Bruce Ponder
From Wikipedia, the free encyclopedia
25 April 1944[1]
- University of Cambridge (MA, MB BChir)
- University of London (PhD)
- Knight Bachelor (2008)
- FMedSci[2]
- FRS (2001)
Sir Bruce Ponder | |
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| Born | Bruce Anthony John Ponder 25 April 1944[1] |
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| Scientific career | |
| Fields | Cancer[3] |
| Institutions | University of Cambridge |
| Thesis | The Nucleoprotein Complexes of Polyoma Virus (1977) |
| Doctoral advisor | Lionel Crawford |
| Website | www |
Sir Bruce Anthony John Ponder FMedSci FAACR FRS FRCP (born 25 April 1944) is an English geneticist and cancer researcher. He is Emeritus Professor of Oncology at the University of Cambridge and former director of the Cancer Research UK Cambridge Institute and of the Cancer Research UK Cambridge Cancer Centre.
Ponder was educated at Charterhouse School and Jesus College, Cambridge.[1][4] He trained in medicine at St Thomas' Hospital, London, and carried out his PhD studies as an Imperial Cancer Research Fund Clinical Fellow with Lionel Crawford in London working on chromatin organisation and DNA sequence specificity using polyoma virus.[5][6]
Research
After completing training in medical oncology, Ponder obtained a 5 year Career Development award from the UK Cancer Research Campaign at The Royal Marsden hospital and The Institute of Cancer Research, London, in which he combined laboratory and clinical research.[7] [8]
He first studied cancer as a breakdown of the normal rules of tissue organisation. To do this he developed new methods to measure the competition between the progeny of normal dividing cells in the lining of mouse intestine, and showed that the descendants of one cell would always by chance ‘win’ over all the others and populate the structural unit known as the ‘crypt’.[9][10][11] When transgenic technologies became available, others including Ponder’s former lab member Doug Winton built on this and showed that a cancer mutation could confer an advantage, so that a future cancer cell would outcompete surrounding normal cells, and moreover that this advantage was increased by concomitant inflammation.[12]
In his clinical work, Ponder began to study familial cancers. ‘Cancer families’ had long been recognised and suspected to have an inherited basis, but the genes were unknown. In the late 1970s Ponder and many others saw the potential to use new methods of linkage analysis using restriction fragment polymorphisms to discover the underlying genes.[13] In 1980 Ponder set up a Familial Cancer clinic, new in the UK, at the Royal Marsden Hospital, and from this base he founded and led a multidisciplinary ‘UK Familial Cancer Study Group’ to promote the study of the genetics, epidemiology and clinical management of familial cancers.[14] Focussing on Multiple endocrine neoplasia type 2[15] he described (with Doug Easton) the genetic patterns of the component cancers,[16] and in 1993 identified ret as the causative gene.[17] This allowed genetic testing to identify family members at risk, in whom cancer might be avoided by prophylactic surgery.[18]
Turning to commoner cancers, during the late 1980s and the early 1990s, Ponder co-founded and was the first chair of the International Breast Cancer Linkage Consortium[19] which made major contributions to the identification of the breast cancer susceptibility genes BRCA1 (by M-C King) and BRCA2 (by M Stratton and A Ashworth). Over the next decade the Consortium coordinated a large international effort which defined the genetic epidemiology of both the BRCA-related and other non-BRCA familial breast and ovarian cancers.[20][21][19][22]
By the mid 1990s it was clear that there were many more small family clusters of breast cancer than would be expected by chance, and most were not due to mutations in BRCA-like genes. Like other familial resemblance, these family clusters were likely to be the combined effect of normal small genetic variations in many hundreds of different genes: so-called ‘polygenic inheritance’.[23] Ponder, with colleagues Pharoah and Easton, showed that these families account for a substantial component of breast cancer, with potential opportunities for prevention.[24] To find the genes by ‘genome wide association studies’ was a challenge.[25] Ponder and Easton, with David Cox at Perlegen Sciences, met this challenge by adapting a technology for high throughput typing of DNA variations which had been developed for a different purpose by Cox. In 2007 they published the first genome-wide association study for cancer, identifying 5 genes in which variants were linked to breast cancer risk, confirmed by replication of the result in 22 laboratories world-wide.[26] The number of these genes is now close to 300. As more variants were found, Ponder’s group adapted the gene regulatory network approach pioneered by Califano to show how their effects combined to affect cellular processes and increase cancer risk.[27]
