ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: PROJECT NARRATIVE Cardiovascular disease and dementia are major health problems among our aging Veterans as well as general population. Vascular pathologies across all vasculature are linked to dementia, particularly the two major subtypes, Alzheimer’s dementia (AD) and vascular dementia (VaD). The current application seeks to fill the scientific gaps by uncovering a novel function of smooth muscle cell (SMC)-expressed Runx2 in regulating cardio/cerebrovascular pathologies and VaD and developing a novel paradigm underlying the Runx2-dependent signaling network in regulating SMC phenotypic switch and calcification. Results from these studies should advance our understanding of basic mechanisms governing SMC phenotypic switch and calcification; and also have important clinical implications in developing potential strategies for maintaining SMC homeostasis and vascular integrity and improving vascular health and quality of life. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

PI_NAMEs: CHEN, YABING  (contact)

PROJECT_TERMS: Ablation;Acceleration;Address;age acceleration;age related;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Aneurysm;Animal Model;Aorta;Apolipoprotein E;APP-PS1;arterial stiffness;Arteries;Atherosclerosis;atherosclerosis risk;Attenuated;Biochemical;Bioinformatics;Blood flow;Blood Vessels;Brain;brain dysfunction;calcification;Cardiovascular Diseases;cardiovascular risk factor;cell type;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular pathology;Cerebrovascular system;Cerebrum;Clinic;Clinical;Clinical Management;Clinical Treatment;cognitive function;Coronary Arteriosclerosis;Databases;Dementia;Diet;Disease;General Population;genetic risk factor;Genetic Transcription;genome-wide analysis;Goals;Health;High Fat Diet;Homeostasis;Human;human tissue;Hypertension;Impaired cognition;improved;In Vitro;in vivo;insight;Ischemic Stroke;Ketosis;Knowledge;Link;Localized Lesion;Mediating;Mediator;Modeling;Molecular;molecular array;mouse model;multidisciplinary;multiple omics;Mus;normal aging;novel;novel strategies;Nutrient;old mice;Organ;Outcome;Oxygen;Pathogenesis;Pathology;Peptides;Peripheral arterial disease;Phenotype;programs;Proteomics;Quality of life;Regulation;Reporting;Resources;risk variant;Role;Serum Response Factor;Signal Transduction;single-cell RNA sequencing;Smooth Muscle Myocytes;Stroke;synergism;Systemic disease;Therapeutic Effect;Tissues;transcription factor;transcriptomics;treatment strategy;Up-Regulation;Vascular calcification;Vascular Dementia;Vascular Diseases;Veterans

PROJECT_TITLE: BCCMA: Interplay of Novel Mediators of Vascular Aging Pathologies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARB-R (01)]


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: BIRMINGHAM

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Project Narrative Glioma is the second cause of cancer death in young adult under 40 years old. The proposed research will develop a model which could be used to study how these tumors are formed. The studies will provide understanding of how genetic mutations contribute to tumor formation and thus lead to novel therapy. The research is relevant to the VA where numerous cases of brain tumors were diagnosed and treated.

PI_NAMEs: HAN, XIAOSI  (contact)

PROJECT_TERMS: Adult;alpha ketoglutarate;Animal Model;Architecture;Astrocytes;ATRX gene;Brain;brain cell;Brain Neoplasms;Cancer Etiology;Cell Survival;cell type;Cells;Cessation of life;Diagnosis;Disease;Dissection;DNA;DNA Sequence Alteration;drug development;Ensure;Enzymes;epigenome;Event;Family;Gene Expression;Genes;Genetic;Genetic Engineering;genomic profiles;Genomics;Glioblastoma;Glioma;Gliomagenesis;Goals;Growth;Human;human embryonic stem cell;human pluripotent stem cell;improved;In Vitro;induced pluripotent stem cell;Inhibition of Cell Proliferation;Intervention;Investments;Isocitrate Dehydrogenase;Isocitrates;knock-down;Lead;Mixed Function Oxygenases;Modeling;Molecular;mortality;mouse model;mutant;Mutation;nerve stem cell;neuro-oncology;Neurons;new therapeutic target;novel;novel therapeutics;Organoids;Pathway interactions;Patients;permissiveness;Proliferating;Publishing;Research;Role;small hairpin RNA;Somatic Cell;Source;stem cell biology;stem cells;Structure;System;Therapeutic Intervention;TP53 gene;Transplantation;tumor;Tumor Promotion;tumor xenograft;tumorigenesis;tumorigenic;Xenograft procedure;young adult

PROJECT_TITLE: Modeling IDH Mutant Gliomas by Genetic Engineering of Brain Organoid

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCB-A (01)]


PHR: Heart failure with preserved left ventricular ejection fraction (HFpEF) caused by resistant hypertension is a leading cause of morbidity and mortality and of particular significance for veterans and the VA medical system. Veterans are more likely than non-veterans to develop co-morbidities that contribute to the development of HFpEF. Treatment options for HFpEF are largely limited to decongestion by diuretics. To address this clinical need, and with an especial focus on African American people, this project will investigate in an innovative way a potential new target, xanthine oxidoreductase, which may reveal a new treatment approach for treating and preventing HFpEF. We will test for causality of activity of xanthine oxidoreductase for HFpEF in the Million Veterans Program. The work may pave the way for clinical trials of inhibition of xanthine oxidoreductase in preventing the onset of HFpEF in at risk individuals.

PI_NAMEs: DELL'ITALIA, LOUIS J. (contact)

PROJECT_TERMS: Address;African American;African American population;Alabama;Alleles;Allopurinol;Blood Pressure;Caffeine;Calcium;Cardiac;Cardiac Myocytes;caucasian American;Clinical;clinical practice;Clinical Research;Clinical Trials;Coffee;cohort;comorbidity;Consumption;Data;Development;Diuretics;EFRAC;epidemiology study;Etiology;Event;febuxostat;Functional disorder;Genes;Genetic;genetic variant;Genetic Variation;Genome Scan;genome wide association study;genomic locus;Genomics;Gout;Health;Health Care Costs;Heart;Heart failure;heart failure with reduced ejection fraction;hospital readmission;Hypertension;Hypoxanthines;Individual;innovation;instrument;Left;Left Ventricular Dysfunction;Left Ventricular Ejection Fraction;Left Ventricular Mass;Left ventricular structure;Mediating;Mediation;Medical;men;Mendelian randomization;Morbidity - disease rate;mortality;Myofibrils;novel;novel strategies;novel therapeutic intervention;Other Genetics;Outcome;Participant;Patients;pharmacologic;Phenotype;Plasma;Predisposition;preservation;prevent;Prevention;Preventive;Production;programs;Proxy;Race;Reactive Oxygen Species;recruit;Reporting;Research Design;Resistant Hypertension;Risk;Risk Factors;Role;Sampling;Sarcomeres;secondary analysis;Serum;Signal Transduction;Symptoms;System;Techniques;Testing;Translating;Urate;Variant;Ventricular;Veterans;Woman;Work;Xanthine Oxidase;XDH gene

PROJECT_TITLE: Genetic variation in xanthine oxidase and heart failure preserved ejection fraction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARA-R (01)]


ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: PROJECT NARRATIVE: In 2014, veterans with HF accounted for nearly 1,200,000 VA outpatient visits and 40,000 primary-diagnosis hospitalizations, and AHF remains the most common cause for hospital admission in the veteran population. This proposal will explore an entirely new approach to understanding how the heart fails, based on learning how heart muscle cells and heart-immune cells “speak” to each other by liberating and modifying chemical signals. Understanding this new language of cell-cell communication in the beating heart could lead to development of an entirely new approach to diagnose and treat patients with heart failure. This proposal is well-aligned with the Department of Veterans Affairs FY 2018 - 2024 Strategic Plan, which states that “VA will seize opportunities driven by rapid advancements in technology and groundbreaking research to provide Veterans cutting-edge treatment.”

PI_NAMEs: GOONEWARDENA, SASCHA NILU (contact)

PROJECT_TERMS: Acceleration;Acute;Adenosine;Adenosine Triphosphate;Admission activity;American;Angiotensin II;Binding;biobank;biological adaptation to stress;Biological Response Modifiers;Blood;Blood Vessels;Bone Marrow;Cardiac;Cardiac Myocytes;Catabolism;Cell Communication;Cells;Cessation of life;Chemicals;Chronic;Clinical;Communication;coronary fibrosis;Coupled;Cues;cytokine;Cytometry;Data;Development;Diagnosis;ecto-nucleotidase;Engineering;Environment;experimental study;Exposure to;extracellular;Fibrosis;Fluid overload;Genetic;genetic analysis;Genetic Engineering;genetic variant;Heart;heart damage;Heart failure;hemodynamics;Hospitalization;Human;IL6 gene;Immune;Immunology;in vivo;Individual;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Innate Immune Response;Laboratories;Language;Learning;Ligands;Macrophage;Mechanical Stress;Mediating;Mediator;military veteran;Modeling;Molecular;monocyte;mouse model;Mus;Myelogenous;Myeloid Cells;Myocarditis;novel;novel strategies;Outpatients;overexpression;Pathologic;Patients;Pattern;Phenocopy;Phenotype;pressure;Prevention;Process;programs;Property;Proteomics;Purines;Research;response;Role;Shapes;Signal Transduction;Strategic Planning;Stress;Surface;System;Technology;Testing;TNF gene;Toll-like receptors;transcriptome sequencing;transcriptomics;Transgenic Mice;Transgenic Model;Transgenic Organisms;translational study;United States Department of Veterans Affairs;Veterans;Visit

PROJECT_TITLE: Coordination of cardiac inflammation/remodeling in heart failure by myeloid catabolism of purinergic DAMPs


PHR: Coronary artery disease (CAD) is a chronic inflammatory vascular condition that remains a leading cause of death in the United States with disproportionate impact on the US veteran population. Cigarette smoking and other tobacco products clearly accelerate the development of CAD; however, the cellular and molecular mechanisms linking smoke with CAD remain poorly understood. In this proposal, we present the matrikine proline-glycine-proline (PGP) and exosome-associated proteases (i.e. proteolytic exosomes) as novel mediators of smoke-induced atherosclerosis. We propose an integrative mouse model of smoke-induced atherosclerosis to investigate the pathogenic role of PGP and its generating proteases. Our pre-clinical experiments will be complimented by translational studies among veterans with CAD. Ultimately, PGP and proteolytic exosomes may represent new biomarkers and targets for the prevention of CAD.

PI_NAMEs: PAYNE, GREGORY ALLEN (contact)

PROJECT_TERMS: Acceleration;Acetylation;Address;Animals;Atherosclerosis;Biological Markers;Biology;Blood Vessels;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cells;Cessation of life;chemokine;Chemotaxis;Chronic;cigarette smoking;Clinical;clinical biomarkers;Clinical Data;clinically significant;cohort;Collagen;combat;Coronary;Coronary Angiography;Coronary Arteriosclerosis;Coupled;Data;design;Development;diagnostic biomarker;digital;Disease;Disparity;endothelial dysfunction;Endothelium;exosome;experimental study;Extracellular Matrix;Extracellular Matrix Degradation;Glycine;Goals;Human;improved;Incidence;indexing;Infiltration;Inflammation Mediators;Inflammatory;Interleukin-8B Receptor;Investigation;Knowledge;Leukocyte Elastase;Ligands;Link;Lung Diseases;Macrophage;Mediating;Mediator;Medical;Medicine;Metalloproteases;Military Personnel;military veteran;MME gene;Modeling;Molecular;Monitor;Morbidity - disease rate;mouse model;Mus;neutrophil;novel;novel diagnostics;novel marker;novel therapeutic intervention;Pathogenicity;Pathology;Patients;Peptide Fragments;Peptide Hydrolases;Peptides;Plasma;pre-clinical;Prevention;Prevention approach;Production;Proline;prolyl oligopeptidase;promoter;receptor;Resources;response;revascularization;Risk;Role;Seminal;Severities;Severity of illness;Signal Transduction;Smoke;Smoker;Smoking;smoking exposure;Smoking History;Smoking Status;System;Techniques;Testing;therapeutic target;Tissues;tobacco products;Tobacco smoke;Transgenic Mice;Translating;translational study;United States;Vascular Diseases;vascular inflammation;Veterans

PROJECT_TITLE: Extracellular matrix-derived chemokines mediate smoking-associated coronary atherosclerosis


ORG_CITY: PITTSBURGH

ORG_STATE: PA

PHR: Many of the ~700,000 military service members deployed during the Gulf War experienced deployment-related respiratory exposures (DRREs) from burn pit combustion products, particulate matter, and chemical toxins. These exposures are now presumed to be linked to the development of lung cancer and other respiratory diseases. Yet, the mechanism by which DRREs in the Persian Gulf render Veterans susceptible to lung cancer is poorly understood. Our findings in mouse models indicate that respiratory exposure to Gulf War Toxins induces sustained inflammation in the lung, driven by alterations in how genes are expressed (epigenetics). We propose to (1) study epigenetic changes in lung specimens from deployed Gulf War Veterans with lung cancer, (2) expose mice to aerosolized gulf war toxins and determine the impact on developing cancer, and (3) reverse epigenetic alterations in cancer causing pathways. If successful, these aims may lead to novel screening for Gulf War Veterans at increased risk of developing lung cancer and potentially a way to reverse these changes.

PI_NAMEs: DHUPAR, RAJEEV ;JOHNSON, RUDOLPH C;SOLOFF, ADAM CHRISTOPHER (contact)

PROJECT_TERMS: 3-Dimensional;4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;Address;aerosolized;Afghanistan;Alveolar Macrophages;Asia;ATAC-seq;Atlases;Burn injury;burn pit;Cancer Etiology;cancer initiation;cancer risk;carcinogenicity;Carcinogens;Caring;Cells;Chemicals;Chronic;cigarette smoke;combustion product;Data;Databases;Development;Diagnosis;diagnostic criteria;digital;DNA Modification Methylases;Endothelium;Enzymes;Epigenetic Process;epithelial to mesenchymal transition;Epithelium;experience;Experimental Models;Exposure to;Fibroblasts;Fire - disasters;Future;Gene Combinations;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Genomics;Goals;Gulf War;Gulf War veteran;Histone Deacetylase Inhibitor;Human;Immune;Immunologics;improved;in vivo;Incidence;Inflammation;Inflammatory;Inhalation;insight;Institute of Medicine (U.S.);Investigation;Link;Lung;lung development;Macrophage;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;military service;Modification;mouse model;Mus;neoplasm registry;novel;novel therapeutics;Oils;operation;Outcome;Particulate;Particulate Matter;Pathology;Pathway interactions;Persian Gulf;Pesticides;Petroleum;Phagocytes;pharmacologic;Predisposition;prevent;Program Development;Pulmonary Emphysema;Pulmonary Inflammation;Pulmonary Pathology;Rationalization;Research;Research Support;respiratory;Respiratory Disease;respiratory health;response;Risk;Risk Assessment;Risk Reduction;Role;screening;service member;Services;Silicon Dioxide;Slice;Specimen;Structure of parenchyma of lung;System;Tobacco-Associated Carcinogen;Toxicant exposure;Toxin;transcriptome sequencing;transcriptomics;tumor initiation;Veterans

PROJECT_TITLE: Lung Cancer Susceptibility in Deployed Gulf War Veterans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 SPLD-T (01)]


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: For over 100 years, U.S. military personnel have been exposed to arsenic, a common environmental contaminant associated with neurocognitive disorders. One potential mechanism linking arsenic to neurocognitive dysfunction is through depletion of the essential fatty acid docosahexaenoic acid (DHA), which is critical for both brain development and function. This project investigates how arsenic-mediated disruption of DHA contributes to neurocognitive dysfunction in mice while exploring the therapeutic potential of targeted delivery of DHA to the brain as a means of addressing neurocognitive disorders in arsenic-exposed veterans.

PI_NAMEs: SARGIS, ROBERT M (contact)

PROJECT_TERMS: Acids;Acute;Address;Adolescence;Adverse effects;Affect;Amygdaloid structure;Anxiety;Area;Arsenic;Arsenicals;base;Behavior;Behavior assessment;Behavioral;behavioral outcome;Blood - brain barrier anatomy;Brain;burden of illness;burn pit;Chemical Weapons;Chemicals;Clinical;combat;Consumption;contaminated drinking water;Data;Defect;Development;Diabetes Mellitus;Disease;Docosahexaenoic acid supplement;Docosahexaenoic acid supplementation;Docosahexaenoic Acids;emerging adult;Environmental Pollutants;Essential Fatty Acids;experience;Exposure to;fatty acid metabolism;Fire - disasters;Fish Oils;Functional disorder;global health;Health;Hippocampus;improved;Individual;Inflammation;innovation;insight;Intervention;Knowledge;Learning;Life;Link;Lipids;Lysophosphatidylcholines;Malignant Neoplasms;Mediating;Memory;Mental Depression;Mental disorders;Mental Health;Metabolic;Military Personnel;military service;military veteran;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;N-3 polyunsaturated fatty acid;neurobehavioral;Neurocognition;Neurocognitive;Neurocognitive Deficit;neurocognitive disorder;Neurologic;Neurons;Neuroprotective Agents;neuropsychiatric disorder;neuropsychiatry;neurotoxicity;Neurotoxins;neurotrophic factor;novel;novel therapeutic intervention;Nutraceutical;Oils;Omega-3 Fatty Acids;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;Pathway interactions;Penetrance;Pesticides;Post-Traumatic Stress Disorders;Prefrontal Cortex;preservation;prevent;Prevention;Production;restoration;Risk;risk mitigation;Role;Serotonin;service member;Services;Signal Transduction;targeted delivery;Testing;Therapeutic;Toxic effect;Toxic Environmental Substances;Toxicant exposure;Veterans;Vietnam;Work;World Health Organization

PROJECT_TITLE: Metabolic and Neurocognitive Impacts of Military-Associated Toxicant Exposures

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


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: The oscillatory neuronal activity is a functionally relevant signal of the cognitive capability of the brain. Aberrant oscillatory activity and network connectivity underlie a wide range of neurological and neuropsychiatric disorders. Therefore, as proposed in this application, a better understanding of the brain-region- and cell type-specific regulation of cortical oscillations during sleep-wakefulness and sensory processing by electrical synapses is important for obtaining better insight into the underlying mechanisms and for the future development of therapeutic interventions.

PI_NAMEs: BASHEER, RADHIKA  (contact)

PROJECT_TERMS: adeno-associated viral vector;Animals;Area;area striata;Attenuated;Auditory;Auditory area;auditory stimulus;Behavioral;Bilateral;biocytin;Brain;Brain region;Cannulas;Cell Nucleus;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;cognitive function;Collaborations;Communication;connexin 36;Connexins;Coupled;Coupling;CRISPR/Cas technology;density;Diffusion;Distal;Dorsal;Dyes;Electrical Synapse;Electrodes;Electroencephalography;Functional impairment;Future;Gap Junctions;Gene Expression;gene-editing approach;Genes;Goals;Guide RNA;Homeostasis;Immunohistochemistry;Impairment;Implant;In Vitro;in vivo;Injections;insight;Interneurons;Ion Channel;knock-down;Knockout Mice;Light;Lighting;Modeling;Mus;Nervous System Disorder;neural;Neurologic;Neurons;neuropsychiatric disorder;Parvalbumins;Pattern;Perception;Performance;Periodicity;Proteins;receptor;Regulation;Resolution;response;Role;Sensory;Sensory Process;sensory stimulus;Signal Transduction;Site;Sleep;Sleep Deprivation;Sleep Disorders;sleep regulation;sleep spindle;Social Interaction;sound;Spottings;Stimulus;Structure;Synapses;Testing;Thalamic structure;therapeutic development;Therapeutic Intervention;Veterans;Visual;Visual Cortex;visual stimulus;Wakefulness;Work

PROJECT_TITLE: The role of electrical synapses in neural dynamics involved in sleep/wake and sensory perception

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURR-A (01)]


ORG_CITY: HOUSTON

ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

ORG_STATE: TX

PHR: Although fibrinogen levels are elevated in pancreatic ductal adenocarcinoma (PDAC) cancer patient plasma and cancer tissues, the mechanistic roles for fibrinogen in the pathogenesis of PDAC are largely unknown. We hypothesize that increased fibrinogen expression in the basal subtype of PDAC plays an important role in cancer progression and a novel therapy (A2 protein) targeting fibrinogen in combination with FOLFIRINOX could be beneficial primarily for PDAC patients with basal subtype tumors. We propose: 1). Determine the functions and molecular mechanisms of tumor-derived fibrinogen in the pathogenesis of the basal subtype of PDAC in vitro and in vivo. 2). Determine the therapeutic efficacy of the novel combination of chemotherapy with A2 protein targeting fibrinogen in the basal subtype of PDAC in PDX mouse models. We expect this project to offer a new, groundbreaking paradigm for VA patient care.

PI_NAMEs: YAO, QIZHI C. (contact)

PROJECT_TERMS: Algorithms;Apoptosis;Binding;Binding Proteins;Biological;Blood flow;Blood Platelets;cancer cell;Cancer Patient;Cell Communication;Cell Line;cell motility;Cell Proliferation;Cells;Chemoresistance;chemotherapy;Classification;Clinical Trials;Coagulation Process;Combination Drug Therapy;cytokine;effective therapy;Epithelium;Event;Fibrin;Fibrinogen;Fibrinogen Receptors;gain of function;General Population;Genes;genetic approach;Genetically Engineered Mouse;Hemorrhage;Hemostatic function;Human;In Vitro;in vivo;Inflammation;Intercellular adhesion molecule 1;Interleukin-6;Invaded;Knockout Mice;Laboratories;loss of function;Malignant neoplasm of pancreas;Malignant Neoplasms;Mesenchymal;military veteran;Modeling;Molecular;Molecular Profiling;mouse model;Mus;Nature;Neoplasm Metastasis;novel;novel therapeutics;overexpression;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Pathogenesis;Pathogenicity;Pathway interactions;Patient Care;patient derived xenograft model;patient prognosis;patient subsets;Patients;Pharmaceutical Preparations;Plasma;Play;polymerization;Polymers;polypeptide;Prevalence;Process;Prognosis;Proliferating;protein expression;Proteins;Proto-Oncogene Proteins c-akt;Recombinants;Regimen;Research;Research Personnel;response;Risk;Role;screening;Signal Pathway;Signal Transduction;STAT3 gene;Survival Rate;targeted treatment;Therapeutic;Thrombosis;Tissues;Treatment Efficacy;treatment strategy;tumor;Tumor Burden;tumor progression;Tumor Promotion;Tumor Subtype;Tumor-Derived;tumor-immune system interactions;tumorigenesis;venous thromboembolism;Veterans;von Willebrand Factor

PROJECT_TITLE: Novel Pathogenic Roles and Mechanisms of Fibrinogen in Pancreatic Cancer

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


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Narrative: This proposal will investigate the role of a novel lymphoma-shed 49kDa Fc receptor like A (FCRLA) molecule in HLA class II-mediated immune disruption of human B-cell lymphomas. The goal of this proposal is to dissect the mechanisms of FCRLA-mediated inhibition of class II-restricted CD4+ T cell recognition of B-cell lymphomas in vitro and in vivo by employing genetically manipulated lymphoma cells, antigen-specific T cells, and FCRLA blocking antibody. The proposed study will determine whether FCRLA shedding plays a significant role in modulating the activity of CD4+ T cells, and if blocking of FCRLA augments antitumor immunity. Overall, these studies will elucidate novel mechanisms for restoring immune detection of lymphoid malignancy, which will likely spur development of novel therapeutic strategies for B-cell lymphomas that may be applicable to other malignancies. The success of this project will also profoundly improve the treatment and survivorship of Veterans and their family members.

PI_NAMEs: HAQUE, AZIZUL  (contact)

PROJECT_TERMS: Adoptive Transfer;Affinity;antibody immunotherapy;Antibody Therapy;Antigen Presentation;Antigen-Presenting Cells;antigen-specific T cells;B-Cell Lymphomas;B-Cell Neoplasm;Binding;Biological Assay;Blocking Antibodies;cancer cell;cancer diagnosis;Cancer Patient;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Line;Cells;CRISPR/Cas technology;Cytotoxic T-Lymphocytes;Data;Detection;Development;Disease;efficacy testing;Enzyme-Linked Immunosorbent Assay;Exposure to;Family member;Fc Receptor;Flow Cytometry;Fluorescence;Foundations;functional restoration;genetic manipulation;Goals;Helper-Inducer T-Lymphocyte;Hematologic Neoplasms;Histocompatibility Antigens Class II;Host Defense;Human;Immune;Immune Evasion;Immune response;Immunologic Surveillance;Immunoprecipitation;Immunosuppression;Impairment;improved;In Vitro;in vivo;Ionizing radiation;knock-down;large cell Diffuse non-Hodgkin's lymphoma;leukemia/lymphoma;Lymphoma;Lymphoma cell;Macrophage;Maintenance;Malignant lymphoid neoplasm;Malignant Neoplasms;Mediating;military service;Modeling;Molecular;Mus;mutant;novel;novel therapeutic intervention;Pathway interactions;Patient-Focused Outcomes;Patients;Peptides;Play;Proteins;Publishing;Radiation exposure;Reagent;Role;Site;Site-Directed Mutagenesis;small hairpin RNA;Solid;Spectrum Analysis;success;survivorship;T-Lymphocyte;Testing;Time;tumor;Tumor Antigens;tumor growth;Tumor Immunity;vector;Veterans;Xenograft Model

PROJECT_TITLE: A Novel Mechanism of Immune Escape by B-cell Lymphoma

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


FUNDING_MECHANISM: OTHERS

ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: Head and neck cancer is the fifth most common cancer among patients in the U.S. Veteran's Affairs Health Care System. Despite improvements in surgical techniques, radiation, chemotherapies and immunotherapy, patients with advanced disease still suffer from poor outcomes. Our lab, among others, have identified that the NRF2 pathway is active in up to 40% of head and neck cancers and that these tumors are more resistant to treatment and have worse outcomes. NRF2 has a role in regulating immune responses and our hypothesis is that targeting NRF2 in combination with immunotherapy will lead to better treatment responses and ultimately better patient outcomes. We have identified two FDA-approved drugs and a novel compound which target the NRF2 pathway effectively. Our goal is to use mouse models to test this combination approach. We believe this will show higher rates of tumor rejection than standard of care alone.

PI_NAMEs: ZOLKIND, PAUL  (contact)

PROJECT_TERMS: advanced disease;analog;anti-PD-1;Antioxidants;Biological;Biology;cancer cell;Cancer Model;Cancer Patient;Carcinogens;cell growth;cell injury;Cell Proliferation;Cells;checkpoint therapy;Chemicals;chemotherapy;Clinical;clinical phenotype;Cytoprotection;cytotoxic;Data;DHFR gene;Diagnosis;Dihydrofolate Reductase Inhibitor;Disease;Drug Targeting;early phase clinical trial;efficacy evaluation;Engineering;Environment;Equilibrium;FDA approved;Flow Cytometry;Gene Activation;Genes;Genomic Library;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Healthcare Systems;Hypoxia;Immune;immune cell infiltrate;immune checkpoint blockade;Immune Evasion;Immune response;Immunotherapy;improved;in vivo;Inflammation;inhibitor;insight;Malignant Neoplasms;Mediating;Metastatic/Recurrent;Methotrexate;Modality;Modeling;Molecular;mouse development;mouse model;Mus;Mutation;neoplastic cell;novel;Nutrient Depletion;Operative Surgical Procedures;Outcome;oxidation;Oxidative Stress Pathway;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phenotype;Positioning Attribute;Pre-Clinical Model;Prevalence;prevent;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Proteomics;Pyrimethamine;Radiation;Resistance;response;Response Elements;Role;Signal Transduction;standard of care;Supporting Cell;Techniques;Testing;Therapeutic Agents;therapy resistant;Toxin;transcriptomics;treatment response;tumor;tumor growth;tumor microenvironment;tumor-immune system interactions;tumorigenesis;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Targeting NRF2 in Head and Neck Squamous Cell Carcinoma


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Despite recent advances in physical rehabilitation, Veterans with lower-limb amputation have poor long-term outcomes, including severely limited functional capacity and high levels of disability. Such poor outcomes are compounded by a lack of exercise participation over time, even with use of lower-limb prostheses. There is a clear need to advance current rehabilitation strategies to better promote sustained exercise following lower- limb amputation. To address this need, our study will determine the efficacy of a walking exercise self- management program to achieve sustained exercise participation. The 18-month intervention is focused on helping Veterans reduce habitual sedentary behavior through a remote exercise behavior-change intervention that includes multiple clinical disciplines, a novel individualized exercise self-management training, and peer support. This innovative approach shifts the conventional rehabilitation paradigm to specifically target life-long exercise sustainability and remove an underlying cause of disability for Veterans with lower-limb amputation.

PI_NAMEs: CHRISTIANSEN, CORY L (contact)

PROJECT_TERMS: 2 arm randomized control trial;Accelerometer;Activities of Daily Living;Acute;Address;Adopted;Adoption;Adverse effects;Amputation;attentional control;Behavior;behavior change;Chronic;Clinic;Clinical;clinical implementation;clinical translation;Colorado;Communities;comorbidity;comparison control;Continuity of Patient Care;design;Diabetes Mellitus;disability;Discipline;Education;Effectiveness;efficacy evaluation;efficacy outcomes;Eligibility Determination;Enrollment;Ensure;Environment;evidence base;Exercise;exercise intensity;exercise intervention;exercise rehabilitation;Focus Groups;functional independence;Future;General Population;Goals;Health;Healthcare Systems;Home;implementation design;improved;Individual;Infrastructure;innovation;Interruption;Intervention;intervention cost;Knowledge;limb amputation;Limb Prosthesis;Link;Lower Extremity;Maintenance;Measures;Medical;Methods;Modeling;Monitor;multidisciplinary;novel;novel strategies;Outcome;Outcome Assessment;Participant;patient retention;Patient Self-Report;Patients;peer;Peer Group;peer support;Performance;Peripheral arterial disease;Persons;Phase II Clinical Trials;Physical activity;physical conditioning;Physical Exercise;Physical Function;Physical Rehabilitation;poor health outcome;population health;primary outcome;Program Sustainability;programs;Prosthesis;prosthesis wearer;Provider;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;rehabilitation paradigm;rehabilitation strategy;Rehabilitation therapy;remote monitoring;Resources;rural area;secondary outcome;sedentary lifestyle;Self Efficacy;Self Management;self-management program;service utilization;social engagement;Social support;Step Tests;Structure;Techniques;Technology;telehealth;telerehabilitation;Testing;Time;Training;Training Support;Translating;translational potential;Treatment Efficacy;trend;trial design;underserved area;Veterans;Walking;wearable data;Well in self;whole health

PROJECT_TITLE: Walking Exercise Sustainability Through Telehealth for Veterans with Lower-LimbAmputation

STUDY_SECTION_NAME: Musculoskeletal Health & Function[RRD2]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF MEDICINE

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

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: CORAL GABLES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Narrative HIV is severely affecting women of racial and ethnic minority backgrounds in the Southern US. Reproductive age women living with HIV have worse HIV outcomes than older women or men. This study will recruit and retain 2,000 women of reproductive age, promote collaboration with other scientists, and will evaluate contributors to suboptimal health outcomes among women in this age group. This study has the potential to improve the health of young women living with HIV, facilitate high impact science, and evaluate the roles of psychosocial conditions on a range of health outcomes of women living with HIV in this age group.

PI_NAMEs: ALCAIDE, MARIA LUISA (contact);GOLUB, ELIZABETH T;KASSAYE, SEBLE G;RANA, AADIA ;SHETH, ANANDI NAYAN;WESTREICH, DANIEL J

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: Address;Affect;Age;age group;Aging;antiretroviral therapy;Area;biobank;Biological;Biological Factors;Bisexual;Caring;Child;Clinical;cohort;Cohort Studies;Collaborations;Communities;community advisory board;Data;data centers;Data Collection;data management;depressive symptoms;Discipline;Disease;Disparity;District of Columbia;Enrollment;Epidemic;ethnic minority;Ethnic Minority Women;experience;Exposure to;follow-up;Future;Gays;Gender;Geography;Gynecologic;Health;health care availability;Health Status;Healthcare;HIV;HIV Infections;HIV/AIDS;improved;Incidence;Individual;Inflammation;Infrastructure;Interdisciplinary Study;Intervention;Interview;Laboratories;Leadership;Longitudinal cohort study;Mediator;men;Mental Depression;Morbidity - disease rate;mortality;multidisciplinary;novel;older men;older women;Opioid;Oral;Oral health;oral microbial community;Outcome;Participant;Periodontal Diseases;Persons;Population;Population Heterogeneity;Positioning Attribute;post pregnancy;Postpartum Depression;Postpartum Period;Poverty;Pregnancy;Pregnancy Outcome;Pregnant Women;Prevalence;Productivity;prospective;Prospective, cohort study;psychosocial;Psychosocial Factor;Race;racial minority women;recruit;reproductive;Reproductive Health;reproductive outcome;Research;Research Personnel;retention rate;Risk;Role;sample collection;Science;Scientist;sex;side effect;Site;Social Behavior;social determinants;social health determinants;social stigma;sociodemographic disparity;sociodemographic factors;Specimen;Standardization;Statistical Models;structural determinants;Structure;substance use;syndemic;systemic inflammatory response;Testing;The Multicenter AIDS Cohort Study;therapy adherence;Time;transmission process;Trauma;Treatment outcome;United States;Violence;Viral;Visit;Woman;Women's Interagency HIV Study;women's outcomes;Women's study;women's treatment;working group;young woman

PROJECT_TITLE: Women HIV Cohort Study: HIV infection and treatment among women of reproductive age


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: BRONX

ORG_NAME: JAMES J PETERS VA  MEDICAL CENTER

ORG_STATE: NY

PHR: NARRATIVE Chronic pain represents a major health problem in veterans and is frequently associated with mental disorders including anxiety, depression or even suicidal tendencies. Our preliminary studies demonstrated that CCL5/CCR5 axis plays an important role in an animal model of neuropathic pain. The proposed study will test whether maraviroc, an FDA-approved CCR5 antagonist may alleviate peripheral nerve injury-induced neuropathic pain. A successful outcome of the application will provide experimental evidence and supporting data for targeting CCL5/CCR5 axis as novel target for pain management.

PI_NAMEs: WANG, JUN  (contact)

PROJECT_TERMS: Adenylate Cyclase;Adrenal Cortex Hormones;Adult;Adverse effects;Affect;Amygdaloid structure;Animal Model;antagonist;Anterior;anti-epileptic agents;Anxiety;atypical facial pain;Blood;Brain;cancer pain;Cannabinoids;CCR5 gene;cell type;Cells;Cellular Structures;Central Nervous System;chemokine;chemokine receptor;Chemotactic Factors;chemotherapy;chronic pain;clinical translation;clinically significant;comorbidity;cytokine;Data;Development;discogenic pain;Economics;Emotional;FDA approved;Female;Fiber;Filament;Flow Cytometry;follow-up;Future;Gene Chips;Gene Expression;General Population;Health;Health care facility;Healthcare Systems;Human;Immune;Immunologics;Inflammation;Inflammatory;Injections;Injury;Intervention;Lesion;Ligands;Macrophage;male;MAP Kinase Gene;Mechanics;Mental Depression;Mental disorders;Metabolism;migration;Molecular;monocyte;mouse model;Mus;nano-string;Natural Killer Cells;Nerve;Nerve Degeneration;nerve injury;Nervous System;neural stimulation;neurobehavioral test;Neuroglia;neuroinflammation;Neuronal Plasticity;Neurons;neuropathology;Neuropathy;neurotransmission;Non-Steroidal Anti-Inflammatory Agents;novel;novel therapeutic intervention;Operative Surgical Procedures;Opiate Addiction;Opioid;Outcome;Outcome Study;Pain;Pain intensity;Pain management;pain reduction;pain relief;pain sensitivity;painful neuropathy;Patients;Penetration;Peripheral;Peripheral nerve injury;Peripheral Nerves;Peripheral Nervous System;Persistent pain;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phenotype;PI3K/AKT;Plasma;Play;pre-clinical;Prevalence;Primary Care;Quality of life;Randomized;RANTES;receptor;Reporting;response;Role;Safety;Sampling;sciatic nerve;sham surgery;side effect;Signal Transduction;social;spared nerve;Spinal Ganglia;spontaneous pain;Steroids;suicidal;synaptic function;T-Lymphocyte;Techniques;Testing;Therapeutic;Tissues;translational study;Translations;treatment group;Tricyclic Antidepressive Agents;Trigeminal Neuralgia;Tumor Cell Invasion;Up-Regulation;Veterans;Weight-Bearing state;Well in self

PROJECT_TITLE: Repurposing of Maraviroc for the treatment of neuropathic pain

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Immunotherapy;Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: N-methyl-D-aspartate receptor (NMDAR) encephalitis is a life-threatening antibody-mediated disorder of the central nervous system (CNS) that presents with prominent psychiatric symptoms, alterations in consciousness, seizures, movement disorders and dysautonomia, for which there are no FDA approved treatments. The IgG antibodies against NMDARs are pathogenic; accordingly, B-cell depleting medications account for the majority of off-label medications used in NMDAR encephalitis. The Extinguish Trial will randomize 116 participants with moderate-to-severe NMDAR encephalitis to receive either inebilizumab (a humanized monoclonal antibody against CD19+ plasma blasts and plasma cells) or placebo in addition to first- line therapies to assess safety and efficacy (motor disability) at 16 weeks (primary outcomes), evaluate the longer-term effect of the investigational agent on cognitive/functional outcomes, and determine the biologic predictors of favorable outcomes for use in future clinical trials.

PI_NAMEs: CLARDY, STACEY LYNN (contact)

PROGRAM_OFFICER_NAME: OHAYON, JOAN M

PROJECT_TERMS: Accounting;Acute;Address;Admission activity;Adverse event;Affect;Age;Antibodies;Antibody Formation;Antibody Therapy;Antibody titer measurement;Autoantibodies;Autoimmune encephalitis;B cell therapy;B-Cell Activation;B-Lymphocytes;Behavioral;Biological;Biological Markers;biomarker identification;Blast Cell;Blood;blood-brain barrier penetration;Brain;Case Series;CD19 Antigens;CD19 gene;Central Nervous System;Central Nervous System Diseases;Cerebrospinal Fluid;Characteristics;Clinical Data;Clinical Trials;Cognitive;Conscious;Consensus;control trial;CXCL13 gene;cytokine;cytotoxic;Data;design;Detection;Developed Countries;Diagnosis;disabled;Disease;Disease Marker;Dose;Double-Blind Method;Dysautonomias;Early treatment;efficacious treatment;Encephalitis;Evaluation;executive function;experience;FDA approved;functional outcomes;Future;future implementation;Goals;Herpes encephalitis;High Prevalence;Hospitalization;humanized monoclonal antibodies;IgG autoantibodies;IL17 gene;Immunoglobulin G;Immunoglobulins;Immunotherapy;improved;In Vitro;indexing;Individual;Intensive Care;Intensive Care Units;Interleukin-10;Interleukin-6;Intravenous;Intraventricular Infusion;Label;Life;Measures;Mediating;Memory;Monoclonal Antibodies;Morbidity - disease rate;Motor;Motor disability;Movement Disorders;MS4A1 gene;Mus;N-Methyl-D-Aspartate Receptors;Nervous System Disorder;Neuromyelitis Optica;Neurons;Neuropsychological Tests;off-label drug;Oligodendroglia;Outcome;Outcome Measure;outcome prediction;Participant;Pathogenesis;Pathogenicity;Pathologic;Patient Care;Patient-Focused Outcomes;Patients;Penetrance;Penetration;Persons;Pharmaceutical Preparations;Phase;Phase III Clinical Trials;phase III trial;Placebos;Plasma;Plasma Cells;Plasmablast;Prediction of Response to Therapy;Prevalence;primary outcome;prospective;Prospective Studies;psychiatric symptom;Quality of life;Randomized;Randomized, Controlled Trials;Resources;response;rituximab;Route;Safety;safety assessment;Screening procedure;Seizures;Serious Adverse Event;Severity of illness;Site;Steroids;Surface;Surface Antigens;Therapeutic Monoclonal Antibodies;Time;treatment group;treatment responders;treatment response;Walking;Work;young adult

PROJECT_TITLE: A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis and Assess Markers of Disease


ORG_CITY: LOS ANGELES

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE – Overall Concussions affect nearly 3 million Americans annually, with up to 30% not recovered 3 months after injury, and the risk for adolescents is even greater. Persistent post-concussive impairments such as migrainous headache, abnormal stress responses and mood dysregulation are common. In this work we will determine the best markers that predict these symptoms in order to provide a firm foundation for future clinical trials to treat these symptoms.

PI_NAMEs: GIOIA, GERARD A.;GIZA, CHRISTOPHER C (contact);RIVARA, FREDERICK P.

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Accident and Emergency department;Acute;Adolescent;Affect;Algorithms;American;Anxiety;Axon;Behavioral;Biochemical;Biological;biological adaptation to stress;Biological Markers;biomarker development;biomarker panel;biomarker validation;Blood;Brain;Brain Concussion;candidate validation;Cardiovascular system;Categories;Childhood;Chronic;Clinic;Clinical;Clinical Trials;Cognitive;cohort;Collaborations;Common Data Element;cytokine;Data;Detection;Development;Diffusion Magnetic Resonance Imaging;Early identification;Early Intervention;Early treatment;endophenotype;Enrollment;Foundations;Functional impairment;Future;Goals;Headache;Image;imaging biomarker;imaging modality;Impairment;Individual;Injury;innovation;Intervention;Lesion;Longitudinal cohort study;Magnetic Resonance Imaging;Measurement;Measures;medical specialties;Membrane;Migraine;mild traumatic brain injury;Molecular;molecular marker;Moods;Movement;National Institute of Neurological Disorders and Stroke;neurobehavioral;Neurobehavioral Manifestations;Neurocognitive;neuroimaging;neuroinflammation;Neurologic;Neuropsychology;novel;patient subsets;Phenotype;Phospholipids;Physiological;Population;Post-Concussion Syndrome;Postural adjustments;prediction algorithm;predictive marker;Prevention;primary care clinic;prospective;Psychophysiology;Radiology Specialty;recruit;Registries;Research;Resolution;respiratory;Risk;risk stratification;Science;screening;Site;Sports Medicine;symptom cluster;symptom treatment;symptomatology;Symptoms;Techniques;Testing;Time;trait;Traumatic Brain Injury;Validation;vestibular system;Work;Youth

PROJECT_TITLE: Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids


NIH_SPENDING_CATS: Brain Disorders;Childhood Injury;Neurosciences;Pain Research;Pediatric;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

PI_NAMEs: GIZA, CHRISTOPHER C (contact)

PROJECT_TERMS: Adolescent;Affect;Age;age difference;Biological;biological adaptation to stress;Biological Markers;Blood;Blood Tests;Brain;Brain Concussion;brain electrical activity;Brain scan;Cardiovascular system;Caring;Categories;Child;Childhood;Classification;Clinical;Clinical Data;cognitive testing;Collaborations;Common Data Element;comorbidity;Data;Data Collection;data collection site;data curation;data dissemination;data sharing;data standards;Dedications;Development;disability;Education;endophenotype;Ensure;Equilibrium;experience;falls;Functional disorder;Funding;Future;Goals;Guidelines;Image;improved;Individual;Information Dissemination;injured;Injury;Lead;Leadership;Link;Measurable;Measures;Medical;meetings;Methods;Molecular;Monitor;National Institute of Neurological Disorders and Stroke;Nature;Nervous System Physiology;Neurobiology;Neurocognitive Deficit;Outcome;Patients;Pattern;Persistent pain;persistent symptom;Persons;Phase;Physiological;Post-Concussion Syndrome;Prevention;Procedures;Process;prognostication;programs;Public Health;Publications;Publishing;Quality Control;Recovery;Research;Research Personnel;Resources;Risk;Role;Saliva;Scientific Inquiry;sex;Site;Sports;Standardization;Structure;Symptoms;Testing;Time;timeline;Training;Training and Infrastructure;Traumatic Brain Injury;treatment trial;Validation;Vehicle crash;Work;Youth

PROJECT_TITLE: CARE4Kids: Administrative Core


NIH_SPENDING_CATS: Brain Disorders;Childhood Injury;Clinical Research;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

PI_NAMEs: COOK, LAWRENCE JOSEPH (contact)

PROJECT_TERMS: Adherence;Adolescent;Adult;Affect;Algorithms;Biological;Biological Markers;biomarker development;biomarker validation;Biometry;Blood;Blood Proteins;Blood specimen;Blood Specimen Collection;Brain Concussion;Child;Clinic;Clinic Visits;Clinical;Clinical Data;Clinical Research;cohort;Collection;Common Data Element;concussive symptom;cost;Data;Data Collection;Data Coordinating Center;data management;data quality;data sharing;data standards;design;Development;disability;Distal;Education;Emergency department visit;endophenotype;Enrollment;Ensure;experience;Goals;Health;Image;imaging biomarker;Individual;Informatics;Injury;Leadership;life span;Measures;medical specialties;Methods;mild traumatic brain injury;Minority;Monitor;Morbidity - disease rate;National Institute of Neurological Disorders and Stroke;neurobehavioral;neuroimaging;Neuropsychology;oculomotor;Outcome;Participant;Phase;Population;Post-Concussion Syndrome;predictive marker;predictive tools;prospective;Protocols documentation;Public Health;Qualifying;Recovery;Registries;Reporting;Research;Research Support;Resources;Risk;risk prediction;risk stratification;Site;Surveys;symptom cluster;Symptoms;System;Technical Expertise;Text;Text Messaging;Time;Traumatic Brain Injury;United States;Universities;Utah;Youth

PROJECT_TITLE: CARE4Kids: Data Coordinating Core


PI_NAMEs: ASARNOW, ROBERT F (contact)

PROJECT_TERMS: Acute;Address;Adolescent;Age;analytical method;Autonomic Dysfunction;Autonomic nervous system;Autonomic nervous system disorders;axon injury;Biological Factors;Biological Markers;Blood Pressure;blood-based biomarker;Brain;Brain Concussion;Brain imaging;Brain Injuries;Breathing;Cardiovascular system;Central Nervous System;Chronic;Clinical;clinical decision-making;Cognitive;cohort;concussive symptom;Congenital neurologic anomalies;Data;Data Analyses;design;detection sensitivity;Development;Educational Status;endophenotype;Equipment;Functional disorder;Gender;Goals;Heart Rate;heart rate variability;Hour;imaging biomarker;imaging modality;innovation;Link;Literature;Longitudinal Studies;Manuals;Measures;Methodology;molecular marker;Nervous System Physiology;Neurobiology;neuroinflammation;neuropsychiatric disorder;Patients;Phase;Physiological;Pilot Projects;Post-Concussion Syndrome;Postural adjustments;predictive marker;Prognosis;Protocols documentation;psychological stressor;Quality Control;Recovery;Research Assistant;Research Project Grants;Research Training;respiratory;response;Rest;Sample Size;Signs and Symptoms;Site;Standardization;Structure;Symptoms;systematic review;Testing;Time;Training;Validation;Variant

PROJECT_TITLE: CARE4Kids: Autonomic Biomarker Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Childhood Injury;Clinical Research;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

PI_NAMEs: THOMPSON, PAUL M (contact)

PROJECT_TERMS: 3-Dimensional;Administrative Supplement;Adolescent;Affect;Anatomy;arterial spin labeling;biobank;Biological Markers;Blood;blood perfusion;Brain;Brain Concussion;Brain imaging;brain magnetic resonance imaging;Brain region;Brain scan;brain volume;Calibration;Cerebrovascular Circulation;Child;Clinical;Clinical assessments;cognitive development;cohort;Collection;combat;Common Data Element;Communities;cost;Data;Data Adjustments;Data Analyses;Data Collection;data collection site;Data Coordinating Center;data harmonization;data quality;design;Detection;Development;Diffusion Magnetic Resonance Imaging;endophenotype;Ensure;experience;falls;Feedback;Functional Magnetic Resonance Imaging;functional outcomes;Funding;Genetic study;Geometry;Goals;Hemorrhage;Image;imaging biomarker;imaging facilities;imaging study;indexing;Individual;Inflammation;Information Theory;injured;innovation;International;Machine Learning;Magnetic Resonance Imaging;Maps;Measurable;Measures;Methods;mild traumatic brain injury;Modality;Modeling;Monitor;Motion;Multimodal Imaging;multimodality;National Institute of Neurological Disorders and Stroke;Nervous System Trauma;neuroimaging;neuropathology;Outcome;Outcome Measure;outcome prediction;Participant;patient population;patient subsets;Perfusion;Phase;phenotypic data;Post-Concussion Syndrome;predict clinical outcome;Predisposition;Process;Productivity;Prognosis;Protocols documentation;Qualifying;Quality Control;Recommendation;Research;Resolution;Rest;Running;Sample Size;Scanning;Site;Standardization;Structure;Subgroup;Testing;Time;tool;Training;Travel;United States;United States National Institutes of Health;Universities;Utah;Validation;volunteer;white matter;White Matter Hyperintensity;Work

PROJECT_TITLE: CARE4Kids: Imaging Biomarker Core


NIH_SPENDING_CATS: Brain Disorders;Childhood Injury;Clinical Research;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

PI_NAMEs: BAZARIAN, JEFFREY JOHN (contact)

PROJECT_TERMS: Acute;Adolescence;Adolescent;Affect;Age;age group;Algorithms;American;axon injury;biobank;Biochemical;Biological;Biological Markers;Blood;Blood specimen;blood-based biomarker;Brain;Brain Concussion;Caring;Categories;Clinical;Clinical Management;Clinical Treatment;Clinical Trials;cognitive function;Collection;Common Data Element;critical period;cytokine;Data;data quality;Dedications;design;Development;Dizziness;Early identification;emotional functioning;endophenotype;Evaluation;executive function;experience;falls;Future;genetic analysis;Goals;Headache;high risk;Human Resources;Image;imaging biomarker;improved;Inflammation;Inflammatory;Injury;Intervention;Lipids;Long term disability;Measurement;Measures;medical specialties;Membrane;Memory;Methods;Mission;Molecular;Monitor;National Institute of Neurological Disorders and Stroke;neurodevelopment;neuroimaging;Neurons;Neuropeptides;neurotransmission;Neurotransmitters;novel;Oxidative Stress;Pathway interactions;Peptides;peripheral blood;Phenotype;Physiological;Physiological Processes;Populations at Risk;Post-Concussion Syndrome;prediction algorithm;prevent;preventive intervention;Procedures;Process;prospective;Protein Analysis;Proteins;Protocols documentation;Psychophysiology;Publishing;Quality Control;Radiology Specialty;Recovery;Reporting;repository;Reproducibility;Research Personnel;Research Project Grants;Resources;Risk;risk prediction;risk stratification;sample collection;Schools;Site;social;specific biomarkers;Standardization;success;Symptoms;targeted treatment;Technical Expertise;Techniques;Time;Training;trait;white matter change;Work;young adult;Youth

PROJECT_TITLE: CARE4Kids: Blood Biomarker Core


NIH_SPENDING_CATS: Brain Disorders;Childhood Injury;Clinical Research;Neurosciences;Pain Research;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

PROJECT_TERMS: Accident and Emergency department;Acute;Adolescent;Age;Agreement;Algorithms;Anxiety;Area Under Curve;Behavioral;Biochemical;Biological;biological adaptation to stress;Biological Markers;biomarker development;biomarker validation;Blood;Blood flow;blood-based biomarker;Brain Concussion;Brain Injuries;Cardiovascular system;cell injury;Centers for Disease Control and Prevention (U.S.);Childhood Injury;Chronic;Clinic;Clinical;clinical phenotype;cognitive performance;cohort;Collaborations;Common Data Element;common symptom;Detection;Development;Diagnostic;disability;Dysautonomias;Early identification;endophenotype;experience;Functional disorder;Functional impairment;Future;Goals;Guidelines;Image;imaging biomarker;Immune;Impairment;improved;Individual;Inflammation;Injury;Lesion;Lipids;Long term disability;Longitudinal cohort study;Measures;Medical;Mental Depression;Migraine;mild traumatic brain injury;Monitor;multidisciplinary;multimodality;Multivariate Analysis;National Institute of Neurological Disorders and Stroke;Nature;neurobehavioral;Neurobiology;neuroimaging;Neurologic;Neurologic Symptoms;Neuropsychology;Neurotransmitters;novel therapeutics;Outcome;Pain;Phase;Phenotype;Physiological;Physiology;Post-Concussion Syndrome;prediction algorithm;Prevention;Prevention strategy;preventive intervention;primary care clinic;prognostic tool;prognostication;programs;prospective;Public Health;Radiology Specialty;Recovery;recruit;Research;research clinical testing;Research Project Grants;Resolution;Resources;risk stratification;Sampling;Science;sex;Site;symptom cluster;Symptoms;Techniques;Testing;Time;trait;Traumatic Brain Injury;Validation;Youth


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative Despite remarkable improvement in responses in de novo AML patients, outcomes in relapsed or refractory AML remain dismal. We bring together a unique academic-industry precision-medicine team of investigators at Vanderbilt University Medical Center, Karyopharm Therapeutics, and Notable Laboratories to develop a predictive analytic tool in the context of developing a promising new combination therapy of the BCL2 inhibitor, venetoclax (VEN), and selinexor (SEL), a selective inhibitor of nuclear export (SINE) compound shown to sensitize patient samples to VEN. We will establish the preliminary efficacy of SEL/VEN in relapsed or refractory AML patients and train a functional assay to predict response and resistance to SEL-VEN therapy.

PI_NAMEs: METHOD, MICHAEL ;SAVONA, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Academic Medical Centers;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;alternative treatment;analytical tool;antitumor effect;Apoptotic;BCL2 gene;Biological Assay;Caring;Cell Line;Cell Nucleus;Cells;Clinical;Clinical Management;clinical practice;Clinical Trials;cohort;Combined Modality Therapy;companion diagnostics;Cytoplasm;Data;Data Set;Dependence;Development;Disease;Disease-Free Survival;Dose;drug sensitivity;effective therapy;Effectiveness;efficacy trial;Evaluation;Excision;Exhibits;exportin 1 protein;Exportins;Family;Flow Cytometry;FLT3 gene;Genetic Anticipation;Genetic Markers;genetic resistance;Genomics;Genotype;high risk;Immunophenotyping;improved;Industry;industry partner;inhibitor;Investigation;Laboratories;Lead;leukemia;leukemia initiating cell;Leukemic Cell;Link;MCL1 gene;Measurement;Medicine;Methods;Minority;Modeling;monocyte;Mutate;Mutation;Neoadjuvant Therapy;new combination therapies;novel;novel therapeutics;Nuclear;Nuclear Export;older patient;Outcome;Patients;Pattern;Phase;phase 1 study;phase 2 study;phase I trial;Phase II Clinical Trials;phase II trial;Phenotype;Phosphotransferases;Population;precision medicine;preclinical efficacy;preclinical study;predicting response;Predictive Analytics;pressure;protein transport;Proteins;RAS Family Gene;Refractory;Regimen;Relapse;relapse patients;Reproducibility;Research;Research Personnel;Resistance;resistance mechanism;responders and non-responders;response;Safety;Sampling;Selection for Treatments;Sensitivity and Specificity;single cell technology;Site;Specificity;standard of care;synergism;targeted sequencing;targeted treatment;Testing;Therapeutic;Time;tool;TP53 gene;Training;translational study;Translations;Tumor Suppressor Proteins;Validation;Work

PROJECT_TITLE: Development of a Phenotype-based Predictive Analytic for Acute Myeloid Leukemia


ORG_CITY: TAMPA

ORG_NAME: JAMES A. HALEY VA MEDICAL CENTER

PHR: Veterans who use prosthetic limbs commonly suffer from skin problems such as scars that create discomfort and pain to the point that wearing the prosthesis is no longer tolerable. The Veteran must then discontinue prosthetic use to allow healing prior to wearing the limb again. Current treatments for skin problems include manual scar mobilization and massage, stretching, desensitization techniques, pain medication, prosthetic adjustment, steroid injection, scar excision and others. Most of these have not proven to be a long-term solution. A dermatologic procedure common in non-amputees for scar and skin lesion management, fractionated laser therapy, may be a long-term solution minimizing discomfort, pain and time out of the prosthesis. This preliminary study seeks to determine if fractional laser therapy can improve prosthetic use, and quality of life of Veterans with amputation who use lower limb prostheses.

PI_NAMEs: HECKMAN, JEFFREY T. (contact)

PROJECT_TERMS: Amputation;Amputees;Analgesics;Area;Articular Range of Motion;Burn injury;Carbon Dioxide;Caring;Cicatrix;Clinic;Clinical;clinical investigation;Clinical Research;Collaborations;Cosmetics;Credentialing;Data;Deglutition;Dermatologic;Dermatologist;Dermatology;desensitization;Effectiveness;efficacy evaluation;Excision;experience;Feasibility Studies;functional restoration;Future;Goals;healing;health related quality of life;Impairment;improved;improved mobility;improved outcome;Individual;Injection of therapeutic agent;Injections;interest;Intervention;Investigation;Lasers;limb amputation;limb loss;Limb Prosthesis;Limb Salvage;Limb structure;Low-Level Laser Therapy;Lower Extremity;Manipulative Therapies;Manuals;Massage;Measures;Methodology;military veteran;Modality;Muscle;novel;novel therapeutics;Operative Surgical Procedures;Outcome;Outcome Measure;Pain;pain reduction;Patient Compliance;patient population;Patients;Pilot Projects;Population;Population Intervention;Private Sector;Procedures;Prosthesis;prosthesis fitting;prosthesis wearer;Protocols documentation;Quality of life;Recording of previous events;recruit;Rehabilitation therapy;Research;residual limb;Role;Sample Size;Sampling;Site;skills;Skin;Skin Care;skin lesion;soft tissue;Speech;standard of care;Steroids;Stretching;success;Techniques;Testing;Time;Tissues;Training;Translations;treatment duration;treatment effect;Veterans;Walking;wound

PROJECT_TITLE: The LASER Pilot Project: Laser Therapy in Amputee Skin Care to Enhance Rehabilitation. A Preliminary Investigation


ADMINISTERING_IC: MH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences

ORG_CITY: SAN JUAN

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PUERTO RICO MED SCIENCES

ORG_STATE: PR

PHR: PROJECT NARRATIVE Individuals show great variability in their vulnerability to addiction, and increased sensitivity to reward cues has been identified as a risk factor for addictive behaviors, particularly for relapse. The neurobiological mechanisms underlying individual differences in reward learning and how these contribute to addiction predisposition remain largely unknown. Using an animal model of increased sensitivity to reward cues, we focus on dissecting the functional role of the ventral hippocampus to nucleus accumbens circuit and how differences at the synaptic level can contribute to endophenotypes associated with addiction vulnerability.

PI_NAMEs: MARIA-RIOS, CRISTINA EMMA (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: addiction;Addictive Behavior;Address;Animal Model;Anxiety;Automobile Driving;Aversive Stimulus;Behavior;behavior influence;Behavioral;behavioral response;Brain;calbindin;calretinin;Cell Nucleus;Choice Behavior;Cognitive;Conflict (Psychology);Cues;Data;Decision Making;design;Desire for food;Disease;dorsal raphe nucleus;Emotional;endophenotype;Ensure;Event;Fiber;Fluorescent in Situ Hybridization;Globus Pallidus;Glutamates;Goals;high risk;Hippocampus;Hypothalamic structure;Individual;Individual Differences;individual response;individual variation;Instinct;Knowledge;Laboratories;Lateral;Learning;maladaptive behavior;Measures;Mediating;Mental Depression;motivated behavior;Motivation;Mus;neural circuit;Neural Pathways;neurobiological mechanism;Neurons;neuropsychiatric disorder;Nucleus Accumbens;Opsin;optogenetics;Output;Photometry;Population;Predisposition;preference;Process;Punishment;Relapse;Research;response;Rewards;Risk;Risk Factors;Role;Safety;segregation;Signal Transduction;Stimulus;Structure;Substance Use Disorder;Sucrose;Synapses;Testing;Time;Tracer;Translating;treatment optimization;treatment strategy;Ventral Striatum;Ventral Tegmental Area;ventral visual stream

PROJECT_TITLE: Ventral Pallidal Circuits Governing Approach/Avoidance Conflict


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Worldwide, heart failure (HF) is among the top causes of morbidity and mortality. In the United States alone, HF affects more than 6 million people with annual direct medical expenditures exceeding $30 billion. Within the VA system, HF is prevalent among 5% of US veterans with an annual mortality rate of 14.5%. Recent studies suggest chronic sterile inflammation contributes to HF progression; however, a failure to establish a causal relationship between systemic inflammation and HF outcomes has essentially halted progress in this field. Here, we propose to study how monocytes, a key player in HF inflammation, amplifies the MitoDAMP mediated inflammatory signal, and how boosting cellular NAD+ may be inhibitory to this process. In doing so, we aim to identify potential therapeutic targets for HF inflammation with the goal to improve the outcomes of Veterans who suffer from HF.

PI_NAMEs: WANG, DENNIS DING HWA (contact)

PROJECT_TERMS: Affect;Aging;American;Anti-Inflammatory Agents;Antiinflammatory Effect;autocrine;Biological Assay;career;Cell Line;Cells;Centrifugation;Chronic;Clinical;Clinical Research;Clinical Trials;combat;Congestive Heart Failure;cytokine;Data;Death Rate;Development;Disease;effective therapy;Encapsulated;exosome;extracellular vesicles;Failure;Foundations;FPR1 gene;Funding;Future;Goals;Health Expenditures;Heart failure;Immune;immunogenic;immunogenicity;improved outcome;In Vitro;in vivo;Individual;Inflammation;Inflammatory;inhibitor;Interleukin-1 beta;Interleukin-6;knock-down;Knowledge;Link;Macrophage;Mediating;Mediator;Metabolic;Mitochondria;Modeling;Molecular;Molecular Target;monocyte;Morbidity - disease rate;mortality;new therapeutic target;nicotinamide-beta-riboside;novel;Oral Administration;Outcome;paracrine;Pathologic;Pathway interactions;Patients;Pattern;Peripheral;Persons;Plasma;Positioning Attribute;pre-clinical;preclinical study;Process;Production;programs;randomized trial;receptor;Reporting;Research;Role;Sampling;Signal Transduction;SIRT1 gene;skills;Source;Sterility;System;systemic inflammatory response;Testing;therapeutic target;therapeutically effective;Tissues;TNF gene;United States;vesicular release;Veterans

PROJECT_TITLE: Boosting NAD to Combat Heart Failure Sterile Inflammation


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Traumatic brain injury (TBI) is a devastating condition with limited treatment options. Incidence and long-term consequences of TBI disproportionately burden Veterans. This project aims at improving prospects for Veterans and other TBI victims through reducing both initial brain damage as well as repair of chronic abnormalities in white matter. Neuroinflammation is a major contributor to acute secondary damage, and white mater loss exacerbates the injury over the long term. We propose to address these two aspects by intra- arterially transplanting glial progenitor cells, engineered to express Nanobodies, selectively blocking neuroinflammation-inducing danger signals. Over the last two decades our research has focused on improving therapeutic agents targeting the brain with an intra-arterial route facilitating minimally invasive administration of high concentrations of drugs with immediate access within the entire lesion.

PI_NAMEs: WALCZAK, PIOTR  (contact)

PROJECT_TERMS: Acute;Address;Adenosine Triphosphate;Animal Model;Animals;behavior test;Binding;Biodistribution;Biomedical Engineering;blood-brain barrier crossing;Bodily secretions;Brain;Brain Injuries;brain parenchyma;brain repair;Case Study;Cell Culture Techniques;Cell Therapy;Cells;cellular targeting;Cerebrum;Chronic;Chronic Phase;clinical practice;clinical translation;Complex;controlled cortical impact;Data;design;Diet;Dose;dysmyelination;efficacy testing;Elements;Emergency department visit;Engineering;Evaluation;experience;Extravasation;Flow Cytometry;Formulation;functional improvement;Goals;Health system;Histology;Hospital Costs;Hospitalization;image guided;imaging platform;Immune response;improved;In Situ;in vivo;Incidence;Inflammation;Inflammatory;Injections;Injury;innovation;Intravenous;Label;Leadership;Lesion;Letters;macromolecule;Mediating;Messenger RNA;Microglia;Military Personnel;minimally invasive;Molecular;Morphology;mouse model;Multimodal Imaging;Mus;myelination;nanobodies;neuroinflammation;Neurologic Deficit;novel;novel therapeutic intervention;Pathology;Patients;Pattern;Pharmaceutical Preparations;Phase;prevent;Production;Productivity;progenitor;Public Health;purinoceptor P2Z;receptor;Rehabilitation therapy;repaired;Research;Resolution;Risk;Route;Safety;safety study;safety testing;service member;Signal Transduction;stem cell delivery;stem cell therapy;stem cells;success;System;targeted treatment;TBI treatment;Techniques;Therapeutic;Therapeutic Effect;therapeutic target;Time;transcriptomics;Transplantation;Traumatic Brain Injury;Traumatic Brain Injury recovery;Veterans;War;white matter;white matter damage;white matter injury;Work

PROJECT_TITLE: Image-guided intra-arterial delivery of stem cells to repair brain damage after TBI

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURC-C (01)]


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Traumatic brain injury (TBI) is a condition with higher prevalence in the veteran population than civilians and is associated with multi-dimensional impairments in function impacting neurocognition, psychological well-being, personality, motor function, and activities of daily living. These impairments have diverse biological causes, producing a challenge for both scientific reproducibly of therapeutic discoveries as well as bench-to-bedside translation of discoveries into veteran healthcare. Project 4 of the proposed linked merit will take a data-science approach to TBI biomarker discovery, integrating data on retinal function and structure, blood biomarkers, biomechanical modeling and outcomes in multiple rodent models of TBI (blast, contusion, percussion, weight drop injuries) produced by Projects 1-3. Harnessing data science and machine intelligence tools we will help identify biomarker signatures predicting TBI impairment and help validate biomarker measures for translation and precision medicine.

PI_NAMEs: FERGUSON, ADAM R (contact)

PROJECT_TERMS: 3-Dimensional;Accounting;Activities of Daily Living;advanced analytics;Affect;animal data;Animal Model;Animal Testing;Artificial Intelligence;assay development;Autoantibodies;Award;Axon;base;bench-to-bedside translation;Big Data;big data management;Biological;Biological Markers;biomarker discovery;biomarker identification;biomarker validation;biomechanical model;blast trauma;Blood;blood-based biomarker;Brain;Brain imaging;candidate validation;Chronic;Cities;Clinical Research;Cognitive;cognitive function;cohort;complex data;Computer Models;Contusions;cytokine;Data;Data Analyses;Data Commons;data dictionary;Data Element;data ingestion;data integration;data management;data modeling;Data Science;Data Set;data sharing;Dimensions;diverse data;Drops;Ensure;ex vivo imaging;experimental study;Explosion;Exposure to;Eye;FAIR principles;Functional disorder;functional outcomes;Healthcare;High Prevalence;Histology;Human;Image;imaging modality;Impairment;improved;Individual;Informatics;information model;Infrastructure;Ingestion;Injury;Iowa;Laboratories;Link;Machine Learning;Magnetic Resonance Imaging;Measures;Mediating;Methods;military veteran;Modeling;Monitor;Motor;Multiple Trauma;Mus;Nerve Degeneration;Nervous System Trauma;Neurocognition;neuroimaging marker;Neurological outcome;Neuronal Dysfunction;Neurons;open data;Optic Disk;Optic Nerve;Optic tract structure;Outcome;Output;Pathology;Pattern;Pattern Recognition;Percussion;Personality;Phase;potential biomarker;pre-clinical;precision medicine;Precision therapeutics;predictive marker;predictive signature;protein expression;Proteomics;Quality Control;Rattus;Reproducibility;Research;Research Personnel;Resources;Retina;Retinal Diseases;Rodent Model;Sampling;San Francisco;Scientist;sensor;Serum;Severities;Shock;Signal Transduction;Site;Statistical Data Interpretation;Statistical Models;statistics;Stress;Structure;Testing;Therapeutic;therapeutic development;therapeutic target;Tissue Model;Tissues;tool;translational medicine;translational therapeutics;transmission process;Traumatic Brain Injury;Tube;Validation;Veterans;Visual;Weight;Well in self;Work

PROJECT_TITLE: BCCMA: Predicting TBI Pathology with Visual and Blood-based Biomarkers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURF-C (01)]


PHR: The prevalence of chronic kidney disease (CKD) in the US is rising concomitant with aging of the general population. We show deletion of kidney megalin worsens acute ischemic kidney failure and accelerates the progression to CKD. This proposal will examine the role of megalin in the transition from acute kidney injury to renal failure.

PI_NAMEs: SHEIKH-HAMAD, DAVID  (contact)

PROJECT_TERMS: Acceleration;Acute;Acute Renal Failure with Renal Papillary Necrosis;Aging;Angiotensin II;Animal Experiments;Antioxidants;Attenuated;Autophagocytosis;Biogenesis;Biological Availability;Biological Process;Calcineurin;Cardiovascular Diseases;Cardiovascular system;Cell Cycle;Cell Cycle Arrest;cell injury;Cell Proliferation;Cell surface;Cells;Chronic Kidney Failure;Clathrin;coated pit;comorbidity;Cultured Cells;Cyclin D1;Data;Development;Diabetes Mellitus;Disease;Disease Progression;Down-Regulation;Endocytosis;Endosomes;Epithelial Cells;Epithelium;exosome;Fibrosis;FRAP1 gene;General Population;Glycolysis;Goals;Health;Human;Hypertension;Hypoxia;Impairment;In Vitro;in vivo;Inflammation;Injury to Kidney;Ischemia;Kidney;Kidney Failure;kidney fibrosis;kidney preservation;Kinetics;LDL-Receptor Related Protein 2;Ligands;Lysosomes;MADH3 gene;MAPK1 gene;Mediating;Metabolic syndrome;Mitochondria;Modeling;Morphology;mortality;Mus;Neurodegenerative Disorders;Outcome;overexpression;Pathway interactions;Peptide Hydrolases;Play;preservation;Prevalence;prevent;Process;Proliferating Cell Nuclear Antigen;Proteins;Publishing;receptor;Recovery;Renal function;renal ischemia;Reperfusion Therapy;Respiration;Role;Signal Transduction;Signaling Molecule;STC1 gene;Stress;Sudden Death;Surface;therapeutic target;Transforming Growth Factor beta;Tubular formation;Up-Regulation;uptake

PROJECT_TITLE: Megalin, and transition from AKI to CKD

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


ORG_CITY: MEMPHIS

ORG_NAME: MEMPHIS VA MEDICAL CENTER

PHR: Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Our proposed studies will provide an innovative and novel treatment trial for chronic gastrointestinal symptoms in veterans with Gulf War Illness that were deployed into war zones. Given that there are currently no specific treatments for these disorders, and that current symptomatic approaches are far from ideal, proof of principle of our trial would be an extremely important advance as it would not only have a beneficial impact on the health of many thousands of our veterans, but also it would substantially reduce the many negative economic effects of this ailment on the VA Health Care System.

PI_NAMEs: VERNE, GEORGE NICHOLAS;ZHOU, QIQI  (contact)

PROJECT_TERMS: Abdominal Pain;Afghanistan;Arthralgia;Atrophic;Bacterial Translocation;Cells;chemoradiation;Chronic;chronic abdominal pain;Clinical Trials;clinically significant;Controlled Clinical Trials;Crohn's disease;Data;Diarrhea;Disease;Disseminated Malignant Neoplasm;Double-Blind Method;Economics;effective therapy;Effectiveness;Energy-Generating Resources;Environmental Epidemiology;Epithelium;Etiology;Fatigue;Freedom;gastrointestinal function;gastrointestinal symptom;Gastrointestinal tract structure;Glutamine;Grant Review;Headache;Health;Healthcare Systems;Human;improved;innovation;intestinal injury;Intestinal Mucosa;Intestinal permeability;Iraq;Malignant neoplasm of esophagus;Measures;Morbidity - disease rate;Myalgia;novel;operation;Oral;Outcome Measure;pain symptom;Patients;Persian Gulf;Persian Gulf Syndrome;Placebo Control;Placebos;primary outcome;Publishing;Randomized;Registries;Reporting;Research;restoration;Services;Severities;Site;Supplementation;symptomatic improvement;Symptoms;Testing;treatment response;treatment trial;Veterans;War

PROJECT_TITLE: Mechanisms of Gulf War Illness


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Neurosciences

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative The KIBRA gene is associated with natural variation in human memory and the complexes it organizes are associated with multiple neuropsychiatric disorders, but the role of KIBRA in regulating circuit dynamics is unknown. Gaining an in-depth understanding of how KIBRA regulates brain circuit function will guide our understanding of how the brain executes complex cognitive functions in health and disease. This work will provide insight into how specific psychiatric disease-relevant molecular mechanisms contribute to brain network function and may highlight new molecular or neurophysiological targets for diagnosis and treatment.

PI_NAMEs: QUIGLEY, LILYANA DREAM (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: allostatic load;Animal Model;Behavioral;behavioral outcome;Biochemical;Biochemistry;Bioenergetics;Biological Assay;Biological Markers;Bipolar Disorder;Brain;brain cell;brain health;Brain region;candidate marker;career;Categories;Cell Physiology;Cell Separation;cell type;Cellular Stress;Clinical;Cognition;Cognitive;cognitive function;Complex;Computer Analysis;Data;Diagnosis;Diagnostic;Disease;electrical measurement;Electrophysiology (science);environmental stressor;Exhibits;experimental study;Genes;Genetic Techniques;Health;Hippocampus;Human;Image;Imaging Techniques;in vivo;Individual;insight;Joints;Life;Light;Major Depressive Disorder;Measurement;Measures;Memory;Mental disorders;Metabolic;Methods;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Mitochondrial Proteins;Molecular;Molecular Genetics;molecular marker;Multivariate Analysis;Mus;neural;neurophysiology;neuropsychiatric disorder;neuropsychiatry;novel therapeutics;optogenetics;Oxidative Stress;Oxidative Stress Induction;Pathologic;Pattern;Peripheral;Phenotype;Photosensitizing Agents;Physiological;Play;Post-Traumatic Stress Disorders;potential biomarker;Procedures;Process;Production;Property;protein expression;Proteomics;Quality Control;Reactive Oxygen Species;Regulation;Research;respiratory;response;Role;Schizophrenia;spatiotemporal;Specificity;Statistical Methods;Stress;synaptic function;Testing;Training;Variant;Work

PROJECT_TITLE: Investigating the Role of KIBRA-Dependent Synaptic Function on Hippocampal and Cortical Network Mechanisms Underlying Complex Cognition


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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;Mental Health;Neurodegenerative;Neurosciences

ORG_DEPT: PSYCHOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative In my dissertation, I will use newly-developed machine learning techniques to study how the brain uses prior knowledge (about the spatial structure of an environment, or how certain types of events unfold in time) to scaffold new learning. By precisely characterizing how this scaffolding process works, my research will help to identify ways in which prior knowledge can be more optimally leveraged to support learning. This will lead to the development of tools to help memory-impaired individuals make better use of intact prior knowledge to support new learning, as well as remedies for groups where deficiencies in prior knowledge prevent them from learning properly.

PI_NAMEs: MASIS, ROLANDO  (contact)

PROJECT_TERMS: Achievement;Age;Alzheimer's Disease;Back;Brain;Childhood;Coffee;Collection;Computer Models;Cues;Dementia;Deterioration;Disease;Distant;Electroencephalography;empowerment;Environment;Episodic memory;Event;experimental study;Functional Magnetic Resonance Imaging;Future;Goals;Home;imaging properties;improved;Individual;innovation;insight;Knowledge;Learning;Learning Difficulty;Life;Life Experience;Location;Machine Learning;Magnetic Resonance Imaging;Memory;memory encoding;Memory impairment;Methodology;Nature;neural;neural correlate;neurofeedback;Pattern;Persons;portability;prevent;Process;programs;Property;Psychology;Research;Retrieval;Robin bird;Role;scaffold;Structure;System;Techniques;Technology;theories;Time;tool;tool development;virtual reality;virtual reality environment;Work

PROJECT_TITLE: Tracking the dynamics of how schemas scaffold recall


ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

PHR: Beta2-glycoprotein I (β2-Gp 1) is a cardiolipin-binding plasma glycoprotein with unknown physiological function. Antibodies to this protein are frequently found in patients with thrombosis and the mechanism is not known. We show that β2-Gp 1 binds to cardiolipin-expressing extracellular mitochondria in the circulation and promotes its phagocytosis by macrophages. In vivo, β2-Gp 1-deficient mice have increased circulating extracellular mitochondria and defective clearance of infused mitochondria from the circulation. We posit that the evolutionarily conserved β2-Gp 1 function as a clearing molecule for damaged mitochondria. In this proposal, we will mechanisms of β2-Gp 1-dependent mitochondrial clearance and the procoagulant effect of anti β2-Gp 1 antibodies induces thrombosis.

PI_NAMEs: THIAGARAJAN, PERUMAL  (contact)

PROJECT_TERMS: abortion;Amino Acids;Anti-phospholipid Syndrome;Antibodies;Antibody titer measurement;Anticardiolipin Antibodies;Antigens;Antiphospholipid Antibodies;Bacterial DNA;beta 2-glycoprotein I;Binding;Binding Proteins;Blood coagulation;Blood Vessels;C-terminal;Cardiolipins;Cells;Characteristics;Charge;Circulation;Complement;COVID-19;Crista ampullaris;Cysteine;disulfide bond;Endothelial Cells;Endothelium;Energy Supply;Epitopes;extracellular;Extracellular Space;Factor XIII;General Population;Glycoproteins;Goals;GTPBP1 gene;Haptoglobins;Human;Impairment;In Vitro;in vivo;Infection;Inflammatory Response;Inner mitochondrial membrane;Interleukin 2 Receptor;Invertebrates;Investigation;Link;Lipoproteins;Macrophage;Mediating;member;meter;Mitochondria;Mitochondrial DNA;mitochondrial membrane;Molecular;Molecular Conformation;monocyte;Mus;novel;Organelles;Patients;Pattern;Phagocytosis;Phospholipids;Physiological;Placenta;Plasma;Play;Property;Proteins;Recurrence;Respiratory Chain;response;Role;Second Pregnancy Trimester;SELP gene;Structure;Sushi Domain;Testing;Thrombosis;tissue injury;uptake;Venous;Vesicle

PROJECT_TITLE: Thrombosis and Antiphospholipid Antibodies

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Genetics;Machine Learning and Artificial Intelligence;Neurosciences;Pediatric;Sleep Research

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Although the role of sleep has been studied in many different contexts, little effort has been dedicated to understanding the role of sleep in the acquisition of communicativebehaviors. With a well-defined neural circuitry underlying a robust and stereotyped learned behavior, along with evidence pointing to changes in song structure during sleep, the songbird is exceptionally suited for examining sleep-based learning mechanisms. Byidentifying circuits mechanisms involved in memory consolidation we will stand better equipped to help those affected by sleep disturbances.

PI_NAMEs: ALAM, DANYAL H (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acute;Adolescent;Adult;Affect;Animal Model;auditory feedback;Award;Behavior;bird song;Birds;Brain;Brain region;Cell Nucleus;Complex;Courtship;CRISPR/Cas technology;critical developmental period;Data Set;Dedications;deep learning;Development;Dissection;Engineering;Environment;Episodic memory;Evolution;Female;fitness;follow-up;Gene Delivery;Generations;Genes;Genetic;genetic approach;Genetic Engineering;genetic manipulation;Genetic Techniques;Goals;Hippocampus;Hour;Human;improved;in vivo;Individual;infection rate;innovation;Invaded;Investigation;Knowledge;Label;learned behavior;Learning;Learning Skill;Ligands;Literature;Machine Learning;male;Mate Selections;Memory;memory consolidation;Mentors;Methods;Molecular;Motor;motor behavior;Motor Cortex;Motor Skills;Nervous System;neural circuit;Neurons;Neurosciences;nonhuman primate;novel;Partner in relationship;pathogenic virus;Pathway interactions;Perceptual learning;Performance;pharmacologic;Pharmacology;Phase;Play;Population;post-doctoral training;Postdoctoral Fellow;pre-doctoral;preference;pressure;Principal Investigator;procedural memory;Process;Production;Research;Research Personnel;Research Project Grants;RNA Interference;Role;segregation;Signal Transduction;Sleep;Sleep disturbances;Songbirds;Speech;Speech Disorders;Stereotyping;Structure;Synapses;System;Technical Expertise;Techniques;Testing;theories;Therapeutic;tool;Toxic effect;Training;transcriptome sequencing;Tropism;tutoring;Uncertainty;vector;Viral;Viral Vector;Virus;vocal learning;vocalization;Work;zebra finch

PROJECT_TITLE: Sleep Based Memory Consolidation in Juvenile Zebra Finch


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Eye Disease and Disorders of Vision;Mental Health;Mental Illness;Neurosciences;Schizophrenia

ORG_CITY: NEW HAVEN

ORG_DEPT: NEUROSCIENCES

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The proposed research is relevant to public health as many mental health disorders including schizophrenia and bipolar disorder exhibit abnormal neuronal network activity. This research will help identify changes that occur in specific types of neurons leading to abnormal neuronal network function to enhance our understanding of how neuronal networks work and lead to future studies on how to prevent and treat these alterations. The proposed research is relevant to the NIH because it builds on our understanding of how neuronal network function develops and how it is impaired in complex disorders.

PI_NAMEs: RODRIGUEZ DIAZ, JEAN CARLOS (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Acute;Adult;Age of Onset;Animal Model;Animals;antagonist;Attention;Award;behavioral phenotyping;Biological Assay;Bipolar Disorder;Brain;career;Cells;Cognitive deficits;Complex;Computer Models;confocal imaging;Data Analyses;density;Development;Disease;Dissociation;Electrophysiology (science);Environmental Impact;Etiology;Exhibits;experience;Exposure to;Foundations;Functional disorder;Future;Generations;Goals;Hippocampus;human model;Immunohistochemistry;Impairment;in silico;in vivo;inhibitory neuron;Injections;Interneuron function;Interneurons;Ion Channel;Ketamine;Link;Long-Term Effects;Maintenance;mature animal;Measures;Mediating;Memory;Mental disorders;Microelectrodes;MK801;Modeling;Molecular;Mus;N-Methyl-D-Aspartate Receptors;neonatal exposure;network models;neural network;Neurons;novel;Oxidative Stress;Parvalbumins;patch clamp;Pathology;Pathway Analysis;Pattern;Perforation;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Physiological;Physiology;Postdoctoral Fellow;Predisposition;Preparation;prevent;Process;Property;protein expression;Proteins;Public Health;Research;Research Personnel;Research Project Grants;Rodent Model;Role;Schizophrenia;Sensory;skills;Synapses;Techniques;Testing;Training;training opportunity;Transgenic Mice;United States National Institutes of Health;Viral Vector;Western Blotting;Work

PROJECT_TITLE: Role of fast spiking interneurons in network synchronization and development


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cardiovascular;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Although race has no biological basis, racism is a known socioenvironmental stressor that has dire effects on physical and mental health in Black Americans. Here, we aim to quantify the neurobiological impact of perceived racism on behavioral and functional correlates of the medial temporal hippocampal system, a region highly sensitive to socioenvironmental stress and implicated in stress regulation and learning and memory. Understanding whether perceived racism impacts MTH neurocognitive integrity will allow researchers to develop individualized interventions, as well as in the future provide evidence to policy makers to direct funding to underserved, under-resourced communities to mitigate the impact of socioenvironmental factors such as racism.

PI_NAMEs: ROSARIO, MICHAEL ANTHONY (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: acute stress;acute traumatic stress disorder;Address;Affective;age related decline;Amygdaloid structure;Animal Model;Anterior;Area;arterial stiffness;Attenuated;Award;Behavior;Behavioral;Behavioral Model;Biological;biological adaptation to stress;Black American;Black race;black women;Black, Indigenous, People of Color;Brain;brain health;BRAIN initiative;cardiorespiratory fitness;cardiovascular disorder risk;cardiovascular health;career development;Chronic;Chronic stress;Cognitive;Collaborations;Communication;Communities;Data;Data Analyses;dentate gyrus;Development;Disparity;diversity and inclusion;emerging adulthood;Environmental Hazards;Episodic memory;Exercise;Experimental Designs;experimental study;Feedback;Fellowship;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Grant;health equity;Health equity research;Hippocampus;Human;improved;Individual;Individual Differences;Intervention;Interview;Lead;Learning;Left;Link;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Manuscripts;marginalization;Measures;Medial;Mediation;Memory;memory encoding;Mental Health;Mentors;Mentorship;Methods;Modality;Modeling;modifiable risk;Mood Disorders;multimodal neuroimaging;multimodality;National Institute of Mental Health;neural;Neurobiology;Neurocognitive;Neurocognitive Deficit;neuroimaging;neuroinflammation;Neurosciences Research;older adult;Outcome;Participant;Pattern;Peer Review;perceived discrimination;Performance;physical conditioning;Policies;Policy Maker;Positron-Emission Tomography;Postdoctoral Fellow;Process;Proxy;Psychosocial Stress;Public Health;Publications;Race;racism;Regulation;Research;Research Domain Criteria;Research Personnel;Research Priority;Research Project Grants;resilience;Resolution;Resources;Risk Factors;Sampling;Science;Scientist;Services;Severities;skills;social consciousness;Social Environment;social health determinants;socioenvironmental factor;Statistical Data Interpretation;Statistical Models;Stimulus;Stress;stressor;Students;symposium;System;Task Performances;Testing;Thick;Training;translational neuroscience;underserved community;United States;United States National Institutes of Health;Universities;Women's Health;Work;Writing;young adult

PROJECT_TITLE: The ABCD Study and Brain Health: Navigating Environmental Hazards and the Quest for Neurodevelopmental Intersectional Health Equity


NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE Encephalopathy due to mitochondrial and peroxisomal elongation (EMPF) is a devastating neurodevelopmental disease with no effective treatment. This project investigates the mechanism of EMPF by exploring the role of mitochondrial and peroxisomal dynamics in early neurodevelopment using patient-derived induced pluripotent stem cells (iPSCs) and cerebral brain organoids. Through these efforts, we hope to uncover novel mechanisms of metabolic signaling in human brain development that may lead to potential therapeutic targets.

PI_NAMEs: ROBERTSON, GABRIELLA LOU PUIG (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: 3-Dimensional;Address;Affect;Biochemical;Biological;Biological Assay;Biology;Brain;Carbon;Cells;Cerebrum;Clinical;confocal imaging;Coupling;Crista ampullaris;Cytometry;Defect;Development;Developmental Delay Disorders;Disease;Disparate;Dominant-Negative Mutation;Dynamin;Dynamin I;effective therapy;Electron Transport;Embryo;Encephalopathies;Epilepsy;experience;Fibroblasts;Generations;Genes;Glycolysis;Guanosine Triphosphate Phosphohydrolases;Heterozygote;Human;human induced pluripotent stem cells;Immunohistochemistry;Impairment;In Vitro;induced pluripotent stem cell;insight;Knock-out;Knowledge;Laboratory Research;Lead;Maintenance;Measures;Metabolic;metabolic profile;Metabolism;Microcephaly;Missense Mutation;Mitochondria;Molecular;Morphology;mouse model;multi-electrode arrays;Muscle;mutant;Mutation;nerve stem cell;neurodevelopment;Neurodevelopmental Disorder;Neurodevelopmental Impairment;neurogenesis;neurological pathology;neuron development;neuronal excitability;Neurons;novel;Organelles;Organoids;patch clamp;patient derived induced pluripotent stem cells;Patients;peroxisome;Phase;Phenotype;Play;post-doctoral training;Postdoctoral Fellow;Production;programs;Proliferating;Prosencephalon;Proteins;Protons;Regulation;Research;Research Personnel;Research Project Grants;Role;Running;Seizures;self-renewal;Signal Transduction;skills;stem cell model;Structure;superresolution imaging;superresolution microscopy;Symptoms;System;Technical Expertise;Technology;Therapeutic;therapeutic target;tool;Training;Transmission Electron Microscopy;two-dimensional;Work

PROJECT_TITLE: The impact of mitochondrial and peroxisomal fission dynamics on metabolic signaling during corticogenesis.


ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

ORG_STATE: MI

PHR: The incidence of central sleep apnea and heart failure is increased in Veterans with spinal cord injury (SCI). The underlying mechanism responsible for the link between the two disorders is unknown. However, it is possible that a decrease in central nervous system serotonin (5HT) induced by SCI may be the cause. Reduced 5HT might initiate central apnea along with increases in sympathetic nervous system activity that ultimately leads to heart failure. Our study will explore this possibility using a spontaneously breathing mouse model with or without genetic depletion of central nervous system 5HT, before and after spinal cord injury. We will also explore if treatment with a serotonin re-uptake inhibitor mitigates harmful outcomes following SCI.

PI_NAMEs: MATEIKA, JASON H. (contact)

PROJECT_TERMS: Affect;Age;Air Movements;airway muscle;Apnea;Arousal;Brain Stem;Breathing;Cardiovascular Diseases;Cardiovascular system;Central Nervous System;Central Sleep Apnea;Cervical spinal cord injury;Chronic;circadian;Classification;constriction;Coupled;Coupling;Diagnosis;Disease;Echocardiography;EFRAC;Elderly;Event;Frequencies;Functional disorder;General Population;Genetic;genioglossus muscle;Geometry;Heart failure;heart function;High Prevalence;HTR2A gene;Hypercapnia;Hypertension;Hypoglossal nerve structure;Hypoxia;improved;Incidence;Individual;Knockout Mice;Lead;Left;Left Ventricular Ejection Fraction;Left Ventricular Function;Left Ventricular Hypertrophy;Link;male;Measures;Mental disorders;military veteran;Modification;Motor Neurons;mouse model;Mus;Myocardial dysfunction;Nerve;Neurologic;Neurons;Obstructive Sleep Apnea;Outcome;Paroxetine;Patients;Physiological;Post-Traumatic Stress Disorders;prevent;receptor;Reflex action;respiratory;Respiratory Muscles;response;Role;Screening procedure;Selective Serotonin Reuptake Inhibitor;Sensory;Serotonergic System;Serotonin;serotonin receptor;Severities;Sleep Apnea Syndromes;Sleep Fragmentations;Spinal cord injury;Structure of phrenic nerve;Sympathetic Nervous System;Testing;Therapeutic;Time;TPH2;Veterans;Wild Type Mouse;Withdrawal

PROJECT_TITLE: 5HT-a common unifying mechanism responsible for central sleep apnea, sympathoexcitation and heart failure in spinal cord injury.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 PULM-N (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);Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Mental Health;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Rehabilitation

ORG_CITY: CHARLESTOWN

ORG_NAME: SPAULDING REHABILITATION HOSPITAL

PHR: Narrative: Older adults are more prone to experiencing poorer long-term physical, mental, and cognitive health due to age-related frailty, which can become exacerbated during episodes of critical illness that results in admission to an Intensive Care Unit (ICU). Prior reports suggest that the cognitive dysfunction is related to physical health but mechanistic links between skeletal muscle and brain have been under explored. Therefore, the goal of this project is to determine the associations between elevated neurotoxic kynurenines with physical and cognitive in older patients in the ICU and after discharge.

PI_NAMEs: YATES, BRANDON  (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;Adherence;Admission activity;age acceleration;age related;Aging;aging process;aging related;Alzheimer's disease related dementia;Area;Award;Biological Markers;Body Weight decreased;Brain;brain dysfunction;brain health;Chronic;Clinical;Cognitive;cognitive function;Critical Care;Critical Illness;Data;Death Rate;Delirium;design;Development;Disease;Early Diagnosis;exercise intervention;exercise intolerance;exercise physiologist;exercise program;exhaustion;Exhibits;experience;Family;Fatty acid glycerol esters;Fellowship;Frail Elderly;frailty;functional disability;Functional disorder;Goals;Health;Home;Hospitalization;Image;Impaired cognition;Impairment;improved;Infiltration;Inflammation;Inflammatory;Inflammatory Response;Intensive Care;Intensive Care Units;Intramuscular;Knowledge;Kynurenine;Left;Life;life span;Link;Literature;Mediating;Memory Loss;Mental Depression;Mental Health;Mentors;Mitochondria;Monitor;mortality;Muscle;Muscle Weakness;Musculoskeletal;Myopathy;NADP;neuromuscular;neuromusculoskeletal;neuropathology;neuroprotection;neurotoxic;neurovascular;Niacinamide;older adult;older patient;Organ;Outcome;Pathway interactions;Patient risk;Patient Self-Report;Patients;Phenotype;Physical activity;physical conditioning;Physical Function;physical impairment;Physiological;Polyneuropathy;Population;Postdoctoral Fellow;Prevalence;Prognosis;prognostic value;Psyche structure;Quality of life;Recovery;Reporting;Research;Research Project Grants;resilience;Resolution;Risk;Severities;Signal Transduction;Skeletal Muscle;skeletal muscle wasting;skill acquisition;skills;standard of care;stressor;Survivors;Syndrome;systemic inflammatory response;Tissues;Training;Tryptophan;Tryptophan Metabolism Pathway;walking speed;Work

PROJECT_TITLE: Neurovascular Contributions to Cognitive and Mental health in Older Adult Critical Care Survivors