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Michel Chrétien
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Michel Chrétien 

Scientific interests
FUNCTIONAL ENDOPROTEOLYSIS AND PRO-PROTEIN CONVERTASES  (PCs)  in :

  • Protective effects of PCSK9 (Q152H) on atherosclerosis and Alzheimer in French Canadian families
  • Cholesterol metabolism (PCSK9 & SKI-1/S1P)
  • Metabolic syndrome, glucose homeostasis, diabetes, and obesity (PC1/3, PC2 & PCSK9)
  • Atherosclerosis, cancer, Alzheimer’s disease, and viral infections (furin, PACE4, PC5, PC7 & PCSK9)
  • Fertility (PC4)
  • Malaria and human evolution (PCSK9)

Summary of my scientific career: AN ADDICTION TO FUNCTIONAL ENDOPROTEOLYSIS
Functional endoproteolysis has been at the center stage of my research activities, first with the Renin-Angiotensin cascade and later with the Prohormone Theory and their Proprotein Convertases (PCs). In 1960, as a trainee in endocrinology, I intuitively thought of improving my clinical skills through a better knowledge of the chemistry of hormones. I completed my residency program in Montréal with Dr. Jacques Genest (1960-62) and at Harvard with Drs. George Cahill and George Thorn (1962-64). While in Montréal, I made my first hesitant step in organic chemistry with Dr. Roger Boucher. I continued on this path (1964-67) with Dr. C.H. Li at UC Berkeley working on the chemistry of pituitary hormones.

My initial intuition served me well since the sequencing of β-LPH and γ-LPH led me to propose the Prohormone Theory [1]. This new paradigm has defined my entire career. It has brought me to unexpected horizons in basic and clinical sciences. In 1967, I came back in Montréal to join the IRCM, which had just been inaugurated. Except for an interlude at the OHRI (1998-2011), I was to spend most of my scientific career at the IRCM. Thanks to Dr. Genest’s visionary efforts, IRCM has offered and continues to offer exceptional infrastructure for a starting independent research career. With the generous start-up funds (IRCM/FRSQ/MRC/Jane Coffin US), I opened the first protein chemistry laboratory in Quebec, acquiring then expensive equipment such as amino-acid-analyzer, high voltage and polyacrylamide gel electrophoresis, fraction collectors, spectrophotometers etc. This was completed by a special Medical Research Council of Canada (MRC) grant to purchase a Beckman automatic sequencer, one of the first three awarded in Canada.

In 1972, I hired Mrs. Suzanne Benjannet, a cell biologist, as Senior Research Assistant. In 1974, I recruited Dr. Nabil G. Seidah as a Research Associate, soon to be joined by superb students and postdoctoral fellows (PDFs), including Dr. Philippe Crine, Dr. Guy Boileau, and Dr. Christina Gianoulakis. In the late 1970s, the expansion of the Prohormone Theory into neuropeptides led us to conclude that the search for the proprotein convertases should become the priority. I took a sabbatical year in neuroscience with Dr. Les Iversen in Cambridge and Dr. Roger Guillemin at the Salk Institute. Upon my return, thanks to Dr. Genest’s support and understanding,  our protein chemistry program was consolidated with the recruitment of Dr. Claude Lazure. In 1984, Dr. Seidah was promoted and opened his own laboratory. We continued to work as a team, receiving our main funding from a MRC group grant initially awarded in 1972.

Simultaneously, my laboratory took a turn toward molecular genetics and molecular morphology with the recruitement of Drs. Majambu Mbikay and Mieczyslaw Marcinkiewicz, whose expertises were primordial to discover and chacterize the elusive PCs in 1990. In a way, we had adopted Linus Pauling’s suggestion: “In research projects, change the approaches to the problem, don’t change the project.”

In 1998, I accepted to replace Dr. David Grimes as scientific director of the Loeb Research Institute (LRI) at the Ottawa Civic Hospital where I transferred my laboratory activities. I was joined by my colleagues Majambu Mbikay, Ajoy Basak and Francine Sirois. In 2012, we were invited back to the IRCM and have opened the laboratory of Functional Endoproteolysis.

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