The Evans Lab studies how hosts and viruses interact, with a focus on the hepatitis C virus (HCV). HCV is responsible for more than half of liver cancers in the Western Hemisphere. While therapies to treat HCV are improving, these drugs will not be available to all patients. Thus further study of this virus is warranted for both therapeutic and vaccine design. One aim of the Evans Lab is to understand how this virus enters host cells. Using a novel HCV permissive polarized cell system, we found that tight junction proteins that we identified as critical to HCV cell entry are used late in this process. We are currently exploring how virion translocation to tight junctions occurs and endocytic signals within tight junction proteins are responsible for virion internalization.
We also study how a liver specific microRNA, miR-122, influences HCV replication and tropism. By modulating miR-122 expression, we created a new cell system that exhibits authentic innate immune responses to HCV infection. We also showed the HCV genetics influences response to miR-122 inhibitors that are currently in clinical development.
Another aim of the Evans Lab is to determine how host differences impact the tight HCV species tropism. By recently showing that pigtail macaques support persistent HCV infection in vivo, we have established the only available immunocompent HCV animal model that will be essential for HCV pathogenesis and vaccine studies. We are further characterizing macaque HCV infections, including how the virus changes during infection and how the host immune system responds.
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Cell Adhesion, Cell Biology, Gap Junctions, Glycobiology, Hepatitis C Virus, Imaging, Infectious Disease, Intracellular Transport, Liver, Lysosomes/endosome, Membrane Proteins/Channels, Membranes, Protein Complexes, Protein Trafficking & Sorting, Retrovirus, Virulence Genes, Viruses and Virology
Multi-Disciplinary Training Area
PhD, Columbia University
Postdoctoral Fellow, The Rockefeller University
Ann Palmenberg Junior Investigator Award
American Society for Virology
Dr. Harold and Golden Lamport Research Award
Icahn School of Medicine at Mount Sinai
The Kavli Foundation and the US National Academy of Sciences
Pew Scholar in Biomedical Sciences
The Pew Charitable Trusts
Blavatnik Award for Young Scientists Postdoctoral Researcher Finalist
New York Academy of Sciences
Israelow B, Mullokandov G, Agudo J, Sourisseau M, Bashir A, Maldonado AY, Dar AC, Brown BD, Evans MJ. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nature communications 2014; 5.
Israelow B, Narbus CM, Sourisseau M, Evans MJ. HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection. Hepatology (Baltimore, Md.) 2014 Oct; 60(4).
Sourisseau M, Goldman O, He W, Gori JL, Kiem HP, Gouon-Evans V, Evans MJ. Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection. Gastroenterology 2013 Jul;.
Goldman O, Han S, Sourrisseau M, Dziedzic N, Hamou W, Corneo B, D'Souza S, Sato T, Kotton DN, Bissig KD, Kalir T, Jacobs A, Evans T, Evans MJ, Gouon-Evans V. KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development. Cell stem cell 2013 Jun; 12(6).
Sourisseau M, Michta ML, Zony C, Israelow B, Hopcraft SE, Narbus CM, Parra Martín A, Evans MJ. Temporal analysis of hepatitis C virus cell entry with occludin directed blocking antibodies. PLoS pathogens 2013 Mar; 9(3).
García-Sastre A, Evans MJ. miR-122 is more than a shield for the hepatitis C virus genome. Proceedings of the National Academy of Sciences of the United States of America 2013 Jan;.
Mullokandov G, Baccarini A, Ruzo A, Jayaprakash AD, Tung N, Israelow B, Evans MJ, Sachidanandam R, Brown BD. High-throughput assessment of microRNA activity and function using microRNA sensor and decoy libraries. Nature methods 2012 Aug; 9(8).
Giang E, Dorner M, Prentoe JC, Dreux M, Evans MJ, Bukh J, Rice CM, Ploss A, Burton DR, Law M. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America 2012 Apr;.
Ploss A, Evans MJ. Hepatitis C virus host cell entry [review]. Current opinion in virology 2012 Feb; 2(1).
Narbus CM, Israelow B, Sourisseau M, Michta ML, Hopcraft SE, Zeiner GM, Evans MJ. HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle. Journal of virology 2011 Nov; 85(22).
Sabo MC, Luca VC, Prentoe J, Hopcraft SE, Blight KJ, Yi M, Lemon SM, Ball JK, Bukh J, Evans MJ, Fremont DH, Diamond MS. Neutralizing monoclonal antibodies against hepatitis C virus E2 protein bind discontinuous epitopes and inhibit infection at a postattachment step. Journal of virology 2011 Jul; 85(14).
Michta ML, Hopcraft SE, Narbus CM, Kratovac Z, Israelow B, Sourisseau M, Evans MJ. Species-Specific Regions of Occludin Required by Hepatitis C Virus for Cell Entry. J Virol 2010 Nov; 84(22): 11696-11708.
Dentzer TG, Lorenz IC, Evans MJ, Rice CM. Determinants of hepatitis C virus nonstructural protein 2 protease domain required for production of infectious virus. . J Virol 2009 Oct; 83(24): 12702-12713.
Eng FJ, Walewski JL, Klepper AL, Fishman SL, Desai SM, McMullan LK, Evans MJ, Rice CM, Branch AD. Internal initiation stimulates production of p8 minicore, a member of a newly discovered family of hepatitis C virus core protein isoforms. J Virol 2009 Jan; 83(7): 3104-3114.
Witteveldt J, Evans MJ, Bitzegeio J, Koutsoudakis G, Owsianka AM, Angus AG, Keck ZY, Foung SK, Pietschmann T, Rice CM, Patel AH. CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. J Gen Virol 2009 Jan; 90(1): 48-58.
Lanford RE, Evans MJ, Lohmann V, Lindenbach BD, Gale M Jr, Rehermann B, Chang KM, Lemon SM. The accelerating pace of HCV research: a summary of the 15th International Symposium on Hepatitis C Virus And Related Viruses [review]. Gastroenterology 2009 Jan; 136(1): 9-16.
Marukian S, Jones CT, Andrus L, Evans MJ, Ritola KD, Charles ED, Rice CM, Dustin LB. Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells. Hepatology 2008 Dec; 48(6): 1843-1850.
Stamataki Z, Coates C, Evans MJ, Wininger M, Crawford K, Dong C, Fong Y, Chien D, Abrignani S, Balfe P, Rice CM, McKeating JA, Houghton M. Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. Vaccine 2007; 25(45): 7773-7784.
Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B, Hatziioannou T, McKeating JA, Bieniasz PD, Rice CM. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007; 446(7137): 801-805.
McMullan LK, Grakoui A, Evans MJ, Mihalik K, Puig M, Branch AD, Feinstone SM, Rice CM. Evidence for a functional RNA element in the hepatitis C virus core gene. Proc Natl Acad Sci U.S.A. 2007; 104(8): 2879-2884.
Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM. Complete replication of hepatitis C virus in cell culture. Science 2005; 309(5734): 623-626.
Mark-Danieli M, Laham N, Kenan-Eichler M, Castiel A, Melamed D, Landau M, Bouvier NM, Evans MJ, Bacharach E. Single point mutations in the zinc finger motifs of the human immunodeficiency virus type 1 nucleocapsid alter RNA binding specificities of the gag protein and enhance packaging and infectivity. J Virol 2005; 79(12): 7756-7767.
Evans MJ, Rice CM, Goff SP. Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. Proc Natl Acad Sci U S A 2004 Aug; 101(35): 13038-13043.
Moradpour D, Evans MJ, Gosert R, Yuan Z, Blum HE, Goff SP, Lindenbach BD, Rice CM. Insertion of green fluorescent protein into nonstructural protein 5A allows direct visualization of functional hepatitis C virus replication complexes. J Virol 2004 Jul; 78(14): 7400-7409.
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Dr. Evans has not yet completed reporting of Industry relationships.
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