I am part of the Oncology, Membrane Traffic and Signaling grouping in the Physiological Laboratory.

Our research is funded by CRUK, Wellcome Trust and North West Cancer Research Fund.

* Our over-arching interest lies in the reciprocal relationship between regulation of endocytic membrane traffic and signal transduction mechanisms. We have a long-standing interest in the links between phosphoinositide metabolism and membrane traffic. More recently we have begun to explore the role of ubiquitin in regulating the properties of endosomes and the stability of selected oncogenes.
* We have a specific focus on de-ubiquitinating enzymes (DUBs). Our laboratory provided the first example of specificity to a particular type of ubiquitin chain linkage (K63, AMSH) and has provided detailed characterisation of two endosomal DUBs, which regulate down-regulation of receptor tyrosine kinases (RTKs). Currently we have projects to identify DUBs which may represent attractive drug targets.
* We have a particular interest in the RTK,Met, which is the receptor for hepatocyte growth/scatter factor. We are interested in how an HGF-specific signaling network is generated and how this might be disregulated in cancer. Increasingly, we are turning towards large-scale proteomics based approaches.
* With regard to phosphoinositide metabolism, our current focus is on the Myotubularin family of PtdIns 3-phosphatases, some of which are mutated in heritable diseases. For example mutations in MTM1 lead to Myotubular Myopathy a form of muscular dystrophy, whilst mutations in MTMR2 lead to a neuropathological condition known as Charcot-Marie-Tooth syndrome. Our laboratory played a key role in establishing the substrate specificity of this family of enzymes.