Prof Irene Leigh

Research

Introduction

Following research into structural proteins expressed during keratinocyte differentiation, it became clear that keratins, desmosomal proteins and connexins were mutated in hereditary skin disease. Mutations in connexins are also the main cause of hereditary sensorineural deafness. A longstanding Cancer Research UK funded programme of research in non-melanoma skin cancer (NMSC)has significant activity in studies on molecular carcinogenesis and the role of viruses (especially human papilloma virus HPV) in skin cancer. The high risk of NMSC in Recessive Dystrophic Epidermolysis Bullosa (RDEB) is the basis of parallel studies funded by the charity Debra.

Key Research Achievements

• Identified the absence of type VII collagen as causative in Recessive Dystrophic Epidermolysis Bullosa (RDEB) 1985
• Developed LH7.2 the diagnostic monoclonal antibody (MAb) for RDEB 1985
• Developed multiple MAb to keratins for cancer diagnosis and characterisation of genetic disease( now widely used through multiple commercial sources)1983-90
• Co-directed research programme identifying mutations in keratins, plectin and desmosomal proteins in hereditary skin disease (Joint with Lane, McLean) and developed mutation bearing keratinocyte lines 1992-2002
• Developed skin tissue engineering for treatment of burns, ulcers, oral and genital mucosa and provided laboratory and clinical service in London
• Directed programme identifying connexin mutations as major cause of hereditary sensorineural deafness as well as skin disease in London (1997-2006)
• Identified HPV as a major co factor in non melanoma skin cancer (ongoing)
• Developed epidermal stem cell marker(MCSP protein) 2001
• Characterising molecular mechanisms in non-melanoma skin cancer including PTPRD deletion (ongoing)
• Identifying mechanisms of NMSC in RDEB (major cause of death)(ongoing)
• Identification of overexpresson of axl-kinase in NMSC as potential target for treatment (CRT)

Publications

Wong T,Gammon L,Liu L, Mellerio JE, Dopping-Heppenstal PJ, Pacy J, Elia G, Jeffery R, Leigh IM, Navsaria H, McGrath JA. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J. Invest Dermatol 2008; 128(9): 2179-89.

Lalli A, Tilakaratne WM, Ariwayawardana A, Fitchett C,Leigh IM, Hagi- Pavli E, Crutchley AT, Parkinson EK, The MT, Fortune F, Waseem A. An altered keratinocyte phenotype in oral submucous fibrosis correlation of keratin K17 expression with disease severity. J Oral Path Med 2008 37: 211-20.

Pourreyron C, Cox G, Nao X, Volz A, Baksh N, Wong T, Fassihi H, Arita K, O’Toole EA, Ocampo-Candiani J, Chen M, Hart IR, Bruckner Tuderman L, Salas- Alanis JC, McGrath JA, Leigh IM, South AP. Patients with recessive dystrophic epidermolysis bullosa develop squamous cell carcinoma regardless of type VII collagen expression. J Invest Dermatol 2007 127 2438-44.

Akgul B, Ghali L, Davies D, Pfister H, Leigh IM, Storey A. HPV8 early genes modulate differentiation and cell cycle of primary human keratinocytes. Exp Dermatol 2007, 16: 590-9.

Purdie KJ, Lambert SR, The MT, Chaplin T, Molloy G, Raghavan M, Kelsell DP, Leigh IM, Harwood CA, Proby CM, Young BD. Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism analysis. Genes, Chromosomes, Cancer 2007 46: 661-9.

Teh MT, Blaydon D, Ghali LR, Briggs V, Edmunds S, Pantazi E, Barnes MR, Leigh IM, Kelsell DP, Philpott MP. Role for WNT 16B in human epidermal keratinocyte proliferation and differentiation. J Cell Sci 2007 120: 330-9.