Dr Simon Cook

Babraham Institute

NHS or other affiliations
Signalling Laboratory

Position: Head of Laboratory
Personal home page: http://www.babraham.ac.uk/pjl_pages/cook/research.html

PubMed journal articles - click here

Dr Simon Cook is pleased to consider applications from prospective PhD students.

Research description

In terms of basic science we are interested in how protein kinase and lipid signalling pathways control cell fate decisions such as proliferation versus differentiation and survival versus death. However, these pathways are frequently de-regulated in human cancer due to mutations in growth factor receptors, KRAS, BRAF or PI3K (or PTEN loss). As a result, tumours frequently evolve to be 'addicted' to these oncoproteins or the signalling pathways they control. This makes them attractive targets for therapeutic intervention and new drugs that target these pathways are in development or are entering the clinic; for example, the MEK1/2 inhibitor AZD6244 which blocks the BRAF-MEK1/2-ERK1/2 signalling pathway. We are interested in understanding why some tumours are intrinsically resistant to such drugs, how cells adapt to long term exposure to these drugs ('acquired resistance') and the remodelling of signalling pathways that this entails.

Research Programme or Virtual Institute
Fundamental Biology of Cancer

Protein Biochemistry Proteomics Microarrays In vitro modelling Microscopy Gene expression profiling FACS/Flow Cytometry

Key publications

Ewings KE, Hadfield-Moorhouse K, Wiggins CM, Wickenden JA, Balmanno K, Gilley R, Degenhardt K, White E, Cook SJ. (2007) ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL. EMBO J. 26:2856-67. Wickenden JA, Jin H, Johnson M, Gillings AS, Newson C, Austin M, Chell SD, Balmanno K, Pritchard CA & Cook SJ (2008) Colorectal cancer cells with the BRAFV600E mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM. Oncogene 27:7150-7161. Balmanno K, Chell SD, Gillings AS, Hayat S & Cook SJ. (2009) Intrinsic resistance to the MEK inhibitor AZD6244 (ARRY-142886) is associated with weak ERK1/2 signalling and strong PI3K signaling in colorectal tumour cell lines. Int J Cancer 125: 2332-2341.