Personal Details:

Professor Sir David Lane is the Director of the Cancer Research UK Transformation Research Group at the University of Dundee, where he leads a research team studying human tumour suppressor gene function. Sir David is also the Founder and Chairman of the Scientific Advisory Board of Cyclacel, a Dundee based biotechnology company developing novel drugs for the treatment of cancer, which recently became listed on NASDAQ. Sir David is currently Executive Director of the IMCB in Singapore, whilst on sabbatical leave from the Universty of Dundee.

Sir David completed undergraduate and postgraduate degrees at University College London where he studied auto-immunity under the supervision of Avrion Mitchison. He carried out Post Doctoral Research first at the Imperial Cancer Research Fund in London with Lionel Crawford and then at the Cold Spring Harbor Labs in New York with Jo Sambrook. On returning to the UK, Sir David set up his own laboratory with CRC funding at Imperial College, London, then moving to the ICRF laboratories at Clare Hall before moving in 1990 to Dundee to help establish the CRC laboratories there.

Sir David has published more than 290 research articles and is internationally recognised for his original discovery of the p53 protein SV40 T antigen complex and for his many subsequent contributions to the field. He is co-author with Ed Harlow of the most successful practical guide to the use of immunochemical methods. The “Antibodies “ manual has sold over 40,000 copies.

Sir David is a member of EMBO, and a Fellow of the Royal Society, the UK’s premier Academy. He is also a Fellow of the Royal Society of Edinburgh, the Royal College of Pathologists and a founder member of the Academy of Medical Science. He has won many international prizes for his work including the Joseph Steiner Prize, the Meyenburg Prize, the Yvette Mayent Prize and the Paul Ehrlich Prize. He has played an active part in UK science, sitting at various times on the Scientific Committee of the CRC, the Cell Board of the MRC and briefly on the council of the ICRF. Sir David has been awarded Honorary Degrees from the University of Abertay, University of Stirling, University of Aberdeen, University of Birmingham and the University of Nottingham.

Sir David is well known for his speaking to non-specialist groups and for his clarifying reviews, of which his commentary “p53, guardian of the genome “ published in Nature, is a key example. Sir David was the second most highly cited Medical Scientist in the UK in the last decade.

David Lane was knighted for his contribution to cancer research in the New Year honours list in January 2000.

References:
Xirodimas, D., Saville, M. K., Bourdon, J.C., Hay, R.T., Lane. D.P., (2004) Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. Vol. 118 (1): 83-97

Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP (2004). Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem.;279(40):42169-42181.

Woods YL, Xirodimas DP, Prescott AR, Sparks A, Lane DP, Saville MK. (2004) p14 Arf promotes small ubiquitin-like modifier conjugation of Werners helicase. J Biol Chem.;279(48):50157-50166.

Bourdon JC, Fernandes KN, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP. (2005) p53 isoforms can regulate p53 transcriptional activity. Genes Dev;19(18):2122-2137.




The molecular basis of human cancer
The development of a malignant tumour is a multi-step process involving the mutation of several specific genes involved in the control of cell growth and programmed cell death. Most common solid tumours start from small benign growths. Very rarely an individual cell within such a lesion may undergo additional genetic changes that will confer on it a selective growth or survival advantage. From the progeny of this altered cell further even more damaged cells may arise which have additional selective advantages. Eventually clones may arise that no longer respond at all to normal regulatory signals and grow in an uncontrolled manner spreading to other sites in the body and giving rise to malignant cancer. The goal of our research is to understand the cause and nature of these accumulating genetic changes so that new diagnostic and therapeutic methods can be developed.

The p53 tumour suppressor gene
Our research has become focused on one particular gene, p53, because it is so often mutated in the common tumours and our fast emerging knowledge of its structure and function are beginning to make clear why its normal function is so important in preventing cells from turning malignant. The p53 protein is normally present in minute levels and is probably inactive, but when cells are exposed to DNA damage or start to divide aberrantly p53 levels rise and the protein is switched on. For this reason we have called p53 "The guardian of the genome". The function of p53 is critical to the way that many cancer treatments kill cells since radiotherapy and chemotherapy act in part by triggering cell suicide in response to DNA damage. This successful response to therapy is greatly reduced in tumours where p53 is mutant so these tumours are often particularly difficult to treat

New treatments for cancer
We hope to use our knowledge of p53 to develop new treatments for cancer. Many tumours make mutant forms of p53 that no longer work properly. In the test tube at least we are beginning to find ways to make these damaged p53s work again. We use modern methods of protein chemistry to try and discover novel molecules that will replace p53 or restore its function. The discovery of such agents would potentially offer a powerful and selective new way of treating the disease.


Recent Academic Awards

• 2005 International Agency for Research on Cancer (IARC) Medal, Lyon
  
• 2005 Sergio Lombroso Award in Cancer Research, Weizmann Institute of Science, Israel
  
• 2006 Inserm Award, France (Prize to Foreign Scientist)
  
• 2006 Hon. Doctor of Science, University of Nottingham