Our Research Interests

Our lab studies human papillomaviruses (HPV); small DNA viruses responsible for virtually all cervical cancers and a growing share of head and neck cancers. HPV’s life cycle is tightly linked to epithelial differentiation: as cells differentiate, the virus hijacks the cell cycle machinery to replicate, using its oncoproteins E6 and E7 to bypass the checkpoints that would normally stop this. Over time, this can drive the genetic instability that leads to cancer.

Current Projects

1. How does HPV use the DNA damage response?

High-risk HPVs co-opt the cell's DNA repair machinery to replicate in differentiating cells. We are interested in how viral proteins trigger this response and what it means for genomic stability and cancer progression.

2. How is the viral life cycle controlled epigenetically?

HPV genomes are histone-associated in the virion as well as in infected cells, adopting a nucleosome pattern similar to that found in cellular DNA. We have found that certain histone post-translational modifications are required for HPV replication. We are interested in understanding how these epigenetic modifications on cellular, as well as viral DNA support HPV replication, and in turn, viral persistence. Identifying epigenetic modifiers and modifications that are required for viral replication may allow for the development of novel therapeutics to treat HPV-associated infections and malignancies

We are also interested in how endogenous retrovirus (ERV) expression is epigenetically regulated in HPV+ cells. We've previously shown that ERV expression increases following both differentiation and caspase inhibition in HPV+ cells but not HPV- cells. Studies in the lab are actively looking at what suppresses ERVs in undifferentiated HPV+ cells or how they become derepressed upon differentiation.

3. How does HPV prevent activation of an anti-viral innate immune response?

During infection, cells typically detect viral genetic material and mount an interferon response to block infection. Our lab has demonstrated that HPVs hijack a non-cell death function of apoptotic caspases to block this response upon differentiation, promoting viral genome amplification. We are currently investigating the mechanisms that may lead to the induction of this immune response and how caspases work to suppress it.