NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Data Science;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: In this proposal, we will investigate mechanisms of oral cancer initiation and progression for the identification of novel candidate drivers of the disease amenable to therapeutic targeting. We will apply system-level computational approaches, including novel taxonomy discovery and Markov network inference and comparison methods, to analyze existing multi-omics mouse and human datasets. Our primary, yet not exclusive, focus will be on the definition of the molecular links between somatic variation, ? ? -catenin/CBP, TAZ/YAP, and mTOR activity, and EMT and CSC phenotypes in early and advanced stages of OSCC, and the hypotheses we generate will be evaluated in in-vitro and in-vivo models we have developed in our laboratories.

PI_NAMEs: MONTI, STEFANO  (contact)

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: Adopted;advanced disease;Automobile Driving;Behavior;beta catenin;Binding;Binding Proteins;Bioconductor;Bioinformatics;Biological;Cancer cell line;cancer initiation;cancer stem cell;candidate identification;candidate validation;Carcinoma in Situ;Cell Proliferation;cell type;Cells;Communities;Computer Analysis;Cyclic AMP;Data;Data Analyses;Data Set;Death Rate;Development;Diagnosis;Disease;disease diagnosis;DNA Sequence Alteration;draining lymph node;Elements;Encyclopedias;epithelial to mesenchymal transition;Erythroplasia;Evaluation;experimental study;FRAP1 gene;Gene Expression;gene regulatory network;Genes;Genetic;Genetic Transcription;Goals;Head and Neck Squamous Cell Carcinoma;Head and neck structure;histone acetyltransferase;HPV negative;Human;human data;human tissue;improved;in silico;In Vitro;in vivo Model;inhibitor;insight;Laboratories;Lesion;Leukoplakia;Link;Malignant - descriptor;malignant mouth neoplasm;Malignant Neoplasms;Maps;Mediating;Metastatic Neoplasm to Lymph Nodes;Methods;methylomics;Modeling;Molecular;Mouth Neoplasms;mouth squamous cell carcinoma;Multiomic Data;multiple omics;Mus;Mutation;Neck Cancer;Neoplasm Metastasis;Network-based;novel;novel therapeutics;Nuclear;Oncogenic;open source;oral lesion;Oral Stage;Pathway interactions;Patients;Pattern;pharmacologic;Phenotype;Play;Population;portability;premalignant;Premalignant Cell;Proteomics;rational design;Reporting;Research;Research Personnel;resistance mechanism;Resources;response;Role;Signal Pathway;Signal Transduction;single cell analysis;single-cell RNA sequencing;small molecule;Squamous cell carcinoma;Survival Rate;Symptoms;System;Taxonomy;The Cancer Genome Atlas;Therapeutic;therapeutic target;therapy resistant;Time;Tissues;tool;trait;tumor;tumor initiation;tumor progression;Variant;Visualization;web portal

PROJECT_TITLE: System-Level Analyses of Multi-Omics Data to Reveal Mechanisms of Head & Neck Cancer

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ADMINISTERING_IC: EY

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: NARRATIVE The mislocalization of key signaling and structural outer segment proteins underlie some of the most severe types of inherited retinal diseases, including the most frequently encountered cases of retinitis pigmentosa – a blinding disease affecting nearly two million people worldwide. Elucidating the intracellular mechanisms guiding these proteins in healthy cells we, as a community, will be better positioned to develop new therapeutic strategies. Furthermore, understanding how the light-sensitive outer segment is normally populated with structural and signaling proteins will be paramount as the community begins to explore new regenerative approaches such as stem cell-derived organoids to treat patients with retinal diseases.

PI_NAMEs: PEARRING, JILLIAN NYDAM (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: absorption;Affect;Afferent Neurons;alpha helix;Architecture;Biological;Biological Assay;Biotinylation;Blindness;Bypass;Cell membrane;Cells;Cilia;Communities;cone-rod dystrophy;cyclic-nucleotide gated ion channels;Defect;Dependence;Destinations;Detection;Disease;Ensure;Future;G-Protein-Coupled Receptors;Gene Delivery;Goals;Golgi Apparatus;in vivo;Inherited;Injury;insight;Integral Membrane Protein;Knowledge;Label;Light;Lipids;Membrane;Membrane Proteins;Molecular;Mus;Natural regeneration;novel;novel therapeutic intervention;Opsin;Organelles;Pathogenicity;Pathway interactions;Patients;peripherin;Persons;Photons;Photoreceptors;Positioning Attribute;Process;Protein Biosynthesis;Proteins;Rapid screening;regenerative approach;response;Retina;Retinal Cone;Retinal Diseases;Retinal Dystrophy;retinal rods;Retinitis Pigmentosa;Rhodopsin;Rod;Rod Outer Segments;Route;sensor;Sensory;Shapes;Signal Transduction;Signaling Protein;Site;Sorting;Stargardt's disease;stem cell organoids;Structural Protein;System;Techniques;Therapeutic;trafficking;Travel;Vertebrate Photoreceptors;Vision

PROJECT_TITLE: Understanding Photoreceptor Trafficking Pathways to the Outer Segment

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE PCDH19-clustering epilepsy (PCE) is a severe developmental and epileptic encephalopathy predominantly affecting girls and caused by pathogenic variants in an X-linked gene. Using a mouse model that we recently developed, we propose to study how this unique inheritance pattern leads to abnormal interneuron development and susceptibility to seizures. This work will provide insight into disease mechanisms and may identify a therapeutic target to treat patients with PCE.

PI_NAMEs: ZIOBRO, JULIE M (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Abnormal Cell;acquired epilepsy;Acute;Affect;Alleles;Brain;Calcium;career;career development;Cell Adhesion Molecules;Cell Communication;Cell Culture Techniques;Cell Death;Cell membrane;cell motility;Cell Proliferation;Cell Separation;Cells;childhood epilepsy;clinical training;clinical translation;clinically relevant;Complement;Data;density;design;Development;Development Plans;Developmental Therapeutics Program;Disease;Doctor of Medicine;Doctor of Philosophy;Electrophysiology (science);Embryo;Epilepsy;epileptic encephalopathies;Excitatory Synapse;experience;Female;field study;Future;Genes;Genetic;girls;Goals;Hippocampus;Histologic;Image;Imaging Techniques;Impaired cognition;Impairment;In Vitro;in vivo;Individual;Induced Hyperthermia;infancy;Inheritance Patterns;inhibitory neuron;Inhibitory Synapse;insight;Interneurons;Knowledge;Label;Learning;Life;Link;male;Measures;Medial;medical specialties;Mentors;migration;Modeling;mosaic;mosaic variant;mouse model;Mus;mutant;neuron development;Neurons;neuropsychiatry;Neurosciences Research;offspring;Parvalbumins;patch clamp;Pathogenicity;Patients;Pattern;Pediatric Neurology;Physicians;Physiological;Population;postnatal;Precision therapeutics;Predisposition;Process;progenitor;Program Development;Proliferating;Prosencephalon;protocadherin 19;Pyramidal Cells;Reporter;Reporting;Research;Research Design;Research Personnel;Rodent;Role;Scientist;segregation;Seizures;Signal Transduction;skills;Slice;Synapses;Testing;Therapeutic;therapeutic target;Training;Training Activity;Translational Research;Variant;Viral;Viral Vector;Visualization;Work;X Inactivation

PROJECT_TITLE: Mechanisms of PCDH19-clustering epilepsy

STUDY_SECTION: NST

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


ADMINISTERING_IC: DE

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Rare Diseases;Social Determinants of Health

ORG_CITY: DURHAM

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Narrative Head and neck cancers are a particular threat to individuals in low-income underserved communities, due to the high prevalence of risk factors such as smoking and human papillomavirus infection. We will develop and validate a device, referred to as Raman Assay using Plasmonics for Identification and Diagnosis (RAPID) using ultrabright surface-enhanced Raman scattering (SERS) “nanorattle” probes for multiplexed detection of squamous cell carcinoma and thyroid cancer, which account for more than 90% of all head and neck cancers. Ultimately, , we envision the RAPID technology to be deployed as a low-cost diagnostic tool capable of head and neck cancer identification, with the potential to reduce the morbidity and mortality of this disease in currently underserved populations.

PI_NAMEs: LEE, WALTER TSONG;VO-DINH, TUAN  (contact)

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: 3D Print;accurate diagnosis;Address;anti-cancer research;Area;Biological Assay;Biological Markers;Biological Models;Biopsy;Cancer Detection;Cancer Diagnostics;cancer type;Caring;Clinic;Clinical;clinical care;clinical translation;Community Healthcare;community setting;convolutional neural network;cost;Cytology;Data Analyses;design;Detection;Developing Countries;Development;Devices;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic platform;Diagnostic Procedure;Diagnostic Services;diagnostic technologies;diagnostic tool;Disease;Distant Metastasis;DNA;Early Diagnosis;Early treatment;Equipment;Evaluation;FDA approved;Fresh Tissue;global health;Goals;Head and Neck Cancer;Head and neck structure;health application;Health Personnel;Healthcare;High Prevalence;Histology;hospital laboratories;Hospitals;Hour;Human papilloma virus infection;Human Papillomavirus;Human Resources;Individual;Infrastructure;instrument;instrumentation;Knowledge;Laboratories;Learning;Lesion;Low income;magnetic beads;Malignant neoplasm of thyroid;Malignant Neoplasms;Medical;Messenger RNA;Methods;miniaturize;Molecular;Molecular Analysis;molecular marker;Morbidity - disease rate;mortality;multiplex assay;multiplex detection;multiplex diagnostics;nanophotonic;nanoplasmonic;new technology;novel;Operative Surgical Procedures;Output;Pathology;Patients;plasmonics;point of care;Point of Care Technology;point-of-care diagnosis;point-of-care diagnostics;Polymerase Chain Reaction;portability;Preparation;Quantitative Reverse Transcriptase PCR;rapid detection;rapid diagnosis;Rapid screening;Reader;Reagent;Research;Resource-limited setting;Resources;Risk Factors;RNA;Sampling;screening;Screening for cancer;Screening procedure;Smoking;Specificity;Squamous cell carcinoma;Stains;Surface;System;Systems Integration;Techniques;Technology;technology validation;Testing;Tissue Sample;Training;Translations;Treatment outcome;underserved community;Underserved Population;Validation;Work

PROJECT_TITLE: RAPID System for Early Detection of Head and Neck Cancer in Low-Resource Settings

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE Cells of the innate immune system can be reprogrammed by exposure to stimuli such as cytokines or pathogens in a phenomenon known as “trained immunity.” This can make immune cells either more inflammatory or less inflammatory in response to subsequent infections, but what determines whether a given stimulus will result in potentiated or diminished inflammation is unclear. This proposal explores the hypothesis that dynamic features of the transcription factor NFκB – not if it is activated, but how it is activated – contribute to the stimulus-specificity of trained immunity through the regulation of latent enhancers that control gene expression.

PI_NAMEs: CHENG, QUEN J (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Address;Adoptive Transfer;Anti-Inflammatory Agents;Binding;Bioinformatics;Candida albicans;Cell Nucleus;Cells;ChIP-seq;Chromatin;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Communicable Diseases;cytokine;Diagnostic;differential expression;DNA;Elements;Enhancers;Environment;Epigenetic Process;epigenome;epigenomics;Exposure to;Faculty;Gene Expression;Genes;Genus Mycobacterium;Glucans;Goals;Grant;helminth infection;histone modification;Immune;Immune response;Immune Response Genes;Immunity;Immunologic Memory;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Response;Innate Immune System;International;K-Series Research Career Programs;Knock-out;Ligands;Macrophage;Measures;Mediating;member;Memory;Mentors;Mentorship;Molecular;monocyte;mouse model;Mus;NF-kappa B;Nucleosomes;pathogen;pathogenic fungus;Pattern;Phagocytosis;Phenotype;Physicians;Positioning Attribute;Predisposition;Principal Investigator;programs;promoter;Psychological Transfer;receptor;Regulation;response;Rest;Science;Scientist;secondary infection;Secondary to;senior faculty;Shapes;Specificity;Stimulus;symposium;Testing;Therapeutic;Time;Tissue Sample;tool;Training;Training Support;transcription factor

PROJECT_TITLE: NFkB dynamics in the stimulus specificity of trained immunity

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Cystic Fibrosis;Emerging Infectious Diseases;Infectious Diseases;Lung;Rare Diseases

ORG_CITY: BETHESDA

ORG_NAME: HENRY M. JACKSON FDN FOR THE ADV MIL/MED

ORG_STATE: MD

PHR: Project Narrative Development of an effective antiviral drug for COVID-19 is widely considered to be a global health priority. COVID-19 severity and death is principally due to a proinflammatory cytokine storm in the lung, which is caused by CFTR loss and consequent activation of NFκB and ENaC signaling. Cardiac glycoside drugs such as ouabain and digitoxin potently block infection by inhibiting the viral spike from binding to ACE2. By inhibiting viral entry, the cardiac glycosides prevent loss of CFTR, and thereby also prevent activation of NFκB and ENaC signaling.

PI_NAMEs: POLLARD, HARVEY BRUCE (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: 2019-nCoV;ACE2;Affect;Air;airway epithelium;airway inflammation;Animal Model;Anti-viral Agents;Apical;Automobile Driving;autosome;Basal Cell;Binding;Biopsy;Cardiac Glycosides;Cell membrane;Cell model;cell type;Cells;Cessation of life;Chloride Channels;Co-Immunoprecipitations;COVID-19;COVID-19 mortality;COVID-19 patient;COVID-19 severity;Cyclic AMP;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;cytokine release syndrome;Data;Development;differentiation in vitro;Digitoxin;Digoxin;Disease;Dose;Endosomes;Epithelial Cells;epithelial Na+ channel;Epithelium;Failure;gene function;Genetic Diseases;global health;Hamsters;Health Priorities;Histologic;Human;Incubated;Infection;Inflammation;Inflammatory;Inflammatory Response;Liquid substance;Lung;Modeling;Mutation;nanomolar;novel;Organ;Ouabain;Penetration;Pharmaceutical Preparations;Phenotype;prevent;Process;protein expression;Proteins;receptor;recessive genetic trait;Recovery;Recycling;Regulator Genes;Reporting;Reproducibility;RNA analysis;SARS-CoV-2 infection;SARS-CoV-2 inhibitor;SARS-CoV-2 spike protein;Secretory Cell;severe COVID-19;Signal Transduction;stem cells;Symptoms;Telomerase;Testing;Time;tool;TRADD gene;Viral;viral entry inhibitor;Virus

PROJECT_TITLE: COVID-19 airway inflammation is due to Spike inhibition of CFTR signaling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-S(02)]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Heart Disease;Immunotherapy;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The mechanism of cardiotoxicity due to immune checkpoint inhibitors (ICI) remains poorly understood due varied clinical symptoms cause due to inflammation. The goal of this project is to unravel the underlying mechanisms by systematically studying the effect of ICIs using multicellular cardiac organoids (CO) derived from patient-specific induced pluripotent stem cells (iPSCs). The results of the study may lead to development of drugs to preserve heart function in cancer patients.

PI_NAMEs: THOMAS, DILIP  (contact)

PROGRAM_OFFICER_NAME: CHEON, YEWON

PROJECT_TERMS: 3-Dimensional;Adverse effects;Affinity;Animal Model;Antibodies;Antitumor Response;Area;Award;Binding;Biological;Biomedical Engineering;Biopsy;Cancer Patient;Cardiac;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular Models;Cardiovascular system;career;career development;Cell Communication;Cell Line;Cell Proliferation;Cells;Chromatin;Clinical;Clinical Treatment;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Collaborations;CRISPR interference;cytokine;Cytometry;D Cells;Derivation procedure;Disease;Dose;drug development;drug efficacy;Early Diagnosis;Early identification;Echocardiography;Electrophysiology (science);Endothelial Cells;endothelial stem cell;Evaluation;Event;experimental study;Exposure to;Female;Fibroblasts;Frequencies;Functional disorder;functional outcomes;Gene Targeting;genome editing;Genomics;Goals;Half-Life;Heart;Heart Diseases;heart function;Heart Injuries;heart preservation;heart rhythm;Histology;Immune;immune activation;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immune system;immune-related adverse events;Immunological Models;Immunology;Immunotherapy;In Vitro;in vivo;Incidence;induced pluripotent stem cell;induced pluripotent stem cell technology;Inflammation;inhibitor;interdisciplinary approach;knock-down;Lead;Ligands;MALAT1 gene;male;Malignant Neoplasms;Measures;Mediating;Mentors;Molecular;Molecular Analysis;Molecular Profiling;Molecular Target;Monoclonal Antibodies;monolayer;mouse model;multidisciplinary;Mus;Myocardial dysfunction;Myocarditis;Organoids;Outcome;Pathway interactions;Patients;PDL1 inhibitors;pembrolizumab;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;Phase;Phenotype;Physiological;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Proteomics;Qi;Reaction;receptor;Reporting;Research;Research Design;response;Sampling;self assembly;single-cell RNA sequencing;small molecule;stem cell biology;Structure;Symptoms;Techniques;Technology;Testing;Therapeutic;Tissue Engineering;Tissues;Toxic effect;Training;transcriptome sequencing;transcriptomics;Tumor Antigens;Validation;Vasculitis

PROJECT_TITLE: Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(OA)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Clinical Research;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Precision Medicine;Rare Diseases

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: Narrative Every tumor is biologically unique. Moving from “one-size-fits-all” to personalized medicine in cancer, we need to develop novel platforms to help us improve our understanding of cellular characterizations of individual’s cancer biology and therapeutics. In this project we will develop a personalized ex vivo platform including individual’s cancerous epithelium and the tumor microenvironment. We will show the utility of our system for testing conventional and novel therapeutics. The patient-specific drug response assay technology has the potential to inform the way treatment decisions are made within the context of pancreatic cancer and perhaps other complex solid tumors.

PI_NAMEs: BISHEHSARI, FARAZ  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: 3-Dimensional;Adjuvant;Antineoplastic Agents;Basic Science;Biological Assay;Cancer Biology;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;Cancerous;CD8-Positive T-Lymphocytes;Cell Communication;Cell Differentiation process;cell type;Cells;Characteristics;chemotherapy;Clinical;Clinical Trials;cohort;Complex;conventional therapy;Decision Making;design;Devices;Disease Progression;Drug Delivery Systems;drug development;drug efficacy;Drug Modelings;Drug Targeting;drug testing;Elements;Endothelium;Environment;Epithelium;experimental study;Failure;Fibroblasts;Fibrosis;functional outcomes;Genes;Goals;Human;Immune;Immunotherapy;improved;in vivo;Individual;individual response;individualized medicine;innovation;Interruption;Macrophage;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;microfluidic technology;Modeling;Molecular;molecular modeling;Molecular Profiling;next generation;novel;novel therapeutics;Organ;organ on a chip;Organoids;Outcome;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic stellate cell;Pathogenicity;Pathology;Pathway interactions;patient subsets;Patient-Focused Outcomes;Patients;personalized medicine;personalized strategies;Pharmaceutical Preparations;Phenotype;pre-clinical;Prediction of Response to Therapy;protein expression;real time monitoring;research and development;Resistance;response;Role;Series;Solid Neoplasm;Source;stellate cell;stem cells;Survival Rate;System;T-Lymphocyte;targeted treatment;Technology;Testing;Therapeutic;therapy resistant;Tissues;treatment response;tumor;tumor behavior;Tumor Immunity;tumor microenvironment;tumor progression;Tumor Promotion;Vascularization

PROJECT_TITLE: Personalized Organoid-Chip Model For Drug Testing in Pancreatic Cancer

STUDY_SECTION: DMP

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Genetics;Human Genome;Rare Diseases;Scleroderma

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Morphea is a disorder of inflammation followed by fibrosis of the skin and soft tissue that produces devastating effects on appearance and joint function in children and adults when untreated. The biggest challenge for those taking care of patients with morphea is that the molecular underpinnings of the disorder have not been systematically investigated, which creates a huge barrier to the development of targeted, less toxic treatments. The combination of single cell RNA sequencing of skin and fibroblast culture models obtained from morphea patients in this study provides a unique opportunity to understand cellular mechanisms driving morphea pathogenesis, and will identify potential drug targets.

PI_NAMEs: JACOBE, HEIDI T;TOROK, KATHRYN S. (contact)

PROGRAM_OFFICER_NAME: PARK, HEIYOUNG

PROJECT_TERMS: Address;Adult;Ancillary Study;Appearance;Atrophic;Autoimmune Diseases;Automobile Driving;Biological;Biological Assay;Biological Markers;biomarker development;Biopsy;Bleomycin;Blood Cells;case control;Cell Differentiation process;cell type;Cells;Child;Childhood;Clinical;Coculture Techniques;cohort;Collagen;CXC chemokine receptor 3;CXCL9 gene;CXCR3 gene;cytokine;Cytometry;Data;design;Development;disability;Disease;Drug Targeting;efficacious treatment;expedited review;Feedback;Fibroblasts;Fibrosis;Functional disorder;Future;Gene Expression Profile;Genes;genetic signature;Genetic Transcription;Goals;Grant;Human;human tissue;Immune;Immunologics;Inflammation;Inflammatory;Inflammatory Response;Infrastructure;innovation;insight;interest;Interferon Activation;Interferon Type II;Interferons;joint function;Lesion;Ligands;Localized scleroderma;Longitudinal Studies;Macrophage;Maps;Measures;Mediating;Medical center;Modeling;Molecular;Morphea;mouse model;multidisciplinary;Mus;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;neglect;new therapeutic target;novel therapeutics;observational cohort study;Outcome;overexpression;Parents;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patient Care;Patient Recruitments;Patients;peripheral blood;Phenotype;Population;Positioning Attribute;Principal Investigator;protein expression;Proteins;psychologic;receptor;recruit;Registries;Research Personnel;Resources;response;Role;Sampling;scleroderma registry;side effect;Signal Transduction;single-cell RNA sequencing;Skin;skin disorder;skin fibrosis;Skin Tissue;soft tissue;System;T-Lymphocyte;targeted treatment;Technology;Testing;therapeutic development;Time;timeline;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;translational study;treatment response;United States National Institutes of Health;Universities;Up-Regulation;Work

PROJECT_TITLE: Ancillary studies to define dysregulated immune and fibrotic pathways in a well-characterized morphea cohort


ADMINISTERING_IC: GM

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Natural Products

ORG_CITY: LA JOLLA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative The xenicanes are a diverse family of anticancer diterpenes from soft corals with complex, heavily oxidized scaffolds that are unique to marine eukaryotes. In this proposal, I describe my strategy to engineer the terpene synthase that assembles xeniaphyllene (the hydrocarbon core common to all xenicanes), identify and characterize the oxidase(s) that generate the characteristic xenicane scaffold by catalyzing an unprecedented carbon–carbon bond cleavage, and assemble these enzymes into a refactored biosynthetic pathway for microbial production of xenicanes. Through this work we will gain key insights into the enzymology of terpenoid biosynthesis and enable the scalable and sustainable production of coral diterpenoids, facilitating the discovery and development of pharmaceutically relevant marine natural products.

PI_NAMEs: SHENDE, VIKRAM VIJAY (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Anabolism;anti-cancer;Aquaculture;Architecture;Binding;Biochemistry;Bioinformatics;Biological;Biological Assay;Carbon;Cell Line;Characteristics;Chemicals;Chemistry;Cloning;combinatorial;Common Core;Complex;coral;Cyclobutanes;Cytochrome P450;Cytochromes;cytotoxicity;Data;design and construction;design,build,test;Development;Directed Molecular Evolution;Diterpenes;Engineering;Enzymatic Biochemistry;enzyme biosynthesis;Enzymes;Eukaryota;Evaluation;Event;Exhibits;Family;Future;Gene Cluster;Genes;Genetic Transcription;Genome;Geranylgeranyl-diphosphate geranylgeranyltransferase;Goals;Hand;Human;Hydrocarbons;improved;In Vitro;in vivo;insight;K-562;Lead;Leukemic Cell;Lyase;lycopene;marine;marine natural product;Medicine;Membrane;Methods;microbial;model development;Mutagenesis;Natural Products;Natural Source;novel;Oxidases;oxidation;Oxidoreductase;Pathway interactions;Peripheral;Pharmacologic Substance;Pichia;Production;promoter;Publications;Publishing;rapid detection;Reaction;reconstitution;Reporting;Research;research clinical testing;scaffold;secondary metabolite;Series;Source;Structure;Techniques;terpene synthase;Terpenes;Terpenoid Biosynthesis Pathway;Therapeutic;transcriptome;Variant;Vertebral column;Work;Yeasts

PROJECT_TITLE: Refactoring Soft Coral Diterpenoid Biosynthesis


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Mental Health;Mental Illness;Neurosciences;Stimulant Use and Misuse

ORG_CITY: TALLAHASSEE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: In humans, social attachment with partners, relatives, or friends act as a protective buffer against many negative consequences of life stress, whereas lack of social attachments can lead to serious pathologies including dysphoria, anxiety, depression, sleep disturbance, cardiovascular problems, and immune system deficits. In this proposal, using a highly social animal model, we will examine the role of a specific oxytocinergic circuitry in the brain that may play a key role in mediating some consequences of partner separation and isolation stress.

PI_NAMEs: KABBAJ, MOHAMED  (contact);WANG, ZUOXIN

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Acute;Aggressive behavior;Animal Model;Anxiety;Area;Behavior;biological adaptation to stress;Brain;Buffers;Cardiovascular system;Cells;Chronic;CRISPR/Cas technology;Data;Dopamine;Dopamine D1 Receptor;Dopamine D2 Receptor;dysphoria;Enterobacteria phage P1 Cre recombinase;Female;follow-up;Foundations;Friends;Gene Expression;Genes;genetic approach;genome editing;Globus Pallidus;Human;hypothalamic-pituitary-adrenal axis;Immune system;Knock-in;Life Stress;Maintenance;male;Mediating;Mental Depression;Microtus;Moods;neurochemistry;Neurons;Nucleus Accumbens;Oxytocin;Oxytocin Receptor;Pair Bond;paraventricular nucleus;Pathology;Pathway interactions;Pharmaceutical Preparations;Play;postsynaptic;prairie vole;preference;presynaptic;psychostimulant;Receptor Gene;response;Role;sex;Side;single cell sequencing;Sleep disturbances;social;social attachment;Social Behavior;Social isolation;Stress;stress management;Structure;System;transcriptomics;Ventral Tegmental Area;Work

PROJECT_TITLE: Breaking bonds in prairie voles


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Aging;Cardiovascular;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: NARRATIVE Large genetic studies in minority populations are rare, yet are imperative for understanding cardiovascular disease (CVD) risk and events. This study will combine epidemiological and clinical data coupled with genetic and transcriptomic data t o study CVD risk and events in Hispanic populations living in the US and in Latin America.

PI_NAMEs: FERNANDEZ-RHODES, LINDSAY ;GRAFF, MARIAELISA  (contact)

PROGRAM_OFFICER_NAME: KUNZ, JOHN FREDERIC

PROJECT_TERMS: Address;Admixture;African ancestry;Architecture;Asian ancestry;barrier to care;biobank;Biological;blood pressure regulation;Brazil;burden of illness;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;causal variant;Cities;Clinical;Clinical Data;clinically significant;Coronary heart disease;Coupled;Data;Disease Outcome;disorder prevention;Disparity;Dyslipidemias;East Asian;Electronic Health Record;Ensure;epidemiologic data;Epidemiology;European;Event;experience;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic architecture;Genetic Predisposition to Disease;genetic risk factor;Genetic study;genome wide association study;genomic locus;Genomics;Genotype;Growth;Health;Hispanic;Hispanic Populations;Hypertension;improved;Individual;Inflammation;insight;interest;Intervention;Investments;Knowledge;Latin America;Latino;Latino Population;Link;lipid metabolism;Maps;Measures;Medical;Medicine;Mendelian randomization;Meta-Analysis;Mexico;Minority Groups;Modeling;Morbidity - disease rate;mortality;Native Americans;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Outcome;Participant;Persons;phenome;platelet function;Population;Population Heterogeneity;precision medicine;predictive modeling;Prevalence;Prospective Studies;Public Health;Publishing;Research;Risk;Risk Factors;risk prediction;risk stratification;risk variant;RNA;Sample Size;Sampling;Sampling Studies;Severity of illness;South America;Stroke;Time;tool;trait;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Translating;translational genomics;translational pipeline;trend;Validation;Variant;Whole Blood;Work

PROJECT_TITLE: Leveraging Hispanic/Latino diversity to map and characterize cardiovascular disease loci

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Carriers of the APOE4 gene are at a significantly increased risk of developing Alzheimer’s disease. In order to understand the cause of this increased Alzheimer’s risk, we will conduct a comprehensive investigation of how the APOE genotype affects normal biological pathways in the brain, defining how these effects progress with time and within brain regions and cell-types. Using a new APOE mouse line and cutting-edge technology, these experiments will dramatically improve our understanding of why APOE4 carriers are more susceptible to AD and how this susceptibility can be prevented.

PI_NAMEs: NURIEL, TAL  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: abeta accumulation;Acceleration;Affect;aged;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Amyloid beta-Protein;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Astrocytes;behavior test;Behavioral;behavioral phenotyping;Bioenergetics;Bioinformatics;Biological;Biological Process;Brain;brain cell;Brain region;cell type;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;conditional knockout;conditioned fear;Development;Disease;Disease susceptibility;Endosomes;entorhinal cortex;Event;Experimental Designs;experimental study;Functional Magnetic Resonance Imaging;Genes;genetic risk factor;Genotype;Histologic;human model;Hyperactivity;Image;Impaired cognition;Impairment;improved;Individual;innovation;Investigation;Knock-in Mouse;Late Onset Alzheimer Disease;lipidomics;Lipids;Literature;Magnetic Resonance Imaging;Maps;mass spectrometric imaging;metabolomics;Microglia;Molecular Biology;mouse model;multiple omics;Mus;Nature;Neurons;novel;novel therapeutic intervention;object recognition;Pathway interactions;Pattern;Physiology;Predisposition;prevent;Process;Protein Isoforms;Publications;Regulation;Reporting;Research;Research Personnel;Resistance;Resolution;Risk;RNA;Role;Series;Site;skills;System;Systems Biology;Technology;theories;Time;transcriptomics;unpublished works;Work

PROJECT_TITLE: Elucidating the Temporal, Spatial and Cellular Effects of Differential APOE Isoform Expression

STUDY_SECTION: CDIN

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


ORG_CITY: SALT LAKE CITY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Narrative This proposal studies novel functions of particles composed of Sm proteins and small nuclear RNAs of viral and cellular origin with the goals of understanding how these molecules contribute to cancers of viral origin and cellular homeostasis.

PI_NAMEs: CAZALLA, DEMIAN  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Untranslated Regions;Base Pairing;Binding;Binding Sites;Biochemical;Biological Models;Cells;Code;Disease;Eukaryota;flexibility;Gene Expression;Gene Expression Regulation;Genetic;genome-wide;Goals;Herpesviridae;Homeostasis;in vivo;interest;Laboratories;Link;Mammalian Cell;Mechanics;Mediating;Messenger RNA;MicroRNAs;Molecular Biology;mRNA Precursor;novel;Nuclear;particle;Primates;Research;Ribonucleoproteins;RNA;RNA Binding;RNA Processing;RNA Splicing;Saimiriine Herpesvirus 2;Small Nuclear RNA;snRNP Structural Core Protein;Spider Monkey;Techniques;Untranslated RNA;Viral;Viral Cancer;Virus Diseases;Work

PROJECT_TITLE: Novel functions for Sm-class RNAs in the regulation of gene expression

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Fibromyalgia;Neurosciences;Pain Research;Pediatric;Prevention

ORG_DEPT: ANESTHESIOLOGY

PHR: Project Narrative In the proposed study, our overarching goal is to examine behavioral and neurobiological correlates of existing widespread pain and identify predictors of newly incident widespread pain in adolescence, and to explore sex- specific trajectories of pain across pubertal development. Our results will contribute significantly to the fundamental understanding of the natural history of pain in adolescents and have the potential to identify critical vulnerabilities and targets for pain prevention and early treatment.

PI_NAMEs: BELTZ, ADRIENE M.;KAPLAN, CHELSEA  (contact)

PROGRAM_OFFICER_NAME: WOLFF, JOSHUA R

PROJECT_TERMS: Adolescence;Adolescent;Adult;Adult women;Affect;Age;Anterior;antinociception;Anxiety;associated symptom;Awareness;Back Pain;Behavioral;Biological Factors;Brain;Brain region;Categories;Central Nervous System;Child;Childhood;chronic pain;chronic painful condition;chronic widespread pain;Clinical;CNS processing;Cognitive;cognitive development;cohort;Data;Data Set;Development;early adolescence;Early Intervention;Early treatment;Etiology;falls;Fatigue;Female;Fibromyalgia;Goals;gray matter;high risk;Hormones;Inflammation;Insula of Reil;Intervention;Knowledge;Life;life span;Longitudinal Studies;male;Mediating;Memory;Mental Depression;midbrain central gray substance;multisensory;Natural History;negative affect;neural;Neurobiology;neuroimaging;Neuronal Plasticity;Neurons;Outcome;Pain;Pain Free;pain processing;pain sensitivity;Painless;Pathogenesis;Patient Self-Report;Pattern;Positioning Attribute;Predisposition;prepuberty;prevent;Prevention;Prospective, cohort study;Puberty;Reporting;Rest;Risk;Risk Factors;Sampling;sex;Sex Differences;Site;Sleep;Sleep disturbances;Somatosensory Cortex;Structure;Symptoms;Testing;Time;Tissues;Visit;Youth

PROJECT_TITLE: Behavioral and neurobiological predictors of widespread pain in early adolescence and sex-specific trajectories of pain during puberty

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


NIH_SPENDING_CATS: Digestive Diseases;Eye Disease and Disorders of Vision;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rare Diseases

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Retinopathy of prematurity (ROP) is the leading cause of blindness in children. There are limited therapeutic options for this severe ocular pathology. Our overall goal is to identify new and more effective therapies for ROP. In particular, we will explore and characterize the potential therapeutic effects of the nuclear receptor farnesoid- X-receptor (FXR) agonists in experimental models of ROP.

PI_NAMEs: THOUNAOJAM, MENAKA CHANU (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: Ablation;Acids;Adult;Affect;Agonist;Air;angiogenesis;Angiogenesis Inhibitors;Angiogenic Factor;Apoptotic;Astrocytes;Back;Bile Acid Biosynthesis Pathway;Bile Acids;Birth;Blindness;Blood Vessels;Blood-Retinal Barrier;Cataract;Cell Death;cell type;Cells;Child;clinically relevant;Data;design;Development;Diabetic Retinopathy;Disease;effective therapy;Endothelial Cells;Endothelium;Environment;Event;Experimental Designs;Experimental Models;Failure;farnesoid X-activated receptor;ganglion cell;Goals;GPBAR1 gene;Growth;Hyperoxia;Hypoxia;improved;In Vitro;in vivo;Infant;Inflammation;Intervention;intravitreal injection;Ischemia;Knockout Mice;Knowledge;Ligands;Liver diseases;Modeling;Molecular;Mus;Nature;neovascular;neovascularization;neuronal survival;new therapeutic target;novel therapeutic intervention;novel therapeutics;Nuclear Receptors;Ocular Pathology;Outcome;Oxidative Stress;Oxygen;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Pattern;Peripheral;pharmacologic;Phase;photoreceptor degeneration;Play;postnatal;premature;Premature Birth;Premature Infant;prevent;Procedures;protective effect;Publishing;receptor;Receptor Activation;receptor expression;Receptor Signaling;Recurrence;Reporting;response;Retina;retina blood vessel structure;Retinal Degeneration;Retinal Detachment;Retinal Diseases;retinal ischemia;Retinal Neovascularization;Retinopathy of Prematurity;Role;side effect;Signal Transduction;Sterols;tauroursodeoxycholic acid;Therapeutic;Therapeutic Effect;Tissues;tool;treatment strategy;Ursodeoxycholic Acid;Uterus;Vascular Endothelial Growth Factors;Visual Fields

PROJECT_TITLE: Bile acid receptor signaling in retinopathy of prematurity

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


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

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Alzheimer’s Disease (AD) is often associated with Cerebral Amyloid Angiopathy (CAA), in which the blood circulation becomes impaired because there is amyloid deposition on the blood vessels. Macrophages are cells that clean up the tissues in which they live. Using a newly-developed mouse strain, we will determine if macrophages keep the blood vessels healthy, and, when macrophages fail, AD and CAA ensue.

PI_NAMEs: LAFAILLE, JUAN  (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: abeta accumulation;Ablation;Acceleration;Adopted;Adult;Affect;Age-associated memory impairment;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Amyloid beta-Protein;Amyloid deposition;Amyloid Proteins;Anatomic Border;Animal Disease Models;arteriole;Astrocytes;Behavior;behavior test;Behavioral;Blood;Blood - brain barrier anatomy;Blood capillaries;Blood Circulation;Blood Vessels;Border Crossings;Brain;brain health;cell type;Cells;Central Nervous System;Cerebral Amyloid Angiopathy;Cerebrovascular system;Characteristics;cognitive function;Cre driver;Data;Defect;Deposition;Development;Endothelial Cells;Endothelium;factor C;Gene Deletion;Gene Expression;Generations;Genetic;Histocompatibility Antigens Class II;imaging study;Immune;impaired capacity;Impaired cognition;Impairment;improved;Individual;Inflammatory;Kinetics;Location;macromolecule;Macrophage;MAF gene;Maintenance;Memory;Microglia;mouse model;Mouse Strains;Mus;Names;neural;normal aging;old mice;Pathologic;Pathology;Pericytes;Physiological;Play;Population;Process;Proteins;Reagent;Regulation;Role;Running;Shapes;Stress;Testing;Tissues;tool;transcription factor;unpublished works;uptake;young adult

PROJECT_TITLE: The role of brain border-associated macrophages in aging and cerebral amyloid angiopathy


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: HOUSTON

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE In this proposal, we expect to gain substantial insights into fundamental characteristics of distinct populations of dental root mesenchymal progenitor cells orchestrating tooth root formation and regeneration. Further, our proposed transplantation experiment will provide a proof-of-principle study for cell-based therapies to achieve periodontal regeneration. This study will thus guide our future efforts to direct or deliver mesenchymal progenitors to restore a functional root-bone apparatus, in addition to fundamentally advancing the understanding of dental root biology.

PI_NAMEs: ONO, WANIDA  (contact)

PROGRAM_OFFICER_NAME: VERBRIDGE, SCOTT SPENCER

PROJECT_TERMS: Ablation;Alleles;Alveolar;alveolar bone;Apical;Area;beta catenin;Biology;bone;Cell Therapy;cell type;Cells;Cementoblast;Characteristics;chemokine;comparative;CXC Chemokines;Defect;Dental;Dental caries;Dental Cementum;Dental Pulp;Dental Sac;Dentin;Epithelial Cells;Epithelium;Erinaceidae;Etiology;experimental study;Face;FOXF1 gene;Future;Gene Expression Profiling;Generations;Genes;Goals;Growth and Development function;In Situ;In Vitro;in vivo;insight;Intake;Knowledge;Ligands;Ligature;LoxP-flanked allele;Mastication;Mediating;Mesenchymal;Mesenchymal Stem Cells;Modeling;Molecular;Natural regeneration;nutrition;Odontoblasts;Operative Surgical Procedures;Osteoblasts;parathyroid hormone-related protein;Pathway interactions;Periodontal Diseases;Periodontal Ligament;Periodontitis;Periodontium;Physiological;Play;Population;Population Heterogeneity;precursor cell;Prognosis;Prosthesis;regenerative therapy;Role;SHH gene;Signal Transduction;single-cell RNA sequencing;stem cells;Stromal Cell-Derived Factor 1;Structure;Structure of periapical tissue;System;Testing;Tissues;tongue papilla;Tooth Apex;Tooth Components;Tooth Diseases;Tooth Loss;Tooth regeneration;Tooth root structure;Tooth structure;Toxin;transcription factor;transcriptome sequencing;Transplantation;Validation;WNT Signaling Pathway;Work

PROJECT_TITLE: Dental Follicle: A Central Regulator of Tooth Root Formation and Regeneration

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Pediatric

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Mannosemetabolism as a regulator of hepatic stellate cell activation and fibrosis Chronic liver disease can lead to irreversible scarring of the liver, which can lead to liver failure, liver cancer, and necessitate liver transplantation. Currently, there are no approved medical treatments to effectively reverse scarring. This project proposes to investigate a new pathway involved in liver scar formation that can potentially lead to new drug targets.

PI_NAMEs: CHU, JAIME C (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: Address;antifibrotic treatment;Apoptosis;Attenuated;attenuation;Automobile Driving;Biology;cancer cell;Catabolism;Cell Death;Cell Proliferation;cell type;Cells;Cellular biology;Child;Childhood;chronic liver disease;Cicatrix;Cirrhosis;Clinical;cohort;Congenital Disorders;Data;Diabetes Mellitus;Disease;Dose;drug discovery;efficacy evaluation;Enzymes;Ethanol;Exposure to;fibrogenesis;Fibrosis;Genetic;glycosylation;Goals;Hepatic Stellate Cell;Hepatitis B Virus;Hepatocyte;Hepatology;Human;In Vitro;in vivo;inorganic phosphate;Isomerase;Link;Liver;Liver diseases;Liver Failure;Liver Fibrosis;liver metabolism;liver transplantation;Malignant neoplasm of liver;Malignant Neoplasms;Mannose;Mediating;Mediator;Medical;Metabolic;Metabolic Pathway;Metabolism;Minor;Modeling;mutant;Mutation;new therapeutic target;non-alcoholic fatty liver disease;novel;Obesity;Pathway interactions;Phenotype;prevent;Public Health;Rattus;Regulation;response;restoration;Rodent;Rodent Model;Role;sugar;Supplementation;Testing;Therapeutic;Thioacetamide;Vitamin A;Zebrafish

PROJECT_TITLE: Mannose metabolism as a regulator of hepatic stellate cell activation and fibrosis

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Emerging Infectious Diseases;Genetics;Infectious Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative This project aims to provide a quantitative understanding of coronavirus biology using single-cell and single-molecule approaches in vitro and with in vivo murine models. We will develop computational models combined with an imaging-based platform to quantitatively assess replication kinetics and spatiotemporal host cell responses of SARS-CoV-2. This platform will then be applied to the study of clinically relevant human genetic variation and pre-existing anti-interferon autoantibodies, emerging viral variants of concern, and to explore the age-associated differences in susceptibility to severe COVID-19 disease.

PI_NAMEs: RICE, CHARLES M (contact)

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: 2019-nCoV;Address;Affect;Age;age difference;age effect;Animals;Autoantibodies;Behavior;Biological Assay;Biology;cell type;Cells;Cellular biology;Cessation of life;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;comorbidity;Complex;Computational Biology;Computer Models;Coronavirus;COVID-19;COVID-19 pandemic;current pandemic;cytokine;Data;Data Set;Disease;Disease Outcome;Dose;Encapsulated;Environment;Epidemiologic Monitoring;Escape Mutant;Event;fitness;Fluorescent in Situ Hybridization;Future;Gene Expression Profile;Genetic;Genetic Transcription;genetic variant;Genetic Variation;Genomics;Genotype;Glean;Hamsters;Heterogeneity;Hour;human disease;Human Genetics;Image;Immune response;Immunity;In Situ;In Vitro;in vivo;in vivo Model;Individual;Infection;Information Systems;insight;interdisciplinary approach;Interferon alpha;Interferon Type I;Interferons;Intervention;Investigation;Kinetics;Knock-in;Knock-out;Knowledge;Life;Link;Lung;Measures;Methods;Modeling;Molecular;Monkeys;mouse genetics;mouse model;Mus;mutant;Mutation;Natural Immunity;Nature;neutralizing antibody;novel strategies;Outcome;overpopulation;pandemic disease;Pathogenesis;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Persons;Phenotype;Play;population based;Predisposition;Process;Production;Respiratory System;response;Risk Reduction;Role;Sampling;SARS-CoV-2 infection;severe COVID-19;Severity of illness;Signal Transduction;single molecule;spatiotemporal;Symptoms;System;Techniques;Testing;Therapeutic;Time;Tissues;transcriptomics;Vaccines;Variant;variants of concern;Viral;viral RNA;Virion;virology;Virus;Virus Diseases;virus genetics;Virus Replication

PROJECT_TITLE: Tracking SARS-CoV-2 one molecule at a time: Spatiotemporal investigation of coronavirus replication dynamics and host response in single cells in vitro and in vivo

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PI_NAMEs: STEINLE, JENA J (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Adrenergic Agents;Adult;Age;Agonist;beta-adrenergic receptor;Biological Assay;Blindness;Blood Vessels;Cells;chemokine;conditional knockout;Cyclic AMP-Dependent Protein Kinases;cytokine;Data;Diabetes Mellitus;diabetic;Diabetic mouse;diabetic rat;Diabetic Retinopathy;Disease;Disease Progression;Down-Regulation;Early treatment;Endothelial Cells;Forskolin;Glucose;Goals;Immunity;improved;in vivo;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;inhibitor;knock-down;Knockout Mice;Macrophage;macular edema;Mediating;Mediator;Molecular;Muller's cell;Mus;Natural Immunity;Neurons;new therapeutic target;novel;novel therapeutics;overexpression;Pathway interactions;Pattern;Permeability;pharmacologic;Phase;prevent;Process;Proteins;receptor;Receptor Activation;Regulation;Reporting;response;Retina;retinal damage;Role;Signal Transduction;Small Interfering RNA;Streptozocin;targeted treatment;Testing;therapeutic development;therapeutically effective;therapy development;TLR2 gene;TLR4 gene;Toll-like receptors;Work

PROJECT_TITLE: PKA and Epac1 inhibit TLR4 to protect the diabetic retina


NIH_SPENDING_CATS: Cardiovascular;Congenital Structural Anomalies;Genetics;Pediatric;Rare Diseases

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE FBN1 is the causative gene for Marfan syndrome, an inherited disorder of fibrillin-1 microfibrils leading to progressive thoracic aortic aneurysm and an elevated risk for aortic dissection and rupture. Based on our recent discovery that the protease ADAMTS6 binds to and cleaves fibrillin-1, and thus regulates microfibril abundance, we will test whether preventing ADAMTS6 cleavage of fibrillin-1 in Marfan syndrome will protect microfibrils from degradation. The clinical promise of this research is that enhancing microfibril abundance by specific targeting of ADAMTS6 in the aortic wall may protect against aortic aneurysm progression or dissection in patients with Marfan syndrome as a novel disease-modifying approach.

PI_NAMEs: MEAD, TIMOTHY JOSEPH (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: ADAMTS;Address;Adult;Affect;Alleles;Aneurysm;Aorta;Aortic Aneurysm;Arteries;autosome;Binding;Binding Sites;Biochemical;Biological;Biological Assay;Birth;Blood Vessels;Cell Culture Techniques;cell growth regulation;Cells;Cessation of life;Chronic;Clinical;conditional mutant;Connective Tissue Diseases;Cytoskeleton;Data;Defect;Development;Disease;Dissection;Elastic Fiber;Embryo;Embryonic Development;experimental study;Extracellular Matrix;Family member;FBN1;fibrillin;Fibrillin Microfibrils;fibrillin-2;Foundations;Future;Genes;Goals;Growth;Growth Factor;Health;heart defect;Hereditary Disease;Homeostasis;Human;In Vitro;Incidence;Inherited;insight;intermolecular interaction;Investigation;Knock-out;life span;Link;LoxP-flanked allele;Maps;Marfan Syndrome;Mechanics;Mediating;Metalloproteases;Microfibrils;Minor;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;mutant;Mutation;novel;Operative Surgical Procedures;Outcome;Patients;Peptide Hydrolases;Peptides;Post-Translational Protein Processing;postnatal;postnatal period;prevent;prospective;Proteolysis;Recombinants;Research;Risk;Role;Rupture;screening;skeletal;Smooth Muscle Myocytes;Structure;Surface Plasmon Resonance;targeted treatment;Testing;Therapeutic;Thoracic Aortic Aneurysm;Tissues;Vascular Smooth Muscle;Work

PROJECT_TITLE: Impact of microfibril turnover on vascular development and disease

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: Project Narrative: The pathogens Acinetobacter baumannii and Klebsiella pneumoniae, particularly when carbapenem-resistant, cause significant morbidity and mortality for patients. They have recently acquired a number of novel resistance mechanisms that render many of our most active antimicrobials less useful. We will employ the latest mechanistic, translational research approaches via a highly integrated set of three Projects and three Cores to design novel therapeutic regimens to restore our ability to successfully treat these bacterial ‘superbugs’.

PI_NAMEs: BULITTA, JURGEN BERND;DRUSANO, GEORGE LOUIS (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Achievement;Acinetobacter baumannii;Affect;American;Aminoglycosides;Antibiotics;antimicrobial;Antimicrobial Resistance;arm;Awareness;Back;Bacteria;Bacterial Pneumonia;beta-Lactamase;beta-Lactams;Binding Proteins;Biological Assay;carbapenem resistance;Carbapenem-resistant Acinetobacter;Centers for Disease Control and Prevention (U.S.);Clinical;Clinical Trials;clinically relevant;combat;Combined Antibiotics;Communication;Coupled;Data;data repository;design;Development;Dimensions;dosage;Dose;efflux pump;Evaluation;experimental study;Feedback;Fiber;Flow Cytometry;Fluoroquinolones;Four-dimensional;Future;Goals;granulocyte;Growth;Health;high dimensionality;High-dimensional Modeling;Infection;Inflammation;inhibitor;insight;Klebsiella pneumoniae;Lactams;Levaquin;Location;Lung infections;mathematical model;Meropenem;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;mutant;National Institute of Allergy and Infectious Disease;New Agents;novel;novel therapeutics;Organism;Outcome;Output;pathogen;Patients;Penetration;Penicillin-Binding Proteins;Pharmaceutical Preparations;Phase;Phenotype;pneumonia model;Polymyxins;predictive modeling;Predisposition;Probability;Productivity;Program Development;programs;prospective;protein expression;Protein Overexpression;Protein Synthesis Inhibitors;Proteomics;receptor;Regimen;Research Personnel;Resistance;resistance mechanism;Resources;Safety;Site;Sorting;standard of care;Structure;success;Superbug;synergism;System;Test Result;Testing;Tetracyclines;Time;Tissues;tool;tool development;Topoisomerase Inhibitors;transcriptomics;Translational Research;Treatment Failure;treatment optimization;Validation;VDAC1 gene;Ventilator

PROJECT_TITLE: Translational development of new agents alone and in combination to combat Gram-negative pathogens important in Ventilator- Associated Bacterial Pneumonia: Leveraging the Gram-negative toolbox that is

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 KAR-M (S1)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

PI_NAMEs: DRUSANO, GEORGE LOUIS (contact)

PROJECT_TERMS: Acinetobacter baumannii;Advisory Committees;American;Animals;Antibiotics;antimicrobial;Area;Arizona;Australia;Awareness;Bacterial Pneumonia;beta-Lactamase;beta-Lactams;Biological Assay;carbapenem resistance;Carbapenem-resistant Acinetobacter;cell killing;Clinic;Clinical Trials;clinically relevant;cohesion;Collaborations;college;combat;Communication;Computer software;Data;data access;data dissemination;data exchange;data management;data repository;design;Development;Dimensions;dosage;drug action;Electronics;Ensure;Evaluation;experience;experimental analysis;Experimental Designs;Feedback;Fiber;Financial Support;Florida;Flow Cytometry;Future;genome sequencing;Goals;Grant;granulocyte;Health;high dimensionality;High-dimensional Modeling;Home Page;Infection;Infectious Diseases Research;Infrastructure;inhibitor;innovation;insight;instrument;Klebsiella pneumoniae;Lactams;Link;Los Angeles;Maintenance;mathematical model;meetings;member;Metabolic;Modeling;Monitor;mouse model;National Institute of Allergy and Infectious Disease;New Agents;novel;Occupational activity of managing finances;Organism;organizational structure;Outcome;Output;pathogen;Pattern;Pediatric Hospitals;Penicillin-Binding Proteins;Personnel Management;Pharmaceutical Preparations;Pharmacy facility;Phenotype;pneumonia model;Population;pressure;Program Research Project Grants;programs;Progress Reports;prospective;Proteomics;Publications;Regimen;Research;Research Personnel;Resistance;resistance mechanism;response;Risk;Safety;Saint Jude Children's Research Hospital;Scheme;Site;Sorting;Structure;symposium;Testing;Therapeutic;Time;tool;Training;Translating;United States National Institutes of Health;Universities;Update;validation studies;Ventilator;Vertebral column;videoconference;whole genome

PROJECT_TITLE: Core 1 Administrative Core


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

PI_NAMEs: LANG, YINZHI  (contact)

PROJECT_TERMS: Acinetobacter baumannii;Acylation;Aminoglycosides;Antibiotics;Bacterial Pneumonia;bacterial resistance;beta-Lactamase;beta-Lactams;Binding;Binding Proteins;Biological Assay;Bronchoalveolar Lavage;Carbapenem-resistant Acinetobacter;Categories;Cell Membrane Permeability;Cell Separation;Cell Wall;Cells;Clinical Data;clinically relevant;combat;Confocal Microscopy;Data;data integration;data modeling;Data Set;Development;dosage;efflux pump;extracellular;Fiber;Flow Cytometry;Fluorescence Anisotropy;Foundations;Genetic Engineering;genome sequencing;Guanosine Triphosphate;Half-Life;Health;Human;Imipenem;In Vitro;Infection;inhibitor;insight;Kinetics;Klebsiella pneumoniae;Label;Lactams;Lead;Mass Spectrum Analysis;mathematical model;Membrane;Molecular;Morphology;Mus;National Institute of Allergy and Infectious Disease;New Agents;novel;novel strategies;pathogen;Pattern;Penetration;Penicillin-Binding Proteins;Peptidoglycan;Permeability;Pharmaceutical Preparations;Plasma;Polymyxins;Population;Predisposition;Program Development;prospective;Protein Biosynthesis;protein expression;Protein Synthesis Inhibition;Proteins;Proteomics;Pseudomonas aeruginosa;receptor binding;Regimen;Reporting;Resistance;resistance mechanism;response;Site;Sorting;Spheroplasts;Superbug;Techniques;Time;transcriptomics;VDAC1 gene;Ventilator;virtual;whole genome

PROJECT_TITLE: Core 2 Mechanistic Assay Core


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

PI_NAMEs: NEELY, MICHAEL N. (contact)

PROJECT_TERMS: Acinetobacter baumannii;Algorithms;Amikacin;Aminoglycosides;Anti-Inflammatory Agents;Antibiotics;antimicrobial;Back;Bacteria;Bacterial Infections;Bacterial Pneumonia;beta-Lactamase;beta-Lactams;Binding Proteins;Biological Assay;Biological Models;Bronchoalveolar Lavage Fluid;carbapenem resistance;Carbapenem-resistant Acinetobacter;Cell Membrane Permeability;Cells;Centers for Disease Control and Prevention (U.S.);Clinical;combat;Combination Drug Therapy;Combined Modality Therapy;cytokine;Data;data modeling;Data Set;design;Development;dimensional analysis;dosage;Dose;Dose Fractionation;Drug Combinations;Drug Modelings;Drug usage;efflux pump;expectation;experience;experimental study;Feedback;Fiber;granulocyte;Growth;high dimensionality;High-dimensional Modeling;Immune system;improved;In Vitro;in vivo;in vivo Model;Individual;Infection;infection burden;inhibitor;innovation;insight;Intervention;Kinetics;Klebsiella pneumoniae;Lactams;Link;mathematical methods;mathematical model;Measures;Membrane;Metabolic;Methods;Modeling;mouse model;Mus;National Institute of Allergy and Infectious Disease;New Agents;novel;novel strategies;novel therapeutics;Organism;outcome prediction;pathogen;pathogenic bacteria;Patients;Pattern;Penetration;Penicillin-Binding Proteins;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Pharmacology;Phase;Plasma;Play;Pneumonia;pneumonia model;Polymyxins;Population;Predisposition;prospective;Prospective Studies;Protein Biosynthesis;Protein Synthesis Inhibitors;receptor;receptor binding;Regimen;Resistance;resistant Klebsiella pneumoniae;Role;Sampling;Scheme;Site;Software Tools;Speed;synergism;System;Therapeutic;Therapeutic Intervention;Time;Tissues;translational model;Translations;Tuberculosis;Update;validation studies;Ventilator;Work;World Health Organization

PROJECT_TITLE: Core 3 Math Modeling Core


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

PI_NAMEs: BULITTA, JURGEN BERND (contact)

PROJECT_TERMS: Acinetobacter baumannii;Acylation;Affinity;Alkynes;Aminoglycosides;Antibiotics;attributable mortality;Azides;Bacteria;Bacterial Pneumonia;beta-Lactamase;beta-Lactams;Binding Proteins;Biochemical;Biological Assay;Biology;carbapenem resistance;Categories;Cell Membrane Permeability;Cell Wall;Cells;Centers for Disease Control and Prevention (U.S.);Cessation of life;Chemical Structure;Chemicals;Clinical;clinically relevant;Collection;Color;combat;Confocal Microscopy;Continuous Infusion;Data;Data Set;Databases;density;Development;Dose;efflux pump;Enzymes;Flow Cytometry;Generations;Goals;Growth;in silico;In Vitro;Infection;inhibitor;innovation;insight;Kinetics;Klebsiella pneumoniae;Knock-out;Label;Lactams;Libraries;mathematical model;Membrane;Modeling;Molecular;Morphology;Mus;New Agents;next generation;novel;Outcome;overexpression;pathogen;Patients;Pattern;Penetration;Penicillin-Binding Proteins;Pharmacology;Phase;Polymyxins;Population;Predisposition;prevent;Prevention;prospective;protein expression;Protein Synthesis Inhibition;Protein Synthesis Inhibitors;Proteins;Proteomics;prototype;Publishing;receptor;Resistance;resistance mechanism;resistant Klebsiella pneumoniae;response;Resuscitation;Reverse engineering;Series;simulation;Site;Sorting;Structure;Sulbactam;Superbug;System;Time;Topoisomerase Inhibitors;transcriptomics;Validation;VDAC1 gene;Ventilator

PROJECT_TITLE: Project 1 Mechanistic Project


PROJECT_TERMS: Acinetobacter baumannii;Aminoglycosides;Antibiotic Resistance;Antibiotics;antimicrobial;Area;Aztreonam;Back;Bacteria;Bacterial Pneumonia;base;beta-Lactamase;beta-Lactams;Binding Proteins;Biological Assay;Biological Models;Carbapenem-resistant Acinetobacter;Carbapenems;Categories;Cefepime;Cells;Cessation of life;Clinical;combat;Combined Modality Therapy;Data;design;Development;Diagnosis;Dimensions;dosage;Dose;Down-Regulation;Drug Combinations;Drug Exposure;effective therapy;efflux pump;Enzymes;Fiber;Flow Cytometry;Fractionation;Genomics;Genotype;Growth;Half-Life;High-dimensional Modeling;improved outcome;in vivo;indexing;Infection;inhibitor;innovation;insight;Intervention;Investigation;Klebsiella pneumoniae;Label;Lactams;Learning;Link;mathematical model;Microbe;Modeling;Morphology;Multi-Drug Resistance;multiple omics;New Agents;Nosocomial Infections;novel therapeutics;Organism;Output;pathogen;Pathway interactions;Patients;Pattern;Penetration;Penicillin-Binding Proteins;periplasm;Pharmaceutical Preparations;Pharmacodynamics;Phase;Phenotype;Physiological;Polymyxins;Population;pressure;Probability;prospective;protein expression;Protein Synthesis Inhibitors;Proteins;Proteomics;receptor binding;Receptor Cell;Recrudescences;Regimen;Reporter;Reporting;Resistance;resistance mechanism;response;Sampling;Site;Sorting;Superbug;Testing;Therapeutic;therapy resistant;Time;Tobramycin;Topoisomerase Inhibitors;transcriptomics;treatment optimization;Treatment outcome;Up-Regulation;Validation;VDAC1 gene;Ventilator;virtual;Work

PROJECT_TITLE: Project 2 Hollow Fiber Project


PI_NAMEs: LOUIE, ARNOLD  (contact)

PROJECT_TERMS: Acinetobacter baumannii;Agar;Algorithms;analog;Antibiotic Resistance;Antibiotic susceptibility;Antibiotic Therapy;Antibiotics;attributable mortality;Bacteria;Bacterial Pneumonia;bacterial resistance;beta-Lactamase;beta-Lactams;Binding;Binding Proteins;Biological Assay;carbapenem resistance;Carbapenem-resistant Acinetobacter;carbapenemase;Carbapenems;Categories;Cessation of life;Clinical;Clinical Drug Development;Clinical Trials;combat;Combined Antibiotics;Combined Modality Therapy;Confocal Microscopy;Data;density;Development;DNA Topoisomerase IV;dosage;Dose;Drug Combinations;Drug Kinetics;effective therapy;efficacy validation;efflux pump;Enzymes;FDA approved;Fiber;Flow Cytometry;functional restoration;Future;genome sequencing;granulocyte;Human;Immune;Immune system;Immunocompetent;improved;in silico;In Vitro;in vivo;Incidence;Infection;inhibitor;innovation;insight;Klebsiella pneumoniae;Lactams;Liquid substance;Lung;mathematical model;Mathematics;Membrane;Microbe;Modeling;mortality;mouse model;Multiple Bacterial Drug Resistance;Mus;New Agents;Nosocomial Infections;novel;optimal treatments;Parents;pathogen;Patients;Pattern;Penicillin-Binding Proteins;Permeability;Pharmaceutical Preparations;pharmacodynamic model;Pharmacodynamics;Pharmacology;Plasma;Play;Pneumonia;pneumonia model;Polymyxins;Predisposition;Primary Infection;Production;prospective;Protein Synthesis Inhibitors;proteomic signature;Regimen;Reporting;Reproducibility;Resistance;resistance mechanism;resistant Klebsiella pneumoniae;Role;Schedule;Site;Superbug;System;Testing;Time;transcriptomics;Translating;treatment arm;Treatment Failure;Treatment outcome;United States;Validation;Ventilator;ventilator-associated pneumonia;Western Blotting;whole genome

PROJECT_TITLE: Building and prospective validation of promising mono- and combination regimens that optimize killing of CRAB and CR-Klebsiella pneumoniae and for resistance suppression in murine pneumonia models


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Health Services;Heart Disease;Pediatric;Prevention

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE Rheumatic heart disease (RHD) is a valvular heart disease caused by the Strep A bacteria that affects over 40 million people, most of whom live in low-resource settings. Regular administration of injectable antibiotics can improve outcomes for children with the earliest forms of RHD, but we do not know if oral antibiotics (which are more practical) can do the same. This study (GOALIE) will determine the effectiveness of injectable as compared to oral antibiotics and measure the costs, impact on quality of life, and patient and parent satisfaction of both approaches.

PI_NAMEs: BEATON, ANDREA ZAWACKI (contact);OKELLO, EMMY

PROGRAM_OFFICER_NAME: EGERSON, D'ANDREA R

PROJECT_TERMS: Absenteeism at work;Acute;Adherence;Affect;aged;Antibiotic Prophylaxis;Antibiotics;Bacteria;Biological Availability;Cessation of life;Child;Child Care;Clinical;clinical practice;Collaborations;Communities;comparative efficacy;Confidence Intervals;cost;cost effectiveness;Cost Measures;cost-effectiveness ratio;Data;Detection;Diagnosis;Disease;Disease Progression;Echocardiography;economic evaluation;Economics;Effectiveness;effectiveness evaluation;Eligibility Determination;Endemic Diseases;Enrollment;Ensure;Enteral;experience;Guidelines;Health;Health Personnel;health related quality of life;Health system;Heart Valve Diseases;High Prevalence;improved outcome;incremental cost-effectiveness;Infrastructure;Injectable;International;Intramuscular;Intramuscular Injections;low and middle-income countries;Methods;Oral;Outcome;Pain;Parents;Patient Outcomes Assessments;patient-level barriers;Patients;Penicillins;Persons;Policies;Positioning Attribute;premature;prevent;Prophylactic treatment;Protocols documentation;Public Health;Quality of life;Quality-Adjusted Life Years;Randomized;randomized trial;Randomized, Controlled Trials;Recording of previous events;recruit;Reporting;Resource-limited setting;Resources;Rheumatic Fever;Rheumatic Heart Disease;satisfaction;scale up;Schools;screening;standard of care;Structure;system-level barriers;Time;Training;Travel;trial comparing;Uganda

PROJECT_TITLE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A non-inferiority randomized trial. (GOALIE)

STUDY_SECTION: SSPT

STUDY_SECTION_NAME: NHLBI Single-Site and Pilot Clinical Trials Study Section[SSPT(OA)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: College Station

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: RNA silencing regulates essentially every biological process in eukaryotes, and their dysregulations causes numerous diseases and physiological disorders in human and in plants. The proposed study is to determine how several newly identified components such as RNA helicases, catalases, U1-70K, and BICE1 contribute to the production of small RNAs for RNA silencing in Arabidopsis. The studies on the new regulatory mechanisms in RNA silencing in the model organism Arabidopsis may enable us to manipulate these components for a better therapeutic strategy to cure physiological disorders that arise from dysfunctions of RNA processing in biotechnology.

PI_NAMEs: ZHANG, XIUREN  (contact)

PROJECT_TERMS: Arabidopsis;Area;Binding Proteins;Biogenesis;Biological Process;Biology;Biotechnology;catalase;Cell Nucleus;Chromatin;Complex;Cytoplasm;Data;Disease;DNA-Directed RNA Polymerase;Double-Stranded RNA;Eukaryota;Functional disorder;Gene Silencing;Genetic Screening;Goals;Human;Laboratories;Mediating;Microprocessor;MicroRNAs;model organism;novel;Pathway interactions;Physiological;Plants;Process;Production;Proteins;Reactive Oxygen Species;Regulation;Research;Ribosomes;RNA;RNA Helicase;RNA Interference;RNA Processing;RNA-Directed RNA Polymerase;sensor;Small Interfering RNA;Small RNA;Specific qualifier value;Structure;Suppressor Genes;Therapeutic;Transcript

PROJECT_TITLE: Functions and mechanisms of new components in RNA silencing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MRAF-C (01)]


ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: PROJECT NARRATIVE Transcriptional regulation of gene expression is central to complex biological processes, such as development, drug responses, and surviving cellular stress. Organisms must properly respond in a coordinated and stabilizing manner to a diversity of cues and insults. The goal of this work is to understand the mechanisms by which factors establish and maintain appropriate levels of gene transcription.

PI_NAMEs: GUERTIN, MICHAEL JOSEPH (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Biological Assay;Biological Process;Cellular Stress;Classification;cofactor;Complex;Computing Methodologies;Cues;Data;Development;Disease;Environmental Risk Factor;Estrogen Receptors;Estrogens;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;hormonal signals;Hormone use;ineffective therapies;Kinetics;Mediating;Modeling;Molecular;nutrition;Organism;Pharmaceutical Preparations;Process;programs;Regulation;Regulatory Element;Repression;Research;Resolution;response;Signal Transduction;Specificity;System;Testing;Time;tool;transcription factor;Transcriptional Regulation;Variant;Work

PROJECT_TITLE: Mechanisms of coordinate gene regulation by transcription factors


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative This proposal is designed to answer important questions about the connections between making ribosomes and human disease. Ribosomes are the cellular factories that synthesize proteins in all human cells. As both cancer and genetic diseases of newborn babies are linked to abnormalities in the making of ribosomes, our work will be crucial for elucidating the underlying mechanisms of these diseases.

PI_NAMEs: BASERGA, SUSAN J (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Automobile Driving;Biogenesis;Biological Assay;Biological Models;Breast Epithelial Cells;Cell Nucleolus;cell type;Cells;Cellular Assay;Cellular biology;Congenital Abnormality;design;Diploidy;Disease;Embryonic Development;Explosion;Failure;Functional disorder;Genetic;Genetic Diseases;genome-wide;Hela Cells;Housekeeping;Human;Human Cell Line;human disease;Human Genetics;human tissue;Image;Inherited;Lead;Light;Link;Malignant Neoplasms;MCF10A cells;Messenger RNA;MicroRNAs;Molecular Biology;Newborn Infant;novel;novel strategies;Organelles;overexpression;Process;Protein Biosynthesis;Proteins;Regulatory Pathway;Reporting;Ribosomes;ribosomopathy;RNA;RNA Interference;Role;screening;Small Interfering RNA;Technology;tissue/cell culture;Tissues;Untranslated RNA;Work;Xenopus

PROJECT_TITLE: Novel regulatory networks driving human ribosome biogenesis


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Injury to the central nervous system can produce severe disabilities, and there is a tremendous need for effective rehabilitation interventions to preserve and improve function, independence, and quality of life. The likelihood of surviving a traumatic brain injury, stroke, or spinal cord injury has continually increased due to advancements in emergency medical care in both military and civilian settings. As a result, many Veterans (including those injured while young) are living with injury-related disabilities that interfere with quality of life, engagement in societal roles, and that predispose them to the development of additional neurological and systemic illnesses as they age. The Brain Rehabilitation Research Center (BRRC) seeks to develop practical and effective strategies to rehabilitate chronic cognitive, emotional, and motor disabilities in Veterans affected by central nervous system injuries by capitalizing on the brain’s ability to show physiological and structural recovery in response to appropriately designed treatments.

PI_NAMEs: BOSE, PRODIP K. (contact);TRIGGS, WILLIAM ;WILLIAMSON, JOHN B

PROJECT_TERMS: Acute;Address;Adjuvant;Affect;Age;Animals;Artificial Intelligence;Basic Science;Beds;Behavior Therapy;Biological Markers;Brain;brain health;Brain Injuries;career development;Caring;Central Nervous System;central nervous system injury;Chronic;Clinical;Clinical Sciences;Cognition;Cognitive;Collaborations;collaborative environment;community reintegration;Development;disability;Elderly;Emergency Care;Emotional;Emotions;experience;Exposure to;Family;Florida;functional improvement;Goals;Health;Home;Hospitals;Human;Impairment;Influentials;Infrastructure;injured;Injury;inter-institutional;Intervention;Investigation;Investments;Life;Measurement;Mental Health;Military Personnel;Mission;Motor;Motor disability;multidisciplinary;neural network;neuroimaging;neuroinflammation;Neurologic;neurological rehabilitation;Neuronal Plasticity;Neurons;neuropsychiatry;neuroregulation;Neurosciences;neurotoxic;Outcome;Performance;Personal Satisfaction;pharmacologic;Physical Medicine;Physical Rehabilitation;Physiological;Play;pre-clinical;preservation;Program Development;programs;Quality of life;Recovery;recruit;rehabilitation research;Rehabilitation therapy;repaired;Research;Research Personnel;resilience;Resources;response;restoration;Role;Scientist;spinal cord and brain injury;Spinal cord injury;Strategic Planning;Stroke;Survivors;Teletherapy;Testing;therapy design;therapy development;Translational Research;Translations;Traumatic Brain Injury;Treatment Efficacy;Universities;Veterans

PROJECT_TITLE: Gainesville Brain Rehabilitation Research Center (BRRC)

STUDY_SECTION: RRDC

STUDY_SECTION_NAME: Centers, Research Enhancement Award Program and Consortiums[RRDC]


ORG_CITY: MANHASSET

ORG_NAME: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

PHR: Overview Narrative This is study of blood immune cells and brain function in patients with Systemic Lupus Erythematosus in long term clinical remission on no corticosteroids or immunosuppressive medication. We believe that studying this population will provide insights into patient heterogeneity, new patterns of immune homeostasis to inform therapeutic strategies and the state of central nervous system inflammation in those with no detectable peripheral organ inflammation. As 25% of patients will flare over 5 years, we will look for predictors of relapse.

PI_NAMEs: DIAMOND, BETTY  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Address;Adrenal Cortex Hormones;Affect;ATAC-seq;B cell repertoire;Biometry;Blood;Blood Cells;blood-brain barrier permeabilization;Brain;Brain imaging;Cells;Central Nervous System;Clinical;clinical remission;cognitive function;cohort;Data Analyses;data integration;Databases;Diamond;Disease;Disease remission;Educational process of instructing;Epigenetic Process;ethnic diversity;Flare;Genetic Transcription;Geography;glial activation;glucose metabolism;Heterogeneity;Homeostasis;Hydroxychloroquine;Immune;immune activation;Immune system;Individual;Inflammation;insight;Interferons;Kynurenic Acid;Learning;Measures;meetings;Memory B-Lymphocyte;Molecular;Monitor;neuroinflammation;Neurologic;novel;Nuclear Antigens;Organ;Pathway interactions;Patients;Pattern;Peripheral;Pharmaceutical Preparations;Population;programs;Proteomics;Quinolinic Acid;racial diversity;Records;Relapse;relapse prediction;Schedule;Serum;Systemic Lupus Erythematosus;Therapeutic;Time;transcriptome sequencing

PROJECT_TITLE: Learning from Remission and Relapse in SLE

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 LP-I (S1)]


NIH_SPENDING_CATS: Autoimmune Disease;Lupus

PROJECT_TERMS: Acceleration;Advisory Committees;Autoimmunity;Committee Members;Communication;Diamond;Disease remission;experience;Funding;insight;International;Learning;Lupus;Manuscripts;Medicine;meetings;Monitor;Patient Recruitments;Persons;Preparation;Program Research Project Grants;programs;Relapse;Reporting;Research;Research Personnel;Resource Allocation;Rheumatology;Sampling;Schedule;Services;Site;Systemic Lupus Erythematosus;Work

PROJECT_TITLE: Administrative Core


PI_NAMEs: ARANOW, CYNTHIA  (contact)

PROJECT_TERMS: Biometry;Blood;Brain;Case Report Form;Cells;Cities;Classification;Clinical;Clinical Data;clinical remission;clinical research site;cohort;Collection;comparison group;Data;data integration;data integrity;data repository;Databases;Disease;Disease remission;Enrollment;Ensure;ethnic diversity;Ethnic Origin;experience;Flare;follow-up;Geography;Goals;Health Insurance Portability and Accountability Act;Immune;Infrastructure;Kynurenine;Laboratories;Learning;London;Long Island;Los Angeles;Lupus;Medical Research;Mexico;Molecular;Monitor;neuroimaging;neuropsychiatry;Notification;Observational Study;Participant;Patients;Physiological;Protocol Compliance;Protocols documentation;Quinolinic Acid;Race;racial diversity;Records;recruit;Relapse;Research;Research Project Grants;Safety;safety study;Serology;Serum;Services;Site;Study Subject;Systemic Lupus Erythematosus;Testing;Time;Visit

PROJECT_TITLE: Core B: Clinical Core


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Data Science;Genetics;Lupus;Networking and Information Technology R&D (NITRD);Neurosciences;Precision Medicine;Prevention

PI_NAMEs: SIROTA, MARINA  (contact)

PROJECT_TERMS: Address;Algorithms;Area;Autoimmune Diseases;B cell repertoire;Bioinformatics;Biometry;Blood - brain barrier anatomy;Brain;Cells;Clinical;Clinical Data;Collaborations;Complex;Computational Biology;computerized data processing;computing resources;Data;Data Analyses;Data Analytics;Data Collection;data dissemination;data harmonization;data integration;data library;data management;Data Management Resources;data repository;Data Set;data sharing;Data Storage and Retrieval;Data Store;design;Disease;Disease remission;disorder prevention;Early Diagnosis;Early treatment;Engineering;Environmental Exposure;Epigenetic Process;experience;Flow Cytometry;Gene Expression;Generations;Genetic;Genetic Transcription;Genomics;glial activation;glucose metabolism;Goals;high dimensionality;Human Resources;Image;Immune;Immunologics;individual variation;Infrastructure;Joints;Learning;Life Style;Medical History;Metabolic;Methods;Molecular;multimodal data;multimodal modeling;multimodality;Nature;Neurologic;neuropsychiatry;Outcome;peripheral blood;Phenotype;precision medicine;Process;programs;Proteomics;Relapse;Research;Research Design;Research Personnel;Rheumatology;sample collection;Secure;Serum;Specific qualifier value;Staging;Standardization;Statistical Data Interpretation;statistical learning;System;Systemic Lupus Erythematosus;Techniques;Technology;Testing;tool;transcriptomics;Tryptophan;Visualization;web platform;Work

PROJECT_TITLE: Core C: Biostatistics and Data Integration Core (BDI Core)


PI_NAMEs: YE, CHUN JIMMIE (contact)

PROJECT_TERMS: Adopted;Adult;Antigens;ATAC-seq;Autoantibodies;B cell repertoire;B-Lymphocytes;Blood;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell type;Cells;cellular targeting;Chromatin;Clinical;clinical remission;cohort;comparison group;Data;demographics;Disease;Disease remission;Epigenetic Process;epigenome;epigenomics;exhaust;Flare;Frequencies;Gene Expression;Genes;Genetic Transcription;genomic profiling;Geography;Goals;Heterogeneity;Hydroxychloroquine;Immune;Immunity;Immunologics;innovation;insight;Interferons;Learning;London;Maps;Membrane Proteins;Memory B-Lymphocyte;Mexico;Molecular;Molecular Profiling;Molecular Target;multi-ethnic;multimodality;new technology;new therapeutic target;novel;Nuclear Antigens;Outcome;Pathogenicity;Patients;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;profiles in patients;protein expression;Proteome;Proteomics;Reaction;Readiness;Regulation;Relapse;relapse prediction;relapse risk;RNA;RNA Sequences;Sampling;Science;segregation;single cell genomics;single cell sequencing;single cell technology;Site;Specificity;Surface;Systemic Lupus Erythematosus;T-Cell Depletion;T-Lymphocyte;Technology;Testing;Therapeutic immunosuppression;Therapeutic Trials;Time;transcriptome;transcriptomics;Withdrawal

PROJECT_TITLE: Project 1: Multiplexed multimodal single-cell genomic profiling of SLE in remission


NIH_SPENDING_CATS: Autoimmune Disease;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Lupus;Neurosciences

PI_NAMEs: MACKAY, MEGGAN  (contact)

PROJECT_TERMS: Address;Autoimmunity;Binding;Biometry;blood-brain barrier permeabilization;Brain;brain abnormalities;brain dysfunction;Brain imaging;brain metabolism;Brain region;Central Nervous System;Clinical;clinical application;clinical remission;Cognition;cognitive change;Collaborations;contrast enhanced;Control Groups;Data;data integration;Disease;Disease remission;Eligibility Determination;ethnic diversity;Evaluation;Excision;Fc Receptor;Flare;fluorodeoxyglucose positron emission tomography;Functional disorder;Functional Magnetic Resonance Imaging;Future;Genes;Geography;glial activation;Goals;Heterogeneity;Hippocampus;Human;Image;imaging approach;imaging biomarker;imaging study;Immune;Immune response;Impaired cognition;improved;Individual;Interferons;Kynurenic Acid;Learning;Magnetic Resonance Imaging;Marker Discovery;Mass Spectrum Analysis;Measurement;Measures;Metabolic;Metabolism;monocyte;mouse model;multimodal data;Multimodal Imaging;multimodality;N-Methyl-D-Aspartate Receptors;Nervous System Physiology;Neuroimmune;Neuropsychological Tests;Neuropsychology;Nodal;Pathology;Pathway Analysis;Patients;Pattern;Performance;Peripheral;Phenotype;Positron-Emission Tomography;racial diversity;recruit;Relapse;relapse risk;Reproducibility;Rest;Sampling;Serum;Site;Subgroup;Systemic Lupus Erythematosus;Testing;Time;Training

PROJECT_TITLE: Project 2: Assessing Brain Dysfunction in Clinically Quiescent SLE


ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE The proposed program project will use synergistic experimental and modeling approaches with human clinical samples and metadata, a collection of clinical fungal strains, and reductionist murine models to understand Candida gastrointestinal colonization. These studies will characterize fungal adaptations, immune activation, commensal bacteria, and their biosynthetic products that regulate the Candida host-pathogen interface. This work will have broad implications for closing knowledge gaps to prevent and mitigate invasive candidiasis.

PI_NAMEs: BENNETT, RICHARD JOHN;HOHL, TOBIAS M (contact);KOH, ANDREW

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Activities of Daily Living;animal facility;Beds;biosynthetic product;Candida;Candida albicans;candidemia;Candidiasis;cathelicidin antimicrobial peptide;cell killing;Cell model;cell type;Cells;Clinical;Clinical Data;cohort;Collaborations;Collection;colonization resistance;commensal bacteria;Communication;Communities;Computer Models;data integration;Data Set;Defect;Disease;Dissection;dysbiosis;Epithelium;Experimental Models;experimental study;gastrointestinal;Gastrointestinal tract structure;Genomics;Germ-Free;Gnotobiotic;Goals;Growth;gut colonization;gut microbiota;Hematopoietic Stem Cell Transplantation;Human;Immune;immune activation;immune function;Immune signaling;Immune system;improved;Individual;Infection;insight;interdisciplinary approach;Internships;Intervention;Intestines;Knowledge;Life;Lymphoid Cell;mathematical model;Measurement;Mediating;Medium chain fatty acid;Mentors;Metabolic;Metadata;microbiota;microbiota composition;Modeling;Molecular;molecular modeling;Morphology;mouse model;Mucous Membrane;Mus;mutant;novel;Output;Paneth Cells;pathogen;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern recognition receptor;Phenotype;predictive modeling;prevent;programs;Receptor Signaling;Regulation;Research;Role;Sampling;Shapes;Signal Pathway;Source;synergism;Technology;Testing;Therapeutic;Toxin;trait;Transplant Recipients;undergraduate student;Virulence Factors;Work

PROJECT_TITLE: Understanding the molecular mechanisms regulating fungal colonization and disease in the mammalian intestinal niche

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 EC-M (S1)]


NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

PHR: PROJECT NARRATIVE As per this program announcement (PAR-22-225), a Project Narrative should only be uploaded to the Overall component but not to the individual projects and cores.

PI_NAMEs: HOHL, TOBIAS M (contact)

PROJECT_TERMS: Administrative Personnel;Candida;Collaborations;college;colonization resistance;Communication;Communities;conflict resolution;Data;data dissemination;Data Reporting;Disease;Education and Outreach;Ensure;Expenditure;Fostering;Funding;Gastrointestinal tract structure;Gnotobiotic;Goals;immunoregulation;Individual;Infectious Diseases Research;Infrastructure;Institution;Internet;Internships;Intestines;Journals;Laboratories;Leadership;Manuscripts;material transfer agreement;mathematical model;Medical;meetings;Metabolic;Methods;Molecular;multidisciplinary;National Institute of Allergy and Infectious Disease;NIH Program Announcements;Occupational activity of managing finances;Office of Administrative Management;organizational structure;outreach;Participant;Peer Review;Preparation;Procedures;Productivity;programs;Progress Reports;Publications;Regulation;Reporting;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Schedule;Scientist;Services;symposium;synergism;The science of Mycology;timeline;Training Activity;training opportunity;Training Programs;Travel;undergraduate student;United States National Institutes of Health;Visit


NIH_SPENDING_CATS: Infectious Diseases;Microbiome

PROJECT_TERMS: Address;Animal Experiments;Autoimmune Diseases;Bacteria;bacteriome;Bone Marrow Transplantation;Candida;Cells;Collaborations;colonization resistance;Communities;Complex;Data;Derivation procedure;Disease;Dissection;Elements;Embryo Transfer;Experimental Models;experimental study;fungus;Gene Modified;Genetic Engineering;Germ-Free;Gnotobiotic;Goals;gut colonization;gut microbiota;Health;host microbiota;Human;immune activation;Immune system;Immunity;Immunocompromised Host;immunodeficiency;in vivo;Individual;Inflammatory;Infrastructure;insight;Integration Host Factors;intestinal barrier;Intestines;Knowledge;microbiota;Mission;Modeling;Molecular;mouse model;Mouse Strains;Mus;Mutant Strains Mice;NIH Program Announcements;novel;Patients;Program Research Project Grants;Publishing;Resistance;System;Testing;Transplantation

PROJECT_TITLE: Gnotobiotic Core


PI_NAMEs: XAVIER, JOAO  (contact)

PROJECT_TERMS: Allogenic;anti-fungal agents;Antibiotics;antimicrobial;Bacteria;Bayesian Analysis;Biochemical Pathway;Biological Process;Biology;Blood;Blood Circulation;Candida;Candida albicans;candidemia;Cell Count;Cell Physiology;chemotherapy;Clinical;cohort;Collaborations;commensal bacteria;Consumption;Data;data integration;Data Set;design;Disease;dynamic system;Ecology;Equilibrium;Experimental Designs;experimental study;feeding;Genes;Genome;genome-wide;Genomics;Goals;Growth;gut bacteria;gut colonization;gut microbiome;gut microbiota;Hematopoietic Stem Cell Transplantation;Hospitalization;Human;Immune;Immune system;Immunity;Immunological Models;improved;Individual;Intestines;Joints;Link;mathematical model;Measures;Metabolic;metabolic phenotype;metabolomics;Metadata;Metagenomics;Microbe;microbiome;microbiota;Modeling;Molecular;Morphology;mouse model;Mus;NIH Program Announcements;Nutrient;pathogen;Patients;Pharmaceutical Preparations;Phenotype;Population;Population Dynamics;pre-clinical;Pre-Clinical Model;predictive modeling;Process;programs;Property;Recombinants;reconstruction;Resistance;resistance mechanism;Risk;Role;Sampling;Sepsis;Series;Shotguns;stable isotope;stool sample;synergism;Testing;Time;trait;Virulence;whole genome;Work;Yeasts

PROJECT_TITLE: Mathematical Modeling Core


PROJECT_TERMS: Address;anti-fungal agents;Antibiotics;Bacteria;Bar Codes;Behavior;Biological Assay;Candida;Candida albicans;cell injury;Cells;Clinical;Data;dimorphism;Disease;dysbiosis;Enabling Factors;Engineering;Environment;Exclusion;Exhibits;experimental study;fitness;fungus;gastrointestinal;Gastrointestinal tract structure;Genes;Genetic;Germ-Free;Gnotobiotic;gut colonization;gut microbiota;Gut Mucosa;high throughput analysis;host colonization;Human;Hyphae;Immune;Immune response;Immunocompromised Host;In Vitro;Individual;Inflammation;Inflammatory Bowel Diseases;insight;Intestines;Intrinsic factor;Knowledge;Life;Link;Maps;Metabolic;Metabolism;microbial;microbiome;microbiota;Modeling;Molecular;Morphology;Mucous Membrane;Mus;Mycoses;NIH Program Announcements;Nosocomial Infections;novel;pathobiont;pathogen;Pathogenicity;Peptides;Phenotype;Play;Population;Production;Property;Quantitative Trait Loci;Recombinants;Resistance;Role;Series;Shapes;Spatial Distribution;Symbiosis;Systemic disease;Systemic infection;Tissues;Toxin;trait;transcription factor;Virulence;Virulence Factors;Yeasts

PROJECT_TITLE: Candida Determinants of GI Tract Colonization


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Infectious Diseases;Microbiome;Transplantation

PROJECT_TERMS: Adaptor Signaling Protein;Allogenic;anti-fungal agents;anti-microbial peptide;Antibiotics;B-Lymphocytes;Blood;Blood Circulation;Candida;Candida albicans;cathelicidin antimicrobial peptide;Cells;Characteristics;chemotherapy;Clinical;Collaborations;colonization resistance;commensal microbes;Compensation;controlled release;Coupled;Data;Data Set;Disease;Disseminated candidiasis;Enterocytes;Epithelial Cells;Epithelium;Experimental Models;experimental study;fitness;fitness test;Gastrointestinal tract structure;Gnotobiotic;gut colonization;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Human;Hypoxia;hypoxia inducible factor 1;Immune;immune activation;immune function;Immune system;Immunologic Stimulation;Immunological Models;immunoregulation;in silico;in vivo;Individual;Injury;Interleukin-1 Receptors;intestinal epithelium;Intestines;Invaded;Knowledge;Lesion;Lymphoid;mathematical model;Mediating;Mediator;Metabolic;metabolomics;microbiota;Modeling;Molecular;Mononuclear;Morbidity - disease rate;Morphogenesis;mortality;mouse model;Mucous Membrane;Mus;mutant;MyD88 protein;Natural Killer Cells;NIH Program Announcements;Oral;organ transplant recipient;pathobiont;pathogenic microbe;Pathway interactions;Patients;Pattern recognition receptor;Phagocytes;pharmacologic;Phenotype;Pilot Projects;Play;predictive modeling;Predisposition;preterm newborn;Process;programs;Prophylactic treatment;restoration;Risk;Risk Reduction;Role;Sepsis;Signal Pathway;Signal Transduction;Source;synergism;Testing;Therapeutic;Tissues;TLR1 gene;TLR2 gene;Transplant Recipients;Virulence;Virulence Factors;Work

PROJECT_TITLE: Immune Regulation of Candida GI Tract Colonization


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Infectious Diseases;Microbiome;Nutrition;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PROJECT_TERMS: Address;Adult;Allogenic;anti-microbial peptide;Antibiotics;antimicrobial peptide LL-37;Bacteria;bacteriome;Bile Acids;Biological Assay;Butyrates;Candida;Candida albicans;carbohydrate metabolism;Cells;Citric Acid Cycle;Clinic;Clinical;colonization resistance;Communicable Diseases;cytokine;Data;Dendritic Cells;Disease;Down-Regulation;Epithelial Cells;Fatty Acids;fecal transplantation;gastrointestinal;Gastrointestinal tract structure;Genes;Germ-Free;Glucose;glucose metabolism;glucose uptake;Glycolysis;Goals;Growth;gut bacteria;gut colonization;gut microbiome;gut microbiota;Hematopoietic Stem Cell Transplantation;Human;human stem cells;Immune;Immune Tolerance;In Vitro;in vivo;Inbred Mouse;Individual;Inflammatory Bowel Diseases;intestinal epithelium;Intestines;Knowledge;Lauric Acids;Libraries;Link;mathematical model;Mediating;Mediator;Medium chain fatty acid;Metabolic;metabolome;metabolomics;Microbe;microbiome;microbiome signature;microbiota metabolites;Molecular;monocyte;Mus;mutant;Myristic Acids;neonatal mice;NIH Program Announcements;pathobiont;Pathogenicity;Phenotype;Play;Pre-Clinical Model;Propionates;Proteomics;Regulation;Resistance;Role;screening;Shapes;Specimen;Stem cell transplant;stool sample;Systemic disease;Testing;Time;transcription factor;Transplant Recipients;Valerates;Volatile Fatty Acids

PROJECT_TITLE: Metabolic Regulation of Candida GI Tract Colonization


NIH_SPENDING_CATS: Bioengineering;Complementary and Integrative Health;Natural Products

ORG_CITY: ATHENS

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative The proposed research program can potentially lead to the development of platforms to support high-level production of various natural products including polysaccharides, terpenoids, and plant polyketides in bacteria. The developed strains can be potentially applied to establish stable and environmentally friendly microbial supply chain for the production of these nutraceutically and pharmaceutically important compounds. The proposed research program will ultimately contribute to natural products based drug discovery and development.

PI_NAMEs: YAN, YAJUN  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acetyl Coenzyme A;Anabolism;Bacteria;Biosensor;Carbon;Conflict (Psychology);Development;drug development;drug discovery;Engineering;Environment;Friends;Genetic;glycosylation;Goals;Growth;high volume manufacturing;human milk oligosaccharides;improved;insight;Knowledge;Logic;Metabolism;microbial;Monitor;Natural Products;Nutraceutical;Performance;Plants;polyketides;Polysaccharides;Process;Production;programs;Research;Series;supply chain;Terpenes;Terpenoid Biosynthesis Pathway;tool

PROJECT_TITLE: Biosensor-driven Platforms for Biosynthesis of Natural Products in Bacteria

STUDY_SECTION: MRAB

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