Research Interests

• To investigate the complexities of carcinogenesis employing transgenic mouse skin models of multistage carcinogenesis.
• Verify relevant mutations, explore molecular mechanism in vivo.
• Identify compensatory sentinel systems that have evolved to inhibit carcinogenesis and which may lead to new treatment modalities.
• Investigate the roles of ras, fos and PTEN loss and their stage–specific synergism
• Identify compensatory roles for p53 and p21 and the progressive roles for AKT, mTOR and GSK3β/β-catenin
• Provide insight [and model platforms] to develop and assess new therapies tailored to reactivate p53/p21/PTEN functions or target ras/MAPK/fos, AKT/mTOR and GSK3b/b-cat/wnt signalling pathways.

1. Yao, D.,  Alexander, C. L., Quinn J. A., Chan, W-C., Wu, H. and Greenhalgh, D.A. (2008) Fos co-operation with PTEN loss elicits keratoacanthoma not carcinoma due to p53/p21WAF-induced differentiation triggered by GSK3b inactivation and reduced AKT activity. J. Cell Sci.121: 1758-1769.  
2. Yao, D., Alexander, C.L., Quinn, J.A, Porter, M.J., Wu, H. and Greenhalgh, D.A. (2006). PTEN loss promotes rasHa-mediated papillomatogenesis via dual up-regulation of AKT activity and cell cycle deregulation but malignant conversion proceeds via PTEN-dependent pathways. Cancer Res. 66: 1302-1312.
3. Bakirtzis, G., Jamieson, S., Aasen, T., Bryson, S., Forrow, S., Tetley, L., Finbow, M., Greenhalgh, D.A. and Hodgins, M.B. (2003). The effects of a mutant connexin 26 on epidermal differentiation. Cell Comm. Adhes. 10: 359-364.
4. Bakirtzis, G., Choudhry, R., Aasen, T., Shore, L., Brown, K., Bryson, S., Forrow, S., Tetley, L., Finbow, M., Greenhalgh, D.A. and Hodgins, M.B. (2003). Targeted epidermal expression of mutant connexin 26 (d66h).  mimics true vohwinkel syndrome and provides a model for the pathogenesis of dominant connexin disorders. Human Mol Gen 12: 1-8.
5. Wang, X-J1, Greenhalgh, D.A.1 and Roop D.R. (2000). Transgenic epidermal co-expression of v-rasHa and TGFa increases hyperproliferation, achieves tumor autonomy and predisposes to malignant conversion via endogenous c-rasHa  activation. Mol Carcinog.27:200-209. [Co-first authors].
6. Wang, X-J1, Greenhalgh, D.A.1 and Roop, D.R. (2000). Activated rasHa expression is necessary to overcome a paradoxical tumour inhibitory effect of p53 loss in transgenic mouse epidermis. Mol. Carcinog. 29: 67-75 [1. Co-first authors].

Dermatology
School of Medicine
College of Medical, Veterinary and Life Sciences
Robertson Building
Glasgow University
56 Dumbarton Road
G11 6NU
0141 330 6914/4012
David.Greenhalgh@glasgow.ac.uk

Grants

Current funding: 

British Skin Foundation;  Analysis of p53, p21 and PTEN mediated inhibition of malignant conversation in transgenic mouse skin carcinogenesis.
[role PI : 01/11-  12/12  £ 29,000].

Previous funding:

British Skin Foundation; Modelling tumour progression in transgenic mouse skin  carcinogenesis [role PI : 09/09-08/10 £ 9K]

CRUK SP2415    Analysis of adhesion signal deregulation in transgenic mouse skin  carcinogenesis via inducible, keratinocyte–specific tumour suppressor gen knockout [role PI £203K 4.01-11.06]

Earlier funding included grants from the Association for International Cancer Research, MRC, BBSRC and Scottish Enterprise. Applications are currently submitted to A.I.C.R. and Wellcome.