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

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

Our key interests lie in understanding the regulation of growth factor receptor trafficking and signalling in mammalian cells.
* Cell surface levels of growth factor receptors are tightly regulated in order to control proliferative signals. Downregulation of activated receptors involves their internalization into endosomes and subsequent sorting to lysosomes. Key to this sorting process is the reversible attachment of ubiquitin moieties to the cytoplasmic receptor tail, which are recognized by multiple components of the ensosomal sorting machinery, including Hrs and STAM, two proteins with ubiquitin interacting motifs (UIM) that have been under investigation in our lab.
* More recently, we have been focussing on the regulation of growth factor receptor dynamics by de-ubiquitination enzymes (DUBs). In particular we have characterized two endosomal deubiquitinating enzymes, AMSH and UBPY which both share a binding site on STAM. AMSH is a JAMM-domain metalloprotease AMSH, which acts preferentially on K63-linked ubiquitin chains, and its depletion from mammalian cells results in enhanced downregulation of EGF receptor (EGFR). In contrast, cells depleted of UBPY show severely decreased levels of Hrs and STAM, an increase in multivesicular endosomes that accumulate ubiquitinated proteins and failure to degrade multiple receptor tyrosine kinases. Both AMSH and UBPY undergo multiple interactions with a subset of CHMP proteins that are key components of the ESCRT (Endosomal Sorting Complex Required for Transport) machinery.
* Current projects in the lab are concerned with the characterization of these two enzymes, as well as with the identfication of other DUBs that may play a role in this pathway.