Hepatitis C virus (HCV) infection is a major human health problem due to its extremely high prevalence (estimated 200 million of chronically infected individuals worldwide) and severe complications of chronic hepatitis. Prior efforts to understand the pathogenesis of this medically important infection have been thwarted by a lack of useful animal models.
The main part of my current work, supported by a Marie Curie fellowship, is to create a new model of chronic HCV which should combine the effects of the tumorigenic potential of the viral proteins with the effects of liver inflammation. The new transgenic model will be based on an inducible expression of the viral proteins, which, if successful, should give rise to the host immune response and liver inflammation. The expertise of my current laboratory is in oncogenesis and the regulation of apoptosis, whereas my host institution is specialised in the study of inflammation and a pharmacological approach to its control. We will combine these two areas of research in order to examine the link between inflammation and tumorigenesis in the context of HCV dependent HCC.
Since the host institution has a strong tradition studying the molecular mechanisms mode of action and the physiological effects of poly-(ADP-ribose) polymerase (PARP) inhibitors in the context of inflammation, we will focus on the role of this nuclear enzyme on the aforementioned processes. The use of PARP inhibitors opens new perspectives in treatment of inflammatory disease with possible benefits for the outcome in terms of cancer development. The collaboration between the laboratories in Pecs and in Montpellier will assure that the transgenic model is exploited both with respect to inflammatory response and to cancer development.
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