Research Unit
The control of gene expression is essential for development of complex organisms. It represents the implementation of the blueprint encoded in our genome and its alteration, either through mutations or epigenetic perturbations, cause developmental malformations, more or less detrimental deficiencies and cancer. The Molecular Genetics Research Unit has investigated those mechanisms from basic principles all the way to their applications in human health.
In particular, Jacques Drouin's team discovered novel regulators of gene expression, such as the Pitx subfamily that controls pituitary and craniofacial development (Pitx1), identity of legs compared to arms (Pitx1), left-right asymmetry (Pitx2), muscle development (Pitx2 and Pitx3) and survival of the dopaminergic neurons that degenerate in Parkinson disease (Pitx3). In recent years, the group has contributed critical insight into the mechanism of action of pioneer factors that remodel the epigenome for specification of cell fate.
The laboratory also discovered the factor Tpit that drives differentiation of the hormone-producing POMC cells of the pituitary and that causes, when mutated, a hormone deficiency that is lethal to newborns but entirely treatable by hormone replacement therapy. Investigations of the mechanisms of hormone action led the group to identify critical deregulations that cause hormone resistance in Cushing disease and that contribute to the development of these highly deleterious adenomas.

- Director, Molecular Genetics Research Unit, IRCM
- Full IRCM Research Professor
- Full Research Professor, Department of Biochemistry (accreditation in molecular biology), Université de Montréal
- Adjunct Professor, Department of Medicine (Division of Experimental Medicine), Department of Anatomy and Cell Biology, and Department of Biochemistry, McGill University
- Fellow, Royal Society of Canada
Awards and honours
- Fellow, Royal Society of Canada
- Ph.D. Honoris Causa, Aix-Marseille University, France, 2014
Degrees and relevant experience
- D.Sc. in Physiology, Université Laval, Supervisor Dr Fernand Labrie
- Postdoctoral Fellowship, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom (1976 -1978), Supervisor Dr Fred Sanger
- Postdoctoral Fellowship, Department of Biochemistry and Biophysics, University of California, San Francisco (UCSF), USA (1979-1981), Supervisor Dr Howard M. Goodman
- Research Scholar, Medical Research Council of Canada (1981-1986)
- Scientist, Medical Research Council of Canada (1986-1991)
- Chair in Molecular Genetics, GlaxoSmithKline (1999-2004)
- Elected to the Academy of Sciences of the Royal Society of Canada (2001)
Projets en cours
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The pituitary as model to understand development and disease
The long term endeavours have been to understand genetic and epigenetic mechanisms controlling gene expression, cell fate specification (cell identity) and organ development.
The reasearch team primarily use the pituitary gland as model for these studies as it represents a simple organ constituted of six different cell types, each dedicated to production of a different hormone (Drouin J 2010 Pituitary Development. In: Melmed S (ed) The Pituitary 3rd Ed. Elsevier-Academic Press,3-19/ 4th Ed. 2017). The work has focused in particular on the pro- preproopiomelanocortin (POMC) gene that encodes the hormones ACTH, the melanotropins and endorphins. Dysfunction of these pituitary cells results in debilitating hormone deficiencies or overproduction. Discoveries of basic mechanisms of pituitary function have led to the identification of novel syndromes, provided diagnostic tools and opened new therapeutic approaches.
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Tri-dimensional tissue organization
The advent of powerful tissue imaging technologies led the team members to collaborate with colleagues in Montpellier, France towards elucidation of the tri-dimensional organization of the pituitary gland. This work revealed the unexpected organization of pituitary cells into homotypic cell networks in which all cells of the same lineage contact similar cells, such that these cells exchange signals for the production of coordinated responses. In addition, these homotypic networks interact with each other as they are set up during organ development.
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Mechanisms of cell specification
The investigation of transcriptional regulatory mechanisms for expression of pituitary hormone-coding genes led to discover a number of critical transcription factors such as the Pitx subfamily of homeodomain proteins, the Tbox factor Tpit, and more recently, the critical role of Pax7 as selector of intermediate pituitary identity. The research unit's members are using the full spectrum of genome technologies to identify other regulators of pituitary cell specification139 and in particular, they are investigating the mechanism used by Pax7 to pioneer chromatin remodelling and reshape the epigenome in order to program an alternate cell fate. Few factors have been shown to have pioneer activity and hence we have a unique system to understand how chromatin is reprogrammed.
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Hormonal regulation of gene expression
Expression of the POMC gene is tightly regulated by central (brain) mediators or systemic (blood-borne) hormones such as glucocorticoids. The members have defined mechanisms of POMC gene activation by hypothalamic CRH as well as negative feedback regulation by glucocorticoids and their receptor GR. Both actions are mediated by transcription factors of the nuclear receptor family, either GR or orphan nuclear receptors of the Nur subfamily. Investigations have led to discovery of new response elements, of mechanisms involving protein-protein tethering that results in mutual antagonism (trans-repression) as well as to identification of key components of glucocorticoid-dependent repression of POMC. Furthermore, the members identified disregulation of these mechanisms in pituitary adenomas that cause Cushing disease.
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Cushing’s disease and pituitary adenomas
In addition to studies of glucocorticoid resistance in pituitary adenomas that cause Cushing disease, the research unit has also investigated the control of cell cycle in normal pituitary development and in these adenomas. This work led to identification of unique mechanisms for cell cycle exit in pituitary progenitors (stem cells) as opposed to the control of cell cycle and tissue maintenance in the adult gland.
Canadian Institute of Health Research (CIHR), Foundation Grant – FDN-154297 (2017-2024), $520,000 per year
Genetic and epigenetic mechanisms of pituitary development, function and disease
Support biomedical research
Contact information
Montreal Clinical Research Institute (IRCM)
110, des Pins Avenue West
Montréal, Québec H2W 1R7