We are broadly interested in how positive-sense RNA viruses interact with cellular lipid biology to promote viral replication, and how this affects the cellular environment. We are currently focusing on the following research questions:

How do positive sense RNA viruses exploit cellular factors to form replication organelles?

HCV replication modifies the cellular lipid landscape, shown here by the increase in lipid droplets (grey circles) and the formation of the double-membraned vesicles comprising the replication organelle (Colpitts et al., unpublished)

As RNA viruses with small genomes, positive-sense RNA viruses rely on interactions with cellular factors. We characterize virus-host interactions that drive intracellular membrane rearrangements to form the replication organelle. We are currently focused on understanding the role of the host protein cyclophilin A. 

How do cells sense and respond to perturbations in lipid metabolism and membrane homeostasis?

The cellular lipid landscape is profoundly modified during positive sense RNA virus replication. We study how cells sense these changes to the lipid environment, and whether this is interpreted by the cell as a danger signal, leading to inflammatory and antiviral responses.

We are particularly interested in the stress sensor protein kinase R (PKR) and its regulation.

How does dysregulation of lipid metabolism contribute to carcinogenesis?

Hepatitis C virus (HCV), a model positive-sense RNA virus that we study, causes chronic infection in the majority of infected individuals. Chronically infected patients are at significantly increased risk to develop severe liver disease and hepatocellular carcinoma. Disrupted lipid metabolism is emerging as a driver of carcinogenesis, although the mechanisms remain poorly understood. We are using HCV as a model to understand how disruptions to cellular lipid metabolism promote a tumor-permissive environment.