NIH_SPENDING_CATS: Hematology;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Project Narrative Myelodysplastic syndromes (MDS) are a collection of acquired or inherited diseases wherein the bone marrow produces too few blood cells, and patients progress to acute leukemia. We idenitified that dysregulation of innate immune signaling and inflammation are critical drivers of MDS pathogenesis. Research initiatives to dissect the genetic, molecular, and cellular underpinnings of MDS, with an emphasis on dysregulated innate immune signaling, will be pursued. Knowledge gained by our basic research findings will facilitate identification of novel therapeutic targets and treatment modalities for MDS.

PI_NAMEs: STARCZYNOWSKI, DANIEL  (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acute leukemia;Age Years;Basic Science;Blood Cells;Bone Marrow;Cardiovascular Diseases;Cells;Chronic;Collection;Development;Disease;Dysmyelopoietic Syndromes;effective therapy;Elderly;Failure;Genetic;Hematological Disease;Hematopoiesis;Hematopoietic stem cells;Hereditary Disease;Immune;Immune signaling;Incidence;Individual;Inflammation;Inflammatory;innate immune function;innate immune pathways;Knowledge;knowledge of results;Life Expectancy;Modality;Modeling;Molecular;mouse model;new therapeutic target;novel;novel therapeutic intervention;Pathogenesis;Patients;Pharmacotherapy;Phenotype;programs;Research;Signal Pathway;Syndrome;Testing;therapeutic target;tool;treatment strategy

PROJECT_TITLE: Decoding innate immune signaling in normal and myelodysplastic hematopoiesis


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: GRADUATE SCHOOLS

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: LAS CRUCES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOLOGY

ORG_FIPS: US

ORG_NAME: NEW MEXICO STATE UNIVERSITY LAS CRUCES

ORG_STATE: NM

PHR: This project is focused on the continuing operation of the Molecular Vector Physiology Laboratory at New Mexico State University, its research- and educational mission.

PI_NAMEs: HANSEN, IMMO ALEX (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Applied Research;Area;Arthropods;Basic Science;Biological Models;Blood;Cell Physiology;Culicidae;Development;disease transmission;Disease Vectors;Education;Foundations;Health;Homeostasis;improved;Knowledge;Laboratories;Methods;Mission;Molecular;molecular vector;Mosquito Control;mosquito reproduction;New Mexico;novel;Nutrient;operation;Persons;Physiology;Population;Regulation;Research;Research Personnel;Research Project Grants;Signal Pathway;Students;sucking;undergraduate student;Universities;Water

PROJECT_TITLE: The Molecular Vector Physiology Laboratory at New Mexico State University

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: Columbus

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: The recent Ebola and Zika crisis have highlighted the need for vaccines against infectious pathogens. While serum IgG is crucial for the provision of immunity in the bloodstream, induction of protective IgG responses often requires multiple doses of vaccines. This proposal will address innate mechanisms that can be exploited to induce brisk and broad immunoglobulin isotype responses, including secretory IgA responses by injected vaccines to improve protection.

PI_NAMEs: BOYAKA, PROSPER N (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Address;Adjuvant;Affect;Affinity;aluminum sulfate;Animal Model;Antibodies;Antibody Formation;Antibody Response;Antigen-Presenting Cells;Antigens;B-Lymphocytes;Binding;Blood;Blood Circulation;Cells;chemokine;cytokine;Data;Dendritic Cells;Development;Dose;Ebola;Edema;efficacy evaluation;Elastases;Enteral;enteric virus infection;Enzymes;Epithelial Cells;Family;Family suidae;Fees;Future;Genes;Germ;germ free condition;Germ-Free;Goals;Growth Factor;Human;Immune;Immune response;Immunity;Immunization;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin G;Immunoglobulin Isotypes;Immunoglobulin Switch Recombination;improved;in vivo;Infection;Infectious Agent;Injections;innovation;Kinetics;Leukocyte Elastase;Licensing;Measures;Memory B-Lymphocyte;Modeling;mucosa-associated lymphoid tissue;Mucosal Immune Responses;Mucosal Immunity;mucosal vaccine;Mucous Membrane;Mus;Myeloid Cells;neutrophil;neutrophil elastase inhibitor;Neutrophil Infiltration;Nose;novel;Oral;oral vaccine;Outcome Assessment;pathogen;Pathway interactions;pharmacologic;Play;Predisposition;prevent;Prevention;Production;protective effect;Rectum;Regulation;Research;response;Role;Rotavirus;Rotavirus Infections;Route;Secretory Immunoglobulin A;Seminal;Serine Protease;Serum;Signal Pathway;Signal Transduction;Site;Specificity;stem;Subunit Vaccines;Supplementation;Surface;Symptoms;T cell response;Testing;Toxin;Transcript;transcriptome sequencing;Tretinoin;Vaccine Adjuvant;vaccine delivery;Vaccines;Virus;Vitamins;Wild Type Mouse;Work;ZIKA

PROJECT_TITLE: Targeting myeloid cells for regulation of alum-based immunity

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: AA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Substance Misuse

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PI_NAMEs: MARTIN-FARDON, REMI  (contact)

PROJECT_TERMS: Abstinence;alcohol abuse therapy;Alcohol consumption;alcohol craving;Alcohol dependence;alcohol effect;alcohol relapse;alcohol seeking behavior;alcohol use disorder;Alcoholism;Alcohols;Amygdaloid structure;Animal Model;Animals;antagonist;Area;Arousal;Behavior;biological adaptation to stress;Brain;Cell Nucleus;Cells;Cellular Neurobiology;Chronic;Collaborations;Complement;Corticotropin-Releasing Hormone;Corticotropin-Releasing Hormone Receptors;CRF receptor type 1;Darkness;Dependence;depressive symptoms;designer receptors exclusively activated by designer drugs;Development;Drug Addiction;Drug usage;Dynorphins;Energy Metabolism;FDA approved;feeding;Female;Funding;Gene Expression;Genetic;hypocretin;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;insight;Lateral;male;Medial;Mediating;Mediation;metabotropic glutamate receptor 3;Molecular;Nature;negative affect;neural circuit;Neurons;Neuropeptides;Neuropharmacology;neuroproteomics;nociceptin;novel;Opioid Receptor;ORL1 receptor;Pathologic;Pharmaceutical Preparations;Physiological Processes;Play;Prefrontal Cortex;Rattus;receptor;Receptor Signaling;Recording of previous events;recruit;Relapse;relapse prevention;response;Role;Side;Signal Transduction;Stress;Structure of paraventricular nucleus of thalamus;Structure of terminal stria nuclei of preoptic region;System;Testing;transmission process;Ventral Tegmental Area;Work

PROJECT_TITLE: Neuropharmacology Component - Martin-Fardon


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Disabled 2 (DAB2) is one of the few proteins that are known for removing the phosphorylation of c-Src protooncogene and Src pathway is frequently activated in triple negative breast cancer (TNBC). We have previously reported that mitochondrial reprogramming to fatty acid oxidation (FAO) is a key regulator of Src activation in TNBC, but the mechanism of regulation is not understood. Since our current preliminary data suggest that FAO regulates DAB2 expression in TNBC, this project will evaluate the significance DAB2 in the metabolic activation of Src in TNBC.

PI_NAMEs: KAIPPARETTU, BENNY ABRAHAM (contact);PARK, JUNHYOUNG

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Affect;Binding;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;cancer subtypes;Cell Nucleus;Cells;Cellular biology;Characteristics;Clinical;clinically significant;Communication;Core Facility;Data;Dependence;disabled;DNA Methylation;Down-Regulation;Drug resistance;Enzymes;Epigenetic Process;epigenetic regulation;Excision;experience;fatty acid oxidation;Fatty Acids;Focal Adhesion Kinase 1;Funding;Genes;Genetic Transcription;Glucose;Glutamine;Histone Deacetylase;Histone Deacetylase Inhibitor;histone modification;hormone receptor-positive;in vivo;inhibitor;knock-down;Laboratories;Leptin;Malignant Breast Neoplasm;Malignant Neoplasms;Mechanics;Mediating;Messenger RNA;Metabolic;Metabolic Activation;metabolomics;Mitochondria;Modeling;Modification;Molecular;Molecular Biology;Mus;Mutation;Neoplasm Metastasis;Nuclear;Outcome;ovarian neoplasm;oxidation;Oxidative Phosphorylation;Pancreas;Pathway interactions;patient derived xenograft model;Patient-derived xenograft models of breast cancer;Phosphorylation;Phosphotransferases;Play;Post-Translational Regulation;predict clinical outcome;Prognosis;promoter;Protein Dephosphorylation;Protein Kinase;Proteins;Proto-Oncogenes;PTK2 gene;Publications;Publishing;Regulation;Reporting;Research;Research Personnel;Resources;Role;Secure;SH3 Domains;Signal Pathway;Signal Transduction;small hairpin RNA;Squamous cell carcinoma;SRC gene;src-Family Kinases;Subgroup;Transcriptional Regulation;translational study;triple-negative invasive breast carcinoma;tumor;tumor progression;Tumor Suppressor Genes;Tumor Suppressor Proteins;Tumor Tissue;tumor xenograft;tumorigenesis;United States National Institutes of Health;v-src Oncogenes;Validation;Xenograft procedure

PROJECT_TITLE: Disabled-2 in the metabolic regulation of oncopathways


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Salivary glands are important for oral health by producing saliva which facilitates digestion, helps swallowing foods, and prevents oral infection. Information has been limited for gene regulators for salivary gland development, postnatal growth or regeneration. The genome organizer SATB1 will be studied in this proposal, testing a hypothesis that SATB1 is a critical regulator for gene expression supporting biological processes and activities of salivary glands.

PI_NAMEs: KOHWI-SHIGEMATSU, TERUMI  (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: 3-Dimensional;Ablation;Acinar Cell;Adult;adult stem cell;Ameloblasts;aquaporin 5;Architecture;Atlases;Autoimmune Diseases;base;Binding;Biological Process;Body System;Categories;Cell Cycle;Cell Differentiation process;Cell Lineage;Cell Maturation;Cell Physiology;cell type;Cells;Cellular Structures;Chromatin;comparison control;Data;Databases;Defect;Deglutition;Dental caries;design;Detection;Development;Digestion;Distal;Ductal Epithelial Cell;effective therapy;Embryo;Embryonic Development;Epidermis;Epigenetic Process;Epithelial Cells;experimental study;fetal;Food;Foundations;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic;Genetic Recombination;Genetic Transcription;Genome;genomic locus;Genomics;Gland;gland development;global run on sequencing;Growth;Growth and Development function;Head and Neck Cancer;Human Genome;Impairment;Infection prevention;irradiation;Knockout Mice;Learning;Link;Location;Lubricants;Malignant Neoplasms;Metabolism;Modeling;Morphogenesis;mouse genome;Mus;Muscle satellite cell;National Institute of Dental and Craniofacial Research;Natural regeneration;Normal Cell;novel;Nuclear;Oral cavity;Oral health;oral infection;Organ;Osteoblasts;Phenotype;postnatal;postnatal development;prevent;Production;progenitor;programs;Proliferating;Property;protein expression;Proteins;recruit;Regulator Genes;Regulatory T-Lymphocyte;RNA;Role;Saliva;Salivary Glands;Sampling;Sjogren's Syndrome;stem cells;Stratum Basale;Structure;T-Cell Activation;T-Cell Depletion;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;thymocyte;Time;tissue culture;Tissues;Tooth structure;Transcript;transcription factor;transcriptome sequencing;Wild Type Mouse

PROJECT_TITLE: Genome organizer SATB1 function in salivary gland and development and growth


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Neurosciences;Substance Misuse

PI_NAMEs: GEORGE, OLIVIER  (contact)

PROJECT_TERMS: Abstinence;acamprosate;addiction;Agonist;alcohol abstinence;alcohol abuse therapy;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol relapse;alcohol research;alcohol seeking behavior;alcohol use disorder;Alcohol withdrawal syndrome;Amygdaloid structure;Animal Model;Animals;antagonist;Atlases;Behavior;behavior prediction;Behavioral;Biological;Brain;Brain imaging;Brain region;Cell Nucleus;Cells;Cellular Neurobiology;Chronic;Complex;Corticotropin-Releasing Hormone;CRF receptor type 1;drug development;Ethanol;Evolution;Exhibits;FDA approved;Female;FOS gene;Funding;Future;Genetic;graph theory;Hyperactivity;hypocretin;Hypothalamic structure;Immediate-Early Genes;inhibitor;innovation;insight;Intervention;intervention effect;Lateral;machine learning framework;male;Maps;Modeling;Molecular;Mus;Naltrexone;neural circuit;neuroadaptation;neuronal circuitry;Neurons;norbinaltorphimine;novel;Opioid Antagonist;ORL1 receptor;Pathway Analysis;Pathway interactions;Pattern;Pharmaceutical Preparations;pharmacologic;pinacolyl methylphosphonic acid;Rattus;recruit;Research Institute;Resolution;Role;success;Testing;Therapeutic Effect;Treatment Efficacy;Visualization

PROJECT_TITLE: Functional Connectomics Component - George


ADMINISTERING_IC: AT

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Disability Research;Opioids;Pain Research;Physical Rehabilitation;Rehabilitation

ORG_CITY: SALT LAKE CITY

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Physical therapists commonly manage patients with chronic musculoskeletal pain (CMP) who are on long-term opioid treatment (LTOT). Mindfulness is an effective psychological approach for both pain and opioid use outcomes in persons with CMP and LTOT but has not been studied in the physical therapy setting. This project will test the feasibility conducting a cluster randomized clinical trial to evaluate the integration of mindfulness principles with evidence-based physical therapy in patients with CMP and LTOT.

PI_NAMEs: MAGEL, JOHN  (contact)

PROGRAM_OFFICER_NAME: GINEXI, ELIZABETH M

PROJECT_TERMS: addiction;Address;American;arm;Behavior;Caring;Cessation of life;chronic musculoskeletal pain;chronic pain;chronic pain management;chronic pain patient;Clinic;Clinical Trials;Cognitive Therapy;combat;Competence;Conduct Clinical Trials;Degenerative polyarthritis;design;Diagnosis;disability;Dose;economic impact;Effectiveness;evidence base;Evidence based treatment;Exercise;Feasibility Studies;feasibility testing;feasibility trial;Future;Goals;Health;Healthcare Systems;improved;Individual;innovation;Intervention;Interview;Location;Manuals;Medication Management;Methods;mind/body;mindfulness;mindfulness intervention;Mindfulness Training;multimodality;Musculoskeletal Pain;National Center for Complementary and Integrative Health;Nonpharmacologic Therapy;Opioid;opioid epidemic;opioid misuse;opioid therapy;opioid use;Outcome;Outpatients;Overdose;Pain;Pain intensity;Pain management;Patient Simulation;Patients;Persons;physical therapist;Physical therapy;pilot test;Play;Population;Practice Guidelines;Preparation;prescription opioid;Prevalence;psychologic;Psychological Techniques;Randomized;randomized, clinical trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Rehabilitation therapy;response;Risk;Role;Site;Spine pain;Standardization;Structure;System;Testing;Therapeutic Intervention;Training;Training Programs;Treatment Protocols;years lived with disability

PROJECT_TITLE: Physical Therapy Integrated with Mindfulness for Patients with Chronic Musculoskeletal Pain and Long-Term Opioid Treatment


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Cystic Fibrosis;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases;Substance Misuse

ORG_CITY: BIRMINGHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Pneumonia is a leading cause of death in the U.S. and an improved understanding of key risk factors is needed to reduce its burden. Alcohol is the most frequently abused substance that also increases susceptibility to bacterial pneumonia. We have identified that CFTR-mediated ion transport is decreased by alcohol, and may be responsible for reduced mucociliary clearance of inhaled pathogens. Hence, we propose to determine mechanistic basis and test novel treatment approach to restore CFTR function and lung defense against bacterial infection.

PI_NAMEs: RAJU, S.VAMSEE  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Acceleration;Address;Affect;airway surface liquid;alcohol abstinence;Alcohol abuse;Alcohol consumption;alcohol effect;alcohol research;alcohol use disorder;Alcoholic Pancreatitis;Alcohols;Anions;Antibiotics;antimicrobial;aspirate;Bacterial Counts;Bacterial Infections;Bacterial Pneumonia;Biological Assay;burden of illness;Cause of Death;Cells;Cessation of life;Chronic;chronic alcohol ingestion;Clinical;Colorado;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cystic Fibrosis Transmembrane Conductance Regulator;cytokine;Data;Death Rate;Defect;Defense Mechanisms;Diabetes Mellitus;Diagnosis;Diet;Disease;Dose;drinking;Enzymes;Epithelium;Exclusion;Exhibits;experience;Frequencies;Functional disorder;General Population;Genetic;Histopathology;Hospitalization;Hydration status;Image;Immunity;Impairment;improved;in vivo;Infection;Infertility;Inflammatory;Inhalation;Inherited;inhibitor;Intervention;Ion Channel;Ion Transport;Klebsiella pneumoniae;Knock-out;Knowledge;Link;Lung;lung health;Lung infections;lung injury;Measures;Mediating;Messenger RNA;Metabolic Clearance Rate;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;Mucociliary Clearance;Mucous body substance;mucus clearance;non-genetic;novel;novel therapeutic intervention;Optical Coherence Tomography;Outcome;overexpression;Pancreatitis;participant enrollment;pathogen;Pathogenicity;Patients;PDE4B;Pharmaceutical Preparations;pharmacologic;phosphodiesterase IV;Phosphorylation;Physiological;Pneumonia;pneumonia treatment;Predisposition;prevent;Property;Proteins;Pulmonary Cystic Fibrosis;pulmonary function;Pulmonary Pathology;radiological imaging;Rat Transgene;rational design;Rattus;recurrent infection;Reporting;Research;restoration;Risk;Risk Factors;Role;Surface;Symptoms;Testing;Therapeutic;therapy development;Time;United States;viscoelasticity;Viscosity;Vulnerable Populations

PROJECT_TITLE: Acquired CFTR Dysfunction in Alcohol-related Lung Pathology

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cystic Fibrosis;Genetics;Human Genome;Lung;Rare Diseases

ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Cystic Fibrosis (CF) is the most common lethal autosomal recessive disorder among Caucasians, occurring in1 per 2,500 to 3,500 U.S. births annually. An overarching goal of our work is to evaluate the role of CFTR translational efficiency during disease pathogenesis, including identification of cellular targets that address mutations refractory to CFTR modular treatment. The project will improve understanding of cystic fibrosis, advance new experimental technologies, and provide mechanistic insight relevant to CF and other genetic conditions.

PI_NAMEs: HARTMAN, JOHN L;SORSCHER, ERIC J (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acceleration;Address;airway epithelium;autosome;bioelectricity;Biogenesis;Biological Models;Birth;Caucasians;Cell model;Cells;cellular targeting;clinical phenotype;clinically relevant;clinically significant;Codon Nucleotides;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Data;deep sequencing;Defect;Disease;disease phenotype;Engineering;Eukaryota;gene interaction;Genetic Diseases;Genetic Models;Genetic Polymorphism;genome-wide;genome-wide analysis;Goals;Homologous Gene;Human;human disease;human induced pluripotent stem cells;improved;in vivo;Individual;Inherited;innovation;insight;Ion Transport;Knowledge;Left;Libraries;Link;Mammalian Cell;Maps;Mediating;Mediator;Medical;Messenger RNA;Methods;Modeling;Modification;Molecular;Molecular Abnormality;molecular phenotype;Molecular Target;monolayer;Mutation;novel;Other Genetics;Pathogenesis;Pathway interactions;Patients;personalized medicine;Pharmaceutical Preparations;pharmacologic;phenomics;posttranscriptional;premature;Process;Protein Biosynthesis;protein folding;protein misfolding;Refractory;Research Design;ribosome profiling;Ribosomes;Risk;Role;Saccharomyces cerevisiae;social;System;Technology;Testing;tool;Transcript;translational impact;Translations;Variant;Work;Yeasts

PROJECT_TITLE: Discovery of novel mechanisms that impact CFTR translation and contribute to cystic fibrosis pathogenesis

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Brain Disorders;Genetics;HIV/AIDS;Infectious Diseases;Neurodegenerative;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative This proposal will build upon data from the previous funding period to understand how genetic variation in the viral accessory protein Tat affects its function and hence neuroHIV. Using complimentary in silico, in vitro, in vivo and ex vivo assays, we propose to delineate the mechanism by which Tat promotes neurotoxicity and neurocognitive impairment. Successful completion of the proposal will have implications in developing novel therapeutics to treat neurocognitive impairment and genetic diagnostic assays.

PI_NAMEs: KORTAGERE, SANDHYA ;NONNEMACHER, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Amino Acid Sequence;Amino Acids;antiretroviral therapy;APOCEC3G gene;Architecture;Astrocytes;Behavior;Behavioral;behavioral outcome;Binding;Biological Assay;Blood specimen;Blood Vessels;Brain;brain tissue;cell type;Cells;Central Nervous System;Cohort Studies;Consensus;convolutional neural network;Data;Defective Viruses;diagnostic assay;diagnostic development;Dose;Etiology;Experimental Designs;experimental study;extracellular;fetal;Frequencies;Funding;Generations;Genetic;Genetic Polymorphism;Genetic Transcription;genetic variant;Genetic Variation;Genome;Histology;HIV;HIV-1;HIV-associated neurocognitive disorder;Impaired cognition;Impairment;in silico;In Vitro;in vivo;in vivo Model;Individual;Induced Neurons;Infection;Integration Host Factors;Lead;Macrophage;Mediating;Medicine;Microglia;Midbrain structure;Modeling;molecular modeling;Molecular Target;monocyte;Mutation;N-Methyl-D-Aspartate Receptors;National NeuroAids Tissue Consortium;Nervous System Physiology;Network-based;neuroAIDS;Neurocognitive;Neurocognitive Deficit;Neuronal Dysfunction;Neurons;Neuropathogenesis;Neuropsychology;neurotoxicity;novel;novel therapeutics;Pathogenesis;Pathway interactions;Patients;peripheral blood;pharmacologic;Positioning Attribute;Prefrontal Cortex;prevent;Production;protein protein interaction;Proteins;Proviruses;Rattus;receptor;Receptor Inhibition;Recovery;Research;response;RNA-Directed DNA Polymerase;Rodent Model;Scoring Method;Surface;Surface Plasmon Resonance;T-Lymphocyte;tat Genes;Testing;Tissues;Trans-Activators;Transactivation;Transcription Coactivator;Transcriptional Activation;Transfection;Variant;Viral;Viral Load result;Virus Integration

PROJECT_TITLE: HIV-1 Tat genetic variation impacts NeuroAIDS


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Neurosciences;Opioids;Substance Misuse

PI_NAMEs: ZORRILLA, ERIC P (contact)

PROJECT_TERMS: Abstinence;Acute;Address;Affective;Agonist;Alcohol consumption;alcohol effect;alcohol reinforcement;alcohol seeking behavior;alcohol use disorder;Alcohols;Amygdaloid structure;Animals;antagonist;Behavior;Brain;CAV2 gene;cell cortex;Cell Nucleus;cell type;Cells;Cellular Neurobiology;Chronic;Collaborations;Data;designer receptors exclusively activated by designer drugs;Disease;Distress;drinking;Drug Metabolic Detoxication;Dynorphins;Emotional;emotional symptom;Ethanol;experience;Female;Generations;Genetic;genetic manipulation;Genetic Recombination;Impairment;Injections;insight;kappa opioid receptors;Label;Ligands;Link;male;Membrane;Methionine;Modeling;Molecular;Molecular Analysis;Molecular Target;Mus;negative affect;neural circuit;Neurobiology;Neurons;neurophysiology;neuroproteomics;nociceptin;Norleucine;novel;Opioid Antagonist;ORL1 receptor;Pathway interactions;Peptide Receptor;Post-Translational Protein Processing;Property;Proteins;Proteome;Proteomics;Rattus;receptor;Recurrence;Relapse;relapse risk;Research;response;Rewards;Role;Site;small molecule;Stress;Symptoms;Synaptic Transmission;System;Testing;Therapeutic;Validation;Virus

PROJECT_TITLE: Neurocircuitry Component - Zorrilla


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Sleep Research

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Circadian rhythms in behavior and physiology are strongly linked with psychiatric disease, but fundamental of how brain circuits are modulated by circadian rhythms to bring about behavioral changes is lacking. The proposed study will begin to fill this gap by determining for the first time how in vivo neural network electrophysiology in the prefrontal cortex is altered by circadian rhythms in freely-behaving diurnal animals. The proposed research is relevant to public health and the mission of NIMH that aims to transform the understanding and treatment of mental illness through basic research.

PI_NAMEs: WATSON, BRENDON O (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Action Potentials;Affect;Affective;Anhedonia;Animal Model;Animals;Attention;Basic Science;Behavior;Behavior Control;behavior prediction;Behavioral;behavioral study;Biological Models;Biology;Brain;brain control;Chronic;circadian;circadian behavioral rhythms;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Cognitive;cognitive function;comorbidity;Darkness;Data;density;Disease;Electrophysiology (science);Equilibrium;Experimental Models;Foundations;Future;Hour;Human;Implant;Implanted Electrodes;improved;in vivo;Intervention;Knowledge;Laboratories;Light;light intensity;Link;Literature;Major Depressive Disorder;Mammals;Measurement;Measures;Medial;Mediator;Mental disorders;Methods;Mission;Modeling;Molecular;Mood Disorders;Moods;National Institute of Mental Health;neural;neural circuit;neural network;Neurobiology;neuronal circuitry;Neurons;neuropsychiatric disorder;Neurosciences;Output;Pathologic;Patients;Pattern;Periodicity;Phase;Physiology;Poaceae;Population;preference;Prefrontal Cortex;Public Health;Rattus;Research;response;Rodent;Seasonal Affective Disorder;Silicon;Sleep;Stress;System;Testing;Therapeutic;Time;tool;Translating;Wakefulness;Work

PROJECT_TITLE: Electrophysiologic characterization of circadian rhythms of prefrontal cortical network states in a diurnal rodent

STUDY_SECTION: BNRS

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


NIH_SPENDING_CATS: Anxiety Disorders;Atherosclerosis;Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Cardiovascular;Clinical Research;Coronaviruses;Emergency Care;Emerging Infectious Diseases;Health Services;Heart Disease;Infectious Diseases;Mental Health;Post-Traumatic Stress Disorder (PTSD);Prevention

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Even before the COVID-19 pandemic, emergency department (ED) healthcare workers (HCWs) were already known to be at greater psychological risk than nearly every other subgroup of clinicians. Psychological and physiological stress factors have been drastically magnified during the COVID-19 pandemic, particularly among frontline ED HCWs in New York City, the initial US epicenter of the outbreak. It is therefore critical to understand the degree of sustained psychological symptoms seen in ED HCWs who treated COVID-19 patients, as well as the downstream impacts on cardiovascular health.

PI_NAMEs: CHANG, BERNARD P.;SHECHTER, ARI  (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: Accident and Emergency department;Acute;acute care;acute traumatic stress disorder;Address;Admission activity;American Heart Association;Anxiety;Atherosclerosis;Buffers;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Caring;Cessation of life;coping;COVID-19;COVID-19 burden;COVID-19 pandemic;COVID-19 patient;COVID-19 treatment;Data;Databases;Development;Disease Outbreaks;Emergency Department patient;Enrollment;Ensure;Environment;experience;Exposure to;follow-up;Fright;Future;healing;Health Personnel;Health protection;Hospitalization;Hospitals;Hour;indexing;Individual;infection rate;Intervention;Life Expectancy;Link;Long COVID;Measures;medical specialties;Mental Health;New York;New York City;pandemic disease;pandemic impact;Participant;Personal Satisfaction;physical conditioning;Physicians;Physiological;Policies;Post-Traumatic Stress Disorders;Prevalence;prospective;protective factors;Psyche structure;psychologic;psychological distress;psychological outcomes;Psychological Stress;psychological symptom;Psychological Tests;Psychophysiology;Public Health;recruit;resilience;Risk;Safety;safety net;Schedule;shift work;Sleeplessness;Societies;Specific qualifier value;Stress;Subgroup;Surveys;Symptoms;Testing;Vaccines;Work

PROJECT_TITLE: Psychological symptoms in healthcare workers following the COVID-19 pandemic and relationship to long-term cardiovascular risk

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


ADMINISTERING_IC: DC

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Neurofibromatosis;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: INDIANAPOLIS

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Neurofibromatosis Type 2 (NF2) is a disease with multiple manifestations, including the vestibular schwannoma, a tumor of Schwann cells. Patients with NF2 can experience hearing loss, facial paralysis, and vertigo due to the location of a vestibular schwannoma on cranial nerve VIII. In this study, we will model NF2 using a human pluripotent stem cell culture system.

PI_NAMEs: STEINHART, MATTHEW REED (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TERMS: Acoustic Nerve;Acoustic Neuroma;Actins;Address;Adherent Culture;Affect;Afferent Neurons;antagonist;Axon;Biochemical Pathway;Biology;Cell Culture System;Cell Proliferation;cell type;Cells;Cephalic;Code;Communities;Complex;CRISPR/Cas technology;Cytoskeleton;Development;Disease;drug development;Drug Targeting;druggable target;Effectiveness;Elements;Embryo;Equilibrium;experience;experimental study;ezrin;Facial paralysis;Foundations;Functional disorder;Genes;Genetic;Genetic Diseases;genetic manipulation;Genetic Markers;Goals;Growth and Development function;Hair Cells;hearing impairment;Human;human model;human pluripotent stem cell;In Vitro;Inner Hair Cells;insight;Investigation;Knock-out;Knowledge;Laboratories;Labyrinth;Location;Modeling;moesin;mouse model;Mus;Mutation;Neurilemmoma;Neurofibromatosis 2;Neurofibromin 2;Neuroglia;Neurons;novel;Operative Surgical Procedures;Organogenesis;Organoids;Pathogenesis;Pathway interactions;Patients;Peripheral;Pharmacotherapy;Phenocopy;Pluripotent Stem Cells;Population;Process;Proliferating;Proteins;radixin protein;receptor;Research;Research Personnel;Schwann Cells;Sensory;single-cell RNA sequencing;skull base;stem cells;Structure;System;targeted treatment;therapeutic effectiveness;therapeutic target;three dimensional cell culture;Tissues;Training Programs;tumor;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenic;Vertigo;Vestibular Nerve;vestibular system;Work

PROJECT_TITLE: Modeling Neurofibromatosis Type 2 with Inner Ear Organoids


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Bioengineering;Cardiovascular

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Historical observations suggest that revolutionary scientific and therapeutic advances often emerge at the interface between disciplines. Therefore, we believe that individuals trained in both engineering principles and cardiovascular science (biology) are critically needed to develop novel therapeutic approaches for treating cardiovascular diseases that are leading causes of death and disability in the Western world. The proposed program aims to provide such training to students pursuing a doctoral degree in bioengineering, with a focus on the cardiovascular system.

PI_NAMEs: SHROFF, SANJEEV G (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: Biomedical Engineering;Cardiovascular system;Training Programs

PROJECT_TITLE: Cardiovascular Bioengineering Training Program

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


NIH_SPENDING_CATS: Cancer;Immunotherapy;Radiation Oncology

ORG_CITY: MADISON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Cancer is increasingly becoming a larger public health burden, with rising incidence of many cancer types and rapidly rising treatment costs worldwide necessitating development of new, effective cancer therapies. We are developing a new approach, representing a dramatic shift in the treatment of metastatic cancer, utilizing immune responses to recognize and destroy cancer (known as immunotherapy) in combination with systemically administered radiation therapy, known as targeted radionuclide therapy (TRT). This grant application proposes experiments that will deepen our mechanistic understanding of the dynamic radionuclide-specific effects of TRT on tumor cells, immune cells, and anti-tumor immunity, with potential for the results to expand treatment options for metastatic cancers in the U.S. and abroad.

PI_NAMEs: KERR, CAROLINE PAULA ANNE (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: 90Y;analog;anti-CTLA4;anti-PD-L1;anti-tumor immune response;Applications Grants;Cancer Patient;cancer therapy;cancer type;Canis familiaris;CD8-Positive T-Lymphocytes;Cells;checkpoint therapy;chelation;Clinical;Clinical Trials;Combination immunotherapy;Combined Modality Therapy;comparative;Data;Dendritic Cells;Development;Disease;Disseminated Malignant Neoplasm;Dose;Dose Limiting;exhaust;exhaustion;Exhibits;experimental study;External Beam Radiation Therapy;Foundations;Goals;Half-Life;Head and Neck Squamous Cell Carcinoma;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immune Tolerance;Immunologics;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;Incidence;Infiltration;insight;Interferon Activation;Interferon Type I;Ligands;Linear Energy Transfer;Location;Lymphocyte;Lymphopenia;Malignant Neoplasms;Melanoma;Methods;Micrometastasis;Microscopic;Modality;Modeling;mouse model;Mus;Mutation;neoantigens;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Outcome;particle;Pathway interactions;Patients;physical property;Positioning Attribute;preclinical study;Predisposition;prevent;Production;professor;Property;Proteins;Public Health;Radiation;radiation delivery;Radiation therapy;Radioisotopes;radiological imaging;Radionuclide therapy;receptor;recruit;Recurrence;research clinical testing;Resources;response;Site;Spatial Distribution;Stimulator of Interferon Genes;Surface;synergism;T cell infiltration;T-Lymphocyte;Therapeutic;Tissues;Toxic effect;Training;Translations;Treatment Cost;Treatment Protocols;treatment response;tumor;tumor heterogeneity;Tumor Immunity;tumor microenvironment;Tumor Promotion;Universities;Wisconsin

PROJECT_TITLE: Targeted radionuclide therapy for tumor immunomodulation and enhancing immunotherapy response


NIH_SPENDING_CATS: Aging;Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Cystic Fibrosis;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Orphan Drug;Pneumonia;Pneumonia and Influenza;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: PROJECT NARRATIVE  Pseudomonas aeruginosa (Pa) cause severe infections in patients with burns, severe wounds, pneumonia, or undergoing nosocomial procedures. Most Pa strains are resistant to many antibiotics limiting the treatment options. Vaccination is perhaps the greatest health advancement of our lifetime. Our vaccine to prevent Pa, regardless of initial injury or Pa strain, will positively impact all of us. Indeed as we age, we all have a greater risk of a potential Pa infection. Our vaccine is aimed at preventing these infections as well. Herein we examine the vaccine formulation for efficacy in rodent models.

PI_NAMEs: PICKING, WENDY L. (contact)

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Achievement;Acute Pneumonia;Adjuvant;Age;Agonist;Antibiotic Resistance;Antibiotics;Antibodies;Antigens;B-Lymphocytes;Burn injury;Catheterization;Cell membrane;Cells;Critical Illness;Cystic Fibrosis;cystic fibrosis patients;Cytoplasm;Development;Distal;Dose;efficacy evaluation;Elderly;emerging antibiotic resistance;Emulsions;enterotoxigenic Escherichia coli;Explosion;Formulation;Goals;Health;Human;human pathogen;IL17 gene;Immune response;Immunoglobulins;Infection;Infection prevention;influenza virus vaccine;Injury;Intubation;Knockout Mice;Licensing;Lipid A;Lung;Manuscripts;Measures;Mediating;middle age;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mucous Membrane;Multi-Drug Resistance;multidrug-resistant Pseudomonas aeruginosa;Mus;Natural Immunity;Needles;novel;novel vaccines;Oils;old mice;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Patients;Pneumonia;Preparation;prevent;Preventive vaccine;Procedures;protective efficacy;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Public Health;Publishing;Rattus;resistant strain;Risk;Risk Factors;Rodent;Rodent Model;Serum;Syringes;Time;TLR4 gene;Toxin;Type III Secretion System Pathway;Vaccinated;Vaccination;vaccine efficacy;vaccine formulation;Vaccines;Virulence Factors;Water;wound

PROJECT_TITLE: A prophylactic vaccine to prevent colonization by Pseudomonas aeruginosa

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Heart Disease;Infectious Diseases;Pediatric;Prevention

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARATIVE There are nearly 5 million adolescents and young adults living with HIV (AYALH) globally who have survived growing up with HIV and are now emerging into adulthood to confront high rates of HIV-related co-morbidities including preclinical cardiovascular disease (CVD) which is associated with premature death and disability. The epidemiology of preclinical CVD among AYALH is not defined, including age of onset, progression, and associated risk factors. In this K01 proposal, Dr. Reif will conduct a prospective cohort study of 500 HIV+ and 500 HIV- participants ages 18-30 years in Haiti followed for 3 years to address this knowledge gap and inform the adaptation of evidence-based CVD interventions for AYALH and for integration into HIV clinics.

PI_NAMEs: REIF, LINDSEY  (contact)

PROGRAM_OFFICER_NAME: MASTERSON, MARY YAA SEDEGAH

PROJECT_TERMS: Address;Adolescent;Adolescent and Young Adult;adolescent health;Adult;Age;Age of Onset;aged;antiretroviral therapy;Area;Black American;Blood Pressure;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder epidemiology;cardiovascular disorder risk;career;career development;Caring;Cessation of life;Chronic;Clinic;cohort;Collaborations;community advisory board;comorbidity;Complement;Data;design;Development;Development Plans;disability;Disease;Disease Outcome;Dyslipidemias;Early Intervention;early onset;effectiveness evaluation;Ensure;Environment;Epidemic;Epidemiologist;Epidemiology;epidemiology study;Event;evidence base;Evidence based intervention;experience;Face;follow-up;Friends;Future;Generations;global health;Goals;Haiti;Health;High Prevalence;high risk;high-risk adolescents;HIV;HIV-1;HIV-infected adolescents;Household;implementation framework;implementation science;improved;Incidence;Intervention;Knowledge;Life Cycle Stages;Life Expectancy;Life Style;lifestyle factors;low income country;Measures;member;Mental Depression;Mentorship;Methods;Microalbuminuria;Modification;Morbidity - disease rate;mortality;multidisciplinary;National Heart, Lung, and Blood Institute;New York;Obesity;Outcome;Paper;Participant;perinatal HIV;Population;population based;pragmatic implementation;pre-clinical;prehypertension;premature;Prevalence;prevent;Prevention;preventive intervention;Primary Prevention;Process;Prospective, cohort study;Provider;psychosocial;Psychosocial Factor;Publishing;Research;Research Methodology;Research Personnel;Risk;Risk Factors;screening;Services;skills;Smoking;social stigma;Stress;therapy duration;Time;Training;Training Support;Unhealthy Diet;United States National Institutes of Health;Viral Load result;young adult;Youth

PROJECT_TITLE: Preclinical Cardiovascular Disease among Adolescents and Young Adults in Haiti

STUDY_SECTION: MCBS

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


NIH_SPENDING_CATS: Brain Disorders;Cannabinoid Research;Chronic Pain;Endocannabinoid System Research;Headaches;Migraine;Neurosciences;Pain Research;Prevention;Therapeutic Cannabinoid Research

ORG_CITY: TUCSON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Our propsal will clarify the role of endocannabinoid (eCB) system in the pathology of migraine headache and seeks to validate enhancing 2AG tone as a novel antimigraine strategy. In three aims, we will 1) determine the levels of eCB components during two models of headache, 2) investigate the mechanisms by which eCB dysregulation contributes to headache, and 3) examine the therapeutic effects of selective MAGL and ABHD6 inhibitors for headache prevention and mitigation. These will lay the foundation for initiating a drug discovery program for targeting eCB signaling for headache with respect to 2AG degradation.

PI_NAMEs: MILNES, TALLY MARIE (contact)

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: 2-arachidonylglycerol;ABHD6 gene;Affect;allodynia;American;Analgesic Overuse Headaches;anandamide;Attenuated;Behavioral;behavioral outcome;cellular pathology;Clinical;CNR1 gene;CNR2 gene;Coupled;Data;Detection;Diglycerides;Dinoprostone;drug discovery;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;enzyme activity;Enzymes;Face;Female;Foundations;Gatekeeping;Glial Fibrillary Acidic Protein;Gliosis;Headache;High Prevalence;Hydrolysis;immunocytochemistry;improved;Inflammation;inhibitor;Injections;Intervention;Knowledge;Lipids;MAGL inhibitor;Maintenance;male;midbrain central gray substance;Midbrain structure;Migraine;migraine treatment;Modeling;Molecular;Molecular Biology;molecular pathology;Neurons;neurotransmitter release;novel;Outcome Measure;Pain;pain behavior;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;Play;postsynaptic;Preclinical Testing;presynaptic;prevent;Prevention;programs;Proteins;Proteomics;Publishing;Rattus;receptor;Recovery;Regulation;Role;sex;sex variable;Signal Transduction;Solid;Spreading Cortical Depression;Symptoms;Techniques;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Time;trend;Work

PROJECT_TITLE: Targeting the Endocannabinoid System for Headache Intervention

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric

ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: Project Narrative: How the complex geometry of the vertebrate head is specified over development is an area of active investigation that is relevant to myriad areas of biology, from ecology and evolution, to genetics and development, to human health and disease. The work proposed here aligns squarely with this imperative, as it seeks to significantly expand our understanding of the genetic, developmental and environmental factors and interactions that participate in craniofacial development.

PI_NAMEs: ALBERTSON, CRAIG  (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: 3-Dimensional;Address;Adult;Affect;Animals;Area;ATAC-seq;Award;Biological;Biological Models;Biology;bone;Bone Tissue;Brain;Candidate Disease Gene;candidate identification;Cells;Chromosome Mapping;Cichlids;comparative genomics;Complex;craniofacial;craniofacial bone;craniofacial complex;craniofacial development;cranium;CRISPR/Cas technology;Data;Data Set;Development;Developmental Process;Disease;Disparate;Ecology;Embryo;Environment;Environmental Risk Factor;Equilibrium;Evolution;Experimental Models;Eye;Face;Feedback;Gene Expression;Genes;Genetic;genetic pedigree;Genome;genome wide association study;genomic data;Genomics;Genotype;Geometry;Goals;Growth;Hand;Head;Health;Heart;Homeostasis;Human;insight;Investigation;Iodine;Jaw;kinematics;Kinetics;Malawi;Maps;mechanical force;mechanical load;Mechanics;mechanotransduction;Modeling;Modernization;Modification;Morphology;multiple datasets;Muscle;Nature;Organ;Outcome;Pattern;Phenotype;pleiotropism;Procedures;Process;Quantitative Trait Loci;Regulation;Research;Scanning;Series;shape analysis;Shapes;Signal Pathway;Signal Transduction;skeletal;Skeleton;soft tissue;Specific qualifier value;Stains;stem cells;System;three-dimensional modeling;Time;Tissues;tool;trait;transcriptome sequencing;Variant;Work

PROJECT_TITLE: Genetic and developmental mechanisms that underlie craniofacial (co)variation

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS SAN ANTONIO

PHR: The mechanisms that drive progressive multiple sclerosis (MS) remain enigmatic; however, expression of the proinflammatory cytokine tumor necrosis factor (TNF) in cerebrospinal fluid of MS patients correlates with disease progression, which suggests that TNF plays a key role in demyelination and glial cell function. Surprisingly, however, TNF-blocking drugs with proven efficacy in other autoimmune diseases triggered onset and exacerbations of MS, which provided evidence that TNF signaling is important for promoting CNS protection and repair. The main goal of this proposal is therefore to understand how TNF signaling through TNF receptor (TNFR) 2 restricts progression of neuroinflammation, chronic astrocyte activation, and pathogenic T cell responses in a pre-clinical progressive EAE model.

PI_NAMEs: FORSTHUBER, THOMAS G. (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Alleles;Animals;Anti-Inflammatory Agents;Astrocytes;astrogliosis;Autoimmune Diseases;Automobile Driving;Biological;Biological Assay;blocking factor;BLR1 gene;Cell Physiology;cell type;Cells;Cerebrospinal Fluid;Chronic;CXCL13 gene;cytokine;Demyelinations;Development;Disease;Disease Progression;Encephalomyelitis;Experimental Autoimmune Encephalomyelitis;Fluorescent in Situ Hybridization;FOXP3 gene;Gene Expression Profile;Goals;Human;Immunologics;Impairment;Inflammatory;innovation;Knockout Mice;Knowledge;Lesion;Leukocytes;Lipid Peroxidation;Mediating;Methods;Microglia;Migration Assay;Modeling;Molecular;mouse model;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Mus;Neuroglia;neuroinflammation;Neurons;neuroprotection;novel strategies;Oligodendroglia;Oxidative Stress;Pathogenicity;Patients;Pharmaceutical Preparations;Play;Population;pre-clinical;prevent;Process;Property;Receptors, Tumor Necrosis Factor, Type II;recruit;Regulatory T-Lymphocyte;remyelination;repaired;Reporting;restraint;RNA;Role;Signal Transduction;single molecule;single-cell RNA sequencing;T cell response;T-Lymphocyte;Testing;TNF gene;TNFRSF1A gene;TNFRSF1B gene;Transgenic Mice;white matter;Work

PROJECT_TITLE: The role of TNFR2 in ameliorating progressive encephalomyelitis

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

PHR: Cardiomyocyte loss is a major cause of morbidity and mortality of ischemic heart disease and heart failure. Accumulating evidence suggests that pre-existing cardiomyocytes can proliferate and are the prominent source of CM renewal in adult mammalian heart; however, the limited regenerative capacity of adult cardiomyocytes impedes the recovery from myocardial infarction. We will study the paracrine regulation of cardiomyocyte proliferation and renewal and identify novel therapeutic targets and strategies for treating these devastating diseases.

PI_NAMEs: XIE, LIANG  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Adult;Aging;Animal Model;APLN gene;Blood Vessels;Cardiac;Cardiac Myocytes;cardiogenesis;cell type;Cells;Chronic;Communication;Cues;Data;Development;Disease;Endothelial Cells;Endothelium;Failure;Fibroblasts;Fibrosis;first responder;G-Protein-Coupled Receptors;Gene Expression;General Population;genetic manipulation;Heart;Heart Diseases;Heart failure;heart function;Hypoxia;improved;in vivo;Induced Cardiomyocytes;integrin-linked kinase;intercellular communication;Knock-out;Knockout Mice;Ligands;Mediating;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Degeneration;Myocardial Infarction;myocardial injury;Myocardial Ischemia;Natural regeneration;Neonatal;new therapeutic target;novel strategies;Nutrient;Organ Size;Oxygen;paracrine;Pathologic;Pathway interactions;Patients;Peptides;Play;Population;Prevalence;prevent;Procollagen-Proline Dioxygenase;Proliferating;protein activation;Proteins;receptor;Receptor Cell;Receptor Inhibition;Recovery;Regenerative capacity;Regulation;Role;sensor;Signaling Protein;single-cell RNA sequencing;Source;Tertiary Protein Structure;Testing;Therapeutic;Ventricular;Ventricular Remodeling

PROJECT_TITLE: Explore the roles of intercellular communication in cardiomyocyte proliferation and renewal.

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Lung;Pulmonary Fibrosis;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Pulmonary fibrosis (PF) syndromes, including adult idiopathic PF (IPF) and childhood interstitial lung disease (chILD), cause significant morbidity and mortality worldwide. Treatment options are limited and the development of new therapeutics is hampered by the lack of available human in vitro models that are needed to understand pathogenesis or develop novel therapies. This proposal seeks to establish a new recombinant human organoid model system, using patient-specific cells to study the role of the alveolar epithelium at the inception of PF.

PI_NAMEs: ALYSANDRATOS, KONSTANTINOS  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Adult;Alveolar;alveolar epithelium;Biogenesis;Biological Models;Boston;career development;Cell Differentiation process;Cell Line;Cells;Cessation of life;Childhood;Critical Care;Data;Data Set;Development;Diagnosis;Disease;disease model;disorder risk;effective therapy;Epithelium;Event;FDA approved;Fibroblasts;fibrogenesis;Fibrosis;Functional disorder;Future;Gases;Genes;Genetic study;genome wide association study;genomic locus;Genotype;Goals;Human;human disease;human model;Hypersensitivity;Idiopathic Interstitial Pneumonia;idiopathic pulmonary fibrosis;Immune;Impairment;In Vitro;in vitro Model;in vivo;in vivo evaluation;induced pluripotent stem cell;Inflammatory;International;Interstitial Lung Diseases;K-Series Research Career Programs;Literature;Lung;lung development;Lung Diseases;Manuscripts;Medicine;meetings;member;Mentors;Mesenchymal;Mesenchyme;Metabolic;Methods;Mitochondria;mitochondrial dysfunction;Modeling;molecular phenotype;Morbidity - disease rate;Morphology;mortality;mouse model;Mutant Strains Mice;Mutation;new therapeutic target;nintedanib;novel;novel strategies;novel therapeutics;Organoids;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Physicians;Pirfenidone;Pluripotent Stem Cells;Population;Preparation;Proteomics;proteostasis;proteostasis loss;Publishing;Pulmonary Fibrosis;pulmonary function decline;Recombinants;Regenerative Medicine;Research;Role;Scientist;self-renewal;single-cell RNA sequencing;Sleep;stem cell biology;stem cell model;stem cells;Stress;Structure of parenchyma of lung;Syndrome;Systems Biology;Testing;Time;timeline;Training;Training Programs;transcriptomics;Universities;Variant

PROJECT_TITLE: Utilizing induced pluripotent stem cells to study the role of alveolar type 2 cell dysfunction in pulmonary fibrosis


ADMINISTERING_IC: ES

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Foodborne Illness;Microbiome;Nutrition;Pediatric;Social Determinants of Health

ORG_CITY: TEMPE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

PHR: Project Narrative We propose to study the role of aflatoxin exposure on child growth, and whether the effect of aflatoxin is mediated by the gut microbiome and inflammation. We will evaluate aflatoxin exposure and height-for-age difference trajectories among children between 6-9 and 24-27 months of age, and will examine markers of inflammation, gut microbiome composition and function, and microbial nutrient extraction and aflatoxin microbial biotransformation. Through a multidisciplinary approach that leverages access to an exposed population and expertise in epidemiology, pediatrics, toxicology, environmental engineering and human microbiome, and bioreactors as model system, we will be able to gather evidence that can be practice- changing, as it will help support large-scale investments in aflatoxin remediation efforts on the part of CDC, USAID and other international public health organizations working to improve global child health.

PI_NAMEs: KRAJMALNIK-BROWN, ROSA  (contact);ROHLOFF, PETER ;VOTH-GAEDDERT, LEE

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: adduct;Affect;Aflatoxin B1;Aflatoxins;Age Months;Albumins;Aspergillus flavus;Biological;Biological Markers;Biological Models;Bioreactors;C-reactive protein;Carbohydrates;Carcinogens;Child;Child Health;Consumption;Country;Data;Diet;dietary;Dose;Drug Metabolic Detoxication;dysbiosis;Environmental Engineering technology;Epidemiology;Erythrocyte Sedimentation Rate;experimental study;Exposure to;fecal microbiome;food preparation;Funding;genome sequencing;Genomics;Growth;Guatemala;gut inflammation;gut microbes;gut microbiome;gut microbiota;Harvest;health organization;Height;High Prevalence;High-Throughput DNA Sequencing;Human Microbiome;Hydrolysis;improved;Inflammation;inflammatory marker;innovation;interdisciplinary approach;International;Investments;Leukocyte L1 Antigen Complex;low and middle-income countries;Maize;Measurement;Measures;Mediating;Mediation;Metabolic Biotransformation;Metabolic Pathway;Metabolism;Metagenomics;microbial;microbial community;microbiome;microbiome composition;Modeling;Molecular;Monitor;National Institute of Environmental Health Sciences;Nutrient;nutrient metabolism;Nutrition Disorders;Pathway interactions;Pediatrics;Physiological;Population;prospective;Prospective cohort;Public Health;remediation;Reporting;response;Risk;Role;rRNA Genes;Rural;Science;Seasonal Variations;Seasons;Seminal;Serum;Starch;stool sample;Structure;systemic inflammatory response;Time;Toxicology;transcriptomics;USAID;Volatile Fatty Acids;whole genome;Work

PROJECT_TITLE: Aflatoxin Exposure, Growth Faltering, and the Gut Microbiome among Children in Rural Guatemala

STUDY_SECTION: KNOD

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


NIH_SPENDING_CATS: Bioengineering;Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Ovarian Cancer;Precision Medicine;Rare Diseases;Women's Health Research

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project narrative Basic patterns in the spatial layout of cells in a tumor can influence patients’ response to therapy and metastasis, and while significant technology development to measure the properties of cells in intact tissues have advanced at pace, detailed and robust investigations have been limited by a lack of computational methods for analyzing spatial tumor data. This proposal addresses this gap by developing and validating new statistical methods and algorithms capable of (i) extracting rich patterns from spatial tumor data, (ii) generalizing across multiple spatial technologies, and (iii) validating on real-world data from ovarian cancer patients. Addressing this gap will lead to new fundamental discoveries in cancer biology and enable the rational design of spatial biomarkers to enable biological discovery and a new generation of single cell spatial properties of tumors.

PI_NAMEs: TANSEY, WESLEY  (contact)

PROGRAM_OFFICER_NAME: MILLER, DAVID J

PROJECT_TERMS: Address;Architecture;base;Bayesian Analysis;Bayesian Method;Benchmarking;Biological;Biological Markers;Biological Testing;Cancer Biology;Cancer Patient;cancer type;cell community;Cells;Clinical;Code;cohort;Collection;Communities;Complement;computer framework;Computer software;Computing Methodologies;Cytometry;Data;Data Analyses;data integration;data modalities;Data Set;Development;Dimensions;experimental study;Generations;Genetic Transcription;Goals;Image;Immunofluorescence Immunologic;improved;In Situ;Individual;innovation;insight;Intestines;Investigation;large scale data;Location;Lung;Machine Learning;Malignant neoplasm of ovary;Malignant Neoplasms;malignant phenotype;Measurement;Measures;Melanoma;Methodology;Methods;Modality;Modeling;Molecular Profiling;Morbidity - disease rate;multi-scale modeling;multidisciplinary;Neoplasm Metastasis;next generation;novel;open source;Ovarian;Pathologist;patient biomarkers;patient response;patient stratification;Patient-Focused Outcomes;Patients;Pattern;Phenotype;programs;Property;Proteins;Proteomics;rational design;Recurrence;Research Project Grants;Resolution;Sampling;scalable algorithms;Signal Transduction;simulation;single-cell RNA sequencing;Software Tools;Spatial Design;Specimen;Statistical Algorithm;Statistical Methods;Statistical Models;Techniques;Technology;technology development;Testing;theories;Tissues;tool;transcriptome;transcriptomics;treatment response;tumor;Tumor Biology;tumor microenvironment;Validation;Visualization software;web interface;Women's mortality

PROJECT_TITLE: Probabilistic Multiscale Modeling of the Tumor Microenvironment

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Disability Research;Hearing Loss;Neurosciences;Prevention;Rehabilitation

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Narrative A cochlear implant can provide auditory sensation to someone who would otherwise be deaf due to a dysfunctional inner ear. However, the signal provided by a cochlear implant does not have the clarity of what would be provided by healthy biological hearing, and the degree to which listeners with cochlear implants can understand spoken language varies considerably from patient to patient. Here we use functional brain imaging to measure the involvement of different brain networks during speech understanding in patients with cochlear implants to better understand individual differences in speech perception.

PI_NAMEs: PEELLE, JONATHAN E (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Address;Adult;American;Anatomy;Attention;audiovisual speech;Auditory;auditory deprivation;Auditory system;Basic Science;behavior measurement;Behavioral;behavioral outcome;Biological;Brain;Brain imaging;Brain Mapping;Clinical;clinical application;clinical outcome measures;Cochlear implant procedure;Cochlear Implants;Cognitive;cognitive ability;cognitive load;cognitive neuroscience;cognitive process;cognitive system;cohort;Communication;Complement;Comprehension;coping;Cues;Custom;Data;deaf;density;diffuse optical tomography;Down-Regulation;Electroencephalography;Ensure;Equipment;Esthesia;Evaluation;experience;flexibility;Goals;Hearing;hearing impairment;hearing restoration;Human;Image;imaging modality;Implant;implantation;improved;indexing;Individual;Individual Differences;individual variation;Knowledge;Labyrinth;Language;Link;Magnetic Resonance Imaging;Measures;Medical Device;medical implant;Memory;Methods;Morphologic artifacts;movie;multimodality;neural;Neuroanatomy;Neurobiology;neuroimaging;Neuronal Plasticity;Noise;normal hearing;novel;optical imaging;Optics;Outcome;Outcome Measure;Patients;Pattern;Performance;personalized approach;Predisposition;Prefrontal Cortex;prevent;Process;recruit;Reproducibility;Research;Resources;response;Rest;Signal Transduction;Solid;Source;Speech;Speech Intelligibility;Speech Perception;speech processing;speech recognition;success;support network;Support System;System;Telephone;Temporal Lobe;Time;Visual;visual speech;Work

PROJECT_TITLE: Individual differences in brain networks supporting speech understanding in patients with cochlear implants

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE This new post-doctoral training program will establish a pipeline to train outstanding surgeon scientists in cardiac surgery. We will leverage the considerable resources at the University of Michigan in medical education; NIH- funded laboratories in basic, translational, and clinical/health services research as well as a talented pool of mentors to attract surgeon scientists during their cardiac surgery residency. Our multi-disciplinary training program for surgeon scientists will prepare them for exceptional careers in cardiac surgery with the ultimate goal of advancing health and health outcomes for patients with cardiovascular diseases.

PI_NAMEs: AILAWADI, GORAV ;CHEN, YUQING EUGENE (contact);LIKOSKY, DONALD S

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TITLE: Surgeon Scientist Training in Cardiac Diseases


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Rare Diseases;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Addition of sugars to proteins (glycosylation) is required for proper development, and defects in glycosylation cause a variety of genetic disorders. Here we propose studies on specific types of glycosylation found on cysteine-rich domains of proteins. We seek to identify proteins with these types of glycosylation, examine how these glycans are affected in a genetic vascular disorder called CADASIL, and learn more about the genes involved in their biosynthesis.

PI_NAMEs: HALTIWANGER, ROBERT S. (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Address;Affect;Anabolism;autosome;Biological;Blood Vessels;CADASIL;Cell surface;Cells;Consensus Sequence;CRISPR screen;Cysteine;Cysteine-Rich Domain;Cytosol;Data;Databases;Defect;Development;Disease;Embryo;Endoplasmic Reticulum;Enzymes;Epidermal Growth Factor;Extracellular Protein;Fucose;Fucosyltransferase 1;Genes;Genetic;Genetic Diseases;Glucosyltransferase;glycoproteomics;glycosylation;Goals;Guanosine Diphosphate Fucose;Homeostasis;Human Genetics;hydroxyl group;Knock-out;Learning;Link;Maps;Methods;Modification;Molecular;Mus;Mutation;NOTCH1 gene;NOTCH3 gene;novel;Play;Polysaccharides;Proteins;Proteome;Research;Role;Serine;Site;Smooth Muscle Myocytes;Structure;sugar;Tertiary Protein Structure;Threonine;Thrombospondins;Vascular Diseases;Vascular Smooth Muscle

PROJECT_TITLE: O-glycosylation of cysteine-rich modules

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Peripheral neuropathy occurs in 30-40% of patients who are treated with neurotoxic chemotherapy and results in dose-limiting pain, numbness and weakness that can lead to long term illness. This proposal aims to use human adult stem cell-derived neurons to investigate a protein, MAP2 (microtubule associated protein 2), which has been recently identified as playing a key role in the development of chemotherapy-induced peripheral neuropathy. A detailed understanding of MAP2 in chemotherapy-induced peripheral neuropathy brings the promise of a therapy that could ultimately prevent the development of this dreaded complication.

PI_NAMEs: STAFF, NATHAN P (contact)

PROGRAM_OFFICER_NAME: ALTSHULER, RACHEL DINA

PROJECT_TERMS: Afferent Neurons;Applications Grants;Area;Axon;axonal degeneration;Axonal Transport;Bioinformatics;Bortezomib;Cell Line;chemotherapy;Chemotherapy-induced peripheral neuropathy;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complication;Development;disease-in-a-dish;Dissection;Dose;Dose Limiting;Drops;effective therapy;experimental study;Exposure to;Genetic Engineering;Glutamate-ammonia-ligase adenylyltransferase;Grant;Human;human adult stem cell;Human Biology;human induced pluripotent stem cells;induced pluripotent stem cell;innovation;Investigation;knock-down;Link;Malignant Neoplasms;Mediating;Microtubule-Associated Protein 2;Microtubules;Mitochondria;Modeling;Molecular;Morbidity - disease rate;Neurons;neuroprotection;neurotoxic;neurotoxicity;Nicotinamide Mononucleotide;novel;Numbness;overexpression;Paclitaxel;Pain;Pathogenesis;Pathology;Pathway interactions;Patients;Peripheral;Peripheral Nervous System;Peripheral Nervous System Diseases;phosphoproteomics;Play;prevent;Process;Proteasome Inhibitor;Proteins;Proteomics;Role;Series;side effect;Signal Pathway;Spinal Ganglia;Sterility;System;Technology;Testing;Therapeutic;therapeutic development;Time;Vincristine

PROJECT_TITLE: Investigating the role of MAP2 in chemotherapy-induced peripheral neurotoxicity

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


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

ORG_CITY: NEW HAVEN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE – MODELING MULTISCALE IMMUNO-MECHANICS IN AORTIC DISEASE Vascular diseases continue to be responsible for significant disability and death. They result from myriad molecular causes, but manifest clinically at the tissue scale. We will develop novel multiscale computational models that integrate, for the first time, immuno-biological and mechano-biological contributions to aortic disease in order to establish both a new paradigm for understanding disease progression as a function of age of onset, immune status, and sex and a better approach for selecting and timing drug therapies.

PI_NAMEs: HUMPHREY, JAY D. (contact);TELLIDES, GEORGE

PROGRAM_OFFICER_NAME: HSU, LI-YUEH

PROJECT_TERMS: adaptive immunity;Address;Adolescent;Age of Onset;Animal Model;Anti-Hypertensive Agents;Anti-Inflammatory Agents;Aorta;Aortic Diseases;Arteries;Biological;Biology;Biomechanics;Blood;blood pressure elevation;Blood Vessels;Caliber;Cardiovascular Physiology;Cardiovascular system;Cells;Cessation of life;Child;Clinical;Collaborations;Combination Drug Therapy;Complement;Computer Models;Coupled;Data;Data Set;Databases;Development;disability;Disease;Disease Progression;early onset;Endothelial Cells;Ensure;Environment;Epidemic;Extracellular Matrix Degradation;Fibroblasts;Foundations;Gene Expression;gene product;Geometry;Goals;Homeostasis;Hypertension;hypertensive;Immune;immunological status;Immunologics;Inflammation;Inflammatory;innovation;Lead;Macrophage;Mathematics;Mechanical Stress;Mechanics;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multi-scale modeling;Natural Immunity;Nitric Oxide;novel;novel strategies;Oxidative Stress;Oxidative Stress Induction;Pathologic Processes;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phenotype;Play;pressure;prevent;Process;Production;Property;repaired;Reproducibility;Research Design;response;Risk;Risk Factors;Role;sex;shear stress;Smooth Muscle Myocytes;soft tissue;Soft Tissue Disorder;Stress;System;T-Lymphocyte;Testing;Thick;Time;Tissues;Vascular Diseases;Viral;Virulent;Work

PROJECT_TITLE: Modeling Multiscale Immuno-Mechanics in Aortic Disease


NIH_SPENDING_CATS: Atherosclerosis;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

PHR: PROJECT NARRATIVE Reducing the mortality rates associated with coronary artery disease will require the development of accurate strategies to risk stratify coronary lesions that will precipitate an acute coronary event. The proposed research will establish and validate computational frameworks to characterize the in vivo plaque stiffness and mechanical stress field, and evaluate the predictive accuracy of these frameworks to identify high-risk coronary lesions in the clinical setting. The outcomes of this research will promote the prognostication of coronary lesions to guide patient management and treatment strategies towards minimizing major adverse cardiac events.

PI_NAMEs: HSU, EDWARD W (contact);TIMMINS, LUCAS H.

PROGRAM_OFFICER_NAME: LUO, JAMES

PROJECT_TERMS: 3-Dimensional;Acute Coronary Event;acute coronary syndrome;Adverse event;Algorithms;Area;Arterial Fatty Streak;Autopsy;Behavior;Biomechanics;Cardiac;Carotid Artery Plaques;Classification;Clinical;Clinical Data;clinical investigation;computer framework;Coronary;Coronary Arteriosclerosis;Coronary artery;coronary lesion;coronary plaque;Data;Death Rate;Detection;Development;Diagnostic;Disease;Disease Progression;elastography;Elements;Environment;Environmental Risk Factor;Evaluation;Event;Exposure to;Failure;Finite Element Analysis;Frequencies;Future;Goals;high risk;Histology;human data;Image;image registration;imaging modality;Imaging Techniques;in vivo;indexing;Lesion;mechanical load;Mechanical Stress;Mechanics;Medical Imaging;Methods;Morphology;Natural History;Outcomes Research;Pathologic;Patients;Pattern;Phenotype;Predictive Value;prognostic value;prognostication;Property;prospective;Prospective Studies;Research;Retrospective Studies;Risk;risk stratification;Role;Rupture;Stress;Testing;Thinness;Thrombosis;Tissues;Translating;treatment strategy;ultrasound;virtual

PROJECT_TITLE: Biomechanical Indices for Coronary Lesion Rupture Risk and Lesion Prognostication

STUDY_SECTION: BTSS

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


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative Novel clinical trial designs can accelerate drug development processes and can contribute to the rigorous examination of new treatments. Our research project focuses on the use of external data, including previous clinical studies and real-world data, in the design and analysis of phase II and III oncology trials. We will develop and validate statistical methods that leverage external data and previous clinical research in the development of new therapeutics.

PI_NAMEs: TRIPPA, LORENZO  (contact)

PROGRAM_OFFICER_NAME: WANG, YANLI

PROJECT_TERMS: Acceleration;Algorithms;androgen independent prostate cancer;arm;Biometry;Characteristics;Clinical;Clinical Data;Clinical Research;clinical trial analysis;Clinical Trials;Clinical Trials Design;Collection;comorbidity;Computer software;cost;Data;Data Collection;data imputation;data quality;Data Set;design;Development;Disease;drug development;Electronic Health Record;Enrollment;Ensure;Evaluation;Experimental Designs;Failure;Future;Glioblastoma;Healthcare;improved;innovation;Investments;Literature;Malignant neoplasm of lung;Malignant neoplasm of prostate;Measurement;Methodology;Methods;novel;novel therapeutics;oncology trial;open source;Outcome;participant enrollment;Patient Representative;Patients;Phase;phase 2 designs;Phase III Clinical Trials;Population;primary outcome;Probability;Procedures;Process;prognostic;Prognostic Factor;Randomized;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;repository;Research;Research Project Grants;Risk;Risk Reduction;Sample Size;small cell lung carcinoma;Statistical Data Interpretation;Statistical Methods;Testing;Time;treatment arm;treatment effect;Treatment outcome;trial design;Underrepresented Minority;Validation;validation studies;Variant

PROJECT_TITLE: Statistical Methods and Validation Analyses for the Integration of External Data in Clinical Trials

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


NIH_SPENDING_CATS: Bioengineering;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BERKELEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Channelrhodopsins are ion channel proteins from motile algae that convert light into cellular electrical signals and are widely used as molecular tools in biomedical research to control the activity of targeted neurons and other excitable cells. This approach, called optogenetics, has led to remarkable advances in our understanding of brain function and has recently shown clinical promise in restoring visual activity in blind patients. Understanding how channelrhodopsins are opened by light and the basis of their diverse functional properties will enable the development of new optogenetic tools for research and clinical applications with the potential to treat diseases of the nervous and cardiovascular systems including arrythmias, epilepsy, visual loss, hearing loss, and chronic pain.

PI_NAMEs: BROHAWN, STEPHEN GRAF (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acceleration;Algae;Architecture;Bacteriorhodopsins;Binding;Binding Proteins;Biological Assay;Biomedical Research;Biophysics;blind;Blindness;Brain;Cardiovascular system;Cations;Cells;Cephalic;chronic pain;Clinical;clinical application;Cloning;comparative;computer studies;Cryoelectron Microscopy;Darkness;Deep Brain Stimulation;desensitization;Development;Disease;Electrophysiology (science);Electrostatics;Engineering;Environment;Epilepsy;Experimental Designs;experimental study;Family;Functional disorder;Generations;Goals;hearing impairment;holographic stimulation;improved;insight;Ion Channel Gating;Ion Channel Protein;Kinetics;Light;light gated;Lipids;member;Membrane Potentials;Membrane Proteins;microbial;Modeling;Molecular;Molecular Conformation;Motility;Nervous System;Nervous System Disorder;Neurons;next generation;novel;Opsin;optogenetics;Oranges;Organism;Patients;Photophobia;physical model;Point Mutation;programs;Property;protein structure;Proteins;Protons;rational design;Reporting;Research;Retina;Rhodopsin;Sampling;Schiff Bases;Sensory;sight restoration;Signal Transduction;Structural Models;Structure;System;Testing;Tissues;tool;Variant;Visual;Work

PROJECT_TITLE: Structural and mechanistic basis of channelrhodopsin function

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lymphatic Research;Lymphedema;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

PHR: PROJECT NARRATIVE/RELEVANCE Breast cancer-related lymphedema (BCRL) is a common and debilitating complication of breast cancer treatment. We have found that the risk of this complication is significantly increased in Black women. The purpose of this study is to uncover the cellular mechanisms that drive racial differences that increase the risk of BCRL development.

PI_NAMEs: BARRIO, ANDREA ;MEHRARA, BABAK J (contact)

PROGRAM_OFFICER_NAME: RICHMOND, ELLEN S

PROJECT_TERMS: Adjuvant Chemotherapy;Age;Anti-Inflammatory Agents;antifibrotic treatment;arm;Asian;Atopic Dermatitis;Automobile Driving;Axillary Lymph Node Dissection;Biology;Biopsy Specimen;black men;black patient;Black Populations;Black race;black women;Body mass index;Breast Cancer Risk Factor;Breast Cancer Treatment;Cardiovascular Diseases;Caring;Caucasians;Cells;Characteristics;Chronic;Clinical;cohort;Complication;Confounding Factors (Epidemiology);Deposition;Developed Countries;Development;Disease;efficacy testing;Eligibility Determination;Epidermis;Epithelium;Exposure to;Fibroblasts;Fibrosis;Functional disorder;Harvest;High Prevalence;high risk;Hospitalization;Immune response;Inflammation;Inflammatory;inflammatory modulation;Inflammatory Response;Injury;Institutional Review Boards;Keloid;keratinocyte;Knowledge;Lead;Link;Liquid substance;Lymph;lymph nodes;Lymphatic;lymphatic dysfunction;Lymphatic function;Lymphedema;Malignant Breast Neoplasm;Measurement;Measures;Melanoma;Mesenchymal;Multivariate Analysis;Neoadjuvant Therapy;novel therapeutics;Operative Surgical Procedures;Pathologic;patient population;Patients;Play;prevent;Procedures;prophylactic;prospective;Publishing;Qualifying;Quality of life;Race;racial difference;racial disparity;radiation response;recurrent infection;Reporting;Research;response;Risk;Risk Factors;Role;Sampling;Sentinel Lymph Node Biopsy;Serum;Skin;skin biopsy;skin disorder;skin fibrosis;Specimen;Swelling;Testing;Time;Tissues;Treatment Efficacy;White Women;Woman;women's treatment

PROJECT_TITLE: Mechanisms of racial disparity in breast cancer-related lymphedema


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Gene fusions of the receptor tyrosine kinase, ROS1, have been shown to drive neoplastic transformation of cells in a range of malignancies and targeted therapy with tyrosine kinase inhibitors (TKI) that have activity against ROS1 kinase domain, has led to significant reduction of tumor burden in patients. Unfortunately, clinical resistance to TKI therapy frequently occurs, which limits its long-term durability as an anti-tumor treatment strategy. This project will explore a novel mechanism by which resistance to ROS1-TKI emerges from an alternate signaling pathway and predict new resistant point mutations in ROS1 that confer resistance to the next generation of ROS1-TKI therapy.

PI_NAMEs: IYER, SUDARSHAN RAJAN (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Address;Affinity;Appearance;Attention;Binding;Biological Assay;Biological Models;Bypass;C-terminal;cancer cell;cancer genome;Cancer Patient;Cell fusion;Cell Line;Cell Survival;cell transformation;Cells;Cholangiocarcinoma;Clinical;clinical implementation;combat;Compensation;crizotinib;Data;Deaminase;design;differential expression;Down-Regulation;Drug Design;Drug resistance;Engineering;experience;Future;gain of function;Gene Expression;Gene Expression Profiling;Gene Fusion;Generations;Genes;Genomic Instability;Glioblastoma;Human;improved;In Vitro;in vivo;Incidence;inhibitor;inhibitor therapy;kinase inhibitor;knock-down;Laboratories;Malignant Neoplasms;Memorial Sloan-Kettering Cancer Center;Mitogen-Activated Protein Kinases;Molecular;Mutagenesis;Mutate;Mutation;Neoplastic Cell Transformation;next generation;Non-Small-Cell Lung Carcinoma;novel;oncogene addiction;Orphan;overexpression;Pathway interactions;patient derived xenograft model;Patients;Phospho-Specific Antibodies;Phosphotransferases;PI3K/AKT;Point Mutation;Protein Overexpression;Receptor Protein-Tyrosine Kinases;Recurrence;Research;Resistance;resistance mechanism;RNA;Role;ROS1 gene;Signal Pathway;Signal Transduction;small molecule;Structure;Symptoms;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;TP53 gene;transcription factor;treatment strategy;tumor;Tumor Burden;Tumor Suppressor Proteins;tumorigenic;Tyrosine Kinase Inhibitor;Western Blotting

PROJECT_TITLE: Resistance Mechanisms in ROS1-Fusion-Driven Malignancies


NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Increasingly sophisticated plaque modification methods (orbital atherectomy, intravascular lithotripsy etc.) are employed before vascular interventions like stenting to tackle complex atherosclerotic disease and yet, operator decisions are guided by personal experience with no established criteria as to which technology to use and when, what constitutes sufficient modification and how to balance benefits and risks. What is needed and what our team of academic and industrial scientists, engineers and clinicians aims to develop are mechanistic insight into the biology of modification, and tools for predicting function from imaging and validated criteria for treatment outcomes. We will relate alterations in lesion micro-morphology (calcium, lipid, fibrous, fibro-fatty content) to changes in spatial micro-mechanical (compliance, stress) and local drug delivery (uptake, retention) response, and correlate image-based quantification of lesion micro-morphology to interventional outcome, providing a framework to predict and optimize therapy.

PI_NAMEs: EDELMAN, ELAZER R (contact)

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: Adipose tissue;Affect;Amaze;Angioplasty;Area;Arteries;Atherectomy;Atherosclerosis;Balloon Angioplasty;Benefits and Risks;Binding;Biology;Biomechanics;Blood Vessels;calcification;Calcium;Cardiovascular Diseases;Characteristics;Clinical;Clinical Data;Clinical Trials;Communities;Complex;Computer Models;Computing Methodologies;Consensus;Coronary;Coronary Arteriosclerosis;Coronary heart disease;Data Analyses;Dedications;deep learning;Devices;Diameter;Dimensions;Disease;Drops;Drug Delivery Systems;drug distribution;Engineering;Equilibrium;Esthesia;Event;experience;experimental study;Feedback;follow-up;Future;grasp;Human;Image;Image Analysis;image processing;imaging modality;implantation;Industrialization;innovation;insight;interdisciplinary approach;Intervention;intervention delivery;Investigation;Learning;Left;Lesion;Link;Lipids;Lithotripsy;local drug delivery;Measures;Mechanics;Methods;Microanatomy;Modeling;Modification;Morality;Morphology;Outcome;Penetration;Performance;Perioperative;Pharmaceutical Preparations;pharmacokinetic model;pre-clinical;predictive tools;Procedures;Property;response;restenosis;Science;Scientist;Shapes;sound;Standardization;Stents;Stress;success;Techniques;Technology;Therapeutic Intervention;Touch sensation;treatment optimization;Treatment outcome;trend;United States National Institutes of Health;uptake;Vascular Diseases;virtual;Visualization;Work

PROJECT_TITLE: Personalized lesion modification optimizes atherosclerosis intervention


ORG_CITY: NEW YORK

ORG_DEPT: BIOLOGY

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative: This project will determine how microorganisms use phenotypic memory mechanisms and gene regulation to survive under fluctuating stresses, including periods of nutrient starvation and exposure to antibiotics. By applying biophysical models, the project will enable precise predictions of bacterial growth and survival in complex environments. Our quantitative analysis of how bacteria use gene regulation and memory to survive will enable improvements in the clinical use of antimicrobials, in understanding treatment outcomes, and in controlling and perturbing host-associated microbial communities.

PI_NAMEs: KUSSELL, EDO L (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Address;Algorithmic Analysis;Antibiotic Resistance;Antibiotics;antimicrobial;Bacteria;bacterial community;bacterial metabolism;bacterial resistance;Bar Codes;Biochemical Pathway;Biological;biophysical model;Biophysics;Carbon;cell growth;Cells;Clinical;Complex;cost;Costs and Benefits;Cues;Culture Media;Custom;Data;daughter cell;design;drug modification;Drug resistance;efflux pump;Environment;environmental stressor;Enzymes;Escherichia coli;experimental study;Exposure to;fitness;Gene Combinations;Gene Expression Regulation;gene induction;Genes;Growth;gut microbiome;host-associated microbial communities;Human;Image Analysis;improved;Inherited;innovation;insight;interest;Knowledge;Laboratories;Lac Operon;LacZ Genes;Libraries;Maps;Measurement;Measures;Memory;Metabolic;Metabolic stress;Microbiology;Microfluidics;microorganism;Microscope;Microscopy;Modeling;molecular pump;monolayer;Mothers;mutant;Mutation;novel;Nutrient;outcome prediction;Periodicals;Phenotype;Physiologic pulse;Physiological;Population;Population Dynamics;predictive modeling;Process;Production;Property;Proteins;Regulation;Repression;Research;Resistance;resistance gene;resistance mechanism;resistant strain;Resolution;response;Site-Directed Mutagenesis;Source;Starvation;Stress;Structure;System;Testing;Time;Treatment outcome;Work

PROJECT_TITLE: Gene Regulation and Memory in Bacterial Metabolism and Antibiotic Resistance

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Atherosclerosis;Bioengineering;Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Machine Learning and Artificial Intelligence;Nanotechnology

ORG_CITY: AMHERST

ORG_DEPT: PATHOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: PROJECT NARRATIVE Arterial stiffness is a predictor of cardiovascular diseases; however, the underlying mechanism by which arterial stiffening promotes abnormal vascular smooth muscle cell (VSMC) function associated with neointima formation in the vessel wall is largely unknown. This proposed research explores the novel roles of survivin as a key regulator of stiffness-mediated VSMC phenotypes, neointima formation, and arterial stiffening. In addition, we employ in vitro porcine aorta decellularized extracellular matrix-based experimental systems, sophisticated single-cell-based analyses, and a mouse model system to examine the interactions between VSMCs and the pathological vascular environment and to identify potential new therapeutic targets for the treatment of cardiovascular disease.

PI_NAMEs: BAE, YONGHO  (contact);HEO, SU CHIN

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: 3-Dimensional;Abnormal Cell;Affect;Amino Acids;Animal Model;Aorta;Arterial Injury;arterial remodeling;arterial stiffness;Arteries;Atherosclerosis;Atomic Force Microscopy;Attenuated;Biochemical;Biocompatible Materials;Biological;Biological Models;Biology;Biomechanics;Biomimetics;Biophysical Process;Blood Vessels;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;cell behavior;cell motility;Cell Physiology;Cell Separation;Cells;Cellular biology;Chromatin;Coronary Arteriosclerosis;Coronary heart disease;Coupled;Data;Development;Disease;Disease Progression;DNA Sequence Alteration;Environment;epigenomics;Event;Extracellular Matrix;Extracellular Matrix Proteins;Family suidae;Feedback;femoral artery;Fluorescent in Situ Hybridization;Gene Expression;Genetic Transcription;Goals;Histologic;Histology;Human;Hyperplasia;Image;In Vitro;in vivo;in vivo Model;inhibitor-of-apoptosis protein;injured;Injury;Invaded;knock-down;Machine Learning;machine learning algorithm;Mechanics;Mediating;Medicine;member;Microscopy;migration;Modeling;Molecular;Monitor;Morphology;mouse model;Mus;nanofiber;nanoscale;neointima formation;new therapeutic target;novel;Nuclear Structure;Optics;overexpression;Pathologic;Pathologic Processes;Pathology;Pharmacotherapy;Phenotype;Physical condensation;Physiological;polyacrylamide hydrogels;Production;Proliferating;Property;protein expression;Protein Family;Proteins;reconstruction;Research;Research Personnel;Research Proposals;Resolution;response;RNA;Role;scaffold;single cell analysis;Smooth Muscle Myocytes;soft tissue;spheroids;Structure;survivin;System;Testing;Therapeutic;three dimensional cell culture;Time;Tissue Engineering;Tissues;transcriptome sequencing;transcriptomics;vascular abnormality;vascular injury;Vascular Smooth Muscle;vascular smooth muscle cell migration;vascular smooth muscle cell proliferation;Work

PROJECT_TITLE: Biomimetic Vascular Matrix for Vascular Smooth Muscle Cell Mechanobiology and Pathology

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


ED_INST_TYPE: PRIMATE CENTERS

NIH_SPENDING_CATS: Childhood Injury;Lung;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Sleep Research

ORG_DEPT: NEUROSCIENCES

PHR: Project Narrative Repeated low oxygen delivery (hypoxia) to the developing fetal brain during pregnancy frequently occurs due to maternal sleep apnea and carries significant risks for disturbances in brain maturation and life-long neurological disabilities. We will undertake fetal tissue oxygenation measurements, pathology and behavioral studies and high field MRI analysis to determine the responses of the fetal brain to repeated episodes of maternal hypoxia. We will define novel cellular and molecular mechanisms that disrupt the establishment of learning and memory circuitry during a critical window in brain development and will test potential new therapies to improve learning and memory disturbances caused by transient intermittent fetal hypoxia.

PI_NAMEs: BACK, STEPHEN ARTHUR (contact)

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: Action Potentials;Acute;Adolescent;Adverse effects;Affect;Agonist;Air;AMPA Receptors;Apnea;awake;Behavioral;behavioral study;Brain;brain based;brain control;Brain region;brain volume;Cell Death;Cellular Morphology;cerebral oxygenation;Cerebrum;Chemosensitization;Childhood;Chronic;Clinical Research;clinically relevant;Data;Dendrites;density;Development;Diffusion Magnetic Resonance Imaging;efficacy evaluation;Electrophysiology (science);Exposure to;fetal;fetal brain injury;Fetal Sheep;Fetal Tissues;Fetus;fetus hypoxia;Fire - disasters;Frequencies;Future;Gestational Age;Glutamates;gray matter;Growth;hippocampal pyramidal neuron;Hippocampus;Histologic;Hour;Hypoxemia;Hypoxia;Impairment;improved;in utero;In Vitro;in vivo;Infant Development;Inflammation;Learning;Long-Term Potentiation;Magnetic Resonance Imaging;Maternal complication;maternal risk;Measurement;Mediating;Memory;Memory impairment;Modeling;Molecular;morphometry;myelination;N-Methyl-D-Aspartate Receptors;Near-Infrared Spectroscopy;neural circuit;neurobehavioral;neurodevelopment;Neuroglia;Neurological disability;neuron loss;Neurons;neurotransmission;novel;novel therapeutics;Outcome;Oxygen;Pathology;Pattern;postnatal;pre-clinical;Pre-Clinical Model;Predisposition;Pregnancy;Pregnant sheep;Pregnant Women;prenatal exposure;prevent;Reproducibility;Reproducibility of Results;response;Risk;Role;Shapes;sheep model;Sleep Apnea Syndromes;Structure;Synapses;Synaptic plasticity;Synaptic Transmission;Testing;Third Pregnancy Trimester;tissue oxygenation;Tissues;Twin Multiple Birth;Vertebral column;white matter;white matter injury

PROJECT_TITLE: Mechanisms of Hypoxia-Mediated Disturbances in Cerebral Maturation in a Fetal Ovine Model of Maternal Sleep Apnea


ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it provides a novel therapeutic target for brain aneurysms, a condition that leads to a high rate of disability and death in stroke patients upon rupture. In particular, our work focuses on the role of a novel degradation pathway in the development of aneurysms and anti-degradation strategy may serve as a new therapy for the disease. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to reducing the burdens of illness and disability.

PI_NAMEs: RUI, YANNING  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Affinity;Aneurysm;Area;Autophagocytosis;Autophagosome;Binding;Biological Assay;Blood Vessels;Brain Aneurysms;brain endothelial cell;burden of illness;Cause of Death;cerebrovascular;Cerebrovascular system;Cessation of life;Circle of Willis;Clinical Trials;CRISPR/Cas technology;Data;Degradation Pathway;Development;Digestion;disability;Disease;Drug Targeting;Endothelial Cells;Endothelium;Event;experimental study;Extracellular Matrix;Extravasation;Focal Adhesions;Foundations;gain of function;Genes;Goals;Health;Human;Impairment;improved;in vivo;Incidence;inhibitor;innovation;Intracranial Aneurysm;Kinetics;knock-down;Knowledge;loss of function;Mediating;Methods;mimetics;Mission;Monitor;mouse model;Mus;Names;new therapeutic target;novel;novel therapeutics;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Permeability;Phosphorylation;Phosphotransferases;Play;preservation;prevent;Process;Property;Public Health;receptor;receptor function;Receptor Gene;recruit;Reporting;Research;Role;Rupture;Stains;stroke patient;Subarachnoid Hemorrhage;System;TANK-binding kinase 1;Testing;Tracer;United States National Institutes of Health;Variant;Vascular Diseases;Vascular Endothelial Cell;Vascular Permeabilities;Work;Zebrafish

PROJECT_TITLE: Role of p62-Mediated Endothelial FA-Phagy in Intracranial Aneurysms

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Atherosclerosis;Biomedical Imaging;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Neurosciences

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE The goal of the current project is to positively identify and characterize injured-but-noninfarct myocardium in the post-ischemic heart, which we call the Intermediate Zone. A better understanding in the roles of the intermediate zone in cardiac impairment will have a broad impact on the diagnosis and personalized care in the management of acute coronary syndromes.

PI_NAMEs: ARORA, RISHI ;ZHAO, MING  (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Acute;acute coronary syndrome;Apoptosis;Arrhythmia;Biological Models;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;Cardiology;Cell Death;cell type;Characteristics;Chronic;Chronic Phase;clinical diagnosis;clinical practice;clinically relevant;Data;Denervation;detection method;Diagnosis;Disparity;EFRAC;Electrophysiology (science);Event;Evolution;Exhibits;Functional disorder;Functional impairment;Goals;Heart;Heterogeneity;Hypertrophy;Image;image guided;Imaging Techniques;Impairment;in vivo;in vivo imaging;Infarction;injured;Injury;insight;Investigation;Ischemia;Knowledge;knowledge base;Life;Link;Maps;Measurement;Methodology;Methods;Molecular;Myocardial;Myocardial dysfunction;myocardial injury;Myocardial Ischemia;Myocardium;Necrosis;nerve supply;Neurons;novel;Oxidative Stress Induction;Pathologic;Pathology;Pathway interactions;Patients;personalized care;Phase;Phosphatidylethanolamine;Prognosis;prognostic value;Proteomics;Reperfusion Therapy;Research;Research Personnel;Residual state;response;Risk;risk prediction;Role;Shapes;Signal Pathway;Signal Transduction;spatiotemporal;Specificity;Technology;Testing;tissue injury;tissue mapping;Tissues;tool;transcriptomics;Ventricular Arrhythmia

PROJECT_TITLE: The identification and pathophysiology of non-infarcted but injured myocardium in the post-ischemic heart

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-C(02)]