Intracellular Signalling

MARC THERRIEN, Ph.D.

• Canada Research Chair in Intracellular Signalling
• Associate Professor, Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal

Our team is interested in deciphering the inner workings of the RAS/MAPK signalling pathway using Drosophila genetics in conjunction with molecular and biochemical approaches. The small GTPase RAS plays a central role in the control of cell proliferation, differentiation and survival by mediating signals elicited by membrane receptors, such as receptor tyrosine kinases (RTKs), to distinct downstream effector pathways.

RAS was first identified as the transforming agent of the Harvey and Kirsten mouse sarcoma viruses, which led to the identification of the three mammalian genes, H-, K- and N-RAS, encoding nearly identical molecules. The subsequent finding that activating mutations in RAS is one of the most frequent genetic lesions associated with tumor formation in humans has stimulated much interest to elucidate the role of RAS in normal and malignant cells. Several RAS effector pathways have been identified to date including the so-called "classical" and evolutionarily conserved MAPK pathway that is the main route used by RAS to transmit its proliferative and differentiative effects.

Our team is currently characterizing the function of novel proteins, such as KSR and CNK, which regulate specific steps during signal transmission within the MAPK module. Secondly, we are investigating the functional and molecular relationship that we recently uncovered between the RAS/MAPK pathway and a Rap1 signalling pathway (which controls cell adhesion and cell shape changes) during Drosophila eye development. Finally, we are exploring the use of Drosophila as an experimental system to study other human oncogenes, namely leukemia-causing oncogenes.

T + 514 343.7837
F + 514 343.6843
marc.therrien@umontreal.ca