Christopher F Basler, PhD Email Christopher Basler

Specific Clinical/Research Interests: Molecular determinants of virulence of emerging viruses, including Ebola virus and Marburg virus

Administrator: Christine Schwall

Current Students: PhD: Megan Edwards, Benjamin Yen

Postdoctoral Fellows: Alicia Feagins, Priya Luthra, Tshidi Tsibane, Heidi Karttunen, Toni Schwarz

Research Personnel: Matthew Kreitman

Summary of Research Studies:

The filoviruses, Ebola viruses and Marburg viruses, are emerging, zoonotic negative-strand RNA viruses. As the 2014 West Africa Ebola virus outbreak makes clear, the unique virulence and high transmissibility of these viruses makes them unique public health threats.  The Basler lab studies filovirus immune evasion and replication mechanisms with the goals of (1) developing therapeutics that target these mechanisms, (2) determining how these mechanisms contribute to viral pathogenesis and (3) understanding how these mechanisms function in different host species.

Basler Lab Website
http://labs.icahn.mssm.edu/basler-lab/

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 , Tsibane , McGraw , House , Keefer , Hicar , Tumpey , Pappas , Perrone , Martinez , Stevens , Wilson , Aguilar , Altschuler , Basler , Crowe . 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;.

Basler CF. Nipah and hendra virus interactions with the innate immune system. Current topics in microbiology and immunology 2012; 359.

Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M, Schudt G, Dolnik O, Basler CF, Becker S, Feldmann H. Inclusion bodies are a site of ebolavirus replication. Journal of virology 2012 Nov; 86(21).

Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, Basler CF. The Marburg virus VP24 protein interacts with Keap1 to activate the cytoprotective antioxidant response pathway. Cell reports 2014 Mar; 6(6).

Basler CF, Woo PC. Editorial overview: emerging viruses. Current opinion in virology 2014 Apr; 5.

Binning JM, Wang T, Luthra P, Shabman RS, Borek DM, Liu G, Xu W, Leung DW, Basler CF, Amarasinghe GK. Development of RNA aptamers targeting Ebola virus VP35. Biochemistry 2013 Nov; 52(47).

Johnson JC, Martinez O, Honko AN, Hensley LE, Olinger GG, Basler CF. Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells. Antiviral research 2014 Jul; 107.

Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell host & microbe 2014 Aug; 16(2).

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).

Weisfuse IB, Tsibane T, Konty KJ, Egger JR, Waddell EN, Rahmat S, Harris E, Olson DR, Basler CF. Seroprevalence of pandemic influenza viruses, New York, New York, USA, 2004. Emerging infectious diseases 2012 Nov; 18(11).

Miller MS, Tsibane T, Krammer F, Hai R, Rahmat S, Basler CF, Palese P. 1976 and 2009 H1N1 influenza virus vaccines boost anti-hemagglutinin stalk antibodies in humans. The Journal of infectious diseases 2013 Jan; 207(1).

Yen B, Mulder LC, Martinez O, Basler CF. Molecular Basis for Ebola Virus VP35 Suppression of Human Dendritic Cell Maturation. Journal of virology 2014 Aug;.

Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Albrecht R, Blum DL, Ramos I, Fernandez-Sesma A, Edwards KM, García-Sastre A, Basler CF, Crowe JE. Human monoclonal antibodies to pandemic 1957 H2N2 and pandemic 1968 H3N2 influenza viruses. Journal of virology 2012 Jun; 86(11).

Martinez O, Leung LW, Basler CF. The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge. Antiviral research 2012 Mar; 93(3).