David P. Lane
Karolinska Institute
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Secondary Section: 21, Biochemistry Membership Type:
International Member
(elected 2022)
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Biosketch
David Lane is an immunologist and molecular cell biologist recognized for his work on tumor suppressor proteins and the use of immunochemical methods to study protein function and conformation. He is known particularly for his work on the p53 protein and its interactions with the Mdm2 and SV40 Large T protein. He showed that cancer associated mutations in p53 led to common conformational changes in the folding of the DNA binding domain of the protein. He showed that p53 accumulates in the majority of human cancers. Lane was born and grew up in London, graduating from University College London with a degree in microbiology and a PhD. in Immunology. After postdoctoral fellowships at the ICRF in London and at the Cold Spring Harbor laboratories in New York he held faculty positions at Imperial College , at the ICRF Clare Hall, at the University of Dundee and most recently at A*STAR in Singapore and at the Karolinska Institute in Sweden. Lane is a Fellow of the Royal Society , a Fellow of the Royal Society of Edinburgh, a Fellow of the Academy of Medical Sciences, a Fellow of the AACR Academy and a member of EMBO as well a member of the National Academy of Sciences.
Research Interests
David Lane's laboratories have had a strong focus on the function and regulation of the p53 tumor suppressor protein. Using antibodies to p53 Lane and colleagues established that high level expression of point misense mutant p53 proteins was a very common feature of a wide range of human malignancies. The over-expression was established to be due to upregulation of the p53 promotor and inhibition of the proteins normally rapid degradation. Lane's laboratory pioneered work to show that some mutant proteins retained partial function and that there activity could be " rescued" with antibody and peptide ligands leading to intense efforts to discover pharmaceuticals with this activity . In tumors where p53 is not mutant p53 function is still reduced due to defects in signaling pathways that regulate the E3 ligases Mdm2/Mdm4. Here Lane's team pioneered work on peptide inhibitors of the p53/Mdm2 interaction that could reactivate the p53 pathway in these cancers. Lane's group has focused on the use of antibodies in research and he is the author with Ed Harlow of the Cold Spring Harbor Antibody Manual that sold in excess of 50,000 copies. Lane is also know for his clarifying commentaries one of which entitled "p53 guardian of the genome" has become exceptionally highly citied.
