Physician Investigator (Cl) Gastroenterology, Mass General Research Institute

Physician Gastroenterology, Massachusetts General Hospital

Professor of Medicine Harvard Medical School

Kevin and Polly Maroni MGH Research Scholar 2013-2018 Mass General Research Institute, Massachusetts General Hospital

Affiliate Faculty Harvard Stem Cell Institute

MD Yale University School of Medicine 1986

antiviral agents; carcinoma, hepatocellular; hepacivirus; hepatitis c; hepatitis c, chronic; interferon-alpha; liver cirrhosis; ribavirin

The major impediment to meaningful advances in the understanding of this important pathogen has been the lack of tractable tissue culture or small animal models.

Our laboratory has successfully developed a cell-based model that recapitulates the early steps of the viral lifecycle. We are currently engaged in investigation seeking to determine the means by which this virus establishes persistence at such a high level.

We are also seeking to characterize the host response to viral replication at the mRNA and protein level, so that a more complete picture of viral pathogenesis and carcinogenesis can be drawn.

Using our system, we are also investigating the activity of putative antiviral compounds, and are using chemical libraries to screen compounds that by regulating HCV replication can identify cellular proteins involved in the HCV lifecycle. We have also generated transgenic mouse models expressing HCV viral proteins in an effort to determine whether the virus itself contributes directly to the malignant transformation that so frequently complicates HCV liver disease.

We are also investigating, using proteomic approaches, possible biomarkers for early detection of hepatocellular carcinoma in patients with high risk conditions such as cirrhosis.