Hair Biology and Basal Cell Carcionoma

Mike Philpott PhD

Graham Neill BSc (Hons), MSc, PhD

Research field

Current research in our lab is focussed on two areas. The first is to understand the role of SHh signalling and in particular the activity of Gli1 and Gli2 in BCC. The main focus of this research is investigating how the Hedgehog/GLI signalling pathway contributes to the formation and progression of epithelial tumours including basal cell carcinoma (BCC) and prostate cancer - this may be linked to the fact that Hedgehog/GLI signalling is associated with the maintenance of stem cell populations and that cancer may represent an amplification of such cells. Our data reveals that in primary epithelial cells over-expression of the GLI transcription factors (GLI1 and GLI2) induces characteristics of stem cell populations including a highly compact morphology and reduced proliferation rates. We wish to understand the mechanisms controlling reduced proliferation to determine if their loss contributes to cell transformation and the tumourigenic phenotype. Other areas of research include understanding how GLI promotes the invasion and metastasis of transformed epithelial cells, and whether or not GLI regulates miRNA expression.

The second area of our research is focussed on the role of the skin as a steroidogenic tissue and effects of steroids on skin function. We are investigating the role of the C/EBP family of transcription factors, the orphan LXR receptors and steroid synthesis in keratinocytes. In hair follicles we are investigating the action of androgens on mesenchymal dermal papilla cells (DP) and have recently shown that DP cells from balding scalp undergo premature senescence in vitro when compared to matched cells from non balding sites. We are now investigating the role of oxidative stress and androgens in this transition.

Key research papers

1 Neill G, Harrison W, Ikram M, Williams T, Green J, Ghali L, Frischauf A-M, O'Toole E, Aberger F, Philpott M. GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes ( in press, Carcinogenesis ).

2 Adiam W Bahta, Nilofer Farjo, Bessam Farjo, Mike P Philpott. Premature senescence of balding dermal papilla cells in vitro is associated with p16 INK4a expression (In Press J Invest Dermatol).

3 Kasper, M., Hanneder, M., Neill, G., Regl, G., Schmid, C., Philpott, MP., Frischauf, AM., and Aberger, F. Selective modulation of Hedgehog/GLI target gene expression by EGF signalling in human keratinocytes. Mol Cell Biol 2006 Aug; 26(16): 6283-98.

4 GW Neill, LR Ghali, JL Green, MS Ikram, MP Philpott, AG Quinn. Loss of PKC a expression may enhance the tumourigenic potential of Gli1 in basal cell carcinoma. Cancer Res. 2003 Aug 1; 63(15): 4692-7.