David Lane obtained his PhD from University College London where he studied auto-immunity. He then carried out postdoctoral studies at the Imperial Cancer Research Fund (ICRF) London where he discovered the p53 tumour suppressor protein, and at Cold Spring Harbor New York where he developed monoclonal antibodies and discovered the p68 RNA helicase. In 1980 he returned to set up his own laboratory at Imperial College London, moving his team in 1985 to the ICRF at Clare Hall and in 1990 to Dundee University. In 1996 he established the cancer therapeutics company Cyclacel Ltd , which has developed two new anti-cancer drugs currently in clinical trial. He has won many international prizes and awards for work and served on the advisory boards of several institutes. He was appointed the Executive Director of IMCB in 2004.

The p53 protein is activated by many cellular stress signals including chemotherapeutic drugs and ionizing radiation. When activated the protein controls cell fate decisions to die or arrest growth. The activation of the p53 response is involved in organismal aging and is an essential defence against cancer development. Over half of all human tumours contain mutations in p53 and the response is compromised in nearly all cancers.

The laboratory is focusing on understanding how the p53 response is controlled and activated. A key step in the pathway is the blocking of the normally very rapid degradation of p53. This rapid breakdown of p53 depends upon its binding to a cellular enzyme called Mdm2. The Mdm2 protein acts as a ubiquitin ligase, modifying p53 by the covalent addition of multiple ubiquitin molecules that cause p53 to be recognized by and degraded in the proteosome. In response to DNA damage or aberrant growth signals this degradation of p53 is blocked and the protein binds to DNA and activates the transcription of genes that can induce cell growth arrest or apoptosis. A key protein involved in activating the p53 response is p14Arf whose levels rise in cells subjected to aberrant growth signals and which acts as an Mdm2 inhibitor. The expression of p14Arf is lost in many cancer cells. The DNA viruses have developed specific means to escape the p53 response and of particular importance in this context is the action of the human papilloma virus. Infection with this virus is required for the development of all cervical cancers. The virus encodes a small protein called E6 that targets p53 for rapid and unregulated degradation; because this mechanism inactivates p53 function, human cervical cancers never have mutations in the p53 gene. Thus in this form of cancer, inactivating the function of E6 would be of major importance.

The laboratory is studying how the p53 pathway is regulated using biochemical, cell culture and animal models. Recent finding have shown that p53 is modified by other members of the ubiquitin family including the SUMO and NEDD8 proteins. How these additional modifications control p53 function is still unclear. The link between modification by the ubiquitin moiety and protein degradation is also unclear as some mutants of Mdm2 appear able to modify p53 but do not target it for degradation and our studies of the E6 protein suggest further complexity in the control of p53 breakdown. The p53 pathway has been conserved in evolution from worms to man and comparative studies of the response in different model organisms may lead to the discovery of critical new regulators of p53 activity. Studying this pathway has lead to the development of new small molecules that can activate the p53 response in the absence of DNA damage. These agents, one of which is in clinical trial, offer the hope of effective therapy for tumours that retain wild type p53.