The overall goal ofthe Modeling Core is to drive the integration of global -OMICS data to identify virus-host networks that control the innate immune response and influence pathogenicity. This will be accomplished through two main objectives a) to design and provide tools to analyze -OMICS data and b) to serve as an engine for integrating -OMICS data into network models of pathogenicity that are subject to further refinement in an iterative fashion. This Core will employ existing bioinformatics and systems biology approaches as well as develop novel approaches to identify cellular proteins and networks which influence influenza virus replication and contribute to virulence in vivo. The modeling core will be the engine for translating -OMICS data into biological insight and has a central role in the successful completion of this program. Co-directors Bandyopadhyay and Krogan have a strong history of innovation and collaboration with each other and others on this proposal and are well suited to direct the modeling efforts. Predictions that are based upon our models will be tested in primary cell culture and in animal model systems by employing targeted -OMICS technologies as well as in vivo experimentation and analysis of clinical phenotypes.

Public Health Relevance

Innate signaling pathways can regulate influenza replication, but there remain critical gaps in our knowledge about how these responses impact viral disease pathogenesis. The modeling core aims to define the cellular networks involved in pathogenic infection and use this information to identify inhibitors (small molecules, blocking antibodies) which can block pathogenesis and human mutations which predispose to infection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-EC-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
New York
United States
Zip Code
Schotsaert, Michael; García-Sastre, Adolfo (2016) A High-Resolution Look at Influenza Virus Antigenic Drift. J Infect Dis 214:982
Hultquist, Judd F; Schumann, Kathrin; Woo, Jonathan M et al. (2016) A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep 17:1438-1452
Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain et al. (2016) Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity 44:46-58
Tripathi, Shashank; Garcia-Sastre, Adolfo (2016) Antiviral innate immunity through the lens of systems biology. Virus Res 218:10-7
Muñoz-Moreno, Raquel; Cuesta-Geijo, Miguel Ángel; Martínez-Romero, Carles et al. (2016) Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection. PLoS One 11:e0154366
Rialdi, Alex; Campisi, Laura; Zhao, Nan et al. (2016) Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science 352:aad7993
Shah, Priya S; Wojcechowskyj, Jason A; Eckhardt, Manon et al. (2015) Comparative mapping of host-pathogen protein-protein interactions. Curr Opin Microbiol 27:62-8
Ayllon, Juan; García-Sastre, Adolfo (2015) The NS1 protein: a multitasking virulence factor. Curr Top Microbiol Immunol 386:73-107
Cooper, Daphne A; Banerjee, Shuvojit; Chakrabarti, Arindam et al. (2015) RNase L targets distinct sites in influenza A virus RNAs. J Virol 89:2764-76
Miller, Matthew S; Rialdi, Alexander; Ho, Jessica Sook Yuin et al. (2015) Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis. Nat Immunol 16:485-94

Showing the most recent 10 out of 20 publications