Clinical studies and treatment of hepatitis C and B
A) Study of the pathogenesis of hepatic and extrahepatic manifestations associated with the human hepatitis C virus (HCV) infection, with particular regard to (i) the mechanisms leading to lipid and glucose metabolism alterations, such as steatosis and insulin resistance, and to (ii) their relationship with the HCV life cycle. The project is focused on;
- Role of lipid droplet-associated proteins in the HCV life cycle (analysis of their expression level in infected livers and of their effects on HCV replication and virion secretion in an in vitro model of infection) (collaboration with Dr Kaori Minehira, University of Lausanne);
- Lipidome profiling of lipid droplets isolated from hepatoma cell lines infected with different HCV genotypes (in particular the genotype HCV-3a, known for causing a severe form of steatosis) ; effects of specific inhibitors of lipid synthesis on HCV replication and virion secretion (collaboration with Prof Howard Riezman and Dr Ursula Loizides-Mangold, Faculty of Sciences, Geneva);
- Relationship between HCV and PTEN phosphatase in vitro and in vivo, with particular regard to the effects of PTEN activity on HCV replication and virion secretion (collaboration with Dr Michelangelo Foti, University of Geneva);
- Effects of conditioned media of hepatoma cell lines infected with HCV on the integrity of insulin signaling in adipocytes and myocytes, with the specific aim to unravel the mechanisms of insulin resistance associated with HCV infection, known for having a significant extrahepatic component (collaboration with Dr Karim Bouzakri, Prof Thierry Berney and Dr Michelangelo Foti, University of Geneva).
B) Study of the host factors affecting the pathogenesis of HCV infection, such as the spontaneous and treatment-induced clearance and the liver disease progression rate, with particular regard to genetic polymorphisms (e.g. IL28B, CCR5, SPP1, TM6SF2, PNPLA3…) and the metabolic alterations (collaboration with the Swiss Hepatitis C Cohort Study Group and other international cohorts).