Alzheimer’s patients. MW189 has the potential to be a first-in-class disease-modifying therapy for Alzheimer’s disease and related disorders.

PI_NAMEs: VAN ELDIK, LINDA J;WATTERSON, DANIEL MARTIN (contact)

PROGRAM_OFFICER_NAME: REFOLO, LORENZO

PROJECT_TERMS: Acute;Acute Brain Injuries;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease therapy;Amendment;American;Area;Attenuated;attenuation;Biological;Brain;brain dysfunction;Brain hemorrhage;Canis familiaris;capsule;Central Nervous System Diseases;Chemistry;Clinical;clinical candidate;clinical development;clinical investigation;Clinical Research;Clinical Trials;Critical Care;cytokine;Dementia;Disease;Disease Progression;Disease susceptibility;Dose;drug candidate;drug development;drug discovery;Drug Formulations;drug quality;effective therapy;Formulation;Foundations;Functional disorder;Future;Human;Impaired cognition;Individual;Inflammation;Inflammatory;Intervention;Investigation;manufacture;Medicine;Morbidity - disease rate;mortality;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;Neurology;novel therapeutic intervention;Oncology;Oral;Oral Administration;Outcome;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology and Toxicology;Phase;phase 3 study;phase II trial;Placebos;Positioning Attribute;preclinical safety;preclinical study;prevent;Production;programs;Public Health;Qualifying;Rattus;Recovery;Reference Standards;research clinical testing;Research Infrastructure;Safety;safety study;Scheme;small molecule;stability testing;Stress Tests;stressor;success;Synapses;Testing;Therapeutic;therapeutic candidate;Toxicokinetics;Toxicology;Work

PROJECT_TITLE: GMP Production and Extended Toxicology of an Oral Formulation Drug for Alzheimer's Disease


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;Cardiovascular;Cerebrovascular;Dementia;Heart Disease;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The causes of Alzheimer’s disease (AD) in most cases are poorly understood, and there are likely many factors that influence the onset, severity, and trajectory of AD. However, many studies suggest that cardiovascular disease risk factors may act together with other genetic or environmental insults to promote AD. This project will examine the impact of the cardiovascular risk factor PAI-1 on cognition, brain vascular function, and changes in vascular gene expression in the context of AD.

PI_NAMEs: LAWRENCE, DANIEL A (contact);MURPHY, GEOFFREY G

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: abeta deposition;Accounting;Affect;Affinity Chromatography;Age;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid beta-Protein;Amyloid deposition;angiogenesis;Behavioral;Blood flow;Blood Vessels;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;cerebrovascular;Cerebrum;Clinical;Cognition;Cognitive deficits;comorbidity;Complex;Data;Dementia;Development;diagnostic biomarker;Disease Progression;Endothelial Cells;Enzyme Precursors;Enzymes;Etiology;extracellular;Failure;Fibrinolysis;Functional disorder;Gene Expression;Genes;Hemostatic function;hyperphosphorylated tau;Hypertension;Impaired cognition;improved;improved outcome;Inflammation;Inflammatory;inhibitor;Light;Link;Literature;Methods;Microvascular Dysfunction;Modeling;Modernization;Morphology;mouse model;Mus;Nature;neural;Neurofibrillary Tangles;neuron loss;neuropathology;Neurosciences;neurovascular;neurovascular coupling;novel;Onset of illness;Other Genetics;Outcome;Pathologic;Pathology;Pathway Analysis;Pathway interactions;pharmacologic;Phenotype;Plasmin;Plasminogen;Plasminogen Activator;Plasminogen Activator Inhibitor 1;Plasminogen Inactivators;Play;Reporting;response to injury;Ribosomes;Risk Factors;Role;Senile Plaques;Severities;Severity of illness;Signal Transduction;Synapses;System;Tauopathies;Testing;Tissues;transcriptome sequencing;Transgenic Organisms;Translating;translatome;Urokinase;vascular abnormality;Vascular Diseases;vascular injury;Vascular remodeling;wound;wound healing

PROJECT_TITLE: The Role of PAI-1 in Cerebral Microvascular Dysfunction and the Development of Alzheimer’s Disease Neuropathology


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_CITY: IRVINE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder resulting in dementia primarily in the elderly populations. The age-dependent increasing plaque load in AD has been correlated with an exacerbated loss of extracellular matrix structures called perineuronal nets (PNNs). Thus, it is imperative we determine the consequences of PNN loss in AD to gain deeper insight into pathology progression as well as the therapeutic potential PNNs may hold.

PI_NAMEs: BARAHONA, ROCIO ALEJANDRA (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Ablation;Acceleration;Affect;Age;age related;aggrecan;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Behavioral;Brain;Cell Death;Cells;Central Nervous System;Cerebral hemisphere;Chondroitin Sulfate A;Chondroitin Sulfate Proteoglycan;Cognitive deficits;Cytoprotection;Data;Dementia;Deposition;Development;Disease;effective therapy;Elderly;Enhancers;Enterobacteria phage P1 Cre recombinase;Exhibits;Extracellular Matrix;Fluorescent in Situ Hybridization;Genes;Genetic Recombination;genome wide association study;Hippocampus;Homeostasis;human tissue;Immunohistochemistry;Immunologic Surveillance;Impaired cognition;Impairment;in vivo;Incubated;inhibitor therapy;inhibitory neuron;Injections;insight;Interneurons;knockout gene;Knowledge;Laboratory Finding;Learning;LoxP-flanked allele;Macrophage;Mediating;Mediator;Memory;memory consolidation;Memory impairment;Microglia;Minor;Modeling;mouse model;Mus;nestin protein;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;neuron loss;neuronal cell body;Neuronal Dysfunction;Neurons;Neurotoxins;novel therapeutics;Outcome;Oxidative Stress;Parvalbumins;Pathogenesis;Pathologic;Pathology;Patients;Play;Population;Predisposition;prevent;Protease Inhibitor;Protein Analysis;Proteins;Regulation;Role;Senile Plaques;Structure;Synapses;Therapeutic;Time;Tissues;transcriptome sequencing;Transgenic Organisms;Viral Vector;Virus;Wild Type Mouse

PROJECT_TITLE: Defining the role of perineuronal nets in Alzheimer's Disease pathology


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Digestive Diseases;Immunotherapy;Nanotechnology;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: QUEENS

ORG_NAME: ST. JOHN'S UNIVERSITY

ORG_STATE: NY

PHR: Scarcity of curative therapy and poor patient survival are critical issues involved in the treatment of highly aggressive pancreatic ductal adenocarcinoma (PDAC). We propose to develop a novel pancreatic cancer cell directed nanoformulations for the simultaneous delivery of novel class of anticancer molecules to target new blood vessels, dense tumor fibrosis and cancer cell for the treatment of PDAC. The proposed research will establish a clinically relevant platform technology for targeted delivery of drugs in lethal PDAC and supports the NIH mission of generating remedies for human diseases by designing a translational nanomedicine.

PI_NAMEs: PATEL, KETANKUMAR D. (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: 3-Dimensional;Address;Albumins;angiogenesis;anti-cancer;anticancer activity;Antineoplastic Agents;Apoptosis;Award;Biological Assay;Blood Vessels;Body Weight;c-myc Genes;cancer cell;Cancer Etiology;cancer type;Cell Culture Techniques;Cell Line;Cell Proliferation;Cell Survival;Cells;Cessation of life;chimeric antigen receptor T cells;Circulation;clinically relevant;Coculture Techniques;Collagen Type I;combinatorial;Combined Modality Therapy;curative treatments;cytotoxicity;density;Deposition;design;Desmoplastic;Development;Drug Delivery Systems;Drug Kinetics;Drug resistance;effective therapy;Emerging Technologies;Endothelial Cells;Environment;Evaluation;Extracellular Matrix;Fibroblasts;Fibrosis;Focal Adhesion Kinase 1;Formulation;Fostering;gemcitabine;Goals;graduate student;Growth;Hematology;Hepatotoxicity;Human;human disease;Hyaluronic Acid;Immune checkpoint inhibitor;Immunohistochemistry;improved;In Vitro;in vivo;indexing;innovative technologies;Intravenous;Investigation;kinase inhibitor;Kinetics;KRAS2 gene;Laboratories;liposomal formulation;liposome vector;Liposomes;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Mentors;Metabolism;Methods;Microsomes;Mission;Monoclonal Antibodies;mortality;nanoformulation;nanoliposome;nanomedicine;nanomolar;nanoparticle;Nanotechnology;nanotherapeutic;Nature;Neoplasm Metastasis;neoplastic cell;novel;Oncogenic;Oncoproteins;Oral;overexpression;Pancreas;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;Pathogenesis;Pathway interactions;Patients;Penetration;Pharmaceutical Preparations;pharmacologic;Plasma;Play;Prognosis;Proliferating;Protac;Proteins;racial diversity;recruit;Research;Research Methodology;Research Proposals;Resistance;Resistance development;Role;Science;Side;Solid Neoplasm;Solubility;Students;Survival Rate;targeted delivery;targeted treatment;technology platform;Testing;therapeutically effective;three dimensional cell culture;three-dimensional modeling;Toxic effect;Training;translational approach;tumor;Tumor Angiogenesis;tumor growth;Tumor Markers;tumor microenvironment;Tumor Volume;tumor xenograft;ubiquitin-protein ligase;undergraduate student;United States National Institutes of Health;Universities;uptake;Vascular blood supply;Western Blotting;Xenograft Model

PROJECT_TITLE: Combination of tumor targeted therapy with stroma modulating agent for PDAC


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Orphan Drug;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

PHR: PROJECT NARRATIVE Hemophilia A is an inherited bleeding disorder with no cure. Treatment involves repeated infusions of coagulation factor VIII throughout the life of the patient, which creates tremendous discomfort and morbidity. In response to these limitations, we seek to develop a novel technology that uses cells encapsulated in a device to deliver factor VIII into the bloodstream, correcting the clotting deficiency of hemophilia A.

PI_NAMEs: MELERO-MARTIN, JUAN M (contact);WANG, BO

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: 3-Dimensional;Activated Partial Thromboplastin Time measurement;Address;Alginates;Allogenic;Biological Assay;Biology;Bioluminescence;Blood;Blood Circulation;Blood coagulation;Blood Coagulation Disorders;Blood Vessels;Canis familiaris;Cell Line;Cell Survival;Cell Transplantation;Cells;Clinical;clinically relevant;Clone Cells;Coagulation Process;Code;Competence;Cytoprotection;Data;density;Dermal;Development;Devices;Diameter;Disease;DNA Transposons;Drug Delivery Systems;Eligibility Determination;Encapsulated;Endothelial Cells;Engineering;Engraftment;Enzyme-Linked Immunosorbent Assay;Enzymes;Evaluation;Excision;Exons;experience;Extracellular Matrix;F8 gene;Factor VIII;Fibrinogen;Fibroblasts;Future;gene therapy;Genetic Engineering;Genome;Genomics;Germ Cells;Greater sac of peritoneum;Hemophilia A;Hemorrhage;Homologous Transplantation;Human;human pluripotent stem cell;Hydrogels;Immune;Immunocompetent;immunodeficiency;immunoreaction;implantation;In Vitro;in vivo;induced pluripotent stem cell;Inflammation;Infusion procedures;Inherited;inhibitor;Internal Ribosome Entry Site;Length;Life;Liver;Maps;Methods;Morbidity - disease rate;Mus;Mutation;new technology;novel;Organoids;Patients;Phenotype;Plasma;Pluripotent Stem Cells;preclinical efficacy;prevent;Production;Productivity;programs;Protein Engineering;Research;response;Risk;Safety;sensor;subcutaneous;System;Tail;Technology;Teratoma;Testing;Therapeutic;Time;Titrations;Transgenes;Translations;Transplantation;Transposase;Tubular formation;United States National Institutes of Health;Vascularization;White Blood Cell Count procedure;Whole Blood;Work

PROJECT_TITLE: Vascular networks genetically engineered for protein drug delivery

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Disability Research;Eye Disease and Disorders of Vision;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Social Determinants of Health

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will inform policy discussions around state and federal proposals to cover vision services by providing rigorous estimates of the effects of routine eye care coverage on access to vision care and fall-related outcomes among dual eligibles. Thus, the proposed research is relevant to the part of NIH’s mission that pertains to enhancing health and reducing illness and disability. This application is also relevant to the part of NEI’s mission that pertains to protecting and prolonging vision, and to the part of NIA’s mission that pertains to improving the health and well-being of older adults.

PI_NAMEs: LIPTON, BRANDY  (contact)

PROGRAM_OFFICER_NAME: LE, JIMMY TOAN

PROJECT_TERMS: Accident and Emergency department;Address;Adult;Age;Age related macular degeneration;Aging;Alzheimer's disease related dementia;Behavioral Model;beneficiary;Black race;Caring;Cataract;Data;Data Sources;Databases;dementia risk;Devices;Diabetes Mellitus;Diagnosis;disability;dual eligible;Ethnic Origin;experience;Eye;Eye diseases;Eyeglasses;fall injury;fall risk;falls;fear of falling;federal policy;Fee-for-Service Plans;Glass;Glaucoma;Health;Health Insurance;health service use;Health Services Accessibility;high risk population;Hip Fractures;Hispanic;human old age (65+);improved;Individual;innovation;Insurance Coverage;Link;Low income;Measures;Medicaid;Medical Care Costs;medically necessary care;Medicare;Medicare claim;Memory Loss;men;Methods;Mission;Modeling;Morbidity - disease rate;mortality;National Health Interview Survey;older adult;ophthalmic examination;Outcome;Patient Self-Report;Personal Satisfaction;Policies;Population;Prevalence;Price;programs;Public Health;public health insurance;Qualifying;Quality of life;Quasi-experiment;Race;Refractive Errors;Reporting;Research;Research Personnel;Risk Reduction;Role;Services;sex;Subgroup;Surveys;Testing;trend;United States National Institutes of Health;Variant;Vision;Visit;Visual impairment;Woman;Work

PROJECT_TITLE: Impact of routine eye care coverage on access to eye care and fall-related outcomes among low-income Medicare enrollees

STUDY_SECTION: ODHS

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


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

ORG_CITY: KENT

ORG_DEPT: BIOLOGY

ORG_NAME: KENT STATE UNIVERSITY

ORG_STATE: OH

PHR: Narrative The problem we aim to solve is beta-amyloid pathology that contribute to the pathogenesis of Alzheimer's disease. We propose to apply a magnetothermal brain stimulation that enables the targeted clearance of beta- amyloid plaques by working synergistically with microglia-mediated innate immune response towards the treatment of Alzheimer's disease.

PI_NAMEs: KIM, MIN HO  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Abeta clearance;abeta deposition;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease therapy;Amyloid beta-Protein;Amyloid deposition;Behavior;beta amyloid pathology;Biochemical;Biological;Brain;brain tissue;Clinical;Cognitive deficits;cognitive function;Data;Dementia;Disease;Dose;Ensure;extracellular;Frequencies;Genetic;glial activation;Goals;Heat-Shock Proteins 70;Human;improved;In Vitro;Innate Immune Response;innovation;insight;Knowledge;Link;magnetic field;mechanical energy;Mechanics;Mediating;Memory impairment;Microglia;minimally invasive;Mus;nanoparticle;neural;Neurodegenerative Disorders;Neurons;neuropathology;Nonpharmacologic Therapy;novel;Pathogenesis;Pathologic;Pathology;Peptides;pharmacologic;Pharmacological Treatment;prevent;Production;Publishing;response;Role;Senile Plaques;Signal Transduction;spatiotemporal;Specificity;superparamagnetism;Synapses;Testing;Therapeutic;Toxic effect;Transducers;Translating;β-amyloid burden

PROJECT_TITLE: Magnetothermal brain stimulation towards the rescue of beta-amyloid pathology


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Neurosciences;Sleep Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Insomnia symptoms are commonly experienced in most clinical populations and are associated with adverse outcomes and decreased quality of life. There is a critical need to identify an objective marker of insomnia symptoms that can be used to improve assessment and treatment planning in order to reduce the public health burden of poor sleep.

PI_NAMEs: GEHRMAN, PHILIP RICHARD (contact);WELJIE, AALIM M

PROGRAM_OFFICER_NAME: LONG, SYLVIA ELISABETH

PROJECT_TERMS: Acclimatization;accurate diagnosis;actigraphy;Acute;adverse outcome;Biological;Biological Assay;Biological Markers;biomarker panel;Blood;Blood specimen;Branched-Chain Amino Acids;Chronic;Chronic Insomnia;circadian;Circadian Rhythms;Clinical;clinical application;clinical diagnosis;clinical subtypes;cohort;common symptom;comorbidity;Data;design;diagnostic strategy;Distress;Eating;Electroencephalography;Environment;Environmental Risk Factor;Exhibits;experience;Fructose;Future;Glucose;Home;Hour;Human;Hydrocortisone;Impairment;improved;indexing;Individual;Indwelling Catheter;Inpatients;Laboratories;Laboratory Study;Lead;light effects;Lighting;Lipids;Mass Spectrum Analysis;Measurement;Measures;meetings;Melatonin;Mental Health;Metabolic;metabolic profile;metabolic rate;Metabolism;metabolome;metabolomics;Modeling;NMR Spectroscopy;novel diagnostics;Nuclear Magnetic Resonance;Outcome;Oxidative Stress;Patient Self-Report;Patients;Periodicity;phenomics;Phenotype;physical conditioning;Plasma;Polysomnography;poor sleep;Population;Protocols documentation;Public Health;Quality of life;Reporting;Research;Sampling;Science;Serum;Severities;Severity of illness;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep disturbances;Sleeplessness;sugar;symptom management;symptomatic improvement;Symptoms;Techniques;Testing;Time;treatment planning;young adult

PROJECT_TITLE: Metabolic Reprogramming in Insomnia as a Function of Objective Sleep Duration

STUDY_SECTION: MESH

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Contraception/Reproduction;Endometriosis;Genetics;Rare Diseases;Women's Health Research

ORG_CITY: KANSAS CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative  Adenomyosis is a significant disease in women. Understanding how the disease develops and identifying those factors which participate in disease progression and manifestation of clinical presentation may allow for new treatments which offer benefits over current therapies as well as the potential development of prognostic and/or diagnostic markers.

PI_NAMEs: CHENNATHUKUZHI, VARGHEESE MANI;NOTHNICK, WARREN B (contact)

PROGRAM_OFFICER_NAME: TINGEN, CANDACE M

PROJECT_TERMS: 3' Untranslated Regions;Adenomyosis;Biological;Biological Assay;Cell Communication;cell motility;Cell Proliferation;Cells;Clinical;conditional knockout;Data;Development;Diagnosis;diagnostic biomarker;Disease;Disease Progression;effective therapy;Endometrial;endometrial stroma;Endometrium;Epithelial Cells;Event;Experimental Models;experimental study;Functional disorder;Gene Expression;Gland;Hormonal;Human;Hysterectomy;Image;In Vitro;in vitro Model;innovation;insight;Invaded;Knockout Mice;Knowledge;Mediating;Mediator;Menstruation;MicroRNAs;migration;mouse model;Myometrial;myometrium;Neurons;Non-Malignant;novel;optimal treatments;Outcome Study;Pain;Pathogenesis;Pathologic;Pathway interactions;Pelvic Pain;Prognostic Marker;Proliferating;RE1-silencing transcription factor;Regulation;Reporter;Reporting;Repression;reproductive;Research;Role;Series;Signal Pathway;Smooth Muscle;Specimen;stem;Testing;theories;tissue injury;tissue repair;Tissues;transcription factor;transcription factor REST;Transcription Repressor;transcriptome sequencing;Uncertainty;Uterine Diseases;Uterus;Woman;Women's Group;young woman

PROJECT_TITLE: REST/NRSF, miRNAs, and tissue remodeling in adenomyosis pathophysiology

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE / PUBLIC HEALTH RELEVANCE Living cells use hundreds of specific chemical reactions to produce energy, to make new components, and to signal important events, but most of these processes are invisible without specific probes. Genetically-encoded fluorescent biosensors allow us to capture real-time “movies” of biochemical processes inside individual cells, providing a vivid picture of how cells normally function and how they malfunction in disease. These sensors are difficult to develop and optimize because many candidates must be screened carefully to find a highly specific, sensitive, and robust reporter for each particular target molecule; our improved screening method dramatically improves the ability to screen for optimized versions of existing biosensors and to develop new ones.

PI_NAMEs: YELLEN, GARY I (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: acetoacetyl CoA;Acetyl Coenzyme A;Address;Adopted;Bathing;Binding Proteins;Binding Sites;Biochemical;Biochemical Process;Biochemistry;Biological Assay;Biosensor;cell behavior;Cells;Cellular Metabolic Process;Chemical Dynamics;chemical reaction;Chemicals;Collection;Color;Computing Methodologies;Data;design;Development;dimer;Disease;DNA;DNA Sequence;Dose;Encapsulated;Enzymatic Biochemistry;Event;Exposure to;Family;Fluorescence;Gel;Generations;Genetic;Genotype;Glucose;glucose sensor;Goals;Grant;Green Fluorescent Proteins;high throughput screening;Homodimerization;Image;improved;Individual;insight;interest;Jellyfish;Libraries;machine learning method;Malonyl Coenzyme A;Mass Spectrum Analysis;Measurement;Measures;Metabolic;Methods;microbial;Microfluidics;Microscope;microscopic imaging;movie;next generation sequencing;novel;Permeability;Phenotype;Process;Production;Proteins;prototype;public health relevance;Publications;Publishing;Reporter;Resistance;Resolution;response;scaffold;screening;Second Messenger Systems;Sensitivity and Specificity;sensor;Series;Signal Transduction;Site-Directed Mutagenesis;Sorting;Specificity;success;Technology;temporal measurement;Testing;Time;tool;transcription factor;Validation;Variant

PROJECT_TITLE: High-throughput optimization of genetically-encoded fluorescent biosensors

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


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;Biomedical Imaging;Brain Disorders;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Despite sex differences in the clinical and biological profiles of Alzheimer’s disease with women showing a cognitive advantage yet greater Alzheimer’s pathology in early disease stages followed by a two-times steeper decline, sex is not considered in our current diagnostic methods. In this study, we will use both in-life biomarker and postmortem neuropathological data to determine how the clinical expression of AD pathology differs in women versus men and understand why these differences occur and how they impact disease diagnosis. By accounting for sex disparities in our current clinical diagnostic approaches, we can improve and tailor risk assessment and diagnostic methods to be optimal for each sex.

PI_NAMEs: SUNDERMANN, ERIN ELIZABETH (contact)

PROJECT_TERMS: abeta accumulation;Acceleration;Accounting;advanced disease;Age;Aging;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease diagnostic;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;Attenuated;Autopsy;Autoradiography;Biochemistry;Biological;Biological Markers;biomarker validation;Brain;brain metabolism;brain size;brain tissue;Buffers;Cessation of life;Clinical;clinical diagnostics;Clinical Markers;clinical translation;clinically significant;Cognition;Cognitive;cognitive function;cognitive performance;cognitive testing;Data;Dementia;density;Detection;detection method;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic criteria;Diagnostic Procedure;diagnostic strategy;Disease;disease diagnosis;Disease Progression;Early Intervention;Equilibrium;Female;Frequencies;Gender;gender difference;Generations;glial activation;glucose metabolism;Glutamates;Health Benefit;Hippocampus;Impaired cognition;improved;In Vitro;in vivo;innovation;Learning;Life;Measures;Mediator;Memory;men;mild cognitive impairment;Modeling;N-Methyl-D-Aspartate Receptors;Neurobiology;Neurofibrillary Tangles;neuroimaging;Neuroimmune;neuroinflammation;neuron loss;Neurons;neuropathology;neurotransmission;Pathology;Positron-Emission Tomography;pre-clinical;prodromal Alzheimer's disease;prospective;Proteins;Proxy;Public Health;receptor density;receptor function;Research;resilience;resilience factor;Resistance;response;Risk;Risk Assessment;Risk Factors;Sensitivity and Specificity;sex;Sex Differences;sex disparity;social culture;Symptoms;tau Proteins;Testing;therapeutic target;Variant;verbal;Woman;women versus men;Work

PROJECT_TITLE: Sex Differences in the Clinical Expression of Alzheimer's Disease Neuropathology and Their Underlying Biological Mechanisms


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Epilepsy;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Prevention;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: NEW HAVEN

ORG_DEPT: NEUROLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Post-traumatic epilepsy, a seizure disorder secondary to traumatic brain injury (TBI), is among the most disabling and difficult-to-treat complications of TBI. Currently, there are no tools to identify patients a priori at highest risk for PTE. Dr. Kim's proposed career development plan has great potential to advance our knowledge of the acute biomarkers of PTE using EEG and MRI, to improve early identification and ultimately provide treatment options for this potentially preventable complication.

PI_NAMEs: KIM, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Acute;Acute Brain Injuries;Address;Admission activity;Algorithms;Animals;Antiepileptogenic;Atrophic;Award;axon injury;Benchmarking;Biological Markers;biomarker development;biomarker identification;Biometry;Blinded;Brain Injuries;care costs;career;career development;Caring;Characteristics;Chronic;Cognition;Collection;Complication;Contusions;cost estimate;Critical Care;Critical Illness;Data;Development;Development Plans;didactic education;disability;Disabling;Disease;early detection biomarkers;Early identification;Electroencephalography;Enrollment;Epilepsy;epileptiform;Epileptogenesis;follow-up;Foundations;Frequencies;Functional Imaging;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Hemorrhage;Heterogeneity;high risk;hippocampal atrophy;Hippocampus;Hospitals;Human;human imaging;Image;Image Analysis;imaging biomarker;improved;Injury;Intervention;Knowledge;Lesion;Location;Machine Learning;Magnetic Resonance;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;magnetic resonance imaging/electroencephalography;Malignant - descriptor;Measures;Mentors;Mentorship;Methods;Monitor;Morbidity - disease rate;Multicenter Trials;multimodal learning;multimodality;neuroimaging;neuroimaging marker;Neurologist;neurophysiology;Outcome;Paper;patient biomarkers;Patient Monitoring;patient oriented research;Patient-Focused Outcomes;Patients;Phase;Population;Post-Traumatic Epilepsy;prediction algorithm;predictive marker;prevent;preventable epilepsy;Prevention trial;prospective;Provider;Publishing;radiological imaging;Research;Research Proposals;Resolution;Rest;Risk;risk stratification;Rodent Model;Sclerosis;Secondary to;Seizures;Severities;signal processing;skills;structural imaging;Structure;TBI Patients;Techniques;Technology;therapy development;Thick;tool;Training;Translating;translational scientist;Traumatic Brain Injury;treatment trial;trial enrollment;United States National Institutes of Health;white matter;Work

PROJECT_TITLE: EEG and MRI Biomarkers to Predict Post-traumatic Epilepsy


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Dementia;Estrogen;Genetics;Hypertension;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID);Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: NARRATIVE  People with uncontrolled hypertension have an almost three-fold increased risk for dementia, and if they are carriers of apolipoprotein E4 (ApoE4, that is, 25% of population), then they have 13 fold increased risk for dementia (female E4 carriers already have twice as much as risk as male E4 carriers). Despite the fact that 80% of people with Alzheimer's also have cerebrovascular diease (mixed dementia) and despite the knowledge that people with mixed dementia have serious adverse effects to amyloid clearing drugs, there is a paucity or lack of preclinical models and none with ApoE3 or ApoE4. We have now developed a novel rat model for mixed dementia, which has several features of mixed dementia including energy deficits, and including ApoE3 and ApoE4: rats have additional advantages over mice because of a more complex brain and larger cerebrospinal fluid and plasma volumes, making it a better preclinical model.

PI_NAMEs: FRAUTSCHY, SALLY ANN (contact)

PROJECT_TERMS: 3xTg-AD mouse;Acceleration;Address;Adverse effects;Affect;Age;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid;Amyloid beta-Protein;Angiotensin II Receptor;antagonist;Anti-Hypertensive Agents;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;APP-PS1;Attenuated;Behavior;Behavioral;behavioral phenotyping;Biochemical;Biological Markers;Blood Plasma Volume;Blood Pressure;blood pressure control;Blood Vessels;Brain;Breeding;cell type;Cerebrospinal Fluid;Cerebrovascular Disorders;Cilostazol;Clinic;Cognitive;cohort;Combined Modality Therapy;comorbidity;Complex;Consensus;Data;Dementia;dementia risk;Demyelinations;diagnostic criteria;Drops;drug efficacy;efficacy evaluation;Endothelial Cells;Endothelium;epidemiology study;Estrogen Antagonists;Estrogen Receptors;Estrogens;Exclusion;Exhibits;exosome;experience;Experimental Designs;Extravasation;FDA approved;Female;Genetic;Glial Fibrillary Acidic Protein;Goals;high salt diet;Human;human female;Hypertension;hypertensive;improved;Inbred WKY Rats;Individual;Inflammation;inhibitor;Intervention;Knowledge;Longitudinal Studies;Losartan;male;men;Menopause;Metabolic;Methods;Microglia;Microvascular Dysfunction;Mitochondria;mixed dementia;Modeling;Mus;mutant;Nerve Degeneration;Neuroglia;neuroimaging;neuroinflammation;neuropathology;Neuropil;neuroprotection;neuropsychiatry;Neuropsychology;neurovascular injury;neurovascular unit;normotensive;novel;Oral;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pericytes;Persons;Pharmaceutical Preparations;Phenotype;Plasma;Polypharmacy;Population;Postmenopause;Pre-Clinical Model;protective effect;Publishing;Rat Strains;Rattus;Research Priority;Risk;Risk Factors;RNA;Rodent;screening;Severities;sex;Signal Transduction;spatial memory;Stroke;Study models;Surrogate Markers;synergism;tau Proteins;Tauopathies;Testing;Therapeutic;tool;transcriptome sequencing;Transgenes;Validation;Vascular Cognitive Impairment;Vascular Diseases;Vascular Endothelial Growth Factors;vascular factor;vascular inflammation;Woman;β-amyloid burden

PROJECT_TITLE: Metabolic and Vascular Factors in tau pathogenesis

STUDY_SECTION: CDIN

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


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

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE  Alzheimer’s disease (AD) is a prevalent and burdensome neurodegenerative disease with no highly effective therapeutic to slow the progression of the disease. Since the molecular mechanisms that mediate the effects of APOE risk factors for AD progression remain unclear, there is a critical need for preclinical research to identify novel ways to diagnose and treat AD in humans. Therefore, this proposal will test the hypothesis that APOE genotype risk factors for AD impact the molecular profiles of astrocytes and change their inflammatory and metabolic phenotypes and contribute to AD pathogenesis.

PI_NAMEs: RAMELOW, CHRISTINA CATHERINE (contact)

PROJECT_TERMS: Address;Adopted;aged;Alleles;Alzheimer's Disease;Alzheimer's disease risk;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Astrocytes;Autopsy;Biochemical;Bioinformatics;Biological Process;Biotin;Biotinylation;Brain;brain control;Brain region;brain tissue;Cell Separation;cell type;Cholesterol;Complement;cytokine;Data;Diagnosis;differential expression;Disease;Disease Progression;Exhibits;Foundations;Future;Genetic;genetic approach;Genetic Risk;Genotype;glial activation;Goals;high risk;Hippocampus;Homeostasis;Human;Immune response;Immunoassay;Impaired cognition;in vivo;Individual;Inflammation;Inflammatory;Inflammatory Response;inhibitor;innovation;interest;Knock-in;Knowledge;Label;Laboratories;Late Onset Alzheimer Disease;Ligase;lipid metabolism;LoxP-flanked allele;MAP Kinase Gene;Mass Spectrum Analysis;Mediating;Mediator;MEKs;metabolic phenotype;Metabolism;Methodology;Microglia;Modification;Molecular;Molecular Profiling;Mouse Protein;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuropathology;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pathologic;Pathway interactions;Phenotype;Phosphoproteins;phosphoproteomics;Play;Pre-Clinical Model;pre-clinical research;Production;protein aggregation;Proteins;Proteome;Proteomics;response;Risk;Risk Factors;risk variant;RNA;Role;selective expression;Signal Pathway;Signal Transduction;Source;sugar;Synapses;Testing;therapeutically effective;Time;TNF gene;transcriptome sequencing;transcriptomics;Validation;Work

PROJECT_TITLE: Astrocyte-specific in vivo molecular signatures of APOE genetic risk in Alzheimer's disease


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;Rare Diseases;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Preservation of healthy blood vessels in the brain is important strategy in protection against cognitive decline. This application is designed to determine functions of two critically important enzymes (BACE1 and BACE2) located in the brain blood vessels. Our proposed studies will define the roles of BACE1 and BACE2 in development of cerebral amyloid angiopathy (CAA). CAA is a disease in which proteins called amyloid build up in the walls of the arteries in the brain. CAA significantly increases the risk and can cause dementia. Currently, there is no disease-specific treatment available to patients with CAA. Successful completion of proposed studies will provide scientific basis for development of therapeutic interventions designed to prevent detrimental effects of CAA on the brain function.

PI_NAMEs: KATUSIC, ZVONIMIR S (contact)

PROJECT_TERMS: abeta accumulation;Abeta clearance;abeta deposition;Abeta synthesis;Age-associated memory impairment;aging brain;Agreement;alpha secretase;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Amyloidosis;Arteries;beta-site APP cleaving enzyme 1;Bioinformatics;Blood Vessels;Brain;brain endothelial cell;Brain Injuries;brain parenchyma;Cell Separation;Cerebral Amyloid Angiopathy;Cerebral hemisphere hemorrhage;cerebral microvasculature;cerebrovascular;cerebrovascular pathology;Cerebrovascular Physiology;Cerebrovascular system;Clinical;cognitive function;Dementia;Deposition;design;Development;Disease;Disease Progression;Elderly;Endothelial Cells;Endothelium;Enzymes;Experimental Models;experimental study;Fluorescence-Activated Cell Sorting;Gene Expression Profile;Gene Modified;Genes;Homeostasis;Homologous Gene;Human;Impaired cognition;Impairment;In Vitro;Injury;Intercellular Fluid;Knockout Mice;Link;Microvascular Dysfunction;Molecular;molecular targeted therapies;mouse model;Mus;Nerve Degeneration;next generation;next generation sequencing;Pathogenesis;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Play;preservation;prevent;Prevention;Production;Proteins;Regulation;Reporting;Risk;Role;Signal Transduction;Site;Sporadic Cerebral Amyloid Angiopathy;therapeutic development;therapeutic target;therapy design;transcriptome;transcriptome sequencing

PROJECT_TITLE: Role of endothelium in pathogenesis of cerebral amyloid angiopathy


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

ORG_CITY: PROVIDENCE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE Alzheimer’s Disease (AD) is a deadly, age-related neurodegenerative disorder that has been studied for decades, but despite the identification of some key mechanisms, the molecular pathways that underlie neuronal dysfunction and degeneration in AD remain unknown. Recently, Chitinase-3-like protein 1 (CHI3L1) has been implicated in the pathogenesis of AD because AD patients have higher cerebrospinal fluid concentrations of CHI3L1 compared to healthy controls that increase in a progression-dependent manner. This proposal addresses the role that CHI3L1 plays in the central nervous system, specifically in the context of AD and neurodegeneration, thus providing critical information that can potentially be used in targeted therapeutics to combat AD and its progression or in other medical advances related to this disease.

PI_NAMEs: CONNOLLY, KEVIN C (contact)

PROJECT_TERMS: AD transgenic mice;Address;Adopted;age related neurodegeneration;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer’s disease biomarker;American;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Apoptosis;Astrocytes;Award;Binding;Biology;Brain;career;Cause of Death;Cell Surface Receptors;cell type;Cells;Central Nervous System;Cerebrospinal Fluid;Characteristics;CHI3L1 gene;Chitinase;combat;conditional knockout;confocal imaging;Data;Dedications;Diagnosis;Disease;Enterobacteria phage P1 Cre recombinase;Event;experimental study;extracellular;Funding;Future;Genes;Genetic;Genetic Transcription;Gliosis;Goals;Growth;Hippocampus;Human;Immune;Immune signaling;Immunity;Impairment;In Vitro;in vivo;Induced pluripotent stem cell derived human neuron;Inflammatory;Injections;Intervention;Knock-out;Laboratories;LoxP-flanked allele;Lung;Lung Diseases;Measurement;Measures;Mediating;Medical;Methods;Molecular;mouse model;Mouse Strains;mutant;Nerve Degeneration;Neurites;Neurobehavioral Manifestations;Neurofibrillary Tangles;Neuroglia;neuroinflammation;neuron apoptosis;neuron loss;Neuronal Dysfunction;Neurons;neurotoxic;neurotoxicity;neurotransmission;Outcome;Pathogenesis;Pathologic;Pathway interactions;Peripheral;Phosphorylation;Play;Pluripotent Stem Cells;presenilin-1;Prevention strategy;Process;protein expression;Proteins;Quantitative Reverse Transcriptase PCR;receptor;Receptor Gene;Recombinants;Reporting;Research;Research Personnel;Research Training;Resources;response;RNA Interference;Role;Scientist;secretase;Senile Plaques;Signal Pathway;Signal Transduction;Signaling Molecule;skills;stem cells;Stress;Structure of parenchyma of lung;success;Synapses;synaptic function;System;targeted treatment;tau-1;Testing;TIE gene;Tissues;Training;Transcript;transcriptomics;Transgenic Mice;United States;Western Blotting

PROJECT_TITLE: The Neuronal Effect of CHI3L1 in Neuroinflammation & Alzheimer's Disease


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

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;Prevention

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Alzheimer's disease (AD) and related dementias affect a growing number of people as the population ages. Currently, nearly 6 million persons in the US have AD; it is estimated that by the year 2050, that number will be 14 million. With this increase in the number of AD patients, there is a corresponding growth in the number of family members and other caregivers affected by this devastating disease, as well as dramatic social and economic costs. The goal of our research training program is to prepare a new generation of investigators to translate mechanistic scientific discoveries into effective tools for diagnosis, treatment, and prevention of AD and related dementias.

PI_NAMEs: KRAEMER, BRIAN C.;PESKIND, ELAINE R. (contact)

PROGRAM_OFFICER_NAME: MARTIN, DAMALI

PROJECT_TITLE: Neurobehavior, Neuropathology, and Risk Factors in Alzheimer's Disease


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE This project is relevant to public health because it explains how light regulates the refractive function the eye. This work has implications for human health because it may provide a way to treat refractive error, including myopia, with light stimulation therapy.

PI_NAMEs: LANG, RICHARD A. (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Acute;Adipose tissue;age effect;Animal Model;Biological Assay;Biology;Brain;Cataract;Cellular biology;Crystalline Lens;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;design;Development;Event;experimental study;Eye;Eye Development;G Protein Gene;G-Protein-Coupled Receptors;gain of function;GTP-Binding Proteins;Health;Human;interest;lens;lens transparency;Light;Link;loss of function;Mammals;Mediating;Methods;MIP gene;Mus;Myopia;Neural Retina;Ocular Physiology;Opsin;Optics;Pathway interactions;Performance;Permeability;Phosphorylation;Predisposition;Property;Public Health;Publishing;Recording of previous events;Refractive Errors;response;Retina;Role;Sense Organs;Signal Transduction;Skin;Tissues;Tupaiidae;Vision;Water;water channel;Work

PROJECT_TITLE: Mechanisms of intrinsic light responses in the ocular lens

STUDY_SECTION: BVS

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Hearing Loss;Neurosciences;Prevention

ORG_CITY: Columbus

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Pathophysiology of the noise-induced hearing loss (NIHL) has been well characterized in the cochlea, but is less clear in the central auditory system. This project investigates the mechanisms of NIHL in the cochlear nucleus (CN) by identifying the pathological changes of the innervating auditory nerve synapses and their postsynaptic CN neurons, and clarifying the altered signal processing after moderate and traumatic noise exposure.

PI_NAMEs: XIE, RUILI  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: 3-Dimensional;Acceleration;Acoustic Nerve;Affect;Age;Auditory;auditory nuclei;Auditory Perception;auditory processing;Auditory system;Cells;Cellular Morphology;Clinical;clinical development;Closure by clamp;Cochlea;Cochlear nucleus;Code;confocal imaging;Confocal Microscopy;Development;Electrophysiology (science);Exhibits;experimental study;Functional disorder;Gene Modified;Goals;Hair Cells;Hearing;hearing impairment;Hearing problem;hidden hearing loss;Hyperacusis;Image;Immunofluorescence Immunologic;Immunohistochemistry;Individual;inhibitory neuron;insight;Intervention;Knowledge;Label;Life;Link;Membrane;Modification;Morphology;Mus;neural;neural network;Neurons;Noise;noise exposure;Noise-Induced Hearing Loss;normal hearing;Outcome;Output;Pathologic;Peripheral;permanent hearing loss;Persons;Physiological;Physiology;postsynaptic;postsynaptic neurons;Presbycusis;prevent;Property;Reporting;Risk Factors;Role;Sensory Hair;sensory input;signal processing;Site;sound;Specificity;speech recognition;spiral ganglion;Structure;Synapses;Synaptic Transmission;Techniques;transmission process;voltage clamp;Whole-Cell Recordings;Work

PROJECT_TITLE: Auditory nerve synaptopathy and the central mechanisms underlying noise-induced hearing loss

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: INDIANAPOLIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Coxsackievirus is a major human pathogen that initiates infection in the mammalian gastrointestinal tract, home to a community of resident bacteria. These bacteria can enhance Coxsackievirus replication and pathogenesis; however, the mechanism remains unclear. The goal of this proposal is to investigate the mechanism of bacterial-mediated enhancement of Coxsackievirus infectivity and stability.

PI_NAMEs: ROBINSON, CHRISTOPHER MICHAEL (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Adult;Affect;Affinity;Amino Acids;Avidity;Bacteria;Binding;Binding Sites;Biological Assay;Biological Models;Breathing;Capsid;Cell Wall;Cell-Matrix Junction;Cells;Chemical Structure;Child;Communities;Coxsackie Viruses;Coxsackievirus Infections;Cryoelectron Microscopy;Data;Development;Disease Outbreaks;Electrostatics;Elements;Enteral;enteric virus infection;Environment;Escherichia coli;Foot Diseases;Future;Gastrointestinal tract structure;Generations;Goals;Gram-Negative Bacteria;Hand's disease;Home;human pathogen;Human poliovirus;improved;In Vitro;in vivo;Individual;Infection;Intestines;Lipopolysaccharides;Mediating;Membrane;Meningoencephalitis;microbiota;mouse model;Mouth Diseases;mutant;novel;novel therapeutics;Oral;particle;Pathogenesis;pathogenic microbe;Population Heterogeneity;Prevention;Reovirus;Route;Salmonella;Salmonella enterica;Structure;thermostability;transmission process;Viral;viral myocarditis;Viral Pathogenesis;viral transmission;Virion;Virus;Virus Replication

PROJECT_TITLE: Bacterial-mediated enhancement of Coxsackievirus

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Aging;Biotechnology;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Glaucoma is a leading cause of blindness worldwide and lowering eye pressure is the only proven  treatment. We have discovered a novel pathway that is disrupted in Lowe syndrome, a rare disease  that causes glaucoma in children, and which leads to abnormally high intracellular levels of  phospholipids. The proposed studies will restore the lipid imbalance that underlies Lowe syndrome  and we anticipate that this study will lead to novel therapeutics not only for this disease, but  also for other more common forms of glaucoma.

PI_NAMEs: SUN, YANG  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: adenovirus mediated delivery;Adult;Alleles;alternative treatment;aqueous;Area;Blindness;cell motility;Cells;Cellular Assay;Cessation of life;Child;Childhood;congenital cataract;Data;Defect;Disease;disease model;effective therapy;Endocytosis;Enzymes;Equilibrium;experimental study;Eye;Female;FRAP1 gene;Functional disorder;gene replacement;Gene Targeting;Generations;Genes;Glaucoma;Goals;Human;human induced pluripotent stem cells;human stem cells;Hydrophthalmos;Hyperoxia;In Vitro;in vivo;inhibitor;Injections;Inositol;inositol-1,4,5-trisphosphate 5-phosphatase;Intervention;Kidney Failure;Light;Link;Lipids;male;Measures;Methods;Modeling;mouse model;Mus;Mutate;Mutation;novel;novel therapeutic intervention;novel therapeutics;Oculocerebrorenal Syndrome;optogenetics;Organ;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phenocopy;Phosphatidylinositols;Phospholipids;Phosphoric Monoester Hydrolases;Physiologic Intraocular Pressure;pressure;Rare Diseases;Regulation;Research;restoration;Role;Signal Pathway;Signal Transduction;small molecule;stem cell model;Stretching;targeted treatment;Testing;Therapeutic;therapeutic target;Trabecular meshwork structure;upstream kinase;Viral;Vision;Wild Type Mouse;Work;X Chromosome;young adult

PROJECT_TITLE: Phosphoinositide signaling in glaucoma: rescue strategies for Lowe syndrome

STUDY_SECTION: DPVS

STUDY_SECTION_NAME: Diseases and Pathophysiology of the Visual System Study Section[DPVS]


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Successful treatments for atherosclerotic heart disease reduce the “bad” cholesterol in the bloodstream, but further therapies are needed, underscoring the public health relevance of this proposal. These challenges will be addressed by 1) developing a precursor to a small molecule drugs which could reduce these cholesterol levels, 2) evaluating whether there is a scientific basis to repurpose currently approved anticoagulant medications to lower cholesterol, and 3) identifying other factors responsible for elevating cholesterol which could be targets themselves for new drugs. As a result, this proposal is directly relevant to the NIH mission of promoting fundamental discoveries and innovative research designs as a basis for improving human health.

PI_NAMEs: CHORBA, JOHN S (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Address;Affect;analog;Antibodies;Anticoagulants;Atherosclerosis;Binding;biochemical tools;Biological;Biology;Blood Circulation;blood lipoprotein;cardioprotection;Cardiovascular system;Cell surface;Cell Surface Receptors;Cells;Chemicals;Cholesterol;Chromosome Mapping;Clinic;Clinical;clinical efficacy;cofactor;Coronary heart disease;cost;cost effective;CRISPR interference;Development;Drug Targeting;Engineering;Event;Exhibits;Foundations;gain of function;Genetic;genetic manipulation;genetic variant;genome-wide;Goals;Health;Health Services Accessibility;Heparan Sulfate Proteoglycan;Heparin;Hepatic;Hepatocyte;Human;Human Genetics;Impairment;improved;improved outcome;In Vitro;in vivo;in vivo Model;inhibitor;innovation;insight;Insurance Carriers;Lead;Liver;Long-Term Effects;loss of function;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Lysosomes;Mediating;Mediator;Mission;Molecular;Molecular Chaperones;Mutation;new therapeutic target;novel;novel therapeutics;Oral;Outcome;Pathway interactions;Patients;Peptide Hydrolases;Pharmaceutical Preparations;Phenocopy;Phenotype;Physiological;Price;Proprotein Convertases;Proteolysis;public health relevance;Receptor Down-Regulation;receptor downregulation;receptor expression;Regulation;Research Design;Resistance;reuptake;Role;Safety;scaffold;screening;Serum;Small Interfering RNA;small molecule;small molecule therapeutics;Subtilisins;Therapeutic;therapeutic target;tissue tropism;Tissues;tool;trafficking;United States National Institutes of Health;Variant

PROJECT_TITLE: Chemical Biology to Modulate PCSK9 and Treat Atherosclerosis


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

PHR: Project Narrative Relevance: A single DNA gene produces many different RNA molecules that differ in size and composition, and each of them plays a distinct role in cellular function and the life of an organism. We are creating new RNA sequencing methods that will enable us to monitor all of these isoforms individually, making it possible to determine their specific roles in human health and disease

PI_NAMEs: GRAVELEY, BRENTON R.;PYLE, ANNA MARIE (contact)

PROGRAM_OFFICER_NAME: MORRIS, STEPHANIE A

PROJECT_TERMS: Algorithms;Alternative Splicing;Catalytic RNA;cDNA Library;Cell Cycle Kinetics;Cell Physiology;Cells;Cellular Stress;Centromere;chemical synthesis;Chemicals;Chromatin;cofactor;Complementary DNA;Complex;Complex Mixtures;computational suite;Data Analyses;Dependence;Detection;Development;Digestion;Disease;DNA;DNA Damage;Doxorubicin;Drosophila genus;epitranscriptomics;Event;Evolution;Gene Expression;Gene Expression Regulation;Genes;Guanosine;Health;Heat-Shock Response;Human;implementation facilitation;indexing;Individual;interest;Ions;Kinetics;Label;Length;Life;Link;machine learning algorithm;Maps;Mass Spectrum Analysis;Medicine;Messenger RNA;Metabolic;Metals;Methodology;Methods;methyl group;Modeling;Modification;Monitor;Mutation;nuclease;Nucleotides;Organism;Paralysed;Pathway interactions;performance tests;Play;Population;Population Heterogeneity;Positioning Attribute;Post-Transcriptional RNA Processing;preservation;Primer Extension;Principal Investigator;Process;programs;Protein Isoforms;Protocols documentation;Pseudouridine;reference genome;Repetitive Sequence;Reporting;RNA;RNA chemical synthesis;RNA-Directed DNA Polymerase;RNase P;Role;Sampling;sequencing platform;single-cell RNA sequencing;Site;Sodium Channel;Specificity;Structure;System;Technology;Testing;Thiouridine;Time;Tissues;Training;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Transfer RNA;Translations;Validation;Variant;viral RNA;voltage

PROJECT_TITLE: High-throughput detection of transcriptomic and epitranscriptomic variation and kinetics using MarathonRT

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-B(50)R]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

PHR: NARRATIVE Cardiac alternans is a recognized risk factor for cardiac arrhythmia, including atrial fibrillation, and sudden cardiac death. This study seeks to investigate the conditions that cause and sustain atrial alternans, and to determine cellular mechanisms of alternans in individual atrial myocytes, in multicellular tissue and at organ level, and to explore therapeutic interventions that reduce alternans risk.

PI_NAMEs: BANACH, KATHRIN  (contact);KANAPORIS, GIEDRIUS

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Action Potentials;Affect;Anesthesia procedures;Animal Testing;Animals;Arrhythmia;Atrial Fibrillation;Attenuated;Buffers;Calcium Signaling;Cardiac;Cell Communication;Cells;Complex;Coupling;Dependence;Development;Diffuse;electrical property;Electrophysiology (science);Endowment;experimental study;Fire - disasters;Gap Junctions;Generations;Goals;Heart;Heart Atrium;Heterogeneity;in vivo;Individual;Intervention;Ion Channel;ITPR1 gene;Link;Membrane;Mitochondria;Modeling;Morphology;Muscle Cells;novel;Organ;Oxidation-Reduction;Perfusion;Peripheral;pharmacologic;Phase;Predisposition;Property;Protocols documentation;Reactive Oxygen Species;receptor;Regional Perfusion;Regulation;Risk;Risk Factors;Role;Sarcoplasmic Reticulum;sex;Sex Differences;Signal Transduction;Source;spatiotemporal;sudden cardiac death;System;Testing;Therapeutic Intervention;Tissues;uptake;voltage;voltage clamp

PROJECT_TITLE: Atrial Excitation-Contraction Coupling, Calcium Signaling and Electro-Mechanical Alternans

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Clinical Research;Emphysema;Lung;Prevention

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative: This project will 1. measure associations between the CD66b+/NE+ exosome burden and important disease metrics in COPD and non-COPD smokers, 2. create novel models of this pathway study, and 3. advance innovative therapeutic strategies to interrupt CD66b+/NE+ exosome-mediated pathology.

PI_NAMEs: RUSSELL, DEREK  (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: Address;alpha 1-Antitrypsin;Alveolar;alveolar destruction;Animal Model;Attenuated;Automobile Driving;Binding;Biological;Biological Markers;biomarker performance;Bronchoalveolar Lavage Fluid;career development;Cause of Death;Cells;Characteristics;Charge;Chronic Bronchitis;chronic inflammatory disease;Chronic Obstructive Pulmonary Disease;Clinical;cohort;Collagen Type I;Data;design;Development;Disease;disease phenotype;Disease Progression;disorder risk;Dissociation;Environment;Equilibrium;exosome;experience;Extracellular Matrix;Flow Cytometry;former smoker;Foundations;Functional disorder;Genetic;Goals;Human;human disease;In Vitro;in vivo;Inflammation;Inherited;innovation;Integrins;Interruption;Knockout Mice;Leukocyte Elastase;Link;Lung;Macrophage-1 Antigen;Measures;Mediating;Medical;Modeling;molecular array;Monitor;mouse model;Mus;nanovesicle;neutrophil;never smoker;novel;Obstruction;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Phase;Phenotype;Process;Prognosis;Property;Protamine Sulfate;Protease Inhibitor;Proteoglycan;Proteolysis;Pulmonary Emphysema;Research Project Grants;Resistance;Respiratory Failure;Risk;Risk Factors;Sampling;Serum;Smoker;Smoking;Source;Specimen;Sputum;Structural Protein;Surface;Symptom Burden;Symptoms;Techniques;Therapeutic;therapeutic target;Tissues;Training;Translating;treatment response;Trypsin;vesicular release

PROJECT_TITLE: Activated Neutrophilic Exosome as Biomarker and Therapeutic Target in COPD

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


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Multiplex panels are rapid tests that can improve patient outcomes by helping clinicians start effective antibiotic therapy sooner, but false positives may lead to unnecessary antibiotics that cause harmful side effects or resistance. This project seeks to improve use of multiplex panel testing in acute care by examining when and for whom multiplex panel testing is associated with improved clinical outcomes and more efficient use of antibiotics and then developing interventions to promote testing in those situations. This project is relevant to public health and the AHRQ mission because antibiotic overuse and emerging antibiotic resistance are an urgent threat to patient safety.

PI_NAMEs: BAGHDADI, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: WILLIS, TAMARA

PROJECT_TITLE: Optimizing Implementation of Multiplex Molecular Panel Testing to Reduce Diagnostic Error

STUDY_SECTION: HCRT

STUDY_SECTION_NAME: Healthcare Research Training [HCRT]


NIH_SPENDING_CATS: Aging;Clinical Research;Health Services

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Skilled nursing facilities (SNFs) have been a target of efforts to improve quality and reduce spending under value-based purchasing initiatives, but robust gains remain elusive. The current study will examine whether physicians that specialize in SNF-based care (SNFists) improve functional outcomes and reduce healthcare utilization (such as hospital readmissions) of patients in SNFs. We will also examine patient functional outcomes and healthcare utilization of SNFists vs. non-SNFists under value-based purchasing initiatives.

PI_NAMEs: RYSKINA, KIRA L (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: accountable care organization;Acute;acute care;Administrator;aging population;beneficiary;bundled payment;Caring;Characteristics;Clinical;Clinical assessments;Communication;Communities;Complex;Continuity of Patient Care;cost;Data;Data Set;Databases;Destinations;Emergency department visit;experience;Familiarity;Fee-for-Service Plans;Frail Elderly;functional improvement;functional outcomes;functional status;Goals;graduate school;Health care facility;health care service utilization;High Prevalence;hospital care;hospital readmission;Hospitalization;Hospitals;Human Resources;improved;improved outcome;Incentives;Intervention;Interview;Length of Stay;Link;Marketing;Measures;medical schools;medical specialties;Medicare;Medicare claim;Nurse Administrator;Nursing Homes;Nursing Staff;older adult;Outcome;Ownership;Patient Care;Patient Discharge;Patient-Focused Outcomes;Patients;Penetration;physical therapist;Physicians;Policies;Population;Prevalence;Primary Care Physician;Process;Protocols documentation;provider factors;Quality of Care;Resources;Role;Sampling;Site;Skilled Nursing Facilities;Specialist;Structure;Time;Training;trend;Work

PROJECT_TITLE: Post-acute care of older adults: the role of skilled nursing facility specialists

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Dental, Oral, and Craniofacial Disease;Regenerative Medicine

ORG_CITY: ANN ARBOR

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE The goal of this Training Program is to provide an interdisciplinary research-intensive training environment for individuals who wish to pursue careers in the oral sciences, with a focus on the regeneration of dental-oral- craniofacial tissues. DDS/PhD, PhD, and Post-doctoral Fellows will be trained in a comprehensive Program that spans across departmental and school boundaries, providing intensive training opportunities in both basic biomedical and clinical science. Our commitment to training oral scientists as independent researchers and life- long learners will help develop a diverse and highly qualified workforce that significantly impacts oral health.

PI_NAMEs: KOHN, DAVID H. (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Tissue Engineering;tissue regeneration

PROJECT_TITLE: Tissue Engineering and Regeneration


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: BOSTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: PROJECT NARRATIVE Exposure to early life stress is associated with vulnerabilities to psychiatric illnesses. We aim here to determine how early life stress alters the development of brain circuitry in males and females to find preventative interventions that are targeted to individuals.

PI_NAMEs: BRENHOUSE, HEATHER C (contact);TSENG, KUEI-YUAN

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Acceleration;Adolescence;Adolescent;Affect;Affective;Age;Amygdaloid structure;Anatomy;Anxiety;anxiety-like behavior;Attention;attributable risk;Automobile Driving;Behavior;Behavioral;behavioral response;Brain;brain circuitry;Cells;cognitive process;Communication;critical period;Data;designer receptors exclusively activated by designer drugs;Detection;Development;disorder risk;early adolescence;early experience;early life adversity;early life stress;Early-life trauma;effective intervention;Electrophysiology (science);ESR1 gene;Estrogen Receptors;Estrogens;Exhibits;experience;Exposure to;Female;genetic approach;Glutamates;Goals;Gonadal Steroid Hormones;high risk;Hormonal;hormonal signals;Hyperactivity;in vivo;Individual;interest;Intervention;Knowledge;Learning;Life Experience;life span;Link;male;maternal separation;Mediating;Mediator;Mental Depression;Mental disorders;Modeling;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Nature;nerve supply;neuronal circuitry;neurophysiology;Neurosecretory Systems;novel;periadolescent;Population;Predisposition;Prefrontal Cortex;prevent;Prevention;preventive intervention;Psychopathology;Puberty;Rattus;Receptor Signaling;Recording of previous events;Regulation;Research;resilience;response;Risk;RNA Interference;Role;sex;Signal Transduction;small hairpin RNA;Specificity;Testing;Time;translational study;Translations;transmission process

PROJECT_TITLE: Mechanisms driving the development of threat sensitivity following early life adversity


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Aging;Neurosciences

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Understanding the normal physiological processes that govern proteostasis in neurons is of fundamental importance. In this proposal we are focused on understanding the BAG3-dependent mechanisms regulating vacuolar dependent pathways in neurons which facilitate tau clearance and promote synaptic health. The results from these studies will provide foundational information for understanding the mechanisms that contribute to the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases.

PI_NAMEs: JOHNSON, GAIL V. W. (contact)

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: Aftercare;Alzheimer's Disease;Area;Autophagocytosis;Awareness;BCL2 gene;Binding;Client;Data;Dendritic Spines;Development;Disease;DNA cassette;Endosomes;Enterobacteria phage P1 Cre recombinase;Esters;Event;Functional disorder;GTPase-Activating Proteins;Health;high resolution imaging;Homeostasis;in vivo;Injections;innovation;insight;Investigation;Kinetics;Leucine;live cell imaging;LoxP-flanked allele;Lysosomes;Maintenance;Mediating;Mediator;Molecular;Morphology;mouse model;Mus;Neurodegenerative Disorders;Neurons;novel;optogenetics;Outcome;overexpression;Pathogenesis;Pathologic;Pathology;Pathway interactions;Pattern;Physiological Processes;Play;Population;Process;promoter;protein aggregation;Proteins;Proteome;Proteomics;proteostasis;Quality Control;Reactive Oxygen Species;recruit;Regulation;repaired;Reporting;Resistance;Role;Signal Transduction;Sorting;Stress;Structure;Synapses;System;Tamoxifen;tau aggregation;tau expression;tau Proteins;tau-1;Tertiary Protein Structure;Testing;trafficking;Vesicle

PROJECT_TITLE: BAG3 regulates Rab35 and the ESCRT/endolysosome pathway

STUDY_SECTION: CMND

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


NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Narrative Cellular heterogeneity is a defining feature of biology, but we currently lack tools that scale with the complexity of tissue heterogeneity. We developed a new method to directly measure biochemical activities in thousands to millions of single cells and will deploy it broadly to provide a more vivid picture of cell-type- specific biochemical activities.

PI_NAMEs: HESSELBERTH, JAY R (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Acceleration;Adoption;Allosteric Regulation;Award;Biochemical;Biochemistry;Bioinformatics;Biological Assay;Biology;Biomedical Research;Cell Cycle;Cell Extracts;Cell Physiology;cell type;Cells;Cellular Assay;Chromatin;cofactor;Complex;Data;Development;Dissociation;DNA;Enzyme Activation;enzyme activity;Enzyme Inhibition;Enzyme Inhibitor Drugs;Enzymes;Event;experimental study;functional status;Gene Expression;Genotype;Glean;Goals;Heterogeneity;High-Throughput DNA Sequencing;Human Biology;human disease;In Situ;in vivo;indexing;Individual;innovation;insight;Lipids;Massive Parallel Sequencing;Measurement;Measures;Messenger RNA;Methods;Modality;Modernization;mRNA Expression;novel strategies;Organ;Phase;Polysaccharides;Post-Translational Protein Processing;Proteins;Regulation;Resolution;RNA;Science;single cell mRNA sequencing;single cell proteins;Tissues;tool;tumor;Whole Organism

PROJECT_TITLE: Biochemistry at single-cell resolution: a new approach to understand functional heterogeneity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BCMB-A(51)]


NIH_SPENDING_CATS: Aging

PHR: Project Narrative We propose a comprehensive training program in the biology of aging that will prepare trainees for careers at the forefront of academics, industry, and biotechnology, thereby promoting the discovery of a deeper biological understanding of the aging process and nurturing a passion to apply their experience to alleviate the cost and suffering associated with age-related disease.

PI_NAMEs: PLETCHER, SCOTT  (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Biology of Aging;career;Training

PROJECT_TITLE: Career Training in the Biology of Aging


ADMINISTERING_IC: CA

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: HOUSTON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Our research aims to improve cancer outcomes by using pharmacologic blockade of DNA damage response together with diffusing alpha-emitters radiation therapy (DaRT), a form of radiation that creates focused clusters of DNA damage, to activate the immune system to combat tumors. The proposed research is expected to advance our abilities to use existing oncologic treatments in a novel way, in order to harness the immune system to improve patient outcomes for aggressive cancers.

PI_NAMEs: SAWAKUCHI, GABRIEL OLIVEIRA (contact)

PROGRAM_OFFICER_NAME: CAPALA, JACEK

PROJECT_TERMS: Address;Affect;Alpha Particle Emitter;Alpha Particles;anti-CTLA4;anti-tumor immune response;Antigens;ATR gene;Binding;Brachytherapy;cancer subtypes;Cell Cycle;Cell Cycle Arrest;cell killing;Cell Maturation;Cells;Clinical;combat;cytokine;Cytoplasm;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;density;Deposition;Diffuse;Diffusion;DNA Damage;DNA lesion;DNA Repair;DNA Repair Inhibition;Dose;ds-DNA;Gases;Gene Activation;High-LET Radiation;immune activation;immune cell infiltrate;immune checkpoint blockade;Immune response;Immune Response Genes;Immune signaling;Immune system;Immunologic Stimulation;Immunologics;immunoregulation;Immunotherapy;Impairment;improved;in vivo;inhibitor;Innate Immune Response;innovation;Interferon Type I;interstitial;ionization;Ionizing radiation;IRF3 gene;Lesion;Linear Energy Transfer;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediator;meter;Methods;micronucleus;Mitosis;Modality;mouse model;novel;Outcome;pancreatic cancer model;particle;Pathway interactions;Patient-Focused Outcomes;Pharmaceutical Preparations;pharmacologic;Phase I Clinical Trials;Photons;Population;pre-clinical;Predisposition;Production;Prognosis;Protons;Radiation;Radiation therapy;Radioactive;Radiopharmaceuticals;Radium-224;Radon;recruit;Research;response;Role;Rupture;Seed Implantation;Signal Transduction;Solid;Solid Neoplasm;Stimulator of Interferon Genes;T-Cell Activation;TANK-binding kinase 1;Testing;Tissues;tool;Transactivation;transcription factor;Transcriptional Activation;Translations;tumor;Tumor Immunity;Tumor Volume;Water;Work

PROJECT_TITLE: Alpha particles combined with ATR inhibition to activate the immune system: mechanisms and pre-clinical translation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CTH-R(56)R]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics;Muscular Dystrophy;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Mutations in the POGLUT1 gene result in a new form of muscle disease. The proposed studies use mouse genetics, stem cell culture and biochemical approaches to examine the mechanisms underlying the pathology of this disease and to identify the target proteins and pathways affected by POGLUT1 mutations, in hopes of establishing a new framework for treating muscle disorders.

PI_NAMEs: DARABI, RADBOD ;JAFAR-NEJAD, HAMED  (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Adult;Affect;Alleles;Animals;Biochemical;Biological Assay;Biology;Body System;Carbohydrates;causal variant;Cell Communication;Cell Culture Techniques;Cell model;Cell Surface Proteins;cell type;Cells;Complex;conditional knockout;consanguineous family;Consensus Sequence;CRISPR correction;CRISPR/Cas technology;Data;Defect;Development;differentiation in vitro;Disease;disease model;Drosophila genus;Embryonic Development;Enzymes;Epidermal Growth Factor;Experimental Genetics;experimental study;Family;fly;Functional disorder;Future;Genes;Genetic Diseases;Glucose;Glucosyltransferase;glycosylation;glycosyltransferase;Growth;Homing;Human;human disease;Immunodeficient Mouse;Impairment;In Vitro;in vivo engraftment;induced pluripotent stem cell;Injury;insight;Knock-in;Knockout Mice;Limb-Girdle Muscular Dystrophies;Link;Maintenance;Mammals;Mediating;Membrane;migration;Molecular;mouse genetics;Mus;Muscle;Muscle Cells;Muscle Development;muscle form;muscle progenitor cell;muscle repair;Muscle satellite cell;Muscular Dystrophies;mutant;Mutation;mutation correction;Myoblasts;myogenesis;Myopathy;notch protein;Notch Signaling Pathway;NOTCH3 gene;novel;novel therapeutic intervention;Pathology;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phenotype;Physiology;Play;Polysaccharides;Post-Translational Protein Processing;postnatal;Process;progenitor;Proliferating;protein function;Protein Glycosylation;Protein Secretion;Proteins;Proteomics;receptor;Regulation;Reporting;response;Role;self-renewal;Siblings;Signal Transduction;Site;skeletal;Skeletal Muscle;Specific qualifier value;stem cells;Structure;Techniques;Testing;Therapeutic;therapeutic target;Transgenes

PROJECT_TITLE: REGULATION OF SKELETAL MUSCLE DEVELOPMENT AND MAINTENANCE BY PROTEIN O-GLUCOSYLTRANSFERASE 1 (POGLUT1)

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


NIH_SPENDING_CATS: Aging;Cardiovascular;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention;Rural Health

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative In this proposal, our interdisciplinary team proposes to use novel approaches and innovative combinations of data to galvanize the use of EHR networks and population based cohorts to advance EHR-based risk predictions for 1) population level inference; 2) making individualized predictions of absolute risk, and 3) improving reproducibility and cross-site validation. We will predict risk of subsequent incident cardiovascular disease (CVD) in older patients (age 50 and older) with type 2 diabetes (T2DM).

PI_NAMEs: ZHONG, HUA JUDY (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Address;Age;Aging;Algorithms;Biological Markers;Cardiovascular Diagnostic Techniques;Cardiovascular Diseases;cardiovascular disorder risk;Caring;Chronic Disease;Clinical;Clinical Data;Clinical Management;Clinical Medicine;Clinical Research;cohort;Complement;Data;Data Analyses;data modeling;Data Set;data standards;data warehouse;demographics;Diabetes Mellitus;Diagnosis;Disease;Disease Outcome;Drug Prescriptions;electronic health data;Electronic Health Record;experience;Health;health care service utilization;Healthcare;Healthcare Systems;improved;Individual;innovation;Institution;Interview;Link;Medical;Medicare;Methodology;Methods;Michigan;Modeling;Nature;Network-based;New York;New York City;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Ohio;older patient;Outcome;patient population;Patients;personalized predictions;personalized risk prediction;Pharmaceutical Preparations;Phenotype;phenotyping algorithm;Physical assessment;Population;population based;Population Characteristics;population health;Population Surveillance;Procedures;Public Health;Records;Reproducibility;Research;restraint;Retirement;Risk;Risk Estimate;Risk Factors;risk prediction;rural patients;Rural Population;Sampling;secondary analysis;Services;Site;Span 20;Statistical Methods;Surveys;System;Time;United States Department of Veterans Affairs;Universities;Validation;Veterans;Visit;web app

PROJECT_TITLE: EHR-based vs population-based CVD risk predictions for older patients with diabetes

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE There is an urgent unmet need to discover new therapies for patients with residual cardiovascular risk due to inflammation despite conventional cholesterol-lowering treatments. The goal of the proposed research is to uncover novel mechanisms by which we can promote the resolution of inflammation and regression of atherosclerotic plaque. Therefore, this work is highly relevant to the mission of both the NIH and the NHLBI as it will help us understand fundamental mechanisms of disease in order to improve human health.

PI_NAMEs: DORAN, AMANDA C (contact)

PROJECT_TERMS: Acetylation;Apoptotic;Area;Arterial Fatty Streak;Atherosclerosis;Biological Response Modifiers;Ca(2+)-Calmodulin Dependent Protein Kinase;Cardiac;Cardiovascular Diseases;cardiovascular risk factor;Cells;ChIP-seq;Cholesterol;Chronic;Clinical;Collagen;cytokine;Data;Development;Disease;Epigenetic Process;Event;Exposure to;Failure;Genes;genetic approach;Goals;HDAC3 gene;Health;high risk;Histones;Human;human disease;hypercholesterolemia;Immune;Immune response;Immunity;Immunologic Memory;Impairment;improved;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inhibitor;insight;Knock-out;Knockout Mice;Laboratories;Lesion;lipid mediator;LoxP-flanked allele;Lysine;Macrophage;Mediating;Mediator;Medical;Methods;Mission;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;mutant;Myelogenous;Myeloid Progenitor Cells;National Heart, Lung, and Blood Institute;Necrosis;novel;novel therapeutic intervention;novel therapeutics;overexpression;oxidized low density lipoprotein;Patients;Pattern;Peptides;Phagocytosis;Play;Process;Production;programs;Recurrence;repaired;Research;Research Personnel;Residual state;Resolution;response;Risk;Risk Factors;Role;Scheme;skill acquisition;Small Interfering RNA;Stimulus;Techniques;Testing;therapeutic target;Thick;Thrombospondin 1;tissue repair;Tissues;Training;transcriptome sequencing;United States National Institutes of Health;Viral;Work

PROJECT_TITLE: Critical Mediators of Inflammation Resolution and Immune Memory in Atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Brain Disorders;Neurosciences

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Project Narrative This project will provide fundamental insight into how diverse layer specific neurons and connections interact to drive decision-related dynamics in the dorsolateral prefrontal cortex and dorsal premotor cortex to control perceptual decision-making, a process that is frequently impaired in psychiatric and movement disorders. Our results will be invaluable for the future development of biophysically realistic computational models of decision- making that incorporate multiple brain areas, layers and cell types. These insights, when combined with precise techniques to perturb neurons and networks are essential for the development of circuit level therapeutics for psychiatric and movement disorders, and the next generation of brain machine interfaces used for recovery of function following brain injury.

PI_NAMEs: CHANDRASEKARAN, CHANDRAMOULI ;LUEBKE, JENNIFER I (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Action Potentials;Address;anatomical tracing;Anatomy;Animals;Area;Automobile Driving;Behavioral;biocytin;biophysical properties;Biophysics;Brain;Brain Injuries;brain machine interface;cell type;Cells;Clinical Research;clinically relevant;Computer Models;Cues;Data;Decision Making;density;Development;discrimination task;Dorsal;Electrodes;Electrophysiology (science);Etiology;executive function;experimental study;Feedback;Fiber;Frequencies;Future;Goals;Impairment;In Vitro;in vivo;insight;Lateral;Lead;Lesion;Life;Light;Membrane;Mental disorders;Methods;Modeling;Monkeys;Morphology;morphometry;Motor;Motor Cortex;Movement Disorders;multimodality;Nature;neural;neural patterning;Neurodegenerative Disorders;Neurons;neurophysiology;next generation;novel;Opsin;Optical Methods;Optics;patch clamp;Pathway interactions;Pattern;Physiological;Play;Prefrontal Cortex;Process;Property;Recovery;Recovery of Function;Research;Resolution;response;Role;Sensory;sensory input;sensory stimulus;Short-Term Memory;Signal Transduction;Site;Slice;Source;stroke patient;Structure;Synapses;Techniques;Testing;Therapeutic;Tracer;Training;Vision;Work

PROJECT_TITLE: Multimodal Characterization of Prefrontal and Premotor Circuits Underlying Perceptual Decision Making in Therhesus Monkey

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Neuroblastoma;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: Project Narrative This research project is relevant to public health because it will identify how the noncoding genome influences chromatin architecture and gene regulation to drive tumorigenesis. The proposed research is highly relevant to the NIH mission regarding the critical need to understand the etiology and mutational events driving malignancies and to develop rational evidence-based approaches to reduce the burden of neuroblastoma and other cancers.

PI_NAMEs: DISKIN, SHARON  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: 3-Dimensional;Affect;Architecture;ATAC-seq;Automobile Driving;Binding;Binding Sites;Biological;Biological Assay;cancer predisposition;causal variant;Cell Line;Cell model;cell type;Cells;Child;ChIP-seq;Chromatin;Chromatin Loop;Chromosomal translocation;Chromosome Mapping;Clinical;clinical biomarkers;clinical development;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Correlative Study;Coupled;Data;Diagnostic;Disease Progression;Distal;DNA;DNA Methylation;Enhancers;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Etiology;Event;evidence base;Evolution;Exhibits;experimental study;Gene Expression Regulation;Genes;genetic manipulation;Genetic Transcription;Genome;genome sequencing;genome wide association study;genome-wide analysis;Genomics;Germ Lines;Germ-Line Mutation;high risk;Histones;Human;improved outcome;in silico;insight;Invaded;Knowledge;Malignant Childhood Neoplasm;Malignant Neoplasms;Maps;Mediating;Mission;multiple omics;Mutagenesis;Mutation;MYC gene;MYCN gene;Nature;Neural Crest Cell;Neuroblastoma;neuroblastoma cell;Nucleic Acid Regulatory Sequences;Oncogenic;Outcome;precursor cell;programs;promoter;Proteins;Public Health;Recurrence;Recurrent disease;Relapse;Reporter;Reporting;Research;Research Project Grants;Resolution;Resources;RNA-Directed DNA Polymerase;Role;Shapes;Somatic Mutation;Structural Protein;Susceptibility Gene;Sympathetic Nervous System;Telomerase;Testing;transcription factor;Transcriptional Activation;transcriptome sequencing;tumor;tumor initiation;tumorigenesis;ultra high resolution;United States National Institutes of Health;Untranslated RNA;Variant;whole genome;Work

PROJECT_TITLE: Elucidating the role of the noncoding genome in neuroblastoma

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The Reducing Health Disparities Through Informatics (RHeaDI) research training program will prepare nurse scientists with knowledge and skills to conduct interdisciplinary informatics and data science research to advance health equity. This competitive renewal will focus on (a) dismantling structures that perpetuate racism and impede health equity; (b) developing and implementing interventions that address social determinants across the lifespan; and (c) developing and advancing innovative holistic and precision health across the lifespan.

PI_NAMEs: BAKKEN, SUZANNE ;SCHNALL, REBECCA  (contact)

PROGRAM_OFFICER_NAME: KEHL, KAREN

PROJECT_TERMS: Informatics;Reduce health disparities