Denise Galloway, PhD
Research Professor of Microbiology; Member, Fred Hutchinson Cancer Research Center
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Our lab continues to study the role that human papillomaviruses plays in various epithelial malignancies. Several broad avenues of investigation are pursued. In the first, we are trying to understand the mechanisms by which the high risk genital HPV oncoproteins, E6 and E7, disrupt normal cell cycle control leading to cellular immortalization. We showed that E6 induces telomerase activity by activating transcription of the TERT gene. Our current model is that NFX1-91 recruits mSin3A and histone deacetylases to the hTERT promoter and repressed transcription. E6/E6AP complexes function as a E3 ubiquitin ligase to degrade NFX1-91. Myc/Max heterodimers recruit the histone acetylases, GCN5 and TIP60 to facilitate hTERT transcription. Additionally, there are other changes in transcription factor binding upon E6 expression, which we are investigating. The second avenue of investigation is focused on seroepidemiological studies to understand the natural history of HPV infection and to determine the risk factors in addition to HPV that lead to the development of cancer. Current efforts are focused on identifying the epitopes on HPV virions that are recognized in natural infection and following vaccination. We are beginning to study the diversity of the B cell repertoire and how it changes with vaccination. Finally, we are studying two families of viruses that are potentially involved in skin cancers, the genus beta HPVs, and the Merkel cell polyomavirus. As above, we have studies at both the mechanistic level and seroepidemiological studies.