Luc DesGroseillers

Contact Information

Département de biochimie
Faculté de Médecine
Université de Montréal
Pavillon Roger-Gaudry, room D-360-2
C.P. 6128, Succ. Centre-ville
Montréal (Québec)
H3C 3J7

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P 514 343-6372
F 514 343-2210
luc.desgroseillers@umontreal.ca

Themes

• Gene expression control
• Cellular dynamics of macromolecules
• Cell signaling

Staufen1: The goal of the research is to decipher the mechanisms by which post-transcriptional gene regulation influences cell proliferation and how its deregulation may lead to cancer. We focus on the roles of the RNA-binding protein Staufen1 in relation to its capacity to interact with cell cycle regulators and modulate cell proliferation in cancer cells. This research has the great potential to advance health-related knowledge through the discovery of novel pathways that control cell proliferation and the understanding of Stau1-cell cycle regulator interaction that may lead to the development of new drugs for cancer treatments.

Cell division is a highly controlled process with several checkpoints that control exit/entry into successive phases of the cell cycle. These processes require the differential expression of many critical cell-cycle effectors. Post-transcriptional regulation of mRNAs is a perfect mechanism to properly link protein synthesis to cell needs with high precision. In this context, we published ground-breaking results that established Stau1 as a major regulator of transport, decay, differential splicing and translation of many RNA transcripts. We further showed that many of them code for proteins involved in cell cycle regulation. The importance of Stau1 was confirmed by the fact that its expression decreases during mitosis due to its interaction with the cell cycle regulator E3 ubiquitin ligase APC/C and that expression of Stau1⁵⁵-FLAG₃ in transformed cells affects mitosis entry and impairs proliferation. Importantly, these phenotypes were not observed in non-transformed cells. In contrast, Stau1 down-regulation halts cell cycle progression of untransformed cells but not transformed cells. Our hypotheses are Stau1 controls the fate of bound-mRNAs involved in the regulation of cell proliferation and that its functions are modulated by interaction with cell cycle regulators. Remarkably, this mechanism is impaired in cancer cells, contributing to their deregulated cell division. Thus our study on Stau1 will allow us to tackle cancers from an innovative angle.

Staufen2: We also want to understand the importance of post-transcriptional regulation of gene expression in DNA damages and apoptosis. We recently made an important advance by showing that the endogenous expression of Staufen2 (Stau2) is down-regulated in response to DNA damaging agents. The human Stau2 is an RNA-binding protein and a major regulator of mRNA transport, decay and translation. We recently showed that Stau2 is an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and that its expression is regulated by E2F1 via the ATR signaling pathway. Strikingly, Stau2 down-regulation enhances levels of DNA damage and promotes apoptosis in CPT-treated cells. In this project, we want to identify the signalling pathway that links DNA damages to Stau2 down-regulation and find the role of Stau2 and Stau2-bound mRNAs in the DNA damage response.

Major ongoing projects :

1. Mechanisms of post-transcriptional regulation that control cell division
2. Identification of cell signalization pathways that control mitosis
3. Importance of mitotic spindle-associated mRNAs on mitosis progression
4. Mechanisms that control DNA damages and apoptosis
5. Characterization of ribonucleoproteic complexes that control cell division

Our ongoing projects aim to :

1. Understand the role of Staufen1 in the regulation of cell proliferation in normal and tumor cells
2. Understand the role of Staufen2 in DNA damages and apoptosis