Scott B. Vande Pol

Primary Appointment

  • Associate Professor, Pathology


Research Interest(s)

How Viruses, Particularly Papillomaviruses, Can Cause Cancer

Research Description

Papillomaviruses cause the most common lethal malignancy in women world-wide: cervical cancer. Our laboratory studies the actions of the papillomavirus E6 oncoprotein. By identifying host proteins that associate with E6, we identify those cellular factors that are critical in signal transduction and cell cycle progression. We use a variety of biochemical and genetic approaches to identify the cellular targets of E6, and then we study the consequences of the interaction and the role of the cellular protein in cancer. E6 targets we have identified include:

Paxillin is a critical adapter molecule involved in the regulation of integrin signaling, and the activation of tyrosine kinase signaling pathways. Ongoing studies are directed at understanding the mechanism by which paxillin activates Focal Adhesion Kinase, and the role of paxillin in cancer.

PTPN3 and PTPN4. We recently discovered that E6 interacts with the tyrosine phosphatases PTPN3 and PTPN4, and then catalyze their degradation in living cells. Tyrosine phosphatases are critical regulators of signal transduction and cell proliferation. We seek to understand how the loss of PTPN3 and PTPN4 serves the viral life cycle and may promote cancer.

PDZ proteins that regulate polarity and signal transduction. E6 interacts with a set of cellular proteins that contain PDZ domains. This interaction is essential for E6 to promote cancer. We seek to understand which of the E6-PDZ interactions are critical for E6 to promote cancer and how these PDZ domain proteins prevent cancer.

A second area of research concerns determining the structure of E6 . E6 structure has frustrated laboratories worldwide for 20 years because the protein is insoluble. We have recently identified new techniques to make soluble E6 proteins, and are engaged in an international collaboration to solve the structure of E6 by NMR.

Potential Rotation Projects: 1. Identify new targets of Papillomavirus oncoproteins that have unknown transformation mechanisms 2. Determine if the degradation of cellular targets by E6 is regulated by cellular signaling 3. Examine the interaction of PTPH1 with novel tyrosine phosphorylated substrates. 4. Express novel E6 proteins for structural analysis.

Selected Publications

  • Martinez-Zapien D, Ruiz F, Poirson J, Mitschler A, Ramirez J, Forster A, Cousido-Siah A, Masson M, Vande Pol S, Podjarny A, Travé G, Zanier K. Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53. Nature. 2016;529(7587): 541-5. PMID: 26789255 | PMCID: PMC4853763
  • Strickland S, Vande Pol S. The Human Papillomavirus 16 E7 Oncoprotein Attenuates AKT Signaling To Promote Internal Ribosome Entry Site-Dependent Translation and Expression of c-MYC. Journal of virology. 2016;90(12): 5611-21. PMID: 27030265 | PMCID: PMC4886775
  • Papillomavirus E6 Oncoproteins Take Common Structural Approaches to Solve Different Biological Problems. PLoS pathogens. 2015;11(10): e1005138. PMID: 26470018 | PMCID: PMC4607424
  • Brimer N, Vande Pol S. Papillomavirus E6 PDZ interactions can be replaced by repression of p53 to promote episomal human papillomavirus genome maintenance. Journal of virology. 2013;88(5): 3027-30. PMID: 24352452 | PMCID: PMC3958089
  • Zanier K, Charbonnier S, Sidi A, McEwen A, Ferrario M, Poussin-Courmontagne P, Cura V, Brimer N, Babah K, Ansari T, Muller I, Stote R, Cavarelli J, Vande Pol S, Travé G. Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science (New York, N.Y.). 2013;339(6120): 694-8. PMID: 23393263 | PMCID: PMC3899395
  • Ansari T, Brimer N, Vande Pol S. Peptide interactions stabilize and restructure human papillomavirus type 16 E6 to interact with p53. Journal of virology. 2012;86(20): 11386-91. PMID: 22896608 | PMCID: PMC3457172
  • Brimer N, Lyons C, Wallberg A, Vande Pol S. Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene. 2012;31(43): 4639-46. PMID: 22249263 | PMCID: PMC3330202
  • Wade R, Brimer N, Lyons C, Vande Pol S. Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS. The Journal of biological chemistry. 2011;286(44): 37932-44. PMID: 21900245 | PMCID: PMC3207406
  • Jha S, Vande Pol S, Banerjee N, Dutta A, Chow L, Dutta A. Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Molecular cell. 2010;38(5): 700-11. PMID: 20542002 | PMCID: PMC2886028
  • Wade R, Brimer N, Vande Pol S. Transformation by bovine papillomavirus type 1 E6 requires paxillin. Journal of virology. 2008;82(12): 5962-6. PMID: 18385245 | PMCID: PMC2395150
  • Wade R, Brimer N, Vande Pol S. Transformation by bovine papillomavirus type 1 E6 requires paxillin. Journal of virology. 2008;82(12): 5962-6. PMID: 18385245 | PMCID: PMC2395150
  • Bohl J, Brimer N, Lyons C, Vande Pol S. The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions. The Journal of biological chemistry. 2007;282(13): 9392-400. PMID: 17237226
  • Cooper B, Brimer N, Vande Pol S. Human papillomavirus E6 regulates the cytoskeleton dynamics of keratinocytes through targeted degradation of p53. Journal of virology. 2007;81(22): 12675-9. PMID: 17804489 | PMCID: PMC2168984
  • Brimer N, Lyons C, Vande Pol S. Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein. Virology. 2006;358(2): 303-10. PMID: 17023019 | PMCID: PMC1892534
  • Jing M, Bohl J, Brimer N, Kinter M, Vande Pol S. Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. Journal of virology. 2006;81(5): 2231-9. PMID: 17166906 | PMCID: PMC1865939
  • Wade R, Vande Pol S. Minimal features of paxillin that are required for the tyrosine phosphorylation of focal adhesion kinase. The Biochemical journal. 2005;393 565-73. PMID: 16253116 | PMCID: PMC1360707