Dr. Clare Sample’s lab focuses on the Epstein-Barr virus, one of the seven human viruses associated with cancer. EBV-associated cancers are largely restricted to B-cell or epithelial cancers. Her research is divided between the latent lifecycle of the virus in B cells, which is associated with cellular proliferation, and the lifecycle in stratified epithelial cells, where the default is high levels of viral replication in the differentiated layers.

In B cells, EBV drives cellular proliferation to enlarge the pool of infected cells, eventually establishing long-term latency in memory B cells. Dr. Sample has investigated the function of the latency-associated EBNA3A and EBNA3C that are essential for EBV-driven proliferation and demonstrated that these are transcription factors that function through a cellular intermediate, the CSL protein, which is the intracellular signaling protein of the Notch pathway.

More recently, her lab has demonstrated that the EBNA3 proteins inhibit the cellular pathways that mediate G1 arrest. The lifecycle of EBV in epithelial compartment is less well-understood despite the fact that EBV must cross the epithelial barrier to infect a new host and that the most common EBV-associated cancers are epithelial-derived. In 2014, Dr. Sample’s lab established the use of organotypic cultures to study the lifecycle of EBV in epithelial cells in stratified epithelium. Unlike epithelial cells in monolayer culture, EBV can infect stratified epithelium, where differentiation spontaneously induces productive replication (new virus production). Her team has recently identified a viral protein that plays an important role in viral spread and may also be involved in viral entry.