Marc Therrien and his team study the signalling mechanisms involved in cell proliferation and differentiation, more specifically those of the RAS-MAPK intracellular pathway. Dysregulation of these mechanisms is the basis for a large number of cancers.
Research theme
Cells use complex molecular networks to relay signals from the cellular membrane to the cell nucleus. One of those networks, called RAS-MAPK signalling pathway, plays a pivotal role in the control of cell proliferation and differentiation. Minimally, that signalling pathway includes the small GTPase RAS and three kinases called RAF, MEK and MAPK. The dysregulation of the RAS-MAPK pathway resulting from mutations in signalling components associated with it is involved in over 50% of cancers in humans, including some of the most frequent cancers, e.g., colorectal cancer and lung cancer.
Marc Therrien and his team work on defining the inventory of associated components and on how the signal is transmitted within the RAS-MAPK pathway. Their work has resulted in identifying several dozen factors that play a major role in the process, as well as in discovering new aspects of the signalling pathways, some of which now represent new anti-cancer therapeutic targets.
Research objectives
The RAS-MAPK signalling pathway uses a wide range of proteins, many of whose function remains poorly understood. In order to shed light on the mechanism of action of certain RAS-MAPK pathway components, Marc Therrien’s laboratory uses Drosophila and various models of human cancer cells, in concert with genetic, biochemical, molecular biology and structural biology approaches. Marc Therrien’s laboratory is currently seeking to elucidate the role of KSR pseudokinases and CNKs scaffolding proteins in the catalytic activation of RAF kinases by the small GTPase RAS.
Furthermore, in collaboration with IRIC’s Medicinal Chemistry Platform, the laboratory develops small molecules directed against various factors of the RAS-MAPK pathway, for the purpose of producing new anti-cancer drugs.