Virology Faculty Member - Raymond Chung

Raymond Chung

Professor of Medicine

Massachusetts General Hospital
Warren 1007C
Boston, MA 2114
Tel: 617-724-7562
Fax: 617-643-0446
Email: rtchung@partners.org



Our laboratory has been focused on the mechanisms of HCV persistence and pathogenesis. Hepatitis C virus infects 170 million persons worldwide and is remarkable for its predilection for chronicity. It is also a leading cause of chronic liver disease, liver cancer, and the need for liver transplantation. We have focused our efforts in development of model systems supportive of HCV replication, elucidating some of the many mechanisms by which viral proteins subvert innate antiviral immunity, particularly type I IFN signaling. We have focused on the actions of HCV core protein, which induces the selective degradation and inhbition of STAT1 phosphorylation. We are also studying suppressors of cytokine signaling (particularly SOCS3) andtheir interaction with IFN signaling in chronic HCV. Another avenue our laboratory has taken is a high throughput screen for small molecules that regulate HCV infection using a tractable replicon model. We have identified a number of small diversity oriented synthesis (DOS) molecules that inhibit HCV replication and are performing target identification to clarify mechanism of action. Similarly, we have used a whole genome siRNA library approach and identified several dozen host genes that participate in HCV replication. These include proteins involved in the secretory pathway and facilitation of intracellular lipid transport We believe that these approaches will add to our understanding of the underpinnings of HCV replication and lead to novel strategies to interrupt its lifecycle.


We have also been interested in understanding the basis for the observation of more progressive HCV-related liver disease in HIV-infected persons, despite the lack of liver tropism for HIV. We have found that HIV (gp120) can upregulate HCV replication through chemokine receptor-dependent means, and that this upregulation of HCV replication is TGF-beta mediated. This finding may help to explain both the increased levels of HCV replication observed in HIV, but also the acceleration of hepatic fibrosis. We are currently studying the mechanisms by which viral proteins induce TGF-beta and, in turn, fibrogenesis.
















Last Update: 10/22/2013



Publications

Peng LF, Schaefer EA, Maloof N, Skaff A, Berical A, Belon CA, Heck JA, Lin W, Frick DN, Allen TM, Miziorko HM, Schreiber SL, Chung RT. Ceestatin, a novel small molecule inhibitor of hepatitis C virus replication, inhibits 3-hydroxy-3-methylglutaryl-coenzyme a synthase. J Infect Dis. 2011 Aug;204(4):609-16.

Zhang L, Jilg N, Shao RX, Lin W, Fusco DN, Zhao H, Goto K, Peng LF, Chen WC, Chung RT. IL28B inhibits hepatitis C virus replication through the JAK-STAT pathway. J Hepatol. 2011 Aug;55(2):289-98. Epub 2010 Dec 13.

Jang JY, Shao RX, Lin W, Weinberg E, Chung WJ, Tsai WL, Zhao H, Goto K, Zhang L, Mendez-Navarro J, Jilg N, Peng LF, Brockman MA, Chung RT. HIV infection increases HCV-induced hepatocyte apoptosis. J Hepatol. 2011 Apr;54(4):612-20. Epub 2010 Sep 29.

Lin W, Wu G, Li S, Weinberg EM, Kumthip K, Peng LF, Méndez-Navarro J, Chen WC, Jilg N, Zhao H, Goto K, Zhang L, Brockman MA, Schuppan D, Chung RT. HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB. J Biol Chem. 2011 Jan 28;286(4):2665-74. Epub 2010 Nov 22.

Shao RX, Zhang L, Peng LF, Sun E, Chung WJ, Jang JY, Tsai WL, Hyppolite G, Chung RT. Suppressor of cytokine signaling 3 suppresses hepatitis C virus replication in an mTOR-dependent manner. J Virol. 2010 Jun;84(12):6060-9. Epub 2010 Apr 7.

Lin W, Tsai WL, Shao RX, Wu G, Peng LF, Barlow LL, Chung WJ, Zhang L, Zhao H, Jang JY, Chung RT. Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner. Gastroenterology. 2010 Jun;138(7):2509-18, 2518.e1. Epub 2010 Mar 12.

Tsai WL, Chung RT. Viral hepatocarcinogenesis. Oncogene. 2010 Apr 22;29(16):2309-24. Epub 2010 Mar 15.

Goldwasser J, Cohen PY, Lin W, Kitsberg D, Balaguer P, Polyak SJ, Chung RT, Yarmush ML, Nahmias Y. Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism. J Hepatol. 2011 Feb 24. [Epub ahead of print]



© 2013 by the President and Fellows of Harvard College