ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Epilepsy;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE There are no disease modifying treatments for epilepsy. Understanding how genetic changes bring about epilepsy may help us to develop better treatment. This project examines how one particular genetic change increases risk of epilepsy in hopes of coming closer to this goal.

PI_NAMEs: HABELA, CHRISTA  (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Actins;Acute;Affect;Angelman Syndrome;Animal Model;Biological Models;career;career development;Cell Line;Cells;Clinical;Control Animal;Cytoplasm;Data;design;Development;Development Plans;Disease;drug response prediction;Electrophysiology (science);Epilepsy;Epileptogenesis;Equilibrium;excitatory neuron;Excitatory Synapse;expectation;experimental analysis;Experimental Animal Model;Experimental Designs;experimental study;FMR1 gene;Foundations;Funding;Future;gamma-Aminobutyric Acid;Gene Deletion;Generalized Epilepsy;Genes;Genetic;Genetic Determinism;Genetic Models;Genetic Predisposition to Disease;Genetic Risk;genetic risk factor;Genotype;glutamatergic signaling;Glutamates;Goals;hippocampal pyramidal neuron;Human;Human Genetics;human induced pluripotent stem cells;immunocytochemistry;improved;In Vitro;in vivo;in vivo Model;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;inhibitory neuron;Inhibitory Synapse;insight;Intellectual functioning disability;Interneurons;Investigation;Knock-out;Laboratories;Lead;Measures;Mediating;Mentors;Mentorship;Modeling;Molecular;Morbidity - disease rate;Morphology;mouse model;multi-electrode arrays;Mus;Mutation;nerve stem cell;neural network;neurodevelopment;Neurodevelopmental Disability;Neurodevelopmental Disorder;neurogenesis;Neurologic;neuron development;Neuronal Dysfunction;Neurons;neuropsychiatric disorder;Neurotransmitters;new therapeutic target;novel;Other Genetics;Parvalbumins;Pathologic;Patient Care;patient derived induced pluripotent stem cells;Patients;Pennsylvania;Pharmacology;Phenotype;Physiology;Population;Positioning Attribute;Predisposition;Property;Proteins;Regulation;Research;research and development;Research Proposals;response;Rhodopsin;Risk;Risk Factors;risk variant;Rodent;Rodent Model;Role;Schizophrenia;Scientist;Seizures;Signal Transduction;skills;Slice;sound;Structural defect;Structure;Susceptibility Gene;Synapses;synaptic function;synaptogenesis;Techniques;Therapeutic Intervention;Training;Translations;Universities

PROJECT_TITLE: Modeling genetic risk for epilepsy using IPSC and animal models.

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ADMINISTERING_IC: DE

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Immunotherapy;Infectious Diseases;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: NEW HAVEN

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: NARRATIVE The number of head and neck cancers caused by the human papillomavirus are dramatically increasing, but current therapies can cause lifelong side effects, and patients with recurrent disease have few effective treatment options. We have identified that demethylation therapy increases immune response in these tumors, and that they are sensitive to demethylation dependent on expression of a cytidine deaminase, APOBEC3B, that ironically is required for survival of untreated cancer cells. In this project, we will conduct a trial and use trial samples to further determine if demethylation enhances response to immune checkpoint inhibitors as a new therapy for human papillomavirus-associated head and neck cancers.

PI_NAMEs: ANDERSON, KAREN S. (contact)

PROJECT_TERMS: Aftercare;apolipoprotein B mRNA editing enzyme;AXIN1 protein;Azacitidine;Bioinformatics;Biological Assay;Biometry;cancer cell;Cancer Etiology;cancer/testis antigen;Cell Death;cell killing;Cell Line;Cell Proliferation;Cell Survival;Cells;cervical and uterine cancer;Cessation of life;Characteristics;Chromatin;Clinical Trials;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;Cytidine Deaminase;Cytoprotection;cytotoxic;cytotoxicity;Data;demethylating therapy;demethylation;Dependence;Diagnosis;Disease;DNA;DNA Damage;Dose;effective therapy;efficacy testing;Epidemic;Flow Cytometry;GAGE;Genes;Genetic Transcription;Genomics;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Health;HPV analysis;HPV-negative head and neck cancer;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Hypermethylation;Immune;immune activation;immune activator;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immunofluorescence Immunologic;In Vitro;in vitro Assay;Incidence;Individual;Infiltration;Innate Immune Response;Interferon Type I;Interferons;knock-down;Lymphocyte;Malignant Neoplasms;Measures;Mediating;Methylation;Molecular;Morbidity - disease rate;Mutagenesis;Mutate;Mutation;Neck;neoantigens;Nivolumab;novel;novel therapeutics;oral HPV-positive head and neck cancers;Outcome;overexpression;participant enrollment;patient population;patient prognosis;Patients;polypeptide;pre-clinical;prevent;Prognosis;programmed cell death protein 1;Recurrence;Recurrent disease;response;Role;Sampling;sensor;side effect;Signal Pathway;Signal Transduction;Specimen;Squamous cell carcinoma;Stains;Supporting Cell;T cell infiltration;T-Lymphocyte;Testing;Testis;The Cancer Genome Atlas;therapeutically effective;therapy resistant;Toxic effect;transcriptome sequencing;tumor;tumor microenvironment;tumor xenograft;Xenograft procedure

PROJECT_TITLE: Project 3: Demethylation of HPV-associated head and neck cancer to trigger APOBEC synthetic lethality and enhance immune response


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Orphan Drug;Prevention;Rare Diseases

PHR: PROJECT NARRATIVE The objective of this Developmental Research Program is to foster and develop innovative head & neck cancer translational research programs, with objectives that align with the overall goals of the Yale SPORE in Head & Neck Cancer. Projects of the highest caliber will be sought to possibly serve as replacements for the primary SPORE projects if they are completed, or if they cannot otherwise proceed.

PI_NAMEs: DECKER, ROY  (contact)

PROJECT_TERMS: anti-cancer research;Area;Award;Budgets;Caliber;Carcinogenesis Mechanism;Clinical;Collaborations;Committee Members;Communities;Development;Direct Costs;Early Diagnosis;Electronic Mail;Ensure;Evaluation;Financial Support;Fostering;Fox Chase Cancer Center;Funding;Funding Mechanisms;Future;Goals;Guidelines;Head and Neck Cancer;Head and neck structure;Human;innovation;Institution;Leadership;Malignant neoplasm of lung;Malignant Neoplasms;meetings;member;Methods;minority investigator;Monitor;Morbidity - disease rate;mortality;Neck Cancer;new therapeutic target;novel;novel therapeutics;Outcome;Pilot Projects;Prediction of Response to Therapy;Process;Productivity;prognosis biomarker;Program Research Project Grants;programs;recruit;Recruitment Activity;Research;Research Personnel;Research Project Grants;Resource Sharing;Risk Assessment;therapy resistant;translational cancer research;translational potential;translational research program;tumorigenesis;Wages;Woman;Work

PROJECT_TITLE: Yale Head and Neck Cancer SPORE Developmental Research Program


ADMINISTERING_IC: HL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cystic Fibrosis;Lung;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PHR: Project Narrative Cystic Fibrosis (CF) is one of the most common inherited childhood diseases, impacting 1 in 4,000 children born in the US (www.cff.org) and is caused by mutations of the CFTR protein that affect its 3-dimensional structure and function. While therapies now exist to treat the most common CFTR mutation, other common mutations do not respond to any of the drugs, so many CF patients are left without treatments. Through the development and use of new mass spectrometric methods, we aim to characterize the structural defects of CFTR variants that do not respond to current treatments and to understand the mechanisms of action of CF drugs to aid in the identification of new strategies of therapeutic intervention.

PI_NAMEs: YATES III, JOHN R (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Affect;Age;Anions;Applications Grants;Attenuated;Biogenesis;carbene;Cells;Cessation of life;Child;Childhood;Clinical Trials;Code;Combination Drug Therapy;Combined Modality Therapy;Cystic Fibrosis;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Defect;design;Detection;Development;Disease;DNA Insertion Elements;Drug Binding Site;Drug Combinations;drug development;Drug Targeting;Effectiveness;Epithelium;Exclusion;FDA approved;Goals;Health;Homeostasis;Immunofluorescence Immunologic;improved;in vivo;Inherited;innovation;insight;Knowledge;Label;Left;Light;Lung;mass spectrometer;Mass Spectrum Analysis;Methods;Molecular;Molecular Conformation;mutant;Mutation;Names;Nature;novel;novel therapeutic intervention;novel therapeutics;Outcome;oxidation;Paint;Patient Compliance;Patients;Peptides;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Point Mutation;Post-Translational Protein Processing;Protein Conformation;protein structure;protein transport;Proteins;Rationalization;Refractory;Regimen;Regulator Genes;Risk;Sampling;Science;side effect;Signal Transduction;Site;Sodium Chloride;Solvents;Stains;Structural defect;Structure;Symptoms;technology development;Therapeutic;Therapeutic Intervention;three dimensional structure;Tissues;trafficking;Variant;VX-809;Western Blotting;Work

PROJECT_TITLE: The CFTR Interactome

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Rare Diseases

PHR: NARRATIVE To ensure significant advances in the prevention, diagnosis and treatment of head and neck cancers, it is essential to foster and train the next generation of scientist who will push forward basic, translational and clinical research in this arena. This program will identify and promote formation of a strong, diverse work force in head and neck cancer.

PI_NAMEs: FERGUSON, KATHRYN M (contact)

PROJECT_TERMS: Accounting;Address;American Cancer Society;anti-cancer research;Appointment;Area;Award;base;Basic Science;bench to bedside;cancer care;Cancer Center;Cancer Etiology;Cancer Hospital;career;Cessation of life;Clinical;Clinical Oncology;Clinical Research;cohort;Collaborations;Color;Communities;community burden;Comprehensive Cancer Center;Dedications;design;Development;Diagnosis;Discipline;Disease;Elements;Ensure;Environment;Faculty;Fellowship Program;Fostering;Fox Chase Cancer Center;Funding;Goals;Growth;Head and Neck Cancer;head and neck cancer patient;Head and neck structure;HPV negative;Human Papillomavirus;Immunotherapy;improved;improved outcome;Institution;interest;knowledge base;Leadership;Malignant Neoplasms;Medical Research;medical schools;Medicine;Mentors;Mission;Molecular;Morbidity - disease rate;mortality;next generation;North Carolina;novel;novel strategies;Philadelphia;Physicians;Prevention;Process;programs;recruit;Reproduction spores;Research;Research Personnel;Resources;Scientist;Talents;therapy resistant;Training;Training Programs;Translating;translational impact;translational medicine;translational oncology;Translational Research;translational research program;translational scientist;Underrepresented Populations;United States;United States National Institutes of Health;Universities;Wages;Work;Yale Cancer Center

PROJECT_TITLE: Yale Head and Neck Cancer SPORE Career Enhancement Program


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative The urgent need for child neurology and epilepsy research focused on the low- and middle-income countries of Africa is illustrated by the genomic diversity of Africa, which exceeds the genomic diversity of the rest of the world combined, and the up-to-90% of children with epilepsy who remain undiagnosed and/or untreated in northern Nigeria. ABV will train a cadre of investigators from the six major cities of northern Nigeria, who long- term will form the first major child neurology and epilepsy research collaborative in Africa. Different levels of training designed to meet the needs of each junior investigator, ranging from a full-time training commitment to training to individual courses and focused mentoring, will be delivered.

PI_NAMEs: ILIYASU, ZUBAIRU ;TREVATHAN, EDWIN  (contact)

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Address;Africa;Africa South of the Sahara;Area;career;Child;Childhood Neurological Disorder;Cities;Clinical Trials;Collaborations;Congresses;Diagnosis;diagnostic development;Diagnostic Services;diagnostic technologies;Educational process of instructing;epidemiology study;Epilepsy;Europe;Faculty;Foundations;Funding;Future;Genomics;Grant;implementation science;Institution;Knowledge;knowledge base;Learning;Mentors;Mentorship;Nervous System Disorder;Neurologic;Nigeria;Nigerian;North America;Pediatric Neurology;Persons;Physicians;Population;Principal Investigator;programs;recruit;Research;research and development;Research Ethics;Research Institute;Research Personnel;Research Project Grants;Research Training;Scientist;Sister;skills;Solid;symposium;Syndrome;Teaching Hospitals;Time;treatment services;United States National Institutes of Health;Universities;Work;Writing

PROJECT_TITLE: Aminu Kano Teaching Hospital-Bayero University Kano-Vanderbilt: Developing Future Leaders in Child Neurology and Epilepsy Research (ABV)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-B(50)]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Estrogen;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunotherapy;Lung;Lung Cancer;Women's Health Research

ORG_CITY: RICHMOND

ORG_DEPT: GENETICS

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Contact PD/PI: Landry, Joseph W Narrative Statement This project is designed to address the problem of sex disparaties in NSCLC progression and treatment. Studies in both cell culture and tumor bearing animals will identify the contribution(s) of bioactive molecules, and differences in the immune system between males and females that can affect NSCLC growth and their response to therapies. Project Narrative Page 7

PI_NAMEs: LANDRY, JOSEPH WILLIAM (contact)

PROGRAM_OFFICER_NAME: WALLACE, TIFFANY A

PROJECT_TERMS: Address;Affect;American Cancer Society;Animals;anti-cancer;anti-PD-1;anti-PD-L1;anti-tumor immune response;Apoptotic;Biological;Biological Assay;Breast;cancer diagnosis;Cancer Model;cancer therapy;Carboplatin;Castration;Cell Culture Techniques;cell killing;Cells;Cellular Assay;Chemicals;chemotherapy;Clinic;Clinical;Colon;Color;Combination Drug Therapy;Complex;Data;design;Development;Diagnosis;Diet;Disease;Environment;Estrogens;FDA approved;Female;Flow Cytometry;Future;gain of function;Genetic;Genetic Predisposition to Disease;Gonadal Steroid Hormones;Growth;Human;human disease;Immune;Immune checkpoint inhibitor;Immune response;Immune system;Immunologic Stimulation;Immunotherapy;improved;improved outcome;in vivo;Incidence;Incubated;inhibitor;Innate Immune System;innovation;Kidney;Knowledge;Lewis Lung Carcinoma;Life Style;lifetime risk;Literature;loss of function;lung cancer cell;Lung Neoplasms;Macrophage;male;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Melanoma;men;Modeling;Monoclonal Antibodies;mortality;mouse development;Mus;Natural Killer Cells;Nature;neoplastic cell;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Operative Surgical Procedures;Outcome;Ovariectomy;Ovary;patient derived xenograft model;Pemetrexed;Pharmaceutical Preparations;Phenotype;Progesterone;Prognosis;receptor;response;Serum;sex;Sex Differences;sex disparity;Smoking;standard of care;Testing;Therapeutic;therapy outcome;Time;TNFSF10 gene;treatment response;tumor;tumor growth;tumor progression;tumor xenograft;United States;Woman;women versus men

PROJECT_TITLE: Development of Mouse and Humanized Models to Study Sex Disparities in Tumor Progression and Treatment of NSCLC

STUDY_SECTION: BMCD

STUDY_SECTION_NAME: Basic Mechanisms of Cancer Health Disparities Study Section[BMCD]


ADMINISTERING_IC: HD

ED_INST_TYPE: UNIVERSITY-WIDE

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

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Cardiovascular;Contraception/Reproduction;Hypertension;Immunization;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative G protein-coupled receptors (GPCR) are therapeutic targets for complications that arise during pregnancy, including the regulation of labor. This project investigates how antibodies can be leveraged as tools to study fine details of GPCR signaling. Antibodies may provide new avenues to therapeutically target GPCRs in situations where high receptor subtype selectivity, specific tissue distribution, or extended circulation times are indicated, such as preeclampsia and other hypertensive disorders of pregnancy, and in assisted reproduction.

PI_NAMEs: SKIBA, MEREDITH ANNE (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Advisory Committees;Agonist;Anti-Hypertensive Agents;Antibodies;antibody engineering;assisted reproduction;Autoantibody binding;B-Lymphocytes;beta-arrestin;Binding;Biological;Biological Assay;Biological Products;Biology;Birth;blood pressure reduction;Cell Separation;Cells;Circulation;clinically relevant;Committee Members;Complex;Cryoelectron Microscopy;desensitization;Development;Discipline of obstetrics;Disease;Drug or chemical Tissue Distribution;Epitopes;Exhibits;fetal;Fetal Death;Fetal health;Future;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;heart function;Hypertension;Immunoglobulin Fragments;improved outcome;In Vitro;in vivo;insight;Institution;Interdisciplinary Study;intravenous administration;Libraries;Ligand Binding;Ligands;Link;Maternal Health;Maternal Mortality;Mentorship;Methods;Molecular;Molecular Conformation;mouse model;Mus;nanobodies;Oxytocin Receptor;pathogenic autoantibodies;Pathogenicity;pathophysiology of preeclampsia;peptide drug;Peptides;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacology;Phase;Physiological;Physiological Processes;Placenta;Pre-Eclampsia;Pregnancy;pregnancy disorder;pregnancy related death;Premature Birth;programs;Property;Protein Engineering;receptor;Receptor Activation;receptor function;Receptor Signaling;Receptor, Angiotensin, Type 1;Recombinants;recruit;reduce symptoms;Regulation;Renal function;Reproductive Biology;Research;response;Sampling;Signal Pathway;Signal Transduction;skills;small molecule;Specificity;structural biology;Structure;synthetic antibodies;Therapeutic;Therapeutic Intervention;therapeutic target;tool;Training;Variant;Visualization;Work

PROJECT_TITLE: Employing biologics to probe GPCR signaling in maternal and fetal health

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Obstetrics and Maternal-Fetal Biology Study Section[CHHD-B]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Pediatric

ORG_CITY: OXFORD

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY OF OXFORD

ORG_ZIPCODE: OX1 2JD

PHR: PROJECT NARRATIVE Little is known about how genomic variants affect human brain development, brain function, and neuropsychiatric disorders. We propose a large-scale study to identify DNA variants and their effects on gene expression in brain tissue and single cells from the brain across human brain development. This will provide functional insight into the neurobiological processes responsible for human brain development and function, and disrupted in neuropsychiatric disorders.

PI_NAMEs: SANDERS, STEPHAN  (contact)

PROGRAM_OFFICER_NAME: PRICE, AMANDA JOY

PROJECT_TERMS: Adolescence;Adult;Affect;Age of Onset;Alleles;Alzheimer's Disease;autism spectrum disorder;Behavior;Biological;Bipolar Disorder;Brain;brain cell;Brain region;brain tissue;Cell Nucleus;cell type;Cells;Chromatin;Code;cohort;Communities;Complement;computerized tools;Copy Number Polymorphism;Corpus striatum structure;Data;data integration;Data Set;Databases;Development;Disease;disorder risk;DNA;epigenetic marker;Epigenetic Process;Etiology;Exhibits;experimental study;fetal;Fetal Development;functional genomics;Gene Expression;Gene Expression Profile;Gene Frequency;Generations;Genes;Genetic;genetic risk factor;genetic variant;genome sequencing;genome wide association study;genomic data;genomic locus;genomic variation;Genotype;histone modification;Human;Human Genome;Individual;insertion/deletion mutation;insight;Link;Methods;Neurobiology;neurodevelopment;Neurodevelopmental Disorder;neuropsychiatric disorder;Neurosciences;next generation;novel;Pattern;postnatal development;Prefrontal Cortex;prenatal;Prevalence;Process;Property;Proteins;Quantitative Trait Loci;rare variant;Regulatory Element;Resources;Risk;risk variant;RNA Splicing;Role;Sampling;Schizophrenia;sex;Single Nucleotide Polymorphism;single nucleus RNA-sequencing;Source;spatiotemporal;Specificity;Spliced Genes;System;Tissues;trait;transcriptome;transcriptome sequencing;transcriptomic profiling;Untranslated RNA;Validation;Variant;whole genome

PROJECT_TITLE: 2/2 - Identification and Validation of Expression Quantitative Trait Loci (eQTLs) in discrete cell types across human brain development


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: NEW YORK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE: Ribonucleases are enzymes that act on RNAs to process them to their mature, functional form, or to degrade them when they are no longer needed by the cell. A newly discovered ribonuclease in the model microorganism, Bacillus subtilis, is the prototype for a large family of similar proteins that are found in many bacterial organisms. Elucidating the structure and function of this ribonuclease could lead to the design of antibiotics that inhibit this enzyme and thereby reduce bacterial virulence.

PI_NAMEs: BECHHOFER, DAVID H (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 5'-exoribonuclease;Adaptor Signaling Protein;Affect;Affinity;Alanine;anti-microbial drug;antibiotic design;Awareness;Bacillus subtilis;Bacteria;Binding;Binding Proteins;Biochemical;Biological Assay;Biological Process;Biology;Biophysics;C-terminal;Catalysis;cell growth;Cells;Characteristics;Code;Coronavirus;design;endonuclease;Endoribonucleases;environmental change;Enzyme Inhibition;Enzymes;Escherichia coli;Exonuclease;experimental study;Family;Family member;follow-up;Gene Deletion;Genes;genome-wide;genomic RNA;Gram-Positive Bacteria;Homologous Gene;In Vitro;in vitro activity;in vivo;insight;Laboratories;Ligands;member;Messenger RNA;microorganism;model organism;Modeling;mRNA Decay;Mutagens;mutant;N-terminal;Names;novel;Nucleotides;Oligonucleotides;Organism;Outcome;Pancreatic ribonuclease;Physiological Processes;Play;poly A specific exoribonuclease;Polyribonucleotide Nucleotidyltransferase;Procedures;Process;Property;Protein Biochemistry;Protein Family;Proteins;prototype;Publishing;recruit;Regulation;Regulatory Element;Reporting;response;Ribonucleases;RNA;RNA Binding;RNA chemical synthesis;RNA Sequences;Role;SARS coronavirus;Sequence Homology;Small RNA;Specific qualifier value;Specificity;Structure;Tertiary Protein Structure;Testing;thermophilic organism;three dimensional structure;Transcript;Virulence;Work

PROJECT_TITLE: YloC, a new ribonuclease of Bacillus subtilis

STUDY_SECTION: PCMB

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative  Allosteric ligands have the potential to revolutionize cardiovascular therapeutics. In this proposal, we will develop novel ligands, identified through our recently performed screen of 1 billion unique chemical entities, to function as biased allosteric modulators for the β1AR as a new family of medicinal molecules for heart failure.

PI_NAMEs: ROCKMAN, HOWARD A (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Adrenergic beta-Antagonists;Adrenergic Receptor;Adverse effects;Agonist;antagonist;Area;beta-arrestin;Binding;Binding Sites;Biochemical;Biology;Biophysics;Cardiac;cardioprotection;Cardiovascular Diseases;Cardiovascular system;Catecholamines;Chemicals;Clinical;Development;DNA;Dose;drug development;experimental study;Family Practice;Fluorescence Spectroscopy;Fluorescent Probes;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;Heart failure;heart function;hemodynamics;Heterotrimeric GTP-Binding Proteins;Histologic;improved;in vivo;innovation;Ischemia;Knockout Mice;Label;Libraries;Ligand Binding;Ligands;Molecular Conformation;Mus;nanodisk;Norepinephrine;novel;Organic Chemistry;Outcome;Pathologic;Pathway interactions;pharmacologic;Phenotype;positive allosteric modulator;Property;receptor;Reperfusion Therapy;Research;Research Personnel;Rest;Second Messenger Systems;Signal Pathway;Signal Transduction;single molecule;Site;Specificity;Structure-Activity Relationship;Therapeutic;therapeutic target;Transducers;Translating;Work

PROJECT_TITLE: Mechanisms of Maladaptation in Heart Failure

STUDY_SECTION: MPPA

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


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Rehabilitation;Serious Mental Illness;Social Determinants of Health;Suicide

ORG_DEPT: PSYCHIATRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE  Social disconnection peaks in middle and late life and leads to an increased risk of suicide, persistent suicidality, and poor response to psychosocial interventions. There is a critical need to develop a mechanistic understanding of the link between social disconnection and suicidality, identify biological targets, and address targets with scalable interventions. We propose a novel psychotherapy, Engage & Connect, aimed to improve functions of the Positive Valence System (PVS) that are impaired in suicidality through increased engagement in rewarding social activities. Our proposal applies state-of-the-art precision imaging methods and a novel social reward task to evaluate circuitry and behavioral changes in the PVS during Engage & Connect. Findings will inform our understanding of the mechanisms underlying the link between social disconnection and suicidality during treatment and guide personalization of psychotherapy to target individuals’ biological and clinical profiles.

PI_NAMEs: SOLOMONOV, NILI  (contact)

PROGRAM_OFFICER_NAME: LYONS, ELIZABETH ANNE

PROJECT_TERMS: active control;Address;Adult;Age;age effect;aged;Aging;Anterior;Behavioral;Behavioral Mechanisms;Biological;Brain;brain based;brain circuitry;Brain Mapping;cingulate cortex;Clinical;Data;Depressed mood;design;Development;Dorsal;efficacious intervention;Feedback;Feeling suicidal;functional improvement;Functional Magnetic Resonance Imaging;Future;geriatric depression;Image;imaging approach;imaging modality;Impairment;improved;Individual;individual patient;innovation;Insula of Reil;Intervention;late life;Learning;Link;Magnetic Resonance Imaging;Major Depressive Disorder;Maps;Measures;Medial;Mediating;Mediation;men;Mental Depression;Methodology;middle age;neuroimaging;novel;Nucleus Accumbens;older adult;Participant;Pilot Projects;Play;Positive Valence;predicting response;Prediction of Response to Therapy;Prefrontal Cortex;Protocols documentation;psychoeducation;psychosocial;Psychotherapy;Randomized;Reaction Time;Recording of previous events;remote delivery;Reporting;response;Rest;reward processing;Rewards;Risk Factors;Role;serial imaging;sex;social;Social Interaction;Social isolation;Social support;Structure;Structure of superior frontal gyrus;suicidal;suicidal risk;Suicide;Suicide attempt;suicide rate;Symptoms;System;Testing;treatment effect;treatment response;Ventral Striatum;Woman

PROJECT_TITLE: Target Engagement During Social Reward Psychotherapy for Mid- and Late-Life Suicidality: A Precision Imaging Trial


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Immunotherapy;Patient Safety;Precision Medicine;Rural Health

ORG_CITY: Columbus

ORG_DEPT: SURGERY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The Early Therapeutics Clinical Network (ETCTN) at The Ohio State University (OSU) will identify new agents  with promising laboratory studies and develop them into new drugs for the treatment of patients with advanced  cancer who have exhausted their treatment options. Physicians, nurses and research coordinators will carefully  monitor patients receiving these drugs to make sure that they are safe. Patients will also undergo sampling of  their blood and have their tumors biopsied. These tissues will be analyzed by modern methods to determine the  levels of the new drug in the bloodstream and test whether they are having the predicted effect on the cancer  cells. The aim of the clinical study may be to simply determine if the drug can be given safely (phase I) and in  other instances the goal of the study will be to see whether the new drug or drug combination can shrink the  tumor and enable the patient to live longer. The consortium will consist of OSU, the University of Kentucky and the University of Utah in order to bring the evaluation of novel agents to three states with a high burden of cancer.

PI_NAMEs: ARNOLD, SUSANNE M;CARSON, WILLIAM E. (contact);GARRIDO-LAGUNA, IGNACIO

PROGRAM_OFFICER_NAME: IVY, S PERCY

PROJECT_TERMS: Advanced Malignant Neoplasm;American;Appalachian Region;Basic Science;Biomedical Research;Biopsy;Blood;Blood Circulation;Cancer Burden;cancer cell;Cancer Center;cancer clinical trial;Cancer Patient;cancer therapy;Cancer Therapy Evaluation Program;cancer type;career;career development;Catchment Area;Clinical;Clinical Investigator;Clinical Research;Clinical Trials;Clinical Trials Network;Collaborations;Comprehensive Cancer Center;Dedications;design;Development;Discipline;Dose;Drug Combinations;Drug Kinetics;Drug resistance;early phase clinical trial;Early Therapeutic-Clinical Trials Network;effective therapy;Enrollment;Ensure;Evaluation;exhaust;experience;Faculty;Funding;Future;genomic profiling;Goals;Grant;Hematologic Neoplasms;Hematology;Immunotherapy;innovation;Investigational Drugs;Investigational Therapies;Kentucky;Laboratories;Laboratory Study;Lead;Leadership;Letters;Malignant Neoplasms;member;Methods;Modality;Modernization;Molecular;Molecular Target;multidisciplinary;New Agents;novel;novel therapeutics;Nurses;Ohio;Oncologist;Oncology;Outcome;Pathway interactions;Patient Monitoring;Patient Selection;Patients;Pattern;Pharmaceutical Preparations;Pharmacodynamics;Pharmacogenomics;Pharmacology;Phase;Physicians;Population;Positioning Attribute;Preparation;prevent;programs;Reporting;Research;Research Personnel;Resistance;resistance mechanism;Resources;response;rural area;Sampling;Schedule;Science;Scientist;Site;skills;Solid Neoplasm;success;Surgeon;targeted treatment;Testing;Therapeutic;Therapeutic Agents;Therapeutic Studies;Tissues;Training;Training and Education;translational scientist;translational study;tumor;Underserved Population;Universities;Utah;Vocational Guidance

PROJECT_TITLE: The Ohio State University as a Lead Academic Organization (LAO) for the Experimental Therapeutics Clinical Trials Network


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative: This proposal seeks to investigate the extent, location, and mechanisms that give rise to new enteric neurons and glia, paving the way for a novel therapeutic strategy in congenital and acquired neuro-intestinal disease. This proposed research is relevant to public health because understanding the mechanisms by which the enteric nervous system responds to injury is expected to result in identification of biomarkers and potential targets for intervention. The proposed research is relevant to the NIH mission to develop fundamental knowledge that will enhance health, lengthen life, and reduce illness and disability; in particular, our research pertains to understanding the causes, diagnosis, prevention, and cure of human diseases.

PI_NAMEs: BELKIND-GERSON, JAIME  (contact);FRANK, DANIEL N

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Ablation;Address;Affect;Age;aged;Agonist;Anatomy;Animal Model;Antibiotics;Bacteria;Biological Assay;biomarker identification;Biopsy;Bromodeoxyuridine;Calcium;Cell Death;cell motility;Cell Physiology;Cell Proliferation;Cells;Cessation of life;Clinical;clinical application;Coculture Techniques;cohort;Colon;Complement;Complex;conditional knockout;density;Diagnosis;Diphtheria Toxin;disability;Disease;Dryness;Enteral;Enteric Nervous System;Esthesia;Excision;experimental study;fecal transplantation;Feces;gastrointestinal;Gastrointestinal Diseases;gastrointestinal function;Gastrointestinal Injury;Gastrointestinal Motility;Gastrointestinal tract structure;Germ-Free;Glial Differentiation;gliogenesis;gut microbiota;Health;host microbiome;Human;human disease;Human Microbiome;Image;improved;In Situ Nick-End Labeling;In Vitro;in vivo;Inflammation;Injury;injury recovery;innovation;Intervention;Intestinal Diseases;Intestinal permeability;Intestines;Knockout Mice;Knowledge;Kynurenine;Label;Life;Location;Malignant Neoplasms;Maps;mature animal;Measurement;Measures;Mediating;metabolomics;Metagenomics;Methods;microbiome;microbiota;Migrating Myoelectric Complex;Mission;Modeling;Motility;motility disorder;Motor;mouse model;Mucous Membrane;Mus;Myelin P0 Protein;Natural regeneration;Nerve;Nerve Regeneration;nerve stem cell;nerve supply;Nervous System Trauma;Neural Crest;neurogenesis;Neuroglia;Neuronal Injury;Neurons;novel;novel therapeutic intervention;Output;Pathway interactions;Patients;Permeability;postnatal;pre-clinical;prenatal;Prevention;Process;Proliferating;promoter;Public Health;Publishing;Quality of life;receptor;Recovery;Recovery of Function;Regenerative response;regenerative therapy;Reporter;Research;response;Role;Schwann Cells;Sensory Disorders;Serotonin;sex;Signal Transduction;Signaling Molecule;Solid;Source;Streptococcus sanguis;System;tegaserod;Testing;Therapeutic;Thick;transcriptomics;translational study;Tryptamines;United States National Institutes of Health;Work;Zebrafish

PROJECT_TITLE: Schwann Cell-derived neuro-gliogenesis

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Serious Mental Illness

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative: Chronic inflammation, especially in middle age, may contribute to impaired brain function in depression by promoting the synthesis and entry into the brain of toxic, intermediary molecules known as kynurenines. Reducing the entry of kynurenines into the brain may reverse their toxic effects on the brain and behavior in depressed patients, while ultimately preventing long term consequences including neurodegeneration and dementia. In this study, we will examine if blocking the entry of kynurenines into the brain with the amino acid leucine will reduce brain toxicity and improve depressive symptoms in patients with midlife depression and chronic inflammation.

PI_NAMEs: HAROON, EBRAHIM  (contact)

PROJECT_TERMS: Affinity;aged;Aging;aging brain;Agonist;Amino Acid Transport System L;Amino Acids;Anhedonia;antagonist;arm;Astrocytes;Basal Ganglia;Behavior;Behavior assessment;Behavioral;Bilateral;Biological Factors;Blood - brain barrier anatomy;Blood specimen;Body mass index;Brain;brain dysfunction;Brain region;C-reactive protein;Caring;Cerebrospinal Fluid;Chronic;Cognitive;cognitive testing;Corpus striatum structure;cytokine;Data;Dedications;Dementia;depressed patient;depressive behavior;depressive symptoms;design;disability;Distress;Dose;Double-Blind Method;drug development;Early Intervention;Elderly;Endotoxins;Enzymes;Equilibrium;Equipment and supply inventories;Excitatory Neurotoxins;excitotoxicity;Expenditure;Fiber;frailty;Functional disorder;Functional Magnetic Resonance Imaging;functional MRI scan;Glutamates;Goals;Herpes Labialis;Human;human old age (65+);immune activation;improved;indexing;Infection;Inflammation;Inflammation Mediators;Inflammatory;inflammatory milieu;Inositol;instrument;Knowledge;Kynurenic Acid;Kynurenine;late life;Leucine;Ligands;Lysine;Magnetic Resonance Spectroscopy;Major Depressive Disorder;Measures;Mediator;Mental Depression;Metabolism;Microglia;middle age;N-Methylaspartate;Nature;Nerve Degeneration;neural circuit;neurocognitive test;neuron loss;Neuronal Dysfunction;Neurons;new therapeutic target;novel;Outcome;Oxidative Stress;Oxygen;Pathologic Processes;Pathology;Pathway interactions;Patient Self-Report;Patients;Peripheral;peripheral blood;Pharmaceutical Preparations;Plasma;pleasure;power analysis;pre-clinical;Pre-Clinical Model;preclinical study;Prefrontal Cortex;prevent;primary outcome;Procedures;Production;prospective;Proxy;Publishing;Quinolinic Acid;Randomized;recruit;Research Design;Rest;Rewards;Rodent;Safety;Sampling;secondary outcome;Source;Standardization;Suicide;targeted agent;Testing;Time;Tissues;Toxic effect;Translating;transmission process;Treatment outcome;treatment response;Tryptophan 2,3 Dioxygenase

PROJECT_TITLE: Leucine as a Probe of Kynurenine-Induced Glutamate and Neural Circuit Dysfunction in Midlife Depression

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE We will use studies in patient samples and in innovative preclinical models to delineate how clonal evolution contributes to malignancy and to the response to cancer therapies. We will model clonal evolution using novel in vivo preclinical models and perform functional studies to delineate the key networks and targets which govern malignancy. This work will delineate how mutational evolution contributes to cancer initiation and progression and use these insights to identify novel therapeutic targets which can intercept/prevent or attenuate malignancy.

PI_NAMEs: LEVINE, ROSS L (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Attenuated;cancer initiation;cancer therapy;Cell Compartmentation;cell type;Cells;Clinical;Clonal Evolution;Clonal Expansion;Dependence;Development;Epigenetic Process;Evolution;functional genomics;gene network;Genomic approach;Hematopoiesis;Homeostasis;in vivo;innovation;insight;Intercept;leukemic transformation;Malignant - descriptor;Malignant Neoplasms;Modeling;Mutation;new therapeutic target;novel;novel therapeutics;Patients;Pre-Clinical Model;prevent;response;Role;Sampling;Signal Transduction;Somatic Mutation;Therapeutic;therapeutic gene;Tissues;tool;treatment response;tumor progression;Work

PROJECT_TITLE: Synergistic role of signaling and epigenetics in leukemic transformation


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Machine Learning and Artificial Intelligence;Major Depressive Disorder;Mental Health;Neurosciences;Sleep Research

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: Project Narrative Hypersomnolence is the most common symptom encountered in the practice of sleep medicine, with population-based prevalence of hypersomnolence disorder estimates of 1.5% and large socioeconomical impact. The biophysical causes of hypersomnolence and how it reflects on sleep brain dynamics are not known, resulting in the absence of robust electrophysiological diagnostic criteria. Here we will leverage a highly specific hypersomnia dataset and advanced analytical techniques to identify biomarkers of hypersomnolence in the space-time dynamics of sleep oscillations.

PI_NAMEs: MALERBA, PAOLA  (contact)

PROGRAM_OFFICER_NAME: BROWN, MARISHKA

PROJECT_TERMS: Acceleration;Address;Adult;advanced analytics;Anxiety;Articulation;Behavior assessment;Behavioral;Biological Markers;biomarker identification;biophysical properties;Biophysics;Brain;Central Nervous System;Characteristics;Classification;Clinical;Cognition;Cognitive;common symptom;comorbidity;Complex;Control Groups;Data;Data Set;density;Detection;Diagnostic;diagnostic criteria;Disease;Disorders of Excessive Somnolence;economic impact;Electrodes;Electroencephalography;Electrophysiology (science);Elements;Event;Excessive Daytime Sleepiness;follow-up;Frequencies;Future;Health;Homeostasis;Hypersomnias;Hypersomnolence;improved;Individual;insight;Intervention;Investigation;Linear Models;Link;Machine Learning;machine learning classification;Major Depressive Disorder;Measures;Medical;Medicine;memory consolidation;memory process;Mental Depression;Methodology;neural;Neuropsychology;non rapid eye movement;Obstructive Sleep Apnea;Outcome Assessment;Parietal;Participant;Pattern;Persons;Phenotype;Physiological;Population;population based;potential biomarker;Prevalence;Process;Property;Quality of life;Research;Role;Scalp structure;Sleep;Sleep Fragmentations;sleep pattern;socioeconomics;Statistical Study;Symptoms;Techniques;Testing;Therapeutic;Time;Work

PROJECT_TITLE: The space-time organization of sleep oscillations as potential biomarker for hypersomnolence

STUDY_SECTION: BNRS

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


NIH_SPENDING_CATS: Aging;Hematology;Neurosciences;Pain Research;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MADISON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Aging of hematopoietic stem cells (HSCs) contributes to age-related blood diseases such as clonal hematopoiesis, myelodysplastic syndromes or acute myeloid leukemia, however, whether the aged bone marrow microenvironment drives the aging of HSCs and age-related hematologic diseases and the underlying mechanisms, remain unclear. Our preliminary data suggest that nociceptive innervation in the bone marrow is essential for controlling HSC aging, and that aged bone marrow microenvironment promotes the clonal expansion of genetically mutated HSCs over wildtype HSCs. The proposed studies will shed new light on the contributions of the aged microenvironment on HSC function, and will help to devise new therapeutic strategies to prevent or improve the course of age-associated hematologic diseases.

PI_NAMEs: GAO, XIN  (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Acute Myelocytic Leukemia;Affect;age related;aged;Aging;aging process;aging related;Attenuated;Blood Cells;Blood Vessels;bone aging;Bone Marrow;Bone Marrow Cells;Calcitonin Gene-Related Peptide;Capsaicin;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Chili Pepper;Chimera organism;Clonal Expansion;Codon Nucleotides;Complex;Data;drivers of aging;Dysmyelopoietic Syndromes;Endothelial Cells;Equilibrium;Fiber;Food;Frameshift Mutation;Goals;Granulocyte Colony-Stimulating Factor;Hematological Disease;Hematopoiesis;hematopoietic stem cell aging;hematopoietic stem cell expansion;Hematopoietic Stem Cell Mobilization;hematopoietic stem cell niche;Hematopoietic stem cells;improved;Inflammation;Ingestion;innovation;Lead;Lymphoid;Marrow;Mediating;migration;Molecular;multidisciplinary;Mus;mutant;Mutate;Mutation;Myelogenous;Nature;Nerve;nerve supply;Nervous System;Neuropeptides;Nociception;Nociceptors;normal aging;novel;novel strategies;novel therapeutic intervention;old mice;Peptide Signal Sequences;Pharmaceutical Preparations;Phenotype;Premature aging syndrome;prevent;Proliferating;Protein Analysis;Regulation;Rejuvenation;RNA analysis;Role;self-renewal;senescence;senolytics;Somatic Mutation;Sorting;stem cell function;Stromal Cells;Sympathectomy;Technology;Testing;Time;Transplant Recipients;Transplantation

PROJECT_TITLE: Regulation and function of aged hematopoietic stem cell (HSC) niche

STUDY_SECTION: DDK

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

PHR: PROJECT NARRATIVE Plasmodium falciparum antigenic diversity is a major obstacle to vaccine development and contributes to the low observed efficacy in Phase III trials of the first licensed malaria vaccine. In this study, we propose to leverage our high resolution epidemiological and entomological longitudinal cohort, coupled with cutting edge human and parasite genetic techniques, to observe discrete, multi-strain transmission events and record strain-specific and strain-transcendent immune responses associated with protection. By elucidating a minimum set of antigenic variants able to confer robust, strain-transcendent protection, we will facilitate the development and delivery of the next generation of P. falciparum vaccines.

PI_NAMEs: PRUDHOMMEOMEARA, WENDY  (contact);TAYLOR, STEVE MYER

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: adaptive immunity;Africa;Antibodies;Antigenic Diversity;Antigens;Apical;Back;Bite;Blood;Cessation of life;circumsporozoite protein;Classification;cohort;Cohort Studies;community transmission;Coupled;Coupling;Culicidae;cytokine;Data;Development;Disease;Enrollment;Epidemiology;epidemiology study;Event;Exhibits;Exposure to;Falciparum Malaria;Flow Cytometry;Genetic;Genetic Techniques;Genotype;Goals;Helper-Inducer T-Lymphocyte;Household;Human;Immune;Immune response;Immunity;immunogenic;Individual;Infection;Infection Control;insight;Integration Host Factors;Kenya;Licensing;Longitudinal cohort;Longitudinal Studies;Malaria;malaria infection;malaria transmission;Malaria Vaccines;Measurement;Measures;member;Memory B-Lymphocyte;Modeling;next generation;novel;novel vaccines;Observational epidemiology;Outcome;Parasites;Peptides;Persons;phase III trial;Phenotype;Plasmodium falciparum;Population;population based;Positioning Attribute;Productivity;Proteins;Recording of previous events;Resolution;response;Risk;Sampling;Shapes;Sporozoites;Subunit Vaccines;Symptoms;System;Testing;Transcend;transmission process;vaccine candidate;Vaccine Design;vaccine development;vaccine effectiveness;vaccine immunogenicity;Vaccines;Variant;Work

PROJECT_TITLE: Once Bitten: Acquisition of Malaria Adaptive Immunity (OBAMA - Immunity)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-U(02)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Emerging Infectious Diseases;Genetics;Infectious Diseases;Prevention

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: There is an urgent need to curb the emergence of novel SARS-CoV-2 variants. This proposal will provide insights into the frequency, risk factors, clinical presentations and viral features of persistent SARS-CoV-2 infections using an integrated research approach combining virology, immunology, bioinformatics, and genomics. This knowledge will allow the implementation of strategies suitable to prevent prolonged SARS-CoV-2 replication and limit the spread of neutralization-resistant viral variants in vulnerable patients.

PI_NAMEs: SIMON, VIVIANA A (contact);VAN BAKEL, HARM

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: 2019-nCoV;3-Dimensional;Acceleration;Accounting;acute infection;Address;Age;antagonist;Anti-viral Agents;Antibodies;Area;B-Lymphocytes;Back;betacoronavirus;Bioinformatics;Biological;Biological Assay;Biological Models;Blood;Case Study;Characteristics;Chronic;chronic infection;Clinical;Clinical Treatment;cohort;Collaborations;Communicable Diseases;Computerized Medical Record;COVID-19;COVID-19 detection;COVID-19 pandemic;COVID-19 patient;Data;Data Set;demographics;Dimensions;electronic data;Environment;Epithelium;Evolution;fitness;Flow Cytometry;Frequencies;Funding;Gender;General Population;Genetic Complementation Test;Genetic Recombination;Genomics;Genotype;global health;Grant;Haplotypes;Health system;Hospitals;Human;Immune;Immune Evasion;Immune response;Immunocompromised Host;Immunologics;Immunology;Individual;Infection;insight;Interferons;Knowledge;Link;Malignant Neoplasms;Maps;Medical Records;Metadata;metropolitan;Minority;Molecular;Molecular Virology;multidisciplinary;Mutation;nasopharyngeal swab;New York City;novel;pandemic disease;pathogen;Pathogenicity;Pathology;patient subsets;Patients;Peer Review;Phenotype;Physicians;Population;Positioning Attribute;Predisposition;pressure;prevent;Process;Prone Position;Property;Proteins;public health emergency;Publications;Recovery;Research;Research Personnel;Resistance;Resolution;Resources;Risk Factors;risk mitigation;RNA;Role;Sampling;SARS-CoV-2 infection;SARS-CoV-2 variant;Scientist;Serum;surveillance data;Surveillance Program;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;Translational Research;transmission process;Vaccination;Variant;variants of concern;Viral;viral genomics;virology;Virus;Work

PROJECT_TITLE: Dissecting the drivers of persistent SARS-CoV-2 infections

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VDT-Q(01)]


ORG_CITY: MILWAUKEE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: PROJECT NARRATIVE Regenerative treatments for patients suffering from heart failure could be enabled by comprehensive understanding of the cellular factors that facilitate successful cardiomyocyte regeneration. Here, we investigate the role of two proteins, Llgl1 and Shroom3, that influence establishment of proper cytoarchitecture and cell-cell junctions in CMs. The proposed studies will provide critical insight into the cellular mechanisms by which cardiomyocytes can enter a regenerative state and then re-integrate and contribute to a functional myocardium.

PI_NAMEs: LINK, BRIAN A;O'MEARA, CAITLIN C (contact)

PROJECT_TERMS: Actins;Adult;Amputation;Automobile Driving;Binding Proteins;Cardiac;Cardiac Death;Cardiac Myocytes;cardiac regeneration;cardiac repair;cardiogenesis;Cell Culture Techniques;Cell Cycle;Cell Shape;Cells;Cellular Morphology;Cellular Structures;Cessation of life;Complex;Cues;Cytokinesis;Cytoskeletal Proteins;Cytoskeleton;Development;Disease;Embryo;falls;Functional Regeneration;Genes;Genetic;Heart;Heart failure;heart function;Heart Injuries;Hypertrophy;Impairment;Injury;insight;Intercalated disc;Intercellular Junctions;interest;Ischemia;Lower Organism;Mammals;Mediating;Modeling;Morphogenesis;mouse model;Mus;Muscle;mutant;Myocardial dysfunction;myocardial injury;Myocardium;Natural regeneration;Neonatal;neonatal mice;novel;Nuclear;Pathway interactions;Patients;Phenotype;Phosphorylation;Phosphotransferases;Physiological;Proliferating;Proteins;Rationalization;Recovery of Function;regenerative;regenerative approach;Regenerative response;regenerative treatment;Regulation;repaired;Reporting;response;response to injury;Role;Signal Pathway;Signal Transduction;Stress;Structural Protein;Structure;Testing;Therapeutic;transcription factor;Transgenic Mice;Zebrafish

PROJECT_TITLE: Modulators of cardiomyocyte structure to promote functional recovery during cardiac regeneration and repair

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


NIH_SPENDING_CATS: Hematology;Nutrition;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE The sum of cell fate decisions for all of organism’s hematopoietic stem cells (HSCs), together with the lineage specifications of progenitor/precursor cells, determines the quality and quantity of its hematopoietic activity. Increasing evidence has shown that cellular metabolisms play important roles in HSC self-renewal, but precisely how specific modes of metabolism steer HSC fate remains unclear. This project utilizes genetic models, metabolic assessments, and single-cell approaches to elucidate the metabolic cues coordinating HSC fate decisions, with a focus on lipid metabolism. The resulting insights into the metabolic requirements of hematopoietic homeostasis will have a major impact on HSC research as well as current clinical practice and the treatment of hematological diseases.

PI_NAMEs: ITO, KEISUKE  (contact)

PROJECT_TERMS: Acetyl Coenzyme A;Address;Affect;Animals;aspirate;Behavior;bioinformatics tool;Biosensor;Bone Marrow;Cell division;Cells;Cellular Assay;Cholesterol;cholesterol biosynthesis;citrate carrier;Clinical;clinical practice;cofactor;cohort;Consumption;Cues;Cytosol;Data;Daughter;daughter cell;Defect;Development;Environmental Risk Factor;Enzymes;Equilibrium;Event;Exhibits;fatty acid metabolism;fatty acid oxidation;Fatty Acids;fluorescence lifetime imaging;Gene Expression;Genes;Genetic;Genetic Models;Glycolysis;Goals;Hematological Disease;Hematopoietic;hematopoietic stem cell fate;Hematopoietic Stem Cell Research;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Homeostasis;Image;image guided;Impairment;improved;In Vitro;in vivo;Individual;innovation;insight;lipid metabolism;Maintenance;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;migration;Mitochondria;Mitochondrial Inheritance;mitochondrial metabolism;Mitosis;Monitor;Mothers;mouse model;Mus;NADH;NADP;Natural graphite;novel therapeutic intervention;Optics;Organism;Outcome;Oxidases;oxidation;Pathway interactions;pharmacologic;Play;Population;precursor cell;Process;Production;Reaction;reconstitution;Research;Role;segregation;self-renewal;Serum;Sister;stem cell division;stem cell fate specification;stem cell function;stem cell homeostasis;Sterols;Sum;System;Techniques;Testing;Transplantation;Work

PROJECT_TITLE: The Roles of Lipid Metabolism in the Maintenance of Hematopoietic Stem Cells


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases

PHR: PROJECT NARRATIVE Listeria monocytogenes is a model intracellular bacterial pathogen that uses actin-based motility to spread cell to cell and disseminate within the host. During intracellular infection, bacteria form long pseudopodia-like protrusions that extend from the infected cell and are taken up by neighboring host cells, facilitating direct cell- to-cell spread. The focus of the proposed studies is to determine the spatiotemporal requirement of Abi1, a host cell protein that localizes to L. monocytogenes-induced protrusions, for protrusion formation and cell-to- cell spread.

PI_NAMEs: HIGGINS, DARREN E (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Actins;Affect;Architecture;Bacteria;Bacterial Proteins;Cell Line;Cell membrane;Cell Proliferation;Cell Separation;Cells;Cerebral endothelium;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;conditional knockout;Confocal Microscopy;Cytoskeletal Modeling;Cytoskeleton;Cytosol;Data;Disease;domain mapping;Elderly;Electron Microscopy;Epidermal Growth Factor Receptor;Epithelial Cells;Filopodia;Fluorescence Microscopy;foodborne pathogen;Generations;Genes;Goals;Green Fluorescent Proteins;HepG2;Human;Immunocompromised Host;Immunofluorescence Immunologic;Immunofluorescence Microscopy;In Situ;Individual;Infection;insight;Integration Host Factors;knock-down;Knock-out;Knockout Mice;Knowledge;Length;Life;Listeria monocytogenes;Listeriosis;live cell imaging;Mass Spectrum Analysis;Modeling;monocyte;Morphology;mortality;Motility;Newborn Infant;non-tuberculosis mycobacteria;Pathogenesis;pathogenic bacteria;Pathogenicity;Persons;Phase;Phosphotransferases;Plaque Assay;Plasma Cells;pregnant;Primary carcinoma of the liver cells;Process;profilin;Proteins;Proteomics;Pseudopodia;Public Health;Receptor Signaling;Regulation;Resolution;RNA Interference;Role;Shigella flexneri;Small Interfering RNA;spatiotemporal;Tail;Time;Transmission Electron Microscopy;uptake;Variant

PROJECT_TITLE: Spatiotemporal Regulation of Protrusion Dynamics During Intracellular Bacterial Dissemination

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-K(90)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: Project Narrative Retinoblastoma is an eye cancer that forms in the developing retina of young children; it is unique in that it cannot be directly biopsied, making tumor tissue unavailable. As a result, there is a lack of understanding of the association between the clinical behavior of this cancer and the mechanisms that drive its behavior. Thus, we propose to use a liquid biopsy of the eye aqueous humor for molecular characterization and prognostic biomarker validation of this cancer to help the design of future clinical trials.

PI_NAMEs: BERRY, JESSE L (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Affect;Age;Aqueous Humor;Award;Behavior;Biological Assay;Biological Markers;biomarker identification;biomarker validation;Biopsy;Blindness;cancer biomarkers;cancer risk;candidate marker;cell free DNA;chemotherapy;Child;Childhood;chromosome 6p gain;Clinical;clinical examination;Clinical Trials;clinically relevant;Collaborations;Communication;design;Detection;Diagnosis;Disease;disease diagnosis;disease prognosis;DNA Methylation;DNA methylation profiling;DNA Sequence Alteration;Early Diagnosis;Epigenetic Process;epigenomics;Evaluation;Excision;Eye;Eye Enucleation;Future;Genetic;genome sequencing;genome-wide;genomic biomarker;Genomics;Goals;Grouping;high risk;in vivo;Injections;Knowledge;Laboratories;liquid biopsy;Logistic Regressions;malignant neoplasm of eye;Malignant Neoplasms;Measures;Methylation;Modality;Modeling;Modification;Molecular;molecular diagnostics;molecular subtypes;Monitor;multimodality;multiple omics;Mutation;MYCN gene;Nature;North America;novel;Operative Surgical Procedures;Outcome;participant enrollment;Pathogenicity;Patients;personalized medicine;Positioning Attribute;precision medicine;precision medicine clinical trials;Prediction of Response to Therapy;Prognosis;prognostic;Prognostic Factor;Prognostic Marker;prognostication;prospective;Prospective Studies;RB1 gene;Recurrence;Relapse;relapse risk;Research;Residual state;Retina;Retinoblastoma;Risk;Risk Marker;Sampling;Source;Specimen;targeted sequencing;Testing;therapeutic target;Time;Treatment Failure;Treatment outcome;treatment response;treatment risk;tumor;tumor behavior;tumor DNA;Tumor Markers;Tumor Subtype;Tumor Suppressor Genes;Tumor Tissue;Tumor-Derived;tumorigenesis;Validation;Variant;whole genome

PROJECT_TITLE: Validation of an aqueous humor liquid biopsy for molecular prognostication and monitoring of children with retinoblastoma.

STUDY_SECTION: MCDC

STUDY_SECTION_NAME: Molecular Cancer Diagnosis and Classification Study Section[MCDC]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Hepatitis;Liver Disease

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: NARRATIVE There is a strong need to develop novel strategies for identifying biomarkers that help distinguish serious liver disease from mild disfunction. In this project, our team will develop novel instrumentation and methodologies for identifying biomarkers of liver disease.

PI_NAMEs: REVZIN, ALEXANDER  (contact);SCHWEIKERT, EMILE ALFRED

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Antibodies;Biological Markers;biomarker identification;Blood;Cells;Circulation;Clinical;detection sensitivity;Development;Diagnosis;Disease;Disease Progression;Early Diagnosis;extracellular vesicles;Fatty Liver;Fibrosis;Functional disorder;Future;Hand;Harvest;Hepatocyte;Inflammation;instrumentation;Label;lipidomics;Lipids;Liver;liver biopsy;Liver Cirrhosis;Liver diseases;liver injury;Maintenance;Malignant neoplasm of liver;Mass Spectrum Analysis;Methodology;Microfluidic Microchips;Microfluidics;Monitor;neural network;new technology;non-alcoholic fatty liver;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel strategies;Organ;Patient Care;patient stratification;Patients;peripheral blood;Physiological;Plasma;Populations at Risk;Proteins;Proteomics;Protocols documentation;Risk;risk stratification;Sampling;screening;Signal Transduction;Spectrometry, Mass, Secondary Ion;Surface;Technology;Testing;Time;timeline;Tissues;Training;transmission process;treatment response;United States;vesicular release

PROJECT_TITLE: Mass spectrometry for highly sensitive and sample-sparing analysis of extracellular vesicles in liver diseases


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Cardiovascular;Coronaviruses;Emerging Infectious Diseases;Heart Disease;Immunotherapy;Infectious Diseases;Lung;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CLEMSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: PUBLIC HEALTH RELEVANCE: Cardiac injury is a common COVID-19 induced complication. The goal for the proposed research is to develop an in vitro 3D myocarditis model to simulate hyperinflammation in COVID-19 hearts for fundamental investigations and drug testing.

PI_NAMEs: MEI, YING  (contact)

PROGRAM_OFFICER_NAME: THAKAR, RAHUL GAUTAM

PROJECT_TERMS: 3-Dimensional;Actinin;Acute;acute COVID-19;Adult;Autopsy;Biopsy;Calcium;Cardiac;Cardiac Myocytes;Cells;Circulation;Clinical;Coculture Techniques;comparative;Complication;COVID-19;COVID-19 cytokine storm;COVID-19 impact;COVID-19 patient;cytokine;cytokine release syndrome;Data;disease model;Dissociation;drug testing;Endothelial Cells;Exclusion;experimental study;fabrication;Fibroblasts;follow-up;Foundations;Goals;Harvest;Heart;Heart Diseases;Heart Injuries;Hospitalization;Human;human model;human pluripotent stem cell;Hyperactivity;Immune;immune cell infiltrate;immune modulating agents;Immune system;In Vitro;Infiltration;Inflammation;Inflammatory;innovation;insight;Interleukins;Investigation;Lung;Macrophage;Metabolic;migration;Modeling;monocyte;Morbidity - disease rate;mortality;Myocarditis;Myocardium;Netherlands;Organ;Organoids;Patients;PECAM1 gene;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Phenotype;public health relevance;recruit;Research;Risk;Role;Sampling;Serum;severe COVID-19;Stains;Stimulus;Stromal Cells;Structure;Time;Tissues;transcriptome;transcriptome sequencing;Vascular Endothelium;Vimentin;viral RNA;VWF gene

PROJECT_TITLE: Human organoid model for COVID-19 myocarditis


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Cardiovascular;Clinical Research;Data Science;Heart Disease;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention

PHR: NARRATIVE. Intradialytic hypotension and cardiac events are common in patients on maintenance hemodialysis and accurate prediction remains a challenge; leading to under-utilization of therapies. Electrocardiograms have rich waveform data and including them in predictive models can improve accuracy and clinical actionability. In this proposal, we examine the utility of deep and transfer learning using electrocardiogram waveform data for prediction of key cardiac outcomes in patients on hemodialysis, which will lead to new paradigms in clinical management of this vulnerable population.

PI_NAMEs: CHARYTAN, DAVID M;DIVERS, JASMIN ;NADKARNI, GIRISH NITIN (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Adrenergic beta-Antagonists;advanced analytics;adverse outcome;Affect;Blood Pressure;Cardiac;Cardiac Output;Cardiology;Cardiovascular system;Cause of Death;Clinical;Clinical Data;Clinical Management;clinically actionable;convolutional neural network;Data;Databases;deep learning;Derivation procedure;Detection;Development;Diagnosis;Dialysis procedure;Early Diagnosis;Early identification;Electrocardiogram;End stage renal failure;Event;follow-up;Functional disorder;Goals;Health;Heart Diseases;Heart failure;heart function;Heart Rate;Hemodialysis;high risk;Hospitalization;Hospitals;Human Resources;Hypotension;Impairment;improved;improved outcome;Incidence;inhibitor;insight;Institution;Intervention;Lead;Left;Left Ventricular Ejection Fraction;Link;Maintenance;Midodrine;Modeling;Monitor;Morbidity - disease rate;mortality;Myocardial;Myocardial dysfunction;Myocardial Infarction;Myocardial Stunning;New York City;North Carolina;novel;Outcome;outcome prediction;Participant;patient population;Patients;Performance;Pharmaceutical Preparations;Physicians;Population;pre-trained model;predictive modeling;Prevention;prognostication;prophylactic;prospective;Prospective Studies;Publishing;recruit;recurrent neural network;Reflex action;Risk;risk prediction;risk prediction model;Sample Size;secondary outcome;side effect;structured data;Techniques;Testing;Therapeutic;Training;transfer learning;Ultrafiltration;Validation;Visit;Vulnerable Populations;wearable device;Work

PROJECT_TITLE: Deep learning on ECGs to improve outcomes in patients on dialysis

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Atherosclerotic cardiovascular disease (CVD) is reaching epidemic proportions throughout the world and is a major burden to healthcare systems and societies worldwide. The objective of this proposal is to explore the novel hypothesis that geranylgeranyl isoprenoids and hepatic Rap1a regulate plasma low-density lipoprotein levels and contributes to the CVD development. Successful completion of these studies will reveal a new mechanism involved in the regulation of cholesterol homeostasis and may offer new therapeutic targets for hyperlipidemia-driven CVD.

PI_NAMEs: OZCAN, LALE  (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Acute;Antibodies;apolipoprotein E-3;Arterial Fatty Streak;Atherosclerosis;Attenuated;Back;Binding;Biochemical;blood glucose regulation;Cardiometabolic Disease;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular disorder therapy;Cause of Death;CETP gene;Cholesterol;Cholesterol Homeostasis;Clinic;Data;Development;Diabetic mouse;Dose;Drug Prescriptions;Epidemic;Etiology;Event;gain of function;geranylgeranyl pyrophosphate;geranylgeranylation;Glucagon Receptor;Glucose Intolerance;glucose production;Goals;Healthcare Systems;Hepatic;Hepatocyte;Human;Hyperlipidemia;improved;in vivo;inhibitor;insight;Insulin Resistance;isoprenoid;Knockout Mice;Laboratories;LDL Cholesterol Lipoproteins;Lesion;Link;Liver;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Mediating;Messenger RNA;Modeling;Molecular;Monomeric GTP-Binding Proteins;mouse genetics;mouse model;Mus;mutant;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Physiological;Physiology;Plasma;pleiotropism;Post-Transcriptional Regulation;prenylation;preservation;prevent;Prevention;Proprotein Convertase 1;Proprotein Convertases;Proteins;Proteomics;RAS Superfamily Proteins;Regulation;Reporting;Residual state;restoration;Role;Serum;small molecule;Societies;Specificity;Subtilisins;targeted treatment;Testing;Therapeutic;therapeutic target;Work

PROJECT_TITLE: Hepatic Rap1a in cholesterol homeostasis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Diabetes;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Tuberculosis

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: Project Narrative Diabetes is the second leading cause of deaths after TB in South Africa and increases the risk of developing TB. The functions of IGF-1 in metabolism, genetics, and immunity in TB and TB/T2DM has not been studies comprehensively. Using advanced training in immunometabolism and immunogenetics this project will define the associations of IGF-1/IGF-1R in patients and assess an IGF-1R inhibitor as adjunctive therapy in vivo, to enhance our understanding of IGF-1 signaling in TB, T2DM and TB/T2DM comorbidity.

PI_NAMEs: PARIHAR, SURAJ P. (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Ablation;Address;Africa;Alternative Therapies;Automobile Driving;Award;biobank;Bioinformatics;Biological Markers;blood glucose regulation;C3HeB/FeJ Mouse;career development;Cause of Death;Cells;Chronic;Clinical;Clinical Data;Clinical Research;cohort;Collaborations;Communities;comorbidity;cytokine;Data;Data Set;Development;Development Plans;Diabetes Mellitus;Diagnostic;diet-induced obesity;Disease;disorder risk;Exhibits;Flow Cytometry;Functional disorder;Genes;Genetic;Genetic Polymorphism;genetic variant;genomic locus;global health;Growth;Health Priorities;Hepatocyte;HIV;Human;Human Genetics;IGF1R gene;Immune;Immune response;Immune Sera;Immune Targeting;Immunity;Immunogenetics;Immunologist;improved;in vivo;Incidence;India;Individual;Inflammasome;Inflammation;Inflammatory;inhibitor;Innate Immune Response;Innate Immune System;innovation;Innovative Therapy;insight;insulin regulation;Insulin-Like Growth Factor I;Interleukin-4;Life;Link;low and middle-income countries;lung lesion;Macrophage;Mediating;Mentors;Mentorship;Metabolic;metabolic abnormality assessment;Metabolic Diseases;metabolic profile;Metabolism;Modeling;monocyte;mortality;mouse model;Mycobacterium tuberculosis;Newly Diagnosed;Non-Insulin-Dependent Diabetes Mellitus;novel;Outcome;Pathogenesis;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;Play;Positioning Attribute;Predisposition;programs;Public Health;Published Database;Publishing;Pulmonary Tuberculosis;Quality of life;Quantitative Trait Loci;Regulation;repository;Research;Research Support;Resistance;Resources;response;Risk;Role;Sampling;Serum;Signal Pathway;Signal Transduction;skills;Smooth Muscle Myocytes;South Africa;Structure;targeted treatment;Testing;Therapeutic;Time;Training;transcriptomics;Tuberculosis;Universities;Vascular Endothelium;Work

PROJECT_TITLE: Insulin-like Growth Factor-1 (IGF-1) signalling in immunometabolism of TB and TB-Diabetes comorbidity

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


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Hypertension;Infectious Diseases;Prevention

ORG_CITY: ELDORET

ORG_COUNTRY: KENYA

ORG_FIPS: KE

ORG_NAME: MOI UNIVERSITY COLLEGE OF HEALTH SCIENCES

PHR: PROJECT NARRATIVE OALWH with hypertension have an increased risk of cardiovascular morbidity and mortality due to suboptimal adherence to HTN medication. There is a critical need to develop interventions that promote patient- centeredness, improves HTN medication adherence and reduce CVD risks. This project will design, pilot and evaluate a community-based medication adherence support for OALWH with HTN.

PI_NAMEs: KIPLAGAT, JEPCHIRCHIR  (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Achievement;Acute myocardial infarction;Address;Adherence;Adverse effects;Africa South of the Sahara;Age;aged;Aging;Agreement;Anti-Hypertensive Agents;antiretroviral therapy;Blood Pressure;blood pressure control;budget impact;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;career development;Caring;Chronic;Chronic Disease;Clinical Trials;cognitive function;Communities;Community Health;comorbidity;Complex;Consolidated Framework for Implementation Research;cost;cost effective;Coupled;Data;design;differences in access;Disease;Doctor of Philosophy;economic evaluation;Evaluation;Event;evidence base;experience;Fellowship;Focus Groups;Funding;General Population;Goals;Health;Health behavior;health care availability;HIV;HIV Infections;Home visitation;human centered design;hybrid type 2 trial;Hypertension;hypertension control;implementation outcomes;implementation research;implementation science;improved;Individual;International;Intervention;iterative design;Kenya;Knowledge;Life Expectancy;low and middle-income countries;medication compliance;Mentors;Metabolic Diseases;Modeling;Morbidity - disease rate;mortality;Myocardial Infarction;Neurocognitive Deficit;novel;older adult;Outcome;Outcomes Research;patient oriented;Persons;Pharmaceutical Economics;Pharmaceutical Preparations;Pharmacists;Phase;pill;Polypharmacy;Population;post intervention;primary outcome;Process;Public Health;Qualifying;Research;Research Infrastructure;Research Personnel;Risk;Risk Reduction;skills;Social support;Societies;theories;therapy design;therapy development;Time;Training;Transportation;Universities;volunteer

PROJECT_TITLE: Community-based Medication Adherence Support for Older Adults Living with HIV and Hypertension (CBA Intervention)


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity

ORG_CITY: GAINESVILLE

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Brown adipocytes consume nutrient substrates to produce heat and increase energy expenditure, representing a potential therapeutic target to counteract human obesity. Mitochondria are central metabolic hubs and dynamically remodel their subcellular networks and membrane architectures to meet distinct metabolic demands. This proposal will elucidate the role of a novel mitochondrial inner membrane protein FAM210A in the regulation of mitochondrial cristae remodeling and brown adipocyte thermogenesis, and thus unravel an important signaling pathway that integrates mitochondrial biology into metabolic disease.

PI_NAMEs: YUE, FENG  (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Adipocytes;Adipose tissue;Animal Model;Architecture;associated symptom;Biochemical;Bioenergetics;Biogenesis;Biological Assay;Biology;Body Composition;Brown Fat;Cardiac;Cardiovascular Diseases;Cells;Chronic Disease;cold stress;combat;Complex;Consumption;Coupled;Crista ampullaris;Data;Dependovirus;Deposition;diet-induced obesity;Energy Metabolism;Family;Fatty acid glycerol esters;feeding;gain of function;glucose tolerance;Goals;Health;High Fat Diet;Histology;Homeostasis;Human;imaging system;Immunoprecipitation;In Vitro;in vitro Assay;in vivo;Inner mitochondrial membrane;insulin sensitivity;knock-down;Knock-out;Knockout Mice;Knowledge;Ligation;Link;Lipids;Liposomes;loss of function;LoxP-flanked allele;Mediating;member;Membrane;Membrane Proteins;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolism;metabolomics;Mitochondria;Mitochondrial DNA;mitochondrial metabolism;Molecular;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;Obese Mice;Obesity;Obesity Epidemic;obesity treatment;OPA1 gene;Outcome;overexpression;Pathologic;Pathway interactions;Phenotype;Physiological;Predisposition;prevent;Protein Family;protein reconstitution;Proteins;Proteomics;Regulation;Regulatory Pathway;Reporting;Resolution;Risk;Role;Series;Serology;Shapes;Signal Pathway;skeletal muscle growth;spatiotemporal;Symptoms;Testing;therapeutic development;therapeutic target;Thermogenesis;Three-Dimensional Imaging;Translations

PROJECT_TITLE: Regulation of Mitochondrial Remodeling in Adipose Thermogenesis

STUDY_SECTION: POMD

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Immunization;Infectious Diseases;Malaria;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: Phnom Penh

ORG_COUNTRY: CAMBODIA

ORG_FIPS: CB

ORG_NAME: INSTITUT PASTEUR DU CAMBODGE

PHR: A newly identified immune evasion mechanism has recently been described in Plasmodium vivax isolates from South-East Asia and concerns the gene amplification of the vaccine target PvDBP, raising the concern that implementation of a PvDBP vaccine may select for multi-pvdbp copy parasites. Through a combination of serological analysis of individuals living in malaria endemic areas of Ethiopia and Cambodia enrolled in a longitudinal cohort, rigorous in vitro phenotyping, and state-of-the-art genomic analysis, we propose here to determine the extent, dynamics and mechanisms of immune evasion conferred by PvDBP gene amplification. Our studies will provide a unique perspective on this newly described immune evasion strategy and will provide immediately-relevant information on how likely pvdbp amplification will compromise a PvDBP vaccine strategy and how to overcome it.

PI_NAMEs: LO, EUGENIA ;POPOVICI, JEAN  (contact)

PROJECT_TERMS: Adult;Alleles;Antibodies;Area;Biomass;Blood;Cambodia;Cambodian;Child;Clinical;Data;deep sequencing;design;Development;Diagnostic;Distant;Eastern Africa;Enrollment;Epidemiology;Epitopes;Erythrocytes;Ethiopia;Evolution;Exposure to;Flow Cytometry;follow-up;Frequencies;Gene Amplification;Genes;Genetic;Genetic Polymorphism;Genomic approach;Genomics;Goals;Human;human monoclonal antibodies;Humoral Immunities;Immune Evasion;Immunity;Immunoglobulin G;Immunologic Tests;immunological status;In Vitro;in vivo;Individual;Infection;Invaded;Length;Ligands;live cell imaging;Longitudinal cohort;Malaria;Malaria Vaccines;Measures;Mediating;Molecular;neutralizing antibody;Parasitemia;Parasites;Participant;participant enrollment;pathogen;Phase II Clinical Trials;phase II trial;Phenotype;Plasmodium vivax;Population;Population Dynamics;Prevalence;Process;prospective test;Protein Isoforms;Proteins;receptor;resilience;response;Serology;Severity of illness;Side;Southeastern Asia;Structure;success;Surface;Testing;Time;time use;Transcend;transcriptome sequencing;Transgenic Organisms;vaccine development;vaccine strategy;Vaccines;Variant;Vivax Malaria;Western Blotting;Work

PROJECT_TITLE: Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplification

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Apathy, defined as lack of enthusiasm or concern for previously exciting or interesting things, is a very common, debilitating, often refractory symptom, and is associated with poor outcomes in neurologic and psychiatric diseases. Transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation, is effective in treating depression but has had limited study in apathy. The current study will use a motivated behavioral task and electroencephalography (EEG) to investigate the use of TMS using Parkinson’s disease as a disease model of apathy, which will have implications across neurologic and psychiatric diagnoses.

PI_NAMEs: SKLEROV, MIRIAM  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Affect;American;Anterior;Area;Autopsy;Award;Basal Ganglia;Behavioral;Brain;brain health;Brain region;candidate marker;career;Caring;cingulate cortex;Clinical;Clinical Trials Design;Cognitive;Crossover Design;Data;Dementia;Development;Diagnostic;Disease;disease model;Dorsal;Electroencephalography;experience;FDA approved;Frequencies;Functional disorder;Funding;Goals;Grant;Impaired cognition;improved;Incentives;innovation;interest;Investigation;Knowledge;Label;Learning;Link;Measures;Medial;Medical;Mental Depression;Mental disorders;Mentors;Mentorship;Methods;Modeling;motivated behavior;Motivation;Motor;Movement Disorders;Nervous System Disorder;Neurodegenerative Disorders;neuroimaging;Neurologic;Neurologist;Neurology;neuropsychiatric disorder;neuropsychiatric symptom;neuropsychiatry;non-motor symptom;noninvasive brain stimulation;North Carolina;novel;Outcome;Parkinson Disease;Participant;Pathologic;Pathology;patient oriented research;Pattern;Performance;Persons;Physiological;Physiology;Positioning Attribute;Prefrontal Cortex;professor;programs;Psychiatric Diagnosis;psychiatric symptom;Psychoses;Quality of life;Questionnaires;recruit;Refractory;Research;Research Personnel;response;Rest;Rewards;secondary outcome;sensory cortex;Severities;Site;skill acquisition;Stress;Structure;Surrogate Markers;Symptoms;tenure track;Testing;Therapeutic;Time;tool;Training;Transcranial magnetic stimulation;Universities

PROJECT_TITLE: Investigation of non-invasive brain stimulation for the treatment of apathy


NIH_SPENDING_CATS: Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Pediatric;Precision Medicine;Prevention;Social Determinants of Health

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Very little is known about the food and beverage-related environments that adolescents experience on their smartphones. We have developed a novel method for capturing everything that appears on smartphone screens. This study will provide the first comprehensive description of the food and beverage environment that adolescents experience on their smartphones and its relationships to their dietary intakes, setting the foundation for precision nutrition interventions and evidence-based policies.

PI_NAMEs: HABER, NICHOLAS ;RAM, NILAM ;REEVES, BYRON ;ROBINSON, THOMAS N. (contact)

PROGRAM_OFFICER_NAME: PRATT, CHARLOTTE A

PROJECT_TERMS: 17 year old;Address;Adolescent;adolescent health;Adult;Age;analytical method;Behavior;behavior influence;Behavior Therapy;Beverages;Cellular Phone;computerized tools;Consumption;Data;Data Collection;data pipeline;Development;Devices;Diet;dietary;Dietary intake;Dietary Intervention;digital;Eating Behavior;encryption;Environment;ethnic minority;evidence base;experience;Exposure to;Female;Food;food environment;Foundations;Health;Hour;human subject;Image;improved;In Situ;Individual;Intervention;Interview;Life;Life Experience;Machine Learning;male;Measures;Methods;Modeling;Modernization;movie;Natural experiment;novel;nutrition;Nutrition Policy;Nutritional;Nutritional Study;personalized intervention;Persons;Policies;precision nutrition;preference;Preparation;Printing;racial minority;Research;Research Personnel;Sampling;Series;Structure;System;Teenagers;Television;temporal measurement;Text;theories;Time;Variant

PROJECT_TITLE: Teen screen diets and their relationships with dietary intake: setting the stage for precision interventions and evidence-based policies

STUDY_SECTION: LCBH

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: SEATTLE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Biomedical science increasingly relies upon sophisticated statistical methods to draw conclusions about biological processes and health outcomes. The aim of this proposal is to train the next generation of biomedical and neuroscience researchers to identify and avoid common pitfalls in designing and analyzing data, by developing three education units intended to be included in a larger curriculum. In particular, we will address the following three core issues: changing one's approach midway through a study, accounting for gaps in the scientific literature that arise from selectively publishing successful trials, and learning to question statistical analyses from a study.

PI_NAMEs: BERGSTROM, CARL T (contact)

PROGRAM_OFFICER_NAME: CRAWFORD, DEVON CHRISTINE

PROJECT_TERMS: Accounting;Address;adjudication;Area;Attention;Awareness;Biological Process;Biological Sciences;Biomedical Research;biomedical scientist;Books;Collaborations;Coupled;Data;Data Analyses;Data Science;Data Set;design;Development;Education;Education Projects;Educational Curriculum;Educational process of instructing;Engineering;Evaluation;Exercise;experience;Fraud;Generations;Goals;guided inquiry;Health;Health Sciences;High School Student;Human Resources;improved;Instruction;instructor;Journals;Knowledge;Lead;Learning;Learning Module;Length;literacy;Literature;Measures;Mechanics;Methods;Modality;Neurosciences;Neurosciences Research;next generation;Outcome;Outcome Measure;Outcomes Research;outreach;Paper;Philosophy;Process;Production;Program Accessibility;Publication Bias;Publications;Publishing;Reader;Reading;Reporting;Reproducibility;Research;Research Misconduct;Research Personnel;response;Risk;Role;Route;Running;Sampling Biases;Science;Scientist;Self-reflection;Series;Shapes;skills;Specific qualifier value;Speed;Statistical Data Interpretation;Statistical Methods;statistics;student training;Students;Surveys;Techniques;Technology;Testing;Thinking;tool;Training;United States National Aeronautics and Space Administration;Universities;Washington;Work

PROJECT_TITLE: Developing user-centric training in rigorous research: post-selection inference, publication bias, and critical evaluation of statistical claims.


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: NEW YORK

PHR: PROJECT NARRATIVE We propose to investigate an important and common class of cancer associated genetic lesions in which cancer driver genes (oncogenes) are amplified as part of circular extra-chromosomal DNA molecules (ecDNAs). There is substantial evidence that ecDNAs are involved in cancer pathogenesis, but progress in the field has been limited by the lack of effective means to induce the formation of specific ecDNAs model organisms. To address this important limitation, we have developed a novel strategy that we will use to study the biology of ecDNAs in normal and cancer cells, and to study their ability to promote cancer formation in genetically engineered mice.

PI_NAMEs: VENTURA, ANDREA  (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Acceleration;Address;Advanced Malignant Neoplasm;Animals;anti-cancer therapeutic;Appearance;Applications Grants;Biogenesis;Biology;cancer cell;Cancer cell line;Cell Line;cell transformation;Cells;Centromere;Chromosomal Duplication;Chromosomal Rearrangement;Chromosomes;Circular DNA;Clustered Regularly Interspaced Short Palindromic Repeats;Cues;Data;daughter cell;DNA Damage;DNA Maintenance;Double Minutes;Drug resistance;Elements;Engineering;Environment;Epidermal Growth Factor Receptor;Epigenetic Process;erbB Genes;Event;Evolution;experimental study;extracellular;extrachromosomal DNA;Future;Generations;Genes;Genetic;genetic approach;genetic element;Genetic Recombination;Genetically Engineered Mouse;genome editing;Genome engineering;Germ Lines;Goals;Horizontal Disease Transmission;Human;human cancer mouse model;in vivo;inducible Cre;innovation;interest;Investigation;Label;Lesion;Link;Maintenance;Malignant Neoplasms;MDM2 gene;Mediating;Metaphase Spread;metaplastic cell transformation;Mitosis;model organism;Modeling;Mouse Strains;Mus;Neoplasm Metastasis;Normal Cell;novel;novel strategies;Nutrient;Oncogene Activation;Oncogenes;Oncogenic;Other Genetics;Pathogenesis;Phenotype;prevent;Reagent;Reporter;Research Proposals;Role;segregation;Series;somatic cell gene editing;System;Technology;Testing;Therapeutic;tool;tumor;tumor heterogeneity;tumor initiation;tumor progression;Tumor Promotion;Tumor stage;tumorigenesis;Visualization;Work

PROJECT_TITLE: Investigating the roles of oncogenic extrachromosomal circular DNAs in cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Narrative Wiskott-Aldrich Syndrome-Like, WASL, is a multifaceted cellular protein with essential roles in the regulation of cytoplasmic F-actin dynamics impacting cell invasiveness, migration, and cell responses to the environment. Additionally, WASL has unexpected functions in the nucleus where it acts to promote and shape transcription and differentiation. We have uncovered a surprising, and previously altogether undescribed role for WASL in regulation of skeletal growth and pattern that is conserved among vertebrates. Characterization of WASL signaling in development will reveal core regulation of patterning and differentiation during development.

PI_NAMEs: HARRIS, MATTHEW P (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Actins;Address;Adopted;Affect;Alleles;Amino Acid Sequence;ANGPTL2 gene;appendage;Articulation;ATAC-seq;Behavior;Binding;C-terminal;cancer invasiveness;cell behavior;Cell Differentiation process;Cell Nucleus;Cell Physiology;Cells;Chromatin;Complement;Cytoplasm;Cytoskeleton;Data;density;Dependence;Development;Developmental Gene;DNA-Directed RNA Polymerase;Elements;Environment;Epigenetic Process;epigenetic regulation;Equilibrium;Event;Experimental Models;Extracellular Matrix;F-Actin;Family member;gain of function;gene discovery;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Gene Expression Regulation;gene function;Generations;Genes;Genetic Epistasis;Genetic Transcription;Growth;Homeobox Genes;in vivo;Investigation;Limb Bud;Limb Development;Limb structure;Link;long bone;loss of function;Mediating;Microfilaments;migration;Modeling;Morphology;mouse development;mRNA sequencing;Mus;mutant;Mutation;Nature;Neoplastic Cell Transformation;novel;Nuclear;Pattern;Phenotype;Phosphorylation;Protein Region;Proteins;Regulation;Reporting;response;Role;Shapes;Signal Transduction;Site;skeletal;Skeletal Development;Skeleton;Specificity;Stains;stem;Structure;Testing;Tetrapoda;Time;tomography;tool;Transcriptional Regulation;transcriptome sequencing;Variant;Vertebrates;Wiskott-Aldrich Syndrome;Wiskott-Aldrich syndrome protein;Zebrafish

PROJECT_TITLE: A novel role for Wasl signaling in the regulation of skeletal patterning

STUDY_SECTION: SBDD

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


ORG_CITY: LAGOS

ORG_COUNTRY: NIGERIA

ORG_FIPS: NI

ORG_NAME: NIGERIAN INSTITUTE OF MEDICAL RESEARCH

PHR: PROJECT NARRATIVE Persistent low-level viremia (LLV) in persons with HIV who are on antiretroviral therapy (ART) is a barrier to achieving the goal of zero transmission and eradication of HIV, but not much is known about the impact of LLV on attaining the ART goal of viral suppression in West Africa. The proposed research will use pharmacoepidemiologic methods to assess the prevalence of LLV and impact on ART outcomes. The study will also use mathematical modeling to predict future LLV with adherence to ART measured by innovative pharmacological techniques.

PI_NAMEs: HERBERTSON, EBIERE CLARA (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adherence;adolescent health;Adult;advanced analytics;Africa;Africa South of the Sahara;African;Anti-Retroviral Agents;Anti-retroviral drug resistance;antiretroviral therapy;Appointment;Award;biological sex;Blood;career;career development;Caring;Cells;Cessation of life;Chronic;Clinical;clinical care;Clinical Pharmacology;clinical prognosis;cohort;Collection;Communicable Diseases;comorbidity;comparative;Country;Data;Data Analyses;Databases;Development Plans;Diphosphates;Drug Exposure;Drug resistance;Dryness;Epidemic;Epidemiologist;Epidemiology;Event;evidence base;experience;Failure;follow-up;Funding;Future;Goals;Guidelines;Hair;HIV;HIV-1;HIV-2;improved;Individual;innovation;insight;Intake;International;Intervention;K-Series Research Career Programs;Knowledge;Learning;Literature;longitudinal, prospective study;mathematical model;Measurement;Measures;Mentors;Methods;Monitor;Names;Nigeria;Outcome;Patient Self-Report;Patients;Persons;Pharmaceutical Preparations;Pharmacoepidemiology;pharmacologic;Pharmacology;Pharmacy facility;pill;point of care;point of care testing;Policies;Policy Maker;population health;Predictive Value;Prevalence;prognostic value;Prospective cohort;Public Health;Records;Regimen;Reproductive Health;Research;Research Design;Research Personnel;Resistance;Resistance development;Resource-limited setting;Retrospective cohort;scale up;Scientist;Site;skills;socioeconomics;Source;Specialist;Spottings;statistics;study population;Techniques;Tenofovir;Testing;therapy outcome;Training;translational physician;translational scientist;transmission process;treatment guidelines;Treatment outcome;Urine;Viral;Viral load measurement;Viral Load result;Viral reservoir;Viremia;Virus Activation;Women's Health

PROJECT_TITLE: Use of Pharmacoepidemiology to Understand Predictors and Impact of Low-level Viremia in Persons with HIV in West Africa


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;HIV/AIDS;Infectious Diseases;Mental Health;Microbiome;Neurosciences;Pediatric;Pediatric - AIDS;Prevention

ORG_CITY: Newark

ORG_DEPT: DENTISTRY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Mental and oral health co-morbidities associated with HIV and lifelong treatment could be driven by biological processes, including microbiota- or aging-mediated mechanisms. A better understanding of how these mechanisms contribute to neurocognitive impairments and oral conditions is needed to support interventions, particularly in adolescence. This proposal focuses on identifying oral microbial taxonomic and functional features, and epigenetic aging markers associated with neurocognition and oral health in adolescents with HIV.

PI_NAMEs: COKER, MODUPE  (contact);SHIAU, STEPHANIE

PROGRAM_OFFICER_NAME: BACCAGLINI, LORENA

PROJECT_TERMS: accelerated epigenetic aging;Adolescence;Adolescent;Adult;Age;age related;age related chronic disease;aged;Aging;aging biomarker;antiretroviral therapy;Attention;Bacteria;bead chip;behavior influence;Bioinformatics;Biological;Biological Markers;Biological Process;Blood specimen;Caring;Child;Chronic;clinically relevant;Cognition;cognitive testing;cohort;commensal microbes;comorbidity;comparison control;cost effective;Data;Data Set;Dental;Dental caries;Dental Hygiene;Dentistry;Development;Disease;disorder risk;DNA Methylation;Epidemiology;epigenetic aging;epigenetic marker;executive function;Funding;General Population;Gingiva;Health;high risk;HIV;HIV Infections;HIV-infected adolescents;Immunologics;Incidence;Inflammatory;insight;interdisciplinary approach;Interdisciplinary Study;Intervention;Leptotrichia;Link;Measures;Mediating;Medicine;Mental Health;Metabolic;Metagenomics;Microbe;microbial;microbial community;Microbial Taxonomy;Microbiology;microbiota;Mouth Diseases;multidimensional data;Neisseria;Neurocognition;Neurocognitive;Neurocognitive Deficit;Neurologic;Neuropsychology;Nigeria;Nigerian;Oral;oral condition;Oral health;oral microbial community;Outcome;Pathogenesis;pathogenic bacteria;pathogenic microbe;Pathology;Pediatrics;peer;Perinatal;Perinatal Exposure;Persons;Population;predictive tools;Prevalence;Prevention strategy;Process;programs;Research;Risk;Role;saliva sample;Salivary;Sampling;scale up;sex;Shapes;Shotguns;social influence;Statistical Models;Streptococcus mutans;Taxonomy;Testing;Therapeutic;United States National Institutes of Health;Variant;Work;Youth

PROJECT_TITLE: Uncovering the Biological Link between Oral and Mental health in Adolescents Living with HIV (uBLOoM)