Papillomaviruses are incredibly diverse, and hundreds of human papillomaviruses have been identified. Although all the HPVs infect squamous epithelial cells and have a differentiation-dependent replication cycle, only a small fraction of them cause cancer. Other viral activities such as evading immune detection are shared by all of the HPVs. We use systematic profiling approaches and classical cell and molecular biological techniques to understand the mechanisms behind these oncogenic and non-oncogenic virus-host interactions. In doing so, we learn how viruses work and cause disease while also using viruses as tools to investigate cell biology. For more information or to inquire about opportunities in the lab, please e-mail Elizabeth White.
A systematic approach to HPV-host interactions
Mechanisms of HPV-Mediated Cellular Transformation
The cancer-associated HPVs are the cause of 5% of all human cancer and the mechanisms by which the HPV E6 and E7 oncoproteins transform cells have been studied for decades. Even so, questions remain about how oncogenic HPVs cause cancer while non-oncogenic HPVs do not. Using systematic proteomic and transcriptional profiling approaches, we identified many virus-host protein-protein interactions and cellular genes whose expression is altered by an HPV oncoprotein. We are using this information to inform our studies on the molecular basis of HPV-mediated transformation, and we anticipate that this information will be broadly applicable to other cancers.
Evasion of Immune Responses by Human Papillomaviruses
Although not all HPVs cause cancer, all of them need to evade detection and clearance by the host immune cells. We are interested in how HPVs interact with host cellular factors to inhibit or alter host innate immune signaling pathways. Our systematic analyses have revealed several immune-related cellular targets and pathways that are altered by HPV oncoproteins. We are investigating the mechanistic basis of these changes, both those that are conserved across diverse HPVs as well as some that are specific to a subset of the viruses.