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.
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.
| Zhao, Nan; Sebastiano, Vittorio; Moshkina, Natasha et al. (2018) Influenza virus infection causes global RNAPII termination defects. Nat Struct Mol Biol 25:885-893 |
| White, Kris M; Abreu Jr, Pablo; Wang, Hui et al. (2018) Broad Spectrum Inhibitor of Influenza A and B Viruses Targeting the Viral Nucleoprotein. ACS Infect Dis 4:146-157 |
| Dornfeld, Dominik; Dudek, Alexandra H; Vausselin, Thibaut et al. (2018) Author Correction: SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses. Sci Rep 8:7782 |
| Zhang, Liang; Wang, Juan; Muñoz-Moreno, Raquel et al. (2018) Influenza Virus NS1 Protein RNA-Interactome Reveals Intron Targeting. J Virol : |
| Hancock, Aidan S; Stairiker, Christopher J; Boesteanu, Alina C et al. (2018) Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells during Influenza A Virus Infection Reveals In Vivo Wnt Pathway Downregulation. J Virol 92: |
| Dornfeld, Dominik; Dudek, Alexandra H; Vausselin, Thibaut et al. (2018) SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses. Sci Rep 8:2092 |
| Heinz, Sven; Texari, Lorane; Hayes, Michael G B et al. (2018) Transcription Elongation Can Affect Genome 3D Structure. Cell 174:1522-1536.e22 |
| Pohl, Marie O; von Recum-Knepper, Jessica; Rodriguez-Frandsen, Ariel et al. (2017) Identification of Polo-like kinases as potential novel drug targets for influenza A virus. Sci Rep 7:8629 |
| Martín-Vicente, María; Medrano, Luz M; Resino, Salvador et al. (2017) TRIM25 in the Regulation of the Antiviral Innate Immunity. Front Immunol 8:1187 |
| García-Sastre, Adolfo (2017) Ten Strategies of Interferon Evasion by Viruses. Cell Host Microbe 22:176-184 |
Showing the most recent 10 out of 39 publications
