Matthew J Evans
ASSOCIATE PROFESSOR
Microbiology
Icahn School of Medicine at Mount Sinai
United States of America
Biography
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.
Research Interest
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
Publications
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Narbus CM, Israelow B, Sourisseau M, Michta ML, Hopcraft SE, etal (2011) HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle. Journal of virology.
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Ploss A, Evans MJ (2012) Hepatitis C virus host cell entry [review]. Current opinion in virology.
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Giang E, Dorner M, Prentoe JC, Dreux M, Evans MJ, etal (2012) 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.
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Mullokandov G, Baccarini A, Ruzo A, Jayaprakash AD, Tung N, etal (2012) High-throughput assessment of microRNA activity and function using microRNA sensor and decoy libraries. Nature methods.
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GarcÃa-Sastre A, Evans MJ (2013) 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.
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Sourisseau M, Michta ML, Zony C, Israelow B, Hopcraft SE, etal (2013) Temporal analysis of hepatitis C virus cell entry with occludin directed blocking antibodies. PLoS pathogens.
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Goldman O, Han S, Sourrisseau M, Dziedzic N, Hamou W, etal (2013) KDR identifies a conserved human and murine hepatic progenitor and instructs early liver development. Cell stem cell.
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Sourisseau M, Goldman O, He W, Gori JL, Kiem HP, Gouon-Evans V, etal (2013) Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection. Gastroenterology.
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Israelow B, Narbus CM, Sourisseau M, Evans MJ (2014) HepG2 cells mount an effective antiviral interferon-lambda based innate immune response to hepatitis C virus infection. Hepatology (Baltimore, Md.).
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Israelow B, Mullokandov G, Agudo J, Sourisseau M, Bashir A, etal (2014) Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nature communications.