Ian Tomlinson is a clinician scientist and cancer geneticist. His work is based on the discovery and analysis of cancer-causing genes, especially inherited genetic variants that predispose to cancer. Using these findings, his research extends to the identification of disease mechanisms in model systems, and to cancer evolution.
Highlights of Ian’s work include the discovery of multiple Mendelian colorectal and kidney cancer predisposition genes. This has led to the identification and characterisation of diverse mechanisms of tumorigenesis, such as activation of mTOR signalling and failure of DNA polymerase proofreading. He has also led consortia that have identified many polymorphisms that influence the risk of colorectal, endometrial and oesophageal cancers. Again, this has identified important mechanisms of tumour predisposition, most strikingly the pervasive influence of variation in bone morphogenetic protein signalling on colorectal cancer risk.
Ian’s work in cancer evolution includes both mathematical models and experimental analyses. He has focussed on the importance of selection in the Darwinian process of carcinogenesis, identifying several driver mutations under selective constraints. As a result, he has identified new models of cancer evolution, chief among them being the so-called ‘just right’ model, based on selection for an optimal, intermediate level of pathway activation in tumours.