Christopher F. Basler
- PROFESSOR Microbiology
Ph.D., Albert Einstein College of Medicine
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ResearchSpecific Clinical/Research Interests: Molecular determinants of virulence of emerging viruses, including Ebola virus, Nipah virus and pandemic influenza virus
Current Students: PhD: Michael Ciancanelli, Charalampos Valmas, Kathleen Prins
Postdoctoral Fellows: Reed Shabman, Lawrence Leung, Osvaldo Martinez, Tshide Tsibane, St. Patrick Reid
Research Personnel: Alejandra Galvez
Summary of Research Studies:
My interests lie in defining molecular determinants of virulence of emerging viruses. Two main avenues of research are being pursued.
1. The interferon (IFN) alpha/beta response is a major component of innate defense against virus infection. As a consequence, viruses have evolved ways to counteract this response. We are interested in defining the mechanisms by which emerging viruses block the IFN system. We have identified IFN-antagonists from a variety of viruses including Ebola virus, Nipah virus and Eastern equine encephalitis virus. The mechanisms by which these proteins function are diverse and a major focus of the lab. Two Ebola virus encoded IFN-antagonists identified by our group serve as useful examples. We have demonstrated that the Ebola virus protein VP35 functions to inhibit IFN-alpha/beta production by blocking the signaling pathways that activate interferon regulatory factor 3, a transcription factor which plays a central role in the induction of the IFN response. A second Ebola virus protein, VP24, acts by a separate mechanism and inhibits the JAK-STAT signaling pathways normally activated upon addition of IFN to cells. In this case, VP24 prevents the nuclear accumulation of activated STAT1 through an interaction between VP24 and the STAT1 nuclear localization signal receptor karyopherin alpha 1. We hypothesize that the combined functions of these two proteins contribute to the high virulence of Ebola virus. Studies on these and other IFN-antagonists seek to define how each protein contributes to viral pathogenesis, to determine whether these anti-IFN functions also affect host adaptive immune responses to infection and to determine whether these proteins are viable targets for antiviral therapeutics.
2. We are also seeking to elucidate the molecular determinants of virulence of the 1918 pandemic influenza virus. The 1918 influenza virus is estimated to have caused more than 20 million deaths worldwide, but the reasons for this high mortality are poorly understood. We are involved in a collaborative "paleovirolgy" project that reconstructed the previously extinct 1918 virus with the expectation that such studies will reveal important new insights into influenza virus pathogenesis. Recent studies are focused on characterizing the 1918 influenza virus-specific immune responses that persist in survivors almost 90 years after the pandemic.
Palese P, Basler C, Garcia-Sastre A. The makings of a killer. Nat Med 2002; 8(9): 927-928.
Salvatore M, Basler CF, Parisien CM, Horvath S, Bourmakina H, Zheng H, Muster P, Palese P, Garcia-Sastre A. Effects of Influenza A Virus NS1 Protein on Protein Expression: the NS1 Protein Enhances Translation and Is Not Required for Shutoff of Host Protein Synthesis. J Virol 2002; 76(3): 1206-1212.
Wang X, Basler CF, Williams BR G, Silverman RH, Palese P, Garcia-Sastre A. Functional Replacement of the carboxy-terminal two-thirds of the influenza A virus NS1 protein with short heterologous dimerization domains. J Virol 2002; 76: 12951-12962.
Basler C, Palese P. Influenza Viruses. In: Creighton T, editor. Encyclopedia of Molecular Medicine. New York, John Wiley and Sons; 2002.
Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3. J Virol 2003; 77: 7945-7956.
Shaw ML, Cardenas WB, Zamarin D, Palese P, Basler CF. Nuclear localization of the Nipah virus W protein allows for inhibition of both virus- and toll-like receptor 3-triggered signaling pathways. J Virol 2005 May; 79(10): 6078-88.
Tumpey TM, Basler CF, Aquilar PV, Zeng H, Solorzamo A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005 Oct; 310(5745): 77-80.
Cardenas WB, Loo YM, Gale M Jr, Hartman AL, Kimberlin CR, Martinez-Sobrido L, Saphire EO, Basler CF. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol 2006 Jun; 80(11): 5168-78.
Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF. Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 2006 Jun; 80(11): 5156-67.
Basler CF, Ciancanelli MJ. Mutation of YMYL in the Nipah virus matrix protein abrogates budding and alters subcellular localization. J Virol 2006 Dec; 80(24): 12070-8.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Basler during 2012 and/or 2013. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Other Activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership.
- Merck & Co., Inc.
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