NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Patient Safety;Prevention

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: PROJECT NARRATIVE Drug-drug interactions (DDIs) are a growing source of preventable harm in patients with kidney disease. The sources of potential harm from DDIs in this population are bidirectional in nature, with kidney disease functioning as both an outcome of DDIs and a factor that alters DDI severity. The goal of this proposal is to understand and quantify these bidirectional relationships in order to improve the safety of pharmacotherapy in this vulnerable population.

PI_NAMEs: MIANO, TODD ANTHONY (contact)

PROJECT_TERMS: Acceleration;Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;Admission activity;Adverse event;Affect;Amiodarone;Animal Model;Antibiotics;Antimicrobial Resistance;Binding Proteins;burden of illness;Chronic Kidney Failure;Clinical;clinical effect;clinically significant;cohort;Cohort Studies;Creatinine;Data;Database Management Systems;Databases;design;Disease;disorder risk;drug development;Drug Exposure;Drug Interactions;Drug Kinetics;Drug Modelings;Drug toxicity;Enzymes;epidemiology study;experience;Fostering;Funding;Future;Generations;Goals;Health;Health system;Hepatic;Hospitalization;Hospitals;Human;improved;Infection;Injury;Inpatients;insight;Investigation;Kidney;Kidney Diseases;Knowledge;Lead;Life;Measures;Mediating;medication safety;Metabolism;Methodology;Methods;models and simulation;Molecular Profiling;Nature;nephrotoxicity;novel;novel strategies;Outcome;Outcome Study;Patients;Pattern;Pharmaceutical Preparations;Pharmacoepidemiology;pharmacokinetic model;Pharmacology;Pharmacotherapy;physiologically based pharmacokinetics;Physiology;Piperacillin-Tazobactam;Polypharmacy;Population;post gamma-globulins;predictive modeling;prevent;Prevention strategy;preventive intervention;Property;prospective;Prospective cohort;Prospective, cohort study;Proteins;Renal function;Research;Research Design;Research Personnel;response;Retrospective cohort study;Risk;Role;rosuvastatin;Safety;Sepsis;septic patients;Severities;simulation;skills;Source;Statistical Models;Testing;Toxic effect;Training;translational approach;translational model;United States Department of Veterans Affairs;Vancomycin;virtual;Vulnerable Populations;Warfarin;Work

PROJECT_TITLE: Drug-drug interactions and kidney disease in hospitalized patients


ADMINISTERING_IC: NS

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Brain Disorders;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BROAD INSTITUTE, INC.

ORG_STATE: MA

PHR: PROJECT NARRATIVE Prion disease is a fatal, devastatingly rapid neurodegenerative disease of humans and other mammals that is caused by the misfolding of the native prion protein, or PrP. Interventions capable of reducing levels of this protein across the brain have recently shown preclinical promise, creating a time-sensitive mandate to illuminate in greater detail how PrP level controls the rates of prion formation, replication and neurotoxicity, and how this control translates across disease timepoints, species and strains. We will leverage new animal models, tool compounds, and biomarkers to systematically assess the impact of PrP lowering across paradigms, in order to illuminate fundamental aspects of prion disease kinetics while building a scientific foundation for future development of PrP-lowering therapeutics.

PI_NAMEs: VALLABH, SONIA MINIKEL (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Animal Model;Antisense Oligonucleotides;Biological Markers;Biological Models;Brain;Cerebrospinal Fluid;clinically relevant;Complement;Data;Dependence;Development;Disease;Disease Progression;disorder control;dosage;Engineering;experimental study;Foundations;Future;Genes;Genetic;genetic manipulation;Hamsters;Heterozygote;Human;human disease;human model;humanized mouse;Infection;insight;Intercept;interest;Intervention;Kinetics;Knock-out;knockout animal;Knowledge;Lead;Learning;Light;Mammals;Measurement;Microtus;Modeling;Molecular;mouse model;Mus;Neurodegenerative Disorders;neurofilament;Neurons;neurotoxicity;novel;Onset of illness;Pathogenicity;Pathologic;Pathologic Processes;Pathology;Patients;pharmacologic;Phase;Plasma;postnatal;pre-clinical;Predisposition;Prion Diseases;prion seeds;Prions;Process;protein expression;Proteins;PrP;PrP gene;Public Health;Rattus;Series;Symptoms;System;Terminal Disease;Testing;Therapeutic;Time;tool;Translating;treatment response;Work

PROJECT_TITLE: How Substrate Dosage Drives Prion Disease Kinetics

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Peripheral artery disease patients that suffer from chronic kidney disease experience worsened symptomology and are at greater risk for limb amputation and death. We propose here to study a novel molecular pathway that links kidney function to peripheral artery disease outcomes. Using modern genetic/molecular models and translational studies in patients, these studies will provide important insights into the causes of worsened PAD outcomes in CKD, and may lead to novel therapeutic approaches for these unfortunate patients.

PI_NAMEs: RYAN, TERENCE E (contact)

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Acceleration;Activities of Daily Living;Affect;American;Amputation;angiogenesis;Aryl Hydrocarbon Receptor;Atherosclerosis;Biological;Biology;Blood capillaries;Blood Vessels;Cardiovascular system;Cell Respiration;Cessation of life;Chronic;Chronic Kidney Failure;claudication;Clinical;comorbidity;Cytochrome P450;Data;density;Dependovirus;Development;Diabetes Mellitus;Disease;Disease Outcome;disorder control;Drug Metabolic Detoxication;effective therapy;Electron Transport;Endothelial Cells;Endothelium;Enrollment;Enzymes;Etiology;Evolution;experience;experimental study;Exposure to;Foundations;Future;Gangrene;Genetic;Growth;Health;hemodynamics;Hindlimb;Human;human data;Impairment;improved;In Situ;In Vitro;Indican;indoleacetic acid;Ingestion;Injury;insight;Ischemia;Isolated limb perfusion;knock-down;Knock-out;Knockout Mice;Knowledge;Kynurenic Acid;Kynurenine;Laboratories;Life;Ligands;limb amputation;Limb structure;Link;Lower Extremity;Mediating;Metabolism;Mitochondria;mitochondrial dysfunction;Modernization;Molecular;molecular modeling;mortality;mortality risk;Mus;Muscle;Muscle Cells;Muscle function;muscle necrosis;muscle strength;Myopathy;Natural regeneration;new therapeutic target;novel;novel therapeutic intervention;Organ;Oxidative Phosphorylation;Pain;Pathology;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;Peripheral arterial disease;pharmacologic;Phenotype;poor health outcome;Pre-Clinical Model;primary outcome;Production;Reactive Oxygen Species;Receptor Activation;receptor binding;Receptor Signaling;Recovery;Renal function;Respiratory physiology;Rest;Risk;Risk Factors;Role;Signal Pathway;Skeletal Muscle;Skeletal muscle injury;small hairpin RNA;Smoking;solute;success;symptomatology;System;Testing;therapeutic development;Tissues;Toxic effect;translational study;Uremia;Waste Products;wasting

PROJECT_TITLE: Molecular mechanisms regulating peripheral arterial disease pathobiology in chronic kidney disease

STUDY_SECTION: VCMB

STUDY_SECTION_NAME: Vascular Cell and Molecular Biology Study Section[VCMB]


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

ORG_CITY: BERKELEY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: PROJECT NARRATIVE This project will develop a suite of statistical and computational methods for genomics that are robust and efﬁcient. This research will enable inference under complex population genetic models, and help biomedical researchers integrate information from various types of genomic data to reveal fundamental biological processes, thereby broadly facilitating efforts to understand the genetic basis of human biology and disease risk.

PI_NAMEs: SONG, YUN S (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: analytical tool;Area;Attention;Basic Science;Big Data;Biological;Biological Assay;Biological Process;Biology;Biomedical Research;Catalogs;Cells;Collaborations;Communities;Complex;computer scientist;computerized tools;Computing Methodologies;Data;Data Analyses;Development;disorder risk;epigenetic variation;Gene Expression Profiling;Genetic;Genetic Models;Genetic Transcription;Genetic Variation;genomic data;Genomics;Goals;Human Biology;human disease;Immunology;mathematical analysis;mathematical model;Metagenomics;Methods;Modeling;mRNA Translation;novel;Population;Population Genetics;Population Heterogeneity;programs;Research;Research Personnel;sound;Statistical Methods;structural biology;Technology;tool;Transcription Process;Translation Process;Translations

PROJECT_TITLE: Robust and efficient statistical inference methods for genomics

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


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: Los Angeles

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Colorectal cancer is one of the most prevalent malignancies and a deadly form of cancer. Most colorectal cancer patients do not respond well to therapeutic treatment. The proposed studies will utilize chemical biology approaches to delineate a previously unknown signaling pathway that drives potent killing of colorectal cancer cells. In the long run, these studies may lead to new and improved therapies against colorectal cancer and other types of cancer.

PI_NAMEs: ZHANG, LIN  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: anti-cancer;anti-tumor immune response;anticancer activity;Antineoplastic Agents;Apoptosis;BCL2 gene;Biology;Bypass;cancer cell;Cancer Etiology;cancer therapy;cancer type;Caspase;Cell Death;Cell Death Induction;cell killing;Cell Survival;Cells;Cessation of life;Chemicals;chemotherapy;Chemotherapy-Oncologic Procedure;clinically relevant;colon cancer patients;Colorectal Cancer;colorectal cancer treatment;Data;Development;DNA;Dose Limiting;Down-Regulation;Epigenetic Process;Event;Evolution;Fluorouracil;Foundations;Genetic;Growth;Human;immune checkpoint blockade;Immune response;Immunocompetent;immunogenicity;Immunologic Surveillance;Immunologics;Immunotherapy;improved;in vivo;Malignant - descriptor;Malignant Neoplasms;Mediating;Mismatch Repair;Mismatch Repair Deficiency;mitochondrial dysfunction;Modeling;Molecular;Mus;Mutation;nanomolar;Natural Compound;Necrosis;neoplastic cell;New Agents;novel;novel anticancer drug;Nude Mice;Pathway interactions;Patients;pharmacologic;Phosphorylation;Phosphotransferases;Play;protein activation;Protein Family;Proteins;Receptor-Interacting Protein;Relapse;Resistance;response;RIPK3 gene;Role;Route;Signal Pathway;Signal Transduction;Stress;targeted agent;targeted treatment;Testing;Therapeutic;therapy resistant;Toxic effect;TP53 gene;Treatment Efficacy;tumor;Tumor Immunity;Tumor Suppression;Virus

PROJECT_TITLE: Targeting defective necroptosis in colorectal cancer

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Malaria;Malaria Vaccine;Orphan Drug;Patient Safety;Pneumonia and Influenza;Prevention;Rare Diseases;Sexually Transmitted Infections;Vaccine Related;Vector-Borne Diseases;Women's Health Research

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Testing of new vaccines and medications in human clinical trials requires a careful assessment of benefit and safety. The applicants for this proposal have the experience and the depth and breadth of knowledge required to participate in human testing of novel vaccines and new therapeutics in the areas of respiratory infection (including influenza), sexually transmitted infections, enteric infections and malaria challenge studies. The proposal includes a main site for clinical trials at the University of Washington in Seattle, a second tier of established and experienced clinical sites in Seattle, Kenya, South Africa, and Peru, and the potential for very broad surge capacity to address emerging or re-emerging infectious disease threats by leveraging the University of Washington's global research network in over 130 countries.

PI_NAMEs: MCCLELLAND, RAYMOND SCOTT;WALD, ANNA  (contact)

PROGRAM_OFFICER_NAME: HALL, CYNDA GAY

PROJECT_TERMS: Address;Adult;Adverse event;Africa South of the Sahara;Area;Biological Assay;Cellular Immunology;Child;Childhood;Clinic;Clinical;clinical development;Clinical Investigator;Clinical Practice Guideline;Clinical Protocols;Clinical Research;clinical research site;Clinical Trials;Collaborations;Committee Members;Communicable Diseases;Conduct Clinical Trials;Contracts;cost;Country;Cytomegalovirus;Data Analyses;Dedications;design;Emerging Communicable Diseases;Enrollment;Ensure;enteric infection;Evaluation;experience;Fred Hutchinson Cancer Research Center;Funding;Geography;global health;Good Clinical Practice;healthy volunteer;Hepatitis;HIV Vaccine Trials Network;Human;Individual;Industry;industry partner;Infectious disease threat;Influenza;Influenza A virus;Influenza A Virus, H1N1 Subtype;Infrastructure;Institution;International;Kenya;Knowledge;Laboratories;Laboratory Research;Lead;Leadership;Location;Malaria;malaria infection;Medical center;Medical Research;medical schools;Medicine;Mentorship;Mission;Molecular Virology;Monitor;National Institute of Allergy and Infectious Disease;neglected tropical diseases;novel;novel strategies;novel therapeutics;novel vaccines;pandemic disease;Participant;participant safety;Peripheral Blood Mononuclear Cell;Persons;Peru;Pharmaceutical Preparations;Phase;Policies;Population;Pregnant Women;Principal Investigator;programs;Qualifying;recruit;Reporting;Research;Research Institute;Research Personnel;Resources;Respiratory Tract Infections;Ribosomal RNA;Risk;Running;Safety;Sexually Transmitted Diseases;Simplexvirus;Site;skills;South Africa;Target Populations;Testing;Therapeutic;training opportunity;United States National Institutes of Health;Universities;Vaccine Clinical Trial;vaccine development;vaccine trial;Vaccines;Washington;Women's Health;Work;ZIKA

PROJECT_TITLE: University of Washington Vaccine and Treatment Evaluation Unit


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: MINNEAPOLIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Narrative While deep brain stimulation (DBS) does offer symptom relief for most patients with Essential Tremor (ET), DBS therapy is not as effective at reducing tremors during voluntary movement and has been shown to lose effectiveness over time. Understanding of the neural, muscular, and failure mechanisms underlying tremor control and progression with DBS could help combat these therapeutic challenges and result in improved patient outcomes. This project will integrate high-field magnetic resonance imaging, patient-specific pathway activation models of DBS, quantitative sensors, and comprehensive electromyography measurements to further understand the mechanisms behind tremor control, tremor progression, and side effect induction with DBS.

PI_NAMEs: BUTLER, REBECCA DORAN (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Adult;Affect;Age;Algorithms;Analysis of Variance;Area;Brain;CCL4 gene;Cell Nucleus;Classification;Client satisfaction;Clinical;Clinical Research;Clinical Trials;cohort;combat;Computer Models;Deep Brain Stimulation;design;Diagnosis;Disease Progression;Distal;Effectiveness;Electromyography;Essential Tremor;experience;Failure;follow-up;Frequencies;Grant;Head and neck structure;Human;Image;Implant;implantation;improved;Intention Tremor;Kinetics;Lead;Linear Models;Location;Lower Extremity;machine learning algorithm;magnetic field;Magnetic Resonance Imaging;Measurement;Measures;Methods;Minnesota;Modeling;Motion;Motor;Movement;Movement Disorders;Muscle;Musculoskeletal Equilibrium;neural;neuromechanism;neurophysiology;novel;Operative Surgical Procedures;Outcome;Output;particle;Pathogenesis;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;Peripheral;Pharmaceutical Preparations;Physicians;Posture;prospective;Recommendation;reduce symptoms;Refractory;Reporting;sensor;side effect;Structure;Surface;Surgical Management;Symptoms;Technology;Thalamic structure;Therapeutic;Time;treatment optimization;Tremor;Universities;Upper Extremity;Visit;wearable sensor technology;zona incerta

PROJECT_TITLE: Progression and differential control of postural and kinetic tremor with deep brain stimulation


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: ANN ARBOR

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative  Mammalian Short INterspersed Elements (SINEs) are mobile genetic sequences that can be subdivided into two general classes: (1) those derived from 7SL signal recognition particle RNA (e.g., human Alu elements); and (2) those derived from transfer RNAs (e.g., canine SINEC_Cf elements). To date, greater than 76 independent Alu retrotransposition events have been implicated as the cause of human diseases, whereas SINEC_Cf retrotransposition events are responsible for various diseases and phenotypic differences in canines. The goal of this R01 proposal is to use molecular biological, evolutionary inference, genetic, genomic, and biochemical approaches to identify sequences and structural elements within human-specific Alu and SINEC_Cf RNAs, as well as host factors, that are critical to promote SINE retrotransposition.

PI_NAMEs: KIDD, JEFFREY M;MORAN, JOHN V. (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: 7SL RNA;Alleles;Alu Elements;Binding;Biochemical;Biological;Biological Assay;Biology;Candidate Disease Gene;candidate identification;Canis familiaris;Categories;causal variant;Cell Line;Cell Separation;Cells;Cellular Assay;Chemicals;Cis-Acting Sequence;Classification;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Complement;Cultured Cells;Data;differential expression;Disease;DNA sequencing;DNA Transposable Elements;Elements;Event;Evolution;Exons;experimental study;Generations;Genetic;genetic element;Genome;Genomic DNA;genomic locus;Genomics;Germ Lines;Goals;Hela Cells;Human;human disease;Immobilization;Integration Host Factors;Introns;Knock-out;Laboratories;Long Interspersed Elements;Malignant Neoplasms;mammalian genome;Maps;Mediating;Michigan;Mobile Genetic Elements;Modeling;Molecular;Mus;Mutation;Open Reading Frames;particle;Paste substance;permissiveness;Phenotype;Poly(A) Tail;Process;Proteins;Retrotransposition;Retrotransposon;Ribonucleoproteins;Ribosomes;RNA;RNA Sequences;Short Interspersed Nucleotide Elements;Signal Recognition Particle;Structural Models;Structure;Technology;Testing;transcriptome sequencing;Transfer RNA;Universities;Untranslated RNA;whole genome

PROJECT_TITLE: Identification of Factors Critical for SINE Retrotransposition

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PUBLIC HEALTH RELEVANCE Mitochondria are critical in producing the energy cells need to survive and function, and failures in mitochondrial energy production contribute to a number of diseases. The goal of our research is to identify the ways in which mitochondria respond to energy defects, specifically through certain types of modifications that further influence their functions and communication with the cell. Insight into how mitochondria respond to energy defects and how these processes contribute to disease pathology will ultimately promote the development of new therapies targeting mitochondrial energy dysfunction in disease.

PI_NAMEs: KWONG, JENNIFER Q. (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Acetylation;Acylation;Acyltransferase;Adult;Affect;Aging;arm;ATP Synthesis Pathway;Biochemistry;Bioenergetics;biological adaptation to stress;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cell Death;Cell Physiology;Cells;Cellular biology;Communication;Communication impairment;coping;cyclophilin D;Data;Deacetylase;Defect;Degenerative Disorder;design;Development;Disease;Engineering;Excision;Exhibits;Failure;Fibrosis;Functional disorder;gene therapy;Goals;Heart;Heart Diseases;Human;Impairment;in vivo;in vivo Model;Individual;innovation;insight;Link;Mass Spectrum Analysis;Mediating;Metabolic;Metabolism;metabolomics;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;mitochondrial metabolism;mitochondrial permeability transition pore;Mitochondrial Proteins;Modeling;Modification;mouse model;Mus;new therapeutic target;novel;overexpression;Pathogenesis;Pathology;Pathway interactions;Pattern;Phosphate Carriers;Physiological;Physiology;Play;Positioning Attribute;Post-Translational Protein Processing;Process;Production;Proteins;Proteomics;public health relevance;Regulation;Research;response;Signal Pathway;Signal Transduction;Sirtuins;Stress;stressor;System;Testing;Tissue Differentiation;Tissues;Work

PROJECT_TITLE: Acylations: a novel pathway in the response to mitochondrial energy dysfunction

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: NEW YORK

ORG_DEPT: NEUROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE As a key brain region for reward and motivation, the nucleus accumbens (NAc) is disrupted in neuropsychiatric disorders such as drug addiction and depression. Within the NAc, cholinergic interneurons (CINs) release acetylcholine to guide reward-learning, but little is known about what regulates CIN activity. By elucidating the connectivity and functional impact of long-range and local inputs onto CINs in the NAc, this project will advance our circuit-level understanding of a brain region highly involved in both normal and pathological behaviors.

PI_NAMEs: JANG, EMILY  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Acetylcholine;Address;Amygdaloid structure;Anatomy;Area;Attention;Behavior;Brain;Brain region;brain reward regions;cell type;Cells;cholinergic;Corpus striatum structure;Disease;Distant;Dopamine;Dorsal;Drug Addiction;Electrophysiology (science);experimental study;Genetic Complementation Test;Glutamates;Goals;Hippocampus;Immunohistochemistry;insight;Interneurons;Learning;Medial;Mediating;Mental Depression;Methods;Microscopy;motivated behavior;Motivation;motivational processes;neuronal cell body;Neurons;neuropsychiatric disorder;Nucleus Accumbens;optogenetics;Output;Parvalbumins;Pathologic;Pattern;Play;Population;Prefrontal Cortex;Process;Property;Rabies;rabies viral tracing;response;Rewards;Role;Shapes;Signal Transduction;Slice;Somatostatin;Stimulus;Surveys;Synapses;Testing;Thalamic structure;Transgenic Mice;Translating;Ventral Striatum;Viral;Virus;Work

PROJECT_TITLE: Long-range and local connectivity of cholinergic interneurons in the nucleus accumbens


ORG_CITY: LOUISVILLE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: The objective of this study is to define how FGF1 protects against atherosclerosis and whether there is a clinical translational potential of the novel non-mitogenic variant FGF1△HBS for preventing atherosclerosis by inhibiting hepatic cholesterol biosynthesis and suppressing intestinal cholesterol absorption without risk of hyperproliferation. We will first optimize the doses of FGF1 protection against atherosclerosis in two distinct atherogenic animal models and determine the roles of endogenous FGF1 in the development of atherosclerosis. Next, we will determine the effects and mechanism of FGF1 on hepatic cholesterol biosynthesis and intestinal cholesterol absorption. This project will reveal new insight into the underlying mechanism behind FGF1 protection against atherosclerosis as well as provide fundamental evidence supporting the non-mitogenic variant FGF1△HBS as a novel therapeutic approach for prevention of atherosclerosis in future clinical practice.

PI_NAMEs: TAN, YI  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Adipose tissue;Agonist;angiogenesis;Animal Model;Apolipoprotein E;Arterial Fatty Streak;Arteries;atherogenesis;Atherosclerosis;Attenuated;Biliary;Binding Sites;Blood;blood glucose regulation;Breeding;Cardiovascular Diseases;Cell Proliferation;Cells;Cholesterol;cholesterol absorption;cholesterol biosynthesis;Cholesterol Homeostasis;Chronic;clinical practice;Clinical Research;clinical translation;Coagulation Process;Data;db/db mouse;Development;Diabetes Mellitus;dietary;Dose;Dyslipidemias;Engineering;Enterocytes;Feces;FGF1 gene;Fluorescein;Future;Genetic Transcription;Heparin Binding;Hepatic;Hepatocyte;Human;Hyperlipidemia;insight;Intestinal Absorption;Intestines;Knockout Mice;Label;LDL Cholesterol Lipoproteins;Life Style;Lipids;Liver;Macrophage;Mediating;Mediator;Metabolic;Metabolic syndrome;Mutation;neovascularization;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;novel therapeutic intervention;Nuclear Translocation;Operative Surgical Procedures;Organ;Organoids;overexpression;Pathogenesis;Pathologic;Patients;Phenotype;Play;prevent;Prevention approach;Radioisotopes;Recombinants;Regulation;Risk;Risk Factors;Role;side effect;Site;Testing;Therapeutic;transcription factor;translational potential;tumorigenic;Up-Regulation;Variant

PROJECT_TITLE: Fibroblast growth factor 1 prevents hyperlipidemia and atherosclerosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: TOLEDO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF TOLEDO

ORG_STATE: OH

PHR: Project Narrative (Relevance) This project will develop methods to synthesize bacterial oligosaccharide-based antigens and their conjugates with fusion protein antigens and adjuvants. The cellular and humoral immune responses elicited by these new materials will be evaluated in cell culture and mice.

PI_NAMEs: SUCHECK, STEVEN  (contact);WALL, KATHERINE A

PROGRAM_OFFICER_NAME: RITCHIE, ALEC

PROJECT_TERMS: Address;Adjuvant;Animal Model;Antibodies;Antibody Response;Antibody titer measurement;Antigen Targeting;Antigen-Presenting Cells;Antigens;Antimicrobial Resistance;Bacteria;Bacterial Antigens;C-terminal;Carbohydrates;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Culture Techniques;Cessation of life;chemical synthesis;Chemistry;Chimeric Proteins;Collaborations;Complex;cost;Cysteine;cytokine;Cytotoxic T-Lymphocytes;design;Development;Dose;Economics;Engineering;Epitopes;Escherichia coli;ESKAPE pathogens;experimental study;Extracellular Domain;Family;Fc domain;Glycoconjugates;Goals;Health;Helper-Inducer T-Lymphocyte;Human;humanized mouse;Hybrids;IgG3;Immune response;Immune system;Immunization;immunogenicity;Immunology;improved;in vivo;Inbred Mouse;investigator training;Lipids;Lipopolysaccharides;Liposomes;Maps;Mediating;Medicine;member;Membrane Proteins;Methods;Molecular;Molecular Biology;mouse model;Mus;novel;novel strategies;Oligosaccharides;OprF protein;Organic Chemistry;pathogen;Pathogenesis;Peptides;Play;Polymers;Polysaccharides;Production;Proteins;Pseudomonas aeruginosa;Publishing;receptor;recruit;response;Rhamnose;Role;Route;Serotyping;single molecule;Site;synthetic biology;T-Lymphocyte;Tertiary Protein Structure;Tumor Antigens;Vaccine Antigen;vaccine candidate;vaccine immunogenicity;Vaccines;Viral Antigens;Work

PROJECT_TITLE: Methods to synthesize oligosaccharide-fusion protein conjugates and enhancement of their antigenicity

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


ADMINISTERING_IC: ES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Philadelphia Regional Center for Children's Environmental Health (PRCCEH) is a new children's center which will provide the infrastructure to translate its findings to communities to identify the most vulnerable and improve prevention, intervention and treatment for children from environmental exposures.

PI_NAMEs: CHEN, AIMIN ;HOWARTH, MARILYN ;SIMMONS, REBECCA A (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: 6 year old;Address;Administrative Efficiency;Advisory Committees;African American;Air Pollution;Area;Asthma;asthma prevention;Behavioral;Bioinformatics;blood lead;burden of illness;catalyst;Child;Child Health;college;Communication;Communities;community engagement;community partners;Day center care;Delaware;Development;Diabetes Mellitus;Discipline of Nursing;Disparity;Doctor of Medicine;Doctor of Philosophy;Ecology;Endocrine Disruptors;Endowment;Environmental Exposure;Environmental Health;Environmental Medicine;environmental toxicology;Epidemiology;experience;Harm Reduction;health knowledge;Health Personnel;Health Professional;High Prevalence;Hospitalization;Housing;implementation science;improved;Infrastructure;Institution;Intervention;Lead;lead exposure;Lead levels;Life;medical schools;member;Mentors;metropolitan;mid-career faculty;Mission;Neurodevelopmental Disorder;Obesity;Occupational Health;Occupational Medicine;Ozone;Parents;Particulate Matter;Pediatric Hospitals;Pediatrics;Pennsylvania;Philadelphia;Policy Maker;Policy Making;Pollution;Population;Premature Birth;Prevention;Prevention program;professor;programs;Reading;Research;Research Personnel;Resources;Risk;Schools;Scientist;Services;social;Testing;Toxicology;Translating;translational health science;Translational Research;Translations;Universities;Vision;web site

PROJECT_TITLE: Philadelphia Regional Center for Children’s Environmental Health


NIH_SPENDING_CATS: Pediatric;Social Determinants of Health

PI_NAMEs: SIMMONS, REBECCA A (contact)

PROJECT_TERMS: Administrative Efficiency;Advisory Committees;Advocate;Air Pollution;Area;asthma prevention;career development;catalyst;Child;Collaborations;Communication;Communities;community organizations;Complement;Development;Education;Educational workshop;Endocrine Disruptors;Ensure;Environmental Health;environmental toxicology;Evaluation;Fostering;Harm Reduction;Health Personnel;Home;innovation;Institution;Intervention;Knowledge;knowledge translation;lead exposure;Leadership;medical schools;meetings;member;Mentorship;minority investigator;Mission;next generation;Pediatric Hospitals;Pennsylvania;Persons;Philadelphia;Pilot Projects;Policy Maker;programs;Reproduction;Research;Resources;Schedule;Schools;Science;Scientist;Series;Services;social media;Social Policies;Social Sciences;Structure;success;symposium;teacher;Testing;translational approach;Translations;Underrepresented Minority;Universities;web site;webinar;Women's Health

PROJECT_TITLE: Philadelphia Regional Center for Children's Environmental Health


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Digestive Diseases;Food Allergies;Immunization;Nutrition;Prevention

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Food allergy is a major health issue in developed countries with a prevalence of up to 6% in U.S. children. In this proposal the mechanisms whereby IgG antibodies to food promote food tolerance will be investigated. Their potential application to treat food allergy will be tested in a humanized mouse model of food allergy.

PI_NAMEs: OETTGEN, HANS C (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Adjuvant;Affect;Affinity;Allergens;Allergic;allergic response;Allergy to peanuts;Anaphylaxis;Animals;Antibodies;Attenuated;B-Lymphocytes;Basophils;Cell Physiology;Cells;Child;cytokine;Developed Countries;Development;effector T cell;Endogenous Factors;Enterocytes;Environmental Risk Factor;Epithelial Cells;Equilibrium;Family;Fc Receptor;Food;food allergen;Food Hypersensitivity;food protection;Fostering;functional restoration;gastrointestinal epithelium;Health;human monoclonal antibodies;humanized mouse;IgE;Immediate hypersensitivity;Immune;Immune response;Immunity;Immunoglobulin G;Immunologics;immunoregulation;Impairment;in vivo;Ingestion;inhibitor;Interleukin-4;Intestines;mast cell;Mediating;Modeling;Monoclonal Antibodies;mouse model;Mus;oral immunotherapy;Pathogenicity;Pathway interactions;Patients;Play;Prevalence;Probability;promoter;protective effect;Reaction;Regulation;Regulatory T-Lymphocyte;response;Role;sensor;Signal Induction;Signal Transduction;Specificity;T-Lymphocyte;Testing;Th2 Cells;therapeutic target;transcriptome;Variant;villin;Work

PROJECT_TITLE: Mast cell regulation of Th2 induction and tolerance breakdown in food allergy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)S]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases

ORG_DEPT: DENTISTRY

PHR: PROJECT NARRATIVE We will determine if the existence of VBNC subpopulations with the ability to resuscitate allows P. gingivalis to survive intracellular stress conditions that it encounters thus allowing P. gingivalis to exist and persist in a chronic state of infection. If successful, this research will identify possible therapeutic protein targets for treating periodontal disease.

PI_NAMEs: PROGULSKE-FOX, ANN  (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Agar;Animal Model;Bacteria;Biological Markers;Cells;Chemicals;Chronic;chronic infection;Data;design;disease model;Event;experimental study;Future;Gene Expression;Genes;Genetic Transcription;Goals;Growth;In Vitro;in vivo;in vivo Model;Infection;insight;Invaded;knockout gene;Metabolic;Metabolism;metabolomics;Methods;Modeling;Molecular;mouse model;Mus;mutant;Names;Nutritional;oral pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Pattern;Periodontal Diseases;Periodontitis;Population;Porphyromonas gingivalis;Proteins;Research;Resuscitation;Role;Site;Stress;Testing;therapeutic protein;transcriptome sequencing;Virulence

PROJECT_TITLE: Investigating the viable but not culturable (VBNC) state in P. gingivalis


NIH_SPENDING_CATS: Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric

PROJECT_TERMS: Applications Grants;Area;candidate identification;career;Career Choice;career development;catalyst;Child;Child Support;Communities;community empowerment;community engagement;community organizations;community partners;Continuing Education;Data;Databases;design;Development;Development Plans;Early identification;Educational Curriculum;Educational workshop;Environmental Health;experience;Extramural Activities;Faculty;Funding;Goals;Grant;Health Professional;health science research;innovation;Institution;interest;knowledge translation;Learning;Link;member;Mentors;Mentorship;Mission;next generation;Philadelphia;Pilot Projects;Policies;Productivity;professor;Program Reviews;programs;recruit;Research;Research Personnel;Scientist;senior faculty;Site;skills;skills training;success;Time;tool;Training;Translating;Underrepresented Minority;United States National Institutes of Health;virtual;Woman;Work


NIH_SPENDING_CATS: Asthma;Clinical Research;Lead Poisoning;Lung;Pediatric;Prevention;Social Determinants of Health

PI_NAMEs: HOWARTH, MARILYN  (contact)

PROJECT_TERMS: Academy;Acceleration;Address;Adolescent;Air;Air Pollution;Area;Asbestos;Asthma;asthma prevention;Awareness;care providers;Caring;Certification;chelation;Chemical Exposure;Child;Child Care;Childhood;Childhood Asthma;Communication;Communities;community partners;community partnership;community setting;Computerized Medical Record;Consultations;Counseling;curriculum development;Dangerousness;Data;design;Dissemination and Implementation;drinking water;Educational Curriculum;Educational process of instructing;Endocrine Disruptors;Environmental Exposure;Environmental Health;Evaluation;Excision;Funding;Harm Reduction;Health;Health care facility;health knowledge;Health Resources;high risk;Home;Home visitation;implementation science;improved;K-12 Faculty;Lead;lead exposure;Lead Poisoning;Learning;Link;Location;Medical;medical specialties;Mentors;Methods;Mission;Parents;Pediatric Hospitals;peer;Philadelphia;Pilot Projects;Policies;Policy Developments;Population;Prevention;Prevention program;Process;programs;Public Policy;Refugees;remediation;Research;Research Personnel;Resources;response;Risk;Risk Assessment;Schools;Science;screening;Series;skills;soil sampling;teacher;Techniques;telehealth;Testing;tool;Toxicology;Training Programs;translational goal;translational health science;Translations;vulnerable community;Vulnerable Populations;Water;water testing;webinar;willingness;Work;Youth


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Cystic Fibrosis;Genetics;Lung;Orphan Drug;Pulmonary Fibrosis;Rare Diseases;Tobacco;Tobacco Smoke and Health

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Idiopathic pulmonary fibrosis (IPF) is a disabling, progressive interstitial lung disease with no known cure and limited therapeutic options that do not halt disease progression. A major and common risk factor for developing IPF is a promoter variant of the MUC5B gene that leads to increased MUC5B expression, yet the mechanistic role of elevated MUC5B in IPF pathogenesis remains unclear due to lack of animal model that can recapitulate its deleterious effects related to mucus. This proposal will develop a ferret model for IPF to provide novel opportunities that define how Muc5b expression contributes to disease progression and evaluate Muc5b-directed therapies, providing a definitive advance for IPF research.

PI_NAMEs: ROWE, STEVEN MARK (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Accounting;Address;Affect;Air;Airway Disease;airway remodeling;Animal Model;Antisense Oligonucleotides;Area;Biochemical;Biopolymers;Bleomycin;cell type;Cellular biology;Characteristics;Chronic;Chronic Bronchitis;Chronic Obstructive Pulmonary Disease;cigarette smoke;cigarette smoking;Clinical;clinically relevant;Collagen;Cyst;Cystic Fibrosis;Data;Defect;Development;Diffuse;Disabling;Disease;Disease Progression;Distal;drug development;drug discovery;Educational workshop;Environment;Equilibrium;Evaluation;Exhibits;experimental study;Exposure to;exposure to cigarette smoke;Ferrets;Fibrosis;fibrotic lung;fibrotic lung disease;gain of function;Gel;Genetic;genetic association;genome wide association study;Gland;Goals;Histopathology;Host Defense;Human;human disease;idiopathic pulmonary fibrosis;improved;Influenza;Interstitial Lung Diseases;Ions;Knowledge;Lung;lung injury;lung repair;Modeling;Molecular;MUC5B gene;Muc5B protein;Mucins;Mucociliary Clearance;Mucous body substance;Mus;National Heart, Lung, and Blood Institute;Nebulizer;new therapeutic target;novel;Outcome;overexpression;Pathogenesis;Persons;pharmacologic;Phenotype;Physiology;Prevalence;Process;promoter;protein function;protein structure;Proteins;Pulmonary Fibrosis;Pyocyanine;repaired;Reporting;Research;Research Personnel;Respiratory Mucin;Risk;Risk Factors;Rodent;Rodent Model;Role;Saline;Severities;Severity of illness;single-cell RNA sequencing;Smoke;Specificity;Structure;Structure of parenchyma of lung;Submucosa;Testing;Therapeutic;therapeutic target;Tissues;Validation;Variant

PROJECT_TITLE: Therapeutic targeting of MUC5B in a novel ferret model of idiopathic pulmonary fibrosis


NIH_SPENDING_CATS: Cardiovascular;Neurosciences

ORG_DEPT: NEUROSCIENCES

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: Overactivation of neuroendocrine and autonomic systems is a common occurrence in prevalent diseases, including salt-dependent hypertension and heart failure. Using a multidisciplinary approach, we propose to investigate mechanisms that mediate activity-dependent neurovascular coupling in the hypothalamus and the impact this process has on neurosecretory neurons that regulate bodily homeostasis in health and disease states. The proposed study will generate novel information on mechanisms underlying altered neuronal function in a heart failure rodent model.

PI_NAMEs: FILOSA, JESSICA A;STERN, JAVIER E (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Acute;Address;adeno-associated viral vector;Area;arteriole;ASIC channel;Astrocytes;Automobile Driving;Blood flow;Blood Vessels;Brain;Brain region;Cannulations;Cardiometabolic Disease;Cardiovascular Diseases;Cells;cellular targeting;Characteristics;Chronic;Data;designer receptors exclusively activated by designer drugs;Disease;Dorsal;Electrophysiology (science);Feedback;Functional disorder;Glucose;Glutamate Transporter;Health;Heart failure;Homeostasis;Hypertension;hypoperfusion;Hypothalamic structure;Hypovolemia;Hypovolemics;Hypoxia;Image;in vivo;innovation;interdisciplinary approach;Isotonic Exercise;Knowledge;Link;Masks;Measurement;Measures;Mediating;Modality;Modeling;Molecular Target;Monitor;Neurons;Neuropeptides;Neurosecretory Systems;neurotransmission;neurovascular coupling;Nitric Oxide;novel;novel strategies;Operative Surgical Procedures;patch clamp;Pathologic;Peripheral;pharmacologic;Physiological;Physiological Processes;Population;Process;Rat Transgene;Regulation;response;Response to stimulus physiology;Rodent Model;Role;Sensory;Signal Transduction;Sodium Chloride;Stimulus;supraoptic nucleus;System;Techniques;therapeutic target;Time;Tissues;two-photon;vasoconstriction;Vasodilation;Vasopressins;Viral Vector;Visualization;Work

PROJECT_TITLE: Inverse neurovascular coupling in the hypothalamus and its role in positive feedback regulation of Vasopressin neurons in health and disease


ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: Project Narrative We need a better understanding of negative blood-oxygen-level-dependent response (NBR) that is often used as an index of neuronal suppression in human functional magnetic resonance imaging (fMRI) studies. This understanding is critical to interpret fMRI data that rely on neurovascular and neurometabolic coupling. The proposed high-resolution NBR research expand our understanding of NBR dynamics and the corresponding physiology, which broadens the utility of fMRI to understand normal human brain functions.

PI_NAMEs: KIM, JUNG HWAN  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: arterial spin labeling;Blood flow;blood oxygen level dependent;Brain;brain dysfunction;Brain Pathology;Brain region;Cerebrovascular Circulation;Characteristics;Computer Models;Core-Binding Factor;Coupling;Data;deoxyhemoglobin;experimental study;Failure;Functional Magnetic Resonance Imaging;Goals;gray matter;hemodynamics;Human;Image;imaging study;indexing;Ipsilateral;Knowledge;Measurement;Measures;Metabolism;Methods;Modality;Modeling;neural;Neurons;Neurosciences;neurovascular;novel;Oxygen;Physiological;Physiology;Reporting;Research;Resolution;response;Sampling;Scheme;Signal Transduction;Somatosensory Cortex;spatiotemporal;Stimulus;Structure;success;Surface;Synapses;temporal measurement;Time;trend;Variant;vasoconstriction;Venous;Visual Cortex

PROJECT_TITLE: Characterization of neurovascular and neurometabolic coupling of the negative BOLD response in human

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Rare Diseases

PHR: Project Narrative Gliomas are incurable tumors. We recently discovered that Collagen 1A1 is expressed at high levels in perivascular cells and also in tumor cells themselves. We will now examine the role of Collagen 1A1 in each cell type. To do so we will explore whether cell-type specific depletion of Collagen 1A1 from glioma cells will halt tumor progression. These result will permit to develop therapeutics targeted to collagen expression.

PI_NAMEs: LOWENSTEIN, PEDRO R. (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Animals;Area;Blood Vessels;Brain;Brain Neoplasms;brain tissue;Cell Compartmentation;cell stroma;cell type;Cells;chemotherapy;COL1A1 gene;Collagen;Collagen Fiber;Collagen Receptors;Data;DDR1 gene;density;evidence base;Excision;experimental study;Fascicle;Gene Deletion;Genetic;Genetically Engineered Mouse;Glioblastoma;Glioma;Goals;Growth;Human;human data;Immune;improved;in vivo;inhibitor;Invaded;knock-down;Lasers;Lesion;Malignant Glioma;Mammary Neoplasms;Mediating;Mesenchymal;Microdissection;Modeling;Molecular;Motion;mouse model;Mus;neoplastic cell;neuropathology;new therapeutic target;Operative Surgical Procedures;Outcome;pancreatic neoplasm;Patients;Pattern;Pericytes;pharmacologic;Play;pre-clinical;preservation;Prognosis;Prostatic Neoplasms;Radiation;Radiation therapy;receptor;Recurrence;Recurrent tumor;resistance mechanism;response;Role;Signal Transduction;single-cell RNA sequencing;Sleeping Beauty;small hairpin RNA;standard of care;Stromal Cells;Structure;System;temozolomide;The Cancer Genome Atlas;therapeutic target;transcriptome sequencing;Transgenic Organisms;tumor;Tumor Cell Invasion;tumor microenvironment;tumor progression;tumor-immune system interactions

PROJECT_TITLE: The Role of Collagen and its Signaling Mechanisms in Glioma Progression and Invasion.


NIH_SPENDING_CATS: Autism;Brain Disorders;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: DAVIS

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Narrative We propose to determine Chandelier (Ch) cell pathophysiology association to ASD symptomatology in specific cortical and subcortical areas known to be involved in Autism Spectrum Disorder (ASD). Ch cells are the interneurons that regulate the final output of projection neurons in the neocortex, hippocampus, and amygdala. This proposal will explore the hypothesis that disturbances in Ch cell number in several areas of the cerebral cortex and subcortical areas contribute to the altered function of the GABAergic system and the symptomatology reported in the ASD brain.

PI_NAMEs: MARTINEZ-CERDENO, VERONICA  (contact)

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: Address;Amygdaloid structure;Anatomy;Antibodies;Area;ASD patient;autism spectrum disorder;Autopsy;Basal Ganglia;Behavior;Brain Diseases;case control;Cell Count;cell type;Cells;Cerebral cortex;Cornus;dentate gyrus;follow-up;Functional disorder;Funding;gamma-Aminobutyric Acid;Glial Fibrillary Acidic Protein;Goals;Grant;Hippocampal Formation;Hippocampus;Human;human tissue;Immunochemistry;Impairment;individuals with autism spectrum disorder;interest;Interneurons;Knowledge;Lateral;MFGE8 gene;Motor;Neocortex;neocortical;nestin protein;neurogenesis;neuronal cell body;Neurons;Output;Patients;Prefrontal Cortex;Proteins;Reporting;Role;Severities;social;somatosensory;stem cells;symptomatology;Symptoms;System;Testing;Tissue Stains;Tissues;Translating;Translational Research;Visual

PROJECT_TITLE: Cortical and subcortical chandelier cell pathophysiology and symptomatology in autism

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE: How the hippocampal-entorhinal cortex system integrates the contextual and spatial features of an experience is an open question. The proposed research will use immersive virtual reality in two rare human cohorts while recording either (1) single neurons or (2) intracranial neural population activity during free movement. The results from the proposed study will provide insight into how humans encode the contextual and spatial dimensions of episodic memories and will ultimately enhance our understanding of the neurophysiology of memory decline in neurological diseases.

PI_NAMEs: MAOZ, SABRINA LEAH LEVY (contact)

PROJECT_TERMS: 3-Dimensional;3D virtual reality;Address;Affect;Animals;Cells;Chronic;Clinical;Cognitive;cohort;Complex;Computer Models;Cues;Data;Development;Dimensions;effective therapy;Electrodes;Electroencephalography;entorhinal cortex;Environment;Episodic memory;Event;experience;flexibility;Foundations;Functional Magnetic Resonance Imaging;Hippocampus;Human;Immobilization;Impairment;Implant;Implanted Electrodes;improved;insight;Joystick;Learning;Location;Maps;Measures;Memory;Memory Disorders;memory encoding;Memory Loss;Mental disorders;Movement;Nervous System Disorder;neural;Neurologic;neuromechanism;Neurons;neurophysiology;neurosurgery;Participant;Patients;Pattern;Performance;Phase;Population;predictive modeling;preservation;programs;Property;Research;research clinical testing;Research Project Grants;Rodent;Signal Transduction;spatial memory;Support System;System;Technology;Texture;Time;virtual reality;virtual reality environment;way finding;wireless

PROJECT_TITLE: Context-based neural representations of space: hippocampal-entorhinal neurophysiology in ambulating humans


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Immunization;Infectious Diseases;Liver Disease;Malaria;Malaria Vaccine;Nanotechnology;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

PHR: NARRATIVE Malaria vaccines that block the parasite lifecycle in the liver depend on cytotoxic T cells that kill infected hepatocytes. This project aims to develop a two-dose vaccine regimen that significantly increases the formation of liver resident memory T cells in the liver using an established mode of priming coupled to a novel, orally-delivered booster vaccine. This project will help improve the efficacy of malaria vaccines and accelerate work toward a protective malaria vaccine.

PI_NAMEs: MURPHY, SEAN C (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: absorption;Acceleration;Antigen Presentation;Antigens;Attenuated;Bile Acids;Bile fluid;Biocompatible Materials;Biology;booster vaccine;CD8-Positive T-Lymphocytes;CD8B1 gene;cell killing;cell type;Cells;Cessation of life;Characteristics;Chemistry;Circulation;Clinical;Clinical Trials;Collaborations;Communicable Diseases;Communities;Coupled;Culicidae;Cytotoxic T-Lymphocytes;Data;Dependovirus;Development;Diabetes Mellitus;Disease;DNA;DNA delivery;Doctor of Philosophy;Dose;Drug Delivery Systems;Engineering;Ensure;Enterohepatic Circulation;Erythrocytes;FDA approved;first-in-human;Formulation;Frequencies;Gene Combinations;gene gun;gene therapy;Goals;Hepatocyte;Human;Immune signaling;Immunity;immunogenicity;Immunology;improved;Infection;Injections;Insulin;Insulin-Dependent Diabetes Mellitus;Intravenous;intravenous administration;Knowledge;Laboratories;Life Cycle Stages;Lipids;Literature;Liver;Malaria;Malaria Diagnostic;Malaria Vaccines;manufacture;materials science;Memory;Methods;Mission;Mus;nanoparticle;National Institute of Allergy and Infectious Disease;next generation;nonhuman primate;novel;Nucleic Acids;Oral;Oral Administration;oral vaccine;Parasites;Performance;Persons;Pharmacology;Phase;plasmid DNA;Plasmodium;Plasmodium vaccine;Polymers;Preclinical Testing;prevent;Radiation;Ramp;rational design;recruit;Regimen;Reporting;Research Personnel;Rhesus;RNA;Safety;Salivary Glands;Scientist;Shapes;Small Intestines;Sporozoites;Sterility;success;Surface;T-Lymphocyte;Testing;Therapeutic;therapeutic gene;tissue resident memory T cell;Tissues;Universities;Vaccination;vaccine development;vaccine distribution;vaccine strategy;Vaccines;vector;Viral;Washington;Work

PROJECT_TITLE: Development of an oral liver-targeted prime-and-trap malaria vaccine


NIH_SPENDING_CATS: Behavioral and Social Science;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pain Research;Palliative Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Metastatic breast cancer substantially contributes to persistent health disparities in morbidity and mortality. The goal of this study is to develop a socio-culturally sensitive, community-based, early palliative care intervention to mitigate disparities in distress and symptom burden in Black women with metastatic breast cancer and to test its preliminary impact through a pilot randomized controlled trial. These findings will inform better equity promotion of palliative care delivery and improved outcomes for underserved and underrepresented patients with advanced cancer.

PI_NAMEs: MAZOR, MELISSA  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;Advanced Malignant Neoplasm;Area;attentional control;Award;Biometry;black women;cancer health disparity;Cancer Patient;care delivery;care outcomes;career development;Caring;Chronic Care;Clinic;Clinical;Clinical Trials;Clinical Trials Design;cognitive interview;Communities;community engaged research;community organizations;Complex;Data;design;Development;Diagnosis;Discipline of Nursing;disparities in morbidity;Disparity;disparity reduction;Dissemination and Implementation;Distress;end of life;Environment;Equity;ethnic diversity;Evaluation;evidence base;Evidence based intervention;experience;Family;Fatigue;Feedback;Focus Groups;Foundations;Funding;Geriatrics;Goals;Grant;Health Disparities Research;health disparity;health equity;Health Services;Healthcare Systems;improved;improved outcome;Individual;innovation;Institution;Internal Medicine;Intervention;intervention delivery;Knowledge;Latinx population;Leadership;Malignant Breast Neoplasm;Malignant Neoplasms;medical schools;Medicine;Mentors;Metastatic breast cancer;Methods;minority patient;Modeling;Morbidity - disease rate;mortality;multidisciplinary;NCI-Designated Cancer Center;Neuropathy;New York City;Not Hispanic or Latino;Nurses;Oncologist;Oncology;Pain;Palliative Care;Palliative Medicine;Patient Care;Patients;physical symptom;Population Heterogeneity;Preparation;primary outcome;programs;psychologic;psychological symptom;racial disparity;racial diversity;racial minority;Randomized, Controlled Trials;Recommendation;Reporting;Research;Research Activity;Research Infrastructure;Research Personnel;Research Support;Rural;Scholarship;Screening for cancer;Self Management;skills;social;social culture;social determinants;social health determinants;Solid;Symptom Burden;symptom management;Testing;therapy development;Time;Training;Training Activity;treatment arm;Underrepresented Populations;Underserved Population;United States National Institutes of Health;White Women;Woman;Writing

PROJECT_TITLE: The Development and Evaluation of a Community-Based, Early Palliative Care Intervention for Black Women with Metastatic Breast Cancer

STUDY_SECTION: NCI

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


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Pediatric;Prevention;Rare Diseases;Vaccine Related

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: The University of Rochester Vaccine and Treatment Evaluation Unit (VTEU) will offer a highly diversified team of investigators experienced in collaborative research and a site with the necessary scientific, clinical, administrative and organizational structure to support NIAID clinical research initiatives to evaluate methods for the treatment and prevention of infectious diseases. Our research capabilities will also provide the VTEU network with a variety of cutting edge technologies to interrogate the host response and develop a deeper understanding of the pathogenesis for many infectious diseases.

PI_NAMEs: BRANCHE, ANGELA RAMONA;FALSEY, ANN R (contact)

PROGRAM_OFFICER_NAME: HALL, CYNDA GAY

PROJECT_TERMS: Address;Adolescent;Adult;Age;Antibiotic-resistant organism;Antibiotics;Area;Biological Products;Categories;Child;Childhood;Cities;Clinic;Clinical;Clinical Research;clinical research site;Clinical Trials;Collaborations;combat;Communicable Diseases;Communities;County;Data;Data Analyses;data management;design;Development;Devices;Diagnostic;Disease;Disease Outbreaks;Drug Kinetics;drug resistant bacteria;Education;emerging virus;Enrollment;Ensure;Enteral;Evaluation;experience;Faculty;fighting;flexibility;Genetic Transcription;Good Clinical Practice;Health;Health Personnel;Hospitals;Human Resources;Humanities;Immune response;Immunization;Immunology procedure;improved;Infant;Infection;Influenza;innovation;Intervention;Investigation;Laboratories;Laboratory Research;Leadership;Malaria;Measles;Methods;microbiome analysis;Multi-Institutional Clinical Trial;Multicenter Trials;Mumps;National Institute of Allergy and Infectious Disease;next generation;novel;novel therapeutics;novel vaccines;older adult;optimism;organizational structure;pathogen;Pathogenesis;Patients;Persons;Pertussis;Pharmacy facility;Phase;Physicians;Policies;Poliomyelitis;Positioning Attribute;pre-clinical research;predictive marker;Pregnant Women;premature;Preparation;preservation;Prevention;Preventive;Procedures;Protocols documentation;recruit;Reporting;Research;Research Personnel;Resources;respiratory;Risk;Sampling;Scientist;Secure;Sexually Transmitted Diseases;Site;Surgeon;Target Populations;Technology;Testing;Therapeutic;Training;Tuberculosis;United States;United States National Institutes of Health;Universities;Vaccination;vaccine access;vaccine evaluation;Vaccines;Vulnerable Populations;War;Work;young adult


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Immunotherapy;Orphan Drug;Precision Medicine;Radiation Oncology;Rare Diseases

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: Project Narrative The overall goal of this application is to enhance the translational applicability of mammalian tumor models by performing a cross-comparative evaluation of in vitro (organoids) and in vivo (xenograft/allograft) models of head and neck cancer. Consistent with the objectives of PAR-17-245, we propose to perform a systematic in- depth comparison of histopathologic, radiologic, genomic, and therapeutic response profiles across these multiple preclinical platforms. In addition to testing standard of care treatment regimens, paired in vitro and in vivo models will be used to screen the activity of novel and FDA-approved agents targeting critical pathways implicated in the pathogenesis of HNSCC.

PI_NAMEs: SESHADRI, MUKUND  (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Adrenergic beta-Antagonists;Allografting;Appearance;Autologous;biobank;Bioinformatics;Biological Models;Biology;biomarker discovery;cancer imaging;Cancer Model;Cetuximab;chemoradiation;Cisplatin;Clinical;Coculture Techniques;Collaborations;comparative;Comprehensive Cancer Center;Credentialing;Critical Pathways;Critiques;Data;Development;Disease;Dissection;drug candidate;drug efficacy;drug repurposing;Drug Screening;efficacy evaluation;Evaluation;Exhibits;experience;FDA approved;Functional Imaging;Future;Gene Expression Profile;Genomics;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Heterogeneity;high-throughput drug screening;Histone Deacetylase Inhibitor;HPV negative;Human;human disease;image guided;imaging biomarker;imaging modality;immune checkpoint blockade;Immunocompetent;Immunological Models;immunological status;immunoregulation;In Vitro;in vivo;in vivo Model;innovation;insight;Investigation;Malignant Neoplasms;Mediating;Modeling;Molecular;Molecular Profiling;mouse model;Multimodal Imaging;multimodality;Mus;Mutation;Neoplasms;novel;novel strategies;novel therapeutics;Organoids;Pathogenesis;patient derived xenograft model;patient population;patient response;Patients;Pharmaceutical Preparations;pre-clinical;precision medicine;Propranolol;Publishing;Quality of life;Radiation;radiation response;Radiation therapy;Radiogenomics;Radiology Specialty;research clinical testing;Research Personnel;Resistance;resistance mechanism;Respiratory physiology;response;Safety;screening;Siblings;Speech;standard of care;System;T-Lymphocyte;targeted agent;Testing;Therapeutic;Therapeutic Trials;transcriptome sequencing;Treatment Efficacy;Treatment Protocols;treatment response;treatment strategy;tumor;tumor immunology;tumor xenograft;Validation;Valproic Acid;Work;Xenograft procedure

PROJECT_TITLE: Radiogenomic Credentialing of Head and Neck Cancer Models

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-N(55)R]


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Pediatric;Prevention;Rare Diseases;Social Determinants of Health;Substance Misuse;Tuberculosis;Vaccine Related;Women's Health Research

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: NARRATIVE Research on HIV and related infections has improved the treatment and prevention of disease, but much more needs to be done to control the epidemic. The proposed Clinical Trials Unit will join together the most active HIV clinical research sites in Baltimore, Maryland, Pune, and Chennai, India, to optimize patient-oriented research and to access key populations affected by this epidemic for participation in clinical trials.

PI_NAMEs: FLEXNER, CHARLES W.;GUPTA, AMITA  (contact)

PROGRAM_OFFICER_NAME: TUCKER, JENESE

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adolescent;Adult;Affect;African American population;AIDS clinical trial group;AIDS prevention;Area;Baltimore;care providers;Caring;Child;Childhood;cis-female;clinical care;Clinical Pharmacology;Clinical Research;Clinical Research Protocols;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;cohesion;Color;Communicable Diseases;Communication;Communities;community advisory board;comorbidity;disorder prevention;Distance Learning;Education;Enrollment;Epidemic;epidemic response;experience;Funding;Government;Health;Hepatitis;high risk;HIV;HIV prevention trials network;HIV vaccine;HIV Vaccine Trials Network;HIV/TB;Home;Human Subject Research;Immunology;improved;India;Infant;Infection;Infrastructure;innovation;Institution;Institutional Review Boards;International;International Maternal Pediatric Adolescent AIDS Clinical Trials;intravenous drug use;Latinx;Leadership;Maryland;Media Campaign;medical schools;men who have sex with men;Mentorship;Microbicide Trials Network;Mission;National Institute of Allergy and Infectious Disease;operation;Participant;patient oriented research;Population;Poverty;Pregnant Women;Prevention Research;Process;Productivity;programs;Protocols documentation;Provider;Publications;Recording of previous events;recruit;Research;research facility;Research Personnel;research study;Resource Sharing;Resources;Science;Scientific Advances and Accomplishments;Scientist;sexually active;Site;smartphone application;social media;Structure;Substance abuse problem;substance user;synergism;System;Therapeutic;Training;transgender;transgender women;treatment research;Tuberculosis;Tuberculosis Vaccines;Underrepresented Populations;United States National Institutes of Health;Universities;Viral hepatitis;web portal

PROJECT_TITLE: Johns Hopkins University Baltimore India Clinical Trail Unit (JHUBI CTU)


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Lung;Orphan Drug;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: TYLER

ORG_NAME: UNIVERSITY OF TEXAS HLTH CTR AT TYLER

PHR: Lung fibrosis is a progressive fatal scarring disorder affecting thousands of US patients annually and currently is incurable. We found that targeting caveolin-1 and tumor suppressor protein, p53 with a novel drug candidate; CSP7, will resolve full-blown lung fibrosis and improve lung function in mice when administered via the airway. The information gained from this project will accelerate the development of this novel and potentially more effective therapeutic candidate for the treatment of idiopathic and other fibrotic lung diseases.

PI_NAMEs: SHETTY, SREERAMA  (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Acceleration;advanced disease;Affect;alveolar epithelium;Apoptosis;Apoptotic;Architecture;Area;Binding;Biodistribution;Biological Availability;Bleomycin;caveolin 1;Cell Aging;Cell surface;Cell Survival;cell type;Cells;Cicatrix;Clinical;Clinical Trials;connective tissue growth factor;Data;Deposition;Development;Diagnosis;Disease;Disparity;Dose;drug candidate;Drug Delivery Systems;drug discovery;Drug Kinetics;Dryness;Dyspnea;effective therapy;efficacy evaluation;efficacy testing;Epithelial Cells;Extracellular Matrix;FDA approved;Fibroblasts;fibrotic lung;fibrotic lung disease;Formulation;Functional disorder;Future;Heterogeneity;idiopathic pulmonary fibrosis;improved;In Vitro;in vivo;Incidence;Individual;Inhalation;Inhalation Device;injured;innovation;Interstitial Lung Diseases;Intervention;Invaded;Lead;Lung;Lung Diseases;lung injury;lung lesion;Lung Transplantation;Maintenance;Measures;Mediating;Medical;Membrane;migration;Minority;Modeling;Molecular;Molecular and Cellular Biology;Morphology;mouse model;Mus;Myofibroblast;Nebulizer;nintedanib;novel;novel therapeutics;old mice;Outcome;Pathogenesis;Pathway interactions;Patients;Peptides;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacotherapy;Pirfenidone;Population;Powder dose form;pre-clinical;pre-clinical assessment;Pre-Clinical Model;preservation;Probability;Prognosis;Proliferating;Property;Publications;Pulmonary Fibrosis;pulmonary function;pulmonary function decline;Refractory;repaired;Reporting;Resistance;Resolution;Safety;scaffold;senescence;side effect;Signal Transduction;Silicon Dioxide;Structure;Structure of parenchyma of lung;success;Tertiary Protein Structure;therapeutic candidate;therapeutic target;therapeutically effective;Toxicology;TP53 gene;Transforming Growth Factor beta;Tumor Suppressor Proteins;Variant;Work

PROJECT_TITLE: Development, Formulation and Inhalational Delivery of a New Peptide for ILD

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Genetics;Lung;Prevention;Pulmonary Fibrosis;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Idiopathic pulmonary fibrosis (IPF) is a devastating end-stage lung disease of unknown etiology and no cure. The strongest risk factor of IPF is the MUC5B promoter rs35705950 minor allele that leads to excessive MUC5B mucin secretion in the distal airways. IPF lung is also characterized by activation of ER stress in the respiratory epithelium. We propose the hypothesis that activation of ER stress leads to excessive MUC5B production in the distal airways that promotes development of pulmonary fibrosis.

PI_NAMEs: CHEN, GANG  (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Aging;airway epithelium;airway remodeling;Alleles;alveolar epithelium;alveolar type II cell;Alveolus;Apoptosis;Binding;Binding Proteins;Biochemical;Biological Assay;biophysical properties;Bleomycin;Cell Physiology;Cells;Cellular Stress;Cyst;Data;Defect;Development;Disease Progression;Distal;Early Diagnosis;effective therapy;Electrophysiology (science);endoplasmic reticulum stress;Environmental Risk Factor;Epithelial Cells;epithelial injury;Epithelium;Etiology;Exposure to;Factor X;Fibroblasts;Fibrosis;Functional disorder;Gene Expression;Genes;Genetic;genetic variant;Genotype;Host Defense;human model;Hypoxia;idiopathic pulmonary fibrosis;Impairment;In Vitro;in vitro Assay;in vivo;Individual;Infection;Inflammation;Influenza;Influenza A Virus, H1N1 Subtype;Injury;injury and repair;Laboratories;Lead;Lung;Lung Diseases;lung repair;Maintenance;Mediating;Messenger RNA;Minor;Modeling;mouse genetics;mouse model;MUC5B gene;Mucins;Mucociliary Clearance;Mucous body substance;Mus;Mutation;Myofibroblast;Natural regeneration;notch protein;novel;novel marker;Onset of illness;overexpression;Peripheral;Persons;Phenotype;Predisposition;prevent;Probability;Production;progenitor;promoter;Proteins;Pulmonary Fibrosis;repaired;response;response to injury;Risk;Risk Factors;RNA Splicing;Role;Signal Transduction;stem cell function;stem cell homeostasis;stem cells;surfactant;System;Telomerase;Testing;therapeutic target;Time;transcription factor;Variant;XBP1 gene

PROJECT_TITLE: Role of the ER stress transcription factor XBP1S in the development of idiopathic pulmonary fibrosis

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Biotechnology;Cancer;Dental, Oral, and Craniofacial Disease;Emerging Infectious Diseases;Genetics;HIV/AIDS;Infectious Diseases;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Narrative Lytic replication of Kaposi’s sarcoma-associated herpesvirus (KSHV) in the oral cavity is critical for both KSHV- induced tumorigenesis and dissemination of the virus. The goal of our study is to evaluate the genome-wide role of the viral interferon regulatory factors of KSHV in order to identify their key targets controlling host-pathogen interactions at the cellular level during oral infection, which is the very first step during infection of humans. We expect that our results can facilitate the future development of novel antiviral approaches, which could ultimately eliminate KSHV transmissions.

PI_NAMEs: PAPP, BERNADETT ;TOTH, ZSOLT  (contact)

PROGRAM_OFFICER_NAME: BACCAGLINI, LORENA

PROJECT_TERMS: Acetylation;AIDS related cancer;Anti-viral Therapy;B-Lymphocytes;Binding;Biological;Cell Communication;cell growth;Cell Nucleus;Cell Survival;Cells;ChIP-seq;chronic infection;Complex;Cytoplasm;Data;Development;DNA Binding;DNA Binding Domain;DNA Viruses;Down-Regulation;Endothelium;Epigenetic Process;Epithelial Cells;Epithelium;Etiology;EZH2 gene;Future;Gene Expression;Gene Expression Regulation;gene induction;gene induction/repression;gene repression;Gene Targeting;Genes;genome-wide;Gingiva;Goals;Herpesviridae;Herpesviridae Infections;Histone Acetylation;histone acetyltransferase;Histone H3;histone methylation;histone methyltransferase;Host Defense;Human;Human Herpesvirus 8;Immune;Immune Evasion;Immune Response Regulation Pathway;Infection;Integration Host Factors;Investigation;Kaposi Sarcoma;Knowledge;Link;Lysine;Lytic;Lytic Phase;lytic replication;Mediating;Medical;Methylation;Multicentric Angiofollicular Lymphoid Hyperplasia;mutant;novel;Nuclear;Oncogenic Viruses;Oral cavity;oral cavity epithelium;oral infection;Oral mucous membrane structure;Palate Kaposi's Sarcoma;particle;pathogen;Pathway interactions;Polycomb;Population;primary effusion lymphoma;promoter;protein complex;Proteins;recruit;Regulation;Repression;Role;Saliva;small hairpin RNA;small molecule inhibitor;Source;Testing;transcriptional reprogramming;transcriptome sequencing;transmission process;tumor;tumorigenesis;Viral;Viral Genes;Viral Genome;viral interferon regulatory factor;viral interferon regulatory factor-1;viral interferon regulatory factor-3;Viral Physiology;Viral Proteins;Viral reservoir;viral transmission;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Immune evasion mechanisms by a tumor herpesvirus in the oral cavity


ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE This study will test the hypothesis that higher levels of persistent chemicals like the DDT metabolite, DDE, that are concentrated in fat, are associated with reduced weight loss and reduced improvement in metabolic health after bariatric surgery. We seek to identify molecular pathways, altered by DDE in fat tissue, that underlie these effects. The goal is to develop a new paradigm for studying effects of persistent chemicals in fat that could ultimately lead to new strategies for treatment and prevention.

PI_NAMEs: CHATZI, VAIA LIDA  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Adipocytes;Adipose tissue;Adolescent;Adolescent obesity;Adult;adult obesity;Age;Animal Model;Animals;Archives;Attenuated;bariatric surgery;Behavioral;Biometry;Blood;Body mass index;Body Weight decreased;Cell Line;Cells;Chemicals;Child;Chlorinated Hydrocarbons;Clinical;Clinical Data;clinically relevant;cohort;Cohort Effect;Complement;Data;Diabetes prevention;dichlorodiphenyltrichloroethane;Dose;Dyslipidemias;Energy Metabolism;Environmental Epidemiology;epidemiology study;Experimental Models;experimental study;Exposure to;Fatty acid glycerol esters;Functional disorder;Future;Gene Expression;Goals;Health;Homeostasis;Human;human study;Hyperglycemia;impaired glucose tolerance;Impairment;improved;In Vitro;innovation;Insecticides;insulin regulation;Insulin Resistance;insulin signaling;interest;Intervention;lipid biosynthesis;Lipolysis;lipophilicity;Measures;Metabolic;Metabolic Diseases;metabolome;metabolomics;Modeling;Molecular;Morbid Obesity;multiple omics;Natural experiment;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;novel therapeutic intervention;Obesity;obesity in children;obesogen;obesogenic;Observational Study;Outcome;Participant;Pathway interactions;persistent organic pollutants;polybrominated diphenyl ether;Predisposition;Prevalence;Prevention;primary outcome;Prospective Studies;Regulation;Research;Research Design;Research Personnel;Rodent;sociodemographics;Subgroup;System;Teenagers;Testing;Thermogenesis;tissue archive;Tissue Sample;Tissue-Specific Gene Expression;Tissues;tool;Toxic effect;toxicant;Toxicology;transcriptome;translational study;Visceral;Youth

PROJECT_TITLE: Effects of DDE exposure on adipose tissue function, weight loss and metabolic improvement after bariatric surgery: A new paradigm for study of lipophilic chemicals

STUDY_SECTION: KNOD

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Patient Safety;Pediatric;Prevention;Rare Diseases;Tuberculosis;Women's Health Research

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: Project Narrative The Botswana Clinical Trials Unit will develop and study strategies for preventing and treating HIV infection and HIV-related illnesses, including tuberculosis, that are relevant to the severe HIV epidemic in sub-Saharan Africa and elsewhere. This will include studies of novel and durable HIV treatment in HIV-infected adults, including pregnant women, and children; strategies to induce antiretroviral-free HIV remission (or eradication) in adults and children; new treatments and prevention approaches for tuberculosis in adults, including pregnant women, and children; and HIV prevention strategies, including pre-exposure prophylaxis and integrated prevention approaches.

PI_NAMEs: LOCKMAN, SHAHIN  (contact);MAKHEMA, JOSEPH MOEKETSI

PROGRAM_OFFICER_NAME: GUBB, STEPHANIE MAJER

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adolescent;Adult;Africa South of the Sahara;African;Age;AIDS clinical trial group;AIDS prevention;Anti-Retroviral Agents;Area;Botswana;Capital;Child;Childhood;Cities;Clinical Research;Clinical Trials Network;Clinical Trials Unit;co-infection;Collaborations;Communities;community engagement;Community Health Education;data management;data quality;Disease remission;Enrollment;Epidemic;Ethics;experience;Grant;HIV;HIV Infections;HIV Vaccine Trials Network;HIV/AIDS;Human Resources;Individual;Infant;Infection;Infusion procedures;Institution;International;International Agencies;International Maternal Pediatric Adolescent AIDS Clinical Trials;Intervention;Laboratories;Lead;Leadership;Mentors;Modality;Multicenter Studies;novel;participant enrollment;Patient Recruitments;pediatric human immunodeficiency virus;placebo controlled trial;Population;pre-exposure prophylaxis;Pregnant Women;prevent;Prevention;Prevention approach;Prevention strategy;Protocols documentation;Public Health Schools;quality assurance;Quality Control;randomized trial;Research;Research Personnel;research study;Resources;sex;Site;Techniques;Therapeutic;Therapeutic Clinical Trial;Training;Tuberculosis;Work

PROJECT_TITLE: Botswana-Harvard T.H. Chan School of Public Health AIDS Initiative Partnership CTU


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Congenital Heart Disease;Congenital Structural Anomalies;Digestive Diseases;Heart Disease;Liver Disease;Lung;Pediatric;Physical Activity;Prevention;Rare Diseases

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because identification of the mechanism by which pulmonary vasodilators improve organ function in people with prior Fontan operation, will help inform improved prevention and early treatment strategies for end-organ dysfunction, which in turn, will save lives, reduce morbidity, and reduce healthcare costs. Successful completion of the proposed research in this application will provide evidence-based proof of principle for future clinical trials to determine the benefits of pulmonary vasodilators patients with clinically proven pulmonary vascular disease based on pulmonary vascular reserve. The proposed research is relevant to the NIH’s mission pertaining to the pursuit of knowledge to extend healthy life and reduce the burdens of illness and disability.

PI_NAMEs: EGBE, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, BRYANNA NICOLE

PROJECT_TERMS: Acute;Aerobic;Age Years;Arteries;Blood;Blood Vessels;burden of illness;Cardiac Catheterization Procedures;Cardiovascular system;Central venous pressure;Cessation of life;Chronic;Cirrhosis;Clinical;Clinical Trials;cohort;Complex;congenital heart abnormality;Cyclic GMP;Data;Detection;Development;Diagnosis;disability;disease diagnosis;Early Diagnosis;Early treatment;endothelial dysfunction;Endothelium;evidence base;Exercise;exercise capacity;Exercise Test;Exposure to;Failure;Fontan Procedure;Functional disorder;Future;Glomerular Filtration Rate;Goals;Grant;Health Care Costs;Heart failure;hemodynamics;Impairment;improved;indexing;innovation;Intestines;Kidney;Kidney Failure;Knowledge;Life;Link;Liver;liver stiffness;Lung;Magnetic Resonance Elastography;Minnesota;Mission;Morbidity - disease rate;mortality;Nitric Oxide;novel therapeutics;Organ;Outcome;Outcome Assessment;Oxygen Consumption;palliation;Patients;Peripheral;Persons;phosphodiesterase V;Physiology;Placebos;Population;Portal vein structure;premature;prevent;Prevention;Prevention therapy;Protein-Losing Enteropathies;Public Health;Publishing;Pulmonary Circulation;pulmonary vascular disorder;Pulmonary Vascular Resistance;Quality of life;Questionnaires;Randomized;reactive hyperemia;Research;response;Risk Factors;Severities;Signal Transduction;Symptoms;Testing;Therapeutic;tonometry;treatment strategy;United States National Institutes of Health;Vascular Endothelium;Vasodilator Agents;Venous

PROJECT_TITLE: Mechanisms of Clinical and Hemodynamic Response to Pulmonary Vasodilator Therapy in Fontan physiology

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Nutrition;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Fasting improves organismal health; however, the impact on intestinal stem cell function remains incompletely characterized. We will investigate how fasting-derived ketone body metabolites influence intestinal stem cell function and fate decisions with a focus on signaling pathways and energetics. These findings will facilitate the identification of diet-mediated metabolites and associated pathways with therapeutic potential for enhancing intestinal regeneration in cases of injury and age-related decline.

PI_NAMEs: SHAY, JESSICA ELIZABETH STEWART (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: 3-hydroxy-3-methylglutaryl-coenzyme A;Acetoacetates;Acetyl Coenzyme A;age related decline;base;beta-Hydroxybutyrate;Cell division;Cells;Citric Acid Cycle;Coenzyme A;Cues;Data;Diet;Disease;Environment;Enzymes;Epithelial Cells;Equilibrium;experimental study;Fasting;fatty acid oxidation;Fatty Acids;G-Protein-Coupled Receptors;Genetic;Genetic Models;Genetic Transcription;Health;Histone Deacetylase;Histone Deacetylase Inhibitor;Homeostasis;Human;improved;In Vitro;in vivo;Inflammation;inhibitor therapy;Injury;intestinal crypt;intestinal epithelium;Intestines;Isotope Labeling;ketogentic;Ketone Bodies;Ketones;Knockout Mice;Label;Leucine-Rich Repeat;Ligase;Longevity;Maps;Mediating;Metabolic;metabolomics;Mitochondria;Modeling;mouse model;Mus;Natural regeneration;Notch Signaling Pathway;novel;Nutritional;old mice;oxidation;oxidative damage;Oxidoreductase;Pathway interactions;Physiological;Process;Production;programs;Publishing;rapid technique;response;response to injury;Role;Signal Pathway;Signal Transduction;stem cell function;stem cell homeostasis;stem cells;stemness;succinyl-coenzyme A;Techniques;Technology;Testing;Therapeutic;tissue injury;tissue regeneration;Tissues;Transferase

PROJECT_TITLE: Ketone body metabolites in intestinal stem cell homeostasis and disease.


NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

PHR: NARRATIVE Recent reports estimate that 1 out of 6 children in the United States meet the diagnostic criteria for at least one neurodevelopmental disorder. The exact causes of these diseases are unknown, and no effective treatments exist. This proposed study will use cutting-edge stem cell and DNA/RNA sequencing technologies to investigate the disease mechanisms underlying 16p11.2 microdeletion syndrome with the intention of identifying specific drug targets for future therapeutic interventions of these devastating brain disorders.

PI_NAMEs: WELLS, MICHAEL FREDERICK (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: 16p11.2;Acceleration;Affect;Attention deficit hyperactivity disorder;autism spectrum disorder;Award;Behavior;Biochemical;Biological Models;Brain;brain cell;Brain Diseases;California;Cell Line;Cell model;cell type;Cells;Censuses;Child;Cilia;cilium biogenesis;CRISPR-mediated transcriptional activation;Critical Pathways;Data Set;Defect;Development;diagnostic criteria;Disease;DNA;DNA sequencing;Drug Targeting;effective therapy;empowerment;experimental study;fetal;flasks;Functional disorder;Future;Gene Expression;Genes;Genetic;genetic risk factor;Goals;High Prevalence;Human;human fetal brain;Human Genetics;human genome sequencing;human model;human stem cell-derived;Impairment;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;insight;Intellectual functioning disability;Intention;Investigation;Laboratories;Language Disorders;Link;Los Angeles;Maintenance;Malignant Neoplasms;Measures;Mediating;medical schools;Methods;microdeletion;migration;Modeling;Molecular;Molecular Abnormality;mosaic;nerve stem cell;neurodevelopment;Neurodevelopmental Disorder;Neuroglia;Neuronal Dysfunction;Neurons;Noise;novel;Pathway interactions;Patients;Phase;Phenotype;Population;Prevalence;Process;progenitor;Proliferating;Protocols documentation;repetitive behavior;Reporting;response;Role;Sample Size;SHH gene;Signal Pathway;single-cell RNA sequencing;social;stem cell model;stem cells;Susceptibility Gene;Syndrome;System;targeted treatment;Techniques;Technology;Testing;Therapeutic Intervention;Tissue-Specific Gene Expression;transcriptome sequencing;United States;Universities;Validation;Variant

PROJECT_TITLE: The role of autism susceptibility genes in the 16p11.2 locus on the development and function of human stem cell-derived neural cells

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases;Vector-Borne Diseases;West Nile Virus

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Host innate immune response plays a crucial role in combating a large number of viral infections. This proposal focuses on the protein OAS1, which is produced during the early part of the host response and helps shape the later adaptive response to clear viral infections. We have discovered that the OAS1 protein uniquely controls the host immune response to virus infections, including against flaviviruses such as West Nile virus. When completed, our studies should create a new paradigm for understanding how OAS1 functions to inhibit viruses.

PI_NAMEs: DIAMOND, MICHAEL S;SARKAR, SAUMENDRA N (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: 3' Splice Site;adaptive immune response;adaptive immunity;Affect;Alleles;Alternative Splicing;Anti-viral resistance;antiviral drug development;Automobile Driving;Binding;Biochemical;Biological Assay;C-terminal;cell type;Cells;Cellular biology;cellular targeting;Code;Data;Diamond;DNA Viruses;Event;experimental study;Family;Family member;Flavivirus;Genes;Genetic Polymorphism;Goals;Grant;Hematopoietic;Host Defense;Human;Human Genome;Immune response;In Vitro;in vivo;Infection;Innate Immune Response;Interferon Type I;Interferons;IRF1 gene;Knock-in Mouse;knockout gene;Knowledge;Laboratories;Laboratory mice;Length;Ligase;loss of function;Maps;Mediating;Mediator;member;Messenger RNA;Molecular;mouse genome;Mus;Mutate;Natural Immunity;Nature;Nucleic Acids;oligoadenylate;Organ;Orthologous Gene;Play;Predisposition;promoter;Property;protein expression;Protein Family;Protein Isoforms;Protein Synthesis Inhibition;Protein Truncation;Proteins;Proteomics;Reporter;response;Ribonucleases;RNA immunoprecipitation sequencing;RNA Viruses;Role;Scheme;Severity of illness;Shapes;Signal Transduction;Site;T-Lymphocyte;Terminator Codon;Testing;Therapeutic;Transferase;Translational Regulation;Translations;Untranslated Regions;Up-Regulation;Vaccinia virus;Viral;Viral Pathogenesis;Viral Physiology;Viral Proteins;Virus;Virus Diseases;Virus Replication;West Nile viral infection;West Nile virus

PROJECT_TITLE: A new mechanism of antiviral activity of 2'-5' Oligoadenylate Synthetase 1

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative Antibiotic-resistant infections caused by Gram-negative bacteria are a major and growing problem. Colistin, an old antibiotic that was almost abandoned because of its toxicity, has become the drug of last resort for these infections. We have identified compounds that greatly potentiate the effects of colistin and propose here to investigate their mechanisms and synergies with colistin in order to enable development of safer, more effective treatments for resistant Gram-negative infections.

PI_NAMEs: KAHNE, DANIEL  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acinetobacter baumannii;analog;Animals;Antibiotic Resistance;antibiotic resistant infections;Antibiotic susceptibility;Antibiotics;ATP Hydrolysis;ATP phosphohydrolase;Binding;Biochemical;Biological;Biological Assay;Cell Death;Cell Membrane Permeability;Cells;Charge;Clinical;Colistin;Complex;Coumarins;Coupled;Couples;Coupling;Crude Extracts;Cytoplasm;Data;Development;Dimerization;Dissociation;DNA Gyrase;Dose Limiting;effective therapy;Electrolytes;Ensure;Enterobacter;experimental study;Failure;Genetic;Glycolipids;Gram-Negative Bacteria;Health;Human;Hydrophobicity;improved;In Vitro;in vivo;Infection;inhibitor;Klebsiella pneumoniae;Knowledge;Lateral;Learning;Lipopolysaccharides;Membrane;Membrane Transport Proteins;Methods;Minor;Molecular Conformation;Monitor;Novobiocin;periplasm;Pharmaceutical Preparations;Phospholipids;Positioning Attribute;prevent;protein complex;Protein Region;Proteins;Pseudomonas aeruginosa;Public Health;Resistance;Role;Route;Side;single-molecule FRET;small molecule;Structure;synergism;Testing;tool;Toxic effect;Tryptophan;unnatural amino acids;Work

PROJECT_TITLE: Studies on the Biological Mechanisms of Antibiotics


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Dendritic cells (DC) are central immune players that bridge innate and adaptive responses, but their functions are often altered or adapted after viral infections. Using cutting edge big-data analysis, we have identified novel transcription factors that may underlie the suppression of DC development and function during acute (short term) and chronic (long term) viral infections. We propose to investigate the role and mechanisms of action of these new DC regulators to increase our basic understanding of DC biology and to better manipulate them for immunotherapies.

PI_NAMEs: ZUNIGA, ELINA I (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Acute;acute infection;Adrenal Glands;Affect;analog;Antigen Presentation;Aryl Hydrocarbon Receptor;Attenuated;Autoimmune Diseases;Big Data;Binding;Bioinformatics;Biology;Bone Development;Bone Marrow;CD4 Positive T Lymphocytes;CD8B1 gene;Cells;Cellular biology;Chromatin;Chronic;chronic infection;cytokine;Data;Data Analyses;Dendritic Cells;Development;Disease;Enhancers;epigenome;Equilibrium;Excision;Exclusion;exhaustion;Exhibits;Gene Expression;Genes;Glucocorticoid Receptor;Glucocorticoids;GMEB-1;Goals;Human;Immune;immune function;Immune response;Immune system;Immunity;immunopathology;Immunotherapy;Impairment;improved;In Vitro;in vivo;Individual;Infection;Inflammatory;Interferon Type I;Knowledge;Lymphocytic choriomeningitis virus;Malignant Neoplasms;Modeling;Molecular;Mus;new therapeutic target;novel;novel therapeutic intervention;pathogen;Play;Production;progenitor;programmed cell death protein 1;promoter;Proteins;receptor;receptor binding;receptor sensitivity;Receptor Signaling;Regulation;Reporting;response;Role;Signal Transduction;Source;stem cells;success;T-Lymphocyte;Technology;Testing;Time;TLR7 gene;transcription factor;transcriptome;Viral;Virus Diseases;Zinc Fingers

PROJECT_TITLE: Molecular Mechanisms Underlying Dendritic Cell Adaptations During Chronic Infection


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Dietary Supplements;Digestive Diseases;Nutrition;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Animal studies suggest that excess linoleic acid increases colon cancer risk, but human studies have not provided conclusive evidence of this relationship. 15-lipoxygenase-1 (ALOX15), the enzyme that metabolizes linoleic acid, is commonly lost in human colon cancers, but we do not know whether the loss of ALOX15 influences the risk of colon cancer by linoleic acid. This project will examine whether ALOX15 loss increases colon cancer risk in the presence of dietary linoleic acid, especially the transformation of benign colon polyps to invasive colon cancer and could show that subjects with low colonic ALOX15 level should avoid excess dietary linoleic acid.

PI_NAMEs: SHUREIQI, IMAD  (contact)

PROGRAM_OFFICER_NAME: EMENAKER, NANCY J

PROJECT_TERMS: Acids;Adenocarcinoma;adenoma;Adverse event;Affect;aldehyde dehydrogenase 1;ALOX15 gene;American diet;Animals;APC mutation;Arachidonate 15-Lipoxygenase;Automobile Driving;Azoxymethane;Benign;beta catenin;Biological Assay;Biological Markers;Breeding;c-myc Genes;Cancer Etiology;cancer invasiveness;carcinogenesis;CD44 gene;CDX2 gene;Cell membrane;Cellular Membrane;Cessation of life;Chemicals;Chemopreventive Agent;Colon;colon cancer risk;colon carcinogenesis;Colon Carcinoma;Colonic Polyps;Colorectal;Colorectal Cancer;Complex;Consumption;Corn Oil;Cyclin D1;Data;Development;Diet;dietary;dietary excess;Disease;DNA Sequence Alteration;Doxycycline;drinking water;Endosomes;Enzymes;Event;gain of function;Genes;Goals;Human;Immunodeficient Mouse;In Vitro;in vivo;Incidence;Induced Mutation;insight;Intake;Integration Host Factors;Intervention;Invaded;Knowledge;KRAS2 gene;KRASG12D;LDL-Receptor Related Protein 1;Lentivirus;LGR5 gene;Linoleic Acids;lipoprotein receptor related protein 5;Lipoxygenase 1;Liquid Chromatography;loss of function;LoxP-flanked allele;Mass Spectrum Analysis;Metabolism;mouse model;Mucous Membrane;Mus;Mutation;novel;novel chemoprevention;Omega-6 Fatty Acids;organoid transplantation;Organoids;permissiveness;peroxidation;phosphatidylinositol 3-phosphate;Phospholipids;Polyunsaturated Fatty Acids;prevent;Prevention strategy;preventive intervention;receptor;Recycling;Regulation;Reporting;Research;Resected;Resolution;Risk;Rodent;Role;Sampling;Signal Transduction;stem cell self renewal;stem cells;stemness;System;Testing;therapy development;Tissues;Transfection;Transgenic Organisms;tumor;tumorigenesis;United States;villin

PROJECT_TITLE: ALOX15 regulation of colon cancer invasiveness via PI3P-linoleic acid metabolism

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Contraception/Reproduction;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative Black women are three times more likely than White women to die from early-onset preeclampsia (EOP; <34 weeks' gestation; a disorder of pregnancy characterized by hypertension and proteinuria) and other childbirth- related issues. Yet we do not know why the disparities exist and how evidence-based practices are implemented to reduce disparities in preeclampsia. The proposed study will identify processes of care to prevent EOP, provider's barriers and facilitators to implementing evidence-based treatment to prevent EOP, and women's awareness of preeclampsia and evidence-based treatment to prevent EOP.

PI_NAMEs: SMITH, SHARLA ANNETTE (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Address;Adherence;American College of Obstetricians and Gynecologists;Area;Aspirin;Awareness;Belief;Biomedical Research;Birth;Black race;black women;care outcomes;career;career development;Caring;Childbirth;Clinic;Clinical;clinical implementation;Communities;Consolidated Framework for Implementation Research;contextual factors;design;Development;Development Plans;Disparity;disparity reduction;Dissemination and Implementation;Dose;early onset;Eclampsia;Educational workshop;Electronic Health Record;Ensure;evidence base;Evidence based practice;Evidence based treatment;experience;Faculty;Focus Groups;Foundations;Funding;Future;Goals;Guidelines;health care disparity;Health Disparities Research;health disparity;High Risk Woman;Hypertension;implementation research;implementation science;implementation strategy;improved;Incidence;Individual;innovation;Intervention;Interview;K-Series Research Career Programs;Kansas;Knowledge;Low income;maternal morbidity;Maternal Mortality;maternal outcome;medical schools;Mentors;Mentorship;Methodology;Methods;Nurse Practitioners;Outcome;outcome disparities;Patients;Perception;Physician Assistants;Pre-Eclampsia;preference;Pregnancy;pregnancy disorder;Prenatal care;prevent;Prevention;Prevention trial;Process;process improvement;Proteinuria;Provider;provider behavior;provider-level barriers;racial disparity;Recommendation;Research;research and development;Research Personnel;Research Project Grants;Research Training;Risk Factors;Schedule;screening;Seizures;skills;Structure;Time;Training;Translating;University resources;uptake;White Women;Wichita;Woman

PROJECT_TITLE: Improving the Quality of Prenatal Care for Low-Income, Urban, Black Women