Dr Daniel Felmlee

Thesis Title: Hepatitis C alters lipid and lipoprotein metabolism

Hepatits C virus (HCV) infection is a major health problem and the leading indication for liver transplantation in the US and Europe. HCV infection associates with disorders in lipid and lipoprotein metabolism including hepatic steatosis, an accumulation of fat in the liver. My previous work at University of Colorado School of Medicine, then University of California, San Diego focused on how HCV replication changes lipoprotein secretion from hepatoma cell lines, leading to lipid accumulation.

Following my interest in virus-host interactions of viral hepatitis, I pursued an MRC postdoc position in Newcastle upon Tyne investigating HCV virus/lipoprotein hybrid particles, lipoviral particles (LVP). I developed and collaboratively executed clinically based experiments that revealed LVPs to be dynamic transient particles dependent on host lipoprotein metabolism and external factors such as diet.

I then pursued and won a competitive fellowship from European Association for Study of the Liver (EASL) in Strasbourg, France. I used state-of-the-art molecular virology techniques using tissue culture models of HCV infection to further investigate functional relevance of lipoprotein and apolipoprotein interactions for viral entry and escape from host humoral defences. 

Hepatitis C virus (HCV) infection is a major health problem with 3% of the global population infected. The natural history of HCV typically involves chronic infection resulting in hepatitis, fibrosis, cirrhosis, and end stage liver disease. A number of individuals who through risk factors or known exposure have been exposed to the virus, but neither have HCV RNA detectable in serum nor detectable anti-HCV antibodies. These exposed yet uninfected patients (EUs) appear to have either robust immune defences or other uncharacterized resistance to HCV infection. In the course of genome analysis of these individuals, we have identified candidate genes that are highly associated with HCV resistance. I seek to further characterize these genes through functional analysis using tissue culture HCV replication models.

Future studies will also focus on characterization of hepatitis B virus (HBV) in newly developed cell culture models and developing models of study for non-alcoholic fatty liver disease (NAFLD) and further inflammation signals that develop to non-alcoholic steatohepatitis (NASH).