PHR: The Pathology and Imaging Core in this PPG seeks to services in 8 tasks to all Projects. These include tasks involving preparation of lungs to examine the pulmonary vascular disease in the animal models, samples from the Pulmonary Hypertension Breakthrough Initiative, and specialized approaches to isolate pulmonary vascular lesions to perform proteomic and genomic studies. The core uses several state of the art methodologies including a new system to localize up to 9 markers in the same section.

PI_NAMEs: TUDER, RUBIN M. (contact)

PROJECT_TERMS: Animal Model;Animals;Blood Vessels;Cells;Collection;Complement;Complement Activation;Data;Disease;experience;experimental study;Functional disorder;Genomics;Goals;high throughput analysis;Histologic;Human;human tissue;Image;imaging approach;immune imaging;Immune system;Immune Targeting;Immunofluorescence Immunologic;Immunohistochemistry;Inflammation;Inflammatory;inflammatory marker;innovation;Investigation;Label;laser capture microdissection;Leadership;Lesion;Lung;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Messenger RNA;Methodology;Methods;Modeling;Morphology;Mus;Newborn Infant;Pathologist;Pathology;Pattern;Phenotype;Preparation;Proteins;Proteome;Proteomics;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;Rattus;Research Personnel;Resources;RNA;Role;Sampling;Services;Structure;System;tissue processing;transcriptomics;Translating;Translations

PROJECT_TITLE: Pathophysiology Core


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

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

ORG_CITY: DALLAS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative for the Overall Component The mission of the UT Southwestern Wellstone Muscular Dystrophy Specialized Research Center is to promote collaborative basic science, translational, and clinical research for the advancement of promising CRISPR/Cas9- mediated genomic editing technologies to permanently restore dystrophin expression and improve the lives of Duchenne muscular dystrophy patients. Our Center provides excellent training for the next generation of researchers and outstanding resources for the muscular dystrophy communities. Our community outreach efforts increase patient and caregiver awareness of our research progress and opportunities to participate in clinical research studies.

PI_NAMEs: BASSEL-DUBY, RHONDA ;IANNACCONE, SUSAN T;MAMMEN, PRADEEP P.A.;OLSON, ERIC N (contact);ROTHERMEL, BEVERLY A;TRIVEDI, JAYA R

PROGRAM_OFFICER_NAME: SURPRIS, MARIPIERRE PAYEN

PROJECT_TERMS: Address;Animal Model;Awareness;Basic Science;Becker Muscular Dystrophy;bench to bedside;biobank;Biological Markers;Biology;biomedical scientist;Biotechnology;Blood;Boston;Cardiac;Cardiomyopathies;Caregivers;Cell Line;Child;Clinic;Clinical;clinical care;Clinical Data;Clinical Research;Clinical Services;clinical translation;clinically relevant;Coin;Collaborations;collaborative environment;commercialization;Communication;Communities;Community Outreach;CRISPR/Cas technology;Dedications;design;Development;Discipline;Disease;DNA Sequence Alteration;Duchenne muscular dystrophy;Dystrophin;dystrophinopathy;Education;education resources;educational atmosphere;Ensure;exon skipping;Family;Foundations;Generations;Genetic;Genome;genome editing;Goals;graduate school;Guide RNA;human induced pluripotent stem cells;improved;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;innovation;insight;Institution;Knowledge;lectures;Mediating;Medical center;Medicine;member;Mission;Modality;Modeling;Muscle;Muscular Dystrophies;neuromuscular;Neuromuscular Diseases;new technology;next generation;novel therapeutic intervention;novel therapeutics;patient advocacy group;patient derived induced pluripotent stem cells;Patient Education;patient outreach;Patients;Phenotype;preclinical study;programs;Publications;recruit;regenerative;Research;Research Personnel;Research Project Grants;research study;Resources;Sampling;Science;Scientist;Series;Source;standard of care;System;Technology;Therapeutic;tool;Training;Translating;Translational Research;translational study;University Hospitals;Vision;Work

PROJECT_TITLE: Myoediting of Duchenne Muscular Dystrophy


ADMINISTERING_IC: HL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Lung;Pulmonary Hypertension

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Persistent perivascular inflammation is observed in many forms of pulmonary hypertension and is now thought to contribute significantly to both the overall vascular remodeling and high pulmonary artery pressures that characterize this lethal disease process. We show that early activation of complement occurs in PH and that this activation is critical in the early recruitment and persistence of inflammatory cells. The purpose of our project is to determine the mechanisms contributing to early and persistent complement activation and to determine if complement activation, in the vessel wall, can ultimately be targeted to ameliorate the disease process.

PI_NAMEs: STENMARK, KURT R. (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: Area;arm;Arthritis;Autoantibodies;Autoimmune;Autoimmune Diseases;Binding;Biological Markers;Blood Vessels;Cells;Chimeric Proteins;Clinical;Complement;Complement 3d;Complement Activation;Complement Inactivators;complement system;Data;Deposition;Diagnosis;diagnostic biomarker;Disease;efficacy testing;Epitope spreading;Epitopes;Goals;Human;Hypertension;Hypoxia;Immune;Immune response;Immunoglobulin G;Immunoglobulins;in vivo;Inflammation;Inflammatory;Injury;Kidney Diseases;Life Expectancy;Lung;lung vascular injury;Malignant Neoplasms;Mediating;natural antibodies;Natural Immunity;neoantigens;novel;Outcome;Pathogenesis;Pathway Analysis;Pathway interactions;Patients;Plasma;Process;Prognostic Factor;Publishing;pulmonary arterial pressure;Pulmonary Heart Disease;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;recruit;Research Personnel;Rodent;Role;Signal Transduction;single photon emission computed tomography;Sterility;Stimulus;targeted delivery;targeted treatment;Testing;therapeutic target;Time;tissue injury;vascular inflammation;vascular injury;Vascular remodeling;X-Ray Computed Tomography

PROJECT_TITLE: Immunoglobulin-Driven Activation of the Complement Cascade is a Critical Determinant of PAH Initiation and Progression


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Heart Disease - Coronary Heart Disease;Hypertension;Kidney Disease

ORG_CITY: SALT LAKE CITY

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Sodium bicarbonate is commonly prescribed to people with chronic kidney disease who have a build-up of acids in their blood. This study will investigate the cardiovascular effects of sodium bicarbonate treatment in people with chronic kidney disease.

PI_NAMEs: MELAMED, MICHAL L;RAPHAEL, KALANI LUKELA (contact)

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Acidosis;Acids;Adverse effects;Affect;Aldosterone;Alkalies;alternative treatment;American;Angiotensin II;Animal Model;Anti-Hypertensive Agents;Aorta;Atrial Natriuretic Factor;base;Bicarbonates;Biological Markers;Blood;Blood Plasma Volume;Blood Pressure;blood pressure elevation;Body Weight;bone;Bone Morphogenetic Proteins;Brain natriuretic peptide;calcification;Cardiovascular Diseases;cardiovascular effects;cardiovascular risk factor;Cardiovascular system;Catabolism;Characteristics;Chronic Kidney Failure;Clinical;Clinical Trials;Data;demineralization;Development;Diuresis;Diuretics;Double-Blind Method;End stage renal failure;Equation;Excretory function;fibroblast growth factor 23;Fluid Balance;Funding;global health;Goals;high risk;Hormones;Human;Hypertension;Impairment;improved;indexing;Individual;inhibitor;innovation;Kidney;kidney preservation;Knowledge;Learning;Liquid substance;Measurement;Mediating;Meta-Analysis;Metabolic acidosis;Modeling;Morbidity - disease rate;mortality;Muscle;N-terminal;Natriuresis;Natriuretic Peptides;novel;Oral;Participant;particle;Patients;Persons;phase III trial;Physiological;pilot trial;Placebo Control;Placebos;Population;prevent;primary outcome;promoter;Public Health;Randomized;Rattus;Renal function;Renin;Renin-Angiotensin-Aldosterone System;Research Personnel;Safety;Sampling;Serum;Sodium;Sodium Bicarbonate;Specimen;Testing;Time;translational impact;treatment group;treatment response;Tumor necrosis factor receptor 11b;Uremia;Vascular calcification;α-Fetoproteins

PROJECT_TITLE: Cardiovascular effects of oral bicarbonate in CKD

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


NIH_SPENDING_CATS: Duchenne/ Becker Muscular Dystrophy;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases

PHR: Project Narrative for the Administrative Core The proposed NIH P50 Grant Application has significant relevance to the public health of our nation. The overall study is both significant and innovative because it proposes that genome editing can permanently restore dystrophin expression within the skeletal muscle of patients with Duchenne muscular dystrophy. The Administrative Core will be charged with the mission of providing effective leadership and management of the UT Southwestern Muscular Dystrophy Specialized Research Center in order to enhance the Center’s opportunity to successfully and significantly contribute to the field of muscular dystrophy research and patient care.

PI_NAMEs: OLSON, ERIC N (contact)

PROJECT_TERMS: Achievement;Advocate;Applications Grants;biobank;Charge;Clinical;clinical care;Communication;Communities;Duchenne muscular dystrophy;Dystrophin;Education;empowerment;Ensure;Environment;Family;Fostering;Foundations;genome editing;Goals;innovation;International;Journals;Knowledge;Leadership;Maintenance;Medicine;meetings;member;Methods;Mission;Modern Medicine;Muscle Cells;Muscular Dystrophies;next generation;novel therapeutics;outreach;parent project;Patient Care;Patients;Public Domains;Public Health;Publishing;Reagent;regenerative;Research;Research Personnel;Resources;Science;Skeletal Muscle;symposium;Training and Education;United States National Institutes of Health;Update;web site;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Infectious Diseases;Lung;Pulmonary Hypertension;Rare Diseases;Scleroderma;Vector-Borne Diseases

PHR: Narrative The immune system likely contributes to the development of pulmonary hypertension by excessive inflammation, which causes disease in the lung blood vessels. Our research investigates how different parts of the immune system, including complement proteins, CD4 T cells, monocytes and macrophages can together cause pulmonary hypertension. Our main approach is by studying mice exposed to schistosomiasis: this is a parasite released by freshwater snails in tropical countries, affecting over 200 million people worldwide, and is a major cause of pulmonary hypertension.

PI_NAMEs: GRAHAM, BRIAN BARKLEY (contact)

PROJECT_TERMS: adaptive immunity;Affect;Alternative Complement Pathway;Anaphylatoxins;antigen challenge;Antigens;Autoimmune;Automobile Driving;biomarker identification;Blood Platelets;Blood Vessels;C3AR1 gene;CD4 Positive T Lymphocytes;Cells;Cessation of life;Clinical;comorbidity;Complement;Complement Activation;Complement component C1;Complex;Country;cytokine;Development;Disease;egg;Elements;Etiology;experience;Exposure to;Extracellular Matrix;Face;Fresh Water;Goals;Heterogeneity;Human;Hypoxia;hypoxia-induced pulmonary hypertension;Immune;Immune system;Immunosuppression;Infection;Inflammation;Innate Immune Response;interstitial;Lectin;Leukocytes;Link;Lung;lung vascular inflammation;Macrophage;Mediating;monocyte;Mus;Natural Immunity;new therapeutic target;Parasites;Pathogenesis;Pathology;patient subsets;Patients;peripheral blood;Persons;Phenotype;Plasma;Pre-Clinical Model;prevent;protective pathway;pulmonary arterial hypertension;Pulmonary Hypertension;pulmonary vascular disorder;Recovery;recruit;Regulatory T-Lymphocyte;Research;Resolution;Role;Schistosoma;Schistosomiasis;Scleroderma;Snails;Source;Sterility;System;T-Lymphocyte;Therapeutic;Thrombospondin 1;Transforming Growth Factor beta;vascular injury;Vascular remodeling

PROJECT_TITLE: Role of Complement-Driven Pulmonary Vascular Inflammation in PH


PHR: Project 3 in this PPG seeks to provide the translational significance to Projects 1,2 and 4, by investigating the proteome (proteins) and transcriptome (mRNA) of lungs of individuals with severe pulmonary hypertension due to idiopathic pulmonary arterial hypertension (IPAH) as compared to normal lungs. We also seek to investigate the presence of markers of complement activation in the serum of a large cohort of well-characterized patients with IPAH and in tissue sections of IPAH patients correlating these data with inflammatory parameters. We apply the same methods to 2 models that most closely approximate the human condition to test if they can better provide preclinical data regarding targeting complement. Finally, we test whether blockade of complement can reduce the PH inflammatory environment and normalize the PH vascular proteome.

PROJECT_TERMS: Address;Animal Diseases;Animal Model;Blood Vessels;Cattle;Cells;cohort;Complement;Complement Activation;Complement Inactivators;complement system;Data;Data Correlations;disease heterogeneity;disease model;Elements;Enhancers;Environment;Evaluation;extracellular;Extracellular Matrix;Fingerprint;Gene Expression;genetic element;Genetic Transcription;Genomic approach;Genomics;Goals;hemodynamics;Heterogeneity;Human;human disease;human tissue;Hypertrophy;hypoxia-induced pulmonary hypertension;Image;Immune;Immunofluorescence Immunologic;Individual;Inflammation;Inflammatory;inflammatory marker;inflammatory milieu;Intervention;Investigation;Lesion;Link;Lung;Lung Diseases;Macrophage;Mediating;member;Messenger RNA;Methods;Modeling;Molecular;Molecular Profiling;mouse model;novel strategies;Patients;Phenotype;Plasma;Plasma Proteins;pre-clinical;primary pulmonary hypertension;Proteins;Proteome;Proteomics;pulmonary arterial hypertension;Pulmonary arterial remodeling;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;Rattus;Role;Sampling;Serum;Structure of parenchyma of lung;SU 5416;synergism;Testing;Therapeutic;Tissues;transcriptome

PROJECT_TITLE: Evaluation of the Dynamic Reciprocity Between Cells and the Vessel Matrix in Pulmonary Hypertension


NIH_SPENDING_CATS: Duchenne/ Becker Muscular Dystrophy;Muscular Dystrophy;Pediatric;Rare Diseases

PHR: Project Narrative: The goal of the UTSW Wellstone Training Core is to provide an environment in which trainees not only learn the technical aspects of genomic editing and their potential application to the treatment and study of Duchenne muscular dystrophy, but also become comfortable communicating and collaborating across disciplines from bedside to lab-bench and back again.

PI_NAMEs: ROTHERMEL, BEVERLY A (contact)

PROJECT_TERMS: Accreditation;Address;Back;Basic Science;Biomedical Research;Blood;career;Career Mobility;Clinical Sciences;Collaborations;Communication;Communities;CRISPR/Cas technology;design;Discipline;Disease;Doctor of Medicine;Doctor of Philosophy;Duchenne muscular dystrophy;educational atmosphere;Elements;Environment;Fellowship;Funding;Generations;Genome;genome editing;Goals;induced pluripotent stem cell;Learning;Mediating;Medical center;Medicine;meetings;Mentors;Mission;Muscle;Muscular Dystrophies;neuromuscular;next generation;Patients;Physicians;Process;programs;recruit;Research;Research Personnel;Sampling;Scientist;Services;Technology;Texas;Training;Training Activity;Training Programs;Translations;Universities;Work

PROJECT_TITLE: Training Core


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Comparative Effectiveness Research;Health Services;Infectious Diseases;Lyme Disease;Neurosciences;Pediatric;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE This comparative effectiveness study will 1) determine if oral doxycycline is not inferior to intravenous ceftriaxone for treating children with Lyme meningitis and 2) identify the factors that patients, parents and clinicians use to guide treatment decisions. Success of this study would comprehensively improve the quality and patient-centered care for children with Lyme meningitis.

PI_NAMEs: NIGROVIC, LISE E. (contact)

PROGRAM_OFFICER_NAME: BOWDEN, NADINE

PROJECT_TERMS: Accounting;Adult;Affect;Aftercare;Antibiotics;Biometry;Boston;Catheters;Ceftriaxone;Cephalic;Child;Child Care;Childhood;Clinical;clinical practice;Collaborations;Communicable Diseases;comparative effectiveness;comparative effectiveness study;Complication;cost;Data Coordinating Center;design;Diagnosis;Doxycycline;Enrollment;Equipment and supply inventories;Europe;European;experience;Fatigue;Fever;Goals;Grant;Guidelines;Headache;Health Care Costs;improved;Informed Consent;innovation;Institutional Review Boards;instrument;Interview;Intravenous;Knowledge;Lyme Disease;Lyme disease diagnosis;Measurement;Medicine;Meningitis;Methods;multidisciplinary;Neuritis;Neurologic;Neurologic Symptoms;Observational Study;Oral;Outcome;Parents;Patient-Centered Care;Patients;Pediatric Hospitals;Pharmaceutical Preparations;preference;prospective;Qualitative Methods;Quality of life;Recommendation;Recovery;recruit;Research;Resolution;Risk;Shapes;shared decision making;side effect;success;Surveys;Symptoms;Time;Treatment Effectiveness;Universities;Update;Utah;Work

PROJECT_TITLE: Comparative effectiveness and complications of intravenous ceftriaxone compared with oral doxycycline in Lyme meningitis

STUDY_SECTION: CRFS

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: SAN ANTONIO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE The chromatin-based DNA damage response (DDR) pathway is an intricate network composed of multiple protein complexes. Dysregulation of the DDR pathway leads to genome instability, developmental defects, cancer predisposition, and premature aging. The goals of our research are to characterize the DDR network, decipher the DNA damage-induced epigenetic codes, and understand the functions of the DNA repair proteins to build a foundation for therapeutic strategy development in the DNA damage-related disorders.

PI_NAMEs: LEUNG, JUSTIN WAI CHUNG (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Biochemistry;Biological Assay;Cancer Etiology;cancer predisposition;Cell Cycle;Cells;Cellular biology;Chromatin;Chromosomes;Code;Confocal Microscopy;Coupled;Defect;Development;Disease;DNA;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Pathway;Epigenetic Process;Foundations;Fractionation;Genetic;Genetic Diseases;Genome;genome editing;genome integrity;Genomic Instability;genotoxicity;Goals;Health;Human;insight;interdisciplinary approach;irradiation;Knowledge;Lasers;Mass Spectrum Analysis;Molecular;Molecular Biology;Mutation;novel;Pathway interactions;Premature aging syndrome;programs;protein complex;protein purification;Proteins;Proteomics;recruit;repaired;Reporter;Research;response;Signal Transduction;Techniques;Therapeutic;Translational Research;translational therapeutics

PROJECT_TITLE: Deciphering the chromatin-based DNA damage response pathway

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


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Duchenne/ Becker Muscular Dystrophy;Genetics;Muscular Dystrophy;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative The Myoediting Core is designed and managed as a shared Scientific Research Resource Core to support the research of the Muscular Dystrophy Specialized Research Center (MDSRC) at UT Southwestern, other Wellstone MDSRCs, as well as serving as a resource for the national and international muscular dystrophy research community. This proposal offers a novel strategy for treating Duchenne muscular dystrophy, called “Myoediting” which involves molecularly modifying the genome of muscle cells affected by this disease, correcting the mutation in a manner that causes permanent skipping of the mutant exons within the dystrophin gene transcript. The Myoediting Core is developing state-of- the-art myoediting tools, technologies and reagents to improve efficacy of current gene repair strategies and to facilitate new strategies.

PI_NAMEs: BASSEL-DUBY, RHONDA  (contact)

PROJECT_TERMS: Acceleration;Address;Affect;biobank;Blood;Cardiac Myocytes;clinical phenotype;Communities;CRISPR/Cas technology;Data;design;Disease;Duchenne muscular dystrophy;Dystrophin;efficacy evaluation;Exons;Free Will;Funding;gene repair;Genes;Genetic Diseases;Genome;genome editing;Genomics;Goals;Guide RNA;Human;human induced pluripotent stem cells;improved;in silico;Individual;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;International;Learning;Link;Mediating;Modeling;Molecular;Muscle Cells;Muscular Dystrophies;mutant;Mutation;mutation correction;Myopathy;next generation sequencing;novel;novel strategies;Patients;Process;Protocols documentation;Reagent;repair strategy;Research;Research Personnel;Research Support;Resources;restoration;RNA Sequences;Services;Site;Techniques;Technology;Therapeutic;Time;tool;Training;training opportunity;Transcript;Update;Visit;web page;web site

PROJECT_TITLE: Scientific Research Resource Core


NIH_SPENDING_CATS: Hematology;Lung;Pulmonary Hypertension

PHR: Pulmonary hypertension (PH) is a progressive and often fatal disease driven by inflammatory mediated vascular remodeling. This project examines the mechanisms by which complement activated platelets drive endothelial activation and monocyte/macrophage proinflammatory differentiation and recruitment, promoting vascular remodeling in pulmonary hypertension. These results will set the stage for future studies targeting the platelet immune response in patients with pulmonary hypertension with novel currently available therapies.

PI_NAMEs: DELANEY, CASSIDY A (contact)

PROJECT_TERMS: Address;Adherence;Adhesions;Anaphylatoxins;Animal Model;Animals;Automobile Driving;Blood;Blood Platelets;Blood Vessels;C3AR1 gene;CCL2 gene;Cell Adhesion Molecules;Cell surface;Cells;chemokine;Chronic;Complement;Complement 3a;Complement 5a;Complement Activation;Complement Factor B;Complement Receptor;Data;Disease;E-Selectin;Endothelial Cells;endothelial dysfunction;Endothelium;Exposure to;functional improvement;Future;Genetic;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;Hemostatic function;Human;Hypoxia;Immune;Immune response;In Vitro;in vivo;Inflammation;Inflammatory;innovation;Integrins;Intercellular adhesion molecule 1;Interleukin-6;interstitial;Laboratories;Leukocytes;loss of function;Lung;Macrophage;Mediating;Mediator;Methods;monocyte;mortality;mouse model;Mus;novel;P-Selectin;Pathogenesis;Patients;Pericytes;pharmacologic;Platelet Activation;prevent;Process;programs;Proliferating;protein expression;Pulmonary Circulation;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;RANTES;recruit;Research;Role;Signal Transduction;targeted treatment;Testing;Thrombosis;tool;Up-Regulation;Vascular Cell Adhesion Molecule-1;vascular inflammation;Vascular remodeling

PROJECT_TITLE: Complement-Driven Platelet Activation in Pulmonary Vascular Remodeling and Pulmonary Hypertension


NIH_SPENDING_CATS: Biotechnology;Duchenne/ Becker Muscular Dystrophy;Gene Therapy;Genetics;Muscular Dystrophy;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PHR: Project Narrative There is no cure available for Duchenne muscular dystrophy. We are using CRISPR/Cas9-mediated genomic editing (we call “Myoediting) to correct the mutation causing Duchenne muscular dystrophy in human cells and animal models. This project represents a close collaboration between clinicians and basic scientists sharing the common goal of advancing Myoediting, an new therapeutic strategy to permanently cure Duchenne muscular dystrophy in humans.

PROJECT_TERMS: adeno-associated virus 9 delivery;Affect;Aging;Animal Model;Animal Muscular Dystrophy;Applications Grants;boys;Brain;Canis familiaris;Cell model;Cell Nucleus;Cessation of life;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;CRISPR/Cas technology;Disease;DNA Sequence Alteration;Dose;Duchenne muscular dystrophy;Dystrophin;Exercise;exon skipping;Exons;Funding;gene correction;gene editing technology;Gene Expression Profile;Gene Mutation;Genes;Genome;genome editing;Genomic approach;Goals;Heart;Hot Spot;Human;in vivo;in vivo monitoring;Individual;Inherited;Injury;life span;Link;Luciferases;Mediating;mouse model;Mus;Muscle;Muscle Fibers;Muscle function;muscle progenitor cell;Muscle Weakness;Muscular Dystrophies;muscular dystrophy mouse model;muscular structure;mutant;Mutation;mutation correction;Myoblasts;Myocardial Degeneration;Myocardium;non-invasive monitor;novel therapeutic intervention;Nuclear;Oligonucleotides;Patients;postnatal;premature;prevent;Proteins;Reading Frames;Reporter;response;Scientist;single nucleus RNA-sequencing;Skeletal Muscle;stem cells;System;Therapeutic;therapeutic genome editing;Time;Tissues;Translating;United States National Institutes of Health;Viral;Work

PROJECT_TITLE: Project 1


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

ORG_STATE: IA

PHR: Veterans as a group, are at high risk of severe disease from SARS CoV-2 (CoV-2) during the COVID-19 pandemic and both breakthrough and reinfection are increasingly documented. Critical questions regarding host immune responses during and following infection remain unanswered. We found that CoV-2 particles and the structural spike protein (S) directly interact with human immune cells, altering normal T cell functions and differentiation, and we hypothesize that CoV2 interference with T cell signaling contributes to the establishment of infection, immune evasion, and reduces effector and memory T cell responses. These findings will facilitate new approaches to therapy and potentially lead to more effective vaccines.

PI_NAMEs: STAPLETON, JACK T. (contact)

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Acute Disease;adaptive immunity;Affinity;Animal Model;Anti-viral Therapy;Antibodies;Antibody Repertoire;Antigens;Autoimmunity;autoinflammatory;Automobile Driving;Avidity;B-Lymphocytes;breakthrough infection;Calcium;CD4 Positive T Lymphocytes;Cell Communication;Cell Differentiation process;Cell Physiology;Cells;Clinical;cohort;Complex;Coronavirus;Coronavirus Infections;COVID-19;COVID-19 pandemic;COVID-19 treatment;cytokine;cytokine release syndrome;Cytoprotection;Data;Development;Disease;Dose;Equilibrium;Etiology;Event;Functional impairment;high risk;Human;human pathogen;Humoral Immunities;Immune;Immune Evasion;Immune response;Immunity;Immunologics;immunoregulation;In Vitro;in vivo;Incubated;Infection;Inflammation;Inflammatory;insight;Investigation;Knowledge;Laboratories;Long COVID;long term memory;Macrophage Activation;Mediating;Memory;Methods;MHC Class I Genes;Middle East Respiratory Syndrome;novel;novel strategies;Outcome;pandemic disease;pandemic virus;particle;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Patients;peripheral blood;Phenotype;Phosphotransferases;post SARS-CoV-2 infection;Preparation;Process;Proliferating;Proteins;Pulmonary Inflammation;receptor function;Receptor Signaling;Regulation;Research Design;Resources;response;Risk;RNA Viruses;Role;Sampling;SARS coronavirus;SARS-CoV-2 infection;SARS-CoV-2 pathogenesis;SARS-CoV-2 spike protein;Severe Acute Respiratory Syndrome;severe COVID-19;Severity of illness;Signal Induction;Signal Pathway;Signal Transduction;Site;Structural Protein;T cell differentiation;T Cell Receptor Signaling Pathway;T cell regulation;T cell response;T memory cell;T-Cell Activation;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;targeted treatment;TCR Activation;Testing;transcriptomics;Vaccination;vaccine formulation;vaccine strategy;vaccine trial;Vaccinee;Vaccines;Variant;Veterans;Viral;Viral Interference;Viral Proteins;Virion;Virus;Virus Diseases

PROJECT_TITLE: SARS CoV-2 Immune Evasion Mechanisms


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Duchenne/ Becker Muscular Dystrophy;Genetics;Heart Disease;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases

PHR: Project Narrative for Project 2 The proposed NIH P50 Grant Application has significant relevance to the public health of our nation. The overall study is both significant and innovative because it proposes that genome editing can restore dystrophin expression in the muscle of patients with Duchenne muscular dystrophy. Project 2 will specifically focus on identifying the molecular profile of DMD-associated cardiomyopathy.

PI_NAMEs: MAMMEN, PRADEEP P.A. (contact)

PROJECT_TERMS: 17 year old;Adult;Age;age group;Age Years;Applications Grants;ATAC-seq;Atrophic;Attention;Attenuated;Autophagocytosis;Autopsy;Becker Muscular Dystrophy;Biological Markers;Birth;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;Cardiomyopathies;Childhood;clinical phenotype;comparison control;coronary fibrosis;CRISPR/Cas technology;Data;Data Set;Development;Disease;DNA Sequence Alteration;Duchenne cardiomyopathy;Duchenne muscular dystrophy;Dystrophin;exome sequencing;Gene Expression;Genes;Genome;genome editing;Goals;Growth;Heart;heart function;Heart Hypertrophy;heart metabolism;Hot Spot;Human;Image;imaging modality;Immobilization;Immunohistochemistry;implantation;improved;induced pluripotent stem cell derived cardiomyocytes;innovation;Innovative Therapy;Investigation;Laboratories;Left;left ventricular assist device;Left Ventricular Mass;Life;life span;Link;Magnetic Resonance Imaging;mdx mouse;Measures;Metabolism;Mission;Modality;Molecular;molecular phenotype;Molecular Profiling;Morbidity - disease rate;mortality;mouse model;Muscle;Muscular Atrophy;Muscular Dystrophies;muscular dystrophy mouse model;Mutation;Neuromuscular Diseases;new therapeutic target;next generation sequencing;novel therapeutics;Pathologic;Patients;Phenotype;Proliferating;Proteins;Public Health;Pyruvate;Quantitative Reverse Transcriptase PCR;Sampling;sex;Signal Pathway;Site;skeletal muscle wasting;Structure;Symptoms;Techniques;Testing;Therapeutic;therapeutic genome editing;Time;transcriptome sequencing;United States National Institutes of Health;Ventricular;Weight;Western Blotting

PROJECT_TITLE: Project 2


ORG_CITY: COLUMBIA

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: SC

PHR: Despite decades of work, the mechanisms that cause high blood pressure (hypertension), a major health concern for veterans, continue to be elucidated. Immune system activation has been linked to the development of hypertension, and is also directly linked to rheumatic diseases like systemic lupus erythematosus (SLE) that predominantly affect women. Rheumatic disease and are a major health concern for the military, and women represent an increasing demographic among veterans. This proposal will explore how immune system activation during SLE impacts kidney function and leads to hypertension with a focus on understanding a specific immune cell type (neutrophils) and the powerhouse of cells (mitochondria). Examining how the immune system impacts blood pressure during this disease will not only provide new insights for women with SLE, but also will add to the overall understanding of hypertension.

PI_NAMEs: RYAN, MICHAEL  (contact)

PROJECT_TERMS: absorption;active duty;Affect;Anti-Inflammatory Agents;Antigens;Antioxidants;Attenuated;Autoantibodies;Autoantibody binding;Autoimmune;Autoimmune Diseases;autoimmune pathogenesis;Autoimmune Process;autoimmune rheumatologic disease;Autoimmunity;Blood Pressure;blood pressure regulation;Blood Vessels;Cell surface;cell type;Cells;Clinical;clinically relevant;Coupled;Data;Development;Disease;Endothelium;Enzymes;Essential Hypertension;Experimental Models;experimental study;extracellular;Funding;General Population;Generations;Health;Healthcare;Human;Hypertension;hypertension treatment;Immune;immune cell infiltrate;Immune system;Immunologics;Immunotherapy;Impaired Renal Function;Impairment;improved;in vivo;Inflammasome;innovation;insight;interstitial cell;Kidney;kidney vascular structure;Knowledge;Link;Mediating;Mediator;Methods;Military Personnel;military veteran;Mitochondria;mitochondrial dysfunction;mouse model;Mus;Myeloid Cells;neutrophil;Oxidative Stress;Pathogenicity;Pathology;Pathway interactions;Patients;Peroxidases;Pharmacological Treatment;Physiological;Plasma;pressure;Prevalence;Production;Publishing;Reactive Oxygen Species;receptor;Renal function;Renal Hypertension;Respiration;Respiratory Burst;Rheumatism;Role;Sodium;Source;Surface;Systemic Lupus Erythematosus;Testing;Therapeutic immunosuppression;Tubular formation;Vascular Diseases;Veterans;Woman;Work

PROJECT_TITLE: Renal mechanisms of hypertension in autoimmune disease


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

ORG_STATE: MO

PHR: Osteoarthritis (OA) is a common form of arthritis, affecting 50+ million adults in the US and for which there is no effective treatment. Post-traumatic OA (PTOA) is a form of OA that develops after a joint injury. It accounts for 12% of all OA and 20% of all joint replacements. Additionally, among combat veterans from ongoing US military operations the frequency of arthritis is estimated at 11.8%. We propose to develop nanotherapeutic approaches that can be delivered into the injured joint to prevent or halt the progression of PTOA. We believe that any intervention that decreases the risk and rate of PTOA reduces the overall burden of OA.

PI_NAMEs: PHAM, CHRISTINE T. (contact)

PROJECT_TERMS: Acceleration;Acute;Adult;Affect;Age;aging population;American;anterior cruciate ligament reconstruction;anterior cruciate ligament rupture;Anti-Inflammatory Agents;Antiinflammatory Effect;Arthritis;Arthroscopy;Behavior;beta catenin;Biological Factors;Cartilage;cartilage degradation;Cartilage Matrix;cartilage repair;Cells;Censuses;Cessation of life;Chondrocytes;Clinic;combat injury;combat veteran;Complex;cost;Data;Degenerative polyarthritis;Development;Diagnosis;Disease;effective therapy;Etiology;Event;Failure;Fibroblast Growth Factor;fibroblast growth factor 18;Frequencies;Gait;General Population;Health;Homeostasis;Impairment;improved;Individual;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;Intervention;joint function;joint injury;Knee;Knee Osteoarthritis;knock-down;Lifelong disability;lifetime risk;Maintenance;Medial meniscus structure;Medical;Meniscus structure of joint;Messenger RNA;military operation;military service;military veteran;Modeling;Morbidity - disease rate;Motion;mouse model;mRNA delivery;nanocomplexes;nanoparticle;nanotechnology platform;nanotherapeutic;nanotherapy;Nature;NF-kappa B;Nucleic Acids;Operative Surgical Procedures;Outcome;overexpression;p65;Pain;Pathogenesis;Pathway interactions;Patients;Penetration;Peptide Nucleic Acids;Peptides;Pharmaceutical Preparations;Phase;Population;preservation;Prevalence;prevent;Prevention therapy;primary outcome;Production;repaired;reparative process;Replacement Arthroplasty;Research;response;Risk;RNA;self assembly;service member;Signal Pathway;Signal Transduction;Small Interfering RNA;Soldier;Surgical Models;Syndrome;Time;Trauma;Traumatic Arthropathy;Treatment Protocols;Up-Regulation;Vertebral column;Veterans;WNT Signaling Pathway

PROJECT_TITLE: Targeted nanotherapy for the prevention of post-traumatic osteoarthritis


ORG_CITY: LOMA LINDA

ORG_NAME: VA LOMA LINDA HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: PROJECT NARRATIVE  Bone injuries are a major health problem. There are 7.9 million bone fractures sustained annually in the U.S. alone. Bone healing is impaired in 10% of fractures with seriously delayed union or nonunion, causing morbidity for patients and enormous healthcare costs. Thus, there is a compelling need to find novel effective therapies that promote fracture healing. In this project, we will use 3D printed fibrin gel/β-tricalcium phosphate (βTCP) scaffolds to test the therapeutic effects of the smoothened agonist, SAG21k, to activate hedgehog signaling in a burst manner and a prolyl hydroxylase domain (PHD)2 protein inhibitor, IOX2, to activate hypoxia signaling in a sustained manner in a clinically relevant femoral segment defect model for nonunions. Our successful completion of the proposed work could lead to the development of novel SAG21k-IOX2-based therapeutics which accelerate bony bridging and, thereby, minimize the chance of developing a nonunion fracture. Our proposed work on the elucidation of the role of chondrocyte-to-osteoblast conversion for SAG21k and IOX2 effects at the fracture site could also identify new therapeutic drug targets for bone healing.

PI_NAMEs: MOHAN, SUBBURAMAN  (contact)

PROJECT_TERMS: 3D Print;Ablation;Acceleration;Adult;Agonist;Animal Model;Ascorbic Acid;Autologous Transplantation;Binding;Blood Vessels;bone;Bone callus;Bone Development;bone epiphysis;bone fracture repair;bone healing;Bone Injury;bone mass;Bone Matrix;bone repair;bone strength;Bone Transplantation;Cartilage;cartilaginous;Cell Therapy;Chondrocytes;clinically relevant;Combined Modality Therapy;comparative efficacy;cost;cost effective;Data;Defect;Development;Diabetic mouse;Diphtheria Toxin;Disadvantaged;Drug Targeting;effective therapy;Effectiveness;Electromagnetic Fields;Embryonic Development;Erinaceidae;Event;Exhibits;Failure;Femur;Fibrin;Fracture;Future;Gel;Genes;Genetic;Growth Factor;healing;Health;Health Care Costs;HIF1A gene;Histologic;hormone deficiency;Hypertrophy;Hypothyroidism;Hypoxia;Immunohistochemistry;Impaired healing;Impairment;inhibitor;injury and repair;intramembranous bone;Invaded;Label;long bone;Maps;Measurement;Mechanics;Mediating;Mesenchymal Stem Cells;mesenchymal stromal cell;microCT;Modeling;Molecular;Morbidity - disease rate;mouse model;Mus;novel;novel therapeutics;old mice;Osteoblasts;Osteogenesis;Oxygen;Pathway interactions;Patients;Phenotype;Physiologic Ossification;Physiologic pulse;Physiological;Play;Polymers;Preparation;Process;Procollagen-Proline Dioxygenase;Proliferating;Proteins;Recombinants;repaired;Rod;Role;Safety;scaffold;sensor;SHH gene;side effect;Signal Induction;Signal Pathway;Signal Transduction;Site;skeletal;Skeletal Development;small molecule;small molecule inhibitor;small molecule therapeutics;smoothened signaling pathway;Source;substantia spongiosa;Testing;Therapeutic;Therapeutic Agents;Therapeutic Effect;therapeutic effectiveness;therapeutic evaluation;Thyroid Hormones;Time;Tissues;Torsion;transdifferentiation;tricalcium phosphate;ultrasound;Work

PROJECT_TITLE: Development of 3D Printed Synthetic Bone Graft Containing Small Molecules for Sequential Activation of Hedgehog and Hypoxia Signaling for Treatment of Nonunion Fractures


FUNDING_MECHANISM: OTHERS

ORG_CITY: NASHVILLE

ORG_STATE: TN

PHR: PROJECT NARRATIVE Heterotopic ossification (HO) is the formation of ectopic bone in extra-skeletal tissues due to aberrant soft tissue healing following musculoskeletal damage. Musculoskeletal injuries range widely, from trauma incurred during combat operations to controlled tissue damage during orthopaedic surgeries. Complications from HO include chronic pain, chronic infection, and impaired wound healing, leading to loss of mobility and inhibiting prosthetics use, thus impeding Veteran independence and return to normalcy. These difficulties can lead to comorbidities like opioid addiction and depression that can lead to overdose or suicide, which are all major issues in overall Veteran health. Current treatment options for HO are limited due to the lack of understanding of the molecular mechanisms that drive ectopic bone formation. In this proposal, we will elucidate the links between abnormal extracellular matrix deposition, aberrant osteogenic signaling, and ectopic bone formation in order to identify new treatment strategies to prevent HO formation in our Veterans.

PI_NAMEs: PECK, SUN H (contact)

PROJECT_TERMS: Affect;Afghanistan;Aftercare;Amputation;Animal Model;Anti-Inflammatory Agents;Area;Atomic Force Microscopy;Automobile Driving;biobank;Biological Markers;Biological Process;biomarker identification;Blast Injuries;Blood;bone;Bone Growth;Brain;Burn injury;Chemicals;chondroitin sulfate glycosaminoglycan;Chondroitinases;chronic infection;chronic pain;circulating biomarkers;clinically relevant;Collagen;collagenase;combat zone;comorbidity;Data;Deposition;Development;diagnostic biomarker;Direct Lytic Factors;Environment;Excision;experience;experimental study;Extracellular Matrix;Fibrosis;Gene Expression;Gene Expression Profile;Genetic;Genotype;Glycosaminoglycans;Growth Factor;healing;Health;Heterotopic Ossification;Heterozygote;high risk;Histologic;Human;Human Genetics;Impaired wound healing;improved;In Vitro;in vivo;Inflammation;inhibitor;injured;Injury;insight;Iraq;Knock-out;Knockout Mice;Life;limb injury;Link;liquid chromatography mass spectrometry;loss of function;Maintenance;Measures;Mental Depression;Methods;Military Personnel;military veteran;Modeling;Molecular;mouse model;Mus;Muscle;Musculoskeletal;musculoskeletal injury;Nature;Normalcy;novel therapeutic intervention;Operative Surgical Procedures;Opiate Addiction;Orthopedic Surgery;Osteogenesis;osteogenic;Overdose;Pathologic;Pathway interactions;patient subsets;Patients;Phenotype;Plasminogen;Play;Predictive Factor;predictive tools;Predisposition;prevent;Production;prophylactic;Prosthesis;Radiation;Recovery;repaired;Replacement Arthroplasty;Risk;Role;Serum;Signal Transduction;Site;soft tissue;Spinal cord injury;standard of care;Study models;Suicide;Tamoxifen;targeted treatment;Therapeutic;Time;tissue repair;Tissues;tomography;transcriptome sequencing;Trauma;treatment strategy;Ulcer;Up-Regulation;Veterans;Work;wound healing

PROJECT_TITLE: The Role of Extracellular Matrix Dysregulation in Heterotopic Ossification


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Acute myeloid leukemia (AML) accounts for 80% of adult acute leukemia and has a five-year survival rate of only 25%. It is more common in men and incidence increases with age. AML is associated with military service in specific groups of Veterans. It also develops following treatment for other cancers, including those common in Veterans. This merit award proposal explores approaches to improving treatment for AML with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), a molecular abnormality present in AML cells in 30% of patients and associated with poor treatment outcomes. The work has the potential to improve outcomes in Veterans who develop this common and unfavorable AML subtype, including following military and medical exposures. The long-term goal is to develop clinical trials of multi-targeting approaches to improving outcomes of patients with AML with FLT3-ITD.

PI_NAMEs: BAER, MARIA R (contact)

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adult;Aftercare;Age;Allogenic;Apoptotic;Award;c-myc Genes;Cell Line;Cells;chemotherapy;Clinical Trials;Development;disorder control;Down-Regulation;efficacy evaluation;efficacy testing;Exhibits;Feedback;FLT3 gene;FRAP1 gene;Genetic Transcription;Goals;Health;Hematopoietic Stem Cell Transplantation;improved;improved outcome;In Vitro;in vivo;Incidence;Induction of Apoptosis;inhibitor;inhibitor therapy;kinase inhibitor;knock-down;Malignant Neoplasms;MCL1 gene;Mediating;Medical;MEKs;men;Military Personnel;military service;Molecular;Molecular Abnormality;Mutate;Mutation;Newly Diagnosed;Oncogenic;Oral;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;PI3K/AKT;PIM-1 Serine/Threonine Kinase;Point Mutation;prevent;Protein phosphatase;Protein Serine/Threonine Phosphatase;Proteins;proto-oncogene protein pim;Proto-Oncogene Proteins c-akt;Receptor Protein-Tyrosine Kinases;Refractory;Relapse;Resistance;Resistance development;response;Sampling;Signal Induction;Signal Pathway;Signal Transduction;Stat5 protein;Survival Rate;targeted agent;Testing;transcription factor;Transcriptional Activation;Transducers;Treatment outcome;treatment response;Tumor Suppressor Proteins;ubiquitin isopeptidase;Veterans;White Blood Cell Count procedure;Work

PROJECT_TITLE: Enhancing FLT3 inhibitor efficacy in acute myeloid leukemia with FLT3-ITD


ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Project Narrative  Anxiety disorders are common and often disabling. They also frequently present with other psychiatric disorders such as major depressive disorder (MDD) and post- traumatic stress disorder; these disorders may share commonalities in their underlying genetic architecture. These commonalities might be informative in the treatment of veterans suffering from PTSD. Additionally, anxiety disorders have known overlapping risk for cardiovascular disease and lung cancer. Anxiety disorders are not only common, but they have broad and understudied health implications for veterans. We propose to perform the largest genetic study of anxiety ever conducted. We will use this information to investigate overlapping genetics between psychiatric disorders and known health risks such as cardiovascular disease and lung cancer.

PI_NAMEs: LEVEY, DANIEL F (contact)

PROJECT_TERMS: Address;Anxiety;Anxiety Disorders;anxiety symptoms;Architecture;Attention;autosome;Behavior;behavioral response;biobank;Biological;Biological Assay;Biology;Cardiovascular Diseases;cardiovascular disorder risk;Clinic;Clinical;clinical translation;clinically relevant;Code;Collaborations;comorbidity;Complex;cost;Data;Data Set;Data Sources;Diagnosis;Disabling;Disease;disorder risk;Distress;Enzymes;Epidemiology;Event;Foundations;functional genomics;Future;Generalized Anxiety Disorder;Genes;Genetic;genetic analysis;genetic architecture;genetic association;genetic information;Genetic Research;genetic resource;Genetic study;genome wide association study;genome-wide;Genomics;Health;Human Genetics;improved;in silico;Individual;insight;Joints;Knowledge;Lead;Life;Light;Longitudinal cohort;Major Depressive Disorder;Malignant neoplasm of lung;Malignant Neoplasms;Mendelian randomization;Mental Depression;Mental disorders;Mentors;Meta-Analysis;Mitochondrial DNA;Molecular;Moods;Neurosciences;Outcome;Participant;Pathway interactions;Patients;Phenotype;phenotypic data;physical conditioning;Polyamine Catabolism;Polyamines;polygenic risk score;Post-Traumatic Stress Disorders;Predisposition;Preparation;Prevalence;programs;psychiatric comorbidity;Psychiatric Diagnosis;psychiatric genomics;Publications;Research;resilience;Risk;risk stratification;Role;Sampling;sex;Sex Chromosomes;Sex Differences;Source;Spermidine/Spermine N1-Acetyltransferase;stress disorder;Suicide;System;Techniques;Testing;Training Programs;trait;translational potential;Translations;United States;Universities;Update;Variant;Veterans;X Chromosome

PROJECT_TITLE: Investigating the Genomic Architecture of Anxiety and Overlap with Mental Health Disorders in the Million Veteran Program.


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

ORG_STATE: IL

PHR: Project Narrative Reduction of myocardial conduction velocity (MCV) in the heart is a primary cause of ventricular tachycardia and sudden cardiac death. There are no treatments for cardiac arrhythmias that improve MCV; however, we have recently described carbon nanotube fibers (CNTf) as a strong, flexible, electrically conductive suture material that is capable of electrically bridging scar tissue in the heart. The goal of this research proposal is to examine the mechanisms whereby CNTf serve as a conduit to restore electrical conduction within the heart.

PI_NAMEs: MCCAULEY, MARK D (contact)

PROJECT_TERMS: Ablation;Acute;Age Months;agent orange;American;Animal Model;Anterior;Anti-Arrhythmia Agents;Area;Arrhythmia;Arteries;Award;Biocompatible Materials;biomaterial compatibility;Biomedical Engineering;Carbon Nanotubes;Cardiac;cardiac implant;Cause of Death;Cessation of life;Charge;Chicago;Chronic;Cicatrix;combat;Coronary heart disease;Coupling;Data;Developed Countries;Development;Disease;Echocardiography;Electric Capacitance;Electric Conductivity;electric impedance;Electrodes;Electrophysiology (science);Event;Fatigue;Fiber;flexibility;Functional disorder;Future;Goals;Healthcare Systems;Heart;Heart Diseases;Histology;Hospitalization;Impairment;Implant;Implantable Defibrillators;implantation;improved;in vivo;Infarction;inflammatory marker;Inflammatory Response;innovation;Laboratories;Left;Ligation;Maintenance;manufacture;Measures;Mechanics;Medical center;Metals;Military Personnel;Mitochondria;Morbidity - disease rate;mortality;Mus;Muscle;Muscle Cells;Myocardial;Myocardial Infarction;Myocardial Ischemia;Myocardium;neonatal exposure;Operative Surgical Procedures;Outcome;Physicians;Platinum;Polymers;Post-Traumatic Stress Disorders;pre-clinical;Predisposition;prevent;Prevention;Property;Publishing;Radiofrequency Interstitial Ablation;Randomized;Rattus;Recovery;Research Priority;Research Project Grants;Research Proposals;Resistance;restoration;Risk;Risk Factors;Rodent;Scanning Electron Microscopy;Scientist;Serum;Sheep;sheep model;side effect;Signal Transduction;Silk;skeletal;Skeletal Muscle;Source;Spinal cord injury;sudden cardiac death;Surface;Surgical Models;Surgical sutures;Tensile Strength;Testing;Therapeutic;Time;Tissues;Ventricular;Ventricular Fibrillation;Ventricular Tachycardia;Veterans;Veterans Health Administration;voltage

PROJECT_TITLE: In Vivo Restoration of Myocardial Conduction with Carbon Nanotube Fibers


PHR: Approximately 200,000 veterans receive cancer care in VHA facilities. About 30% of them undergo radiation therapy as part of their treatment. With increasing cancer survival rates, the long-term adverse side effects of cancer therapies, including radiation therapy have becoming widely apparent. Damage to endothelial cells, in particular in microvessels is believed to drive many long-term health problems after radiation therapy, including heart failure and lung fibrosis after radiation therapy to the chest and cognitive decline after radiation therapy to the brain. The proposed research aims at understanding how mitochondria in endothelial cells mediate the radiation-induced microvascular damage and provide proof of concept for developing new mechanism-based treatments. The proposed research is directly relevant to VA healthcare because of the high disease burden of cancer with its increasingly recognized implications for vascular disease and the enormous health care cost it causes in veterans.

PI_NAMEs: GRUMBACH, ISABELLA MARIA (contact)

PROJECT_TERMS: Affect;Behavior;Binding;Biological Assay;Blood - brain barrier anatomy;Blood capillaries;Blood Vessels;blood-brain barrier disruption;Brain;burden of illness;Calmodulin;Cancer Burden;cancer care;Cancer cell line;cancer survival;cancer therapy;Cardiovascular system;Cell Aging;cell injury;Chest;Chronic;clinical practice;combat;Cranial Irradiation;Cytoprotection;Data;Development;Diastolic heart failure;DNA Damage;DNA Repair;effective therapy;Effectiveness;Endothelial Cells;endothelial dysfunction;Endothelium;Equipment;Fibroblasts;Functional disorder;Genetic Models;Goals;Health;Health Care Costs;Healthcare;Heart failure;Impaired cognition;improved;In Vitro;in vivo;inhibitor;Injury;innovation;insight;Intervention;Ion Channel;Laboratories;Long-Term Effects;Malignant Neoplasms;Mediating;Membrane Potentials;Microvascular Dysfunction;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Mitochondrial Matrix;mitochondrial membrane;Modeling;Molecular;nanoparticle;Normal tissue morphology;novel;Outcome;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Patients;Phosphotransferases;Positioning Attribute;prevent;Production;programs;Publishing;Pulmonary Fibrosis;Radiation;radiation adverse effect;radiation effect;Radiation Injuries;radiation mitigator;Radiation Syndromes;Radiation therapy;radiation-induced injury;Reactive Oxygen Species;Reporting;Research;Respiratory Burst;side effect;Survival Rate;Techniques;Testing;Time;Tissues;tool;uptake;Vascular Diseases;Veterans;Veterans Health Administration

PROJECT_TITLE: Leveraging mitochondrial function to combat radiation therapy-induced microvascular disease


ORG_CITY: PROVIDENCE

ORG_NAME: PROVIDENCE VA  MEDICAL CENTER

ORG_STATE: RI

PHR: Posttraumatic Stress Disorder (PTSD) is a highly prevalent and chronic psychiatric disorder in Veterans and the broader US population. It is a terrible disorder, associated with significant stigma, diminished psychosocial functioning, poor physical health, and lessened quality of life. The disorder is complex and multifaceted; diagnosis is often difficult, and the mechanism of the illness is not fully understood. We proposed a novel approach in this CDA-2 application to generate novel biological markers of PTSD symptomatology and to link each of the PTSD symptom domains with a deficit in specific brain networks. To understand this complex and heterogeneous illness, we will employ modern analytical tools and machine learning algorithms. Doing so would represent the innovative first step towards characterizing heterogeneity in this disorder, and, if successful, could lead to objective markers of circuit dysfunction that can be targeted by specific interventions.

PI_NAMEs: ZAND VAKILI, AMIN  (contact)

PROJECT_TERMS: advanced analytics;Affect;analytical method;analytical tool;Arousal;Award;Awareness;Basic Science;Biological;Biological Markers;Brain;brain based;career;Caring;Chronic;Clinical;clinical care;clinical heterogeneity;Clinical Research;Clinical Sciences;clinical training;Cognition;comorbidity;Complex;computerized tools;Data;Data Science;design;Diagnosis;Diagnostic;diagnostic strategy;diagnostic tool;Diffusion Magnetic Resonance Imaging;Disease;disease classification;DSM-V;Epidemic;experience;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Health;Heterogeneity;improved;Individual;individualized medicine;innovation;Intervention;Lead;Learning;Link;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;Maps;Mental Depression;Mental disorders;Mental Health;Mentors;Mentorship;Methodology;Modeling;Modernization;Moods;neural network;Neurobiology;neuroimaging;neuroregulation;novel;novel strategies;Patients;Pharmacotherapy;phenomenological models;Phenotype;physical conditioning;Physicians;Population;Positioning Attribute;Post-Traumatic Stress Disorders;programs;Psychiatric Diagnosis;Psychiatrist;Psychiatry;psychosocial;Psychotherapy;Qualifying;Quality of life;Research;Rest;Scientist;service member;Services;Severities;skills;social stigma;substance use;Suicide;symptom cluster;symptomatology;Symptoms;System;Testing;Time;tool;tractography;Training;translational study;Veterans;Vietnam;Work

PROJECT_TITLE: Developing Computational Nosologies of Posttraumatic Stress Disorder (PTSD)


ORG_CITY: NEW YORK

ORG_NAME: VA  MEDICAL CENTER

ORG_STATE: NY

PHR: Lower airway dysbiosis characterized by the enrichment of the lungs with oral commensals is a poorly understood phenomenon, but a common event that increases in the diseased lung. Veterans with lung dysbiosis may be at-risk for increased pathogen susceptibility and infection. Chronic dysbiosis is associated with increased lung PD1+ T cells and Tregs which may mediate the poor immune response to respiratory pathogens, something that I will study using a pre-clinical murine model in this project. I will use next-generation sequencing with multi- omic bioinformatics and measurement of microbial metabolites to identify functional host-microbiota signatures in chronic dysbiosis associated with increased pathogen susceptibility. I will evaluate the mechanisms involved in determining the altered lower airway immunity against respiratory pathogens induced by chronic dysbiosis. My proposal is relevant for the veteran population as pneumonia is one of the main causes for VA hospital admission, thus identification of modifiable targets is a priority.

PI_NAMEs: WU, BENJAMIN G (contact)

PROJECT_TERMS: Acetates;Acute;Affect;Airway Disease;Alveolar Macrophages;Antibiotics;Antigens;aspirate;Bioinformatics;Biological Assay;C57BL/6 Mouse;career;CD28 gene;CD3 Antigens;Cell Physiology;Cell Separation;Cells;Cessation of life;checkpoint inhibition;Chronic;chronic inflammatory lung disease;Chronic Obstructive Pulmonary Disease;Clinical;cohort;Culture-independent methods;Data;Development;Diagnosis;Disease;dysbiosis;Ecology;epidemiologic data;Evaluation;Event;exhaustion;Experimental Designs;experimental study;Foundations;Frequencies;Future;Gastroesophageal reflux disease;Genus Mycobacterium;Hospitalization;host microbiota;Human;Human body;human subject;IL17 gene;Immune;Immune checkpoint inhibitor;Immune response;Immunity;immunoregulation;Impairment;in vivo;Infection;infection risk;Inflammation;Inflammatory;inflammatory marker;International;Investigation;Laboratories;Lung;Lung Diseases;lung microbiota;Malignant neoplasm of lung;Measurement;Measures;Mediating;Mentors;Mentorship;metabolome;metabolomics;metatranscriptome;metatranscriptomics;Methodology;microbial;microbial signature;microbiota;microbiota profiles;military veteran;Molecular;mortality;mouse model;Mucosal Immunity;multiple omics;Mus;new therapeutic target;next generation sequencing;oral commensal;Outcome;pathogen;Pathogenicity;Pathway Analysis;Pathway interactions;Pattern;Phenotype;Physicians;Pneumonia;Population;pre-clinical;Predisposition;Prevotella;Prevotella melaninogenica;Process;Production;programmed cell death protein 1;Propionates;Proteins;Publications;Pulmonary Inflammation;Recovery;recruit;Recurrence;Regulatory T-Lymphocyte;Research;Research Personnel;Resources;respiratory challenge;respiratory colonization;respiratory microbiota;Respiratory Mucosa;respiratory pathogen;Respiratory Tract Infections;response;Risk;risk stratification;Role;Scientist;single-cell RNA sequencing;Specificity;Streptococcus;Streptococcus mitis;Streptococcus pneumoniae;Systems Biology;T cell regulation;T cell response;T-Lymphocyte;Techniques;Testing;TLR4 gene;Training;transcriptomics;Translational Research;trend;United States Department of Veterans Affairs;Up-Regulation;Urothelium;Veillonella;Veillonella parvula;Veterans;Volatile Fatty Acids

PROJECT_TITLE: Lung Dysbiosis and Increased Host Susceptibility to Respiratory Pathogens


ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

PHR: Schizophrenia is a leading cause of disability for Veterans, but remains poorly treated. A primary focus of Dr. Tregellas’ research is developing a better understanding of the neurobiology underlying schizophrenia and developing new, more effective treatments for the illness. Much of this work is aimed at reducing activity of the hippocampus, which is now considered a core feature of schizophrenia. Dr. Tregellas’ current study is determining if low-dose levetiracetam , typically used at higher doses to treat seizures, can reduce hippocampal activity and improve schizophrenia symptoms. He also is interested in how antipsychotic medications used to treat schizophrenia symptoms cause weight gain and metabolic problems in patients, and how exercise might alter these effects. Related to this, Dr. Tregellas is interested in understanding the neurobiology of obesity not only in schizophrenia, but also in non-mentally ill Veterans, who have obesity rates substantially higher than in the general population.

PI_NAMEs: TREGELLAS, JASON R (contact)

PROJECT_TERMS: Affinity;American;Anticonvulsants;Antipsychotic Agents;Attention;Award;Behavior;Behavioral;Biological Psychiatry;Brain;Brain imaging;brain research;cardiometabolism;Cardiovascular Diseases;career;Cause of Death;Clinical Nutrition;Clinical Trials;Cognition;cognitive process;college;Congresses;Coupled;Dedications;disability;Dose;Eating;effective therapy;Energy Intake;Energy Metabolism;Epilepsy;Exercise;exercise intervention;Functional disorder;Funding;General Population;Goals;Grant;Health;Healthcare;high risk;Hippocampus;Human;Hyperactivity;imaging facilities;Impaired cognition;improved;Individual;instrumentation;interest;International;Interview;Journals;Levetiracetam;Life;Magnetic Resonance Imaging;Manuscripts;Measures;Medical center;meetings;Mental disorders;Metabolic;mild cognitive impairment;mortality;mouse model;Neurobiology;neuroimaging;neuronal excitability;Neurons;neuropsychopharmacology;Neurosciences;Nicotinic Agonists;Non-Insulin-Dependent Diabetes Mellitus;Obesity;obesity prevention;Paper;Pathology;Patients;Peer Review;Pharmaceutical Preparations;pharmacologic;Prevalence;Process;Productivity;Psychiatry;Publications;Publishing;Quality of life;Radio;Reducing Agents;Research;Resistance;response;Rest;Risk;Schizophrenia;Science;Scientist;Seizures;Sensory;Series;Societies;symposium;symptom treatment;Symptoms;Therapeutic;therapeutic development;therapy development;trend;United States National Institutes of Health;Veterans;Washington;Weight;Weight Gain;Work

PROJECT_TITLE: CSR&D Research Career Scientist Award Application


PHR: Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) are closely related blood malignancies that are most prevalent in aging populations. Occurring typically after the age of 60, these malignancies are usually fatal. As the proportion of Veterans reaching old age is increasing, understanding the molecular mechanisms underpinning the role of aging in these diseases is critical for effective treatment. Furthermore, environmental exposure to various toxic chemicals has been linked to higher incidence of both MDS and AML, likely putting Veterans at an increased risk for both diseases. Unfortunately, treatments for MDS and AML are largely ineffective, as evidenced by a 5-year survival rate of less than 25% for AML patients. The proposed studies aim to increase the efficacy of existing treatments for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) by identifying and characterizing RNA processing phenotypes that predict age-related disease progression and drug resistance.

PI_NAMEs: GILLEN, AUSTIN E (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;Affect;Aftercare;Age;age-related disease;Aging;aging related;aging related disease;Alternative Splicing;AML/MDS;Animal Model;Award;Big Data;Biological Assay;Biological Markers;Blood;cancer cell;Cancer Patient;Cell Culture Techniques;Cells;Cellular Assay;Clinical;Clinical Management;clinically relevant;Data;Data Analyses;data resource;Development;Disease;Disease Progression;Disease Resistance;Drug resistance;drug sensitivity;Dysmyelopoietic Syndromes;effective therapy;Environment;Environmental Exposure;Event;experience;experimental study;Exposure to;fitness;Gene Expression Profile;Genes;Goals;Grant;Hematopoietic Neoplasms;Heterogeneity;Human;human old age (65+);improved;In Vitro;in vivo;Incidence;individual patient;insight;Link;Malignant Neoplasms;Mentors;Messenger RNA;Methods;Modeling;Molecular;Molecular Profiling;Molecular Target;mouse model;Mus;Mutate;Mutation;new therapeutic target;novel;old mice;Outcome;patient response;Patients;Pharmacotherapy;Phenotype;Play;Poison;Polyadenylation;Population;Population Heterogeneity;predict clinical outcome;predicting response;Prediction of Response to Therapy;predictive marker;pressure;Process;programs;Protein Isoforms;Regulation;Reporting;Resolution;response;Risk;RNA Processing;RNA Splicing;Role;Sampling;single cell sequencing;single-cell RNA sequencing;Site;software development;Software Tools;Specimen;Spliceosomes;Survival Rate;Techniques;Testing;The Cancer Genome Atlas;therapy resistant;Tissues;Transplant Recipients;Transplantation;treatment response;tumorigenesis;Variant;Veterans

PROJECT_TITLE: Cellular Heterogeneity and Aging in MDS and AML


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: The VA provides health care to more than 250,000 Veterans with psychotic-spectrum disorders, including schizophrenia, a chronic illness associated with significant disability and high health care costs. The symptom of avolition, a deficit in initiating and sustaining goal-oriented behavior, is a strong predictor of poor outcomes in patients with schizophrenia and is resistant to currently available treatments. An improved understanding of the neurobiology of avolition, and validated neurobiological models that translate across species, can lead to more effective interventions. This project seeks to uncover the underlying mechanisms of avolition using a powerful combination of neuroscientific tools and a translational paradigm that taps parallel mechanisms across humans and rodents. Successful completion of this project will yield a broadened knowledge of the neurobiology of avolition. Further, evidence garnered from this study can help advance the development of novel neuroscience-informed interventions to improve the lives of Veterans with schizophrenia.

PI_NAMEs: ABRAM, SAMANTHA  (contact)

PROJECT_TERMS: Address;Advanced Development;Animal Model;Area;Behavior;Behavioral;Brain;Caring;Chronic Disease;Clinical;clinical predictors;Clip;cognitive function;Consensus;debilitating symptom;design;Development;disability;Disease;effective intervention;Electroencephalography;Episodic memory;Equipment and supply inventories;Event-Related Potentials;Exhibits;experience;Failure;Frequencies;Functional disorder;functional improvement;Funding;Future;goal oriented behavior;Goals;Hand;Health Care Costs;Healthcare;Hippocampus;Human;improved;Individual;insight;Internet;Interpersonal Relations;Intervention;Investigation;Knowledge;Lateral;Literature;Measures;Mediating;Memory;Memory impairment;memory process;mental representation;Methods;Modeling;Motor;motor deficit;Movement;multimodality;Network-based;neural;Neurobiology;neurophysiology;Neurosciences;neurotransmission;novel;Occupational;Outcome;Parietal Lobe;Participant;Patients;Pattern;personalized medicine;Persons;Phase;positive emotional state;Pre-Clinical Model;pre-clinical research;Prediction of Response to Therapy;Preparation;Process;programs;Protocols documentation;Psychoses;psychotic;Rattus;Reaction Time;remediation;Research;Research Personnel;Resistance;response;Retrieval;reward anticipation;reward processing;Rewards;Rodent;Role;Schizophrenia;Signal Transduction;social;success;Symptoms;Test Result;Testing;Time;tool;training opportunity;Transcranial magnetic stimulation;Translating;translation to humans;translational model;Veterans;Well in self;Work

PROJECT_TITLE: An EEG Study of Reward Processing and Memory Dysfunction in Schizophrenia


ORG_CITY: TUCSON

ORG_NAME: SOUTHERN ARIZONA VA HEALTH CARE SYSTEM

ORG_STATE: AZ

PHR: Spinal cord injury (SCI) is a debilitating condition without meaningful treatment. The Department of Veterans Affairs provides care and disability compensation for over 42,000 veterans suffering from SCI, with the annual healthcare cost for SCI victims being 6.5 times greater than that of the average veteran. Treatment of SCI involves intensive care immediately following injury, as well as rehabilitation and treatment for any resulting complications. Unfortunately, recovery post-SCI often plateaus after about 12 months. The reason behind the development of this plateau phase is not fully understood. If the plateau phase could be prevented or reversed, perhaps continual recovery following injury could be possible. The proposed studies will attempt to address this gap in knowledge, which could prove beneficial for not only the patients themselves, but also for the healthcare system in general.

PI_NAMEs: SCHOLPA, NATALIE E (contact)

PROJECT_TERMS: Address;ADRB2 gene;Adrenergic Agonists;Affect;Age;Agonist;Antioxidants;Area;Behavioral;beta-2 Adrenergic Receptors;Biogenesis;Bioinformatics;Biology;Blood Vessels;career;career development;Caring;Cell Physiology;Clinical;clinical application;Clinical Trials;Communication;Complex;cost;Data;Development;Development Plans;Devices;disability payment;Disease;Doctor of Philosophy;educational atmosphere;Epigenetic Process;epigenome;Event;experience;Exposure to;FDA approved;Female;formoterol;Functional disorder;Gene Expression Profiling;Genes;Genetic;Genetic Transcription;Genomics;Goals;Health Care Costs;Healthcare;Healthcare Systems;Human;improved;in vivo;Individual;Injury;injury recovery;innovation;Intensive Care;Investigation;Knowledge;Laboratories;Lesion;Locomotor Recovery;loss of function;Maintenance;male;Mediating;Mediator;Medical;Mentors;Mitochondria;mitochondrial dysfunction;Modification;Molecular;Mus;Nature;Neurosurgeon;novel strategies;Oral;Oxygen;Pathology;Patients;pharmacologic;Pharmacology;Phase;Play;prevent;Publishing;Qualifying;Recovery;Rehabilitation therapy;Reporting;Research Personnel;Role;service member;Site;skills;Spinal Cord;Spinal cord injury;Therapeutic;therapeutic target;Time;Training;Trauma;treatment group;United States;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Writing

PROJECT_TITLE: The Role of Epigenetics in Mitochondrial Biogenesis-Mediated Recovery after Spinal Cord Injury


ORG_CITY: KANSAS CITY

ORG_NAME: KANSAS CITY VA MEDICAL CENTER

PHR: Heart failure is the number reason for admission among patients in the Veteran (VA) health system without cure, consuming a significant portion of VA medical resources. This proposal is to test a hypothesis that targeting UCH-L1, a deubiquitinating enzyme, is a novel approach for the treatment of heart failure and circulating UCH-L1 serves as novel biomarker of heart failure. The outcome will pave the way for translational studies of targeting UCH-L1 to treat and manage cardiac disease and heart failure.

PI_NAMEs: CUI, TAIXING  (contact)

PROJECT_TERMS: Admission activity;Animal Model;Automobile Driving;Autophagocytosis;Biological Markers;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cessation of life;Circulation;Clinical;Complex;Consumption;Deubiquitinating Enzyme;diagnostic value;exosome;Failure;FRAP1 gene;Functional disorder;Genes;Genetic;Geometry;Health system;Heart;Heart Diseases;Heart failure;Hsc70 protein;Human;Hydrolase;improved;in vivo;inhibition of autophagy;inhibitor;Knock-out;Link;Mediating;Mediator;Medical;Medical Research;Membrane Proteins;Mission;Molecular;mouse model;Mus;myocardial damage;novel;novel diagnostics;novel marker;novel strategies;novel therapeutics;Outcome;overexpression;Pathogenicity;Pathologic;Pathology;Pathway interactions;patient population;Patients;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Physiological;Pilot Projects;pressure;prognostic value;programs;Proteasome Inhibition;Protein Dephosphorylation;Proteins;Regulation;Research;Resources;Risk Factors;Risk Reduction;Role;Signal Transduction;Sirolimus;Site;Symptoms;Testing;Therapeutic;Time;Transgenic Organisms;translational study;Ubiquitin;ubiquitin isopeptidase;Up-Regulation;Veterans;Wild Type Mouse

PROJECT_TITLE: To explore the potential of UCH-L1 as a novel therapeutic and diagnostic target in heart failure


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: STANFORD

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: STANFORD UNIVERSITY

PHR: Overall - Interaction of external inputs with internal dynamics:  influence of brain states on neural computation and behavior  Project Narrative Neural activity in the brain is thought to give rise to the entirety of our mental lives, including sensation, perception, cognition, deliberation and action. The proposed research seeks to establish a fundamental understanding of how the activity of populations of neurons reflect these processes, on a moment by moment basis and with quantitative rigor, to help establish a principled theory of the relation between internal neural states and our mental lives. Thus this research will lead to a deeper understanding of the function and dysfunction of the central nervous system, and ultimately contribute to the ability to diagnose and treat neuropsychiatric disease and injury. 1

PI_NAMEs: DEISSEROTH, KARL A. (contact);GIOCOMO, LISA

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: 3-Dimensional;Acceleration;analog;Astronomy;Back;Bayesian Analysis;Behavior;Behavioral;Brain;BRAIN initiative;Brain region;cell assembly;cell cortex;cell type;Cells;Central Nervous System;Chemistry;Clinical;clinically relevant;Cognition;Collaborations;Communities;computational neuroscience;computational platform;Computer Models;computerized tools;Computing Methodologies;control theory;Data;design;Diagnosis;Dimensions;Education and Outreach;empowerment;Ensure;Environment;Esthesia;experience;experimental study;feeding;frontal eye fields;Functional disorder;Hydrogels;Image;Individual;Injury;insight;laboratory experiment;Language;Laws;Learning;Macaca;Maintenance;Measurement;Measures;Medial;meetings;Methods;millisecond;Modeling;Molecular;Monitor;Monkeys;Motor;multimodality;multisensory;Mus;neural;neural circuit;neural model;neuronal circuitry;Neurons;neuropsychiatric disorder;Neurosciences;new technology;next generation;nonhuman primate;Optics;Outcome;outreach;Pattern;Perception;Phenotype;Play;Population;Positioning Attribute;Preparation;Process;Psyche structure;Research;Rodent;Science;Sensory;sensory input;single cell sequencing;social;spatiotemporal;Stream;success;Synapses;System;Technology;technology development;technology platform;temporal measurement;Testing;Text;theories;Time;Tissues;two-photon;Uncertainty;Update;Visual;Visual Cortex;Work;Writing


NIH_SPENDING_CATS: Neurosciences

PI_NAMEs: DEISSEROTH, KARL A. (contact)

PROJECT_TERMS: Accounting;Administrative Coordination;Animals;Behavior;Brain;clinical center;Collaborations;Communication;Communities;Complex;data dissemination;data sharing;Doctor of Philosophy;Drug usage;Education;Educational process of instructing;Elements;Environment;Funding;Goals;graduate student;Human Resources;Human Subject Research;interest;Lead;Logistics;Measures;neural;next generation;Occupational activity of managing finances;organizational structure;outreach;Persons;Postdoctoral Fellow;Progress Reports;Protocols documentation;Publications;Reagent;Regulation;Reporting;Research;Research Project Grants;Resources;Role;Safety;Safety Management;Science;Scientist;Shoulder;Side;Structure;success;Technology;Technology Transfer;Training;Training Activity;Training and Education;University resources;Vision;Visit;web page

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Asthma;Complementary and Integrative Health;Drug Abuse (NIDA only);Lung;Neurosciences;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: NARRATIVE  The human lung is widely innervated, and yet how signals from the lung impact the nervous system and how signals from the nervous system impact lung function is poorly understood. In this study, we will test the property and function of a newly uncovered neural circuit that senses aerosol signals such as allergen in lung, transmits it to the brain, and then back to the lung to control airway constriction. Given that increased airway constriction is a key feature of asthma exacerbation, our findings will provide insights into the use of neural modulation as a novel therapeutic option for treating airway diseases such as asthma.

PI_NAMEs: SUN, XIN  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEN G

PROJECT_TERMS: Ablation;Address;Adult;Aerosols;Afferent Neurons;Air;Airway Disease;airway hyperresponsiveness;Allergens;Alveolus;Anxiety;Asthma;asthma exacerbation;attenuation;Back;Brain;Brain region;Brain Stem;Breathing;Cell Nucleus;cell type;Central Nervous System;Child;Chronic;constriction;Data;Dementia;Disease;dorsal motor nucleus;Efferent Neurons;Electrophysiology (science);Epithelium;expectation;Experimental Genetics;Foundations;functional loss;Ganglia;Gases;Genetic;Health system;Human;Hypothalamic structure;Imaging Device;improved;In Situ;in vivo;in vivo calcium imaging;Individual;Injections;insight;Interoception;Irritants;Knowledge;Label;Light;Link;Lung;Maps;Meditation;Mental Depression;Molecular;mouse model;Mus;Nerve;Nervous System;neural;neural circuit;Neuroanatomy;Neuroendocrine Cell;neuronal cell body;Neurons;neurotransmission;novel therapeutics;Nucleus solitarius;optical imaging;optogenetics;Organ;paraventricular nucleus;Peripheral;Physiology;prevent;Property;Psyche structure;pulmonary function;Qi Gong;Recombinant adeno-associated virus (rAAV);Respiration;respiratory;response;RNA;sensor;Sensory;Side;Signal Induction;Signal Transduction;single nucleus RNA-sequencing;Smooth Muscle;spatial relationship;Spinal;Spinal Cord;Spinal cord posterior horn;Stress;Synapses;Techniques;Testing;Three-Dimensional Imaging;tool;Toxin;transmission process;Tube;Vagotomy;Viral

PROJECT_TITLE: Dissecting the Interoception Circuit that Controls Airway Constriction


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

PI_NAMEs: SHENOY, KRISHNA V (contact)

PROJECT_TERMS: Adopted;Algorithmic Analysis;Algorithms;Animals;Architecture;Archives;base;Behavior;Behavioral;Benchmarking;Brain;Catalogs;Code;Collaborations;Communication;Communities;Computer Models;Computer software;computerized data processing;Consumption;Creativeness;Custom;Data;data access;Data Analyses;data analysis pipeline;data curation;data format;data handling;data management;data modeling;data pipeline;Data Science Core;Data Set;data sharing;data standards;Data Storage and Retrieval;database query;Databases;Discipline;Doctor of Philosophy;Documentation;Environment;experience;experimental study;Feedback;flexibility;Genetic;Goals;graphical user interface;Guidelines;Industrialization;laboratory experiment;Lead;Link;Measurement;member;Metadata;migration;Mus;neural;Neurosciences;Online Systems;open data;open source;Optics;Postdoctoral Fellow;Process;recruit;repository;Reproducibility;Research;Research Personnel;Rest;Retrieval;Route;Running;searchable database;Software Engineering;Sorting;Source Code;Speed;Standardization;Statistical Data Interpretation;Students;success;System;Testing;Time;tool;Training;Universities;Work;working group;Writing

PROJECT_TITLE: Data Science Core


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Pediatric

ORG_CITY: SALT LAKE CITY

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF UTAH

PHR: PROJECT NARRATIVE Human milk oligosaccharides assist in promoting the healthy development of the brain, gut, and immune system of infants and are produced in an infant-specific manner where biological responses drive their structures. Unfortunately, existing analytical methodologies remain limited in fully separating all their isomeric permutations, thus precluding their accurate structural characterization. To address these challenges, we will develop a bioanalytical workflow consisting of a new multidimensional separations platform to be used in conjunction with the development of chemical probes and gas-phase sequencing strategies.

PI_NAMEs: NAGY, GABE  (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Address;advanced analytics;Biological;Biological Process;Brain;Chemicals;Chromatography;Communities;Coupled;Development;Dimensions;Gases;Glycobiology;Goals;gut-brain axis;Heterogeneity;Human Milk;human milk oligosaccharides;Immune system;improved;Infant;Infant formula;ion mobility;Isomerism;Laboratories;Liquid Chromatography;liquid chromatography mass spectrometry;Mass Spectrum Analysis;Methodology;Molecular Structure;Monosaccharides;Periodicity;Phase;Positioning Attribute;programs;Recycling;Research;Resolution;response;Role;Structure;Techniques

PROJECT_TITLE: A bioanalytical research program to unravel the human milk glycome


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Prevention;Social Determinants of Health;Substance Misuse

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE Military spouses report higher levels of alcohol misuse and mental disorders than their civilian counterparts and these rates are higher when they are in a relationship with a service member with alcohol misuse. Partners Connect intervenes with the concerned partner (CP) to support them in effectively communicating with their service member to encourage service member help seeking behaviors for alcohol abuse disorders. A two- stage SMART trial will reveal how to address the wide range of symptoms CPs present with by evaluating what additional intervention helps increase service member help-seeking.

PI_NAMEs: OSILLA, KAREN CHAN (contact)

PROGRAM_OFFICER_NAME: WHITAKER, DAMIYA EVE

PROJECT_TERMS: Absenteeism;adaptive intervention;Address;Alcohol abuse;alcohol measurement;alcohol misuse;alcohol risk;alcohol seeking behavior;alcohol use disorder;Anxiety;Behavioral Mechanisms;binge drinking;brief intervention;care seeking;Caring;Communication;Communities;comparison control;Coping Skills;demographics;depressive symptoms;design;deter alcohol use;Disease;Domestic Violence;drinking;Educational process of instructing;efficacy evaluation;Ethnic Origin;Evaluation;experience;Family;fitness;follow-up;generalized anxiety;Goals;Heavy Drinking;help-seeking behavior;high risk drinking;Impairment;improved;innovation;Intervention;Interview;Mediating;Mediator;meetings;Mental Depression;Mental disorders;Mental Health;Military Personnel;military service;Modeling;novel;Online Systems;Outcome;Partner Communications;peer;personalized normative feedback;Pilot Projects;Policies;prevent;Probability;programs;Psychological reinforcement;Race;Randomized;recruit;Reduce health disparities;Reporting;Resources;Risk;Rural;rural area;Sampling;Self Care;Sequential Multiple Assignment Randomized Trial;service gap;service member;Services;sexual violence;skills;social;Social support;Spouses;Suicide;Surveys;Symptoms;Telephone;Testing;Training;treatment planning;treatment services;trial design;Unmarried;Waiting Lists;web site;web-based intervention;Work

PROJECT_TITLE: A SMART evaluation of an adaptive web-based AUD treatment for service members and their partners

STUDY_SECTION: IPTA

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


NIH_SPENDING_CATS: Bioengineering;Genetics;Neurosciences

PI_NAMEs: ENGBERG, KRISTIN  (contact)

PROJECT_TERMS: 3-Dimensional;Address;adenovirus mediated delivery;Anatomy;Animals;Attention;Automobile Driving;Axon;Back;Behavior;Brain;Categories;Cells;Chemistry;Collaborations;combinatorial;Communities;Complex;Cre driver;Data Analyses;Data Set;data streams;design;Development;Doctor of Philosophy;Educational process of instructing;Elements;Enhancers;Ensure;fluorophore;Gene Transfer Techniques;Generations;Genes;Genetic;Goals;Hydrogels;immunological status;Individual;insight;Label;Link;Mammals;Measures;Methods;Modernization;Molecular;Molecular Analysis;Molecular Profiling;Nature;Nervous System;neural;neural circuit;Neurons;Neurosciences;next generation;Noise;novel;Opsin;Optics;optogenetics;Paper;Pattern;Population;Primates;promoter;Property;real world application;recombinase;Recording of previous events;Reporting;Resolution;Resources;Rodent;Running;Science;Signal Transduction;Specificity;Speed;Structure-Activity Relationship;System;Technology;Time;Tissues;tool;transcriptomics;Transgenic Organisms;Translating;Typology;Update;Viral;Viral Vector;Virus;Visualization;Work

PROJECT_TITLE: Resource Core 1 - Primate/rodent Molecular Anatomy Core (PMAC)


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Genomic organization in the 3-dimensional nuclear space emerges as a new epigenetic regulator of transcriptional specificity that affects various developmental processes. The olfactory system provides an ideal system for deciphering, in vivo, the developmental intermediates of genomic compartmentalization and for obtaining structural insight into compartments with critical roles in neuronal gene regulation. Importantly, by revealing that genomic compartments dissipate in a humanized model of Alzheimer’s disease, not only do we explain the long-standing puzzle of olfactory deficits as a prodromal symptom of neurodegeneration, but we also open new routes for prognoses and pharmaceutical screens based on nuclear architecture perturbations.

PI_NAMEs: LOMVARDAS, STAVROS  (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: 3-Dimensional;Affect;Alleles;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapeutic;Anosmia;Architecture;Astronomy;Bar Codes;Biological Assay;cell type;Cells;Chemicals;Chromatin;Chromosomes;Complement;Complex;Detection;Development;Developmental Process;diagnostic tool;Disease;DNA;Down-Regulation;Enhancers;Environment;Environmental Risk Factor;Epigenetic Process;Essential Genes;Etiology;Exhibits;experimental study;Future;Gene Activation;Gene Expression;Gene Expression Regulation;Gene Silencing;Generations;Genes;Genetic;Genetic Enhancer Element;genetic manipulation;Genetic Transcription;Genome;Genomics;Health;Heterochromatin;Human;Human body;humanized mouse;hyposmia;in vivo;Individual;insight;interdisciplinary approach;Label;Link;Maps;Molecular;molecular imaging;mouse model;Mus;mutant;Natural regeneration;Nerve Degeneration;nerve stem cell;Neuronal Differentiation;Neurons;neurotoxicity;Nose;novel;Nuclear;Odors;Olfactory dysfunction;Olfactory Epithelium;Olfactory Pathways;olfactory receptor;olfactory sensory neurons;Organism;Output;Pharmacologic Substance;Prognosis;prognostic tool;Property;receptor expression;Receptor Gene;Research;Resolution;Role;Route;segregation;single cell genomics;single molecule;Specificity;Stereotyping;superresolution imaging;Symptoms;System;Technology;tool;Transcriptional Activation;Transcriptional Regulation;Variant;Viral;Volatilization

PROJECT_TITLE: Interrogating genome folding trajectories in health and disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-S(70)R]


ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: 8. Project narrative The assembly of tissues and organs during embryonic development and their subsequent maintenance for decades are remarkable processes, requiring cells to choose appropriate cell fates via cell-cell communication, stably adhere to one another, yet also be able to change shape and move. Defects in cell communication or cell adhesion underlie certain birth defects, while inappropriate activation of cell signaling, as occurs after mutation of the tumor suppressor APC, drives colon and other cancers, and altered adhesion and motility underlie cancer metastasis. We have developed model systems using both the fruit fly Drosophila and in cultured mammalian cells to define the molecular basis of these remarkable properties during normal development and how they go wrong in disease.

PI_NAMEs: PEIFER, MARK A. (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actomyosin;Address;Adherens Junction;Adhesions;animal tissue;Animals;APC gene;Apical;Biological Models;Biology;Buffers;cancer initiation;Cell Adhesion;cell assembly;Cell Communication;Cell membrane;Cell Shape;Cells;Colon;Colon Carcinoma;Complex;Congenital Abnormality;Cues;Cytoskeleton;Defect;detector;Development;developmental disease;Disease;Drosophila genus;egg;Embryonic Development;Ensure;Epithelium;Event;F-Box Proteins;gastrulation;Genetic;Goals;Homeostasis;Human;in vivo;Intercellular Junctions;Lead;Link;Maintenance;Malignant Neoplasms;Mammalian Cell;Microscopy;Modeling;Molecular;Morphogenesis;Motility;Mutate;Mutation;Neoplasm Metastasis;Organ;Phosphotransferases;Positioning Attribute;Process;Property;Protein Array;protein complex;Proteins;Resistance;response;Shapes;Signal Transduction;Tissues;tool;Tumor Suppressor Proteins;tumorigenesis;ubiquitin-protein ligase;WNT Signaling Pathway;Work;zygote

PROJECT_TITLE: Regulating cell fate and shaping the body plan during morphogenesis and their alteration during oncogenesis

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


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

PI_NAMEs: CROW, AILEY  (contact)

PROJECT_TERMS: Address;Adult;Area;Attention;Back;Behavior;Behavioral;Brain;brain based;Brain region;Categories;Cells;cellular imaging;Cognition;Collaborations;Color;Communities;Computer Analysis;Crows;Dedications;design;Development;Devices;Diameter;Doctor of Philosophy;Dorsal;Educational process of instructing;Esthesia;experience;Experimental Designs;Fiber;Fluorescence;Genetic;Goals;Head;Image;Imaging technology;improved;in vivo;interest;Investigation;Joints;lens;Lighting;Maps;Measures;member;Methods;Microscope;Modernization;Motor;Mus;Nature;Neocortex;neural;neural circuit;Neurons;new technology;next generation;Noise;nonhuman primate;novel;Operative Surgical Procedures;Opsin;Optics;optogenetics;Outcome;Population;portability;Positioning Attribute;Preparation;Primates;Process;Publishing;ratiometric;real world application;Research Project Grants;Resolution;Resources;Rest;Rodent;Science;Scientist;sensor;Sensory;Signal Transduction;Site;Specific qualifier value;Speed;Structure-Activity Relationship;Supervision;Systems Development;technological innovation;Technology;theories;tool;Training;Translating;two-photon;United States National Institutes of Health;Validation;virtual;Visit;Work;Writing

PROJECT_TITLE: Resource Core 2 - Primate/rodent Optics Core (POC)


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Health Services;Heart Disease;Hypertension;Infectious Diseases;Prevention

ORG_CITY: KAMPALA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: INFECTIOUS DISEASES RES COLLABORATION

PHR: Project Narrative Effective, cost-effective, scalable, sustainable, and equitable implementation strategies to improve care for people living with HIV and co-morbid hypertension in sub-Saharan Africa are urgently needed. Our study will compare the effectiveness, scalability, and cost-effectiveness of a lower-resource intensive vs. a higher- resource intensive strategy to integrate hypertension care into HIV clinics in Uganda.

PI_NAMEs: LONGENECKER, CHRIS TODD;SEMITALA, FRED C (contact)

PROGRAM_OFFICER_NAME: MINTZER, KEITH A

PROJECT_TERMS: Address;Adherence;Adoption;Africa South of the Sahara;Anti-Hypertensive Agents;antiretroviral therapy;Awareness;Blood;Blood Pressure;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Caring;Cessation of life;Chronic;Climate;Clinic;Clinical;Cluster randomized trial;Collaborations;comorbidity;compare effectiveness;Consolidated Framework for Implementation Research;Coronary heart disease;cost;Cost Analysis;cost effective;cost effectiveness;Cost Effectiveness Analysis;Cost effectiveness research;cost-effectiveness evaluation;Data;Data Set;design;Development;Diagnosis;Diagnostic Equipment;disability;disability-adjusted life years;economic impact;Economics;effectiveness evaluation;effectiveness outcome;effectiveness testing;Equity;evidence base;Expenditure;formative assessment;Foundations;Goals;Gold;Government;Grant;Guidelines;Health;Health Services;Heart failure;HIV;HIV Infections;HIV/AIDS;Household;human centered design;Hybrids;Hypertension;hypertension control;hypertensive;implementation framework;implementation outcomes;implementation science;implementation strategy;implementation/effectiveness;improved;incremental cost;incremental cost-effectiveness;innovation;Institution;integrated care;International;Intervention;Investments;Knowledge;LDL Cholesterol Lipoproteins;low and middle-income countries;Measurement;Methods;Modeling;Monitor;multidisciplinary;Patients;peer;peri-urban;Persons;Pharmaceutical Preparations;preservation;prevent;Prevention;primary outcome;process evaluation;Quality of Care;Randomized;Research Design;Resources;Risk Reduction;screening;service delivery;Service delivery model;Stroke;supply chain;therapy development;Training;treatment as usual;Uganda;Update;uptake;Use Effectiveness;Variant;Work

PROJECT_TITLE: PULESA-UGANDA-Strengthening the Blood Pressure Care and Treatment cascade for Ugandans living with HIV-ImpLEmentation Strategies to SAve lives


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes a severe lung disease named COVID-19, has spread out of control worldwide and is causing severe illness and death partly due to its relatively high transmission rates and infectivity. Highly effective vaccines have been developed in record time; however, new SARS-CoV-2 variants have appeared recently with mutations that correlate with higher infection rates and the ability to escape specific immunity, causing major concerns. The goal of this proposal is to understand the mechanisms that mediate SARS-CoV-2 virus entry and immune escape leading to high infectivity and pathogenesis, by manipulating the host ubiquitin system, and identify host factors that can be targeted for therapeutic intervention.

PI_NAMEs: RAJSBAUM, RICARDO  (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;ACE2;Affect;Affinity;antagonist;Antibodies;antiviral drug development;Appearance;Binding;Biochemical;Bioinformatics;Biological Assay;biosafety level 3 facility;Blocking Antibodies;Cell Line;Cells;Cessation of life;Clinical Trials;Co-Immunoprecipitations;Coronavirus;COVID-19;Data;Disease;Economics;env Gene Products;Epidemic;Family;Flaviviridae;Flavivirus;Future;Goals;Health;Human;Immune;Immune Evasion;Immunity;Impairment;In Vitro;in vivo;in vivo Model;infection rate;Integration Host Factors;interferon antagonist;Interferons;Knowledge;Ligase;Link;Lung Diseases;Lysine;Mass Spectrum Analysis;Mediating;member;Membrane Proteins;Molecular;multiple myeloma M Protein;Mus;Mutagenesis;mutant;Mutation;Names;Nature;neutralizing antibody;novel;novel coronavirus;Outcome;Outcome Study;pandemic disease;Pathogenesis;pathogenic virus;Pathogenicity;pharmacologic;Play;previous epidemic;Process;Protein Family;Proteins;public health emergency;Publishing;receptor;Receptor Cell;Recombinants;Reporting;RNA Viruses;Role;SARS coronavirus;SARS-CoV-2 infection;SARS-CoV-2 spike protein;SARS-CoV-2 variant;Severe Acute Respiratory Syndrome;Site;Structural Protein;System;targeted treatment;Testing;Therapeutic Intervention;Time;transmission process;TRIM Motif;Ubiquitin;Ubiquitination;Vaccines;Variant;Viral;Viral Matrix Proteins;Viral Packaging;Viral Structural Proteins;Virion;Virus;Virus Receptors;Virus Replication

PROJECT_TITLE: The Role of the Host Ubiquitin System in Promoting SARS-CoV-2 replication and Pathogenesis

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


NIH_SPENDING_CATS: Bioengineering;Neurosciences

PI_NAMEs: LO, MAISIE KY (contact)

PROJECT_TERMS: 3-Dimensional;Anatomy;Animals;Behavior;Biomedical Engineering;Brain;Cells;combinatorial;Communities;design;Doctor of Philosophy;Education;Educational Curriculum;Educational process of instructing;Educational workshop;Elements;Engineering;Ensure;experience;Familiarity;Family;Fiber;Foundational Skills;Generations;Image;Infrastructure;innovation;Link;member;Methodology;Methods;Mission;Modernization;Molecular;molecular phenotype;neural;Neurosciences;neurotechnology;new technology;novel;Optics;optogenetics;Paper;Photometry;Positioning Attribute;Primates;Publishing;Recording of previous events;Recurrence;Research Personnel;Research Project Grants;Resolution;Resources;Rodent;Specific qualifier value;Structure;Teaching Method;Technology;Time;Tissues;tool;Training;undergraduate education;United States National Institutes of Health;Validation;Viral;Visualization

PROJECT_TITLE: Resource Core 3 - Teaching/Training/Dissemination Core (TTDC)


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: ALBUQUERQUE

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF NEW MEXICO

ORG_STATE: NM

PHR: Narrative Advances in lightsheet technology have spurred important discoveries in biology, both in health and disease. However, current methods have limitations in acquisition speed, spatial resolution, and the number of possible labels that can be imaged which restrict the types of biological questions that can be addressed. Through this proposal we will develop new user-friendly imaging modalities that will not only improve the spatiotemporal resolution of the current state-of-the-art but will also enable classification of 12+ different cell types in tissue that is cleared for large millimeter sized volumes.

PI_NAMEs: CHAKRABORTY, TONMOY  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: 3-Dimensional;adaptive optics;Address;Architecture;Binding;Biological;Biological Process;Biology;cancer cell;Cell Communication;cell type;Cells;Characteristics;Classification;Color;Complex;Coupled;Coupling;Data;design;Development;Disease;Disseminated Malignant Neoplasm;Engineering;Environment;Event;fluorescence microscope;fluorophore;Health;high resolution imaging;Image;Imaging Device;imaging modality;improved;interest;Label;Light;Lighting;live cell imaging;Methods;Microscope;Microscopy;millimeter;minimally invasive;Molecular;Morphology;next generation;novel;optical imaging;Optics;Organ;Organism;Organoids;Outcome;Pattern;Penetration;Phenotype;Physiological;prevent;programs;Research;Research Personnel;Resolution;Sample Size;Sampling;Scanning;spatiotemporal;Specimen;Speed;spheroids;Techniques;Technology;temporal measurement;therapeutic target;Time;Tissue imaging;Tissues;treatment response;tumor microenvironment;user-friendly

PROJECT_TITLE: Transformative lightsheet microscopy techniques for subcellular imaging in physiologically relevant 3D environments