Faculty : Departmental- Primary

Emmanuel Thomas, M.D., Ph.D.

My research focus is aimed at limiting the morbidity and mortality associated with HCV infection and the subsequent development of HCC through several broad efforts. The first involves defining the intrinsic innate immune response hepatocytes mount immediately following infection with HCV. The second area of research is focused on determining the antiviral mechanisms of action of the agents used to treat HCV infection (i.e. interferon and ribavirin). Data gleaned from these studies will be utilized to develop novel antivirals and innovative treatment regimens for HCV infected individuals. In addition, a better understanding of hepatocyte-specific antiviral pathways may lead to the identification of adjuvants that specifically stimulate hepatocytes to strengthen the efficacy of vaccines targeting HCV. Lastly, we have initiated several clinical studies aimed at preventing HCC.

Specific areas of interest of the laboratory program include the function of the type III interferons (IFNs) also know as interferon lambda (λ). There are three different type III IFNs and they are designated as IFNλ 1,2 and 3 or IL29, IL28A and IL28B, respectively. These interferons are specifically produced by hepatocytes in response to HCV infection. The IFNs are secreted from the cell, and following interaction with specific cellular receptors, mediate their action by inducing the expression of numerous genes, many of which exert potent antiviral and antitumor activity. Although, type I (α,β) and III IFNs induce similar genes, they do so with different kinetics and they also demonstrate tissue specific expression with the type III IFNs mainly produced by hepatocytes and other epithelial cells.

Another area of research is focused on increasing our understanding of the antiviral mechanisms of action of the agents used to treat HCV infection. Currently, the “standard of care” treatment regimen for HCV is combined therapy with interferon, ribavirin and a viral protease inhibitor. Interferon and ribavirin’s mechanisms of action are poorly characterized. Although there are several proposed mechanisms of action, each with some supporting experimental evidence, there is no consensus as to their predominant mechanism of action for these antiviral agents. It is hoped that a better understanding of the mechanism of action of these agents will lead to improvements in the current treatment regimen. My work on these antiviral agents focuses on studying their mechanisms of action using data obtained from cell culture models and corresponding clinical trials. Ultimately, data gleaned from these studies can be used to identify novel antiviral agents with activity against HCV as well as many oncogenic viruses by stimulating the innate antiviral response specifically in infected cells.

View published research articles by Dr. Thomas in the National Library of Medicine.