Core B - Genomics Core

NIH Pandemic-Era Grants

Pandemic Era Grants

2019

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Principal Investigator: Steven M Wolinsky
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2019
Award: $1,680,980
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY 
The innate immune recognition of dengue virus infection triggers antiviral immune responses; however, there is 
little information about how the virus regulates these measures or how these responses affect dengue virus 
(DENV) disease pathogenesis and immunity. System biology approaches aimed at deciphering the complex 
interactions between DENV and host genes and pathways require accurate high-throughput measurements 
and comprehensive datasets and models. The purpose of this HIPC is to take advantage of recent advances in 
human immune profiling methods to characterize the early states of the human innate immune system 
following DENV infection and before and after vaccination against this infectious disease. The goal of the 
Genomics Core is to provide a central knowledge base and resource to define the human immune repertoire 
and develop predictors of disease and vaccine responses by using high throughput sequencing and 
bioinformatics that facilitate investigations of human immunity in well-characterized human cohorts. Other 
HIPC investigators will use this information to derive human immune profiles or signatures for disease in 
naturally acquired infection with known dengue immune status (Project 1), vaccine responsiveness and human 
challenge studies (Project 2), or DENV infection ex vivo with DENV strains of different virulence (Project 3). 
Network analysis of the human immune profiling data will identify pathways and genes for RNAi knockdown to 
determine how perturbations of the regulatory networks influence host responses during DENV infection. 
These studies are key to the overall goal of the HIPC to use high-throughput systems biology approaches to 
create molecular signatures that will define the human immune response profiles that correlate with the 
outcome of dengue virus infection or vaccination.

Terms: <Affect><Antiviral Agents><Antiviral Drugs><Antivirals><Basal Transcription Factor><Basal transcription factor genes><Binding><Bio-Informatics><Bioinformatics><Breakbone Fever Virus><CD94 Antigen><Cell Body><Cells><ChIP Sequencing><ChIP-seq><Class I Genes><Clinical><Communicable Diseases><Complex><DENV infection><Data><Data Set><Dataset><Dengue><Dengue Fever><Dengue Infection><Dengue Virus><Dengue virus infection><Disease><Disorder><Drug Therapy><Envelope Protein><Flavivirus><Gene Expression><General Transcription Factor Gene><General Transcription Factors><General Viruses><Genes><Genetic Markers><Genomics><Genotype><Goals><Group B Arbovirus><High Throughput Assay><High-Throughput Nucleotide Sequencing><High-Throughput Sequencing><Human><Human Genetics><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunity><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunology><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Information Resources><Innate Immune System><Investigation><Investigators><KLRD1 Protein><Killer Cell Lectin-Like Receptor Subfamily D, Member 1><Killer Cell Lectin-Like Receptor Subfamily D, Member 1 Isoforms 1, 2><Killer Cell Lectin-Like Receptor Subfamily D, Member 1 Protein><Kp43 antigen><MHC Class I><MHC Class I Genes><Massive Parallel Sequencing><Massively Parallel DNA Sequencing><Massively Parallel Sequencing><Measurement><Measures><Messenger RNA><Methods><Modeling><Modern Man><Molecular Fingerprinting><Molecular Interaction><Molecular Profiling><NK Cell Receptor><NK receptor><Natural Killer Cells Antigen CD94><Network Analysis><Non-Polyadenylated RNA><Outcome><Pathogenesis><Pathway Analysis><Pathway interactions><Pattern><Pharmacotherapy><Population><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Predisposition><Quelling><RNA><RNA Gene Products><RNA Interference><RNA Seq><RNA Silencing><RNA sequencing><RNAi><RNAseq><Receptor Gene><Research Personnel><Research Resources><Researchers><Resources><Ribonucleic Acid><Risk><Sequence-Specific Posttranscriptional Gene Silencing><Serotyping><Severity of illness><Signal Pathway><Spinal Column><Spine><Structure><Susceptibility><Systems Biology><Technology><Testing><Transcript><Transcription Factor Proto-Oncogene><Transcription factor genes><Vaccination><Vaccines><Variant><Variation><Vertebral column><Viral Diseases><Virulence><Virus><Virus Diseases><Yellow fever virus><anti-viral agents><anti-viral drugs><anti-viral immunity><anti-virals><antiviral immunity><backbone><base><biomarker identification><breakbone fever><cell type><chromatin immunoprecipitation-sequencing><cohort><dengue viral infection><disease severity><drug treatment><env Antigens><env Gene Products><env Polyproteins><env Protein><genetic biomarker><high throughput screening><histone modification><host response><immunological status><immunoresponse><information resource><knock-down><knockdown><knowledge base><knowledge resource><knowledge resources><knowledgebase><mRNA><marker identification><molecular profile><molecular signature><mosquito-borne><mosquitoborne><pathway><response><scRNA-seq><single cell RNA-seq><single-cell RNA sequencing><transcription factor><transcriptome sequencing><vaccine response><viral infection><virus infection><virus-induced disease>