Associate Dean, Research
Canada Research Chair in Functional Architecture of Signal Transduction Complexes
Functional Architecture of Signal Transduction Protein Complexes
Our research program combines integrative biochemistry, molecular biology and cellular biology approaches with new tools in mass spectrometry and proteomics to characterize the function of novel proteins within signal transduction complexes.
We are principally interested into two main areas of research:
1. The study of signal transduction initiated by the Wnt and Hedgehog families of growth factors:
Wnt and Hedgehog are secreted glycoproteins with essential roles during development but also in the adult for the control of cell proliferation, determination of cell fate and cell survival. Their importance is best revealed in the case of several human cancers where mutations are found within proteins of their corresponding signalling pathways. We are studying the molecular processes by which Wnt and Hedgehog signals are integrated in cells to produce the desired biological response. Using mass spectrometry based proteomic approaches; we are identifying new proteins acting in these pathways and are characterizing their functions.
2. The study of the Cullin families of E3 ubiquitin ligases:
The molecular machineries underlying cell division and many growth factor signalling pathways, including Wnt and Hedgehog, are tightly regulated by ubiquitin-mediated events. Several human cancers have thus been associated with defects in ubiquitination. Cullin-RING ubiquitin ligases (CRL) form the largest family of E3 ubiquitin ligases in humans. CRL are modular protein complexes composed of a scaffolding Cullin molecule, the RING containing protein Roc1 and of a substrate specific receptor protein. Each of the five major Cullin families in humans utilizes a different family of substrate specific receptors. Using proteomic methodologies we have recently identified a family of roughly 30 WD40 domain containing proteins that serves as substrate specific receptors for Cullin-4. We are currently studying the cellular function of these proteins and ultimately trying to identify the cellular substrates for this class of E3 ligase.