Agency for Science, Technology and Research (A*STAR), Singapore
Professor Sir David Lane is one of the scientists credited with the landmark discovery of cancer gene p53 in 1979. p53, called the “Guardian of the genome” is considered the most significant of all the genes altered in cancer cells because mutations of the gene are known to cause almost 50 percent of all human cancers.
Prof. Lane is currently the Chief Scientist of A*STAR, where his main role is to advise and engage in scientific development across the Biomedical Research Council (BMRC) and the Scientific Engineering Research Council (SERC) at the strategic level. He is the Director of the p53 Laboratory, which primarily focuses on research on protein interactions and how to develop drugs to inhibit such interactions using p53 as a model system. The laboratory works closely with Industry and currently has major collaborations with the Merck (MSD) on peptide based therapies and with local company ASLAN on antibody based therapies.
He was previously the Executive Director of A*STAR’s Institute of Molecular and Cell Biology (IMCB), Chairman of its scientific advisory board, Chairman of BMRC, founding CEO of A*STAR’s Experimental Therapeutics Centre (ETC), as well as Director of the Cancer Research UK Cell Transformation Research Group. He also held the position of Chief Scientist with Cancer Research UK and Scientific Director of the Ludwig Institute.
For his efforts in cancer research, Prof. Lane was knighted in 2000 and has won many prominent awards such as the Paul Ehrlich Prize in 1998, the Buchanan Medal in 2004, the Medal of Honor from the International Agency for Research on Cancer in 2005, the Royal Medal from the Royal Society of Edinburgh in 2008 and President’s Science and Technology Medal from the Singapore Government in 2017.
Prof. Lane has published more than 400 research articles in international peer reviewed journals, many of which have been very highly citied. He also co-authored a successful practical guide to the use of immunochemical methods called “Antibodies” with Ed Harlow, which has sold more than 50,000 copies.
Constrained Peptides and Mini Proteins as Novel Therapeutics Targeting p53
Many important targets for human therapy are deemed “difficult “because of their intracellular location and lack of binding sites for small molecules. This problem is now being addressed by developing new larger molecules that can for example act as excellent inhibitors of protein-protein interactions or promote the correct folding of mutant proteins by acting as molecular chaperons. The p53 pathway provides an outstanding target and test system for these new approaches and we have used synthetic biology methods to develop powerful reporter systems. The challenge of these larger molecules that includes stapled and cyclic peptides, monobodies and other mini-protein domains is ensuring their effective entry into the correct intracellular compartment. The study of natural products and toxins is providing novel insights into this process and the ability of synthetic biology and protein evolution methods to access huge libraries of variants of mini proteins and constrained peptides suggest that a whole new synthetic pharmacy is within reach. Most progress has been made using hydrocarbon stapled peptides where the first generation of molecules that bind and inhibit Mdm2 and Mdm4 and thus activate p53 as a transcription factor are in clinical trial. In this model second generation molecules of great specificity and potency are being developed using novel stapling methods, unnatural amino acids and new delivery methods.