ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative  We have developed a panel of cre-expressing rat lines that will allow the manipulation of different area postrema cell types that respond to endogenous and pharmacologic signals that can suppress appetite to treat individuals with obesity. These studies will allow for rational design of agents for the therapy of obesity that target the most advantageous components of these circuits for novel weight-loss therapies.

PI_NAMEs: GOFORTH, PAULETTE B.;MYERS, MARTIN G (contact);SEELEY, RANDY J

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: Affect;Agonist;amylin receptor;Anorexia;Appetite Depressants;Aversive Stimulus;Behavioral;Behavioral Assay;Biological Assay;Blood - brain barrier anatomy;Body Weight decreased;Brain;cell type;Cells;Chronic Disease;combat;Complex;Data;design;designer receptors exclusively activated by designer drugs;Desire for food;detection of nutrient;Development;Dorsal;Eating;Electrophysiology (science);feeding;gamma-Aminobutyric Acid;GDF15 gene;Gene Modified;Genetic;GIPR gene;Glutamates;Human;Image;improved;Individual;Injections;islet amyloid polypeptide;Mammalian Genetics;Mediating;Medical;Methods;Modeling;Mus;Nausea;Nausea and Vomiting;neural;Neurons;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;Obesity;Obesity Epidemic;obesity treatment;parabrachial nucleus;Pathologic;Pattern;Pharmaceutical Preparations;pharmacologic;Physiological;Population;RAMP3;rational design;Rattus;receptor;Regulation;Reporter;response;Risk;Role;Satiation;Signal Transduction;single cell analysis;Structure of area postrema;System;Therapeutic;weight loss intervention

PROJECT_TITLE: Defining roles for area postrema neuron cell types in food intake and nausea

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ADMINISTERING_IC: HG

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Machine Learning and Artificial Intelligence

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE Most human complex diseases and traits are highly polygenic with GWAS disease signal spread throughout the genome, thereby implicating a large number of genes for the disease. In order to provide actionable insights to inform drug treatments and CRISPR screening assays, it is extremely important to powerfully identify and rank genes and gene sets representing biological processes based on their association to a disease or trait using both GWAS and functional genomics data. My proposed research will develop and evaluate statistical and machine learning methods to 1) to identify and rank genes for a trait using both common variant and rare variant association studies and gene-level annotations from functional data, 2) identify disease- associated gene sets characterizing cell types and cellular processes from functional data and 3) pinpoint short genomic regions (~ few 100bp in size) linked to disease-associated genes and gene sets from (1) and (2) where disease signal is concentrated.

PI_NAMEs: DEY, KUSHAL KUMAR (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Alleles;Architecture;Area;ATAC-seq;Base Pairing;Base Sequence;Benchmarking;Biological Assay;Biological Process;Cell Physiology;cell type;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Complex;complex data;computer framework;computerized tools;CRISPR interference;CRISPR screen;Data;deep learning;deep learning model;Disease;Disease Progression;disorder risk;Drug Design;Drug Targeting;Enhancers;epigenomics;experimental study;functional genomics;Future;Genes;genetic architecture;Genetic Diseases;genetic variant;Genome;genome wide association study;genomic data;Genomic Segment;Genomics;Goals;Heritability;Hi-C;Human;human disease;Human Genetics;insight;Intervention;Knock-out;Link;machine learning method;Manuscripts;Maps;Mentorship;method development;Methods;novel strategies;Nucleic Acid Regulatory Sequences;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phase Transition;Price;Process;Public Health Schools;rare variant;Research;Resolution;risk variant;Shapes;Signal Transduction;single cell analysis;single cell ATAC-seq;single cell genomics;single-cell RNA sequencing;Specificity;statistical and machine learning;Statistical Methods;statistics;Testing;Time;Tissues;tool;Training;trait;transcriptome sequencing;transcriptomics;Untranslated RNA;Variant;Work

PROJECT_TITLE: New approaches for leveraging single-cell data to identify disease-critical genes and gene sets

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Pediatric;Urologic Diseases

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE: NOVEL ROLE OF NEPHRON EPITHELIALIZATION IN NUCLEAR SIGNALING Formation of tubules is essential for the development of the kidney and urinary tract, and failure of this process results in urogenital anomalies, which occur in almost 2% of the world population and represent nearly one- fourth of all birth defects. Kidney tubule malformations result from disruption of either of two groups of proteins, the planar cell polarity (PCP) or exocyst proteins, but how they affect the formation of tubules in the developing kidney is not well understood. This study is significant because it will uncover how these protein groups work together to form the kidney tubules, improving our understanding of the mechanisms underlying prevalent birth defects involving the kidney.

PI_NAMEs: MILLER, RACHEL KATHERINE (contact)

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Actins;Address;Adherens Junction;Adhesions;Affect;Area;Attenuated;Automobile Driving;beta catenin;Biological;Birth;Body System;Cadherins;cell assembly;Cell Communication;Cell Nucleus;Cells;Childhood;Complex;Congenital Abnormality;congenital anomalies of the kidney;Data;Defect;Development;Developmental Process;Embryo;End stage renal failure;Epithelium;experimental study;Failure;Funding;Generations;Genetic;Genitourinary system;Goals;Grant;Human;Image;improved;in vivo;insight;Intercellular Junctions;Kidney;Kidney Transplantation;malformation;Mediating;Microfilaments;Modeling;Morphogenesis;nephrogenesis;nephron progenitor;Nephrons;novel;Nuclear;Pathologic;Pathway interactions;planar cell polarity;polymerization;Polymers;Population;Process;Proteins;Quantitative Evaluations;Regulation;Renal function;Renal tubule structure;Research;Role;Signal Transduction;stem cells;Testing;Urinary tract;Vesicle;WNT Signaling Pathway;Work;working group;Xenopus

PROJECT_TITLE: Novel Role of Nephron Epithelialization in Nuclear Signaling

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Immunotherapy;Neurosciences;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Cancer treatments harnessing the power of the immune system (immunotherapies) have revolutionized the treatment of various cancers, but they have not proven successful in patients with brain tumors, as these patients have dramatically weakened immune systems. This proposal is relevant to public health because it will examine factors that weaken these patients’ immune systems and may also impact patients with cancer outside the brain to a lesser degree. Knowledge from this proposal may uncover novel immunotherapeutic strategies and ways to reverse this immunosuppression, thereby enhancing existing immunotherapies, thus contributing to the NCI’s mission of alleviating the burden of cancer on patients.

PI_NAMEs: WACHSMUTH, LUCAS  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;anti-tumor immune response;ARRB2;B-Cell Activation;beta-2 Adrenergic Receptors;Bone Marrow;Brain;Brain Neoplasms;Breast Cancer Model;Cancer Burden;cancer infiltrating T cells;cancer therapy;CD8-Positive T-Lymphocytes;Cell Physiology;Cell surface;Cellular immunotherapy;Cephalic;Chronic;Data;Enhancers;Exhibits;Family;Gene Expression;Genes;Goals;Immune;immune depression;Immune system;Immune System Diseases;immunodeficiency;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;Implant;improved;In Vitro;in vivo;in vivo Model;Inflammation;inhibitor;insight;Intervention;Intracranial Neoplasms;Knock-in;Knock-out;Knowledge;Lead;Licensing;Light;Link;lymphoid organ;Lymphopenia;Malignant Neoplasms;Mediating;Membrane Proteins;Metastatic malignant neoplasm to brain;Mission;Mus;neoplastic cell;novel;Nuclear;Pathology;Patients;Phenotype;Play;prevent;Primary Brain Neoplasms;Prognosis;protein function;Proteins;Public Health;receptor;Role;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;Sphingosine-1-Phosphate Receptor;success;Surface;Sympathetic Nervous System;T-Cell Activation;T-Lymphocyte;Therapeutic;transcription factor;tumor;Tumor Immunity;Wild Type Mouse;Work

PROJECT_TITLE: Mechanistic insights into immune suppression in brain tumors:  a role for beta-arrestin 2


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: HANOVER

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE During cell division, cells inherit an identical and complete set of all chromosomes; however, mistakes sometimes occur leading to cells with abnormal numbers of chromosomes and to a condition called aneuploidy. Aneuploidy is the leading cause of pregnancy miscarriages and birth defects in humans. The goal of this proposal is to understand the causes and consequences of aneuploidy in human embryonic cells which will lead to new strategies to prevent aneuploidy and improve the success of reproductive and regenerative medicine therapies.

PI_NAMEs: GODEK, KRISTINA M (contact)

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: Abbreviations;Acceleration;Anaphase;Aneuploid Cells;Aneuploidy;Apoptosis;Attention;Automobile Driving;Biological Assay;blastocyst;Cell Cycle;Cell Cycle Arrest;Cell division;Cell Survival;Cells;Chemicals;chromosome missegregation;chromosome number abnormality;Chromosome Segregation;Chromosomes;Congenital Abnormality;Data;daughter cell;Defect;Development;Diploid Cells;Diploidy;Disadvantaged;DNA sequencing;Embryo;embryo cell;embryo tissue;Embryoid bodies;Foundations;Genome;genome integrity;Genomic approach;Goals;Grant;Human;Human Development;human embryonic stem cell;Impairment;improved;Inherited;Karyotype;Kinetochores;Knowledge;Label;Measures;Meiosis;Microtubules;Mitosis;Mitotic;Molecular;Pathway interactions;Pregnancy;premature;preservation;prevent;quantitative imaging;Regenerative Medicine;Reproductive Medicine;reproductive success;response;restraint;segregation;Signal Pathway;Somatic Cell;Spontaneous abortion;Structure;Teratoma;Testing;Time;Totipotent;Work

PROJECT_TITLE: Causes and Consequences of Aneuploidy in HeSCs


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE We seek to discover new principles for selective catalysis, and to apply those principles to the discovery of valuable organic reactions. The fruit of this effort will be new classes of small- molecule, chiral organic catalysts engineered to induce rate acceleration and stereoselectivity in a wide range of challenging transformations through networks of attractive non-covalent interactions. These catalysts form the basis for conceptually novel and efficient methods for the synthesis of chiral organic compounds of known or potential utility in public health.

PI_NAMEs: JACOBSEN, ERIC N (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Development, Elucidation, and Application of New Principles in Stereoselective Catalysis

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: MILWAUKEE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative Hypertension and obesity are strongly comorbid conditions that afflict an overwhelming fraction of the American populace, and hypothalamic pathways involved in coordinated control of blood pressure and metabolism are implicated in the development and maintenance of each. The current proposal will investigate the role of the angiotensin signaling within a specific subtype of neuron within the hypothalamus in normal cardiometabolic control, how that pathway is fundamentally altered during obesity, and how those alterations mechanistically contribute to the maintenance and elaboration of obesity and associated hypertension.

PI_NAMEs: GROBE, JUSTIN L (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Age;American;Angiotensin II;Angiotensin II Receptor;Angiotensin Receptor;Angiotensin Type 1a Receptor;Angiotensins;Animal Model;Animals;Area;attenuation;Autocrine Communication;Basal metabolic rate;Behavioral Mechanisms;Biology;Blood Pressure;blood pressure control;blood pressure elevation;Body Weight decreased;Brain;Brain region;cardiometabolism;cardiovascular health;Cardiovascular system;Cell Nucleus;cell type;Cells;Cellular biology;Clinical;comorbidity;Consumption;Data;desensitization;Development;Diet;diet-induced obesity;Disinhibition;Electrolytes;Electrophysiology (science);Energy Metabolism;excessive weight gain;Exhibits;Fatty acid glycerol esters;feeding;Female;Functional disorder;Funding;Genetic;genetic manipulation;GTP-Binding Proteins;High Prevalence;Homeostasis;Hormones;Human;Hypertension;Hypothalamic structure;improved;in vivo;in vivo evaluation;innovation;insight;Intervention;Ion Channel;Leptin;Liquid substance;Maintenance;male;Mediating;Metabolic Control;Metabolism;Methods;Modality;Modeling;Molecular;Molecular Biology;mortality;Mus;National Health and Nutrition Examination Survey;neural circuit;Neurons;Neurosecretory Systems;neurotransmission;novel;obese person;Obesity;Overweight;paracrine;Pathogenesis;Pathway interactions;Peptides;pharmacologic;Phenotype;Physiological;Physiology;Process;protein activation;Publishing;receptor;Receptor Activation;Receptor Signaling;Renin-Angiotensin System;Resistance;response;Risk Factors;Role;Second Messenger Systems;Signal Pathway;Signal Transduction;Signaling Protein;Smoking;Stimulus;Structure of nucleus infundibularis hypothalami;Sympathetic Nervous System;synergism;System;Thinness;Tissues;transcriptome;transcriptome sequencing;Transgenic Animals;Viral;Weight;Work

PROJECT_TITLE: Angiotensin receptor G protein signal switching in AgRP neurons in cardiometabolic control

STUDY_SECTION: IVPP

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Lung;Precision Medicine;Pulmonary Fibrosis;Rare Diseases;Scleroderma

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc), and many SSc-ILD patients do not respond favorably to treatment with immunosuppression. This study will investigate whether specific patient characteristics, imaging features and potential blood biomarkers, can be used to determine which patients with SSc-ILD are most likely to experience a positive improvement in their lung disease in response to immunosuppressive therapy. Integrating predictive clinical and biological factors into our SSc-ILD model of care may improve health outcomes for these patients and provide novel mechanistic insights into treatment responsive versus resistant SSc-ILD subgroups.

PI_NAMEs: VOLKMANN, ELIZABETH R (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Affect;Aftercare;alternative treatment;Area;Biologic Characteristic;Biological;Biological Factors;Biological Markers;Blood;Bronchoalveolar Lavage;Caring;Cause of Death;Cessation of life;Characteristics;Clinical;Clinical Data;clinical predictors;cohort;Connective Tissue Diseases;Cutaneous sclerosis;Cyclophosphamide;cytokine;Data;Data Analyses;Deterioration;Development;Disabling;Disease;disease model;disease phenotype;Disease Progression;disorder subtype;Dyspnea;evidence base;experience;FDA approved;Fibrosis;fibrotic interstitial lung disease;Focus Groups;follow-up;Funding;Future;Glass;Goals;Health;health care availability;High Resolution Computed Tomography;Image;Immunosuppression;improved;indexing;Infiltration;Inflammatory;innovation;insight;Interstitial Lung Diseases;Lavage;link protein;Lung;Lung Diseases;Measurement;Measures;Modeling;mortality;Mycophenolate;Myositis;novel;Observational Study;Outcome Measure;Patient Care;Patient Participation;patient subsets;Patient-Focused Outcomes;Patients;Peripheral;Phenotype;Physiology;Plasma;Population;precision medicine;predicting response;Prediction of Response to Therapy;predictive modeling;prospective;Prospective cohort;Proteins;Pulmonary Fibrosis;pulmonary function;quantitative imaging;radiological imaging;Randomized, Controlled Trials;Research Personnel;Resistance;response;Rheumatoid Arthritis;Sampling;Schedule;Scleroderma;Serum;Severity of illness;skills;Specimen;standard care;standard of care;Stem cell transplant;Systemic Scleroderma;Testing;Therapeutic immunosuppression;Thoracic Radiography;Time;tool;Training;treatment response;trial comparing;United States National Institutes of Health;Vital capacity

PROJECT_TITLE: Identifying predictors of treatment response in systemic sclerosis-related interstitial lung disease

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

PHR: Project Narrative Prediction and prevention of psychosis is an international priority given the tremendous personal and public health burden associated with the illness. Progress in this initiative has been hindered by a poor mechanistic understanding of risk and by the siloed nature of research on the high-risk stages of psychosis versus related disorders such as depression. To inform generalizable prediction and prevention, this proposal will identify shared and differential vulnerabilities of two neurobehavioral dimensions with known relevance to psychotic and depressive illness – stress and reward processing – among youth with emerging manifestations of these disorders.

PI_NAMEs: MILLMAN, ZACHARY BEN (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: acute stress;Adolescent;Affective;Affective Symptoms;Age;attenuated psychosis syndrome;Behavior;biological adaptation to stress;Biological Markers;Clinical;Computer Models;Corpus striatum structure;Data;Decision Making;Depressive disorder;depressive symptoms;design;Detection;Diagnostic;Dimensions;disability;Disease;Disease susceptibility;disorder risk;Ensure;Equilibrium;expectation;Functional disorder;Functional Magnetic Resonance Imaging;Generations;Goals;high risk;Hormonal;Hydrocortisone;Impairment;improved;Individual;International;Knowledge;Learning;Mediating;Mental Depression;Mental disorders;Methodology;Modeling;Mood Disorders;Nature;neural;neurobehavioral;Neurobiology;neurodevelopment;neuroimaging;Neurosciences;Outcome;Pathogenesis;Pathogenicity;Pattern;peer;personalized intervention;phenomenological models;Positioning Attribute;Prefrontal Cortex;Prevention;preventive intervention;Process;Protocols documentation;Psychiatry;Psychological reinforcement;Psychopathology;Psychoses;psychosis risk;psychotic;Psychotic Disorders;Public Health;recruit;Research;response;reward processing;Rewards;Risk;Sampling;Schizophrenia;Severities;Signal Transduction;Stress;stress reduction;Syndrome;System;Technical Expertise;Theoretical model;trait;Youth

PROJECT_TITLE: Shared and differential vulnerabilities of stress and reward processing in psychosis-risk syndromes or early-stage depression

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: Brain function depends on the continuous delivery of energy sources through its blood supply. Impaired blood flow through vasculature in the brain is an early event in Alzheimer’s disease (AD). We found, for the first time, that pathogenic forms of tau, a protein that contributes to cause AD, accumulate in cells of the brain vasculature, causing brain vascular dysfunction. Our studies will define how pathogenic tau drives brain vascular dysfunction in AD. These studies will have a lasting impact, because they will reveal new mechanisms of AD. With our studies progress will be made towards bringing TOMA or other immunotherapies to Veterans sooner.

PI_NAMEs: GALVAN, VERONICA  (contact)

PROJECT_TERMS: Address;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer’s disease biomarker;Area;Biological;Blood flow;Blood Vessels;Brain;brain cell;brain dysfunction;brain endothelial cell;Cell Aging;Cell Physiology;Cells;cellular targeting;cerebral microvasculature;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Cytoskeleton;Dementia;Disease;Disease Progression;early detection biomarkers;Endothelial Cells;Endothelium;Energy-Generating Resources;Etiology;Event;Excision;Failure;Functional disorder;Goals;Histopathology;Human;Immunotherapy;Impairment;In Vitro;in vivo;Incidence;Intervention;Investigation;Knowledge;Link;Maps;Microtubule Stabilization;Microtubules;Microvascular Dysfunction;Modeling;Molecular;mouse model;Neurons;Nitric Oxide Synthase;Oxidative Stress;Pathogenicity;Pathology;Pathway interactions;postsynaptic neurons;Process;Proteins;Research;Role;senescence;targeted treatment;tau aggregation;tau mutation;tau Proteins;Tauopathies;Testing;Therapeutic;Time;tool;Toxic effect;transmission process;Vascular blood supply;Vascular Diseases;Vascular Endothelial Cell;Veterans;Work

PROJECT_TITLE: Pathogenic soluble aggregated tau as a driver of brain vascular dysfunction in Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURD-E (01)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Project Narrative: The proposed research is relevant to public health because Alzheimer's disease (AD) is the most common cause of dementia worldwide. The current application aims to understand a novel mechanism underlying lipid deficiency-induced tau toxicity and pathology in AD and related dementia. Positive results may lead to new understanding of AD pathogenesis and development of novel drugs for effective treatment of AD.

PI_NAMEs: CHEN, LIZHEN ;DUPREE, JEFFREY L.;HAN, XIANLIN  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Acceleration;Address;Affect;aging population;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;Animal Model;Animals;Apolipoprotein E;apolipoprotein E-4;Brain;brain dysfunction;Cell Nucleus;Cells;Cholesterol;Code;Cytoskeleton;Dementia;Development;effective therapy;Fatty Acids;Fluorescence Microscopy;Frontotemporal Dementia;galactosylceramide sulfotransferase;Gene Expression;Genes;genetic risk factor;Histology;Human;Impaired cognition;Knock-in;Knock-in Mouse;Knockout Mice;Knowledge;Late Onset Alzheimer Disease;lipid metabolism;lipidomics;Lipids;Maintenance;Membrane Microdomains;Metabolism;Mixed Function Oxygenases;Molecular;mouse model;Mus;Myelin;Nerve Degeneration;Neuroglia;neuron loss;Neurons;novel;novel therapeutics;Oligodendroglia;Outcome;particle;Pathogenesis;Pathology;Pharmaceutical Preparations;Phosphorylation;Play;prevent;Protein Isoforms;Public Health;Reporting;Research;Role;Sampling;single nucleus RNA-sequencing;Site;spatiotemporal;Specificity;Sphingolipids;Sulfoglycosphingolipids;tau aggregation;tau expression;tau Proteins;tau-1;tau-protein kinase;Tauopathies;Testing;Therapeutic;Toxic effect;transcriptome sequencing;transcriptomics;Transgenic Mice;treatment strategy;ultra high resolution;Up-Regulation;Work

PROJECT_TITLE: The role of sulfatide in the development of tauopathy in the context of ADRD

STUDY_SECTION: CMBG

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


ED_INST_TYPE: SCHOOLS OF EDUCATION

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

ORG_CITY: Nashville

ORG_DEPT: PSYCHOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative Children’s reading and math skills are critical to their future educational outcomes, career readiness, and overall health and well-being (e.g., ACT, 2020; Cain & Oakhill, 2006; DeWalt et al., 2004; Geary, 2011; Heilmann, 2020; Krajewski & Schneider, 2009; Ritchie & Bates, 2013), yet many children struggle with math and learning to read (National Center for Education Statistics, 2020). This proposal will examine individual differences in word reading and math ability in the functional role and connectivity of executive function, an underlying cognitive mechanism of reading and math. Ultimately, this increased understanding may offer a more directed approach to improve academic skills in struggling learners, thereby increasing educational and health outcomes for at-risk children.

PI_NAMEs: MARTINEZ-LINCOLN, AMANDA  (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Academia;Academic skills;Area;Attention;Award;base;behavior measurement;Behavioral;Brain;Brain imaging;Brain region;career;career preparation;Child;Child Development;Church;Cognitive;cognitive process;comorbidity;Compensation;Complex;Data;design;Development;Education;effective intervention;Evidence based intervention;executive function;Exhibits;flexibility;fourth grade;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Growth;Health;Imaging Techniques;improved;Individual;Individual Differences;insight;Knowledge;Language;Learning;Learning Disabilities;Link;mathematical ability;mathematical difficulties;Mathematics;Meta-Analysis;Methodology;neurobiological mechanism;Neurobiology;neuroimaging;Neurosciences;Outcome;Parkinson Disease;Personal Satisfaction;Phase;phonology;Play;Problem Solving;Process;Productivity;programs;Reader;Reading;reading ability;reading difficulties;recruit;remediation;Research;Resources;Risk;Role;Sampling;Short-Term Memory;skill acquisition;skills;Special Education;statistics;Techniques;Training;United States National Institutes of Health;Universities

PROJECT_TITLE: Examination of the Role of Executive Function during Reading and Math in Children

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Biobehavioral and Behavioral Sciences Study Section[CHHD-H]


NIH_SPENDING_CATS: Kidney Disease;Nutrition

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE: Inflammation is a common factor among individuals with kidney disease, a major contributor of death in the US. Many aspects of kidney function are linked to the circadian clock, however, its contribution to inflammation is not well known. This project intends to define the role of the circadian clock in activation of renal inflammation, thus identifying novel targets that may be used for treatment to improve the quality of life in individuals with kidney disease.

PI_NAMEs: CRISLIP, GENE RYAN (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Advisory Committees;American;ARNTL gene;Award;Biomedical Research;career;career development;Cell Separation;Cells;Cessation of life;chemokine;Chronic;Chronic Kidney Failure;circadian pacemaker;Clock protein;Communities;conditional knockout;Consumption;cytokine;Data;design;Diet;dietary;Distal;Duct (organ) structure;Education;Environment;Excretory function;experimental study;Female;Fibrosis;Florida;Foundations;Future;Gene Expression;Genes;Goals;high salt diet;Homeostasis;Immune;immune activation;immune cell infiltrate;Immune response;Immune system;immunoregulation;improved;Individual;Inflammation;Inflammatory;inflammatory marker;Injury;Injury to Kidney;insight;Intake;Interleukin-5;Investigation;Kidney;kidney cell;Kidney Diseases;Knockout Mice;Laboratories;Link;Literature;Luciferases;male;Measures;Mediating;Mentors;Mentorship;mouse model;Mus;Nephrons;neutrophil;novel;Nutrient;Organ;Peripheral;Physiological;Play;Potassium;Process;Production;Public Health;Quality of life;recruit;renal damage;Renal function;Research;Research Personnel;response;Role;salt sensitive;Services;single-cell RNA sequencing;skill acquisition;skills;skills training;Sodium;Sodium Chloride;solute;Testing;timeline;Tissue Inhibitor of Metalloproteinase-1;TNF gene;Training;treatment duration;Tubular formation;Universities;Work

PROJECT_TITLE: Renal Circadian Clock Protein Regulation of Immune Activation

STUDY_SECTION: DDK

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


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Black Americans are at higher risk of Alzheimer’s Disease (AD) and earlier cognitive decline than other ethnic groups in the US, with the highest risk in Black women. The proposed study of 2,500 participants from the Black Women’s Health Study (BWHS) will take advantage of the blood samples and data on stressors, illnesses, behaviors and other variables collected in the BWHS. The goal of the proposed study is to ascertain the effect of early life (e.g., childhood violence victimization) and midlife (e.g. experiences of interpersonal racism) stressors together with genetic variants and plasma biomarkers associated with AD on cognitive decline in Black women.

PI_NAMEs: BARNES, LISA L;ROSENBERG, LYNN  (contact)

PROGRAM_OFFICER_NAME: PERCY-LAURRY, ANTOINETTE LOIS

PROJECT_TERMS: Adult;Affect;Age;Agreement;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;Behavior;Behavioral;Biological;Biological Markers;Black American;Black race;black women;Blood;Blood specimen;blood-based biomarker;Body Size;Childhood;Cognition;Cognitive;cognitive change;cognitive testing;cohort;Complex;Data;demographics;Development;Diabetes Mellitus;Diet;Disease;Disease Progression;Disparity;early life stress;Education;effective therapy;Enrollment;Ethnic Population;Exercise;experience;Feasibility Studies;follow-up;Follow-Up Studies;Genetic;Genetic Markers;genetic variant;genome wide association study;genome-wide;Genotype;Glial Fibrillary Acidic Protein;Goals;Healthcare;high risk;Impaired cognition;Joints;Knowledge;Life;Life Cycle Stages;Link;Liquid substance;Literature;Longitudinal cohort;Longitudinal Studies;Low Birth Weight Infant;Measures;Medical History;middle age;novel;older adult;Parents;Participant;participant enrollment;Pattern;Persons;Pharmaceutical Preparations;physical abuse;Pilot Projects;Plasma;Population;Population Study;Populations at Risk;prevent;Prevention;psychologic;public database;Questionnaires;Race;racism;recruit;Reproductive History;Research Personnel;Risk Factors;Role;Sampling;Smoking;SNP array;social;social factors;Social Interaction;socioeconomics;Stress;stressor;Symptoms;Telephone;Testing;Time;Update;Violence;violence victimization;willingness;Woman;Women's Health

PROJECT_TITLE: Lifetime stressors and Alzheimer's Disease genetic variants and biomarkers in relation to cognitive decline among Black Women'sHealth Study participants.

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Hematology;Infectious Diseases;Sepsis;Wound Healing and Care

ORG_CITY: LUBBOCK

ORG_DEPT: SURGERY

ORG_NAME: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER

PHR: Project Narrative Most chronic wound infections are due to the presence of biofilm, which makes the microbes causing the infection exceptionally difficult to kill. In order to combat this healthcare challenge, researchers are pursuing biofilm dispersal agents, which can induce microbes to leave the safety of the protective biofilm and become more susceptible to killing by antibiotics. In this project we will investigate the risk versus reward of using biofilm dispersal as a way to treat wound infections.

PI_NAMEs: RUMBAUGH, KENDRA P (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Adherence;Affect;Anti-microbial susceptibility;Antibiotic susceptibility;Antibiotic Therapy;Antibiotics;antimicrobial;Bacteremia;Bacteria;Basic Science;Biochemical;Blood;Blood Circulation;Blood Vessels;Cells;Cessation of life;chronic infection;chronic wound;clinical biomarkers;Clinical Research;Clinical Trials;combat;cytokine;Data;Debridement;experimental study;global health;Goals;hazard;Healthcare;Immune response;improved;In Vitro;in vivo;indexing;Infection;Investigation;Knowledge;Learning;Mediating;Medical;Methods;Microbe;Microbial Biofilms;model organism;Modeling;Motility;Mus;opportunistic pathogen;Persons;Phenotype;Physiological;Predisposition;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Research Personnel;Rewards;Risk;Safety;Sepsis;Soft Tissue Infections;Testing;therapeutic development;Therapeutic Uses;transcriptome;transcriptomics;Translations;Vascular Permeabilities;Virulence;Virulent;wound;wound bed;Wound Infection;Wound models;wound treatment

PROJECT_TITLE: Bacterial and host response to biofilm dispersal in wound infections

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IMII-U (01)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Clinical Research;Contraception/Reproduction;Dementia;Estrogen;Menopause;Neurodegenerative;Neurosciences;Prevention;Women's Health Research

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Women are more vulnerable to Alzheimer’s disease (AD) than men as they age, and substantial evidence suggests that declining ovarian hormones during menopause contribute to the sex difference in Alzheimer’s risk, as greater lifetime exposure to ovarian hormones (through early puberty and late menopause) predicts reduced vulnerability to AD. Prior research suggests that a reduction in ovarian hormones following menopause may promote AD through a reduction in neural metabolism or disruption of intrinsic network connectivity, but the protective effect of developmental ovarian exposure on these processes is not well understood. In the proposed research, we will test the hypothesis that greater lifetime exposure to ovarian hormones moderates AD-promoting effects of menopause by measuring lifetime ovarian exposure, cognitive function, brain metabolism, network connectivity and brain markers of AD pathology in a single study.

PI_NAMEs: ANDREANO, JOSEPH M (contact);DICKERSON, BRADFORD C

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acceleration;Accounting;Affect;Age;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid;Amyloid deposition;amyloid pathology;Biological Markers;Brain;brain metabolism;Brain region;cell growth;Cerebrum;Characteristics;Cognition;Cognitive;cognitive function;Development;Estradiol;Estrogens;Excision;experience;Exposure to;Foundations;Functional Magnetic Resonance Imaging;Genes;Genetic Predisposition to Disease;Genetic Risk;Genotype;glucose metabolism;Impairment;Individual;Laboratories;Lead;Life;life span;Light;Measures;Mediating;Memory;men;Menarche;Menopausal Status;Menopause;Metabolic;Metabolism;middle age;Midlife women;Modeling;Nerve Degeneration;neural;neural model;neuroimaging;neuron development;Neuronal Injury;Ovarian;Ovarian hormone;Participant;Pathology;Pattern;Performance;Perimenopause;Persons;Play;Positron-Emission Tomography;Postmenopause;Premature Menopause;Premenopause;Process;protective effect;Puberty;Public Health;Research;Research Personnel;resilience;Rest;Risk;Risk Reduction;Role;Sample Size;Sampling;Sex Differences;Symptoms;synaptic function;Synaptic plasticity;Testing;therapy development;Woman

PROJECT_TITLE: Influence of the Menopausal Transition and Lifetime Ovarian Exposure on Neural Metabolism, Connectivity and Pathology


NIH_SPENDING_CATS: Aging;Arthritis;Autoimmune Disease;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Physical Activity;Prevention;Rheumatoid Arthritis

PHR: Project narrative Despite the clear beneficial effects of physical fitness and exercise to improving health during aging, we do not know the best amounts and intensities for optimal lifelong immune health. This project will address gaps in understanding how exercise improves immune system health in older patients with rheumatoid arthritis (RA) by studying 1) how exercise training alters RA immune cell function, immune cell metabolism, and markers of premature immune cell aging; and 2) if a remotely supervised high-intensity exercise training program for older RA patients is safe, acceptable, and feasible. Results from this project will lead to novel treatments to improve inflammation and immune system health during aging.

PI_NAMEs: ANDONIAN, BRIAN JAMES (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Address;Adherence;Aerobic Exercise;Aging;aging mechanism;Biological Aging;Biological Assay;Caloric Restriction;Cardiopulmonary;career;career development;Cell Aging;Cell Physiology;Cell Respiration;Cells;Cellular Metabolic Process;Chronic;chronic inflammatory disease;Clinical;clinical care;clinical translation;combat;Competence;Counseling;cytokine;Data;Development;Development Plans;diet and exercise;Disease;Dose;Educational Intervention;Exercise;exercise intensity;exercise intervention;exercise prescription;exercise program;Exercise Test;exercise training;experience;extracellular;functional decline;Funding;Future;Gene Expression;Geroscience;Goals;hallmarks of aging;Health;human old age (65+);Immune;immune function;immune health;Immune System Diseases;Immunologic Markers;immunoregulation;Impairment;improved;Inflammation;Inflammatory;Inflammatory Arthritis;Intervention;Investigation;Knowledge;Leadership;Life Style;lifestyle intervention;Link;Mentors;Metabolism;Mitochondria;Modeling;Molecular;novel;Obesity;older adult;older patient;Older Population;Organ;parent project;Pathway interactions;Patients;Peripheral;personalized medicine;Persons;Physical Exercise;Physical Fitness;Physiology;Pilot Projects;Play;post intervention;premature;programs;promote resilience;Randomized;Randomized, Controlled Trials;recruit;Regulatory T-Lymphocyte;Research;resilience;response;Rheumatism;Rheumatoid Arthritis;Rheumatology;Role;safety assessment;Sampling;Science;sedentary;senescence;senescence associated secretory phenotype;Skeletal Muscle;skill acquisition;skills;Statistical Data Interpretation;Stress;T-Lymphocyte;Testing;therapeutic target;Training;Training Programs;translational research program;United States National Institutes of Health;Venous blood sampling;Work

PROJECT_TITLE: The Effect of Exercise on T Cell Aging in Rheumatoid Arthritis

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Palliative Care;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PONCE

ORG_NAME: PONCE SCHOOL OF MEDICINE

ORG_STATE: PR

PHR: Project Narrative The goal of this K08 is to prepare the PI (Normarie Torres-Blasco, Ph.D.) to become an independent investigator to address health equity through access to culturally adapted interventions for Hispanic/Latinx patients-caregivers coping with advanced cancer. The research goal of this proposal is to refine and pilot an intervention titled: Caregivers-Patients Support to Latinx Coping with Advanced-Cancer (CASA), five 60-minute telehealth sessions for patient- caregiver dyads. This study aims to use a collaborative intervention planning framework that blends community-based participatory research and dissemination and implementation models to modify and assess the feasibility and acceptability of the CASA intervention.

PI_NAMEs: TORRES-BLASCO, NORMARIE  (contact)

PROGRAM_OFFICER_NAME: WALLACE, TIFFANY A

PROJECT_TERMS: acceptability and feasibility;Address;Advanced Malignant Neoplasm;American Cancer Society;Anxiety;anxiety symptoms;cancer diagnosis;Cancer Intervention;Cancer Patient;career development;Caregivers;Caring;Clinical Psychology;cohesion;Collaborations;collaborative approach;Communication;Communities;community based participatory research;Conflict (Psychology);coping;cultural values;culturally appropriate intervention;Data;design;Diagnosis;Disparate;Dissemination and Implementation;Doctor of Philosophy;doctoral student;effectiveness testing;effectiveness/implementation study;efficacy testing;experience;Face;Family;Feasibility Studies;feasibility testing;Feeling hopeless;Fellowship;Foundations;Funding;Future;Goals;Grant;Health;Health Disparities Research;health disparity;health equity;Health Sciences;Hispanic;implementation evaluation;implementation research;implementation science;Improve Access;improved;innovation;Institute of Medicine (U.S.);Intervention;Investigation;Language;Latinx;Latinx population;Learning;Malignant Neoplasms;member;Mental Depression;Methods;minority healthcare;Modeling;Modification;National Cancer Institute;Not Hispanic or Latino;novel;Outcome;Palliative Care;Patients;Personal Satisfaction;pilot test;Population;pre-doctoral;preference;Procedures;Provider;Psychiatric Social Work;psychological distress;psychosocial;Psychotherapy;Publishing;Puerto Rico;Quality of life;Randomized, Controlled Trials;Recommendation;reduce symptoms;Reporting;Research;Research Institute;Research Personnel;Resources;response;Risk;Series;service gap;Services;Site;skills;skills training;Source;Spirituality;telehealth;Training;underserved community;Universities;Vulnerable Populations;Writing

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


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

ORG_CITY: Newark

ORG_DEPT: PHARMACOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Narrative: Hypoglycemia unawareness is a serious complication of diabetes resulting from recurrent hypoglycemia (RH) during intensive-insulin therapy; however little is known about the underlying mechanism due to lack of an animal model. We have established the first mouse model for hypoglycemia awareness/unawareness and our data suggest that the anti-narcolepsy drug modafinil may restore both hypoglycemia awareness and impaired glucose sensing by perifornical hypothalamus orexin glucose-inhibited (GI) neurons. This proposal seeks to define the central pathways which control the awareness of hypoglycemia and how modafinil corrects them after RH.

PI_NAMEs: ROITMAN, MITCHELL F;ROUTH, VANESSA H (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TITLE: Orexin glucose-inhibited neurons and hypoglycemia unawareness

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biotechnology;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Physical Activity;Physical Rehabilitation;Prevention;Rehabilitation

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on elucidating the molecular mechanisms underlying the protective effect of physical activity (PA) on cardiovascular structure and function, functional capacity, and heart failure (HF) development in older adults, who are at greater risk for HF-related morbidity and mortality, with the use of high throughput proteomic profiling. Identifying promising protein candidates contributing to the benefits of PA has the potential to inform protective doses of PA, which may strengthen national recommendations for PA for the prevention of HF, and to provide new targets for therapeutic intervention for HF.

PI_NAMEs: HEGDE, SHEILA  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Activities of Daily Living;adjudication;Adult;Affect;Age;age effect;age related;age related changes;aging biomarker;aptamer;ATF6 gene;Atherosclerosis Risk in Communities;Biological;Biological Markers;Cardiac;Cardiac rehabilitation;Cardiopulmonary;cardiorespiratory fitness;Cardiovascular Physiology;Cardiovascular system;career;Clinic;Clinical Investigator;Clinical Trials;Clinical Trials Design;cohort;Collaborations;Data;Data Analyses;Data Science;Dedications;design;Development;Dose;Echocardiography;EFRAC;Event;Exclusion;Exercise;exercise intervention;Exercise Test;exercise training;experience;Foundations;Funding;Future;Genetic;genomic data;Goals;Grant;Heart failure;heart failure with reduced ejection fraction;heart function;high dimensionality;high risk;Hospitals;imager;Impairment;improved;Individual;insight;Institution;interest;Intervention;Intervention Studies;K-Series Research Career Programs;late life;Leadership;Learning;Left;Left Ventricular Ejection Fraction;Leisures;Life Style Modification;Link;Longitudinal cohort study;Measures;meetings;Mendelian randomization;Mentors;Methods;Molecular;Morbidity - disease rate;mortality;Multicenter Studies;multidimensional data;multidisciplinary;National Heart, Lung, and Blood Institute;new therapeutic target;novel;Observation in research;older adult;Outcome;Pathway interactions;Patient Recruitments;pharmacologic;Physical activity;Plasma;Plasma Proteins;preservation;prevent;Prevention;preventive intervention;Professional Organizations;programs;prospective;protective effect;Proteins;proteomic signature;Proteomics;Public Health;Quality of life;Randomized;Recommendation;Research;Research Design;Research Personnel;Risk;sedentary;skills;STC1 gene;Structure;Therapeutic Intervention;Time;Training;Ventricular;VO2max;Woman;working group

PROJECT_TITLE: Reducing Heart Failure Risk in Late-Life With Physical Activity: Impact on Cardiac Structure and Function and Proteomic Signatures

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR (OA)]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Nutrition

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Mitochondrial specific phospholipid cardiolipin plays many crucial roles in bioenergetics. In the heart, linoleic acid is specifically concentrated in cardiolipin, likely linking to proper cardiac function. This study aims to determine the molecular basis underlying the mechanisms to specifically regulate the cardiac cardiolipin, which will expand our fundamental understanding of cardiac bioenergetics, a major determinant of cardiac health and disease.

PI_NAMEs: SENOO, NANAMI  (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Academia;Achievement;Acylation;Automobile Driving;Award;Bioenergetics;Biology;Cardiac;Cardiac health;Cardiac Myocytes;Cardiolipins;Cardiomyopathies;career;career development;Cells;Common Ventricle;Congestive Heart Failure;Crowding;Data;data integration;Development Plans;Diabetes Mellitus;Drosophila genus;Endoplasmic Reticulum;Energy Metabolism;Environment;Enzymes;Equilibrium;Fatty Acids;genetic approach;Genetic Diseases;Goals;Heart;Heart Diseases;Heart failure;heart function;induced pluripotent stem cell derived cardiomyocytes;Inner mitochondrial membrane;Institution;Ischemia;knock-down;Knowledge;Link;Linoleic Acids;lipid metabolism;Lipids;Mentorship;Metabolic;Metabolism;Mitochondria;mitochondrial dysfunction;Mitochondrial Membrane Protein;Modeling;Molecular;Muscle;novel;Oleic Acids;Organ;Organelles;Oxidative Phosphorylation;Pathway interactions;pharmacologic;Phospholipids;Physiological;Play;preference;Production;Regulation;Research;Research Personnel;Respiration;Role;Shapes;Site;skills;Solid;Source;Specificity;Subcellular Fractions;System;Systems Integration;Testing;theories;Tissues;Training

PROJECT_TITLE: Molecular basis to regulate the cardiac-specific form of mitochondrial phospholipid cardiolipin

STUDY_SECTION: MTI

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


NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Data Science;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention

PHR: PROJECT NARRATIVE Preventive treatment (e.g., statins) can reduce the risk of cardiovascular disease but are most effective when targeted to high-risk individuals. New artificial intelligence techniques may predict risk of heart attack and stroke from medical imaging. The proposed study will develop and test whether artificial intelligence can identify persons at high-risk for future cardiovascular events based on chest imaging and assess whether these predictions are better than existing risk scores.

PI_NAMEs: RAGHU, VINEET  (contact)

PROGRAM_OFFICER_NAME: PRICE, CANDICE

PROJECT_TERMS: 3-Dimensional;Address;Adipose tissue;Ambulatory Care;Aorta;Area;arm;Arteries;Artificial Intelligence;Atherosclerosis;Automobile Driving;biobank;Biological Aging;blood lipid;Blood Pressure;Calcium;Calibration;Cardiovascular Diseases;cardiovascular disorder epidemiology;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular imaging;Cardiovascular system;career;career development;CDKN2A gene;Cessation of life;chest computed tomography;Chest imaging;Cholesterol;Chronic Disease;Clinical;cohort;Collaborations;Communities;comorbidity;Complement;computer scientist;cone-beam computed tomography;Coronary;Coronary Arteriosclerosis;Coronary artery;coronary artery calcium;Data;Decision Making;deep learning;deep learning model;demographics;Development;Diabetes Mellitus;Diameter;Discrimination;Disease;Disease Pathway;diverse data;DNA Methylation;Doctor of Philosophy;Early Diagnosis;Ensure;Epidemiology;epigenetic clock;Epigenetic Process;Equation;Etiology;Event;experience;follow-up;Framingham Heart Study;Functional disorder;Future;General Hospitals;Genetic;Genetic Techniques;genomic locus;Genomics;Geriatrics;Germ-Line Mutation;Goals;Grant;Guidelines;hands on research;hazard;Heart;Hematopoiesis;high risk;high risk population;IL6 gene;Image;imaging modality;improved;indexing;Individual;innovation;insight;instructor;Jackson Heart Study;large datasets;LDL Cholesterol Lipoproteins;Learning;Length;Leukocytes;Lung;Malignant neoplasm of lung;Massachusetts;Measures;Medical Imaging;Medical Research;medical schools;meetings;Mentorship;Methods;Modeling;Molecular;mortality;multiple omics;Myocardial Infarction;older adult;Outcome;Pathway interactions;Patients;Peripheral;Persons;Phenotype;Physicians;Populations at Risk;Preparation;prevent;Prevention;Preventive care;preventive intervention;Preventive treatment;primary outcome;Primary Prevention;Public Health Schools;radiologist;Radiology Specialty;Recommendation;Research;research faculty;Research Personnel;Research Training;Resolution;responsible research conduct;Risk;Risk Assessment;Risk Estimate;Risk Factors;risk prediction;Risk Reduction;ROC Curve;Roentgen Rays;Scientist;screening;Single Nucleotide Polymorphism;skills;Stroke;subcutaneous;Techniques;telomere;Testing;Thoracic Radiography;tool;Training;uptake;Variant;Visceral;Writing;X-Ray Computed Tomography

PROJECT_TITLE: Deep learning to assess cardiovascular disease risk from chest imaging

STUDY_SECTION: MCBS

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


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: RELEVANCE: Colorectal cancers occur in up to 8% of Veterans, in whom there is a critical need for precision oncology tools to select appropriate components of a multimodal treatment strategy for rectal cancers. Veteran rectal cancer patients could gain significant quality-of-life benefits from being selected for non-operative management due to their increased age as well as impact of surgical co-morbidities. Veteran rectal cancer patients have also specifically shown a survival benefit to targeted administration of adjuvant chemotherapy. In this VA Merit Award, we will build on our initial exciting results to validate novel computational image Rectal Response Classifier (ciRRC) tools that leverage routine MRI scans to (i) identify rectal cancer patients who can be safely recommended non-operative management as they achieved pathologic complete response after neoadjuvant therapy, as well as (ii) select high-risk rectal cancer patients who will gain added benefit from targeted chemotherapy; towards improving patient outcomes and survival in Veteran rectal cancer patients.

PI_NAMEs: VISWANATH, SATISH EASWAR (contact)

PROJECT_TERMS: Adjuvant Chemotherapy;Adjuvant Therapy;Aftercare;Age;Agreement;Artificial Intelligence;Award;Biological;biomarker validation;Blood Vessels;BRAF gene;cancer diagnosis;cancer imaging;Cancer Patient;chemoradiation;chemotherapy;Chemotherapy and/or radiation;Clinical;Clinical Trials;clinically actionable;cohort;colon cancer patients;Colorectal Cancer;combat;Combined Modality Therapy;comorbidity;Computers;cost;Data;Descriptor;Desmoplastic;Development;Diagnostic;digital;Disease;Distant Metastasis;Early Diagnosis;Endoscopy;Ensure;Evaluation;Extravasation;Fecal Incontinence;Financial Hardship;General Population;Graph;Habitats;Heterogeneity;high risk;Histopathology;Image;Image Analysis;improved;In complete remission;in vivo;Indiana;Injury;innovation;Institution;Invaded;KRAS2 gene;Lesion;Life;Lymph;Lymphatic;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Michigan;Midwestern United States;Military Personnel;military veteran;Modeling;Morphology;morphometry;MRI Scans;mutant;Mutation;mutational status;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;novel;NRAS gene;Ohio;Operative Surgical Procedures;Organ Preservation;Ostomy;Outcome;Pathologic;patient subsets;Patient-Focused Outcomes;Patients;Pelvis;perineural;personalized medicine;Phenotype;Physiological;Population;precision oncology;predictive marker;Predictive Value;Protocols documentation;psychological stressor;Quality of life;quantitative imaging;Radiation;Radiation Fibrosis;radiation resistance;radiomics;Reaction;Reader;Recommendation;Rectal Cancer;Rectal Neoplasms;Rectum;research clinical testing;Residual Neoplasm;response;risk minimization;Sensitivity and Specificity;Sepsis;Serum;Specimen;Structure;success;support tools;Survival Rate;Techniques;Therapeutic;therapy resistant;Tissues;tool;treatment response;treatment strategy;Triage;tumor;Tumor Cell Invasion;Validation;Veterans;Visual

PROJECT_TITLE: Artificial Intelligence Imaging Predictors for Rectal Cancer Management

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCC-S (01)]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Bipolar Disorder;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Mental Health;Mental Illness;Prevention;Serious Mental Illness;Substance Misuse;Tobacco;Tobacco Smoke and Health

PHR: PROJECT NARRATIVE Bipolar disorder is associated with high rates of tobacco use (cigarette smoking) and, currently, there is a lack of effective treatments for addressing tobacco use in this population. This study will evaluate a behavioral intervention called episodic future thinking, which encourages people to actively visualize future, positive events that they think will be benefited by quitting smoking, that has the potential to intervene on some of the cognitive processes that lead to smoking behavior in bipolar disorder. This study may contribute to a new behavioral intervention that can be applied in clinical practice to target the cognitive processes that contribute to smoking in bipolar disorder and to encourage people with bipolar disorder to participate in smoking cessation treatment.

PI_NAMEs: GOLD, ALEXANDRA KATE (contact)

PROGRAM_OFFICER_NAME: LAO, GUIFANG

PROJECT_TERMS: acceptability and feasibility;addiction;Address;Adult;arm;Attention;Auditory;Behavior Therapy;Behavioral;Bipolar Disorder;Cardiovascular system;career;Cigarette;cigarette craving;cigarette smoke;cigarette smoking;Clinical;clinical practice;Clinical Research;Clinical Trials;Cognitive;cognitive process;comorbidity;Consumption;Counseling;Cues;Development;discounting;effective therapy;Event;Feedback;Future;General Population;Goals;Health behavior;improved;Individual;Intervention;intervention refinement;Link;Manuals;Mental disorders;Mentors;Methodology;mortality;Motivation;open label;Outcome;Participant;Pathway interactions;Persons;Phase;Population;Process;Psyche structure;psychosocial;Randomized;randomized trial;Reporting;Research;Research Project Grants;retention rate;Rewards;satisfaction;Scientist;Self Efficacy;severe mental illness;simulation;Smoke;Smoking;smoking abstinence;Smoking Behavior;smoking cessation;Smoking Cessation Intervention;Statistical Models;Substance Use Disorder;suicidal risk;Testing;Thinking;Time;Tobacco use;Tobacco Use Disorder;Training;Training Activity;Training Programs;verbal;Visual;Visualization

PROJECT_TITLE: Future self: An episodic future thinking intervention for comorbid tobacco use disorder and bipolar disorder

STUDY_SECTION: IPTA

STUDY_SECTION_NAME: Interventions to Prevent and Treat Addictions Study Section[IPTA]


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: The overall goal of the Colorado StARR Program (CSP) is to recruit, train, and retain outstanding resident-investigators focused on translational research in heart, lung, and blood disorders. This career development training will be achieved through seamless integration with our ACGME-accredited Medicine, Pediatric, and Surgery housestaff training programs, a structured milestone-driven training program that includes individualized career development plans, pairing our resident-investigators with outstanding, dedicated mentors with extensive disease-specific research expertise and a wide array of cutting-edge approaches to research, and providing appropriate oversight of the mentor-mentee relationship.

PI_NAMEs: ABMAN, STEVEN HERBERT;BUTTRICK, PETER N.;SCHWARTZ, DAVID ALBERT (contact)

PROGRAM_OFFICER_NAME: SCHOPFER, DAVID WESLEY

PROJECT_TERMS: academic program;Accreditation;Area;Caliber;career;career development;Career Mobility;Childhood;Clinical;Collaborations;Colorado;Communities;Community Physician;Dedications;design;Development;Development Plans;Eligibility Determination;Ensure;Environment;Ethics;experience;Faculty;falls;Feeling;Fellowship;formal learning;Fostering;Funding;Goals;Growth;Heart Diseases;Hematological Disease;high standard;House Staffs;improved;interest;Knowledge;Leadership;Learning;Lung Diseases;medical schools;Medicine;Mentors;Mentorship;Methodology;Monitor;next generation;Operative Surgical Procedures;Pediatrics;Physicians;Positioning Attribute;Program Development;programs;Records;recruit;Research;research facility;Research Methodology;Research Personnel;Research Training;role model;Science;Scientist;Site;skill acquisition;skills;social;Structure;Student Persistence;Students;Surveys;synergism;Technology;Textiles;Training;training opportunity;Training Programs;Translational Research;Universities;Vision;Widespread Disease

PROJECT_TITLE: Colorado StARR Program (CSP)

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-I (O2)]


NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Hematology;Orphan Drug;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Significant growth in treatment options for patients with acute myeloid leukemia (AML) has increased the importance of understanding patients’ values and preferences to determine appropriate therapy. This project aims to evaluate the feasibility of implementing a novel patient decision support tool to improve treatment decision-making for older adults with AML. This tool uses best-worst scaling, an innovative, yet robust method to elicit patient values, which may be widely applicable to other treatment settings across oncology.

PI_NAMEs: RICHARDSON, DANIEL R (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;Adult;Advocate;aged;Award;Back;cancer care;care delivery;career;Caregivers;Client;Clinical;clinical practice;Collaborations;Consolidated Framework for Implementation Research;Data;Decision Making;design;Development;Diagnosis;digital;Doctor of Philosophy;drug development;effectiveness evaluation;efficacy evaluation;Equipoise;experience;Future;Goals;group intervention;Growth;Hospitals;implementation determinants;implementation evaluation;implementation framework;implementation measures;implementation science;implementation strategy;improved;innovation;Intervention;Interview;K-Series Research Career Programs;leukemia;leukemia treatment;Maps;Measures;Mentors;Mentorship;Methodology;Methods;Newly Diagnosed;novel;novel therapeutics;older adult;older patient;Oncologist;Oncology;Outcome;Outcome Measure;Participant;Patient Care;patient oriented;Patients;personalized medicine;pilot trial;preference;primary outcome;Process;Quality of life;Randomized;Recommendation;recruit;Reporting;Research;Research Personnel;Resources;response;Risk;Services;shared decision making;success;support tools;Surveys;System;Theoretical Domains framework;Time;tool;Training;treatment as usual;trial design;Work

PROJECT_TITLE: Developing a Values Elicitation Tool to Improve Treatment Decision-Making in Acute Myeloid Leukemia


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

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project narrative: The cause of AD is not well understood and lacks an effective treatment. We will test the hypotheses that AD may be a pathological disorder driven by activation of a distinct microglia subset/lineage (~5% of total), resulting in neuroinflammation, amyloid deposits and cognitive decline in animal models, which will be validated using well-defined post-mortem brain tissues from AD patients. These studies will provide new insight into the pathogenic mechanisms that contribute to AD and may lead to the discovery of novel diagnostic biomarkers and new therapeutic approaches to this disease and perhaps other neurodegenerative diseases.

PI_NAMEs: CANTOR, HARVEY  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: 3-Dimensional;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Animal Model;Antibody Therapy;Autopsy;Brain;brain tissue;Clinical;cognitive function;Collaborations;Coupled;Data;Deposition;Development;diagnostic biomarker;Digestion;Disabled Persons;Disease;Disease associated microglia;Disease Progression;effective therapy;Engineering;Engraftment;Foundations;Genes;Genetic;Goals;Human;human disease;human induced pluripotent stem cells;Impaired cognition;improved;Inflammasome;Inflammatory;Inflammatory Response;insight;Integrin alphaXbeta2;Integrins;ITGAX gene;ITGB2 gene;Letters;Ligation;Mediating;Microglia;Modeling;Molecular;Monoclonal Antibodies;mouse model;Mouse Strains;Mus;Neurites;Neurodegenerative Disorders;neuroinflammation;neuropathology;novel;novel diagnostics;novel therapeutic intervention;Organoids;osteopontin;Pathogenicity;Pathologic;Pathology;Pathway interactions;Phagocytosis;Phenotype;pluripotent stem cell differentiation;preclinical study;Principal Investigator;Production;programs;receptor;Regulation;Regulatory Pathway;Reporter;Reporting;response;Senile Plaques;side effect;single-cell RNA sequencing;targeted treatment;tau Proteins;Tauopathies;Testing;Therapeutic;therapeutic development;Therapeutic Effect;therapeutic evaluation;therapeutic target;TNF gene;TREM2 gene;uptake;Writing

PROJECT_TITLE: Contribution of a novel OPN-producing CD11c+ microglial subset to AD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-Z (55)]


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

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: PROJECT NARRATIVE Decline in proteostasis is a defining feature of aging and Alzheimer’s disease (AD) but the signaling pathways responsible for protein quality control are only in part known. We have recently found an important role for the disaccharide maltose in preserving proteostasis in the central nervous system during aging. In this application, we propose to investigate the mechanisms responsible for the effects of maltose-induced signaling on improving proteostasis, which may help design effective therapies to preserve and/or reinstate proteostasis in AD patients.

PI_NAMEs: DEMONTIS, FABIO  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: age related;age related neurodegeneration;Aging;aging brain;Agreement;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Amylases;Behavioral Assay;Biochemical;Brain;Cell Compartmentation;Cell Nucleus;Central Nervous System;Chemicals;Cognitive;combat;Cytoplasm;design;Detergents;Disaccharides;Drosophila genus;effective therapy;Enzymes;functional decline;Genetic Transcription;Heat shock proteins;Homeostasis;Human;improved;Intervention;knock-down;Knowledge;Luciferases;Maltose;MAPT gene;Mediator;Metabolism;Mitochondria;Molecular Chaperones;Mutation;Nerve Degeneration;Neuroglia;Neurons;neurotoxicity;novel;Organelles;Organism;Organoids;overexpression;Pathogenesis;Patients;preservation;prevent;Property;Proteins;proteostasis;proteostasis loss;Quality Control;Regulation;Retina;RNA Interference;Role;sensor;Signal Induction;Signal Pathway;Signal Transduction;stem;System;tau aggregation;tau interaction;tau mutation;tau Proteins;Tauopathies;Testing;thermal stress;Tissues;tool;transcription factor;Transgenic Organisms

PROJECT_TITLE: REGULATION OF PROTEOSTASIS AND TAUOPATHY BY MALTOSE-INDUCED SIGNALING

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE This project will develop a voice assistant (VA) to improve the quality of life and wellbeing of persons living with dementia (PLwDs) and their care partners. Specifically, the VA will deliver customized and tailored cognitive stimulation therapy (CST) at scale — one of the most effective interventions for maintaining cognitive functioning and wellbeing of PLwDs. Given the wide adoption of VAs, this project has the potential to positively impact a large population of PLwDs and their care partners including those living in remote and rural areas.

PI_NAMEs: ABDULLAH, SAEED  (contact)

PROGRAM_OFFICER_NAME: RICE, ELISE

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adopted;Adoption;Adult;Alzheimer's Disease;Aptitude;Caring;clinical efficacy;Cognition;Cognitive;cognitive function;Communities;cost;Data;Dementia;dementia care;design;Devices;Ecosystem;effective intervention;eHealth;empowerment;Ensure;evidence base;experience;Focus Groups;formative assessment;Goals;Government;Group Interviews;health data;Health Professional;health training;Home;Home environment;human old age (65+);implementation evaluation;implementation process;improved;Individual;informal care;interest;International;Intervention;Intuition;Lead;Manuals;Measurement;Methods;Mind;Modeling;Natural Language Processing;older adult;Older Population;Outcome;Participant;Pathway interactions;Personal Satisfaction;Persons;Pilot Projects;Population;privacy preservation;Protocols documentation;Quality of life;Randomized, Controlled Trials;Recommendation;remote location;Research;Resources;Role;rural area;smart speaker;speech recognition;Strategic Planning;successful intervention;Technology;Therapeutic Intervention;Time;United Kingdom;United States;uptake;usability;Vision;Visual;Voice;Vulnerable Populations;Work

PROJECT_TITLE: Voice Assistant to Provide Cognitive Stimulation Therapy at Scale

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-F (90)]


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

ORG_CITY: EAST LANSING

ORG_NAME: HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES

ORG_STATE: MI

PHR: PROJECT NARRATIVE Multiple organ dysfunction syndromes (MODS) frequently occur in pediatric patients and severe MODS patients needed Veno-Arterial extracorporeal membrane oxygenation support (ECMO) (label as ECMO patients) as a palliating maneuver to recover their cardiopulmonary function. The major knowledge gap exists regarding the cellular and molecular mechanisms underlying MODS deterioration for their advanced life support. The proposed work will provide a comprehensive overview of cellular and molecular mechanism associated with deterioration of MODS patients who may require ECMO support, which will be applicable for early diagnostic purposes.

PI_NAMEs: SHANKAR, RAMA  (contact)

PROGRAM_OFFICER_NAME: DIXON, CINNAMON ANNE

PROJECT_TERMS: Attention;Automobile Driving;Award;Big Data;big-data science;Bioinformatics;Biological Markers;Biomedical Research;Blood specimen;California;Cardiopulmonary;Cells;Childhood;Chromatin;clinical biomarkers;Computational Biology;Data;Data Set;Death Rate;Deterioration;Development;Diagnosis;Diagnostic;diagnostic biomarker;Disease;Disease Progression;early detection biomarkers;Early Diagnosis;epigenetic variation;experience;experimental study;Extracorporeal Membrane Oxygenation;Functional disorder;Genes;Genetic Markers;Goals;graph neural network;Health;Health system;Heterogeneity;high risk;Histones;Hospitals;Immune;Immune response;Immune system;Immune System Diseases;Immunology;Infection;Inflammatory Response;innovation;insight;Intensive Care Units;Intervention;Knowledge;Label;Lead;Life;Machine Learning;machine learning method;Malignant Neoplasms;Mentors;Methods;Michigan;Molecular;molecular marker;Multiomic Data;multiple omics;Multiple Organ Failure;neutrophil;novel;novel diagnostics;novel therapeutic intervention;novel therapeutics;Outcome;palliate;Pathology;Patients;pediatric patients;Pediatrics;Phase;Prognostic Marker;Program Accessibility;progression risk;Rare Diseases;Recovery;Regulator Genes;Regulatory Element;Research;Sample Size;Signal Pathway;single cell ATAC-seq;single-cell RNA sequencing;statistics;Survival Rate;Techniques;Therapeutic;Time;transcriptome sequencing;Translational Research;Trauma;Universities;Variant;Work

PROJECT_TITLE: Single cell multi-omics approaches in identifying driving cells and genes in pediatric MODS patients requiring ECMO support

STUDY_SECTION_NAME: Pediatrics Study Section[CHHD-A]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Cerebrovascular;Clinical Research;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_NAME: STATE COLLEGE OF OPTOMETRY

ORG_STATE: NY

PHR: Project Narrative Myopia and glaucoma pose significant public health concerns - half the world’s population is projected to be myopic by 2050 and glaucoma is estimated to affect more than 120 million people worldwide by 2040, which in turn will increase the global prevalence of myopic glaucoma significantly. Evidence shows that myopic patients are at higher risk of glaucomatous degeneration, however the mechanisms behind the myopia-glaucoma association remain unknown. The proposed research aims to identify the effect of myopia on three retinal neurovascular cell types crucial for ganglion cell survival, and their relationship with glaucoma susceptibility, in a novel non-human primate model of myopia that will be subsequently induced with glaucoma.

PI_NAMEs: LIN, CAROL  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Affect;Anatomy;Animal Model;Architecture;Astrocytes;attenuation;Axon;Blindness;Blood capillaries;Blood flow;Blood Vessels;career development;Cell Density;Cell Physiology;Cell Survival;cell type;Cells;Cellular Structures;Clinical;college;Data;density;Development;diagnostic biomarker;Disease;Disease Progression;Doctor of Philosophy;Electrophysiology (science);Elements;Exhibits;experience;Experimental Models;Extracellular Matrix;Eye;Eye diseases;ganglion cell;Glaucoma;Goals;Growth;Health;high risk;Human;Incidence;Injury;innovation;instructor;Link;Longitudinal Studies;Macular degeneration;Maintenance;Mechanical Stress;Mentors;Metabolism;Methodology;Modeling;multidisciplinary;Myopia;Nature;Neuroglia;Neurons;neurovascular;neurovascular unit;nonhuman primate;novel;optic nerve disorder;Optometry;Outcome;Oxygen Consumption;Papillary;Pathology;Patients;Persons;Physiological;Physiology;Population;Predisposition;Prevalence;prevent;Prevention;Program Development;programs;Public Health;Radial;Research;Research Personnel;Research Training;Residencies;response;Retina;Retinal Ganglion Cells;Risk Factors;skills;stressor;Stretching;Structure;Thinness;Time;Translational Research;Vision

PROJECT_TITLE: The Effect of Myopia on Retinal Ganglion Cells, Astrocytes and Vasculature, and its Relationsip to Glaucoma Susceptibility

STUDY_SECTION_NAME: Special Emphasis Panel[ZEY1 VSN (04)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Neurosciences

PHR: Project Narrative Cognitive dysfunction is a highly prevalent feature of depression that is resistant to existing treatments and predictive of higher relapse rates, worse social and occupational functioning as well as elevated risk for neurodegenerative disorders. This proposal is a mechanistic randomized controlled trial that integrates advances in cognitive neuroscience to determine whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype. This research has the potential to identify an inflammatory mechanism underpinning a particularly debilitating feature of depression and to offer proof-of-concept for anti- inflammatory interventions as adjunctive treatment for cognitive dysfunction in depression.

PI_NAMEs: MAC GIOLLABHUI, NAOISE  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Acceleration;Acute;Address;advanced analytics;Affect;Ambulatory Care Facilities;antagonist;anti-depressive agents;Anti-Inflammatory Agents;Antiinflammatory Effect;Area;Assessment tool;Behavior;Biological;Biological Markers;Blood;C-reactive protein;career;case-based;Clinical;Clinical Research;Clinical Trials;Cognition;Cognitive;Cognitive deficits;cognitive function;cognitive neuroscience;cognitive performance;cognitive testing;Data;debilitating symptom;dementia risk;Depressed mood;depressed patient;depressive symptoms;Diffusion;Environment;Etiology;evidence base;Executive Dysfunction;executive function;Exhibits;experimental study;follow-up;Functional impairment;General Hospitals;Genetic Research;Goals;Immune;Immune signaling;Immunology;Impaired cognition;Impairment;improved;indexing;Individual;Inflammation;Inflammatory;infliximab;Infusion procedures;inhibitor;innovation;Intervention;Intravenous infusion procedures;Knowledge;Link;Massachusetts;Measures;Mediating;Mental Depression;Mentorship;Methodology;Methods;Modeling;Moods;Motivation;Motor;National Institute of Mental Health;Nature;neural circuit;Neurodegenerative Disorders;novel;Observational Study;Occupational;Outcome;Outpatients;Participant;Pathway interactions;Performance;Persons;Phenotype;Physiology;Placebos;Play;poor sleep;Process;prospective;Psychiatry;Randomized;Randomized, Controlled Trials;Reaction Time;recruit;Relapse;remote assessment;Research;Research Design;Research Domain Criteria;Resistance;Resources;response;Risk;Role;Sampling;Scientist;Signal Transduction;social;Specific qualifier value;Speed;Stress;Testing;theories;Time;TNF gene;TNFR-Fc fusion protein;tool;Training;treatment response

PROJECT_TITLE: The role of inflammation in cognitive dysfunction in acute depression as determined by experimental inhibition of tumor necrosis factor-alphasignaling in a randomized controlled trial.

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: Multiple sclerosis (MS) afflicts nearly 50,000 veterans, and the military population is at special risk to develop MS compared to civilians. Despite recent medical advances, there remains a substantial unmet need for additional effective MS treatments. Injury to the brain and spinal cord in MS is caused by autoimmune inflammatory T cells that enter the central nervous system and attack the myelin sheath. T cell activity is regulated by lipid and vitamin A metabolism. Our project focuses on the role of a metabolic enzyme we recently discovered to be expressed in T cells. Inhibiting this enzyme protects animals from developing MS- like symptoms. A detailed understanding of the molecular and cellular mechanisms of immune suppression by targeting this metabolic enzyme may lead to new approaches to treat or prevent MS and possibly other autoimmune or inflammatory disorders. If successful, this project has the potential to substantially reduce the impact of MS on veterans, their families, and the American public.

PI_NAMEs: ZABEL, BRIAN A. (contact)

PROJECT_TERMS: Acyl Coenzyme A;Acyltransferase;Affect;All-Trans-Retinol;American;Animal Model;Animals;antagonist;Antigens;Autoimmune;autoreactive T cell;autoreactivity;Biology;Blood;Brain;CCR6 gene;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Cellular biology;Central Nervous System;central nervous system demyelinating disorder;chemokine receptor;Clinical;Clinical Trials;cohort;combat;Data;Demyelinating Diseases;Demyelinations;diacylglycerol O-acyltransferase;differential expression;Diglycerides;Disease;Disease Progression;Disease remission;drug development;Enzyme Inhibition;Enzymes;Esters;Experimental Autoimmune Encephalomyelitis;Family;FOXP3 gene;Frequencies;Gene Expression Profile;Genetic;Goals;Health;Heterogeneity;Histologic;Human;Immune;immune checkpoint;Immunosuppression;improved;In Vitro;in vivo;Incidence;individual patient;Infiltration;Inflammation;Inflammatory;inhibitor;Injury;insight;Knockout Mice;Lesion;Leukocytes;Lipid A;Lipids;Medical;Metabolic;Metabolic Pathway;Metabolism;Military Personnel;Modeling;Molecular;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Mus;Myelin;Myelin Sheath;neutrophil;novel;novel strategies;novel therapeutics;Obesity associated disease;obesity treatment;Pathogenesis;Pathogenicity;Pathology;patient response;Persons;Pharmaceutical Preparations;Phase;Play;Population;pre-clinical;Predisposition;prevent;Process;programs;Proliferating;promoter;protective effect;Publishing;receptor;receptor expression;Regulatory Pathway;Regulatory T-Lymphocyte;Relapse;Research Project Grants;Retinoids;Risk;Role;S100A8 gene;selective expression;side effect;small molecule;Spinal Cord;Symptoms;T cell differentiation;T-Cell Homing Receptors;T-Cell Proliferation;T-Lymphocyte;Tamoxifen;Testing;Therapeutic;Therapeutic Uses;tissue injury;Toxic effect;trafficking;transcriptomic profiling;translational potential;Triglycerides;Veterans;Vitamin A

PROJECT_TITLE: New Approaches to Combat CNS Inflammation: Targeting a Metabolic Enzyme in Demyelinating Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURB-H (01)]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_CITY: PISCATAWAY

ORG_DEPT: BIOMEDICAL ENGINEERING

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

PHR: PROJECT NARRATIVE In this exploratory, collaborative research proposal, we investigate an innovative approach to abrogate the neuroinflammatory crosstalk that promotes Alzheimer’s disease (AD) progression using state-of-the-art technologies of nanoparticles, stem cells, and brain-like mimetic human organoids. This proposal aims to test therapeutic nanotechnology based on a series of amphiphilic macromolecule for their potential amelioration of neuroinflammation and inhibition of the progression of AD. This project is relevant to public health as it aims to suppress AD progression and inhibit neurodegeneration associated with aging disorders.

PI_NAMEs: GEBRIL, HODA ;MOGHE, PRABHAS V (contact);UHRICH, KATHRYN ELIZABETH

PROGRAM_OFFICER_NAME: RUNKO, ALEXANDER PETER

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Abeta clearance;Acceleration;Address;aging related disease;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapy;amphiphilicity;Amyloid beta-Protein;amyloid fibril formation;Anti-Inflammatory Agents;Antiinflammatory Effect;Astrocytes;Attenuated;Binding;Biochemical;Biological Assay;Brain;brain parenchyma;burden of illness;California;Cause of Death;CD36 gene;Cell Line;cell type;Clinical;clinical phenotype;Coculture Techniques;Communication;Communities;Complex;cytokine;Data;Death Rate;Dementia;Deposition;design;Deterioration;Disease;Disease Progression;Elderly;Exhibits;extracellular vesicles;Genes;glial activation;Growth Factor;Homeostasis;Human;In Vitro;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inflammation Mediators;Inflammatory;inflammatory marker;innovation;Interruption;Lead;Libraries;macromolecule;Mediating;Mediator;Memory Loss;Microglia;mimetics;Modeling;monomer;multimodality;Mus;Mutation;nanoparticle;Nanotechnology;Nerve Degeneration;Neurites;Neurofibrillary Tangles;Neuroglia;neuroinflammation;neuron loss;neuronal circuitry;neuronal survival;Neurons;neuroprotection;neurotoxic;neurotoxicity;Neurotransmitters;Organoids;Outcome;Pathogenesis;Pathologic;Pathology;Pharmaceutical Preparations;Phenotype;Physiological;Play;Population;prevent;Prevention;Production;progressive neurodegeneration;Property;Public Health;Reactive Oxygen Species;receptor;receptor binding;reduce symptoms;Reporting;Repression;Research Proposals;Role;scavenger receptor;Science;Senile Plaques;Series;Signal Pathway;socioeconomics;stem cells;Symptoms;Synaptic plasticity;Testing;therapeutic evaluation;transcriptomic profiling;United States;Universities

PROJECT_TITLE: Nanotechnology for Glial Targeting and Inhibition of Neuroinflammation for Alzheimer’s Disease

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Caregiving Research;Clinical Research;Dementia;Health Services;Neurodegenerative;Neurosciences;Palliative Care

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Over two-thirds of all deaths associated with Alzheimer's disease and related dementias (ADRD) occur in nursing homes with the quality of end-of-life care varying by type of ownership. Twelve percent of US nursing homes have received investments from real estate investment trusts (REITs) with the impact on end-of-life care being unknown. Using a novel database of REIT investments in nursing homes, this is the first study of the relationships between these investments and the quality and cost of care at the end-of-life for residents with ADRD.

PI_NAMEs: BRAUN, ROBERT TYLER;UNRUH, MARK AARON (contact)

PROGRAM_OFFICER_NAME: JAIN, KRITI MUNJAL

PROJECT_TERMS: Accountability;acute care;Address;Affect;Alzheimer's disease related dementia;Antipsychotic Agents;Area;associated symptom;Back;Capital;care costs;Caring;Cessation of life;Clinical;cost;Data Set;Databases;decubitus ulcer;Diagnosis;Economics;Emergency department visit;end of life;end of life care;Enrollment;Enteral Feeding;Equipment;Event;experience;Family;Goals;Government;Health Care Costs;health care quality;health care service;health care service utilization;Healthcare;Home Nursing Care;hospice environment;Hospitalization;Hospitals;Impaired cognition;improved;Income;Individual;Infusion procedures;insight;Institution;Insurance;Intensive Care Units;Investments;Length of Stay;Life;Maintenance;Measures;Medicare;Medicare claim;National Institute on Aging;novel;Nursing Homes;Nursing Staff;operation;Outcome;Ownership;Pain management;Performance;Persons;Pharmaceutical Preparations;Play;Policy Maker;Population;Prevalence;Privatization;Property;psychiatric symptom;Qualifying;Quality of Care;Registered nurse;Reporting;Research;Resources;Role;Source;Tax Exemption;Taxes;Time;Trust;United States Centers for Medicare and Medicaid Services

PROJECT_TITLE: REIT Investments in Nursing Homes and the Quality of End of Life Care for Residents with Alzheimer's Disease and Related Dementias

STUDY_SECTION: ODHS

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


FUNDING_MECHANISM: OTHERS

ORG_CITY: DURHAM

ORG_NAME: DURHAM VA MEDICAL CENTER

PHR: Early initiation of heavy drinking (prior to age 14) in Veterans is associated with higher rates of mental health disorders compared to other veterans and civilians. Further, military personnel aged 18-25, engage in heavy drinking at higher rates than their civilian peers, and those under 21 drink alcohol at the highest rates. Research shows that engaging in risky drinking behavior during this period induces persistent neurological changes. We have found, in a preclinical model, that adolescent alcohol exposure paired with adult stress induces an elevated anxiety- like behavior, which may be reversible. If awarded, this Career Development project will assess the persistence and pharmacological reversibility of the enhanced anxiety response to adult stress after adolescent alcohol exposure. We will also evaluate the neural circuits, neural and astrocytic mechanisms, and synaptic functions that underly these effects.

PI_NAMEs: HEALEY, KATI LYNN (contact)

PROJECT_TERMS: Acute;Adolescence;Adolescent;adolescent alcohol exposure;adolescent binge drinking;Adult;Affective;Age;age group;aged;alcohol exposure;alcohol use disorder;Alcohols;Anhedonia;Animal Model;Animals;Anticonvulsants;Anxiety;anxiety-like behavior;anxiety-related disorders;Astrocytes;Attenuated;Award;Behavior;behavioral study;binge drinking;Brain;Brain region;Career Choice;career development;Chemosensitization;Clinical;clinically relevant;critical period;Data;depressive symptoms;design;Development;Disease;Dorsal;drinking behavior;Electrophysiology (science);Ethanol;Etiology;experience;FDA approved;Female;FOS gene;gabapentin;Genetic;Goals;Health;Healthcare;Heavy Drinking;High Prevalence;high risk drinking;Hippocampus;Human;human model;Hyperactivity;Immunohistochemistry;Individual;interest;Laboratories;LacZ Genes;Life;Longevity;male;Measures;Medial;Mediating;Mental Depression;Mental disorders;Mental Health;Mentors;Methods;Military Personnel;military veteran;Molecular;Mood Disorders;negative affect;Nerve Degeneration;neural;neural circuit;Neurobiology;neurogenesis;Neuroimmune;Neurologic;neuromechanism;Neurons;neurotransmitter release;neurotransmitter uptake;novel;patient screening;peer;pharmacologic;Phenotype;Physiologic pulse;Pre-Clinical Model;Predisposition;Prefrontal Cortex;Proxy;Rattus;Recording of previous events;Recurrence;Reporting;Research;response;Risk;Rodent;Role;sex as a biological variable;Stress;stressor;Structure;Substance Use Disorder;Synapses;synaptic function;Testing;Training;Transgenic Organisms;Veterans;young adult

PROJECT_TITLE: Adolescent/young adult alcohol exposure and subsequent vulnerability to stress induced anxiety

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURA-N (01)]


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Clinical Research;Genetic Testing;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Precision Medicine;Prevention

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE: Earlier identification of individuals at high risk for coronary artery disease is needed to allow for initiation of prevention strategies to reduce morbidity, mortality, and healthcare costs. Polygenic scores, which can estimate an individual’s genetic predisposition for disease early in life, have the potential to advance risk prediction beyond current methods based solely on clinical factors. This proposal seeks to combine newly available data and statistical methods to advance the actionability of polygenic scores by improving their performance across diverse ancestral groups, making them more interpretable in the clinical setting, and identifying new uses for them in guiding preventive therapies.

PI_NAMEs: PATEL, ANIRUDDH  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Address;Advisory Committees;Age;age group;Anti-Inflammatory Agents;Bayesian Method;biobank;C-reactive protein;Calibration;Cardiology;Cardiovascular system;career development;Cause of Death;Classification;Clinical;clinical application;Clinical Research;clinical risk;clinical translation;Clinical Trials;clinically actionable;cohort;Coronary Arteriosclerosis;Cost Effectiveness Analysis;Data;Data Set;design;Disease;disorder prevention;disorder risk;DNA;Drug Targeting;Early identification;Environment;Epidemiology;Equity;European;Family;functional genomics;Future;General Hospitals;General Population;Genes;Genetic;genetic architecture;Genetic Predisposition to Disease;Genetic Risk;genetic variant;genomic data;Genomics;Goals;Health;Health Care Costs;high risk;high risk population;HIV;improved;indexing;Individual;Inflammation;Inflammation Mediators;Inflammatory;Inherited;Intervention;Learning;Life;life span;Life Style;Maps;Massachusetts;Mediating;Mentors;method development;Methodology;Methods;Modeling;Morbidity - disease rate;mortality;non-genetic;Onset of illness;outcome disparities;Pathway interactions;Performance;Pharmaceutical Preparations;Physicians;Population;Population Heterogeneity;portability;Positioning Attribute;precision medicine;predictive tools;Prevention;prevention clinical trial;Prevention strategy;Prevention trial;preventive intervention;Preventive therapy;Probability;Program Development;Protocols documentation;Public Health;racial population;Recording of previous events;Reporting;Research;Research Design;Risk;Risk Estimate;Risk Factors;Risk Marker;risk prediction;risk prediction model;risk stratification;rosuvastatin;Science;Scientist;secondary analysis;Site;skills;Statistical Methods;statistics;Stratification;Subgroup;Sum;targeted treatment;Testing;tool;Training;trait;translational genetics;treatment arm;treatment effect;Variant

PROJECT_TITLE: Advancing the clinical actionability of polygenic scores for coronary artery disease


PHR: Osteopontin (OPN) is a protein implicated in many cancers including lung and colon cancers, and melanoma. Thrombin, the key blood clotting enzyme, cuts OPN into two fragments with new functions not seen in intact OPN. We created a knock-in (KI) mouse in which normal OPN is replaced by one resistant to thrombin cutting. Mouse melanoma growth and spreading are suppressed in the OPN-KI mice. We have identified a monoclonal antibody (mAb) A6 that binds to OPN and blocks its cleavage by thrombin. A6 suppresses melanoma growth and spreading in normal mice. We have “humanized” A6 and its efficacy against different human cancer cells will be tested in a humanized mouse model. We have developed a co-lead, mAb C6r, directed against the thrombin-cleaved OPN fragment, OPN-R. These mAbs represent a novel immuno- oncologic therapeutic in the treatment of many cancers commonly encountered in our Veterans.

PI_NAMEs: LEUNG, LAWRENCE L (contact)

PROJECT_TERMS: Affinity;Alanine;anti-tumor immune response;Anticoagulants;Arginine;Arthritis;Binding;Binding Sites;Blocking Antibodies;Blood coagulation;Breast;Breast Carcinoma;C-terminal;Cancer Biology;cancer cell;Cancer Model;Carboxypeptidase;CD34 gene;Cells;Cerebrospinal Fluid;clinical candidate;clotting enzyme;Collaborations;Colon Carcinoma;coronary fibrosis;Development;drug candidate;Drug Costs;efficacy testing;Enzyme-Linked Immunosorbent Assay;Funding;Glioblastoma;Goals;Grant;Granulocyte-Macrophage Colony-Stimulating Factor;Growth;Human;human cord blood CD34+ cell;human model;humanized antibody;humanized mouse;IL3 Gene;immunodeficiency;immunogenic;improved;in vivo;Inflammatory Arthritis;inhibiting antibody;inhibitor;integrin alpha9 beta1;Integrin Binding;Intellectual Property;Japan;Joints;Knock-in;Knock-in Mouse;Knockout Mice;Laboratories;Lead;Legal patent;Licensing;Liquid substance;Lung Carcinoma;Macrophage;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Melanoma;Metastatic Neoplasm to the Lung;Modeling;Monoclonal Antibodies;mouse model;Mus;N-terminal;Neoplasm Metastasis;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;Oral;Oryctolagus cuniculus;osteopontin;Outcome;Ovarian Carcinoma;ovarian neoplasm;Peptides;Phage Display;Pharmaceutical Preparations;Play;prevent;Process;Property;Proteins;reconstitution;Resistance;Role;Series;side effect;Site;Structure;success;Technology;Testing;Therapeutic;therapeutic candidate;Thrombin;Translations;tumor;tumor growth;Tumor Immunity;Tumor Promotion;Tumor stage;Tumor Suppression;Tumor-associated macrophages;Universities;Veterans;Wild Type Mouse;Xenograft procedure

PROJECT_TITLE: Monoclonal antibody inhibition of thrombin cleavage of osteopontin as a novel therapeutic to enhance host antitumor immunity and reduce cardiac fibrosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 IMMA-G (01)]