- 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.
Basler CF. Nipah and hendra virus interactions with the innate immune system. Current topics in microbiology and immunology 2012; 359.
Ramanan P, Edwards MR, Shabman RS, Leung DW, Endlich-Frazier AC, Borek DM, Otwinowski Z, Liu G, Huh J, Basler CF, Amarasinghe GK. Structural basis for Marburg virus VP35-mediated immune evasion mechanisms. Proceedings of the National Academy of Sciences of the United States of America 2012 Dec; 109(50).
Luthra P, Ramanan P, Mire CE, Weisend C, Tsuda Y, Yen B, Liu G, Leung DW, Geisbert TW, Ebihara H, Amarasinghe GK, Basler CF. Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. Cell host & microbe 2013 Jul; 14(1).
Martinez O, Ndungo E, Tantral L, Miller EH, Leung LW, Chandran K, Basler CF. A mutation in the Ebola virus envelope glycoprotein restricts viral entry in a host species- and cell-type-specific manner. Journal of virology 2013 Mar; 87(6).
Martinez O, Johnson JC, Honko A, Yen B, Shabman RS, Hensley LE, Olinger GG, Basler CF. Ebola virus exploits a monocyte differentiation program to promote its entry. Journal of virology 2013 Apr; 87(7).
Shabman RS, Hoenen T, Groseth A, Jabado O, Binning JM, Amarasinghe GK, Feldmann H, Basler CF. An upstream open reading frame modulates ebola virus polymerase translation and virus replication. PLoS pathogens 2013 Jan; 9(1).
Tsibane T, Ekiert DC, Krause JC, Martinez O, Crowe JE, Wilson IA, Basler CF. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses. PLoS pathogens 2012; 8(12).
Miller MS, Gardner TJ, Krammer F, Aguado LC, Tortorella D, Basler CF, Palese P. Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis. Science translational medicine 2013 Aug; 5(198).
Yu x, Tsibane t, McGraw pa, House fs, Keefer cj, Hicar md, Tumpey tm, Pappas c, Perrone la, Martinez o, Stevens j, Wilson ia, Aguilar pv, Altschuler el, Basler cf, Crowe je. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008 Sep 25; 455(7212).
Brown CS, Lee MS, Leung DW, Wang T, Xu W, Luthra P, Anantpadma M, Shabman RS, Melito LM, Macmillan KS, Borek DM, Otwinowski Z, Ramanan P, Stubbs AJ, Peterson DS, Binning JM, Tonelli M, Olson MA, Davey R, Ready JM, Basler CF, Amarasinghe GK. In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity. Journal of molecular biology 2014 Feb;.
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.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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