Multiscale Analysis of Influenza Host-Pathogen Interactions: Fluomics
Icahn School of Medicine at Mount Sinai

The pathogenic outcome of a virus infection is complex and depends on the ability of the virus to replicate, the ability of the host to mount an immune response, and the degree to which the virus interferes with the host response. Our hypothesis is that these outcomes are initiated by molecular interactions that occur in the primary target cells at early times after infection. Using an integrated systems biology approach, the multidisciplinary Fluomics team aims to identify the key host genes and networks that are involved in the early stages of influenza virus infection and influence viral pathogenicity. This approach will identify novel host targets for therapeutic intervention during influenza virus infection.

The Fluomics project involves the examination of clinically relevant influenza A viruses that produce pathogenically diverse responses. Infections performed in primary human target cells ex vivo, as well as in vivo mouse infections, are analyzed using state-of-the-art “OMIC” technologies to provide a global picture of the host response. Specifically, data on changes to the transcriptome, epigenome, proteome (including post-translational modifications) and the metabolome are collected along with functional genomic (RNAi and cDNA) data. Through the integration of these datasets, predictive models are generated that identify key genes and networks likely to be involved in virus replication and host responses. The model is then refined through biological and pharmacological perturbations of nodes within the network, followed by validation studies in the mouse model. In addition, we will screen a well-characterized human cohort for polymorphisms in the key genes predicted to be involved in influenza pathogenesis. By examining responses of these variants to infection ex vivo, we aim to identify new host polymorphisms that impact on influenza disease.

Our underlying main hypothesis is: “Host genes and networks that influence virus replication and host responses at early stages of the infection process are responsible for regulating influenza disease outcome and represent targets for therapeutic intervention.”

Individual Lab Websites

Icahn School of Medicine at Mount Sinai: García-Sastre Laboratory
Icahn School of Medicine at Mount Sinai: Shaw Laboratory
Icahn School of Medicine at Mount Sinai: Marazzi Laboratory
Icahn School of Medicine at Mount Sinai: Albrecht Laboratory

Northwestern University: The Drucker Laboratory (Wolinsky and Kim Laboratories)

Oregon State University: Moulton Laboratory

The Salk Institute for Biological Studies: Benner Laboratory

Sanford-Burnham Medical Research Institute: Chanda Laboratory

University of California, San Diego: Dennis Laboratory

University of California, San Francisco: Krogan Laboratory
University of California, San Francisco: Bandyopadhyay Laboratory