Research
Many components of our immune system protect us from microbial infection; among them is the interferon system, the primary line of defense against viruses. Virus infection is often self limiting because it triggers the synthesis of many antiviral proteins, including interferon, which ultimately inhibit virus replication. We want to understand how cells sense virus infection, how this sensing leads to induced synthesis of the antiviral proteins and how specific members of this family of protein protect us from specific viruses.
Biography
Education & Professional Highlights
Education & FellowshipsBachelor of Science - University of Calcutta
West Bengal, India
1965
Master of Science - University of Calcutta
West Bengal, India
1967
Doctor of Philosophy - McMaster University
Hamilton Ontario, Canada
1974
Fellowship - Yale University
New Haven, CT USA
- Chairman, Department of Molecular Genetics
- Thomas Lord Chair of Molecular Biology
Research
My research interest is in understanding how mammals respond to virus infection, both at the cellular level and at the organism level. The interferon (IFN) system plays a major role in shaping the innate immune antiviral response and a focus of our research is on the analysis of the mechanism of IFN induction by virus infection; we are deciphering the signaling mechanism of Toll like receptors, the RIG-I-like helicase receptors and the cytoplasmic DNA-sensing cGAS/STING receptor, which are activated by viruses. We uncovered an unexpected link between innate immunity and growth factor receptors by our observation that the EGF receptor is essential for many of these signaling pathways. Another focus of our research is on understanding the mode of antiviral actions of a set of IFN-induced proteins, called IFITs. Recently we have generated several mouse strains in which one or more IFIT genes have been knocked-out. Challenging these genetically modified mice with different viruses has revealed interesting and unexpected facets of IFN-action. It appears that a specific IFN-induced protein can inhibit the replication of only a limited set of viruses in a specific cell type. Thus, Ifit2, but not Ifit1, can inhibit the replication of neurotropic RNA viruses in neurons, but not in other cell types. Another study has revealed that IRF-3, a transcription factor responsible for inducing IFN synthesis, has an unrelated second function. Upon activation by virus infection through the RIG-I pathway it triggers apoptosis by transporting the pro-apoptotic protein, Bax, to mitochondria. The apoptotic action of IRF-3, in addition to its transcriptional action, protects mice from viral pathogenesis.
Our Team
Selected Publications
View publications for Ganes Sen, PhD
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Fensterl V, et al. Interferon-induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis. 2012. PLoS Pathog. 8: e1002712. PMCID: PMC3355090.
Yamashita M, et al. Epidermal growth factor receptor is essential for toll-like receptor 3 signaling. 2012. Sci. Signal. 5, ra50. PMCID: PMC3431157.
Chattopadhyay, S., T. Kuzmanovic, Y. Zhang, J.L. Wetzel and G.C. Sen. 2016. Ubiquitination of the transcription factor IRF-3 activates RIPA, the apoptotic pathway that protects mice from viral pathogenesis. Immunity. 44(5):1151-61. PMCID: PMC4991351.
Wang, C., X. Wang, M. Veleeparambil, P.M. Kessler, B. Willard, S. Chattopadhyay, and G.C. Sen. 2020. EGFR-mediated tyrosine phosphorylation of STING determines its trafficking route and cellular innate immunity functions. EMBO J. 39(22):e104106. PMCID: PMC7667877
Raja, R., G.C. Sen. 2021. The antiviral action of the RIG-I induced pathway of apoptosis (RIPA) is enhanced by its ability to degrade Otulin, which deubinquitinates IRF3. Cell Death Differ. doi: 10.1038/s41418-021-00870-4. PMCID: PMC8901756
Sharma, N., C. Wang, P. Kessler, G.C. Sen. 2021. Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. PLos Pathog. 17(9):e1009950. doi: 10.1371/journal.ppat.1009950. PMCID: PMC8483329
