Our lab is interested in the mechanisms by which human papillomaviruses (HPVs) and human polyomaviruses contribute to cancers. Most of our research has focused on the HPVs that have a high risk of progression to cervical cancers, such as HPV 16. More recently we have also studied the role that genus beta HPVs, such as HPV 5 and 8 play in skin cancer. We have sought to determine how the E6 and E7 oncoproteins disrupt the cell cycle checkpoints that normally maintain genomic integrity, how HPV 16 E6/E7 facilitates the immortalization of primary human cells in culture, and how these oncoproteins disrupt the response to DNA damage.
In addition to mechanistic studies, we have had long-standing collaborations with epidemiologists and clinicians to understand the natural history of genital HPV infections, and the risk factors that cause only a small subset of women infected with high risk HPVs to progress to cancer. To aid in these studies we have developed serologic assays to detect and characterize HPV-specific antibodies. The recent establishment of multiplex assays in our lab is affording a more comprehensive assessment of the prevalence of HPV infections. It is clear that protection from infection is based on neutralizing antibodies, generated either following natural infection or through vaccination. We are studying the B cell memory response (Bmem) by isolating HPV 16 - specific Bmem and cloning out individual antibodies.
More recently we have begun to study a different group of viruses, the human polyomaviruses (HPyVs). Of particular interest is Merkel Cell polyomavirus (MCPyV), which is involved in the etiology of Merkel Cell carcinoma. Our lab identified a novel gene in the +1 frame of the Large T antigen (LT) that we have called ALTO. ALTO is evolutionarily related to the middle T antigen of rodent PyVs and defines a new clade of PyVs. Our efforts are currently focused on identifying the role of ALTO in the virus life cycle and in tumorigenicity.
Copyright © 2003-2013 Molecular & Cellular Biology Program, University of Washington
Fred Hutchison Cancer Research Center | University of Washington
Institute for Systems Biology | Seattle Biomed