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Dr. Vincent Giguère

Research

The focus of Dr. Giguère’s laboratory is to investigate the mechanisms governing the transcriptional control of bioenergetic pathways in normal and cancer cells by nuclear hormone receptors. 
Nuclear receptors constitute a class of transcription factors that directly relays hormonal signals originating from outside the cell to its nucleus where they bind to specific sequences within the regulatory regions of their target genes. Dr. Giguère’s laboratory is exploring the roles played by members of the superfamily of nuclear receptors in development, physiology and diseases, especially hormone-dependent cancers. To this end, they use an approach referred to as physiological genomics.

1)    In particular, Dr. Giguère’s group is studying the transcriptional control of energy metabolic pathways. Nuclear receptors have been shown to play important roles in this process as they can translate hormonal, nutrient and metabolite signals into specific gene expression networks to satisfy energy demands in response to distinct physiological cues. The estrogen-related receptors (ERRα, β and γ) are nuclear receptors that have yet to be associated with a natural ligand, and are thus considered orphan receptors. However, the activity of the ERRs is exquisitely sensitive to the presence of coregulatory proteins known to be essential for the control of energy homeostasis and for all intents and purposes, these co-regulators function as protein ligands for the ERRs. In particular, functional genomics and biochemical studies have shown that the ERRs operate as the primary conduits for the activity of members of the family of PGC-1 coactivators. As transcription factors, the ERRs control vast gene networks involved in all aspects of energy homeostasis, including fat and glucose metabolism as well as mitochondrial biogenesis and function. Mouse models have shown that all three ERRs are indispensable for proper development and/or survival of the organism when subjected to a variety of physiological challenges.

2)    Dr. Giguère’s group is also working on the identification and functional characterization of transcriptional networks in cancer cells and has implicated ERR signaling as a key determinant of breast cancer heterogeneity.

3)    The team is also investigating the role of microRNA 378* as an inhibitor of  ERR γ function in breast cancer cells. MicroRNA 378* acts as a molecular switch that orchestrates a genetic program necessary for cancer cells to adapt to glucose as a the most prominent source of bioenergetic fuel. Given their extended roles in the control of cellular energy homeostasis, the ERRs represent leading targets for therapeutic interventions for metabolic diseases such as obesity, diabetes and heart failure, as well as for many types of cancer whose proliferating cells require an increase in metabolic rate for their growth and survival.

Dr Giguere's recent publication

Updated Jan 16, 2012