Our research is funded by BBSRC, MRC, Wellcome Trust, Horizon 2020, Parkinsons UK, Michael J. Fox Foundation and North West Cancer Research.
* Our interests cover aspects of membrane trafficking (endocytosis, autophagy, mitochondrial dynamics) and cell signaling with a view to understanding mechanisms that lead to pathologies such as cancer and neurodegeneration (Parkinsons Disease). We use a broad array of traditional molecular cell biology approaches, but also "big data" approaches such as proteomics and next generation sequencing. One particular focus is on the ESCRT-0 complex which is critical for lysosomal sorting of receptors but also co-ordinates a number of signalling events.
* We are broadly interested in ubiquitin biology with a specific focus on deubiquitylating enzymes (DUBs). Our laboratory provided the first example of specificity to a particular type of ubiquitin chain linkage (Lys63, AMSH) and has provided detailed characterisation of two endosomal DUBs, which control down-regulation of receptor tyrosine kinases (RTKs). Currently we have projects to identify other DUBs germane to cancer and neurodegeneration, which may represent attractive drug targets. We contribute to a drug discovery programme in this area together with other academic centres and industry partners.
* We have a particular interest in the RTK, Met, which is the receptor for hepatocyte growth/scatter factor. This receptor plays a key role in normal development but disregulation can lead to cancer and metastasis. Our main contribution in this area has been to define the Met degradation pathway and characterise the dependence upon proteasome activity.
* Our proteomics efforts are being applied to understand acquired drug resistance in cancer and the contingencies associated with specific mutations of oncogenes or tumour suppressors such as KRAS and VHL.