Prof. Vincent Giguère's Legacy: Molecular endocrinology and nuclear receptors

In 1994, Prof. Giguère was recruited by McGill University to head the Molecular Oncology Group (MOG), a division of the Department of Medicine. While leading this vibrant group, which became part of the Goodman Cancer Research Centre (now the GCI) in 2008, he worked closely with collaborators at McGill to establish a program of national and international significance in cancer metabolism, a nascent field at the time. He led applications to the CFI and Terry Fox Research Institute (TFRI) to establish a core facility and research team dedicated to identifying the metabolic vulnerabilities of cancer. This TFRI program was renewed in 2015 under Prof. Giguère’s leadership and again in 2019 with Prof. Peter Siegel as leader.  

Another important aspect of Prof. Giguère’s engagement has been his work with pharmaceutical and biotechnology companies, which has ensured that his technological advances and research discoveries have been translated and commercialized. 

Prof. Giguère’s legacy of creativity and discovery includes the development of highly innovative research methods and technologies such as the co-transfection assay, the most important technique for directly monitoring the activity of a transcription factor. He used this approach to determine the functional domains of the glucocorticoid receptor, the first mammalian transcription factor to be cloned. The schematic diagram representing the functional domains of nuclear receptors derived from these experiments has not changed since then and is still in use in many textbooks today.  

Applying the same ground-breaking methodology, Prof. Giguère discovered a nuclear receptor for retinoic acid, the active form of vitamin A. This discovery completely transformed the field of vitamin A research and subsequent work on retinoid signaling by his own team and many other groups led to our current understanding of the molecular basis of the teratogenic effects of retinoids in humans, the aetiology of acute promyelocytic leukemia (PML) and other malignancies, and eventually a cure for PML using high doses of retinoic acid in combination with other therapeutic agents.  

He then revealed the unanticipated existence of orphan nuclear receptors without known hormone ligands. Based on this revolutionary finding, the identification and subsequent study of novel receptor/hormone response systems completely transformed the science of endocrinology. For example, Prof. Giguère’s discovery and characterization of the estrogen-related receptors (ERRs) revealed a major regulatory node of cellular metabolism that is highly relevant to metabolic disorders, cardiovascular disease, several prominent cancers, and many other diseases. While the ERRs are orphan receptors, Prof. Giguère discovered their first synthetic ligands and has been instrumental in efforts to develop drugs that modulate their function to treat disease.