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IRCM Researchers

Creating new
knowledge

Exploring new avenues to develop tomorrow’s medical knowledge through an approach that integrates basic and clinical research

Our research units are led by principal investigators who collaborate in a spirit of collegiality and with the vision of bridging the gap between research and patients. They train the next generation of scientists and are independent and creative minds who work tirelessly to improve health.

 

Nabil G.
Seidah

Director, Biochemical Neuroendocrinology Research Unit

Current research

"Our research focuses on clinical applications of inhibitors of convertases in the treatment and diagnostic of major pathologies, such as cardiovascular diseases, cancer/metastasis and viral infections."

Nabil G. Seidah, research director

Biochemical Neuroendocrinology

Our 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. The team is concentrating on the activation mechanism and regulation of these enzymes, and on the identification of their substrates and potential inhibitors. We are also deciphering in details the in vivo physiological roles of the PCs in cells, in mice and in human.

Our group aims to explore the clinical implications of the proprotein convertases in disease states, as for PCSK9 in hypercholesterolemia. Our 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 PCSK5, Furin, PCSK7 and PCSK9. PCSK9 is a special target for the treatment of familial hypercholesterolemia. Anti-PCSK9 treatments are now available worldwide. We have also identified a new role of PCSK9 inhibition in the treatment of cancer/metastasis and some viral infections. We recently discovered a new role for PCSK7 in triglyceride regulation and fatty liver disease and are developing antisense oligonucleotide silencing approaches to treat this pathology. 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.

We have demonstrated the critical role of Furin-like convertases in the activation of the cellular entry of SARS-CoV-2, the ethological agent of COVID-19. Small molecule inhibitors are now available for pre-clinical studies as antivirals in anticipation of future pandemics.

We also demonstrated that PCSK7 regulates triglycerides via enhanced degradation of ApoA-V. Its absence reduces the levels of hepatic apoB and lipid droplets and enhances recovery from hepatic steatosis, providing novel preclinical validation for the treatment of NASH.

We recently investigated the implication of PCSK9 and PCSK7 in cancer and metastasis. Our findings demonstrate that the loss of expression of either PCSK9, PCSK7, or both convertases results to a drastic reduction in tumor growth and hepatic metastasis.

Discover PubMed publications

Available positions Clinical studies

Team
  • Alexandra Evagelidis Assistante de recherche Research Assistant Alexandra.Evagelidis@ircm.qc.ca
  • Anna Roubtsova Stepanova Assistante de recherche Research Assistant Anna.Roubtsova.Stepanova@ircm.qc.ca
  • Annik Prat Chercheuse associée Research Associate Annik.Prat@ircm.qc.ca
  • Chloe Porcheron Étudiante au doctorat PhD Student Chloe.Porcheron@ircm.qc.ca
  • Delia Susan-Resiga Chercheuse associée Research Associate Delia.Susan-Resiga@ircm.qc.ca
  • Gabriela Simoes Lopes-Letendre Stagiaire avec crédits Intern With Credits Gabriela.Simoes.Lopes-Letendre@ircm.qc.ca
  • Hadi Bayat Stagiaire postdoctoral Post-Doctoral intern hadi.bayat@ircm.qc.ca
  • Jisca Borgela Adjointe administrative Administrative Assistant Jisca.Borgela@ircm.qc.ca
  • Mailys Le Devehat Assistante technique de laboratoire Lab Technical Assistant Mailys.LEDEVEHAT@ircm.qc.ca
  • Rachid Essalmani Chercheur associé Research Associate Rachid.Essalmani@ircm.qc.ca
  • Vatsal Sachan Stagiaire postdoctoral Postdoctoral Fellow Vatsal.Sachan@ircm.qc.ca
Affiliations
  • 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
Degrees and 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)
Publications
  • Porcheron C., Le Dévéhat M., Roubtsova A., Bayat H., Evagelidis A., Jafarzadeh L., Sachan V., Labrecque N., Fonta Holder A., Susan-Resiga D., Essalmani R., Boudreau G., Prat A., Cusseddu R., Côté J-F., Khatib A.M., Delisle J-S., Seidah N.G. “Blockade of colon cancer metastasis via single and double silencing of PCSK7 / PCSK9: enhanced T-cells cytotoxicity in mouse and human” Journal for ImmunoTherapy of Cancer (in press) [IF=10.9]
  • Sachan V., Susan-Resiga D., Lam K., Seidah N.G. "The Biology and Clinical Implications of PCSK7". Endocrine Review 46:281–299, 2025 [IF=20.3] PMID: 39661471
  • Bergeron A.C., Wong-Chong E., Joncas F.H., Castonguay C., Calon F., Seidah N.G., Blais J., Robitaille K., Bergeron A., Fradet V., Gangloff A. “Lipid Profile, PCSK9, ANGPTL3 and Lipoprotein (a) Levels in Men Diagnosed With Localized High-Grade Prostate Cancer and Men At-Risk of Prostate Cancer.” Cancer Med. (3):e70587. [IF=3.4] PMID: 39888285
  • Ajoolabady A., Pratico D., Mazidi M., Davi I.G., Lip G.Y.H., Seidah N.G., Libby P., Kroemer G., Ren J. “PCSK9 in Metabolism and Diseases". Metabolism 163:156064, 2025 [IF=10.8] PMID: 39547595
  • Ongaro L., Zhou X., Wang Y., Zhou Z., Schultz H., Buddle E.R.S., Brûlé E., Lin Y-F., Schang G., Castonguay R., Su G.H., Seidah N.G., Ray J.C., Karp S.J., Boehm U., Lee S.J., Bernard D.J. "Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis". Science 387:329–336, 2025. [IF=47.7] PMID: 39818879
  • Moon S.H., Chung I., Yoon N.H., Jin J., Yoon W.K., Seidah N.G., Oh G.T. “Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a 2 therapeutic strategy to mitigate myocardial infarction-induced 3 inflammation”. Biochem. Mol. Biol. Reports 57:553-558, 2024 [IF = 3.9] PMID: 39622633
  • Prabhala P., Duval S., Evagelidis A., Le Dévéhat M., Sachan V., Seidah N.G. “Shedding of GPP130 by PC7 and Furin: implication in lung cancer progression”. Preprints (in press since November 13, 2024)
  • Platko K., Gyulay G., Lebeau P.F., MacDonald M.E., Lynn E.G., Byun J-H., Igdoura S.A., Holden R.M., Roubtsova A., Seidah N.G., Krepinsky J.C., Austin R.C. “Gdf10 is a negative regulator of vascular calcification”. J. Biol. Chem. 300:107805, 2024 [IF=5.5] PMID: 39307303
  • Mikaeeli S., Ben Djoudi Ouadda A., Evagelidis A., Essalmani R., Pereira Ramos O.H., Faraj M., Fruchart-Gaillard C., Seidah N.G. “Insights into PCSK9-LDLR regulation and trafficking via the differential functions of MHC-I proteins HFE and HLA-C”. Cells. 13(10), 857, 2024. [IF=6.0] PMID: 38786080
  • Hendrix S., Tan J.M.E., Ndoj K., Kingma J., Valiloo M., Zijlstra L.F., Ottenhof R., Seidah N.G., Loregger A., Kober D.L., Zelcer N. “SPRING is a dedicated licensing factor for SREBP-specific activation by S1P”. Mol. Cell. Biol. 44:123-137, 2024. [IF=5.1] PMID: 38747374
  • Sachan V., Le Dévéhat M., Roubtsova A., Essalmani R., Laurendeau J-F., Garçon D., Duval S., Hamelin J., Evagelidis A., Chong M., Paré G., Chernetsova E., Gao Z-H. Robillard I., Ruiz M., Estall J., Faraj M., Austin R.C., Sauvageau M., Prat A., Scott Kiss R.S., Seidah N.G. "PCSK7: a Novel Regulator of Apolipoprotein B and a Potential Target Against Non-Alcoholic Fatty Liver Disease". Metabolism: Clinical and Experimental. 150:155736, 2024 [IF=13.9] PMID: 37967646
  • Roubtsova A., Scipione C., Garçon D., Boffa M.B., Seidah N.G., Koschinsky M., Prat A. “Surface LDLR is a major receptor for lipoprotein(a) clearance in male mice lacking PCSK9”. BBA Molecular and Cell Biology of Lipids 25:159288, 2023 [IF=5.8] PMID: 36708961 DOI: 10.1016
  • Fruchart Gaillard C., Ben Djoudi Ouadda A., Ciccone L., Girard E., Mikaeeli S., Evagelidis A., Le Dévéhat M., Susan-Resiga D., Cassar Lajeunesse E., Nozach H., Pereira Ramos O., Thureau A., Legrand P., Prat A., Dive V., Seidah N.G. "Molecular interactions of PCSK9 with an inhibitory nanobody, CAP1 and HLA-C: functional regulation of LDLR levels". Molecular Metabolism 67:101662, 2023 [IF=8.6] PMID: 36566984
  • Roubtsova A., Lacoste S., Chamberland A., Garcon D., Marcinkiewicz E., Metivier R., Sotin T., Paquette M., Bernard S., Cariou B., Le May C., Koschinsky M.L., Seidah N.G., Prat A. “PCSK9 deficiency results in a specific shedding of excess LDLR in female mice only: role of hepatic cholesterol”. BBA Molecular and Cell Biology of Lipids 1867:159217, 2022 [IF=5.8] PMID: 35985474
  • Seidah N.G., Garçon D. “Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond”. Current Atherosclerosis Reports 29:1-10 [IF=6.0] PMID: 35904732
  • Seidah N.G., Prat A. “The multifaceted roles of PCSK9”. Endocrine Reviews 43(3):558–582, 2022. [IF=20.3] PMID: 34626468 - By invitation from Daniel Drucker
  • Selected as the Endocrine Reviews Featured Article on the week of December 13-19, 2021
  • Byun J.H., Lebeau P.F., Platko K., Carlisle R.E., Faiyaz M., Chen J., MacDonald M.E., Makda Y., Yousof T., Dickhout1 J.G., Krepinsky J.C., Prat A., Seidah N.G, Austin R.C. "Inhibitory antibodies against PCSK9 reduce surface CD36 and mitigate diet-induced renal lipotoxicity". Kidney360 3:1394-1410, 2022 [IF=10.6] PMID: 36176646 – Selected for Cover Page of August 2022
  • Essalmani R., Jain J., Susan-Resiga D., Andréo U., Evagelidis A., DerbaIi RM., Huynh D., Dallaire F., Laporte M., Delpal A., Sutto-Ortiz P., Coutard B., Mapa C., Wilcoxen K., Decroly E., Pham T., Cohen E.A, Seidah N.G. “Distinctive roles of Furin and TMPRSS2 in SARS-CoV-2 infectivity”. J. Virology 96:e0012822, 2022 [IF=5.1] PMID: 35343766 - BioRxiv https://www.biorxiv.org/content/10.1101/2020.12.18.423106v2
  • Susan-Resiga D., Girard E., Essalmani R., Roubtsova A., Marcinkiewicz J., Chamberland A., Derbali RM, Evagelidis A., Byun J.H., Lebeau P.F., Austin R.C., Seidah N.G. "Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by Furin". J. Chem. 297:101177, 2021 [IF=4.2] PMID: 34508778; BioRxiv 10.1101/2021.04.11.439364.
  • Seidah N.G., “The PCSK9 discovery, an inactive protease with varied functions in hypercholesterolemia, viral infections, and cancer”. J. Lipid Res. FH series. 62:100130, 2021. By invitation from Henry N. Ginsberg [IF=4.5] PMID: 34606887; https://doi.org/10.1016/j.jlr.2021.100130
  • Peyot M-L., Roubtsova A., Lussier R., Chamberland A., Essalmani, R., Madiraju M., Seidah N.G., Prentki M., Prat, A. “Substantial PCSK9 inactivation in b-cells does not modify glucose homeostasis or insulin secretion in mice”. BBA-Molecular and Cell Biology of Lipids 1866:158968, 2021 [IF=4.5] PMID: 33992809
  • Seidah N.G., Pasquato A., Andreo U. “How do enveloped viruses exploit the secretory proprotein convertases for infectivity and spread?” Viruses. Special Issue "In Memory of Stefan Kunz" 13:1229, 2021 [IF=5.8] PMID: 34202098
  • Seidah N.G., Antonella Pasquato, Ursula Andreo “How do enveloped viruses exploit the secretory proprotein convertases for infectivity and spread?” Viruses. Special Issue "In Memory of Stefan Kunz" [IF=3.8] PMID: 34202098
  • Seidah N.G., Antonella Pasquato, Ursula Andreo “How do enveloped viruses exploit the secretory proprotein convertases for infectivity and spread?” Special Issue "In Memory of Stefan Kunz". Viruses. 13:1229, 2021 [IF=3.8] PMID: 34202098 
  • Susan-Resiga D., Girard E., Essalmani R., Roubtsova A., Marcinkiewicz J., Chamberland A., Derbali RM, Evagelidis A., Lebeau P.F., Austin R.C., Seidah N.G.  "Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR that is shed by Furin". BioRxiv, 2021 https://biorxiv.org/cgi/content/short/2021.04.11.439364v1 doi: https://doi.org/10.1101/2021.04.11.439364
  • Bellamine A., Pham N.Q.T., Jain J., Wilson J., Sahin K., Dallaire F., Seidah N.G., Durkee S., Radošević K., Cohen E.A. “L-Carnitine Tartrate downregulates the ACE-2 receptor and limits SARS-CoV-2 infection”. Nutrients 13:1297, 2021 [IF=4.6] PMID: 33919991
  • Al Rifai O., Susan-Resiga D., Essalmani R., Creemers J.W.M., Seidah N.G., Ferron M. “Genetic analysis of the contribution of the proprotein convertases to the in vivo regulation of FGF23”. Front Endocrinol(Lausanne) 2021 Jun 4;12:690681 .doi: 10.3389/fendo.2021.690681 PMID: 3414962
  • Moradi A., Maleki M., Ghaemmaghami Z., Khajali Z., Moghadam M.H., Kalyinia S., Noohi F., Mowla S.J.,
  • Seidah N.G., Malakootian M. “Mutational spectrum of LDLR and PCSK9 genes Identified in Iranian Patients with Premature Coronary Artery Disease and Familial Hypercholesterolemia”. Frontiers in Genetics 2021 Feb 11;12:625959 https://doi.org/10.3389/fgene.2021.625959  [IF=3.8] PMID: 33732287 
  • Lebeau P., Wassef H., Byun J.H., Platko K., Ménard J., Ason B., Jackson S., Dobroff J., Shetterly S., Richards W.G., Al-Hashimi A.A., Donyoon Won K., Mbikay M., Prat A., Tang A., Paré G., Pasqualini R., Seidah N.G., Arap W., Chretien M., Austin R.C. “The loss-of-function PCSK9-Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury”. J. Clin. Invest. 131:e128650, 2021 [IF=12.3] PMID: 33211673
  • Essalmani R., Jain J., Susan-Resiga D., Andréo U.,Evagelidis A., DerbaIi RM., Huynh D., Dallaire F., Laporte M., Delpal A., Sutto-Ortiz P., Coutard B., Mapa C., Wilcoxen K., Decroly E., Pham T., Cohen E.A, 
  • Seidah N.G. “Implications of Spike-glycoprotein processing at S1/S2 by Furin, at S2’ by Furin and/or TMPRSS2 and shedding of ACE2: cell-to-cell fusion, cell entry and infectivity of SARS-CoV-2”. BioRxiv, 2021  https://www.biorxiv.org/content/10.1101/2020.12.18.423106v1 doi: https://doi.org/10.1101/2020.12.18.423106
  • Duval S., Abu-Thuraia A., Elkholi I.E., Chen R., Seebun D., Mayne J., Côté J.-F., Figeys D., Seidah N.G. “Shedding of Cancer Susceptibility Candidate 4 (CASC4) by the Convertases PC7/Furin Unravels a Novel Secretory Protein Implicated in Cancer Progression.” Cell Death & Disease 11:665-, 2020 [IF=6.0] PMID: 32820145
  • Gan E.S., Tan H.C., Le, D.H.T., Huynh T.T., Wills B., Seidah N.G.  Ooi E.E., Yacoub S. “Dengue Virus Induces PCSK9 Expression to Alter Antiviral Responses and Disease Outcomes”. J. Clin. Invest. 31:137536, 2020 [IF=12.3] PMID: 32644974
  • Garcon D., Moreau F., Ayer A., Dijk W., Prieur X., Roubtsova A., Seidah N.G., Prat A., Cariou B., Le May C. “Circulating rather than intestinal PCSK9 regulates postprandial lipemia in mice.” Atherosclerosis, Thrombosis and Vascular Biology 40:2084-2094, 2020 [IF=6.6] PMID: 32673528
  • Löw K., Ducrest A.L., San-Jose L.M., Simon C., Uva V., Seidah N.G., Pasquato A., Kunz S., Roulin A.  “Molecular evolution of the proopiomelanocortin system in Barn owl species”. PLOS ONE 15:e0231163, 2020 [IF=2.8] PMID: 32369484
  • Coutard B., Valle C., de Lamballerie X., Canard B., Seidah N.G., Decroly E. “The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade”. Antiviral Research 176:104742, 2020 [IF=4.9] PMID: 32057769 
  • Paquette M., Gauthier D., Chamberland A., Prat A., De Lucia Rolfe E., Rasmussen J., Kaduka L., Seidah N.G., Bernard S., Christensen D., Baass A. “Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis”. Clin. Biochem. 77:20-25, 2020 [IF=2.6] PMID: 31972148
  • Durand L., Duval S., Evagelidis A., Guillemot J., Dianati V., Sikorska E., Schu P., Day R., Seidah N.G. “The motif ExExxxL in the cytosolic tail of the secretory human proprotein convertase PC7 regulates its trafficking and cleavage activity”. J. Biol. Chem 295:2068-2083, 2020 [IF=4.0] PMID: 31915245
  • Mikaeeli S., Susan-Resiga S., Girard E., Ben Djoudi Ouadda A., Day R., Prost S., Seidah N.G. “Functional analysis of natural PCSK9 mutants in modern and archaic humans”. FEBS J. 287:515-528, 2020 [IF=4.7] PMID: 31386798
  • Ibrahim N.S., Lazaris A., Petrillo S., Huck L., Essalmani R., Gao Z-U., Seidah N.G., Hussain S., Metrakos P. “Angiopoietin1 maintains vessel co-option and mediates resistance to anti-angiogenic drug in colorectal cancer liver metastasis”. Cancers 20; 12(1). pii: E35, 2020 [IF=6.2] PMID: 31877668
  • Ashraf Y., Duval S., Sachan V., Essalmani R., Susan-Resiga D., Gerhardy S., Kirchhofer D., Tagliabracci V.S., Prat A., Kiss R.S., Seidah N.G. “Proprotein Convertase 7 (PCSK7) Reduces apoA-V Levels”. FEBS J. 287:3565–3578, 2020 [IF=4.7] PMID: 31945259
  • Chong M., Yoon G., Susan Resiga D., Cheillan D., Pare G., Seidah N.G. “Hypolipidemia among PMM2-CDG patients is associated with low circulating PCSK9 levels: a case report followed by observational and experimental studies”. J. Med Genet. 57:11-17, 2020 [IF=5.8] PMID: 31391289 
  • Lebeau P.F., Byun J.H., Al-Hashimi A. A, Platko K., Lhoták S., MacDonald M., Mejia-Benitez A., Prat A., Igdoura S. A, Trigatti B., Seidah N.G., Austin R. C. PCSK9 knockout exacerbates diet-induced non-alcoholic steatohepatitis, fibrosis and liver injury in mice. J Hepatology Report 1: 418-429 2019, 2019 [IF>7] PMID: 32039393 DOI: 10.1016/j.jhepr.2019.10.009 
  • Ben Djoudi Ouadda A., Gauthier M.-S., Susan-Resiga D., Girard E., Essalmani R., Black M., Marcinkiewicz J., Hamelin J., Evagelidis A., Forget D., Ly K., Day R., Galarneau L., Corbin F., Coulombe B., Çaku A., Tagliabracci V.S., Seidah N.G. "Ser-Phosphorylation of PCSK9 by Fam20C-Kinase Enhances its Ability to Degrade the LDLR". Arteriosclerosis, Thrombosis and Vascular Biology 39:1996-2013, 2019 [IF=6.6] PMID: 31553664
  • Löw K., Hardes K., Fedeli C., Seidah N.G., Constam D., Pasquato A., Steinmetzer T., Roulin A., Kunz S. “A novel cell-based sensor detecting the activity of individual basic proprotein convertases”. FEBS J. 286:4597-4620, 2019 [IF=4.7] PMID: 31276291
  • Lebeau P., ByunJ-H., Platko K., MacDonald M.E., Poon S., Faiyaz M., Seidah N.G., Austin R.C. “Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducing de novo PCSK9 expression in mice”. J Biol Chem 294:9037-9047, 2019 [IF=4.0] PMID: 31004037
  • Seidah N.G. "The Elusive Inhibitory Function of the Acidic N-terminal Segment of the Prodomain of PCSK9: the Plot Thickens". J. Mol. Biol. 431:904-907 [IF=4.9] PMID: 30658056
  • Sachan V., Lodge R., Mihara K., Hamelin J., Power C., Gelman B.B., Hollenberg M.D., Cohen E.A., Seidah N.G. “HIV-induced neuroinflammation: Impact of PAR1 and PAR2 processing by Furin”. Cell Death and Differentiation 26:1942-1954, 2019 [IF=8.3] PMID: 30683917
  • Seidah N.G., Prat A., Pirillo A., Catapano A.L., Norata G.D., “Novel strategies to target PCSK9: beyond monoclonal antibodies.”. Cardiovascular Res. 115:510-518, 2019 [IF=6.3] PMID: 30629143
  • Brumpton B.M., Fritsche L.G., Zheng J., Nielsen J.B., Mannila M., Surakka I., Rasheed H., Åberge Vie G., Graham S., Elvestad Gabrielsen M., Laugsand L.E., Aukrust P., Vatten L.J., Damås J.K., Ueland T., Janszky I., Zwart J-A., INVENT, van´t Hooft F.M., Seidah N.G., Hveem K., Willer C., Smith G.D., Åsvold B.O. “Variation in serum PCSK9, cardiovascular disease risk and potential unanticipated effects of PCSK9 inhibition: A GWAS and Mendelian randomization study in the HUNT Study, Norway”. Circ. Genomics and Precision Medicine 12:e002335, 2019 [IF=23] PMID: 30645169
     

Roles of proproptein convertases in health an disease

Functional profiling

Each convertase and its inhibitors/silencers are tested in cells and animal models and finally in human patients.

Biochemistry and Genomics

The mechanism of action of each convertase and the identification of physiological and pathological substrates and/or targets in disease states.

Disease modeling

Use mouse KO and transgenics and human SNPs and variants as guides to functional significance of each convertase and potential treatments in a clinical setting.

Important Discoveries

2025

Blockade of colon cancer metastasis via single and double silencing of PCSK7 / PCSK9: enhanced T-cells cytotoxicity in mouse and human

2025

The Biology and Clinical Implications of PCSK7

2024

Insights into PCSK9-LDLR regulation and trafficking via the differential functions of MHC-I proteins HFE and HLA-C

2024

PCSK7: a Novel Regulator of Apolipoprotein B and a Potential Target Against Non-Alcoholic Fatty Liver Disease

2023

Molecular interactions of PCSK9 with an inhibitory nanobody, CAP1 and HLA-C: functional regulation of LDLR levels

2022

PCSK9 deficiency results in a specific shedding of excess LDLR in female mice only: role of hepatic cholesterol

2022

Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond

2022

The multifaceted roles of PCSK9

2022

Distinctive roles of Furin and TMPRSS2 in SARS-CoV-2 infectivity

2021

Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by Furin

2021

Substantial PCSK9 inactivation in β-cells does not modify glucose homeostasis or insulin secretion in mice - PubMed (nih.gov)

2021

How do enveloped viruses exploit the secretory proprotein convertases for infectivity and spread? - PubMed (nih.gov)

2020

Shedding of cancer susceptibility candidate 4 by the convertases PC7/furin unravels a novel secretory protein implicated in cancer progression - PubMed (nih.gov)

2020

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade - PubMed (nih.gov)

2019

Ser-Phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C (Family With Sequence Similarity 20, Member C) Kinase Enhances Its Ability to Degrade the LDLR (Low-Density Lipoprotein Receptor) - PubMed (nih.gov)

2017

The Proprotein Convertases in Hypercholesterolemia and Cardiovascular Diseases: Emphasis on Proprotein Convertase Subtilisin/Kexin 9 - PubMed (nih.gov)

2003

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia - PubMed (nih.gov)

2003

The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation - PubMed (nih.gov)

Tools

The multifaceted biology of PCSK9

How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread? - PubMed (nih.gov)

The Proprotein Convertases in Hypercholesterolemia and Cardiovascular Diseases: Emphasis on Proprotein Convertase Subtilisin/Kexin 9 - PubMed (nih.gov)

Implications of Spike-glycoprotein processing at S1/S2 by Furin, at S2’ by Furin and/or TMPRSS2 and shedding of ACE2: cell-to-cell fusion, cell entry and infectivity of SARSCoV- 2

Furin cleaves SARS-CoV-2 spike-glycoprotein at S1/S2 and S2’ for viral fusion/entry: indirect role of TMPRSS2 | bioRxiv

The biology and therapeutic targeting of the proprotein convertases - PubMed (nih.gov)

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia - PubMed (nih.gov)

The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation - PubMed (nih.gov)
 
Press review
Press review
Grants

CIHR (Grant Projet) #191678
The unique and complementary functions of PCSK7 and PCSK9 in cardiometabolic health and disease
PI: Nabil G. Seidah
Annual:244,800 $ - Total amount: 1,224,000$
Period: 01/04/ 2024 to 31/03/2029

CQDM#SYN-366
Therapeutic potential of PCSK7 inhibitors in the development of liver metastases
PI: Nabil G. Seidah
Annual: 431,838,67$ - Total amount: 647,758$
Period: 01/04/2024 to 30/06/2025

CIHR (Foundation Scheme Grant) #148363
The proprotein convertase and their partners in health and disease
07/2016 to 06/2023

CANADA RESEARCH CHAIR HOLDER: 950-231335
The Proprotein Convertases and their Relationship to Health and Disease
03/2017 to 02/2024

CIHR Team Grant # HAL 157986: 
Canadian HIV-Ageing Multidisciplinary Programmatic Strategy (CHAMPS) in NeuroHIV
Program HIV/AIDS and co-morbidities: Towards a transformative understanding of HAND (HIV-Associated Neurocognitive Disorders)
04/18 to 03/23

CIHR Project Grant 
PCSK9, a novel contributor to the development of castration resistant prostate cancer
04/2019 to 02/2022

Économie, Sciences et Innovation Québec (PSO2/PSO3)
PC7 ASOs as regulators of NAFLD
2019 to 2022

CIHR Project Grant
Retention of PCSK9 in the endoplasmic reticulum acts as a co-chaperone to protect against liver injury/dysfunction
03/2020 to 03/2025
 
Recognitions and honors
  • 2025 “Lifetime Career Award” - Recherche – Volet Fondamental / Ensemble de carrière, University of Montréal, Department of Medicine, for a career in Fundamental Biomedical Sciences
  • 2024 UdeM: congratulation letter from the Vice-Dean of Medical Faculty on being ranked first for the CIHR grant. Project Title: The unique and complementary functions of PCSK7 and PCSK9 in cardiometabolic health and disease
  • 2023 J. Allyn Taylor International Prize in Medicine: Biotherapeutics for Cardiovascular Disease. https://www.robarts.ca/taylor_prize/index.html
  • 2023 Biology and Biochemistry in Canada Leader Award:  https://research.com/u/nabil-g-seidah 
  • 2023  “Bravo Recherche” Distinction from Dean of Medical Faculty of the University of Montreal selected distinguished research lab with a UdeM supported Canada Chair. 4th May 2023. https://distinctions.umontreal.ca/luniversite-honore/bravo-recherche/
  • 2023 UdeM: congratulation letter from the Dean of Medical Faculty for discovering the molecular mechanism by which a key protein regulates LDL cholesterol
  • 2023 Elected “Lifetime Member” of the International Proteolysis Society (IPS)
  • 2021 Kuwait Prize-2021 (KFAS) for Applied and Basic Science
  • 2021 Fellow of the Canadian Academy of Health Sciences (FCAHS)
  • 2019 McGill University Louis and Artur Lucian Award for Research in Circulatory Diseases
  • 2018 Lefoulon DeLalande Award of Institut de France: Research & Innovation in Cardiovascular Disease
  • 2018 Akira Endo Award: Major Contribution in the Development of Treatments to Prevent Atherosclerosis
  • 2016 CIHR (ICRH) Distinguished Lecturer Award in Cardiovascular Sciences
  • 2015 Anne and Neil McArthur Research Award
  • 2014 Jacques Genest Award from the Canadian Society of Endocrinology & Metabolism 
  • 2013 Simon Pierre-Noël Memorial Lecture Award in Lipid Research 
  • 2013 Queen Elizabeth II Diamond Jubilee Medal
  • 2011 Wilder-Penfield Prize in Biomedical Research in Québec
  • 2009 Pfizer Distinguished Cardiovascular-Metabolic Research Jean-Davignon Award 
  • 2003-2024 Canada Chair Tier 1 in Precursor Proteolysis
  • 2001 McLaughlin Medal of the Royal Society of Canada
  • 2001 Prize: Léo-Parizeau ACFAS 
  • 1999 Member, Order of Canada 
  • 1999 Medal of Honor, PMAC Health Research Foundation 
  • 1997 Officer, Order of Québec 
  • 1995 MRC Distinguished Scientist Award 
  • 1994 Manning Award of Distinction 
  • 1991 Fellow of the Royal Society of Canada 
  • 1983 Marcel Piché Award, Montreal 
  • 1977 The Clarke Institute of Psychiatry Award, Toronto
     

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