Raymond Chung Laboratory

Lab Members:

Wenyu Lin
Sun Sok Kim
Yoshitaka Kamegaya, M.D.

Address:

Massachusetts General Hospital
Jackson 825
55 Fruit St.
Boston, MA 02114
Phone: 617-724-7562

Current Projects

Hepatitis C Persistence and Pathogenesis

We have developed a novel, inducible, cell-based model that supports HCV RNA replication, viral protein synthesis and the evolution of HCV quasispecies. As such, we will be able to use this model to dissect the key determinants at both the viral and host level that lead to successful propagation and persistence of HCV. We have also used our system to elucidate the mechanisms of action of interferon and ribavirin, the only clinically active agents against HCV. We are currently examining the action of a number of potentially active compounds on HCV RNA replication. We are also examining the effects of viral replication itself on the host cellular response so that we may gain an understanding of the means by which the virus in so doing, we hope to identify pathways that may be exploited or circumvent the antiviral response to establish persistent infection.

Transgenic models of HCV pathogenesis

We have established a number of HCV structural protein transgenic mice to test the hypothesis that HCV directly causes hepatocellular carcinoma. We have evidence that HCV acts as an accelerant of HCC growth once tumors have formed, and are currently investigating the genetic alterations that underlie this observation. We also plan to use our cell-based inducible model in a transgenic line so that the contribution of an evoked host immune response to HCV liver pathogenesis may be ascertained. Finally, we are exploring the mechanisms behind the findings that HCV protein expression increases insulin resistance in transgenic mice.

HCV and HIV Coinfection

We are currently examining plasma, peripheral blood mononuclear cells, and liver tissue from HCV and HCV-HIV infected persons to explore the basis for the observation of accelerated natural history of liver disease in HIV-HCV coinfected hosts. We are exploring tissue cytokine alterations to address the possibility that the cytokine milieu of the liver enhances liver injury and contributes to diminished viral clearance. We are also investigating the hypothesis that extrahepatic replication in HIV-coinfected persons may underlie their relative resistance to antiviral therapy.

Our laboratory projects include:

A randomized, controlled trial to evaluate the efficiency of PEG-IFN alfa 2a, HCV disease in slowing progression in HIV -coinfected patients.
Analysis of determinants of outcome in acute HCV infection.
Viral evolution in persons with HCV and HIV receiving highly active antiretroviral therapy.
A pilot study of postexposure prophylaxis in health care workers after occupational exposure to HCV.
Insulin resistance in HCV-related liver disease
A prospective study of insulin resistance in patients undergoing liver transplantation for HCV.
A multicenter study of acute liver failure.
Evaluation of cost-effectiveness of antiviral therapy for HCV and HIV.
A multicenter study of intravenous N-acetyl cysteine in the treatment of non-acetaminophen related acute liver failure.
Cell-mediated immunity in hepatitis C virus infection.
Evaluation of novel proteomic biomarkers to detect hepatocellular carcinoma.
Evaluation of innate antiviral response genes as predictors of outcome in HCV disease.

Past Lab Members

  • Ash Chawla, MD, Philadelphia PA, U. Penn GI Division
  • Ana Contreras, MD, Guadalajara, Mexico, University of Guadalajara
  • Wenping He, MD, Chicago IL, Abbott Laboratories
  • Alex Monto, MD, San Francisco, CA, UCSF GI Division
  • Afroz Saquib, MD, Worcester, MA, UMASS Medical Center

Recent Publications:

  • Blackard JT, Komurian-Pradel F, Perret M, Sodoyer M, Smeaton L, St Clair JB, Chapman S, Taylor LE, Paranhos-Baccala G, Chung RT. Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection. J Med Virol. 2006 Feb;78(2):202-7.

  • Yachimski P, Chung RT. Hepatitis B virus infection in liver transplant candidates and recipients.MedGenMed. 2005 Apr 18;7(2):20.

  • Hiasa Y, Blackard JT, Lin W, Kamegaya Y, Horiike N, Onji M, Schmidt EV, Chung RT. Cell-based models of sustained, interferon-sensitive hepatitis C virus genotype 1 replication. J Virol Methods. 2006 Mar;132(1-2):195-203.

  • Yachimski P, Chung RT. Update on Hepatitis B and C Coinfection in HIV. Curr Infect Dis Rep. 2005 Jul;7(4):299-308.

  • Blackard JT, Smeaton L, Hiasa Y, Horiike N, Onji M, Jamieson DJ, Rodriguez I, Mayer KH, Chung RT. Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons. J Infect Dis. 2005 Jul 15;192(2):258-65.

  • Lin W, Choe WH, Hiasa Y, Kamegaya Y, Blackard JT, Schmidt EV, Chung RT. Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. Gastroenterology. 2005 Apr;128(4):1034-41.

  • Kamegaya Y, Hiasa Y, Zukerberg L, Fowler N, Blackard JT, Lin W, Choe WH, Schmidt EV, Chung RT. Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology. 2005 Mar;41(3):660-7.

  • Blackard JT, Yang Y, Bordoni P, Sherman KE, Chung RT. Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy. J Infect Dis. 2004 Apr 15;189(8):1472-81.