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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 vesicular stomatitis virus 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, 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.
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Papers共 306 篇Author StatisticsCo-AuthorSimilar Experts
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bioRxiv the preprint server for biology (2024)
LABORATORY INVESTIGATIONno. 9 (2023): 100190-100190
JOURNAL OF VIROLOGY (2023)
Journal of virologyno. 12 (2023): e0130423-e0130423
JOURNAL OF VIROLOGY (2023)
Proceedings of the National Academy of Sciences of the United States of Americano. 16 (2023)
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Researchno. 5 (2023): 189-193
Journal of virologyno. 8 (2023): e0074923-e0074923
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