Scott B. Vande Pol, MD, PhD

Scott B. Vande Pol, MD, PhD

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Papillomavirus oncoproteins and the development of cancer

The Vande Pol lab studies papillomavirus oncoproteins as probes to elucidate cellular pathways regulating cellular signal transduction, and the development of cancer.  Projects: Oncoprotein E6 and the regulation of integrin signaling and Cdc48.

Papillomaviruses are causative agents of the most common lethal malignancy in women world-wide: cervical cancer.  Cervical cancers require the continuous expression of two virally encoded oncoproteins, E6 and E7.  This laboratory studies the actions of the E6 oncoproteins.  By identifying host proteins that associate with viral oncoproteins, those cellular factors that are critical in signal transduction and cell cycle progression are identified. Previously, this laboratory identified paxillin as a target for viral transformation by BPV-1 E6 oncoproteins. Paxillin is a critical adapter molecule involved in the regulation of integrin signaling, and the activation of tyrosine kinase signaling pathways.  The identification of paxillin as an E6 interactor is one of the first observations that connect integrin signaling to viral life cycles.  A graduate student in the laboratory created a paxillin null ES cell line and proved the critical role of paxillin in integrin signal transduction.   Ongoing studies are directed at understanding the mechanism by which paxillin activates the tyrosine kinase FAK, and the mechanism by which the interaction of E6 with paxillin results in the transformation of cells.

A second unrelated project examines a new target of cancer associated papillomavirus E6 oncoproteins: the tyrosine phosphatase PTPH1.  This laboratory recently discovered that E6 can interact with PTPH1 and then catalyze the degradation of PTPH1 in living cells. This is the first example of an E6 oncoprotein directly manipulating phosphotyrosine metabolism.  It has now been determined that loss of PTPH1 results in the destabilization of critical adaptor molecules that regulate the formation of tight junctions.  The Vande Pol laboratory now seeks to identify the mechanism by which loss of PTPH1 results in this phenotype. Recently, another group found that PTPH1 is mutated in some colon cancers, providing an independent confirmation of the possible importance of this phosphatase in the development of cancer.

Finally, using a proteomics approach, a new cellular target of E6 molecules from both cancer-associated and non-cancer associated papillomaviruses that regulates a portion of the secretory pathway has been identified.  It is this laboratory's hypothesis that the targeted degradation of this molecule by E6 proteins is responsible in part for the ability of papillomavirus transformed cells to escape immune surveillance.  This is the first E6 target common to both cancer and non-cancer associated E6 types.