Group Leader:
Geoff Margison
I first joined the Department of Chemical Carcinogenesis at the (then) Paterson Laboratories, in 1966 as a research technician. In 1967, I went to Manchester University, obtained a BSc degree and then returned to the Paterson to undertake a Ph.D. studying the biochemical effects of chemical methylation of DNA. I obtained my Ph.D. in 1973. My first postdoctoral fellowship was at the Max-Planck Institute for Brain Research in Cologne, Germany, between 1973-1975, before accepting a visiting fellowship at the International Agency for Research on Cancer in Lyon, France. I rejoined the Cancer Research Campaign Carcinogenesis Department (which became Cancer Research UK Carcinogenesis Group), at the Paterson in 1976. I was awarded a tenure in 1978, a Special Appointment in 1992 and since 1997 have been Group Leader.
Postdoctoral Fellow
Vitaly Latypov
Scientific Officers
Mandy Watson
Gail McGown
Mary Thorncroft
Graduate Student
Andrew Marriott
Carcinogenesis Group
The group's objective is to investigate the mechanisms by which members of a family of chemicals, called alkylating agents, exert their biological effects in living organisms. These kinds of agents are present in the external environment but can also be generated by normal endogenous cellular processes. Their biological effects include mutation, malignant transformation (carcinogenesis) and cell death. The latter is exploited in the use of some of these agents as chemotherapeutic antitumour agents. The biological effects of the agents are thought to be mediated by various types of DNA damage. DNA repair processes are present in all living organisms and protect against the potentially lethal effects of endogenous DNA damage. In man, the same processes are thought to protect cells against malignant transformation, but unfortunately, they can also be responsible for tumour resistance to chemotherapy. Understanding these processes may therefore contribute both to the prevention and treatment of cancer.
The group has been involved in developing strategies to improve the efficacy of cancer therapies by targeting certain DNA repair processes. This has resulted in the development of PaTrin-2 , a potent inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (MGMT: for which we have established a series of focussed international MGMT meetings). We have also identified a family of proteins that are related to alkyltransferases, which we have imaginatively called Alkyltransferase-like proteins, and we are in the process of characterizing these.