Cancer Research UK Skin Tumour Laboratory

Principal Investigator:

Catherine Harwood PhD MRCP

 

Research field

The clinical skin cancer group is exploring the fundamental hypothesis that cutaneous human papillomaviruses (EV-HPV) co-operate with u ltraviolet radiation in the development of cutaneous sqamous cell carcinomas by altering the balance between proliferation and cell death through blockade of UV-induced apoptosis; that there is a hierarchy of oncogenicity in contributory viruses, which may be reflected in genetic changes in tumours and that a better understanding of the viral-host interaction is leading to targeted therapeutic and preventative strategies in high-risk individuals The HPV and cancer group seeks to better understand the role of cutaneous HPV in NMSC development and finding that Bak, an apoptogenic member of the Bcl-2 family, is activated and stabilised in the skin by UV and is targeted for proteolysis by HPV E6 proteins, has proposed a new model of Bak activation. The epithelial differentiation group is studying the role of AKT kinases in epidermal development and differentiation. These kinases are targeted by cutaneous HPV and misregulated during epidermal tumourigenesis.

Key research papers

1 Jackson , S., C. Harwood, M. Thomas, L. Banks, and A. Storey. 2000. Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Genes Dev. 14:3065-73.

2 Purdie, K.J., T. Surentheran, J.C. Sterling, L. Bell, J.M. McGregor, C.M. Proby, C.A. Harwood, and J. Breuer. 2005. Human papillomavirus gene expression in cutaneous squamous cell carcinomas from immunosuppressed and immunocompetent individuals. J Invest Dermatol. 125:98-107.

3 O'Donovan, P., Perrett, C.M., Zhang, X., Montaner, B., Xu, Y.Z., Harwood , C.A. , McGregor, J.M., Walker , S.L., Hanaoka, F. and Karran, P. (2005) Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science. 309:1871-4.

4 O'Shaughnessy R.F.L., Welti J. C., Cooke J. C., Avilion A. A., Monks R., Birnbaum M. J. and Byrne, C. (2007) AKT-dependent HspB1 (Hsp27) activity in epidermal differentiation J. Biol Chem. 282:17297-17305.

5 O'Shaughnessy R.F.L, Akgul B., Storey A., Pfister H., Harwood C. and Byrne C. (2007) Cutaneous human papilloma virus early genes downregulate Akt1 while Akt2 upregulation associates with tumourigenesis. Cancer Res., 67:17