Previous and current research:
During my PhD at Liverpool University, I explored the roles of PI 3-kinase and the small GTPase, Rab5 in early endosome fusion under the supervision of Dr. Mike Clague. In the course of this work I characterized the function of a lipid-binding adaptor protein, Early Endosomal Autoantigen 1, in homotypic endosome fusion and began to explore the interplay between phoshoinositide binding and the tyrosine phosphorylation of a related endosomal protein, hepatocyte growth factor receptor substrate (Hrs). And at the MRC Laboratory of Molecular Biology where I was a Research Training Fellow in Dr Harvet McMahon's group, I focused on clathrin-mediated vesicle trafficking and in particular the contribution of phosphoinositide-binding ANTH/ENTH and BAR domain proteins to vesicle formation and the induction/maintenance of membrane curvature.

The current focus is on the role of adaptor proteins in regulating hormonal responsiveness and receptor trafficking in prostate cancer models. In addition I assist in the day-to-day running and supervision of other projects focussing on urological cancers include genomic profiling and matrix metalloprotease-mediated cellular invasion in conjunction with the genomics, bioinformatics, matrix metalloprotease research groups on the Addenbrookes site.

So far we have targeted Huntingtin Interacting Protein (HIP1), a lipid-binding adaptor protein reported to be a prognostic marker for recurrent prostate cancer. HIP1 may prove to be one of number of regulatory adaptors capable of undergoing nucleocytoplasmic translocation and to regulate transcriptional responses to stimuli and influence DNA damage repair. Recent reports have implicated the IRS-1 adaptor protein, Epsin1, APPL and EGFR in such trafficking events. The identities of their DNA and nuclear protein targets and their contribution to cancer progression largely remain to be explored. To address these points we are actively developing approaches based on chromatin immunoprecipitation, subcellular fractionation and imaging working initially in prostate cancer cell-lines.

Future projects:
The long-term goal is to enhance the value of these proteins as cancer markers and potentially uncover novel treatment targets by applying these approaches and the information derived from them to other models and clinical material.

This research is closely associated with other research projects in David Neal's Urological Research Group.