NIH_SPENDING_CATS: Cardiovascular;Genetics;Prevention

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF HOUSTON

ORG_STATE: TX

PHR: Project Narrative: Smooth muscle cells secrete exosomes, which are very small particles containing various bioactive lipids, microRNAs or proteins and if increasing may contribute to calcium deposition in the artery wall leading to arterial hardening and increasing risk for cardiovascular disorders. This grant application for the first time explores a molecular mechanism regulating exosome release at the DNA level and determines whether the deficiency of this regulation causes arterial calcification and hardening. Our findings will help answer an important question how arterial hardening starts within cells at the very early stage of patients with cardiovascular risk factor such as hyperphosphatemia and will help develop new strategies for treatment and prevention of cardiovascular disorders.

PI_NAMEs: LI, PINLAN ;ZHANG, YANG  (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Abbreviations;Acceleration;acid sphingomyelinase;Aging;Agonist;Applications Grants;arterial stiffness;Arteries;Atherosclerosis;Binding;calcification;Calcium;Calmodulin;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular risk factor;Cathepsins B;Cell membrane;Cell secretion;Cells;Ceramides;Chronic Kidney Failure;Code;Collagen;Defect;Deposition;Development;Diabetes Mellitus;Disease;DNA;DNA Methylation;DNA Modification Methylases;Early Endosome;Endosomes;enzyme activity;Enzymes;Epigenetic Process;epigenetic regulation;exosome;Extracellular Matrix;EZH2 gene;Face;Functional disorder;galactosylgalactosylglucosylceramidase;Gene Deletion;Gene Expression;gene repression;Genes;Genetic Transcription;histone methylation;Histone-Lysine N-Methyltransferase;Histones;Hypertension;Image;interstitial;Knock-out;Knockout Mice;late endosome;Lead;Link;Lipids;Lysine;Lysosomes;Medial;Mediating;Membrane Proteins;Metabolism;Methylation;Methyltransferase;MicroRNAs;mineralization;Molecular;Multivesicular Body;Mus;Muscle Cells;new therapeutic target;novel;novel therapeutic intervention;osteogenic;particle;patch clamp;Pathologic;Pathologic Processes;Patients;Phenotype;Play;prevent;Process;Production;programs;Proteins;receptor;Regulation;Reporting;Repression;Research;Role;sensor;Signal Transduction;Smooth Muscle;Smooth Muscle Myocytes;Sphingolipids;Sphingomyelinase;Sphingomyelins;Sphingosine;sphingosine 1-phosphate;Stimulus;Testing;Time;trafficking;Vascular calcification;Vesicle;Vitamin D

PROJECT_TITLE: Epigenetic Regulation of Lysosomal Ceramide Signaling and Function in Arterial Myocytes: Role of Kmt6 Gene


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: GENETICS

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Mutations which alter chromosome structure and copy number can have profound consequences for human development and disease. Comprehensive analysis of this source of genetic variation is difficult in humans, however. We will study both naturally occurring and laboratory engineered structural and copy number variants using yeast as a model in order to understand how they affect traits both positively and negatively.

PI_NAMEs: DUNHAM, MAITREYA J (contact);SCHACHERER, JOSEPH

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Affect;Agar;Aneuploidy;Bar Codes;base;Beer;Beverages;Biology;Caenorhabditis elegans;Chromosome Structures;Chromosomes;Collaborations;Collection;Complement;Complex;Copy Number Polymorphism;Data;Data Analyses;design;Dissection;DNA Resequencing;dosage;Engineering;Environment;Eukaryota;experimental study;Fermentation;fitness;fitness test;Food;Frequencies;gene environment interaction;Gene Expression;Genetic;genetic architecture;genetic linkage;genetic variant;Genetic Variation;Genome;genome wide association study;genome-wide;Genomics;Genotype;Growth;Heritability;Human;Human body;Human Development;human disease;Hybrids;Individual;Industrialization;Insecta;Knowledge;Laboratories;Libraries;Literature;Measures;Messenger RNA;Methods;model organism;Modeling;Molecular;molecular phenotype;Mutation;nanopore;novel strategies;Phenotype;Plants;pleiotropism;Population;Process;Proteins;rare variant;Resources;Role;Saccharomyces cerevisiae;Saccharomycetales;Sampling;Series;Soil;Source;Structure;Surveys;Technology;Testing;trait;Universities;Variant;vector;Washington;whole genome;Wine;Work;Yeast Model System;Yeasts

PROJECT_TITLE: Species-wide survey of the phenotypic impact of genomic structural variation in yeast

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ORG_CITY: DAVIS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Narrative Human disease-causing mutations in connexin channels affect the transport of ions and molecules across the plasma membrane, causing deafness, blindness, as well as neurological and skin disorders. We seek to understand the molecular mechanisms underlying ion and molecule transport in connexin channels, with the goal of elucidating how human mutations alter these processes. This information is critical for the rational development of therapeutic approaches to treat the disorders caused by human connexin mutations.

PI_NAMEs: CONTRERAS, JORGE ENRIQUE (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Address;Affect;Arrhythmia;Binding Sites;Biological Assay;Biological Process;biophysical properties;Blindness;Brain Ischemia;Cell membrane;Cells;Chimera organism;Communication;Compensation;Complement;congenital skin disorder;Connexins;crosslink;Cysteine;Cytoplasm;Data;deafness;design;Development;Diffusion;Disease;disease-causing mutation;Docking;Drug Design;Drug Targeting;Dyes;experimental study;extracellular;Functional disorder;gap junction channel;Genes;GJB2 gene;GJB6 gene;Glutamates;Goals;Grant;Health;Heart failure;Human;human disease;Human Pathology;innovation;Ion Channel;Ion Transport;Ions;Kinetics;Knowledge;Measurement;Mediating;Modeling;Molecular;molecular dynamics;molecular modeling;molecular recognition;Mutagenesis;Mutation;N-terminal;Nervous System Disorder;Nitric Oxide;novel;Organ;Pathologic;Pathology;Pathway interactions;Permeability;Physiological;prevent;Process;Progress Reports;Property;Protein Isoforms;Proteins;Publishing;Regulation;Research;Resolution;Role;Signal Transduction;Site;skin disorder;Stimulus;Structure;Sudden Death;Testing;Therapeutic;therapeutic development;Tissues;Transport Process;unnatural amino acids;uptake;voltage;voltage clamp

PROJECT_TITLE: Gating and Regulation of Connexin Hemichannels


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: We propose to study SERCA, the enzyme that controls calcium in muscle. Calcium misregulation leads to myopathies of skeletal muscle. Our evidence suggests that SERCA is regulated by proteins of the muscle cytoskeleton, and that contractions of muscle can transmit signals to SERCA through these proteins to modulate its activity. If we can verify this idea, we will gain important insights into the role that SERCA plays in maintaining healthy skeletal muscle, and how to manipulate its activity to combat myopathy.

PI_NAMEs: BLOCH, ROBERT J (contact);KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Ablation;Acceleration;Adrenergic Agents;Affinity;Alternative Splicing;Anisotropy;ANK1 gene;Ankyrins;ATP phosphohydrolase;Binding;Biological Assay;Biomechanics;Ca(2+)-Transporting ATPase;Calcium;Cell membrane;Chimeric Proteins;combat;Complement;Complex;connectin;COS Cells;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cytoskeletal Proteins;Cytoskeleton;derepression;Dissociation;endoplasm;Enzymes;experimental study;Fluorescence;Fluorescence Resonance Energy Transfer;Frequencies;Functional disorder;Health;Heart;Homeostasis;In Situ;insight;Integral Membrane Protein;Kinetics;Learning;Link;Measures;Mechanical Stress;member;Membrane;Metabolic Clearance Rate;Methods;millisecond;Modeling;Molecular;Molecular Conformation;Muscle;Muscle Contraction;Muscle Proteins;mutant;Myopathy;novel;obscurin;overexpression;Pathogenicity;Pathway interactions;Periodicity;phospholamban;Phosphorylation;Physiological;Play;Positioning Attribute;Protein Splicing;Proteins;Pump;Regulation;Relaxation;reuptake;Role;Ryanodine Receptor Calcium Release Channel;Sarcolemma;sarcolipin;Sarcomeres;Sarcoplasmic Reticulum;sensor;SERCA1;Signal Transduction;skeletal;Skeletal Muscle;Stress;Striated Muscles;Testing;therapeutic target;Time;transmission process;Tubular formation;uptake

PROJECT_TITLE: Cytoskeletal Regulation of SERCA in Muscle

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cardiovascular;Dental, Oral, and Craniofacial Disease;Genetics;Heart Disease;Infectious Diseases;Microbiome;Prevention;Rare Diseases

ORG_CITY: RICHMOND

ORG_DEPT: DENTISTRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative Streptococcus sanguinis is a common bacterium in the mouth, where it is associated with oral health; however, if it enters the bloodstream through periodontal disease, routine activities such as chewing, or dental procedures, it can cause a serious infection of the heart called infective endocarditis. We propose to perform an unprecedented search for factors required by S. sanguinis to cause this disease with the goal of finding targets for a new kind of antibiotic that prevents disease, but can also be taken daily without promoting antibiotic resistance.

PI_NAMEs: KITTEN, TODD O.;XU, PING  (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: Affect;Antibiotic Resistance;Antibiotics;Bacteria;Binding;Bioinformatics;Biological Assay;Blood;Blood Circulation;Blood Platelets;ChIP-seq;commensal bacteria;Death Rate;Dental;Dental Care;Dentists;Development;Disease;Endocarditis;Environment;fitness;gene conservation;Gene Expression;Gene Expression Regulation;gene function;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;Growth;Heart;Heart Valves;Human;in vivo;indexing;Infection;Infective endocarditis;Libraries;Mastication;member;Methods;Microbial Biofilms;Modeling;Molecular;mutant;Mutation;new therapeutic target;novel strategies;novel vaccines;nutrition;Open Reading Frames;Oral;oral bacteria;Oral cavity;oral commensal;Oral health;oral lesion;oral streptococci;Oryctolagus cuniculus;Output;Pathogenesis;Pathway Analysis;Patients;Periodontal Diseases;Phagocytosis;Phenotype;prevent;Prevention strategy;prophylactic;protein expression;Research;RNA;Saliva;screening;Serum;Streptococcus;Streptococcus sanguis;Systems Biology;Technology;Therapeutic;Tooth structure;Toothbrushing;transcription factor;Transcriptional Regulation;transcriptome sequencing;Virulence;Virulence Factors;virulence gene;Western Blotting

PROJECT_TITLE: Oral Streptococcal Fitness And Virulence genes

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Thorp Narrative Lay Due in significant part to limited therapeutic options and incomplete understanding of mechanisms of pathophysiology, diastolic dysfunction (DD) and Heart Failure with Preserved Ejection Fraction (HFpEF) encompasses approximately half of all heart failure cases. Our data implicate maladaptive metabolism of innate immune cells in the progression of DD during HFpEF. The studies outlined in this proposal are among the first to test the therapeutic proof of principle, mechanistic basis, and clinical relevance of immune metabolism during DD.

PI_NAMEs: THORP, EDWARD BENJAMIN (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acceleration;Area;Basic Science;Behavior;Calibration;Cardiac;cardiometabolism;CD36 gene;Cells;Cellular biology;Cellular Metabolic Process;Characteristics;Clinical Research;clinically relevant;combinatorial;comorbidity;coronary fibrosis;Data;deep sequencing;Disease Progression;disorder risk;EFRAC;Epidemic;Fatty acid glycerol esters;Functional disorder;Generations;Genes;Heart;Heart failure;Hyperlipidemia;Hypertension;hypertensive;Immune;Immune Targeting;Immunotherapeutic agent;Impairment;imprint;improved;in vivo;Individual;Inflammation;Inflammatory;insight;Link;Lipids;Macrophage;Metabolic;Metabolic Pathway;Metabolic syndrome;Metabolism;metabolomics;Mitochondria;Morbidity - disease rate;mortality;Mus;Myelogenous;Myeloid Cells;Myelopoiesis;Myocardial;Pathology;Pathway interactions;Patients;Performance;peroxisome;preservation;programs;Relaxation;Research;Research Priority;Resolution;Respiration;Risk Factors;Role;Signal Transduction;Stress;synergism;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapeutically effective;tool;United States National Institutes of Health;Ventricular

PROJECT_TITLE: Contributions of Myeloid Metabolism to Diastolic Dysfunction

STUDY_SECTION: MPPB

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


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Surgeons remain at the forefront of the care for patients with cancer. The clinical experience of surgeons gives them a particular perspective on cancer. There is a need for research expertise among surgeons and those interested in surgical oncology so that these individuals are fully prepared to tackle the important future research needs in basic cancer biology, translational cancer research and cancer epidemiology.

PI_NAMEs: GOLDENRING, JAMES RICHARD (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Grant;Surgical Oncology;Training

PROJECT_TITLE: Surgical Oncology Training Grant

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

ORG_CITY: CORAL GABLES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative  Cancer is the second leading cause of death in the United States and sustained conceptual as well as therapeutic innovation is needed to reduce disease burden. Thus, it is imperative to start training the next generation of cancer researchers as early as possible. We propose a comprehensive summer undergraduate research program that integrates mentored cancer research with educational initiatives in computational and public health-based approaches to provide research experiences and skills that will facilitate successful entry into oncology research careers.

PI_NAMEs: RAI, PRIYAMVADA  (contact);VOLMAR, CLAUDE-HENRY

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Academic skills;Academic Training;Address;Affect;anti-cancer research;Area;Bioinformatics;Biological Markers;Biology;Biomedical Research;Biotechnology;burden of illness;Cancer Burden;Cancer Control;cancer health disparity;Cancer Research Project;career;career development;Catchment Area;Cause of Death;Clinical Oncology;Clinical Trials Design;commercialization;Communities;Community Health;Community Outreach;Complement;Comprehensive Cancer Center;Country;Coupled;Data Analyses;Data Set;Databases;Development;Diagnosis;Disease;drug development;drug discovery;Education;Educational Curriculum;Educational workshop;efficacy evaluation;Ensure;Environment;Epigenetic Process;epigenome;experience;Exposure to;Faculty;faculty mentor;faculty research;Feedback;Fellowship Program;field trip;Florida;Future;Genome;Goals;hands on instruction;Health Disparities Research;Immunotherapy;Incidence;Incubators;Individual;Infrastructure;innovation;insight;Institution;Instruction;interest;Knowledge;Literature;Location;Malignant Neoplasms;medical schools;Mentors;Methodology;Mining;Modernization;Monitor;next generation;novel;Oncologist;Oncology;Outcome;outreach;Participant;Patients;peer;peer coaching;peer networks;personalized medicine;phase I trial;Physicians;Population;Positioning Attribute;programs;Public Health;Qualifying;Reading;recruit;Research;Research Institute;Research Personnel;Research Project Grants;Resources;screening;skills;sociodemographics;socioeconomic disparity;Students;summer program;symposium;technological innovation;Therapeutic;therapeutic target;tool;Training;Training and Education;Treatment outcome;trial design;Tumor Biology;undergraduate research;undergraduate research experience;undergraduate student;United States;Universities;Validation;Writing

PROJECT_TITLE: Comprehensive Research Experiences to Advance Training and Education (CREATE) for Future Cancer Researchers


NIH_SPENDING_CATS: Genetics;Human Genome;Microbiome

ORG_CITY: AUSTIN

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative The proposed research examines the patterns of adaptation and gene exchange in bacteria and viruses that are associated with humans and relevant to human health. Recognition of these factors is vital to our understanding of the ways that bacteria and viruses evolve, since such processes have led to new routes and agents of infection.

PI_NAMEs: OCHMAN, HOWARD  (contact)

PROJECT_TITLE: Elucidating the Evolution of Microbial Genes, Genomes and Communities

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


NIH_SPENDING_CATS: Cancer;Clinical Research;Comparative Effectiveness Research;Health Services;Palliative Care;Patient Safety

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE Personal payments from the pharmaceutical industry influence physician prescribing, but little is known about whether these payments affect patients. This study proposes to evaluate the association between industry payments to physicians and the quality, patient outcomes, and costs of cancer care.

PI_NAMEs: MITCHELL, AARON P (contact)

PROGRAM_OFFICER_NAME: DAVIDOFF, AMY

PROJECT_TERMS: acute care;Address;Adverse event;Affect;cancer care;Cancer Patient;cancer therapy;cancer type;care costs;care delivery;Caring;Cessation of life;Clinical Oncology;Clinical Practice Guideline;Communities;Community Physician;cost;cost outcomes;Data;Decision Making;Drug Industry;Drug toxicity;end of life care;Etiology;Event;Fee-for-Service Plans;financial relationship;financial toxicity;Future;Goals;Guidelines;Health;Health system;Healthcare Systems;high risk;Hospitalization;improved;Industry;insight;interest;Internist;Intervention;Investigation;Link;Malignant Neoplasms;Manufacturer;Medical;Medical Oncologist;Medicare;Methods;Oncologist;Oncology;Outcome;Outcome Measure;Patient Selection;Patient-Focused Outcomes;Patients;payment;personal narratives;Pharmaceutical Preparations;Physicians;Policies;Policy Maker;Prevalence;Quality of Care;Recommendation;Research;Selection for Treatments;Testing;therapy duration;Time;treatment pattern;Treatment-related toxicity

PROJECT_TITLE: Understanding the Importance of Industry Relationships for Cancer Care Quality, Outcomes, and Costs

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Childhood Leukemia;Genetics;Hematology;Lupus;Lymphatic Research;Lymphoma;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: PROJECT NARRATIVE Patients with B-cell mediated autoimmune lymphoproliferative diseases, including systemic lupus erythematosus (SLE), and those with indolent, pre-malignant B-cell clones are vulnerable to developing aggressive B-cell malignancies. Our proposed studies will delineate how the hormone, prolactin (PRL), by signaling specifically through the long and intermediate isoforms of the prolactin receptor (LF/IFPRLR), drives the evolution of high- grade B-cell malignancies in vulnerable individuals and sustains these malignancies. Our investigations will identify isoform-specific knockdown of the LF/IFPRLR as an effective, less-toxic, and affordable approach to treat a broad spectrum of B-lymphoproliferative disorders with widely divergent outcomes.

PI_NAMEs: SWAMINATHAN, SRIVIDYA  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: activation-induced cytidine deaminase;Adult Precursor B Lymphoblastic Leukemia;Affect;Alternative Splicing;Apoptotic;autocrine;Autoimmune;Autoimmune Diseases;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;B-Cell Neoplasm;B-Lymphocyte Subsets;B-Lymphocytes;BCL2 gene;Biological;Burkitt Lymphoma;cancer cell;Cell Count;cell killing;Cell Proliferation;Cell Survival;cell transformation;Cells;Cessation of life;Childhood;Chronic Lymphocytic Leukemia;Clinical;clinically relevant;Clone Cells;Cytokine Receptors;Development;disease model;DNA;Early Intervention;Enzymes;Equilibrium;Evolution;Growth;high risk;Hormones;Human;Immune;Immunologic Surveillance;In Vitro;in vivo;Incidence;Indolent;Induction of Apoptosis;innovation;Intervention;Investigation;knock-down;large cell Diffuse non-Hodgkin's lymphoma;Left;Legal patent;Lymphoid Cell;Lymphoid Tissue;Lymphoproliferative Disorders;Malignant - descriptor;Malignant Neoplasms;Measures;Mediating;Modeling;Molecular;mouse model;Mus;MYC gene;Neoplasms;novel;Outcome;overexpression;Pathogenicity;Pathologic;Pathway interactions;Patients;Persons;Phenotype;premalignant;prevent;Production;Prolactin;Prolactin Receptor;Proliferating;Protein Isoforms;Proto-Oncogenes;Refractory;Research;Risk;RNA Splicing;Role;Signal Transduction;STAT3 gene;Subgroup;Symptoms;Systemic Lupus Erythematosus;Testing;Therapeutic;Therapeutic Intervention;Vulnerable Populations

PROJECT_TITLE: Targeting the long isoform of the prolactin receptor to treat autoimmune diseases and B-cell malignancies

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


ADMINISTERING_IC: AI

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_DEPT: SOCIAL SCIENCES

PHR: The proposed research is relevant to public health because understanding how to best use vancomycin to treat C. difficile infection is likely to improve patient outcomes, thus ensuring continued success with this important option for the treatment of the most common healthcare- associated infection. This proposal is relevant to the part of NIH’s mission that pertains to fostering fundamental creative discoveries and innovative research strategies as a basis for ultimately protecting health.

PI_NAMEs: GAREY, KEVIN W (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Agar;Anti-microbial susceptibility;Antibiotic susceptibility;Antibiotics;antimicrobial;bactericide;biobank;Biological;Biological Assay;Bioluminescence;Cell Wall;Characteristics;Clinical;clinical database;Clinical Microbiology;clinical practice;Clinical Trials;clinically relevant;clinically significant;Clostridium difficile;Collection;Colon;Creativeness;Data;Databases;Development;Diagnosis;Disease;Effectiveness;Ensure;Evaluation;Failure;FDA approved;Fostering;Foundations;Functional disorder;Future;Glycopeptides;Goals;Grouping;Growth;Health protection;Healthcare;healthcare-associated infections;Hospitalization;impression;improved;Infection;inhibitor;innovation;Measures;Mediating;Methods;minimal inhibitory concentration;Mission;Modeling;molecular diagnostics;Mutation;Oral;Organism;Outcome;outcome prediction;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase;point-of-care diagnostics;Predisposition;Production;Public Health;Recommendation;Recurrence;recurrent infection;Research;Research Personnel;research study;Resistance;resistance mechanism;Resolution;Site;Stream;Subgroup;success;Symptoms;Techniques;Testing;Time;Toxin;Translational Research;Treatment Failure;United States;United States National Institutes of Health;Vancomycin;Vancomycin Resistance;Work

PROJECT_TITLE: Vancomycin Susceptibility Measures to Evaluate C. difficile infection Outcomes

STUDY_SECTION: EDIT

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: DURHAM

ORG_DEPT: NEUROSCIENCES

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Epigenetic regulation and synaptic signaling emerged as convergent cellular and molecular pathways affected in multiple cohorts of patients with ASD, suggesting that epigenetic dysregulation during development might lead to dysfunctional neural circuits in autism. However, which neural cell types are affected by autism-associated epigenetic changes and how these changes influence formation and function of specific neuronal circuits is currently unknown. Dissecting cell type-specific epigenetic and neuronal circuitry changes is paramount to precise understanding of autism pathogenesis and selection of targets for precision medicine.

PI_NAMEs: VELMESHEV, DMITRY  (contact)

PROGRAM_OFFICER_NAME: KISHORE, SANDEEP

PROJECT_TERMS: Affect;Alleles;Area;ASD patient;ATAC-seq;autism spectrum disorder;autistic;Autopsy;Award;Bar Codes;Brain;brain tissue;Candidate Disease Gene;cell cortex;Cell Nucleus;cell type;Cells;Child;Chromatin;Chromatin Remodeling Factor;clinical heterogeneity;cohort;comparison control;Cre lox recombination system;Data;Data Set;Development;DNA-Binding Proteins;effective therapy;Engineering;Enterobacteria phage P1 Cre recombinase;Epigenetic Process;epigenetic profiling;epigenetic regulation;Exhibits;Gene Expression;Gene Expression Profile;Generations;Genes;Genetic Engineering;Genetic Heterogeneity;genetic risk factor;Genetic Transcription;Genome;Genomic approach;Genomics;global health;Goals;helicase;Heterogeneity;Human;in vivo;insight;Joints;Label;Lead;Libraries;loss of function;loss of function mutation;Maps;Modeling;Molecular;molecular pathology;mouse model;Mus;Mutate;Neocortex;neocortical;neural circuit;Neurodevelopmental Disorder;Neuroglia;neuronal circuitry;Neurons;novel;Oligonucleotides;Pathogenesis;Pathway interactions;Patients;Phase;Phenotype;Poly A;Postdoctoral Fellow;precision medicine;Process;Protocols documentation;Publishing;Rabies virus;rabies virus barcoding;Recurrence;Regulatory Element;Reporter;Research;Research Personnel;Research Project Grants;Risk;Risk Factors;RNA;sequencing platform;Signal Transduction;single cell genomics;single nucleus RNA-sequencing;single-cell RNA sequencing;skills;Synapses;Synaptic Transmission;System;Systems Biology;targeted treatment;Techniques;Testing;Tissues;tool;Training;transcriptome sequencing;transcriptomics;United States;vector;Viral;viral RNA;Virion;Virus;Wild Type Mouse;Work;XCL1 gene

PROJECT_TITLE: Analysis of epigenetic and neuronal circuit changes in autism on the single-cell level


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Lupus

ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Systemic lupus erythematosus (SLE) is a life-threatening disease of the immune system that primarily affects women in childbearing age with death rates approaching 10% in 5 years. The major causes of death include infections due to the toxicity of immunosuppressant medications. Therefore, a significant unmet need exists for non-toxic medications in SLE. Our research has been directed to develop safe and effective treatments that are focused on the very causes of lupus pathogenesis, such as the depletion of a natural antioxidant, reduced glutathione (GSH), which underlies inflammation in SLE through activating a regulatory protein called the mechanistic target of rapamycin (mTOR). Along this line, we have initiated a clinical trial in SLE patients aimed at the replenishment of GSH with an amino acid precursor, N-acetylcysteine (NAC). As shown by our pilot study completed in 2011, NAC was tolerated by all patients at the 1.2 g/day and 2.4 g/day dosages, while 33% of those receiving 4.8 g/day had reversible nausea. Placebo and 1.2 g/day NAC did not influence disease activity. Although the 2.4 g/day and 4.8 g/day NAC dosages showed preliminary evidence for therapeutic efficacy, 4.8 g/day NAC achieved greater clinical improvements. NAC raised GSH, blocked mTOR, and expanded anti-inflammatory cells. Importantly, the safety of NAC has been widely confirmed and efficacy has been noted in follow-up case reports. While NAC is inexpensive compared to current therapies burdened with serious side-effects and widely accessible in health food stores, it is unavailable as an oral medication by prescription. Therefore, the proposed phase II trial will employ the SLE Responder Index (SRI), as a clinically meaningful primary outcome to evaluate the efficacy of NAC over 1 year. To minimize potential intolerance of NAC and subject withdrawal during the trial, the design includes an open-label dosage titration period. Patients who tolerate 2.4-4.8 g daily NAC for 3 months will be randomized or assigned 1:1 to continue treatment on their tolerated dosage of NAC or matching placebo for 9 additional months. Beyond the premise of validating clinical efficacy and durability of this therapy, the proposed studies will test the assumption that depletion of GSH and activation of mTOR predict clinical responsiveness to NAC in SLE. The proposed studies are expected to lead to the development of a novel, uniquely safe, and affordable medication with the potential to favorably alter the long-term outcomes of SLE.

PI_NAMEs: MCDERMOTT, MICHAEL P;PERL, ANDRAS  (contact);WALLACE, DANIEL J.

PROGRAM_OFFICER_NAME: MANCINI, MARIE

PROJECT_TERMS: Acetaminophen;Acetylcysteine;Address;Affect;Age;Amino Acids;Anti-Inflammatory Agents;Antidotes;Antinuclear Antibodies;Antioxidants;Autoimmune Diseases;B-Cell Activation;Biological Markers;biomarker driven;Case Study;Cause of Death;CD3 Antigens;CD8B1 gene;Cell Lineage;Cell secretion;Cells;child bearing;Clinical;clinical efficacy;Clinical Management;clinical practice;clinical predictors;Clinical Trials;clinically relevant;Complex;Cyclic AMP;Cysteine;Death Rate;design;Development;disabling symptom;Disease;DNA;dosage;Double-Blind Method;Down-Regulation;Dropout;Drops;Drug Prescriptions;effective therapy;efficacy evaluation;Enrollment;Etiology;Fatigue;Feedback;follow-up;FOXP3 gene;FRAP1 gene;Functional disorder;Generations;genetic regulatory protein;Glutathione;Health Food;Human;IL17 gene;IL2RA gene;Immune;Immune System Diseases;Immunologics;Immunosuppressive Agents;improved;in vivo;indexing;Infection;Inflammation;Inflammatory;innovation;Interferons;Interleukin-4;Intervention;intravenous administration;Kidney Diseases;Knowledge;Kynurenine;Life;Liver Failure;Lupus;lupus prone mice;Mediating;Metabolic;Metabolic Pathway;metabolome;Methylation;Mitochondria;mortality;Multicenter Trials;Mus;Nausea;Nephritis;novel;open label;Oral;Outcome;Outcome Measure;Oxidation-Reduction;Oxidative Stress;Participant;Pathogenesis;Pathway interactions;Patients;Peripheral Blood Lymphocyte;Permeability;Persons;Pharmaceutical Preparations;Phase;phase II trial;Pilot Projects;Placebo Control;placebo controlled study;Placebos;Plasmablast;predict clinical outcome;primary outcome;Production;promoter;Proteins;Randomized;Randomized Controlled Clinical Trials;reactive oxygen intermediate;Reduced Glutathione;Regulatory T-Lymphocyte;Research;Research Design;Role;Safety;Sample Size;sensor;side effect;Signal Transduction Pathway;Sirolimus;Specific qualifier value;System;Systemic Lupus Erythematosus;T-Cell Activation;T-Cell Development;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;Time;Titrations;Toxic effect;Treatment Efficacy;treatment response;Withdrawal;Woman;Work

PROJECT_TITLE: SLE Treatment with N-acetylcysteine


NIH_SPENDING_CATS: Arthritis;Genetics;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: SAINT LOUIS

ORG_DEPT: ORTHOPEDICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: RELEVANCE Bony fractures are very common during orthopaedic trauma. Approximately ten percent of the 16 million fractures occurring annually in the United States do not progress to timely union; especially in patients under inflammatory conditions, including diabetes and rheumatoid arthritis (RA). The main goal of this study is to define Dnmt3b-mediated molecular and epigenetic changes to further elucidate a novel pathway in fracture repair. This work will enhance our understanding of mechanisms by which systemic inflammation (via the NF- κB pathway) affects the fracture healing process through Dnmt3b and identify downstream targets of Dnmt3b (such as Rbpjκ) as novel candidates for therapeutic intervention.

PI_NAMEs: SHEN, JIE  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Ablation;Acceleration;Address;Affect;Binding;Bone callus;bone fracture repair;bone quality;Bone Regeneration;Cell Differentiation process;cell type;Cells;Chondrocytes;Chronic;chronic inflammatory disease;Clinical;Clinical Research;Complex;cytokine;Data;Defect;Diabetes Mellitus;diabetic;Disease;DNA Methylation;DNA Modification Methylases;DNMT3B gene;Enzymes;Epigenetic Process;epigenetic regulation;epigenome;Event;Fibroblasts;Fracture;fracture risk;gain of function;Genetic;Genetic Transcription;Goals;healing;Human;Impaired healing;Impairment;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inhibitor;Knowledge;loss of function;Mediating;Mesenchymal Stem Cells;Methylation;Molecular;Mus;new therapeutic target;notch protein;novel;older patient;Orthopedics;Osteitis;Osteoblasts;osteoprogenitor cell;Pathway interactions;Patients;pharmacologic;Population;Process;progenitor;promoter;protective effect;Publications;response;Rheumatoid Arthritis;Role;Series;Signal Transduction;Smoking;stem cell differentiation;stem cell proliferation;systemic inflammatory response;Testing;therapeutic candidate;Therapeutic Intervention;tool;Transgenic Mice;Trauma;United States;Up-Regulation;Work

PROJECT_TITLE: Epigenetic Regulation of Bone Regeneration in Inflammatory Disease

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Nanotechnology;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Current influenza (flu) vaccines are not effective in protection against viruses with antigen drifts/shifts even after annual update. This, along with a constant threat of unpredicted emergence of a new virus with pandemic potential, urges the need to develop a “Universal” flu vaccine that can elicit heterosubtypic immunity against both seasonal and pandemic flu viruses. To address this unmet medical need specifically, this proposal is to develop a safe and potent mucosal adjuvant to vigorously stimulate heterosubtypic immunity of licensed flu vaccines against diverse flu A viruses.

PI_NAMEs: WU, MEI X (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: Address;Adjuvant;Adjuvanticity;Adverse effects;Adverse event;Affect;Agonist;alveolar epithelium;Alveolar Macrophages;Alveolus;Animal Model;Antigen-Presenting Cells;Antigens;Binding;Biological Response Modifiers;Biomimetics;Body Temperature;Body Weight;Bone Marrow Cells;Cause of Death;CD8-Positive T-Lymphocytes;cell type;Cells;Cessation of life;Cholera Toxin;Clinical;cross immunity;cross reactivity;Cyclic GMP;Cytosol;Dendritic Cells;Distant;Dose;Dreams;emerging virus;Encapsulated;Endocytosis;Epithelial Cells;Exhibits;experience;flu;Flu virus;Gap Junctions;Gene Activation;Generations;global health;H1N1 vaccine;Hemagglutinin;high risk;human model;Immune response;Immunity;Immunization;Immunologic Surveillance;Influenza;Influenza A Virus, H1N1 Subtype;Influenza A Virus, H3N2 Subtype;Influenza A Virus, H5N1 Subtype;Influenza A Virus, H7N9 Subtype;influenza virus strain;influenza virus vaccine;Innate Immune System;ITGAM gene;Licensing;Lipids;Liposomes;Lung;lung histology;Mediating;Medical;Membrane;Membrane Proteins;Mucous Membrane;Mus;Names;nanoparticle;Neuraminidase;neutralizing antibody;novel;pandemic disease;pandemic influenza;pandemic potential;pandemic virus;Pathologic;Pathway interactions;Phase;Phospholipase A2;Poly I-C;Population;pre-pandemic;prevent;Probability;Production;Pulmonary Inflammation;Pulmonary Surfactant-Associated Protein A;Pulmonary Surfactants;recruit;Respiratory System;response;Role;seasonal influenza;Seasons;Stimulator of Interferon Genes;Surface;T cell response;Time;Uncertainty;universal influenza vaccine;Update;Vaccination;vaccine efficacy;Vaccines;Viral;Viral Vaccines;Virus;Virus Diseases;Wild Type Mouse

PROJECT_TITLE: Biomimetic nanoparticles to enhance the breadth of influenza vaccines

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Contraception/Reproduction;Fibroid Tumors (Uterine);Patient Safety;Women's Health Research

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative  This project is relevant to public health because hysterectomies (i.e., surgical removal of the uterus) are a common surgical procedure performed in women over the age of 60. Ureteral injuries are a serious complication of hysterectomies due to poor visualization of the ureter (which needs to remain intact to preserve urinary func- tion) and nearby blood vessels (which need to be severed for uterus removal). Our aim is to establish a novel photoacoustic imaging technology that will enable surgeons to avoid the ureter and better target the uterine arteries while detecting surgical tool tips to mitigate a serious complication of hysterectomies.

PI_NAMEs: BELL, MUYINATU A. LEDIJU (contact)

PROGRAM_OFFICER_NAME: KING, RANDY LEE

PROJECT_TERMS: absorption;Acceleration;Acoustics;Acute Kidney Failure;Advanced Development;Age;Anatomy;Arteries;auditory feedback;Benchmarking;Biomedical Technology;Biometry;Blood Vessels;Cadaver;Cessation of life;Clinical;clinical translation;Clutterings;Complication;contrast imaging;Contrast Media;Custom;deep learning;design;Detection;Development;Dyes;Engineering;Excision;experience;experimental study;Faculty;Family suidae;FDA approved;Feedback;Foundations;Future;Goals;Gynecologic;Gynecologic Surgical Procedures;Hemoglobin;Hemorrhage;Hospitals;Human;Hysterectomy;Image;image guided;Imaging Device;imaging system;Imaging technology;in vivo;Injury;innovation;Kidney Failure;Laparoscopic Surgical Procedures;Length of Stay;Letters;Light;mechanical pressure;Metals;Methods;Methylene blue;minimally invasive;Mission;molecular imaging;Morphologic artifacts;National Institute of Biomedical Imaging and Bioengineering;novel;Operative Surgical Procedures;optical fiber;Optics;Patients;Pelvis;Penetration;Performance;photoacoustic imaging;Pilot Projects;Positioning Attribute;preference;preservation;Procedures;Property;Prostatectomy;Public Health;Radical Prostatectomy;Recovery;Repeat Surgery;Research;Research Support;Resources;Robot;robot assistance;Robotics;Sepsis;Series;Signal Transduction;simulation;sound;Structure;Surgeon;System;Techniques;Technology;Testing;Thoracic Surgical Procedures;Time;tool;Translations;transmission process;trend;Ultrasonography;Universities;Ureter;urinary;Urine;Uterine myomectomy;Uterus;Vagina;Veterinary Pathology;Visualization;Visualization software;Woman;Work

PROJECT_TITLE: Photoacoustic Image Guidance of Hysterectomies

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Epilepsy is marked by paroxysmal seizures, and it can be extremely difficult to determine which brain regions are involved. Brain stimulation is a way that brain excitability can be probed and altered for the diagnosis and treatment of epilepsy. This project uses newly available brain stimulation technology to quickly and accurately localize patient-specific epilepsy networks to improve diagnosis and treatment of focal epilepsy.

PI_NAMEs: LUNDSTROM, BRIAN NILS (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TITLE: Novel diagnostic stimulation to quantify cortical excitability and guide epilepsy therapy

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Immunotherapy;Liver Cancer;Liver Disease;Rare Diseases

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE (from parent application) Nivolumab, a novel PD-1 immune checkpoint inhibitor, has shown unprecedented results in a phase II clinical trial in hepatocellular carcinoma, a tumor type that is refractory to other targeted therapies, and has been granted accelerated FDA approval. Unfortunately, the determinants of sensitivity and resistance to this immunotherapy have not been established yet. Here, by combining the use a novel mouse model of HCC immune surveillance, human HCC samples, and transcriptional and immune profilings, we will establish the tumor intrinsic signaling pathways that promote immune escape in HCC, the underlying mechanisms of immune escape, and their effects on response to anti-PD-1 therapy, providing the rationale for improved patient selection and strategies to overcome resistance.

PI_NAMEs: LUJAMBIO, AMAIA  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Acceleration;Address;Affect;anti-PD-1;anti-PD1 therapy;Applications Grants;bak protein;BAY 54-9085;beta catenin;Biological Markers;biomarker identification;cancer cell;cancer immunotherapy;Cessation of life;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;CTNNB1 gene;design;Diagnosis;Excision;Exclusion;experimental study;FDA approved;Genes;genetic element;Genetic Transcription;Genetically Engineered Mouse;Grant;Health;Hepatocyte;Human;human disease;Immune;Immune checkpoint inhibitor;Immune Evasion;Immune response;Immune system;immunogenicity;Immunologic Surveillance;Immunotherapy;Impairment;improved;inhibitor;Liver;liver cancer model;Malignant neoplasm of liver;Modeling;mouse model;Mus;Mutation;MYC gene;neoplastic cell;Nivolumab;novel;Oncogenes;Oncogenic;overexpression;parent grant;Parents;Pathway interactions;patient biomarkers;Patient Selection;patient stratification;Patients;pembrolizumab;Phase;Phase II Clinical Trials;Phenotype;PIK3CG gene;Primary carcinoma of the liver cells;programmed cell death protein 1;PTEN gene;Refractory;Resistance;response;Sampling;Signal Pathway;T cell infiltration;Tail;targeted treatment;Testing;TP53 gene;transcriptomics;Transplantation;tumor;Tumor Antigens;Tumor Escape;Tumor Immunity;Tumor Suppressor Genes;vector;Veins

PROJECT_TITLE: Tumor-intrinsic signaling pathways restrict anti-tumor immunity in hepatocellular carcinoma


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

PHR: Bacterial lipopolysaccharide, also known as endotoxin, is an essential building block of Gram-negative bacterial cell walls and recognized by human antimicrobial protein GBP1. This project will determine how both intracellular and extracellular Gram-negative bacterial pathogens alter their lipopolysaccharides in order to avoid recognition by cytosolic and secreted GBP1. The characterization of these bacterial immune escape strategies may identify novel drug targets for the treatment of bacterial infections.

PI_NAMEs: COERS, JOERN  (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Acceleration;Acylation;Anti-Bacterial Agents;anti-microbial peptide;Antibiotics;antimicrobial;Apolipoproteins;Bacteria;bacterial genetics;Bacterial Infections;Bacterial Meningitis;Binding;Binding Proteins;Biological Assay;Biological Process;candidate identification;capsule;Cell Death;Cell secretion;cell type;Cell Wall;Cells;Cellular Immunity;Cerebrospinal Fluid;Cytosol;Data;Detergents;Disaccharides;Drug Targeting;Encapsulated;Endothelial Cells;Endotoxins;enteric pathogen;Enzymes;Epithelial Cells;extracellular;Extracellular Protein;Fatty Acids;genetic approach;Goals;Gram-Negative Bacteria;guanylate;Host Defense;Human;human pathogen;Immune;Immune Evasion;Immune system;Immunity;In Vitro;Infection;Infection Control;Inflammasome;inhibitor;Innate Immune Response;inorganic phosphate;Interferons;Kinetics;Length;Libraries;Licensing;Lipid A;Lipids;lipopolysaccharide-binding protein;Lipopolysaccharides;Macrophage;Mass Spectrum Analysis;Mediating;Mediator;Membrane;Microcapsules drug delivery system;Modification;Molecular Target;Multi-Drug Resistance;new therapeutic target;novel;novel strategies;novel therapeutic intervention;pathogen;pathogenic bacteria;Pathway interactions;Patients;Pattern recognition receptor;Penetration;Permeability;Plasma;Polymyxin B;polypeptide;Protein Secretion;Proteins;Pseudomonas aeruginosa;Pulmonary Cystic Fibrosis;Resistance;response;Role;Route;Salmonella typhimurium;screening;Shigella flexneri;Side;Structure;Surface;surfactant;synergism;targeted treatment;Testing;Therapeutic;TLR4 gene;treatment strategy;Virulence Factors;Work

PROJECT_TITLE: Novel roles for lipopolysaccharide modifications in immune evasion

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Immunization;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PHR: Project Narrative Allogeneic blood or marrow transplantation (AlloBMT) is the most effective consolidation strategy to prevent disease relapse in adults with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who achieve remission, but the risk of relapse following transplant remains unacceptably high and is now the most significant cause of post-transplant mortality. Newly developed therapies that stimulate the immune system to fight leukemia have proven successful in ALL and AML patients with relapsed disease. The focus of this application is to use these new therapies following alloBMT to prevent relapse of AML and ALL with a long-term goal of identifying the patients in whom such post-transplant therapy is most necessary and successful.

PI_NAMEs: WEBSTER, JONATHAN ALLEN (contact)

PROJECT_TERMS: Acute leukemia;Acute Lymphocytic Leukemia;Acute Myelocytic Leukemia;Adoption;Adult;Advisory Committees;Allogeneic Bone Marrow Transplantation;Allogenic;Antibody Therapy;Antigen Targeting;Award;B cell therapy;B-Cell Acute Lymphoblastic Leukemia;B-Lymphocytes;Bioinformatics;Biometry;Bispecific Antibodies;Blood;Bone Marrow Transplantation;CD19 Antigens;CD19 gene;CD3 Antigens;CD8B1 gene;Cells;clinical investigation;Clinical Sciences;Clinical Trials;conditioning;Coupled;Cyclophosphamide;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Development;Disease;Disease remission;Donor Lymphocyte Infusion;Dose;Educational Curriculum;Eragrostis;Evaluation;Faculty;fighting;Future;Gene Expression;Gene Mutation;Goals;graft vs host disease;graft vs leukemia effect;Grant;Hematologic Neoplasms;high risk;Homologous Transplantation;IL3RA gene;immune reconstitution;Immune system;Immunologic Stimulation;Immunologics;Immunology;Immunosuppression;improved;Intervention;Isogenic transplantation;Laboratories;leukemia;leukemia relapse;Link;Maintenance;Maintenance Therapy;Measurable;Mediating;medical schools;member;Mentors;Mentorship;mortality;Mutation;neoplastic cell;novel strategies;novel therapeutics;older patient;Oncology;Patient Selection;Patients;Phase;Play;Population;post-transplant;Pre-B Acute Lymphoblastic Leukemia;prevent;professor;programs;prophylactic;Prophylactic treatment;Public Health Schools;Publications;randomized trial;Recommendation;Recovery;recruit;Recurrent disease;Reducing Agents;Refractory;Regimen;Regulatory T-Lymphocyte;Relapse;relapse prevention;relapse risk;Remission Induction;Research;Research Personnel;Research Project Grants;Residual Neoplasm;response biomarker;Role;Safety;safety assessment;skills;Source;Specificity;Supportive care;T-Cell Activation;T-Cell Depletion;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;targeted agent;targeted treatment;therapy development;Toxic effect;Transplant Recipients;Transplantation;Transplantation and Immune System;transplantation therapy;Treatment Failure;United States;Universities

PROJECT_TITLE: Bispecific Antibody Maintenance Therapy after Allogeneic Bone Marrow Transplant

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


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

ORG_CITY: BIRMINGHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative - Toxin secretion and trafficking by Mycobacterium tuberculosis The ability to control the timing and mode of host cell death plays a pivotal role in microbial infections. Most pathogenic bacteria use toxins to evade and/or subvert immune responses, to survive and replicate in the host. In this project we investigate the novel molecular mechanisms, by which CpnT, the only known exotoxin of M. tuberculosis, is secreted, how the toxin is trafficked into the cytosol of macrophages infected with M. tuberculosis and which role these mechanisms play in virulence and pathogenesis of M. tuberculosis.

PI_NAMEs: NIEDERWEIS, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: Address;Antibodies;Apoptosis;Bacteria;Biological Assay;C-terminal;Cell Death;Cells;Complex;crosslink;Cytosol;cytotoxic;Data;Elements;ELF3 gene;Exotoxins;experimental study;Genes;Grant;Human;Hydrolysis;Hypoxia;Immune response;In Situ;In Vitro;in vivo;Infection;Lipid Bilayers;Liposomes;Macrophage;Mass Spectrum Analysis;Membrane;membrane assembly;Membrane Proteins;microbial;Molecular;Molecular Analysis;Molecular Conformation;mouse model;Mus;mutant;Mutate;Mycobacterium tuberculosis;N-terminal;Necrosis;novel;Operon;Pathogenesis;pathogenic bacteria;Pathway interactions;Peptide Hydrolases;Permeability;Phagosomes;Phenotype;Play;Pore Proteins;Property;Proteins;Research Project Grants;Resolution;Role;Route;Structure;System;Toxin;trafficking;Tuberculosis;tuberculosis granuloma;VDAC1 gene;Virulence;Water

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-D(02)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Precision Medicine

PHR: Project Narrative The two most prescribed biologics in Ulcerative Colitis are vedolizumab and adalimumab, however, efficacy for these advanced therapies plateaus at approximately 30%. Our data indicate that persistence of distinct neutrophil subsets in the intra-epithelial space results in ongoing intestinal stem cell (ISC) injury, negatively impacting the epithelial crypt microenvironment and treatment efficacy for biologics. Thus, proposed studies will identify new mechanisms of therapeutic resistance to biologics and identify molecular targets to optimize/improve responsiveness.

PI_NAMEs: DULAI, PARAMBIR SINGH;SUMAGIN, RONEN  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: 3-Dimensional;Achievement;adalimumab;Affect;Aftercare;Animal Model;Animals;Automobile Driving;base;Binding;Biological Products;Biological Response Modifier Therapy;Biopsy;Blood Vessels;cell injury;Cells;Chronic;Clinical;clinical remission;clinically relevant;Coculture Techniques;Colitis;Colon Injury;colonic crypt;Control Groups;Controlled Clinical Trials;cost;Cues;CXCL5 gene;Data;digital;Disease remission;Double-Blind Method;Epithelium;Exhibits;Functional disorder;Genes;genetic approach;genetic signature;Head;healing;Health Expenditures;Histologic;Homeostasis;Homing;Human;Immunosuppressive Agents;improved;in vivo;Inflammation;Inflammatory Bowel Diseases;inhibitor;Injury;innovation;Intercellular adhesion molecule 1;intestinal crypt;intestinal epithelium;Intestines;intraepithelial;ITGAM gene;Knock-out;Lamina Propria;Mediating;Messenger RNA;Microscopic;Modeling;Molecular;Molecular Target;Mucous Membrane;murine colitis;Mus;neutrophil;novel;Organoids;Participant;Patients;Persons;Pharmaceutical Preparations;Phenotype;Placebo Control;Population;pre-clinical;predicting response;predictive signature;prognostic;Proteins;RANTES;Reporter;resistance mechanism;Resolution;responders and non-responders;response;Signal Transduction;Sodium Dextran Sulfate;Space Perception;stem cell division;stem cell survival;stem cells;Steroids;T cell therapy;T-Lymphocyte;Therapeutic;therapy outcome;therapy resistant;transcriptome;transcriptomics;Treatment Efficacy;treatment response;Ulcerative Colitis;United States;Work

PROJECT_TITLE: Identifying Neutrophil Specific Mechanisms for Resistance to Biologics in Ulcerative Colitis

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: BERKELEY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT SUMMARY Nef is an HIV-1 accessory protein whose function is essential for the virus to undermine host defenses, yet is not targeted by any existing antirtrovirals. Nef downmodulates many substrates, including CD3, CD4, CD8, CD28, CXCR4, MHC-I, SERINC3/5, and for HIV-1 group O and SIV, BST2/tetherin by hijacking a family of heterotetrameric adaptors known as the adaptor protein (AP) complexes. This proposal will use cryo-EM and biochemistry and biophysics to determine the mechanism by which Nef hijacks AP complexes and downmodulates so many different substrates.

PI_NAMEs: HURLEY, JAMES H (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adaptor Protein Complex 2;Adaptor Signaling Protein;Affect;Alleles;Anti-viral Agents;Automobile Driving;Basic Science;Binding Sites;Biochemistry;Biophysics;CD28 gene;CD3 Antigens;CD8B1 gene;Cell membrane;Cell surface;Cell Surface Proteins;Cells;Clathrin;Clathrin-Coated Vesicles;Complex;Cryoelectron Microscopy;CXCR4 gene;Cytosol;design;Detergents;Down-Regulation;Family;follow-up;Funding;Goals;HIV;HIV-1;Host Defense;Human;Image;Immune system;Immunity;Infection;insight;Integral Membrane Protein;latent virus activation;Lipids;Location;Lysosomes;Mediating;member;Membrane;Membrane Lipids;Membrane Protein Traffic;Monomeric GTP-Binding Proteins;Mutation;Pathway interactions;Pattern;Phenotype;prevent;Process;Production;protein complex;Proteins;reactivation from latency;receptor;reconstitution;Reporting;Research Proposals;Role;Route;Seminal;Signal Transduction;Site;SIV;Sorting;Structure;Substrate Interaction;Tail;trans-Golgi Network;Viral;Viral Antigens;viral fitness;Virion;Virus

PROJECT_TITLE: Allostery and Hijacking of Host Membrane Traffic by HIV-1 Accessory Proteins


NIH_SPENDING_CATS: Cancer

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative: These studies will investigate how key cancer cell signaling pathway genes are regulated by chemical modifications. New chemical methods will be developed and applied to elucidate the functions of these modifications and our findings can lead to new strategies for the treatment of cancer.

PI_NAMEs: COLE, PHILIP A (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Address;AKT Signaling Pathway;Binding;Biochemical;Biological Assay;Biophysics;C-terminal;cancer cell;cancer therapy;Cell membrane;Cells;Chemicals;combat;Complex;Core Protein;Dedications;Development;Disease;Enzymes;Event;Excision;Family;FDA approved;FRAP1 gene;Glucocorticoids;Grant;Hand;insight;interest;Kinetics;Knowledge;Ligase;Malignant Neoplasms;Measurement;Mediating;member;Methods;Mind;Modification;Molecular;Mutate;N-terminal;next generation;novel;novel therapeutic intervention;Oncogenic;Pathway interactions;Pharmaceutical Preparations;phosphatidylinositol 3,4,5-triphosphate;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipids;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphorylation Site;Phosphotransferases;PIK3CG gene;polypeptide;Portraits;Post-Translational Protein Processing;programs;protein function;Protein Kinase;Protein Kinase C;protein protein interaction;protein structure;Protein Subunits;Proteins;PTEN gene;Reaction;Recombinants;recruit;Regulation;Research;Research Personnel;Serum;Signal Pathway;Signal Transduction;Signaling Protein;Site;Structure;Substrate Specificity;therapeutic development;therapeutic target;Training;tripolyphosphate;tumor;Tumor Suppressor Genes;Ubiquitin;ubiquitin isopeptidase;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Chemical Approaches to Cell Signaling Enzymes

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Hearing Loss;Infectious Diseases;Neurosciences;Regenerative Medicine;Rehabilitation

ORG_DEPT: OTOLARYNGOLOGY

PHR: Project Narrative The removal of damaged cells from the sensory organs of the inner ear helps promote tissue repair and homeostasis. The proposed studies will examine the roles of inflammatory cells and epithelial supporting cells in this repair process. Additional studies will determine whether inflammatory cells are responsible for balance disorders caused by infection with cytomegalovirus and by cochlear implantation.

PI_NAMEs: WARCHOL, MARK  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Acoustic Nerve;Acute;Affect;Afferent Neurons;Brain;Cause of Death;Cell Death;cell injury;Cell Survival;cell type;Cells;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Cochlea;Cochlear implant procedure;Cochlear Implants;Cytomegalovirus;Cytomegalovirus Infections;Data;Development;Dizziness;Eating;Effector Cell;Epithelium;equilibration disorder;Equilibrium;Excision;experience;experimental study;Exposure to;Family;hair cell regeneration;Hair Cells;Head Movements;Hearing;Homeostasis;Human;implantation;Infection;Inflammation;Inflammatory;Inflammatory Response;injured;Injury;injury recovery;Innate Immune System;Inner Ear Infection;Inner Hair Cells;Knowledge;Labyrinth;lateral line;Lesion;Macrophage;macula;Mechanics;Mediating;member;Membrane;method development;migration;Modeling;Morphology;Motion;mouse model;Mus;Natural Immunity;Natural regeneration;Neomycin;neonatal mice;neuromast;noise exposure;normal aging;Organ;ototoxicity;ototoxin;Pathology;Peripheral;Phagocytes;Phagocytosis;Phagocytosis Inhibition;Phosphatidylserines;Phosphotransferases;Pilot Projects;Play;Population;prenatal;prevent;Process;receptor;Recovery of Function;recruit;repaired;response;Role;Sensory;Sensory Hair;Signal Pathway;Signal Transduction;Site;sound;Stereotyping;Supporting Cell;Surface;System;Testing;tissue repair;Tissues;transmission process;Utricle structure;Vertebrates;Vertigo;Vestibular function;Vestibular Hair Cells;Vestibular loss;Vestibular Nerve;vestibular system;vibration;Virus Diseases;Zebrafish

PROJECT_TITLE: Macrophage Response to Otic Pathology

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: PROJECT NARRATIVE  The proposed research is relevant to Veterans’ health because it focuses on developing a new, non-invasive set of tools to identify the disease progression of multiple sclerosis (MS) before it becomes irreversible, thereby creating the potential for new treatments. More than 30,000 Veterans have been diagnosed with MS since 1998 and 17,000 are treated within the Veteran Affairs Healthcare System yearly.1 The high healthcare burden in the Veteran population, resulting from the physical and cognitive impairment caused by MS, has led the creation of the VA MS Center of Excellence Network.2  The results of our work are expected to have a positive impact because they will facilitate the monitoring of Veterans who have MS and other traumatic and non-traumatic pathologies of the central nervous system.  Thus, the proposed research is relevant to the VA ORD’s mission “to improve Veterans' health and well- being via basic, translational, clinical, health services, and rehabilitative research.”

PI_NAMEs: BAGNATO, FRANCESCA ROSARIA (contact)

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Area;Axon;axon injury;Binding;Biometry;Brain;Central Nervous System;cerebral atrophy;Classification;Clinical;Clinical Trials;Clinical/Radiologic;Cognitive;Contralateral;Data;Demyelinations;Development;Diagnosis;Diffusion;disability;Disease;disease diagnosis;Disease Progression;Fiber;Foundations;Future;Goals;Health;Health Services;healthcare burden;Healthcare Systems;Image;Impaired cognition;Impairment;improved;in vivo;indexing;Individual;Injury;innovation;International;Intervention;Investigation;Lesion;Life;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measurement;Measures;Methods;Microscopic;military veteran;Mission;Monitor;mortality;Motor;Multiple Sclerosis;multiple sclerosis patient;Myelin;Nerve Degeneration;Neurologic Dysfunctions;Neurological outcome;neuroprotection;novel;Outcome;Pathologic;Pathology;Patients;Personal Satisfaction;Persons;physical impairment;predict clinical outcome;Protons;Proxy;Radiology Specialty;Recovery;Rehabilitation therapy;repaired;Research;Risk Factors;Sample Size;Sampling;Specificity;Techniques;Testing;Time;tissue injury;Tissues;tool;Veterans;Veterans Health Administration;Water;Work

PROJECT_TITLE: Improving the Assessment of Myelin and Axonal Integrity in Early Multiple Sclerosis


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: PHILADELPHIA

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE The Penn Skin Biology and Diseases Resource-based Center (Penn SBDRC) enables and accelerates skin disease research and its translation by providing critical infrastructure, resources, and expertise to skin investigators. The overall goals of this Center are to promote collaborative, multi-disciplinary research among skin investigators, to draw new investigators with diverse perspectives to skin research, to foster an environment that supports and cultivates the next generation of skin researchers; to accelerate and increase the impact of skin investigations by providing expertise, cutting-edge technologies, and valuable tissue resources for conducting rigorous skin research, and ultimately, to translate of research findings into innovative therapies for skin disease.

PI_NAMEs: GRICE, ELIZABETH ANNE (contact)

PROGRAM_OFFICER_NAME: GARCIA-CAZARIN, MARY

PROJECT_TERMS: Academy;Acceleration;Advisory Committees;barrier to testing;Bioinformatics;Biology;Biomedical Research;Blood specimen;Budgets;career;Cells;Clinic;Clinical;Collaborations;Communication;Communities;Community Outreach;Cutaneous;Data Science;Dermatologist;Dermatology;design;Diagnosis;Discipline;Disease;disease model;diversity and inclusion;Educational workshop;effectiveness evaluation;Ensure;Environment;Evaluation;Experimental Designs;experimental study;Faculty;Financial Support;Fostering;Funding;Funding Mechanisms;Funding Opportunities;Future;Genomics;Goals;Health;High School Student;Histologic;Human;imaging approach;improved;Informatics;Infrastructure;innovation;Innovative Therapy;Interdisciplinary Study;intravital imaging;Investigation;Laboratories;Learning;lectures;Medicine;member;Mentors;Mentorship;Molecular;Monitor;multidisciplinary;new technology;next generation;operation;Patients;Pennsylvania;personalized approach;phenomics;Phenotype;Philadelphia;Positioning Attribute;Prevention;programs;Reproducibility;Research;Research Personnel;Research Project Grants;research study;Resources;Schools;Series;Services;Skin;skin disorder;Structure;success;summer internship;Surveys;symposium;Techniques;Technology;tissue resource;Tissues;Training;transcriptomics;Translating;Translational Research;Translations;Underrepresented Minority;volunteer;Woman


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

PROJECT_TERMS: Academy;Acceleration;Achievement;Advisory Committees;Area;Award;Basic Science;Biology;Budgets;career;collaborative environment;Communication;Communities;Community Outreach;Core Facility;Critiques;Data;Databases;Dermatology;design;disabled;Disadvantaged;Disease;diversity and inclusion;Education;Educational workshop;effectiveness evaluation;Environment;Evaluation;Faculty;Financial Support;Fostering;Funding;Funding Mechanisms;Funding Opportunities;Future;Goals;Grant;Health;High School Student;Individual;innovation;Innovative Therapy;interdisciplinary approach;Learning;lectures;Medicine;meetings;member;Mentors;Monitor;multidisciplinary;Newsletter;next generation;operation;Outcome;Philadelphia;programs;Research;Research Personnel;Research Project Grants;Resources;Services;Skin;skin disorder;Structure;success;summer internship;Surveys;symposium;tool;Training;Translating;Translational Research;Twitter;Underrepresented Minority;United States National Institutes of Health;Universities;web site;Woman

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Data Science;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Networking and Information Technology R&D (NITRD)

ORG_CITY: ABUJA

ORG_COUNTRY: NIGERIA

ORG_FIPS: NI

ORG_NAME: INSTITUTE OF HUMAN VIROLOGY

PHR: PROJECT NARRATIVE The goal of our Research Hub, which is called ‘INFORM Africa’ (Role of Data Streams In Informing Infection Dynamics in Africa), is to understand how we can use big data from the different sources on infections or disease in Africa, starting with Nigeria and South Africa, in order to explain better what we do daily as a community that puts us at risk of infection and the spread of the virus like with COVID-19 and HIV. If we know this, we may be able to prevent future epidemics and pandemics from happening or at least be better prepared for them so that the spread and deaths is reduced. Making all data that still protects the privacy of those that provided it easily available for all scientists to work together on the data will help us know what to do much faster.

PI_NAMEs: ABIMIKU, ALASH'LE G. (contact);DE OLIVEIRA, TULIO DE PAIVA NAZARETH ANDRADE;NARANBHAI, VIVEK ;STAFFORD, KRISTEN A.;XIONG, CHENFENG

PROGRAM_OFFICER_NAME: NEWSOME, BRAD

PROJECT_TERMS: 2019-nCoV;Academia;Accounting;Acquired Immunodeficiency Syndrome;Address;Adoption;Affect;Africa;African;Baltimore;Big Data;Big Data Methods;Cellular Phone;Cessation of life;Clinical;Clinical Research;Collaborations;college;Communicable Diseases;Communication;Communities;Computational Biology;Country;COVID-19;COVID-19 pandemic;COVID-19 pandemic effects;COVID-19 risk;Data;Data Analyses;Data Analytics;data hub;data integration;data management;data platform;Data Science;data sharing;Data Sources;data streams;data-driven model;Demographic Factors;Disease;DNA Sequencing Facility;epidemiologic data;Epidemiology;experience;Funding;future epidemic;future pandemic;Genetic;Genetic Variation;genomic variation;Genomics;Goals;Government;Government Agencies;Health system;HIV;Human;improved;Individual;Industry;industry partner;Infection;infection risk;Infectious Disease Epidemiology;information processing;insight;Intervention;Leadership;Link;Malaria;Maryland;Measures;Modeling;Molecular Virology;Movement;next generation sequencing;Nigeria;Nongovernmental Organizations;novel;open data;Outcome;pandemic disease;pandemic preparedness;Pathway interactions;Pattern;Pilot Projects;Play;Policy Maker;Population;post-pandemic;pre-pandemic;prevent;privacy protection;Private Sector;Privatization;Process;programs;Public Health;Public Sector;quantum;rapid growth;Readiness;Research;Research Personnel;Research Project Grants;Resources;response;Risk;Risk Factors;Role;SARS-CoV-2 infection;SARS-CoV-2 transmission;Scientist;Seroprevalences;Severe Acute Respiratory Syndrome;Source;South Africa;statistics;syndemic;Time;tool;transmission process;Transportation;Tuberculosis;United States;United States National Institutes of Health;Universities;uptake;Viral;viral genomics;virology;Virus;Visualization;Work;Zambia

PROJECT_TITLE: Role of Data Streams In Informing Infection Dynamics in Africa- INFORM Africa

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


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Digestive Diseases;Liver Disease

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE The liver is our largest metabolic organ. It filters the blood coming from the digestive tract before it reaches the rest of the body, and secretes bile, a digestive aid, back into the intestine. This controlled traffic of molecules in and out of the liver is mediated by epithelia. Epithelial cells act as sophisticated gatekeepers that form polarized membrane domains to restrict the transporters and gated channels responsible for the trafficking of molecules across the cell membrane to either the blood facing or the bile facing surfaces. This ensures that molecule transport is directional. Hepatocytes, the main epithelial cell type in the liver, organize these polarized domains with an architecture that is different from that of all other epithelia in the body. When this unique architecture is lost, as in fibrotic liver diseases, hepatocyte function is compromised. This proposal seeks to determine, on a molecular level, how hepatocytes acquire their distinct polarity.

PI_NAMEs: MUESCH, ANNE  (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: Apical;apical membrane;Architecture;Back;Bile Acids;bile canaliculus structure;bile duct;Bile fluid;Binding;Biogenesis;Blood;Blood capillaries;Blood Coagulation Factor;blood filter;Blood Vessels;Cell membrane;cell type;Cell-Cell Adhesion;Cells;constriction;Cyclic AMP-Dependent Protein Kinases;Cytokeratin;Data;Development;differentiation in vitro;Drug Metabolic Detoxication;Duct (organ) structure;Ductal Epithelial Cell;Engineering;Ensure;Epithelial Cells;Epithelium;Excretory function;Gastrointestinal tract structure;Gatekeeping;gene therapy;Glycogen;Hepatic Tissue;Hepatocyte;interstitial;Intestines;Knowledge;Length;Lipids;Liver;Liver diseases;Liver Fibrosis;Measures;Mediating;Membrane;Membrane Protein Traffic;Metabolic;Modeling;Modification;Molecular;Morphology;mutant;neglect;Organ;Phenotype;Phosphorylation;Phosphotransferases;Physiological;Population;programs;Proteins;Protocols documentation;Regulation;Resistance;Rest;rho;Role;Running;Scaffolding Protein;sensor;Side;Signal Transduction;Signaling Protein;Structure;Substrate Specificity;Surface;System;Testing;tissue culture;Tissue Stains;Toxicology;trafficking;Transplantation;Tubular formation;Update;venule;Xenobiotics

PROJECT_TITLE: Cell-cell adhesion-mediated signaling determines epithelial polarization in the liver

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Different regions of the skin vary in their characteristics such as thickness, pigmentation, innervation, and presence, size and density of hair follicles and sweat glands, that are reflected in differential responses to injury and to diseases such as androgenetic alopecia and psoriasis that predominate in specific skin regions. We propose to identify novel mechanisms that establish and maintain skin heterogeneity. Improved understanding of these mechanisms has potential to reveal new therapeutic targets for diseases that affect specific skin regions and have a major negative impact on quality of life; data obtained in this project will also inform strategies for generating specific skin types, including hair follicle- and sweat gland-bearing skin, for reparative skin grafting.

PI_NAMEs: MILLAR, SARAH E. (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Acne;Address;Adipocytes;Adult;Affect;Area;bisulfite sequencing;Candidate Disease Gene;candidate identification;cell type;Cells;Characteristics;Chromatin;Chromatin Structure;Cleavage Under Targets and Release Using Nuclease;comparative;Data;density;Dermal;Dermis;Development;differential expression;Disease;DNA Methylation;DNA Modification Process;Dorsal;Ear;Embryo;Embryonic Development;Enhancers;Epidermis;Epigenetic Process;Experimental Genetics;experimental study;Extensor;face skin;fetal;Fetal Development;Fibroblasts;Gene Deletion;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic analysis;Genetic Markers;Genetic study;Genetic Transcription;Growth;Hair;Hair follicle structure;hair regeneration;Heterogeneity;Hi-C;Histology;histone modification;Human;improved;in vivo;inhibitor;Leg;Life;Location;loss of function;Maintenance;Male Pattern Baldness;Molecular;mouse genetics;mouse model;Multiomic Data;multiple omics;Mus;Natural regeneration;Nature;nerve supply;new therapeutic target;novel;Palmoplantar Keratosis;Pathway interactions;Pattern;Phenotype;Pigmentation physiologic function;Population;postnatal;programs;Psoriasis;Quality of life;Rare Diseases;regional difference;Repression;response to injury;Sampling;Scalp structure;Signal Transduction;single cell analysis;single cell ATAC-seq;single-cell RNA sequencing;Site;Skin;skin disorder;Skin graft;skin organogenesis;Sweat Glands;System;Testing;Therapeutic;therapeutic target;Thick;Tissue-Specific Gene Expression;tongue papilla;tool;transcription factor;transcriptome sequencing;Variant;Vitiligo;wound healing;XCL1 gene

PROJECT_TITLE: Molecular mechanisms controlling skin heterogeneity

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


PI_NAMEs: SEYKORA, JOHN T. (contact)

PROJECT_TERMS: Animal Model;Animals;Archives;Autopsy;barrier to testing;Biological Assay;Biological Markers;Biology;Biopsy Specimen;Cells;Collaborations;Collection;Consultations;cost effective;Coupled;Cutaneous;Dermatology;detection assay;Development;Disease;Environment;Equipment;exome sequencing;experience;Experimental Models;Faculty;Formalin;Gene Expression;Genomic DNA;genomic RNA;Genomics;Genotype;Goals;Grant;Heterogeneity;Histologic;Histology;Human;Image;Immunofluorescence Immunologic;Immunohistochemistry;improved;In Situ Hybridization;in vivo;in vivo imaging;Infrastructure;innovation;insight;Institution;Investigation;Knowledge;Laboratories;laser capture microdissection;Lasers;Libraries;medical schools;member;Messenger RNA;Microscopy;Mission;Molecular;Molecular Target;Mus;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;next generation sequencing;novel;Paraffin;Pennsylvania;phenomics;Phenotype;Population;Production;Proteins;Protocols documentation;Reporting;Research;Research Personnel;Resources;RNA;Sampling;Scientific Advances and Accomplishments;service utilization;Services;single cell sequencing;single-cell RNA sequencing;Skin;skin barrier;skin biopsy;skin disorder;Specimen;success;Suspensions;Talents;Techniques;Technology;therapeutic target;tissue processing;Tissues;transcriptome;transcriptome sequencing;transcriptomics;two-photon;Universities;Veterinary Schools;Water

PROJECT_TITLE: Cutaneous Phenomics and Transcriptomics


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Lung;Orphan Drug;Rare Diseases

ORG_CITY: SEATTLE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE The proposed project is relevant to public health because it seeks to develop new therapeutics for COVID-19. Computational protein design will be used to generate novel proteins with antiviral and anti-inflammatory activity. The proposed project aligns with the NIH’s mission to reduce illness and disability.

PI_NAMEs: BAKER, DAVID  (contact);FULLER, DEBORAH H.;VEESLER, DAVID

PROGRAM_OFFICER_NAME: BASU, DIPANWITA

PROJECT_TERMS: 2019-nCoV;ACE2;Acute;Acute Respiratory Distress Syndrome;Aerosols;Affinity;Animals;antagonist;Anti-Inflammatory Agents;Anti-viral Agents;anti-viral efficacy;Antibodies;Avidity;Binding;Binding Proteins;Binding Sites;Capillary Leak Syndrome;Cells;clinical development;Computing Methodologies;cost;Coupled;COVID-19;COVID-19 mortality;COVID-19 pandemic;COVID-19 therapeutics;COVID-19 treatment;cytokine;Cytokine Receptors;cytokine release syndrome;design;Development;disability;Disease;Disease Outbreaks;Drug Compounding;Drug Kinetics;economic behavior;economic impact;efficacy evaluation;emerging pathogen;Endothelial Cells;Epithelial Cells;Escherichia coli;future pandemic;Genetic;Glycoproteins;Goals;High Performance Computing;Human;IL1R1 gene;immunogenicity;improved;in vivo;Infection;Inflammatory;Inflammatory Response;Influenza Hemagglutinin;inhibitor;innovation;Interleukin 2 Receptor;Interleukin-1 beta;Interleukin-2;Interleukin-6;Interleukins;Intravenous;K-18 conjugate;Lead;Life;manufacture;Mesocricetus auratus;Methods;mimetics;Mission;Modeling;Monoclonal Antibodies;Mus;Nebulizer;neglect;novel;novel coronavirus;novel therapeutics;Organ failure;Outcome;pandemic disease;parallel computer;pathogen;pathogen genome;Peptides;Pharmaceutical Preparations;Phase I Clinical Trials;preclinical development;prophylactic;Protein Engineering;Proteins;Protocols documentation;Public Health;public health priorities;rational design;receptor;receptor binding;Research;Rodent Model;Route;Safety;SARS-CoV-2 infection;SARS-CoV-2 spike protein;Sepsis;Signal Transduction;small molecule;Social Behavior;Specificity;subcutaneous;System;Testing;Therapeutic;therapeutic protein;therapeutically effective;United States National Institutes of Health;vaccine development;Viral;Viral Physiology;Virus;Virus Diseases;Work

PROJECT_TITLE: De Novo Design of Minibinder Antagonists for COVID-19 and Future Pandemics


NIH_SPENDING_CATS: Biotechnology;Clinical Research

PI_NAMEs: PAYNE, AIMEE S (contact)

PROJECT_TERMS: 3-Dimensional;Acceleration;Age;Applications Grants;B-Lymphocytes;biobank;Biological;Biological Assay;Biology;Blood specimen;Body System;Cell Line;Cell Physiology;Cells;Chemicals;Clinical;Clinical Data;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communities;Computerized Medical Record;Consultations;Data;Dermatology;Disease;disease model;Drug Delivery Systems;efficacy evaluation;Evaluation;exome;experience;experimental study;FDA approved;Fibroblasts;Fostering;Freezing;functional adaptation;Future;Gene Modified;Genetic;Genetic Engineering;Genetic Screening;genome resource;Genotype;Goals;Grant;hands-on learning;high throughput screening;Human;human disease;Immunodeficient Mouse;in vitro Model;in vivo;in vivo Model;Inflammatory;Informed Consent;Infrastructure;innovation;Institution;Institutional Review Boards;interest;Investigation;keratinocyte;Link;Manuscripts;Medical;Medicine;melanocyte;Modeling;Molecular Abnormality;Neoplastic skin;novel;novel therapeutics;Participant;Pathway interactions;Patients;pharmacologic;Phenotype;Publications;Research;Research Infrastructure;Research Personnel;Research Support;Resources;Robotics;Sampling;Services;sex;Site;Skin;skin disorder;Skin Physiology;Skin Tissue;skin xenograft;small hairpin RNA;Small Interfering RNA;small molecule;small molecule libraries;stem;targeted treatment;Technology;Tissue Engineering;Tissues;Training Technics;transcriptomics;Translational Research

PROJECT_TITLE: Skin Translational Research


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

ORG_NAME: TUFTS MEDICAL CENTER

PHR: Acute myocardial infarction (AMI) remains a major cause of global morbidity and mortality. Current therapy for AMI focuses on rapidly restoring blood flow through an occluded coronary artery. However, reperfusion itself can cause myocardial damage, known as reperfusion injury. Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has grown exponentially and is the subject of several clinical trials in AMI. We have now identified a novel paradigm whereby VA-ECMO worsens heart damage by depleting critical regulators of mitochondrial function and further shown that targeting these mechanisms may reduce heart damage in AMI. By employing highly translational models and clinically relevant interventional approaches, these studies introduce new mechanisms involving VA-ECMO and myocardial reperfusion injury, provide penetrating insight into cardioprotection and generate proof of concept data for the development of new therapeutic approaches to limit LV injury in AMI.

PI_NAMEs: KAPUR, NAVIN KUMAR (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Acute;Acute myocardial infarction;Address;Animal Model;Blood;Blood flow;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;Cardiolipins;Cardiology;cardioprotection;Cardiovascular system;Cicatrix;Clinical Trials;clinically relevant;Coronary;coronary artery occlusion;Data;Development;Devices;Drug Combinations;Drug Delivery Systems;Enzymes;Extracorporeal Membrane Oxygenation;Heart Arrest;heart damage;heart dimension/size;Heart failure;Heart Transplantation;hemodynamics;Hospital Mortality;Hospitalization;Impairment;implantation;improved;improved outcome;Infarction;Injury;insight;Intervention;Knowledge;Left;Left Ventricular Function;Left ventricular structure;mechanical circulatory support;Mechanics;Mediating;Medicine;Membrane;Metabolism;Mitochondria;Modeling;Molecular;Molecular Biology;Morbidity - disease rate;mortality;Myocardial;myocardial damage;myocardial infarct sizing;myocardial injury;Myocardial Reperfusion;Myocardial Reperfusion Injury;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Outcome;Oxidative Stress;Oxygen;Patients;Penetration;Physiology;porcine model;preservation;prevent;Pump;Recovery;Reperfusion Injury;Reperfusion Therapy;Reporting;Respiratory Failure;Risk;Role;Self-Help Devices;Specialist;Stress;System;Systemic blood pressure;Testing;therapeutic evaluation;Time;translational model;translational study;Treatment Efficacy;United States;Venous;Ventricular;ventricular assist device

PROJECT_TITLE: New Approaches to Mitigate Left Ventricular Injury with VA-ECMO in Acute Myocardial Infarction

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


NIH_SPENDING_CATS: Cancer;Natural Products;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Narrative The identification of new regulators and/or signaling pathways triggered by antitubulin drugs will shed light on the mechanisms underlying chemoresistance. Our study identifies PKR as a critical regulator of paclitaxel chemosensitivity. Targeting the PKR-Bcl2 axis is expected to have enhanced efficacy in the treatment of paclitaxel-resistant and/or recurrent ovarian cancer patients.

PI_NAMEs: DONG, JIXIN  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Affect;Agonist;Animal Model;anti-tumor agent;Apoptotic;BCL2 gene;Biochemical;Biological;Biological Markers;Breast Cancer Cell;cancer cell;Cancer Cell Growth;Cancer Patient;cancer therapy;cancer type;Cell Death;Cell Death Induction;Cells;Cellular Metabolic Process;Cellular Stress;Chemoresistance;Clinic;Clinical;Clinical Trials;cytokine;cytotoxicity;Data;DNA Damage;Double-Stranded RNA;Drug resistance;drug sensitivity;Eukaryotic Initiation Factors;Family;FDA approved;Human;Immune response;Immunocompetent;improved;In Vitro;in vivo;inhibitor;Innate Immune Response;Interferons;Knowledge;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Messenger RNA;Metabolism;Microtubules;Mitosis;Mitotic;Molecular;Molecular Target;Multi-Drug Resistance;new therapeutic target;novel;Outcome;Paclitaxel;Pathway interactions;patient response;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;pre-clinical;Prognostic Marker;Prokaryotic Initiation Factor-2;protein expression;protein function;Protein Kinase;protein kinase R;protein profiling;Proteins;Recurrence;Regulation;Resistance;response;Role;Signal Pathway;Signal Transduction;Signaling Protein;Stress;Testing;Text;Therapeutic;therapeutic target;Transcriptional Regulation;Translating;Tubulin;tumor;tumorigenesis;Validation;Virus Diseases

PROJECT_TITLE: Targeting PKR-Bcl2 Signaling to Overcome Paclitaxel Resistance in Ovarian Cancer


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;Neurodegenerative;Neurosciences

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: Project Narrative Nearly 6 million U.S. adults are currently living with Alzheimer’s disease. Since 1994, the Adult Changes in Thought (ACT) study has collected observational, clinical, and laboratory data on more than 5,500 older adults and is following them over time for signs of dementia and Alzheimer’s disease. This conference grant will provide support for the annual ACT Symposium, which highlights innovative study results, promotes collaborations, and provides opportunities for junior researchers to receive feedback on their work in order to accelerate research on brain aging and Alzheimer’s disease.

PI_NAMEs: GATTO, NICOLE M. (contact)

PROGRAM_OFFICER_NAME: GHALEH, MARYAM X

PROJECT_TERMS: Acceleration;Adult;Aging;aging brain;Alzheimer's Disease;Alzheimer's Disease patient registry;Alzheimer's disease related dementia;brain tissue;British;Clinical;Collaborations;Communities;Consultations;Creativeness;Data;data sharing;Dementia;Discipline;Disease;DNA;Early Diagnosis;Equipment;Evaluation;Feedback;Funding;Future;Grant;human old age (65+);Image;Infrastructure;innovation;Institution;Internal Medicine;International;Journals;Laboratories;Learning;Medical;Medicine;Methods;Mind;Minority Groups;molecular phenotype;National Institute on Aging;Neurobiology;Neurology;New England;older adult;Paper;Persons;Prevention;Principal Investigator;Publishing;Recommendation;Research;Research Personnel;research study;resilience;Resources;Scientist;symposium;Time;Traumatic Brain Injury;Travel;trend;Underrepresented Minority;Universities;Washington;Woman;Work

PROJECT_TITLE: Annual Adult Changes in Thought (ACT) symposium on aging, dementia, and Alzheimer's disease


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Digestive Diseases;Genetics;Human Genome;Liver Disease;Microbiome

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative The human microbiota produce a rich diversity of small molecules that fundamentally shape human physiology and have been linked to diseases including metabolic disease, neurodegenerative disorders, and cancer. This project will define a causal link between a class of prominent microbiome-derived molecules and the unfolded protein response, a stress response pathway that is important for protein homeostasis. Understanding how these small molecules influence health and disease may enable the development of novel biomarkers and microbiome- derived therapeutics to improve human health.

PI_NAMEs: MAIER, NOLAN KENJI KWAISUN (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Academic support;Acids;Affect;Animal Disease Models;Animal Model;Autoimmune Diseases;Bacteria;Bile Acids;biological adaptation to stress;Biological Assay;Biological Process;Biology;biomarker development;biomarker identification;Biomedical Research;Biosensor;career;Cells;Cellular biology;Chemicals;Circulation;Complex;Correlative Study;Data;design;Development;Diabetes Mellitus;Disease;Disease susceptibility;Endoplasmic Reticulum;endoplasmic reticulum stress;Environment;experimental study;Exposure to;feeding;Foundations;Genetic;Genetic Models;genome-wide;Genomics;Goals;Growth;gut microbes;gut microbiome;Health;Hepatocyte;high throughput screening;Homeostasis;host microbiome;Human;Human Biology;Human Cell Line;human disease;Human Microbiome;human microbiota;improved;Individual;Injury;insight;Lead;Link;Lithocholic Acid;Liver;Liver diseases;liver injury;Malignant neoplasm of liver;Malignant Neoplasms;Measures;Mediating;medical schools;Mentors;Metabolic Diseases;microbiome;microbiome composition;Microscopy;Molecular;Monitor;multidisciplinary;Mus;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;novel marker;Observational Study;Pathway interactions;physiologic model;Physiological;Physiology;programs;Proteins;Proteomics;proteostasis;Published Comment;receptor;Regulation;Research;Resistance;response;Role;Secondary to;Severities;Shapes;Signal Pathway;Signal Transduction;skills;small molecule;stressor;Technical Expertise;Therapeutic;Therapeutic Intervention;therapeutically effective;Training;Variant;Work

PROJECT_TITLE: Linking a prominent gut microbiome-derived metabolite to host proteostasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-Q(20)L]


NIH_SPENDING_CATS: Bioengineering;Data Science;Machine Learning and Artificial Intelligence

PI_NAMEs: MARGOLIS, DAVID  (contact)

PROJECT_TERMS: abstracting;Address;Applications Grants;Area;Artificial Intelligence;Basic Science;biobank;Bioinformatics;bioinformatics resource;bioinformatics tool;Biology;Biomedical Computing;biomedical informatics;Biometry;clinical epidemiology;clinical investigation;Clinical Trials Design;Computer software;Computerized Medical Record;Custom;Cutaneous;Data;data resource;Data Science;Data Set;Data Store;Databases;Dermatology;design;Disease;Epidemiology;Evaluation;experience;Extramural Activities;Faculty;Generations;Genetic;Genomics;Goals;Health system;high standard;Human;imaging approach;improved;Informatics;innovation;interest;Knowledge;Machine Learning;Measurement;Medical;Medical Informatics;Medical Records;Metagenomics;Methodology;Methods;microscopic imaging;Nature;online tutorial;Outcome;Pattern;Pennsylvania;Phenotype;population stratification;Proteomics;Reproducibility;Research;Research Design;Research Personnel;Research Project Grants;Resources;Science;Services;sex as a biological variable;single cell sequencing;Skin;skin disorder;Source;Subjects Selections;success;Texture;Translational Research;Translational trial;Translations;Universities;Variant;Work

PROJECT_TITLE: Data Sciences and Informatics


ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Multiple Myeloma (MM) is an incurable cancer characterized by the development of devastating lytic bone disease and accompanied by compromised immunosurveillance. We found that matrix metallopeptidase-13 (MMP-13) secreted by MM cells induces bone resorption resulting in lytic bone lesions, and discovered that MMP-13 binds to the novel immune checkpoint protein programmed death-1 homologue (PD-1H), which is expressed on osteoclasts, antigen presenting cells and T cells. This grant for the first time investigates the role of MMP-13/PD-1H interaction and their functions in linking bone disease and immunosuppression in MM, hence will form the basis for novel treatment strategies and help better understand the role of MM bone disease in the suppressed myeloma immune environment.

PI_NAMEs: FU, JING ;LENTZSCH, SUZANNE  (contact);MAPARA, MARKUS Y

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Address;Adoptive Transfer;Antigen-Presenting Cells;antigen-specific T cells;Binding;bone;Bone Diseases;Bone Resorption;Bone Resorption Stimulation;Cell Lineage;Cells;checkpoint receptors;collagenase 3;Cytoskeletal Modeling;Development;Disease;Disease Progression;Disease remission;Dose;Environment;Goals;Grant;Hand;healing;Hematopoietic;Homologous Gene;Human;Immune;immune cell infiltrate;Immune Cell Suppression;immune checkpoint;Immune checkpoint inhibitor;Immune response;Immunologic Surveillance;Immunosuppression;In Vitro;in vivo;in vivo Model;Integral Membrane Protein;knock-down;Knock-out;Lesion;Link;Lytic;Malignant Neoplasms;Mediating;Metalloproteases;Mixed Lymphocyte Culture Test;Modeling;mouse model;Multiple Myeloma;Mus;novel;osteoclast activating factor;Osteoclasts;Pathologic;Pathway interactions;Patients;Phenotype;Play;Population;profiles in patients;programmed cell death protein 1;Proteins;receptor;Receptor Signaling;Regulation;Research;Role;Signal Pathway;Signal Transduction;skeletal;Structure;T-Lymphocyte;Testing;Time;treatment strategy;Work

PROJECT_TITLE: Binding of MMP13 to Immune Checkpoint Receptor PD-1H links Bone Disease with Immune Suppression in Multiple Myeloma

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Genetics;Human Genome;Substance Misuse

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: RELEVANCE TO PUBLIC HEALTH Evidence from human genetic analyses and from animal models suggests that susceptibility to addiction has a moderate to high heritable component. This course will offer training in how to leverage genetic and genomic resources from multiple species to understand these components and their role in human addiction.

PI_NAMEs: CHESLER, ELISSA J (contact)

PROGRAM_OFFICER_NAME: WU, DA-YU

PROJECT_TERMS: Acceleration;Active Learning;addiction;Animal Model;Applied Genetics;Appointment;Atmosphere;Awareness;Behavior;behavioral phenotyping;Bioinformatics;Biological;Biology;Brain Diseases;career;career development;Chronic;Communities;Computer software;Data Analyses;data resource;Data Set;design;Development;Drug Addiction;Educational workshop;efficacious treatment;Enrollment;Epigenetic Process;Faculty;faculty-student interactions;Food;Fostering;Funding Opportunities;Genetic;genetic analysis;genetic approach;Genetic Models;genetic resource;Genetic study;genome resource;Genomic approach;Genomics;Hand;Heritability;Human;Human Genetics;human model;Institution;Instruction;Laboratories;Learning;lectures;Literature;Maine;member;Methodology;Methods;model organism;Modernization;mouse model;Mus;new technology;Participant;Phenotype;Predisposition;Public Health;Reproducibility;Research;Research Personnel;Resources;Role;Scientist;skills;societal costs;Structure;Students;success;symposium;The Jackson Laboratory;Therapeutic;Time;tool;Training;Translational Research;Underrepresented Minority;Woman;Work

PROJECT_TITLE: Short Course on the Genetics of Addiction