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 Home / About Us > Dr Nabil G. Seidah

Contact info

Dr Nabil G. Seidah
Institut de recherches cliniques de MontrÚal
110, des Pins Avenue West
MontrÚal, QC H2W 1R7

Tel: 1-514-987-5609
Fax: 1-514-987-5592
E-mail: nabil.seidah@ircm.qc.ca

 

Research keywords

  • Proprotein convertases
  • Enzymology
  • Cholesterol and lipids
  • Neuroendocrinology
  • Viral infections
  • Cancer
  • Biochemistry
  • Molecular & cell biology
  • Proteomics and sequence analysis
  • Mutagenesis
  • Genomic
  • Animal models including knockouts and transgenes
  • Human pathologies

 

Nabil G. Seidah, PhD
Professor of Biochemistry
Canada Research Chair in Precursor Proteolysis


Biographical Sketch

Dr Seidah obtained his BSc in 1969 from Cairo University in Giza, Egypt, and his PhD in Biophysics in 1973 from Georgetown University, in Washington, DC. In 1974, he started studying the processing of precursor proteins at the Clinical Research Institute of Montreal (IRCM) and in 1976 he discovered ▀-endorphin and largely contributed to the biochemical characterization of proopiomelanocortin (POMC, the ▀-endorphin precursor). Since 1983, he has been the director of the IRCM's Biochemical Neuroendocrinology Laboratory.

Dr Seidah discovered and cloned seven (PC1, PC2, PC4, PC5, PC7, SKI-1 and PCSK9) of the nine known enzymes belonging to the convertase family. During this period, he also greatly contributed to demonstrating that the proteolysis by the proprotein convertases is a wide mechanism that also concerns "non-neuropeptide" proteins such as growth factors, a-integrins, receptors, enzymes, membrane-bound transcription factors, and bacterial and viral proteins. Recently, he showed that point mutations in the PCSK9 gene cause dominant familial hypercholesterolemia, likely because of a gain of function related to the ability of PCSK9 to enhance the degradation of cell surface receptors, such as the low-density lipoprotein receptor.

Over the last 36 years, Dr Seidah has attracted more than 100 graduate students and post-doctoral fellows. He is member of numerous scientific associations, including the Cancer Research Society and the American Heart Association. In 1991, he was elected fellow of the Royal Society of Canada. He is the recipient of several awards, including the 1995 Medical Research Council Scientist Award, and was made a member of the Order of Quebec in 1997 and the Order of Canada in 1999. In 2001, he received the McLaughlin Medal of the Royal Society of Canada and the Parizeau Prize of the Association Canadienne-Franšaise pour l'avancement des sciences. He has been endowed with a Canada chair since 2003. He has been invited as a speaker to more than 320 national and international conferences. He organized the first Keystone Conference on the proprotein convertases and in 2006 was the chair of a prestigious Gordon Research Conference on Proprotein Processing, Trafficking and Secretion. He has been selected to present the prestigious "Jacques Benoţt" lecture at the 7th International Congress of Neuroendocrinology held in Rouen France in July 2010.

Dr Seidah is internationally recognized as a world leader in convertases and their physiological roles. His numerous publications that tally more than 587 peer reviewed manuscripts have been widely recognized, and in fact he is cited as the most recognized protease expert in Canada and 6th worldwide. Indeed, Pubmed cites N.G. Seidah as the topmost in Canada and the 1st out of the worldwide 20 top scientists working on "Proprotein Convertases" since 1971.


Selected Scientific Contributions

1- 1976: The discovery of human and sheep ▀-endorphins: Isolation and sequence human and sheep ▀-endorphins which are more potent homologues made of 31 amino acids (Seidah NG et al.: Fragment of sheep ▀-lipoprotein with morphine-like activity. Lancet 1: 1017, 1976; Seidah NG et al.: Morphine-like activity of sheep ▀-lipoprotein and of its tryptic fragments. Can J Biochem 55: 35-40, 1977; Seidah NG et al.: The complete sequence of sheep ▀-endorphin. Biochem Biophys Res Commun 74: 1528-1535, 1977)

2- 1978: Description the complete biosynthetic pattern of ▀-endorphin as endproducts of proopiomelanocortin (POMC) and ▀-LPH (Seidah NG et al.: In vitro biosynthesis and chemical characterization of ▀-lipoprotein, gamma-lipoprotein and ▀-endorphin in rats pars intermedia. PNAS 75: 3153-3157, 1978)

3- 1983: Discovery of 7B2 the chaperone of PC2 (Seidah NG et al.: Isolation & NH2-terminal sequence of a highly conserved human & porcine pituitary protein belonging to a new super family: Immunocytochemical localization in pars distalis and pars nervosa of the pituitary and in the supraoptic nucleus of the hypothalamus. Arch Biochem Biophys 225: 525-534, 1983)

4- 1984: Amino acid sequence of atrial natriuretic factor (Seidah NG et al.: Amino acid sequence of homologous rat atrial peptides: Natriuretic activity of native and synthetic form. PNAS 81: 2640-2644, 1984)

5- 1990-2010: Discovery of the convertases and relationships to pathologies - it took 18 more years to identify the PCs, which cleave numerous precursors. I discovered or co-discovered 7 of the 9 PCs:

  • Seidah NG et al.: cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases. PNAS 93: 3388-3393, 1996
  • Seidah NG et al.: Mammalian subtilisin/kexin isozyme SKI-1: a widely expressed proprotein convertase with a unique cleavage specificity and cellular localization. PNAS 96: 1321-1326, 1999
  • Seidah NG et al.: The novel secretory proprotein convertase NARC-1: Its Potential role in liver regeneration and neural differentiation. PNAS 100: 928-33, 2003
  • Abifadel M et al., Seidah NG and Boileau C: Mutations in the PCSK9 gene at 1p32 as a cause of autosomal dominant hypercholesterolemia. Nat Genetics 34: 154-156, 2003
  • Benjannet S et al. and Seidah NG: NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the LDLR and LDL-cholesterol. J Biol Chem 279: 48865-48875, 2004.
  • Essalmani R et al., Seidah NG and Prat A: Genetic deletion of PC/6 leads to early embryonic lethalithy. Mol Cell Biol 26: 354-361, 2006
  • Benjannet S et al.: The proprotein convertase PCSK9 is inactivated by Furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 281: 30561-30572, 2006
  • Nassoury N et al.: The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 7: 950-965, 2007
  • Poirier S et al.: The Proprotein Convertase PCSK9 Induces The degradation of LDLR and its closest family members VLDLR and ApoER2. J Biol Chem 283:2363-2372, 2008
  • Essalmani R et al.: In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a major substrate. PNAS 105: 5750-5755, 2008
  • Zaid A et al.: PCSK9: hepatocyte-specific LDL receptor degradation and critical role in liver regeneration. Hepatology 48:646-54, 2008
  • Szumska D et al.: VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase PCSK5. Genes Dev 22: 1465-1477, 2008
  • Mayer G, Poirier S and Seidah NG: Annexin A2 is a C-terminal PCSK9 binding protein that regulates endogenous LDLR levels. J Biol Chem 283: 31791-801, 2008
  • Poirier S et al.: Dissection of the endogenous cellular pathways of PCSK9-induced LDLR degradation: evidence for an intracellular route. J Biol Chem 284: 28856-28864, 2009
  • Sun X, Essalmani R, Seidah NG and Prat A: The role of PC5/6 in intestinal tumorigenesis. Molecular cancer 8: 73-82, 2009
  • Seidah NG: PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets 13: 19-28, 2009
  • Dubuc G et al., Seidah NG and Davignon J: A new method for measurement of total plasma PSCK9 ľ clinical applications. J Lipid Res 51:140-149, 2010
  • Gupta N et al., Seidah NG and Straarup EM: A locked nucleic acid antisense oligonucleotide silences PCSK9 and enhances LDLR expression ex vivo and in vivo. PLoS One 5:e10682, 2010
  • Khatib A-M et al., Seidah NG, Villoutreix B and Calvo F: Regulation of VEGF-C-induced functions and fin regeneration in zebrafish by the proprotein convertases. PLoS One 5: e11438, 2010 [IF=4.4]
  • Davignon J, Dubuc G and Seidah NG: The influence of PCSK9 polymorphisms on serum LDL cholesterol and risk of atherosclerosis. Curr Atheroscler Rep. 12: 308-315, 2010
  • Benjannet S et al. and Seidah NG: Effects of the prosegment and pH on the activity of PCSK9: evidence for an additional processing event. J Biol Chem 2010 (in press) [IF=5.8]
  • Chitramuthu BP, Baranowski D, Cadieux B, Seidah NG and Bennett HP. Molecular cloning and embryonic expression of zebrafish PCSK5/6 co-orthologues: Functional assessment during lateral line development. Dev Dyn 239:2933ľ2946, 2010 [IF=3.1]
  • Seidah NG: What lays ahead for the proprotein convertases? From fundamental research to translational applications. Ann N Y Acad Sci (in press), 2010 [IF=2.7]
  • Maret D et al., Seidah NG, Del Maestro RF and Colman DR: Surface expression of precursor N-cadherin promotes tumor cell invasion. Neoplasia (in press) [IF=5.1]
  • Click here for PubMed listing


    Research Interests

    The in depth study of the proprotein convertases and their roles in vivo and implication in pathologies, e.g., hypercholesterolemia, cancer/metastasis, viral infections and neuropathological behavioral disorders. The three major aims deal with:

    1- An extensive analysis of the structure-function and cellular biology of PCs.

    2- Analysis of the in vivo functions of PCs in genetically modified mice and human.

    3- Implication of PCs in dyslipidemia, cardiovascular disorders, cancer/metastasis, neurodegenerative diseases and viral infections.

   
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