It is estimated that 3% of the world’s population are chronically infected by the hepatitis C virus (HCV). The most unwanted complication of chronic hepatitis is cirrhosis, a massive liver fibrosis, which can lead to liver failure and hepatocellular carcinoma.The pathological outcome of HCV infection depends on viral- as well as host determinants. The development of in vitro cell culture systems has lead to significant progress in the understanding of the HCV life cycle, in particular viral replication, while viral entry and viral exit are still enigmatic. Upon infection, HCV subverts many different cellular pathways in favor of its own life cycle and virus-host interactions play a crucial role for the establishment of chronic infection.One metabolic pathway drastically altered upon HCV infection is the phosphatidylinositol-4 phosphate (PI4P) pathway. HCV induces a membranous web which is highly enriched with the membrane component phosphatidylinositol-4 phosphate (PI4P). Phosphatidylinositol 4-Kinase IIIα (PI4KIIIα), the cellular kinase crucially involved in the synthesis of the HCV membranous web, is recruited by the HCV nonstructural protein 5A (NS5A) and it is believed that this interaction stimulates PI4KIIIα kinase activity. Our laboratory is interested in understanding the molecular mechanisms of how HCV influences the PI4P pathway and how this subversion of PI4P metabolism influences the pathogenesis of chronic liver disease and progression to liver cancer.Ongoing Projects in our group include:- Role of phosphoinositol 4-phosphate metabolism and PI4K kinases in the pathogenesis of chronic liver disease and liver cancer.- Regulation of PI4K gene expression by miRNA and/or ceRNA or by long-noncoding transcripts and effect of disregulated gene expression on tumor growth and survival- Dissection by RNASeq of transcript landscape modifications (both in coding and long non-coding RNAs) induced by interferon treatment in hepatic cell lines.