Lurie Cancer Center Member
Laimonis A Laimins, PhD
Professor, Microbiology-Immunology; Feinberg School of Medicine
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My laboratory studies human papillomaviruses and my laboratory has identified important mechanisms regulating the productive life cycle of high-risk human papillomaviruses. We have found that E5 plays an important role in maintaining cell proliferative capacity upon differentiation as well as in modulating trafficking of proteins through the ER. This is mediated at least in part through interactions with cellular proteins Bap31 and A4. The E1^E4 proteins of high-risk HPVs also play important roles in the late phase of the life cycle but the mechanisms responsible have been difficult to identify. We have also shown that E6 activates low levels of caspases upon differentiation along with the ATM-DNA damage response and that these activities are important for the HPV life cycle. We have also observed that E6 suppresses STAT-1 expression and this is necessary for stable maintenance of HPV episomes as well as amplification. Additional important activities for E6 include blocking of p300 acetylation of p53 and activation of p63 upon differentiation. E7 complements E6 action by enhancing HIF-1 activity by modulating HDAC binding.