University of Dundee

Understanding how disruptions in signalling pathways cause human disease

My laboratory focuses on unravelling the roles of components that regulate protein phosphorylation and ubiquitylation pathways emerging from the analysis of human disease. The aim of our work is to discover how these pathways are organised, how they recognise signals, how the signal moves down the pathway to elicit physiological responses and to comprehend what goes wrong in human disease. We hope that these findings will enable us to play the engineer in devising new strategies to treat disease. Wherever possible, we will work closely with pharmaceutical companies, as well as chemical biologists, to help with the development of tool compounds that specifically inhibit the signalling components with which we are working. In combination with genetic approaches, these tool compounds will be very powerful in helping us to decipher the physiological roles of signalling pathways and in validating to what extent inhibiting these networks effectively suppresses disease.Possible projects include 1. Understanding the important role that LRRK2 protein kinases plays in Parkinson’s disease. This project aims to build on recent progress that our laboratory has made (PMID:27474410 and 26824392). It is aimed a deciphering how LRRK2 is regulated and functions and how mutations in this enzyme cause Parkinson’s disease. 2. Defining the important role that SGK3 kinase plays in cancer and mediating resistance to PI3K pathway therapies (PMID: 27481935 and 25177796). The goal of this project will be to identify the critical substrates for the SGK3 kinase and study how they regulate cancer relevant biology.  3. We would like to initiate a new project to study the phosphorylation of hydroxylated proline residues of protein in biology. The aim would be to discover proteins that are phosphorylated on hydroxylated proline and then identify the kinases and phosphatases that act on these.