NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: NARRATIVE  This project proposes long-term follow-up of cognitively normal older individuals, with evidence of brain amyloid plaque build-up, who are participating in a clinical trial to determine if anti-amyloid treatment can slow cognitive decline in the very earliest stages of AD.

PI_NAMEs: AISEN, PAUL S.;SPERLING, REISA A. (contact)

PROGRAM_OFFICER_NAME: RYAN, LAURIE M

PROJECT_TERMS: abeta accumulation;Acceleration;active method;Address;Age;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-Protein;Applications Grants;asymptomatic Alzheimer's disease;Atrophic;Attenuated;Australia;Biological Sciences;blind;Blinded;Brain;Canada;Classification;Clinical;Clinical Trials;Cognition;Cognitive;cognitive function;cohort;Companions;comparison group;Data;data sharing;Dedications;Dementia;design;Detection;Disease;Dose;Double-Blind Method;Education;efficacy evaluation;Eligibility Determination;eligible participant;Enrollment;Evaluation;Foundations;functional decline;Functional disorder;functional outcomes;Funding;Gender;Goals;high risk;imaging biomarker;Immunotherapy;Impaired cognition;inclusion criteria;indexing;Individual;Intervention;Japan;Learning;Long-Term Effects;Longterm Follow-up;Magnetic Resonance Imaging;Medicine;meetings;Minority;Modification;Monoclonal Antibodies;monomer;Nerve Degeneration;Observational Study;Older Population;open label;Participant;Performance;Pharmaceutical Preparations;Pharmacodynamics;Phase;placebo controlled trial;Placebos;Population;Positioning Attribute;Positron-Emission Tomography;pre-clinical;prevent;Prevention therapy;Prevention trial;primary outcome;Prior Therapy;Privatization;Process;Protocols documentation;public-private partnership;Randomized;Reporting;response;Risk;screening;Secondary Prevention;Senile Plaques;Site;tau Proteins;Testing;treatment effect;United States;United States National Institutes of Health

PROJECT_TITLE: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: WORCESTER

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PEDIATRICS

ORG_FIPS: US

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE Mutations in the cellular protein sorting regulator VPS45 cause a very severe form of congenital neutropenia characterized by low numbers and abnormal function of neutrophils, the form of white blood cells responsible for defense against bacterial infections. Normal function of neutrophils requires formation, mobilization and fusion of cellular granules; when dysregulated, these defects lead to an “intracellular traffic jam” in VPS45 deficiency and other white blood cell granule disorders. Our in vivo and in vitro studies in transgenic mice, yeast, isolated cells, and will lead to elucidation of the molecular basis of severe neutropenia in children with VPS45 mutations.

PI_NAMEs: MUNSON, MARY ;NEWBURGER, PETER E (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Affect;Age;Agranulocytosis;Alpha Granule;Apoptosis;Architecture;Bacterial Infections;Binding;Biochemical;Biochemistry;Biogenesis;Biological;Biological Assay;Biology;Blood Platelets;Bone Marrow;Cell Separation;Cells;Cellular biology;Child;Classification;Collaborations;Complex;Congenital Abnormality;consanguineous family;Cytoplasmic Granules;Defect;Development;Disease;Embryo;Endosomes;Exocytosis;experimental study;Fibroblasts;Functional disorder;Genes;Genetic;genetic regulatory protein;granule cell;Granulocyte Colony-Stimulating Factor;Hematopoietic;Host Defense;Human;human disease;In Vitro;in vivo;Infection;insight;Investigation;kindred;Lead;Leukocytes;Life;Mammalian Cell;Measures;Mediating;Membrane;Membrane Fusion;Missense Mutation;Molecular;mouse model;Mus;mutant;Mutation;Myelofibrosis;Neutropenia;neutrophil;novel;Organ;Organelles;Pathogenicity;Pathology;Pathway interactions;Patients;Phagocytes;Phenotype;Physiological;Protein Family;Protein Sortings;protein transport;Proteins;Recombinants;recruit;Recurrence;Regulation;Resistance to infection;Secondary to;Severe congenital neutropenia;SNAP receptor;Sorting;Stem cell transplant;success;Syndrome;syntaxin binding protein 1;System;Testing;trafficking;Transgenic Mice;translational therapeutics;Vesicle;vesicle transport;Visual;Whole Organism;Yeasts

PROJECT_TITLE: Pathobiology of VPS45 severe congenital neutropenia

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Prevention

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Obesity and its adverse cardiovascular consequences represent major public health problems. Data from experimental models and human studies suggest that a class of medications known as phosphodiesterase type 5 inhibitors may increase the metabolic rate of adipose tissue and improve metabolic health. Thus, we propose a clinical trial to examine the effects of a once-daily phosphodiesterase type 5 inhibitor in obese adults.

PI_NAMEs: BRITTAIN, EVAN L (contact);DAMON, BRUCE M.

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Abdomen;Adipocytes;adipose imaging;Adipose tissue;adult obesity;Anatomy;aspirate;Biogenesis;Biology;Body Composition;Body measure procedure;Body Weight decreased;Brown Fat;cardiovascular risk factor;Cardiovascular system;Cells;Chronic;Clinical Trials;Data;diabetes risk;doubly-labeled water;energy balance;Energy consumption;Energy Metabolism;Enzyme Inhibition;Evaluation;Exhibits;Experimental Models;experimental study;Exposure to;Fatty acid glycerol esters;Fatty Acids;Future;Gene Expression;Genes;Genetic Transcription;guanylate;Health;Human;imaging biomarker;Imaging Techniques;improved;inhibitor;insulin sensitivity;Intervention;lifestyle intervention;Link;lipid metabolism;Lipids;Magnetic Resonance Imaging;Measures;Metabolic;metabolic rate;Metabolism;Methods;Mitochondria;molecular marker;Mus;Natriuretic Peptides;non-invasive imaging;obese person;Obesity;Participant;Perfusion;Periodicity;Pharmaceutical Preparations;pharmacologic;Phenotype;phosphoric diester hydrolase;Physical activity;Physiological;Placebos;primary endpoint;Protocols documentation;Public Health;Publishing;Randomized;Research Personnel;Resistance;response;Rest;Sampling;Second Messenger Systems;secondary endpoint;Signal Transduction;Spectrum Analysis;Stimulus;subcutaneous;tadalafil;Techniques;Technology;Temperature;Thermogenesis;Thermometry;Time;Tissue Sample;Tissues;Transgenic Mice;Weight Gain;Wild Type Mouse

PROJECT_TITLE: Effect of PDE5 Inhibition on Adipose Metabolism in Humans

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Food allergy is a serious and rapidly growing public health concern. The lack of a thorough understanding of disease mechanisms has adversely affected the development of highly effective therapies. Our proposed studies aim to identify the mechanisms that give rise to food-allergic, changes in the gut bacteria early in life, how these changes affect the immune system to promote food allergy, and how can therapy with bacteria and their products restore immune tolerance to food and prevent food allergy. Our studies offer the possibility of better diagnosis and prediction of disease outcome in food allergy as well as potential intervention strategies in disease therapy.

PI_NAMEs: CHATILA, TALAL AMINE (contact);RAKOFF-NAHOUM, SETH

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Affect;Agonist;Anti-Bacterial Agents;Antibody Response;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Automobile Driving;Bacteria;Bacterial Antibodies;bile acid metabolism;Bile Acids;Cell Differentiation process;Cells;Child;combinatorial;commensal bacteria;Development;Diagnosis;Diet;Dietary Supplementation;Disease;Disease Outcome;dysbiosis;effective therapy;Environmental Risk Factor;Epidemic;Epithelial Cells;Exhibits;Failure;Food;food allergen;food antigen;Food Hypersensitivity;gut bacteria;gut dysbiosis;gut microbiome;gut microbiota;Human Milk;human subject;IgE;Immune;Immune system;Immune Tolerance;Immunoglobulin A;Immunologics;immunoregulation;Individual;Infant;insight;Intervention;Licensing;Life;Life Style;Lipid A;Long-Term Effects;Mediating;Metabolism;microbial;microbiota;Modernization;Molecular;Mucous Membrane;Mus;novel;Oral;oral tolerance;Pathogenesis;Pathogenicity;Pathway interactions;Play;Population;Prevalence;prevent;Process;Production;Public Health;Reaction;Regulation;Regulatory T-Lymphocyte;resistin;response;Role;Solid;Supplementation;Th2 Cells;Therapeutic Intervention;TLR4 gene;Toll-like receptors;Tryptophan;Weaning

PROJECT_TITLE: Targeting microbial dysbiosis in Food Allergy to restore tolerance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


ADMINISTERING_IC: DE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

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

ORG_CITY: PORTLAND

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Every year, millions of people in the U.S. need some sort of endodontic treatment due to dental pulp infection and necrosis. Regenerative strategies in infected teeth are unpredictable mostly because bacterial lipopolysaccharide (LPS) remain in the dentin and activate the immune system, hindering dental pulp regeneration. In this proposal, we aim to engineer a hydrogel that can neutralize LPS and control the function of a critical cell of the immune system, the macrophage, to modulate the scaffold's integration with the host tissue, promoting dental pulp tissue formation, and benefiting millions of patients.

PI_NAMEs: MIRANDA FRANCA, CRISTIANE  (contact)

PROGRAM_OFFICER_NAME: THIRUMANGALATHU, SHOBA

PROJECT_TERMS: 3D Print;Acute;Adopted;Adsorption;Affect;Anti-Inflammatory Agents;Antibiotics;Antibodies;Antigen-Antibody Complex;antimicrobial;Bacteria;Binding;Biocompatible Materials;Biomimetics;Blood;Cell Survival;Cells;chemokine;Clinical;craniofacial;cytokine;Data;Dental;Dental Pulp;Dentin;Dentists;Deposition;Development;Disinfection;Endodontics;Engineering;Environment;Event;Extracellular Matrix;Flow Cytometry;Foreign-Body Reaction;Fostering;Gelatin;Genetic Transcription;Goals;Growth Factor;Hydrogels;Immune;Immune response;Immune system;Immune Targeting;Immunohistochemistry;immunoregulation;implantation;in vivo;individual variation;Infection;Infiltration;Inflammation;Inflammatory;injured;Knowledge;Lipopolysaccharides;Lymphocyte;Macrophage;Macrophage Activation;mechanotransduction;Mediating;Mediator;Mentored Research Scientist Development Award;Modeling;monocyte;Mouth Diseases;Mus;nanobodies;Natural regeneration;Necrosis;neutrophil;NF-kappa B;novel;novel strategies;Outcome;pathogen;Patients;Penetration;Persons;Phagocytosis;Phase;Phenotype;polarized cell;Predisposition;Process;programs;Property;Pulp Canals;recruit;regenerative;regenerative approach;regenerative treatment;repaired;Research;response;scaffold;Scientist;Signal Transduction;Site;Spleen;stem cell proliferation;Stimulus;subcutaneous;success;Th2 Cells;Therapeutic;Time;Tissue Engineering;Tissue Microarray;tissue regeneration;tissue stem cells;tissue support frame;Tissues;tool;Tooth structure;Training Programs;Vascularization

PROJECT_TITLE: Engineering Immunomodulatory Scaffolds for Dental Pulp Regeneration

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR(01)]


ADMINISTERING_IC: HD

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

ORG_CITY: DURHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE The research proposed will provide an understanding of the physical mechanisms and the molecular pathways involved in the patterning and morphogenesis of the semicircular canals, required for sensing balance and acceleration, using zebrafish as a model system. The fundamental, molecular-mechanical principles revealed from this study will be widely applicable to other morphogenetic events involving topological remodeling of simple epithelia. Moreover, since semicircular canals can develop abnormally in association with several congenital syndromes, my research will improve our understanding of these diseases and other inner ear associated disorders.

PI_NAMEs: MUNJAL, AKANKSHI  (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Ablation;Acceleration;Alagille Syndrome;Atlases;automated image analysis;Award;Biological Models;biophysical model;biophysical properties;biophysical tools;Biophysics;Biosensor;candidate validation;career;career development;Cells;Cellular biology;CHARGE syndrome;Collaborations;Complex;Congenital Abnormality;CRISPR/Cas technology;Data Set;Deposition;Development;Developmental Biology;Disease;Ear Diseases;Embryo;Epithelium;Equilibrium;Etiology;Event;experience;Extracellular Matrix;Feedback;Fingers;fundamental research;gene synthesis;Generations;Genes;Genetic;Genetic Transcription;Glycosaminoglycans;Goals;Grant;Growth;HAS3 gene;Head;Heparan Sulfate Proteoglycan;Heparitin Sulfate;high resolution imaging;Hyaluronan;Hydrogels;Image;Image Analysis;improved;in vivo;inner ear diseases;insight;Interdisciplinary Study;Jaw;Laboratories;Labyrinth;Lasers;Liquid substance;Literature;Maps;mechanical force;mechanical properties;Mechanics;Mediating;meetings;Mentors;Mentorship;Microfluidics;Modeling;Molecular;molecular mechanics;Morphogenesis;morphogens;mutant;novel;Organ;Otic Vesicle;particle;Pathway interactions;Pattern;Phase;Physics;Polymers;Postdoctoral Fellow;pressure;Process;Production;programs;Property;Proteoglycan;Publications;Publishing;quantitative imaging;Quantitative Microscopy;Regenerative Medicine;Regulation;Reporter Genes;Research;Resolution;response;Role;Semicircular canal structure;Sequence Analysis;Shapes;Signal Transduction;Simple Epithelium;single cell sequencing;single-cell RNA sequencing;skill acquisition;Specific qualifier value;student mentoring;Swelling;Syndrome;Technology;Testing;Theoretical model;Tissues;tool;Training;transcription factor;transcriptome;Transgenic Organisms;Translational Research;Velocimetries;versican;Vertebrates;Viscosity;Water;Work;Writing;Xenopus;Zebrafish;zebrafish development

PROJECT_TITLE: Identifying the role of dynamic ECM-derived forces in zebrafish semicircular canal morphogenesis

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Pediatric;Prevention;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: SEMIPARAMETRIC METHODS FOR MODELING OF TIME-DEPENDENT ENVIRONMENTAL EXPOSURES Narrative We seek to develop and implement a family of innovative statistical models to assess the effects of time- dependent environmental exposures, pinpoint critical windows of vulnerability, and identify susceptible subpopulations. We will apply these methods to ongoing collaborations to address critical scientific questions in environmental health research and to improve our understanding of how environmental exposures affect health. The statistical tools developed from this project will be disseminated to the general research community and will expand the analytic toolkits for environmental health research.

PI_NAMEs: LIU, MENGLING  (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Address;Adolescence;Affect;analytical tool;Arsenic;Bangladesh;Blood Pressure;Characteristics;Chemical Exposure;Child;Child Health;Chronic Kidney Failure;cohort;Collaborations;Communities;Complex;Computer software;data structure;Development;Disease;Environment;Environmental Exposure;Environmental Health;Environmental Impact;Event;Exhibits;experience;Exposure to;Family;fire fighter;flexibility;Goals;hazard;Health;Human;Human Development;human subject;Impairment;improved;indexing;Individual;innovation;interest;Intervention;Investigation;Life Cycle Stages;Linear Regressions;Longitudinal Studies;Metabolic syndrome;Methodology;Methods;Modeling;multiple datasets;Names;National Institute of Environmental Health Sciences;non-genetic;novel;open source;Outcome;Pattern;Predisposition;Procedures;Process;Proportional Hazards Models;Reduce health disparities;Research;response;semiparametric;simulation;Slice;Social Environment;Statistical Methods;Statistical Models;Structure;Study Subject;Subgroup;synergism;Testing;Time;tool;Vacuum;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(91)]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Substance Misuse

ORG_CITY: Boulder

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative PUBLIC HEALTH RELEVANCE: Drug addiction is characterized by motivated behaviors involving the pursuit of rewards and the avoidance of negative stimuli. While it is known that the ventral tegmental area (VTA) controls such motivated behaviors, the specific cell-types and circuits that govern these behaviors are unclear. This research program will determine the involvement of several different types of VTA neurons and circuits in motivated behaviors, which may provide new cellularly targeted addiction intervention strategies.

PI_NAMEs: ROOT, DAVID H (contact)

PROGRAM_OFFICER_NAME: POLLOCK, JONATHAN D

PROJECT_TERMS: addiction;Aversive Stimulus;Behavior;Behavioral;Biological Assay;Brain Mapping;Calcium;calcium indicator;cell type;cellular targeting;conditioned place preference;Cues;Data;design;Disease;Dissection;Dopamine;Drug Addiction;drug reward;Genetic;Glutamates;Habenula;Image;Individual;innovation;Intervention;Lateral;Learning;Literature;Mediating;Modeling;motivated behavior;Motivation;Neuromodulator;Neurons;Neurotransmitters;novel;Nucleus Accumbens;optogenetics;Output;Pathway interactions;Pattern;Phenotype;Population;programs;public health relevance;Rabies virus;Research;response;Rewards;Role;Self Stimulation;sensor;Specificity;Stimulus;Techniques;Testing;Time;tool;Transgenic Organisms;Tyrosine 3-Monooxygenase;Ventral Tegmental Area;vesicular glutamate transporter 2;Viral;Viral Vector

PROJECT_TITLE: Genetic dissection of ventral tegmental area glutamate and GABA neurons in reward and aversion

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


NIH_SPENDING_CATS: Digestive Diseases;Hepatitis;Hepatitis - C;Infectious Diseases;Liver Disease

ORG_CITY: GALVESTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: Despite the availability of effective antivirals, ~71 million people are still infected with chronic hepatitis C virus (HCV) that causes 399,000 liver disease-related deaths per year. This project aims to reveal, at last, the molecular mechanism of action of the key antiviral component of successful HCV therapy, which targets HCV NS5A. This project could have a broad impact on rational drug design for NS5A-like viral (or cellular) targets that induce membrane remodeling.

PI_NAMEs: YI, MINKYUNG  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Address;Anti-viral Agents;Biological Models;Cells;Cessation of life;Cholesterol;Chronic Hepatitis C;Data;Development;dimer;Drug Design;Environment;fitness;functional mimics;Goals;Hepatitis C virus;Human;imaging system;In Vitro;in vitro Model;inhibitor;innovation;Knowledge;Liver Cirrhosis;Liver diseases;Mechanics;Mediating;Membrane;Molecular;Molecular Conformation;Molecular Mechanisms of Action;N-terminal;nanomolar;novel;Outcome;Persons;Play;polyproline;prevent;Primary carcinoma of the liver cells;Research;Resistance;RNA replication;RNA Viruses;Role;Testing;Vesicle;Viral;viral RNA;Virion;Virus;Virus Replication

PROJECT_TITLE: Mechanistic function of HCV NS5A targeted by the potent inhibitors

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Cardiovascular;Emergency Care;Heart Disease;Neurosciences;Organ Transplantation;Transplantation

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: There are over 350,000 victims of out-of-hospital cardiac arrest each year in the United States, and the success rates from cardiopulmonary resuscitation (CPR) average only about 10%. In addition, organ shortage is the greatest challenge facing organ transplantation, with far fewer donors than needed, and many patients dying awaiting transplant. We are studying the molecular determinants and blood flow requirements for survival from cardiac arrest, and ways of improving resuscitation to increase the number of survivors from cardiac arrest while also increasing the number of organ donors for transplants, the latter who have failed resuscitative efforts.

PI_NAMEs: HALPERIN, HENRY R (contact)

PROGRAM_OFFICER_NAME: SOPKO, GEORGE

PROJECT_TERMS: Biological Markers;Blood flow;Blood Vessels;Brain;Brain Death;Brain Injuries;Cannulas;Cardiopulmonary Resuscitation;Cerebrovascular Circulation;Cerebrum;Childhood;Circulation;Data;Diameter;Donor person;Emergency Situation;Evolution;Extracorporeal Membrane Oxygenation;Goals;Heart Arrest;hemodynamics;improved;Inflammatory;inflammatory marker;Intervention;Magnetic Resonance;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Measurement;Measures;Metabolic;metabolic rate;Metabolism;metabolomics;Molecular;Morbidity - disease rate;natural hypothermia;Neurologic;Organ;Organ Donor;Organ Preservation;Organ Transplantation;out-of-hospital cardiac arrest;outcome prediction;Oxygen;patient population;Patients;Pediatrics;Physicians;Postoperative Period;preservation;programs;Reactive Oxygen Species;Resources;Resuscitation;success;Surgeon;survival prediction;Survival Rate;Survivors;System;Technology;Testing;Time;Training;Transplantation;underserved area;United States

PROJECT_TITLE: The Hemodynamic and Metabolic Effects of Advanced Circulatory Support for Resuscitation

STUDY_SECTION: CICS

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


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: SALT LAKE CITY

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE We are developing software to support team-based, long-term genomic analysis in challenging settings such as undiagnosed disease clinics and rapid genome sequencing programs to rapidly diagnose critically ill newborns in neonatal intensive care units. We will test the utility of our software for assisting diagnostic analysis in a team- based setting within individual clinics and for facilitating research consortium-level collaborative diagnostics within NHGRI’s Undiagnosed Diseases Network.

PI_NAMEs: MARTH, GABOR T (contact);TRISTANI-FIROUZI, MARTIN

PROGRAM_OFFICER_NAME: RIDER, RENEE ANNE

PROJECT_TERMS: Address;adjudication;Adopted;Bioinformatics;Caring;Clinic;Clinical;clinical research site;clinically relevant;clinically significant;cloud based;cohort;Collaborations;Communication;Communities;Complex;computational pipelines;computer infrastructure;Computer software;critically ill newborn;dashboard;Data;data access;data infrastructure;Data Set;design;Diagnosis;Diagnostic;diagnostic strategy;Discipline;Disease;Ensure;Environment;Evaluation;Funding;Genes;Genetic;genetic counselor;Genetic Diseases;genetic disorder diagnosis;Genome;genome sequencing;genomic data;Genomics;Genotype;Goals;Hand;implementation science;improved;Individual;Infrastructure;insight;Intuition;Joints;Knowledge;Literature;longitudinal analysis;Medical;Medicine;member;Modernization;Molecular;molecular diagnostics;National Human Genome Research Institute;Neonatal Intensive Care Units;novel;Pathogenicity;Pathologist;Patients;Periodicals;Phenotype;phenotypic data;Physicians;Process;programs;rapid diagnosis;Reporting;Research;Resources;response;Secure;Site;software development;software systems;Software Tools;Support System;support tools;System;Testing;Time;tool;United States National Institutes of Health;Universities;Update;Utah;Variant;Visual;web based software;web-based tool;whole genome

PROJECT_TITLE: Calypso: a web software system supporting team-based, longitudinal genomic diagnostic care


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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;Biomedical Imaging;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Rehabilitation;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE This project will determine the disease altering properties of high intensity exercise by randomizing 150 cognitively intact, sedentary elders (ages 65-80 years) at genetic risk for Alzheimer's disease into two groups: one engaged in a high-intensity home-based cycling program and the other engaged in their habitual level of physical activity. Both groups will be monitored over an 18-month period with cognitive testing and MRI brain scans serving as primary outcomes to determine the disease altering characteristics of aerobic exercise. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing disease course will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.

PI_NAMEs: ALBERTS, JAY L.;RAO, STEPHEN MARK (contact)

PROGRAM_OFFICER_NAME: MCLINDEN, KRISTINA

PROJECT_TERMS: Accelerometer;Aerobic Exercise;Age;Alleles;Alzheimer's Disease;Alzheimer's disease risk;Amyloid;Anti-Inflammatory Agents;apolipoprotein E-4;Auditory;Biological Markers;Biomechanics;Blinded;Brain;Brain imaging;brain magnetic resonance imaging;Brain scan;brain volume;cardiorespiratory fitness;Caring;Cerebrum;Characteristics;Clinical;clinically significant;Cognition;Cognitive;cognitive function;cognitive testing;Dementia;Deterioration;Diagnosis;Disease;Disease Progression;Effectiveness;efficacy evaluation;Elderly;Episodic memory;executive function;Exercise;exercise intensity;exercise intervention;exercise regimen;Exhibits;experience;fitness;fitness test;follow-up;Functional Magnetic Resonance Imaging;Gait;Genetic Risk;genetic risk factor;Goals;group intervention;Health;Health Care Costs;Heart Rate;Hippocampus;Home;Homeostasis;Image;Impaired cognition;improved;Individual;Inflammatory;Interval training;Intervention;Late Onset Alzheimer Disease;lifestyle factors;Link;Lipids;Literature;Longitudinal, observational study;Magnetic Resonance Imaging;Measures;Memory;Moderate Exercise;Monitor;neuroinflammation;Neurons;neuroprotection;Neuropsychological Tests;Older Population;Onset of illness;Other Genetics;Outcome;Outcome Measure;Participant;patient engagement;Patient Self-Report;Patient-Focused Outcomes;Performance;Perfusion;Phenotype;Physical activity;Physical Exercise;Physical Fitness;Physical Function;Plasma;Posture;primary outcome;processing speed;programs;Property;Quality of life;Radial;Randomized;Randomized, Controlled Trials;recruit;Role;sedentary;Series;System;Testing;Time;Translations;Vascular Dementia;Verbal Learning;VO2max;white matter;World Health Organization

PROJECT_TITLE: CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimers Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative  Regular exercise is highly effective for preventing and counteracting cardiovascular disease, and appears to work in part by affecting the cells of the heart itself. This proposed research program aims to identify the heart cells affected by exercise, determine the key interactions among those cells and characterize the underlying mechanisms. In addition to advancing our understanding of the effects of exercise, this work will suggest new therapeutic targets for heart disease, a rapidly growing public health threat.

PI_NAMEs: ROSENZWEIG, ANTHONY  (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Adult;Affect;Animal Model;Award;Bioinformatics;Biological;Biological Assay;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cell Culture Techniques;Cell Lineage;cell type;Cells;Chromatin;Clinical;Environment;Exercise;Fibrosis;flexibility;gain of function;Gene Expression;Generations;Heart;heart cell;Heart Diseases;Heart failure;Heart Hypertrophy;Hypertrophy;In Vitro;in vivo;Inflammation;insight;Label;loss of function;Mediating;meetings;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;National Heart, Lung, and Blood Institute;Nature;new therapeutic target;novel therapeutic intervention;Pathologic;Pathway interactions;Patients;permissiveness;porcine model;pre-clinical;Pre-Clinical Model;prevent;Process;Prognosis;programs;Proliferating;Public Health;Research;Research Personnel;response;Science;single nucleus RNA-sequencing;Stress;Testing;Therapeutic;Time;tool;transcriptome sequencing;translational potential;Transposase;Treatment Failure;Work;Zebrafish

PROJECT_TITLE: Understanding the Cardiac Benefits of Exercise at the Cellular and Molecular Level


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Diabetes;Digestive Diseases;Hepatitis;Liver Disease;Obesity

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: We have developed new drugs that we believe will be useful for treating insulin resistance and nonalcoholic steatohepatitis (NASH), which is a common disease in the U.S. caused by having too much fat in the liver. The goal of this project is to test this idea in mice and to determine the mechanisms by how these drugs work. Successful completion of these studies could pave the way to clinical development of a pharmaceutical therapy for treatment of NASH.

PI_NAMEs: FINCK, BRIAN N (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Affect;Attenuated;attenuation;Automobile Driving;Awareness;Branched-Chain Amino Acids;Carbohydrates;Cardiometabolic Disease;Cellular Metabolic Process;Chronic;Chronic Disease;Cirrhosis;Clinical;clinical development;Clinical Trials;Cytosol;Data;Development;Diabetes Mellitus;Disease;drug efficacy;Drug Targeting;Drug usage;efficacy testing;Fatty acid glycerol esters;Fatty Liver;Fibrosis;Future;Genetic;genetic inhibitor;Genetic Models;Goals;Grant;Hepatic;Hepatic Stellate Cell;Hepatocyte;improved;inhibitor;Insulin;Insulin Resistance;insulin sensitivity;insulin sensitizing drugs;Lesion;Ligands;Link;Lipids;Liver;Liver Failure;Liver Fibrosis;liver inflammation;Liver parenchyma;Mediating;Medical;Metabolic;Metabolic Diseases;Metabolism;Mitochondria;Molecular;Molecular Mechanisms of Action;mouse model;Mus;next generation;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;novel therapeutics;Nuclear Receptors;Obesity;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Play;PPAR gamma;Primary carcinoma of the liver cells;Progressive Disease;Public Health;pyruvate carrier;Pyruvate Metabolism Pathway;Resistance;response;Risk;stellate cell;Stimulus;Testing;Therapeutic;therapeutic development;Thiazolidinediones;Work;zaprinast

PROJECT_TITLE: Targeting the mitochondrial pyruvate carrier to treat insulin resistance and nonalcoholic fatty liver disease


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

ORG_DEPT: OPHTHALMOLOGY

PHR: NARRATIVE: Refractive error such as high hyperopia (severe farsightedness) can cause irreversible vision loss secondary to structural and functional alterations in the eye. By understanding the genetic and molecular mechanisms of small eyes and hyperopia, we will improve public health by identifying biological targets for therapeutic design. These studies may also prove useful for limiting ocular growth in the other end of the pathologic spectrum, myopia.

PI_NAMEs: PRASOV, LEV  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Affect;Alleles;Amblyopia;analysis pipeline;Angle-Closure Glaucoma;Animal Model;Area;autosome;Basic Science;Binding;Bioinformatics;Biological;Biological Assay;Biology;Blindness;Candidate Disease Gene;candidate identification;Cardiac;career development;Cell Culture Techniques;Cell Death;Child;Cleavage Under Targets and Release Using Nuclease;clinical heterogeneity;clinical practice;Code;cohort;Collaborations;conditional knockout;Data;de novo mutation;Defect;design;Development;Developmental Biology;developmental genetics;Disease;disease mechanisms study;disease phenotype;DNA;Environment;experience;Eye;Eye Development;Eye diseases;Family;Foundations;Functional disorder;Future;gene discovery;Gene Expression Profile;Gene Targeting;Genes;Genetic;Genetic Diseases;Genetic Heterogeneity;Genetic Transcription;genetic variant;Genitourinary system;genome sequencing;genomic locus;Genomics;Genotype;Goals;Growth;Heritability;Heterogeneity;Human;human disease;Hyperopia;Impairment;improved;in silico;In Vitro;Inheritance Patterns;Inherited;innovation;insight;Institution;Investigation;Knock-in Mouse;Knockout Mice;Knowledge;Laboratories;large datasets;Lead;Learning;Length;Link;Medical;Mentors;Microphthalmos;Modeling;Molecular;Molecular Diagnosis;Molecular Target;Morphology;mouse model;Mus;Myelin;Myopia;N-terminal;National Eye Institute;novel;novel therapeutics;Ophthalmology;Outcome;overexpression;Pathogenesis;Pathologic;Pathway interactions;Patient Care;Patients;Pattern;Phenotype;Physiological;Public Health;Reagent;recruit;Refractive Errors;Research;Research Personnel;Retina;Retinal Degeneration;Role;Sampling;Scientist;Secondary to;Serous;single-cell RNA sequencing;skills;Strabismus;Structure;Structure of retinal pigment epithelium;System;targeted treatment;Techniques;Testing;Tissues;Training;transcription factor;Transcriptional Activation;Transcriptional Regulation;Validation;Variant;Vision;Visual Fields;Visual impairment;whole genome;Work

PROJECT_TITLE: Defining the genetic landscape of nanophthalmos and the role of MYRF


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative There are conditions that overlap or even mimic Alzheimer’s disease, confounding clinical diagnosis, and thus representing a barrier to effective treatment. Here we propose a collaboration with two NIH Alzheimer’s Disease Research Centers to build advanced Artificial Intelligence tools that, combined with a 3D shape scanner, convert dissection photographs (routinely acquired by research centers) into 3D datasets. We will use these tools to unravel the connection between brain shape and microscopic diagnosis of AD mimics, and will also distribute them as part of our widespread software package FreeSurfer (over 40,000 worldwide licenses), so they can be freely used by research laboratories around the world.

PI_NAMEs: IGLESIAS GONZALEZ, JUAN EUGENIO (contact)

PROGRAM_OFFICER_NAME: HSIAO, JOHN

PROJECT_TERMS: 3-Dimensional;Alzheimer's Disease;Alzheimer's disease diagnosis;Amyloid;Amyloid beta-Protein;Anatomy;Artificial Intelligence;Atlases;Autopsy;Back;Bayesian learning;Biological Assay;Biological Markers;Blood Vessels;Brain;brain shape;cerebral atrophy;Cessation of life;Clinical;clinical care;clinical diagnosis;Clinical Trials;Collaborations;Computer software;cost;Data;Data Analyses;Data Set;Dementia;Dementia with Lewy Bodies;design;Development;Diagnosis;Diagnostic;diagnostic criteria;Disease;Dissection;DNA-Binding Proteins;economic impact;effective therapy;Elderly;Goals;heterogenous data;Hippocampus;Image;Image Analysis;image registration;improved;in vivo;in-vivo diagnostics;Individual;Laboratories;Laboratory Research;late life;Lesion;Licensing;Life;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;Massachusetts;Measurement;Measures;Methods;Microscopic;MRI Scans;multidisciplinary;Nerve Degeneration;neuroimaging;neuropathology;novel;object shape;open source;Pathology;Patients;Pattern;Photography;Positron-Emission Tomography;prevent;Prospective cohort;protein TDP-43;Qualifying;reconstruction;Research;Research Personnel;response;Sample Size;Scanning;Semantics;Shapes;Site;Slice;Structure;Surface;Techniques;Technology;Testing;therapeutically effective;Thick;Three-Dimensional Image;Time;tool;ultra high resolution;United States National Institutes of Health;Universities;Validation;Washington;white matter

PROJECT_TITLE: Diagnosing the undiagnosable: studies of Alzheimer disease mimics and confounders via "neuropathometry" of dissection photos with 3D scanning

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: Project Narrative Vast quantities of genomic data are now available to describe patterns of genetic variation and gene expression both within human populations and across species. These data need to be interpreted in light of the fundamental forces of mutation, recombination, natural selection, and genetic drift that have shaped our genomes over millions of years of evolution. This proposal describes a series of projects that make use of new computational methods to address fundamental questions in human evolutionary genomics, including how human diversity has been shaped by introgression from our archaic hominin cousins, how new mutations influence human health and fitness, and how the evolution of gene expression contributes to unique aspects of human biology and disease.

PI_NAMEs: SIEPEL, ADAM CHARLES (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Alleles;Area;Artificial Intelligence;biophysical model;Birds;Chiroptera;comparative genomics;Computing Methodologies;CRISPR screen;Data;deep neural network;Demography;Detection;Enhancers;epigenomics;Essential Genes;Event;Evolution;fitness;Funding;Gene Expression;Genes;Genetic Drift;Genetic Recombination;Genetic Variation;Genome;genomic data;Genomics;Goals;Graph;graph neural network;Health;Human;Human Biology;human disease;human genomics;Immunity;innovation;insight;intelligence genetics;lens;Light;Link;Malignant Neoplasms;Mammals;Measures;Methodology;Methods;Modernization;Molecular Evolution;Mutation;Natural Selections;novel;Paper;Pattern;Phenotype;Phylogeny;Polygenic Traits;Population;Population Genetics;Printing;Productivity;programs;promoter;Publishing;Radiation;reconstruction;Regulatory Element;Research;RNA;Sampling;Series;Shapes;Software Tools;South American;statistics;Techniques;Training;Transcriptional Regulation;transcriptome sequencing;Variant;Work

PROJECT_TITLE: Evolutionary Human Genomics: Demography, Natural Selection, and Transcriptional Regulation

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Lung;Mental Health;Neurosciences;Pediatric;Sleep Research

ORG_CITY: HOUSTON

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: NARRATIVE Pediatric Obstructive Sleep Apnea (OSA) is a common childhood disease that can have enduring neurologic sequelae. The proposed mentored training award allows the candidate to acquire the skills and research experience to develop as a physician-scientist. The proposal investigates the behavior, electrophysiology, and contributions of individual brain cells that contribute to changes in response to OSA in children.

PI_NAMEs: CHANDRAKANTAN, ARVIND  (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: Acute;Address;Affect;Age;Anatomy;Anesthesia procedures;Anesthesiology;Award;Behavior;Behavioral Model;behavioral phenotyping;Brain;brain cell;cell type;Chemosensitization;Child;Childhood;Chronic;Clinical;Clinical Research;clinically relevant;Cognitive;college;Coupled;critical period;Data;Decision Making;dentate gyrus;Development;Disease;Disease Progression;education planning;Electrophysiology (science);Emotional;Exhibits;experience;Exposure to;Functional disorder;fundamental research;Funding;Funding Applicant;Health;Hippocampus;Human;Hypoxia;Immunohistochemistry;Impaired cognition;improved;Incidence;Individual;Induced Neurons;Infant;Injury;Institution;Intervention;Knowledge;Learning;life-long learning;Long-Term Potentiation;Measurable;Medicine;Memory;memory encoding;Mentored Research Scientist Development Award;Mentors;Mentorship;Modeling;Molecular;mouse model;multidisciplinary;Mus;neonatal mice;neonate;neurobehavior;Neurobiology;Neurocognitive;neurogenesis;Neurologic;Neurologic Dysfunctions;Neurons;normoxia;novel;Obstructive Sleep Apnea;Onset of illness;Operative Surgical Procedures;Outcome;Oxygen saturation measurement;Pediatrics;Perioperative;Perioperative complication;Phenotype;Physicians;Physiological;Polysomnography;Positioning Attribute;postnatal;Postoperative Hemorrhage;Pre-Clinical Model;professor;Research;Research Training;Resources;respiratory;response;restoration;Risk;School-Age Population;Scientist;Site;skill acquisition;Slice;Stains;standard care;success;Surgeon;Synapses;synaptic function;Synaptic plasticity;Testing;Therapeutic;Time;Training;translational study;Work

PROJECT_TITLE: Contribution of Pediatric OSA in Memory and Learning

STUDY_SECTION: MCBS

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


ORG_CITY: Los Angeles

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Project Narrative  The application of chemical properties to alter the reactivity of reagents for the synthesis of biomedically important compounds provides an opportunity to enhance the biomedical sciences. The chemical properties of hydrogen-bond-donor organocatalysts will enable the general, selective synthesis of 2-deoxy-β-glycosides, which remains elusive despite the importance of carbohydrates in biological systems, biological chemistry and medicine. Additionally, the properties of sulfur and the C–S bond will provide novel photochromic materials, addressing the stagnant synthetic approach to Stenhouse adducts, which are used in drug delivery, dynamic phase transfer, polymers, liquid crystals, wavelength-selective photoswitching, and chemosensing applications.

PI_NAMEs: PICAZO, ELIAS  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Strategic Molecular Activations for the Selective Synthesis of 2-Deoxy-Beta-Glycosides, and for the Synthesis of Novel Donor-Acceptor Stenhouse Adducts


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Dissemination and Implementation Research;Infectious Diseases;Patient Safety

PHR: Narrative: Significant opportunities exist to improve antibiotic prescribing in dentistry. We need evidence-based tools to assist dentists with selecting antibiotics to optimize treatment of dental infections, to improve patient safety, and to combat antibiotic resistance. I propose to create and test a scalable web-based clinical decision support tool to improve antibiotic prescribing at the University of Illinois at Chicago College of Dentistry.

PI_NAMEs: DURKIN, MICHAEL JOSEPH (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Adherence;Adoption;Adverse drug event;Allergic Reaction;Antibiotic Resistance;Antibiotics;Cellular Phone;Chicago;Clinic;Clinical;clinical decision support;clinical implementation;Clostridium difficile;college;combat;Communities;Computer software;cost;Data;Decision Making;Dental;Dental Clinics;Dental General Practice;dental infection;Dental Records;Dental Schools;Dental Students;Dentistry;Dentists;design;Development;diarrheal disease;Dissemination and Implementation;Drug resistance;Effectiveness;effectiveness evaluation;electronic health record system;Electronics;Endodontics;Event;evidence base;Faculty;Federal Government;Feedback;Focus Groups;Funding;Future;Goals;Grant;Health Care Costs;Illinois;implementation evaluation;implementation framework;implementation science;improved;Infection;Informatics;innovation;Intervention;Intervention Studies;Knowledge;Life;Logic;Maintenance;Measures;Methods;Mouth Diseases;Multi-Drug Resistance;National Institute of Dental and Craniofacial Research;novel;Online Systems;Oral health;Organism;Outpatients;Paper;Patient Care;patient safety;Patients;pilot test;Policies;practice-based research network;primary outcome;programs;Provider;Public Health;Publications;Questionnaires;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Research;Resources;response;Risk;satisfaction;Science;secondary outcome;Series;Site;Societies;Strategic Planning;support tools;Surveys;System;Technology;technology validation;Testing;theories;therapy design;Time;tool;treatment optimization;United States;Universities;urgent care;volunteer;web app;web site;Writing

PROJECT_TITLE: Using Implementation Science and Informatics to Develop and Pilot Test Antibiotic Stewardship Clinical Decision Support

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Burden of Illness;Caregiving Research;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Dementia;Health Services;Neurodegenerative;Neurosciences;Palliative Care

ORG_CITY: DETROIT

ORG_DEPT: MISCELLANEOUS

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: PROJECT NARRATIVE This project will uncover short and longer-term effects of the COVID-19 pandemic on the use of long-term care (LTC) and adverse consequences related to gaps in care. By focusing on high-need older adults in the U.S. and comparing effects for those living with and without Alzheimer’s Disease and Related Dementias (ADRD), the project will provide guidance to public health officials on how to improve the stability and resiliency of LTC arrangements to meet older adult’s care needs in the context of an aging population.

PI_NAMEs: TRUSKINOVSKY, YULYA  (contact)

PROGRAM_OFFICER_NAME: DUAN, LEWEI

PROJECT_TERMS: Address;Adult;adverse outcome;Affect;Aging;aging population;Alzheimer's disease related dementia;Area;Assisted Living Facilities;Beds;care outcomes;Caregivers;Caring;Cessation of life;Communities;community-level factor;COVID-19;COVID-19 impact;COVID-19 pandemic;COVID-19 pandemic effects;Data;Death Rate;Dementia;dementia care;Emergency department visit;Environment;Family;Family Caregiver;Generations;geographic difference;Geography;Health;Health and Retirement Study;health care availability;health care service utilization;health data;Healthcare;high risk;Home;Home Nursing Care;Hospitalization;human old age (65+);Impaired cognition;improved;Infrastructure;late life;Link;long term COVID-19 pandemic impacts;Long-Term Care;Marketing;Measures;Medicare claim;mortality risk;neglect;Nursing Homes;older adult;pandemic disease;pandemic impact;pandemic potential;patient home care;Patient Self-Report;Persons;programs;Public Health;Reporting;Research;Residential Treatment;resilience;Risk;school closure;Self Care;Services;Signal Transduction;Soil;Source;Sterile coverings;Surveys;Techniques;Time;Training;trend;Variant;Virus;Work

PROJECT_TITLE: The Effects of the COVID-19 Pandemic on Long-Term Care for High-Need Older Adults with and without Alzheimer’s Disease and Related Dementias

STUDY_SECTION: SSPB

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Emergency Care;Neurosciences;Patient Safety;Rural Health

ORG_CITY: MINNEAPOLIS

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Research to advance the care of those seeking emergency care including the critically ill and injured is sorely needed. The Upper Midwest (previously University of Minnesota) SIREN hub will leverage its considerable practical experience in the conduct of emergency care clinical trials, including substantial experience in the conduct of Exception From Informed Consent (EFIC) trials, to ensure the recruitment, high quality conduct, and retention of diverse participants inclusive of rural patient populations into SIREN clinical trials. Our team is highly qualified to serve as a SIREN Hub, with strong local and national leadership, national engagement with network activities, the academic depth to develop and contribute to clinically relevant trial concepts, and exceptional experience in diverse domains of acute critical care, pre-hospital, and emergency care research.

PI_NAMEs: MINER, JAMES R. (contact);PUSKARICH, MICHAEL A.

PROGRAM_OFFICER_NAME: SCOTT, GRETCHEN CARLYLE

PROJECT_TERMS: Acceleration;Accident and Emergency department;Acute;acute care;acute coronary syndrome;Address;Admission activity;American Indians;Award;Caring;Clinical;clinical care;Clinical Investigator;Clinical Nursing Research;Clinical Research;Clinical Trials;Clinical Trials Network;clinically relevant;Collaborations;community consultation;community engagement;cost effective;COVID-19;COVID-19 pandemic;Critical Care;Critical Illness;Data;demographics;Disease;Emergency Care;Emergency medical service;Emergency research;Enrollment;Ensure;Ethics;experience;Faculty;Funding;Growth;Hand;healthcare burden;Heart Arrest;Hispanic;Hospitalization;Hospitals;Human Resources;Immigrant;Informed Consent;innovation;Institution;Intensive Care Units;investigator training;Lead;Leadership;Logistics;medical specialties;meetings;member;Methodology;Methods;Midwestern United States;Minnesota;multidisciplinary;Nature;Neurological emergencies;Neurology;next generation;operation;Outcome;Participant;participant enrollment;patient population;Patient Recruitments;Patients;Phase;Population;Positioning Attribute;Pre-hospitalization care;Prehospital Emergency Care;Procedures;promote resilience;prospective;Publications;Qualifying;recruit;Research;Research Methodology;Research Personnel;Resources;Respiratory distress;Rural;rural patients;Sepsis;severe injury;Site;Speed;Stroke;Structure;success;support network;Time;Training;Trauma;United States;Universities

PROJECT_TITLE: SIREN - Upper Midwest Hub


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research

PHR: NARRATIVE This study proposes to use neuroimaging and cognitive measures to examine Alzheimer's disease modifiable risk factors and biomarkers in non-demented older Latinos and non-Latino Whites. This effort will greatly improve our understanding of the relationship among AD-related brain changes, modifiable risk factors and cognitive decline in Latinos. Findings from this study will also help inform the design of prevention interventions, especially those targeting risk factors and AD neurodegeneration in this understudied population.

PI_NAMEs: QUIROZ, YAKEEL T. (contact)

PROGRAM_OFFICER_NAME: ELLIOTT, CERISE

PROJECT_TERMS: Address;Administrative Supplement;affective disturbance;Aging;aging brain;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;amyloid pathology;Biological Markers;Boston;Brain;Brain Pathology;Cardiovascular Diseases;cardiovascular risk factor;Chronic stress;Cognition;Cognitive;cognitive performance;cohort;Communities;Dementia;dementia risk;design;Development;Diabetes Mellitus;Early Diagnosis;Eligibility Determination;Enrollment;Exhibits;follow-up;Functional Magnetic Resonance Imaging;Funding;Goals;good diet;Grant;High Prevalence;Hypertension;Image;Impaired cognition;improved;in vivo;Individual;Intervention;Knowledge;Latino;Latino Population;life-long learning;Link;Massachusetts;Measures;Memory;middle age;modifiable risk;molecular marker;Moods;Nerve Degeneration;network dysfunction;neuroimaging;non-demented;normal aging;novel;older adult;Onset of illness;Participant;Pathology;Patient Self-Report;Physical activity;Population;Positron-Emission Tomography;pre-clinical;Prevalence;Prevention;preventive intervention;recruit;Registries;Research;Rest;Risk;Risk Factors;Risk Marker;Sleep;Sleep disturbances;Spanish;tau Proteins;Time;Visit;Work

PROJECT_TITLE: Boston Latino Aging Study (BLAST): Understanding Alzheimer's risk and biomarkers in older Latinos


NIH_SPENDING_CATS: Genetics;Human Genome;Infertility

ORG_DEPT: BIOLOGY

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Programmed DNA double-strand breaks represent a considerable risk for genome integrity, yet most organisms introduce such breaks into their genome at some point in their life cycle. By defining the molecular mechanisms that render programmed DNA breakage safe, this project will provide significant insight into diseases associated with aberrant break repair, including many cancer predisposition syndromes. It will also provide insight into the evolutionary function of programmed DNA breakage by investigating breakage in the context of gene inheritance and fertility and in the context of gene copy-number changes.

PI_NAMEs: HOCHWAGEN, ANDREAS  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Architecture;cancer predisposition;Cell Cycle Progression;Cell Physiology;Cells;Chromosome abnormality;Chromosome Breakage;Chromosomes;Congenital Abnormality;Copy Number Polymorphism;Defect;Development;developmental disease;Disease;DNA;DNA copy number;DNA Double Strand Break;DNA Repair;Environment;Eukaryota;experimental study;Fertility;Gene Dosage;Genes;Genetic;genetic variant;Genetic Variation;Genome;genome integrity;genome-wide;Genomic Instability;genomic locus;Genomics;Germ Cells;Germ Lines;Goals;Health;high risk;Human Cell Line;Infertility;insight;Laboratories;Length;Lesion;Life Cycle Stages;Location;Loss of Heterozygosity;Malignant Neoplasms;Measures;Meiosis;Meiotic Recombination;Mental disorders;Molecular;Molecular Biology;neuronal cell body;novel;Organism;phosphoproteomics;Process;programs;repaired;Research;Ribosomal DNA;Risk;Role;Saccharomyces cerevisiae;surveillance network;Syndrome;Testing;Time;Work;Yeasts

PROJECT_TITLE: Mechanisms of programmed chromosome breakage


NIH_SPENDING_CATS: Diabetes;Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Nutrition;Prevention

ORG_NAME: SAINT LOUIS UNIVERSITY

PHR: Project Narrative (Public Health Relevance Statement) The proposed research is relevant to public health because diabetic retinopathy with increasing prevalence, represents a major economic burden not only due to medical cost involved but also because working age adults are mostly affected by vision threatening diabetic retinopathy. The proposed experiments described in this project will use biochemistry, bioinformatics, molecular biology and two novel mouse models to determine how cellular iron accumulation impacts ketone body synthesis and utilization. The goal of this work is to increase our understanding of the role of ketone body β-hydroxybutyrate in iron induced inflammation and retinal cell death, opening new avenues for the treatment of diabetic retinopathy and other iron overload associated retinal degeneration.

PI_NAMEs: GNANA-PRAKASAM, JAYA PRANAVA  (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: 3' Untranslated Regions;Acceleration;Acetoacetates;Acetone;Address;Adult;Affect;Age;Anabolism;Animals;Antioxidants;Area;beta-Hydroxybutyrate;Biochemistry;Bioinformatics;Biology;Blindness;Blood;Blood Vessels;Cell Death;Cell Death Induction;Cell Survival;cell type;Cells;Circulation;Collaborations;Colon;Data;Degenerative Disorder;diabetes management;Diabetes Mellitus;diabetic;Diabetic mouse;Diabetic Nephropathy;Diabetic Retinopathy;Diet;DNA;DNA Repair;Economic Burden;Energy Supply;Environment;Enzymes;Epigenetic Process;experience;experimental study;Family;Fasting;Fatty Acids;FOXO3A gene;Frequencies;ganglion cell;Genetic;Genetic Models;Glucose;glycemic control;Goals;Hepatic;Histone Deacetylase;Histone Deacetylase Inhibitor;Homeostasis;Human;Hyperglycemia;IL18 gene;improved;in vitro Assay;Inflammasome;Inflammation;Inflammatory;inhibitor;insight;Insulin Resistance;Interleukin-1 beta;Iron;Iron Chelation;Iron Overload;ketogentic;Ketone Bodies;Ketones;Kidney;Knockout Mice;Knowledge;Link;Liver;marenostrin;Measures;Mediating;Medical Care Costs;Medicine;Metabolic;Metabolism;Mitochondria;Molecular Biology;mouse model;Mus;N-Acetylcysteinamide;Nature;Nerve Degeneration;Neurons;neuroprotection;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;Nutrient;Ophthalmology;Oxidative Stress;Oxidoreductase;Physiological;Prevalence;Production;Public Health;public health relevance;Reaction;Regulation;Reporting;Research;Response Elements;Retina;Retinal Degeneration;Retinal Neovascularization;retinal neuron;Risk Factors;Role;screening;senior faculty;Serum Iron Level;Severities;side effect;Signal Pathway;Signal Transduction;supportive environment;Testing;Therapeutic;Tissues;Training;Transferase;Universities;Untranslated Regions;uptake;Urine;Vision;Work

PROJECT_TITLE: Iron and Diabetic Retinopathy

STUDY_SECTION: DPVS

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: KANSAS CITY

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative Latinos experience substantial disparities in ADRD diagnosis and care compared to their non-Latino white peers, putting them at an increased risk for steeper cognitive decline, morbidity, mortality and caregiver burden. This K01 will address this research gap by 1) Examining the current primary care models of ADRD care to identify what services are offered and how they are delivered across a variety of settings and 2) Testing the feasibility and acceptability of Alianza Latina, a health systems approach to reduce disparities in ADRD diagnosis and care experienced by Latinos. These aims are fully in line with my long-term goal of establishing an independent research program to address disparities in ADRD experienced by Latinos.

PI_NAMEs: PERALES PUCHALT, JAIME  (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Aging;Alzheimer's Disease;Alzheimer's disease caregiver;Alzheimer's disease model;Alzheimer's disease related dementia;Area;Attitude;Award;Behavioral Symptoms;bilingualism;Burn injury;care systems;career development;Caregiver Burden;Caregivers;Caring;Chronic Care;Cities;Clinic;Clinical assessments;collaborative care;Communities;community center;community engaged research;comparative efficacy;cost;cost effectiveness;County;cultural competence;Data;Dedications;dementia care;design;Detection;detection platform;Diagnosis;disability;Disparity;disparity reduction;Early Diagnosis;Emergency department visit;Epidemiology;ethnic minority;evidence base;evidence based guidelines;experience;feasibility testing;Financial Support;Florida;Foundations;Funding;geographic difference;Goals;Health;health care delivery;health disparity;Health Insurance;Health system;Healthcare;Healthcare Systems;Heart Diseases;human old age (65+);Impaired cognition;improved;innovation;Insurance Coverage;interest;intervention refinement;Interview;K-Series Research Career Programs;Kansas;Knowledge;Language;late life;Latina;Latino;Latino Population;Learning;Linguistics;Link;Malignant Neoplasms;Managed Care;Memory;Mentored Research Scientist Development Award;Mentors;Mentorship;Morbidity - disease rate;mortality;National Institute on Aging;novel;Older Population;Outcome;Patient Care;Patients;peer;Population;Preparation;Prevention;Primary Care;primary care clinic;primary care practice;primary care provider;programs;Psychosocial Assessment and Care;public health priorities;Qualitative Research;Quality of Care;Reaction;Research;Research Personnel;Research Proposals;Research Training;Resources;Risk;Services;skills;Solid;Source;standard care;Structure;symposium;System;systems research;Texas;Time;Training;United States National Institutes of Health;Work

PROJECT_TITLE: Feasibility of a Novel Systems Approach for Improving Utilization of Alzheimer's Disease Services Among Latinos Attending Primary Care Practices


NIH_SPENDING_CATS: Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: This research provides a network of locations capable of implementing research designed to test promising interventions to improve survival and quality of life for people with life threatening emergencies. Establishing this research network should produce quicker results than would otherwise be possible, reducing the time it takes to improve clinical care.

PI_NAMEs: AUFDERHEIDE, TOM PAUL;BEISER, DAVID GUSTAV (contact)

PROJECT_TERMS: Adult;Agreement;Applications Grants;Budgets;career;Chicago;clinical care;clinical center;Clinical Trials;Clinical Trials Network;Collaborations;Contracts;design;dissemination strategy;Educational Curriculum;Emergency Care;Emergency Situation;Enrollment;experience;Faculty;Fellowship;Funding;Goals;Grant;Health;Helicopter;Hospitals;Illinois;improved;Indiana;Infrastructure;innovation;Institution;Intervention;Investments;K-Series Research Career Programs;Leadership;Life;Location;Medical center;medical schools;Medicine;Mentors;Mentorship;Methodist Church;Methods;multidisciplinary;patient retention;Patients;Pediatric Hospitals;Performance;Persons;Politics;Population Heterogeneity;Positioning Attribute;Qualifying;Quality of life;Recommendation;Recording of previous events;recruit;Research;Research Design;Research Personnel;Retirement;screening;Secure;Site;Social Sciences;Structure;Study Subject;System;Testing;Texas;Time;Training;Underserved Population;United States National Institutes of Health;Universities;Wisconsin;working group

PROJECT_TITLE: Renewal of The Mid-America CTSA Consortium (MACC) as a Regional Clinical Center for SIREN


ED_INST_TYPE: UNIVERSITY-WIDE

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

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE We propose a novel, non-cognitive, non-invasive behavioral marker of preclinical Alzheimer’s disease called multisensory integration based on findings that reveal a functional interplay of multisensory, cognitive, and mobility processes. Our proposed study will: 1) provide a deeper understanding of the functional neural networks involved in multisensory integration processes in preclinical Alzheimer’s disease; 2) determine whether functional multisensory activation in prefrontal cortex predicts future mobility decline and falls in preclinical Alzheimer’s disease; 3) assess the validity of multisensory integration as an early marker for preclinical Alzheimer’s disease; and 4) provide insights into the neurobiology of Alzheimer’s disease. Results from this project will guide future multisensory-based interventions aimed to alleviate disability and maintain functional independence of older adults at-risk for Alzheimer’s disease that can significantly augment existing interventions. 1

PI_NAMEs: MAHONEY, JEANNETTE R. (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: abeta accumulation;Address;Adverse effects;Affect;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;Area;Area Under Curve;Attention;Basal Ganglia;Behavioral;Behavioral Model;blood oxygen level dependent;Brain;Clinic;Cognitive;cognitive function;cognitive process;Communities;Data;Dementia;Deposition;Development;disability;Disease;Disease Marker;Disease Progression;Equilibrium;Experimental Designs;fall risk;falls;Fostering;functional independence;Functional Magnetic Resonance Imaging;Funding;Future;Gait;Impaired cognition;Individual;Infrastructure;innovation;insight;interest;Intervention;Intervention Studies;Investigation;Link;Longitudinal cohort;longitudinal design;Longitudinal Studies;Longitudinal, observational study;Magnetic Resonance Imaging;Measures;Mediating;Memory;mild cognitive impairment;Mobility decline;Mobility disability;Modality;Motor;motor disorder;multisensory;National Institute on Alcohol Abuse and Alcoholism;neural;neural correlate;neural network;Neuroanatomy;Neurobiology;Neuropsychological Tests;novel;novel marker;older adult;Outcome;Parietal;Participant;Performance;Peripheral;Plasma;Positron-Emission Tomography;pre-clinical;Prefrontal Cortex;prevent;Process;Reaction Time;Recording of previous events;recruit;Reporting;Research;Research Priority;Resources;response;Sensory;sensory input;sensory integration;somatosensory;Statistical Models;Structure of superior frontal gyrus;therapy design;Thick;Time;United States National Institutes of Health;Visual;Work

PROJECT_TITLE: Visual-somatosensory integration as a novel marker of Alzheimer's disease

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Immunization;Infectious Diseases;Neurosciences;Pain Research;Vaccine Related

ORG_CITY: LEBANON

ORG_NAME: DARTMOUTH-HITCHCOCK CLINIC

ORG_STATE: NH

PHR: PROJECT NARRATIVE The prevalence of idiopathic dry eye disease is on the rise in the United States. Characterized by ocular pain and inflammation, this anterior eye disease is believed to involve dysregulation of the adaptive immune system and negatively impacts the economic productivity, quality of life, and visual acuity of those afflicted. This proposal will significantly advance our understanding of neuro-immune interactions in human dry eye by innovating a preclinical disease model to study a population of highly proinflammatory adaptive immune cells that are typically absent in laboratory mice, but which have recently been shown to dominate the ocular surface of humans. This mechanistic analysis in mice will yield data critical to the development of novel treatments for human neuro- inflammatory diseases of the anterior eye.

PI_NAMEs: SKORPUT, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adaptive Immune System;Address;Animal Model;Animals;Anterior;Anti-Inflammatory Agents;Antigens;Applications Grants;Automobile Driving;Blood;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Communication;Cell Physiology;Cells;Chronic;Circulation;Clinical;clinically relevant;Cornea;cytokine;Data;Desiccation;Development;Disease;disease model;Dry Eye Syndromes;economic impact;Environment;Exhibits;experience;Exposure to;Eye;Eye diseases;eye dryness;Eye Infections;Functional disorder;Funding;genetic approach;Genitalia;Herpesvirus 1;Homeostasis;Human;Hypersensitivity;Immune;Immunologic Memory;Immunologics;in vivo;Incidence;Inflammation;Inflammatory;innovation;insight;Investigation;Knowledge;Laboratories;Laboratory mice;Mediator;Memory;Modeling;mouse model;Mucous Membrane;multidisciplinary;Mus;Nervous System;Neurogenic Inflammation;Neuroimmune;neuroimmunology;Neuroimmunomodulation;neuroinflammation;Neuropeptides;Nociceptors;novel;ocular pain;ocular surface;Pain;pathogen;pathogen exposure;Pathology;Patients;Peripheral;Phenotype;Population;pre-clinical;Pre-Clinical Model;Predisposition;Prevalence;Prevention;Productivity;Quality of life;Research;Research Personnel;Research Project Grants;Rodent;Rodent Model;Sensory;Shapes;Skin;Stress;Substance P;T memory cell;T-Cell Activation;T-Cell Depletion;T-Lymphocyte;T-Lymphocyte Subsets;Testing;tissue resident memory T cell;Tissues;TNF gene;United States;Vaccination;Virus;Virus Diseases;Visual Acuity;Work

PROJECT_TITLE: Impact of tissue resident memory T cells on the neuro-immunepathophysiology of anterior eye disease

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


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: IOWA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative Cone–rod homeobox (CRX) and neural retina leucine zipper (NRL) are the key transcription factors that control photoreceptor differentiation and maintenance. Mutations in the genes encoding CRX and NRL underlie severe retinal diseases in humans, including retinitis pigmentosa, cone-rod dystrophy, and Leber congenital amaurosis. Through the proposed structural and biochemical analyses, we aim to advance our understanding of the mechanisms of the CRX and NRL function to enable development of new targeted therapies for treating the visual disorders.

PI_NAMEs: ARTEMYEV, NIKOLAI O (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: Affinity;attenuation;Binding;Biochemical;Biological Assay;Biology;cell type;Chromatin;Complex;Cone;cone-rod dystrophy;CREB1 gene;CREB3 gene;CRX protein;Defect;defined contribution;design;Development;Dimerization;Disease;disease-causing mutation;DNA;DNA analysis;DNA Binding;DNA-Protein Interaction;Elements;Exhibits;follow-up;FOS gene;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;genetic regulatory protein;Genetic Transcription;Glean;Goals;Heterodimerization;Homeobox;homeodomain;Homeodomain Proteins;Homeostasis;Human;Individual;Inherited;insight;Knock-out;Knowledge;Leber's amaurosis;Length;Leucine Zippers;Link;Maintenance;Mediating;Molecular;mutant;Mutation;Mutation Analysis;Nature;Neural Retina;new therapeutic target;Outcome;Pathogenicity;Phenotype;Photoreceptors;postmitotic;programs;promoter;Protein Family;protein protein interaction;Proteins;Regulation;Regulatory Element;Research;response;Response Elements;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;retinal rods;Retinitis Pigmentosa;Rhodopsin;Rod;Signal Pathway;Site;spatiotemporal;Specific qualifier value;Specificity;Structure;synergism;targeted treatment;Testing;Therapeutic;therapeutic target;Tissues;transcription factor;Transcriptional Regulation;treatment strategy;Vertebrate Photoreceptors;Vision Disorders;Work

PROJECT_TITLE: Molecular underpinnings of photoreceptor transcriptional regulation by CRX and NRL

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ORG_CITY: MADISON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Agonist-activated PI3K signaling and nuclear PI signaling in stress have fundamental roles in many biological functions including in the immune system, cardiovascular and neuronal diseases, and cancers. Here we have discovered the regulation of PI3K signaling by a novel scaffolding molecule, IQGAP1 which brings all components of PI3K pathway in close functional proximity for concerted and spatial generation of the second messenger phosphatidylinositol-3,4,5-trisphosphate in any subcellular compartments, including plasma membrane and endosomes. PIPKI scaffolded by IQGAP1 in cytosol is also present in the nucleus. In the nucleus, PIPKI and its PIP2 product controls gene expression through a poly (A) polymerase Star-PAP and the tumor suppressor p53. PIP2 associated with Star-PAP and p53 serve as substrate for a novel nuclear PI 3- kinase, which is counteracted by nuclear PTEN. This has identified a novel nuclear PI stress signaling pathway encompassing PIPKI, Star-PAP, p53, IMPK and PTEN. These cytosolic and nuclear PI signaling pathways have clear diagnostic and therapeutic applications in cancer and neuronal diseases.

PI_NAMEs: ANDERSON, RICHARD A. (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Agonist;Binding;biological adaptation to stress;Biological Process;cancer cell;Cardiovascular Diseases;Cell membrane;Cell Nucleus;Cell Physiology;Cell Proliferation;Cell Survival;Cytosol;Diabetes Mellitus;Diagnostic;Disease;DNA Repair;EGF gene;Endosomes;Epidermal Growth Factor Receptor;Event;Gene Expression;Generations;Genes;Immune System Diseases;inorganic phosphate;inositol polyphosphate multikinase;Link;Malignant Neoplasms;MAP4;Membrane;Microtubules;Neurodevelopmental Disorder;Neurons;novel;Nuclear;Outcome;Pathway interactions;PDPK1 gene;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phosphotransferases;PIK3CG gene;Polymerase;Process;Protein Dephosphorylation;PTEN gene;receptor;Regulation;Research;Resistance;Role;scaffold;Second Messenger Systems;Signal Pathway;Signal Transduction;Stress;System;Therapeutic;TP53 gene;Tumor Suppressor Proteins

PROJECT_TITLE: Phosphoinositide Signaling in the Cytosol and Nucleus

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative Proper development of the cerebral cortex is critical for cognitive function, and defects during cortical development have been linked to numerous neurodevelopmental diseases. This proposal will examine how gene expression in neural stem cells is controlled at the level of mRNA stability, and how dysregulation of mRNA degradation contributes to neurodevelopmental diseases.

PI_NAMEs: SERDAR, LUCAS  (contact)

PROGRAM_OFFICER_NAME: KOSTER, MARANKE IRENE

PROJECT_TERMS: Ablation;Address;Affect;Apoptosis;Area;autism spectrum disorder;Brain;Cell Cycle;Cell Cycle Regulation;Cell Physiology;Cell Proliferation;cell type;Cells;Cerebral cortex;cognitive function;cohort;conditional knockout;Data;Data Set;Defect;density;Development;Developmental Delay Disorders;Disease;Electroporation;Embryo;Equilibrium;Event;Excision;excitatory neuron;Exhibits;experimental study;Frequencies;Gene Expression;Gene Expression Regulation;Genes;Image;imaging approach;Impairment;in utero;In Vitro;in vivo;Inherited;insight;Intellectual functioning disability;Knockout Mice;Knowledge;Label;Learning Disabilities;Link;loss of function;Maintenance;Measures;Mediating;Messenger RNA;Metabolic;Microcephaly;Missense Mutation;Monitor;mouse model;mRNA Decay;mRNA Stability;mRNA Transcript Degradation;Mus;mutant;Mutate;nerve stem cell;neural;Neurodevelopmental Disorder;neurogenesis;Neurons;Nonsense Mutation;novel;Patients;Poly(A) Tail;Population;Post-Transcriptional Regulation;posttranscriptional;Process;progenitor;Proteins;Radial;Regulation;RNA;RNA analysis;RNA Decay;RNA Stability;Role;self-renewal;stem cell fate;stem cell proliferation;stem cell survival;stem cells;Technology;Testing;Thick;Transcript;Transcriptional Regulation;transcriptome sequencing;Work

PROJECT_TITLE: The role of the mRNA decay factor CNOT3 in cortical development


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Caregiving Research;Clinical Research;Health Services;Palliative Care

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Concern has been raised by policymakers due to increasing private equity (PE) and publicly traded corporation (PTC) investment in hospice agencies and their purported effects on hospice care. PE- and PTC- owned hospices are under pressure to deliver short-term, above market returns to investors, which could have detrimental effects on hospice care. Leveraging a mixed methods approach to study the impact of PE and PTC hospice acquisitions could have important policy and clinical implications.

PI_NAMEs: BRAUN, ROBERT TYLER (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Administrator;Affect;Aging;Applications Grants;Area;Atlases;Behavior;care costs;care delivery;career;Caring;Characteristics;Client satisfaction;Clinical;clinical care;cost;Cross-Sectional Studies;Data;Databases;econometrics;Education;end of life;end of life care;Endowment;Equity;Event;Fee-for-Service Plans;Foundations;Funding;Geriatric Assessment;Geriatrics;Goals;Growth;health care delivery;health care service organization;Health Policy;Health Resources;Health Sciences;Health Services;Healthcare;Holly;Hospice Care;hospice environment;hospice utilization;improved;Incentives;Industry;instructor;Intervention;Interview;Investments;Leadership;Long-Term Care;Marketing;medical schools;Medicare;Medicare claim;Mentored Research Scientist Development Award;Mentors;Methodology;Methods;mid-career faculty;Modeling;National Institute on Aging;novel;Nursing Staff;operation;Organizational Culture;Outcome;Ownership;patient population;Patients;payment;Perception;Physician Executives;Physicians;Policies;Policy Maker;population health;pressure;Privatization;Process;professor;Provider;Public Health;Qualitative Methods;Qualitative Research;Quality of Care;Quality of life;Quasi-experiment;Reducing Agents;Research;Research Design;Research Personnel;response;Role;service providers;skill acquisition;skills;Structure;success;Training;trend;United States Centers for Medicare and Medicaid Services;Universities;Work

PROJECT_TITLE: Do Acquisitions of Hospice Agencies by Private Equity Firms and Publicly Traded Corporations Impact End-of-Life Quality and Cost of Care?

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD)

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative The preference of cell migration toward a stiffer substrate (termed “durotaxis”) is important for many biological processes, ranging from embryo development to tumor metastasis; however, its underlying mechanisms remain elusive, largely due to its multiplex nature and that predictive mathematical models lag behind the descriptive experimental finding. While it is well documented that focal adhesion (FA), an integrin-based multi-protein transmembrane linkage, defines the functional unit of durotaxis and adapts distinctive FA-localized spatial-temporal dynamics to substrate mechanics, it is not understood how FA mediates the mechanosensing of substrate stiffness and drives durotaxis. By iterative model-experiment dialogues, we aim to provide the first predictive multi-scale mathematical model to decipher the mechanisms of durotaxis, beginning with molecular mechanisms of FA-mediated mechanosensing, to crosstalk between FA and cell edge protrusion/retraction, all the way to the durotaxis at a whole-cell level.

PI_NAMEs: LIU, JIAN  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actins;Address;Affect;Back;Behavior;Binding;Biological Process;Cell Adhesion Molecules;cell motility;Cells;chemical reaction;Chemicals;Complex;Couples;Coupling;Cytoskeleton;Data Analyses;Development;Developmental Process;Embryonic Development;Environment;Event;Experimental Designs;Experimental Models;experimental study;Extracellular Matrix;Feedback;Feeds;Focal Adhesions;Generations;Goals;grasp;in silico;Individual;infancy;insight;Integral Membrane Protein;Integrins;Link;live cell imaging;mathematical model;Measures;Mechanics;mechanotransduction;Mediating;Modeling;Molecular;Monitor;Movement;multi-scale modeling;Nature;Neoplasm Metastasis;Pattern;predictive modeling;preference;Process;Protein Dynamics;Proteins;Research;Research Personnel;Resolution;Role;Shapes;skills;Stress Fibers;synergism;temporal measurement;Testing;Time;tool;Traction;transmission process;tumor;user friendly software;Work

PROJECT_TITLE: Predictive multi-scale model of focal adhesion-based durotaxis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(80)S]


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: LOS ANGELES

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE  Inorganic arsenic is the most ubiquitous naturally occurring toxic substance and a well- known epigenetic toxicant. However, its mechanisms of action on the epigenome are still unclear, especially with regards to how arsenic exposure can lead to remarkably different epigenetic alterations at distinct genomic loci. Our work will examine the role of epigenetic crosstalks, i.e. the fundamental pathways that connect epigenetic marks to each other, in determining locus sensitivity of arsenic exposure.

PI_NAMEs: ALLARD, PATRICK  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Arsenic;Automobile Driving;bisulfite sequencing;Body System;Cell Differentiation process;Cleavage Under Targets and Release Using Nuclease;Data;Deposition;differentiation in vitro;DNA;DNA Methylation;DNA Transposable Elements;embryonic stem cell;Environment;environmental chemical;environmental chemical exposure;Environmental Exposure;Environmental Impact;Epigenetic Process;epigenetic regulation;epigenome;Exposure to;Gene Silencing;Genes;Genetic Transcription;genome-wide;genomic locus;Germ Cells;Goals;Health;histone methylation;histone modification;Histones;Human;Hypermethylation;in vivo;Intercistronic Region;Intracisternal A-Particle Elements;knock-down;Mediating;Metabolic;Metabolism;metabolomics;Methyltransferase;Modeling;Molecular;Mouse Embryonic Stem Cells;Organ;overexpression;Pathway interactions;Poison;Predisposition;Repetitive Sequence;Repression;Research;response;Role;sodium arsenite;stem cell differentiation;Structure of primordial sex cell;Testing;Toxic Environmental Substances;toxicant;transcriptome sequencing;Untranslated RNA;whole genome;Work

PROJECT_TITLE: Role of epigenetic crosstalks in directing locus sensitivity to arsenic

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-A(06)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Cardiovascular;Emerging Infectious Diseases;Heart Disease;Infectious Diseases

ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

PHR: Project Narrative: Multidrug resistance (MDR) in pathogenic Gram-positive bacteria poses a serious public-health problem. We have identified a series of novel compounds based on a new molecular scaffold that exhibit bactericidal activity against many Gram-positive pathogens, accompanied by improved solubility. We propose to optimize this compound by making a series of analogs which we will characterize with regard to drug-like properties and in vitro and in vivo activity.

PI_NAMEs: CHEUNG, AMBROSE LIN YAU (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: activity-based protein profiling;Affinity Chromatography;analog;Animal Model;Anti-Bacterial Agents;Antibiotic Therapy;Antibiotics;aqueous;Bacteria;bactericide;Binding;Binding Proteins;biochemical tools;Biological Assay;biophysical tools;carbonyl group;Cells;crosslink;cytotoxicity;Daptomycin;Data;Defect;Derivation procedure;design;drug development;drug discovery;drug disposition;Drug Kinetics;Dyes;efficacy evaluation;efficacy study;Electron Microscopy;Endocarditis;Ensure;Enterococcus;Enterococcus faecalis;Enterococcus faecium;Evaluation Studies;Exhibits;Frequencies;Genetic;Genomics;Goals;Gram-Positive Bacteria;Hospitals;improved;In Vitro;in vivo;Infection;Infection Control;Infectious Skin Diseases;Infective endocarditis;Lead;Length of Stay;Libraries;Linezolid;Lipid Bilayers;Lipids;lipophilicity;Mass Spectrum Analysis;Measures;medical schools;Medicine;Membrane;methicillin resistant Staphylococcus aureus;Microsomes;Minnesota;Modeling;Modification;Molecular;Multi-Drug Resistance;Mus;mutant;Mutation;New Agents;Nosocomial Infections;novel;Organism;Oryctolagus cuniculus;pathogen;Pathogenicity;Pharmaceutical Preparations;Plasma Proteins;Positioning Attribute;Procedures;Property;Proteomics;Public Health;Publishing;Quinazolines;quinoline;Quinolones;Research;Resistance;Safety;scaffold;screening;Series;Serum;simulation;Solubility;Specificity;Staphylococcus aureus infection;Staphylococcus epidermidis;Streptococcus pneumoniae;Structure;Structure-Activity Relationship;Toxic effect;Universities;Vancomycin;Work

PROJECT_TITLE: Membrane-active quinoline and quinazoline antibacterials that target Gram positive pathogens

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Aging;Climate-Related Exposures and Conditions;Eye Disease and Disorders of Vision;Prevention

ORG_CITY: FORT WORTH

ORG_NAME: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR

PHR: Project Narrative Oxidative stress plays a crucial role in cataract formation, therefore understanding the antioxidant repair mechanism in the lens is essential for cataract prevention and treatment. By using an innovative double knockout model, we will study the mechanisms of how the glutaredoxin (Grx) system, a group of thiol-based antioxidant enzymes, preserves lens transparency. We will also develop new Grx-activating compounds and evaluate their efficacy as a potential pharmacological strategy against cataract.

PI_NAMEs: WU, HONGLI  (contact)

PROJECT_TERMS: Adenosine Triphosphate;Affect;Age;age related;Aging;aging population;antioxidant enzyme;Antioxidants;Attention;Binding;Blindness;Cataract;Collaborations;Complex;Crystallins;Data;Development;Disulfides;Dose;Drug Targeting;Elderly;enzyme activity;Enzymes;Epithelial Cells;Equilibrium;Euthanasia;Exposure to;Eye diseases;Family;Female;Functional disorder;GATA1 gene;Genes;Genetic Transcription;glutaredoxin;glutaredoxin 2;Glutathione;Glutathione Disulfide;glutathione peroxidase;Grx1 protein;Heme;Heterocyclic Amines;high risk;Histology;Homeostasis;Hydrogen Peroxide;Individual;innovation;insight;Isoenzymes;Knock-out;Knockout Mice;lens;lens transparency;male;Mammalian Cell;Measures;meter;Microscope;Mitochondria;Modeling;Monitor;Morphology;Mothers;mouse model;Mus;novel therapeutics;NQO1 gene;nuclear factor-erythroid 2;Organ Culture Techniques;oxidation;Oxidation-Reduction;oxidative damage;Oxidative Stress;Oxygenases;Pathway interactions;Persons;pharmacologic;Play;Post-Translational Protein Processing;Predisposition;preservation;Prevalence;Prevention;protective effect;protein aggregation;Protein Isoforms;Proteins;repair enzyme;repaired;response;Risk Factors;Role;Series;Signal Transduction;success;Sulfhydryl Compounds;Superoxide Dismutase;Surface Plasmon Resonance;System;Techniques;Testing;Texas;Therapeutic;Therapeutic Agents;thioltransferase;Time;Tissues;treatment group;trend;TXN gene;Ultraviolet Rays;UV induced;UV Radiation Exposure;Western Blotting;Wild Type Mouse

PROJECT_TITLE: Mechanistic Insights and Therapeutic Potential of the Glutaredoxin (Grx) System in the Lens


ADMINISTERING_IC: CA

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE Despite unprecedented activity and FDA approval of BTK inhibitors such as ibrutinib (IBR) and acalabrutinib (ACA), and BCL-2 antagonist venetoclax (VEN) for patients with chronic lymphocytic leukemia (CLL), these targeted agents have limitations and do not result in cures as single agents alone. By simultaneous inhibition of pro-survival and proliferative BTK signaling and anti-apoptotic BCL-2 function, we aim to use this combination approach to target high-risk CLL that has poor response to single agents alone. Using a clinical protocol (NCT04169737) combining ACA and VEN, we will analyze pharmacodynamic and molecular endpoints from CLL cells during therapy to evaluate the impact of these drug combinations on efficacy, identify biomarker for response and relapse, and correlate omics changes with biology of the disease.

PI_NAMEs: GANDHI, VARSHA  (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Achievement;Adverse event;Agammaglobulinaemia tyrosine kinase;Alkylating Agents;antagonist;Apoptotic;arm;B-Cell Antigen Receptor;B-Lymphocytes;BCL-2 Protein;BCL1 Oncogene;Binding;Biochemical;Biological Markers;Biology;biomarker identification;Blood;Blood Cells;Blood specimen;Bone Marrow;Cells;chemokine;chemotherapy;chromosome 17p loss;Chronic Lymphocytic Leukemia;chronic lymphocytic leukemia cell;Clinic;Clinical;Clinical Data;Clinical Protocols;Clinical Trials;Clonal Evolution;cohort;Combined Modality Therapy;Cyclophosphamide;Cytogenetics;Data;del(11q);Dependence;design;Disease;Disease remission;disorder risk;Dose;driver mutation;Drug Combinations;Drug Kinetics;Drug usage;effective therapy;efficacy evaluation;Event;fludarabine;Functional disorder;Generations;Genes;genome sequencing;genomic profiles;genotoxicity;Goals;high risk;human old age (65+);Immuno-Chemotherapy;improved;In complete remission;Incidence;inhibitor;Investigation;Laboratories;Link;lymph nodes;Maintenance;MCL1 gene;Measurable;Measures;Messenger RNA;migration;Molecular;Molecular Profiling;Moon;Mutation;nucleoside analog;Oral;Outcome;Pathogenesis;Pathway interactions;patient subsets;Patients;Pharmaceutical Preparations;Pharmacodynamics;phase I trial;Phase III Clinical Trials;Phosphotransferases;Plasma;pre-clinical;Prognosis;Prognostic Factor;Progression-Free Survivals;Proliferating;Protein Family;Proteins;Proteome;Proteomics;Ramp;Randomized;Receptor Signaling;Recurrent disease;Refractory;Relapse;Research Personnel;Residual Neoplasm;Residual state;Resistance;response;response biomarker;rituximab;Role;Sampling;Second Primary Cancers;selective expression;Signal Transduction;standard of care;success;targeted agent;targeted treatment;Testing;therapeutic target;Time;tositumomab;TP53 gene;transcriptome;transcriptome sequencing;Translational Research;treatment response;trial comparing;Tumor Debulking;Tumor Lysis Syndrome;Tyrosine Kinase Inhibitor;whole genome

PROJECT_TITLE: A combination strategy to target pathophysiology of chronic lymphocytic leukemia


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NOTRE DAME

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Project Narrative: Vision loss is among the top ten disabilities in the United States, with an estimated burden on society of over $35 billion and approximately 285 million people worldwide being visually impaired and 39 million being blind. Many of the causes of vision loss are slow and chronic. We will examine why zebrafish regenerate retinal neurons following a rapid acute damage, but not a slow chronic damage, which may result in the development of novel therapies to restore vision to humans who suffer from chronic retinal degenerative diseases.

PI_NAMEs: BLACKSHAW, SETH ;HYDE, DAVID R (contact);PERKINS, BRIAN D;QIAN, JIANG

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: Acute;Agonist;antagonist;ATAC-seq;Attention;Behavior;Bioinformatics;blind;Blindness;Bypass;Candidate Disease Gene;Cells;Central Nervous System;Chromatin;Chronic;comparative;Competence;Cone;CRISPR/Cas technology;cytokine;Data Set;Development;disability;DNA Sequence Alteration;early onset;epigenomics;Exhibits;Fishes;Future;gamma secretase;Gene Expression;Gene Expression Profiling;Generations;Genes;Gliosis;Growth Factor;Hour;Human;Immune;Inflammation;inhibitor;Injections;Injury;knock-down;Knowledge;Ligands;Light;Mammals;Medical;Methods;Microglia;Modeling;Molecular;Molecular Analysis;Muller's cell;multiple omics;Mus;mutant;N-Methylaspartate;Natural regeneration;nerve stem cell;neuron regeneration;Neurons;novel therapeutics;Nuclear Pore Complex;Nuclear RNA;overexpression;Paper;Persons;photoreceptor degeneration;Play;Population;prevent;Process;programs;Proliferating;Proteins;receptor;regenerative;Regenerative capacity;Regenerative response;regenerative therapy;Reproducibility;response;Retina;Retinal Cone;retinal damage;Retinal Degeneration;retinal neuron;retinal regeneration;Role;Science;sight restoration;Signal Pathway;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;small molecule;Societies;Source;species difference;Stimulus;Testing;transcription factor;transcriptome sequencing;Translations;United States;Vertebrate Photoreceptors;Visual;Visual impairment;Work;Zebrafish

PROJECT_TITLE: Elucidating and bypassing molecular mechanisms that suppress Muller glia-dependent regeneration of cones in two zebrafish models of chronic retinal damage

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


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Lung;Machine Learning and Artificial Intelligence;Precision Medicine;Prevention;Pulmonary Hypertension;Rare Diseases;Scleroderma

PHR: PROJECT NARRATIVE In the current proposal, we will (1) employ innovative Bayesian trajectory analyses with machine-learning techniques to determine if novel strain-based measures of right ventricular (RV) contractile function improves prediction of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) by identifying at-risk phenotypes earlier in the disease course, (2) establish the relationship between strain-based measures of RV contractility and contractile reserve with direct pressure-volume hemodynamic chamber-level assessments, and (3) develop a new multivariate algorithm that utilizes innovative imaging based techniques thereby allowing for an early detection strategy that improves upon existing techniques in identifying SSc patients at risk for emerging RV dysfunction and PAH.

PI_NAMEs: MUKHERJEE, MONICA  (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: adverse event risk;Affect;Algorithm Design;Algorithms;Autoimmune Diseases;Awareness;Biological;Biological Markers;Biometry;Cardiopulmonary;case control;Cause of Death;Characteristics;Clinical;clinical application;Clinical Management;clinical phenotype;clinically relevant;cohort;Complex;Coupling;Data;Depressed mood;design;Detection;Development;Diagnosis;disability;Disease;Dyspnea;Early Diagnosis;Early identification;Early Intervention;Early treatment;Echocardiography;Fibrosis;Guidelines;Heart failure;hemodynamics;Heterogeneity;high risk;Image;imaging biomarker;Imaging Techniques;improved;improved outcome;indexing;innovation;Machine Learning;Measurement;Measures;Methodology;Methods;Modeling;Morbidity - disease rate;mortality;Myocardial;Nature;novel;Outcome;patient population;patient stratification;patient subsets;Patients;Performance;Phenotype;Physiological;Population;Positioning Attribute;predicting response;pressure;Process;Prognosis;prognostic;prospective;pulmonary arterial hypertension;Pulmonary Heart Disease;Pulmonary Hypertension;pulmonary vascular disorder;quantitative imaging;rate of change;Recommendation;recruit;Research;response;Rest;Right Ventricular Dysfunction;right ventricular failure;Right Ventricular Function;Risk;screening;Secondary to;Stress;Subgroup;systemic autoimmune disease;Systemic Scleroderma;targeted treatment;Technical Expertise;Techniques;Testing;Therapeutic;Therapeutic Intervention;Tissues;Validation;Vascular Diseases;Ventricular

PROJECT_TITLE: Early Detection of Right Ventricular Dysfunction and Emerging Pulmonary Hypertension in Systemic Sclerosis

STUDY_SECTION: RIBT

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