Biography
Research Interests:
The central research focus of the St-Pierre laboratory is the understanding of metabolic adaptation to physiological and pathological conditions. We are particularly interested in the plasticity of mitochondrial functions and how they contribute to overall energy homeostasis. During the last decade, our team contributed significantly to understanding the role of the master regulators PGC-1s in cancer, with a particular focus on poor outcome breast cancers. We showed that PGC-1alpha plays a key role in setting the metabolic state of poor outcome breast cancers and that it promotes breast cancer growth. Recently, we focused our investigation of the role of PGC-1s in breast cancer progression and we are pursuing research projects on metabolic adaptations fueling metastasis and therapeutic resistance. The St-Pierre laboratory is enriched by numerous national/international collaborations that complement our own expertise in metabolism.
As experimental approaches, we use a combination of real-time bioenergetics measurements and metabolomics methodologies to determine the steady state of central metabolites as well as their fate through the metabolic network. These metabolic measurements are coupled with transcription profiling to uncover regulatory nodes orchestrating metabolic changes in cancer.
Selected Publications:
Andrzejewski S, Klimcakova E, Johnson RM, Tabariès S, Annis MG, McGuirk S, Northey JJ, Chénard V, Sriram U, Papadopoli DJ, Siegel PM, St-Pierre J. (2017). PGC-1alpha promotes breast cancer metastasis and confers bioenergetic flexibility against metabolic drugs. Cell Metabolism. In press.
Audet-Walsh É, Yee T, McGuirk S, Vernier M, Ouellet C, St-Pierre J, Giguère V. (2017). Androgen-dependent repression of ERRγ reprograms metabolism in prostate cancer. Cancer Research 77(2): 378-389.
Uetani N, Hardy S, Gravel SP, Kiessling S, Pietrobon A, Wong NN, Chénard V, Cermakian N, St- Pierre J, Tremblay ML. (2017). PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms. JCI insight 2(13)
Audet-Walsh É, Papadopoli DJ, Gravel SP, Yee T, Bridon G, Caron M, Bourque G, Giguère V, St- Pierre J. (2016). The PGC-1α/ERRα axis represses one-carbon metabolism and promotes sensitivity to anti-folate therapy in breast cancer. Cell Reports 14(4): 920-31.
Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H, Clish CB, DeBerardinis RJ, Feron O, Frezza C, Ghesquiere B, Gottlieb E, Hiller K, Jones RG, Kamphorst JJ, Kibbey RG, Kimmelman AC, Locasale JW, Lunt SY, Maddocks OD, Malloy C, Metallo CM, Meuillet EJ, Munger J, Nöh K, Rabinowitz JD, Ralser M, Sauer U, Stephanopoulos G, St-Pierre J, Tennant DA, Wittmann C, Vander Heiden MG, Vazquez A, Vousden K, Young JD, Zamboni N, Fendt SM. (2015). A roadmap for interpreting (13)C metabolite labeling patterns from cells. Current Opinion in Biotechnology 34: 189-201.
Dupuy F, Tabariès S, Andrzejewski S, Dong Z, Blagih J, Annis MG, Omeroglu A, Gao D, Leung S, Amir E, Clemons M, Aguilar-Mahecha A, Basik M, Vincent EE, St-Pierre J, Jones RG, Siegel PM. (2015). PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer. Cell Metabolism 22(4): 577-89.
Andrzejewski S, Gravel SP, Pollak M, St-Pierre J. (2014). Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer & Metabolism 2: 1-14. Commentary by Luengo et al. BMC Biology (2014) 12:82.
Arnold AS, Gill J, Christe M, Ruiz R, McGuirk S, St-Pierre J, Tabares L, Handschin C. (2014). Morphological and functional remodelling of the neuromuscular junction by skeletal muscle PGC-1alpha. Nature Communications 5: 1-11.
McGuirk S, Gravel SP, Deblois G, Papadopoli DJ, Faubert B, Wegner A, Hiller K, Avizonis D, Akavia UD, Jones RG, Giguère V, St-Pierre J. (2013). PGC-1alpha supports glutamine metabolism in breast cancer. Cancer & Metabolism 1(1): 1-11.
Klimcakova E, Chénard V, McGuirk S, Germain D, Avizonis D, Muller WJ, St-Pierre J. (2012). PGC-1α promotes the growth of ErbB2/Neu-induced mammary tumors by regulating nutrient supply. Cancer Research 72(6): 1538-1546.
Austin S, St-Pierre J. (2012). PGC-1α and mitochondrial metabolism - emerging concepts and relevance in ageing and neurodegenerative disorders. Journal of Cell Science 125(Pt 21): 4963-4971.
Austin S, Klimcakova E, St-Pierre J. (2011). Impact of PGC-1α on the topology and rate of superoxide production by the mitochondrial electron transport chain. Free Radical Biology & Medicine 51(12): 2243-2248.