Cardiovascular and Metabolic Diseases

Biochemical Neuroendocrinology

Under the direction of Nabil G. Seidah

Research Unit

Nabil G. Seidah’s research focuses on a family of nine mammalian protein convertases (PCs): PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1 and PCSK9. These enzymes are involved in the activation of hormone precursors, growth or transcription factors, receptors, or envelope proteins for pathogenic agents. His team is concentrating on the active mechanism and regulation of these enzymes, and on the identification of their substrates and potential inhibitors. By advancing the understanding of the physiological roles of the PCs in cells, in mice and in human, Dr Seidah's group is aiming to explore the clinical implications of the proprotein convertases in disease states, as for PCSK9 in hypercholesterolemia. The team uses a broad range of techniques: protein and peptide biochemistry, enzymology, molecular and cell biology, proteomics and genetics. 

The laboratory possesses a unique collection of PC mutants and has complete and/or conditional knockouts in mice on PC5, Furin, PC7 and PCSK9. PCSK9 is a special target for the treatment of familial hypercholesterolemia.  The role PC7 plays in the central nervous system appears to be connected to the development of anxiety, as mice whose PC7 (Pcsk7) gene has been knocked out present an anxiolytic phenotype. Recently a new function of PC7 in triglyceride regulation has emerged. The key roles SKI-1 and PCSK9 play in cholesterol homeostasis have led the team to expand its horizons and devote considerable efforts to developing pharmacological applications related to cardiovascular and cardiometabolic diseases.

Nabil G. Seidah

Research Unit Director

  • Director, Biochemical Neuroendocrinology Research Unit, IRCM
  • Full IRCM Research Professor
  • Full Research Professor, Department of Medicine (accreditation in molecular biology, and in biochemistry and molecular medicine), Université de Montréal
  • Adjunct Professor, Department of Medicine (Division of Experimental Medicine), McGill University
  • Canada Research Chairholder in Precursor Proteolysis

Awards and honours

  • Personnality of the Week of La Presse, on August 12 (2018)
  • McGill University Louis and Artur Lucian Award for Research in Circulatory Diseases (2018)
  • Grand Prix scientifique of the Lefoulon-Delalande-Institute of France Foundation (2018)
  • Akira Endo Award (2018)
  • CIHR (ICRH) Distinguished Lecturer Award in Cardiovascular Sciences (2016)
  • Anne and Neil McArthur Research Award (2015)
  • Jacques Genest Award (2014), Canadian Society of Endocrinology and Metabolism
  • Simon Pierre-Noël Memorial Lecture Award in Lipid Research (2013)
  • Queen Elizabeth II Diamond Jubilee Medal (2013), Governor General of Canada
  • Recipient, 2011 Wilder-Penfield Prize du Québec
  • Jean-Davignon Pfizer Distinguished Cardiovascular-Metabolic Research Award (2009)
  • Canada Chair Tier 1 in Precursor Proteolysis (2003-2024)
  • McLaughlin Medal (2001), Royal Society of Canada
  • Recipient, Léo-Pariseau Prize (2001), ACFAS
  • Member, Order of Canada (1999)
  • Medal of Honor, PMAC Health Research Foundation (1999)
  • Officer, Order of Québec (1997)
  • MRC Distinguished Scientist Award (1995)
  • Manning Award of Distinction (1994)
  • Fellow, Royal Society of Canada (1991)
  • Marcel Piché Award (1983), IRCM
  • The Clarke Institute of Psychiatry Award, Toronto (1977)

Degrees and relevant experience

  • PhD in chemistry, Georgetown University, Washington DC, USA (1969-1973)
  • Postdoctoral fellowship, Department of Biophysics and Chemistry, Université de Montréal (1973-1974)
  • Sabbatical year, Dr. François Rougeon’s laboratory, Institut Pasteur (1987-1988)
  • Senior research scientist, Dr. Michel Chrétien’s laboratory, IRCM (1974-1983)
Nabil G. Seidah
Research Unit Director
Annik Prat
IRCM Researcher
Ali Ben Djoudi Ouadda
Postdoctoral fellow
Ann Chamberland
Research Assistant
Julie Cruanes
PhD student
Mouna Derbali
Research Assistant
Stéphanie Duval
PhD student
Rachid Essalmani
Research Associate
Alexandra Evagelidis
Research Assistant
Ioanna Gianopoulos
MSc student
Emmanuelle Girard
Research Associate
Sandrine Lacoste
Research Associate
Sahar Mikaeeli
M.Sc. Student
Sepideh Mikaeeli
PhD student
Anna Roubtsova
Research Assistant
Vatsal Sachan
PhD student
Delia Susan-Resiga
Research Associate
Brigitte Mary
Administrative Assistant
Alexis Baass
Associate Director
Éric A. Cohen
Research Unit Director
Benoit Coulombe
Research Unit Director
Mathieu Ferron
Research Unit Director

Major Discoveries

Publications

2018

  • Invited Speaker: International Chair Therapeutic Innovation, LERMIT laboratory, Saclay, France June 28-29, 2018.
  • Invited Speaker: 18th International Symposium on Atherosclerosis (ISA 2018); Toronto, ON, Canada, June 9-15, 2018.
  • Invited Speaker:Akiro Endo award recipient at opening ceremony of the 18th International Symposium on  Atherosclerosis (ISA 2018); Toronto, ON, Canada, June 9, 2018. 
  • Invited Speaker: Guest Lecturer. Institute of Cardiovascular  & Medical Sciences - University of Glasgow, Scotland, May 10, 2018
  • Invited Speaker: Richard Lewar Centre of Excellence in Cardiovascular Research’s 2018 Annual Michael J. Sole Cardiovascular Scientific Day at the University of Toronto, ON, Canada, April 11, 2018.

2017

  • Invited Speaker: “The biology and multifaceted functions of the proprotein convertases”. Dr. Maud L. Menten Memorial Lecture series in the Department of Biochemistry, University of Western Ontario, London, ON, Canada, November 24, 2017.
  • Invited Speaker: “The biology and functions of the proprotein convertases PCSK9 & PCSK7”. International Proteolysis Society (IPS2017); Banff, Alberta, Canada; October 28 - November 2, 2017. 
  • Invited Speaker: “Present knowledge and future studies on the biology and functions of the proprotein convertases PCSK9 & PCSK7”. Cardiovascular and Metabolic Diseases Research Division; IRCM, Montreal, QC, Canada, October 24, 2017.
  • Invited Speaker: “From the physiological roles of the proprotein convertases in the secretory pathway to their clinical implications”. Faculty of Medicine, Department of Anatomy and Cell Biology and Faculty of Dentistry, McGill University, Montreal, QC, Canada; Invitation Deiter Reinhardt; September 20, 2017.
  • Invited Speaker: “What regulates the sorting of the PCSK9-LDLR complex to endosomes/lysosomes”. 38th Steenbock Symposium on “Protein Trafficking in the Secretory Pathway”. University of Wisconsin-Madison, Madison, WI, USA, June 22-25, 2017. 
  • Invited Speaker: “The sex/tissue-specific regulation of the LDLR in absence of PCSK9 activity and its clinical relevance”. OSSD Montreal, Hyatt Regency hotel, Quebec, May 15, 2017
  • Invited Speaker-CMET Distinguished Lecturer Seminar: “Les approches novatrices dans la gestion des lipides”. Formation Médicale Continue de l’Hôpital Charles-Lemoyne, Longueuil, QC, Canada, May 4, 2017.
  • Invited Speaker-CMET Distinguished Lecturer Seminar: “The physiological and pathological implications of the multifaceted proprotein convertases”. Center of Excellence in the Study of Dental and Musculoskeletal Tissues. Health Sciences’ Deans Seminar. University of Missouri, Kansas City, Missouri, USA, May 10, 2017. 
  • Invited Speaker & Group Leader: “Ancestral PCSK9 & beyond”. 7th meeting - Fondation Leducq, Stockholm, Sweden. Apr 19 – 22, 2017.
  • Special Lecture: “The implication of PCSK9 in cardiometabolic disorders”. 81st Annual Scientific meeting of the Japanese Circulation Society (JCS), Kanazawa, Japan, March 17-19, 2017.
  • Invited Speaker: “The biology and functions of the proprotein convertases in health and disease”. Child Health and Human Development Program at the
  • Research Institute of the McGill University Health Centre. Montreal, QC, Canada, March 13, 2017.
  • Special Lecture: “What is PCSK9 and why is it important? The saga of PCSK9: discovery, biology and clinical applications”. Sanofi Canada, Medical Science Liaisons (MSL) in Cardio-Diabetes. Laval QC, Canada; January 24, 2017.

CIHR (Foundation Scheme Grant) #148363
“The proprotein convertase and their partners in health and disease”
(Principal Investigator: Nabil G. Seidah) 2016-2023

Canada Research Chair Holder: 950-231335
“The Proprotein Convertases and their Relationship to Health and Disease”
(Principal Investigator: Nabil G. Seidah) 2017-2024

Univalor/Liphorus: Ministère de l'Économie, des Sciences et de l'Innovation du Québec
“Monoclonal antibodies anti-human PC7 as inhibitors of the complex ApoA5/PC7 in vivo”
(Principal Investigator: Nabil G. Seidah) 2017-2018

ASPIRE-2 (Pfizer): The 2nd Annual ASPIRE Cardiovascular Competitive Research Grants Program Pfizer: WI218345
“PCSK9 in pancreatic cell function” 
(Principal Investigators: Marc Prentki, Nabil G. Seidah) 2016-2019

Fondation Leducq FLQ #13 CVD 03
“The function and regulation of PCSK9: a novel modulator of LDLR activity”
(Coordinator North America: Nabil G. Seidah, Coordinator Europe: Bo Angelin 
Co-applicants: Robert Day, Yves Dory, Guillaume Paré, Benoit Coulombe, Robert Dufour, Alexis Baass,  Annik Prat, Marianne Abifadel, Bertrand Cariou, Cedric Le May, Jean-Pierre Rabes,  Mathilde Varret, Anders Hamsten, Ferdinand van’t Hooft, Mats Rudling) 2013-2018

ASPIRE-1 Cardiovascular Competitive Research Grants Program Pfizer: WI207162
“Investigating the role of PCSK9 in health and disease”
(Principal Investigator: Nabil G. Seidah) 2015-2018

CIHR Catalyst Grant program, Sex and variables # 145572
“The sex/tissue-specific regulation of the LDLR in absence of PCSK9 activity and its clinical relevance”
(PI: Nabil G. Seidah; Annik Prat Co-applicant) 
01-04-2016-01-04-2018

XIVe Commission mixte Québec/Flandre 2016-2018 : projet 14-302
“PCSK9 : Anticorps simple chaine et maladies cardiovasculaires”
(Principal Investigators: Nabil G. Seidah, Serge Muyldermans) 2016-2018

Fonds France-Canada Recherche (FFCR)
Optimisation des anticorps à simple chaîne (sdAb‐VHH) anti‐PCSK9 dans les maladies cardiovasculaires PCSK9
“Single domain antibodies and cholesterol regulation”
(Principal Investigators: Nabil G. Seidah, Vincent Dive) 2016-2018

Liphorus Pharmaceuticals Inc.
“Non-Peptidic Small Molecule Inhibitors of PCSK9”
Research Contract (Nabil G. Seidah) 2015-2018 

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110, des Pins Avenue West
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Cardiovascular and Metabolic Diseases