The Montreal Clinical Research Institute’s (IRCM) biochemical neuroendocrinology unit, led by Dr. Nabil G. Seidah, is seeking a highly motivated Postdoctoral Researcher to join our dynamic team. This position will explore the biology and clinical applications of proprotein convertases (PCs) in cancer/metastasis, cardiovascular diseases, and other pathologies.
Our team investigates a family of nine mammalian protein convertases (PCs): PC1, PC2, Furin, PC4, PC5, PACE4, PCSK7, SKI-1, and PCSK9. These enzymes play critical roles in the activation/inactivation of hormone precursors, growth factors, receptors, and envelope proteins for pathogenic agents. Our focus is on the mechanisms of activation and regulation of these enzymes, exploring their in vivo physiological roles in cells, mice, and humans, and identifying their substrates and potential inhibitors.
Key areas of research include
- Investigating the role of PCSK7 and PCSK9 in cancer metastasis and other pathologies.
- Investigating PCSK9’s clinical applications, particularly its role in hypercholesterolemia and its therapeutic potential for treating cancer, metastasis, and fibrosis and liver disease.
- Exploring the newly identified role of PCSK7 in triglyceride regulation and fatty liver disease, with an emphasis on antisense oligonucleotide therapies and MASLD treatment.
- Expanding our work on PCSK9 and PCSK7’s roles in cardiovascular and cardiometabolic diseases as well as in other pathologies.
Our laboratory is equipped with a unique collection of PCSK mutants, including complete and/or conditional knockouts in mice for PCSK5, Furin, PCSK7, and PCSK9. Our research spans a broad range of techniques, including protein and peptide biochemistry, enzymology, molecular and cell biology, proteomics, transcriptomics, and genetics. The team’s efforts have resulted in significant breakthroughs, including the development of anti-PCSK9 treatments for familial hypercholesterolemia, the identification of PCSK7’s role in triglyceride regulation, and preclinical validation for treatments of Metabolic dysfunction associated steatotic liver disease (MASLD) and other pathologies such the regulation of immune checkpoint proteins implicated in cancer/metastasis.
The position offers
- A stimulating scientific environment in the heart of Montreal, in the Canadian province of Quebec. IRCM is a world-renowned clinical research institute bringing together multidisciplinary researchers from across the globe.
- The opportunity to contribute to cutting-edge biomedical research, technological innovation, and career development in an exciting, collaborative atmosphere.
Key publications from our laboratory
- Sachan V., Susan-Resiga D., Lam K., Seidah N.G. "The Biology and Clinical Implications of PCSK7". Endocrine Review 46:281-299, March 2025 [IF=20.3]
- Sachan V., Le Dévéhat M., Roubtsova A., Essalmani R., Laurendeau J.F., Garçon D., Susan-Resiga D., Duval S., Mikaeeli S., Hamelin J., Evagelidis A., Chong M., Paré G., Chernetsova E., Gao Z.-H., Robillard I., Ruiz M., Trinh V.Q.-H., Estall J.L., Faraj M., Austin R.C., Sauvageau M., Prat A., Kiss R.S., Seidah N.G. “PCSK7: A Novel Regulator of Apolipoprotein B and a Potential Target Against Non-Alcoholic Fatty Liver Disease”. Metabolism 150:155736, January 2024
- Seidah N.G., Prat A. “The multifaceted roles of PCSK9”. Endocrine Reviews 43(3):558–582, 2022.
- Seidah N.G., Benjannet S., Wickham L., Marcinkiewicz J., Chamberland A., Jasmin S.B., Stifani S., Basak A., Prat A. and Chrétien M. “The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation”. PNAS, 100:928-33, 2003. # Citations > 1500.
- Abifadel M., Varret M., Rabès J-P., Allard D., Ouguerram K., Devillers M., Cruaud C., Benjannet S., Wickham L., Erlich D., Derré A., Villéger L., Farnier M., Beucler I., Bruckert E., Chambaz J., Chanu B., Lecerf J-M., Luc G., Moulin P., Weissenbach J., Krempf M., Prat A., Junien C., Seidah N.G. and Boileau C. “Mutations in PCSK9 cause autosomal dominant hypercholesterolemia”. Nat Genet. 34: 154-156, 2003. # Citations > 3700.
Learn more about our research and publications at: Nabil Seidah.
Summary of responsibilities
We have recently identified the critical roles of PCSK7 and PCSK9 in regulating liver steatosis and cancer metastasis, linking these two convertases with the inflammation and the immune system. The candidate will continue this work to identify the molecular mechanisms involved with the aim of developing therapies targeting the two convertases.
The project aims to investigate the roles of PCSK7 and PCSK9 in tumor progression of solid cancers, two members of a 9-membered proprotein convertase subtilisin-kexin family (PCSKs), focusing on their molecular mechanisms and potential as therapeutic targets. We have recently identified a novel critical role of PCSK7 in anti-tumoral immune response by regulating expression levels of diverse immune checkpoint proteins (ICPs) on T-lymphocytes, responsible for T-cell dysfunction/exhaustion. ICPs are short-lived cell surface proteins expressed in immune cells that bind to partners proteins/receptors found in antigen presenting cells (APC) or tumor cells. This binding prevents the activation and cytotoxic activity of immune cells.
Additionally, PCSK9 has been implicated in modulating CD8+ T-cells activation via the degradation of major histocompatibility complex I (MHC-I) responsible for antigen presentation by APC or tumor cells, and the increased signalling of the T-cell receptor (TCR)/LDLR receptor complex.
Indeed, these convertases may influence T cell activation, differentiation, and immune surveillance mechanisms, which are critical in the context of tumor immunity. We reported synergistic and complementary functions of both convertases since their loss reduced the development of liver metastasis in colorectal cancer by >90% compared to ~50% in single knock-out in mice.
Understanding their roles in regulating the balance between immune tolerance and activation will be key to identifying novel immunotherapeutic strategies.
The candidate will participate in this work to identify the cellular and molecular mechanisms by which PCSK7 and PCSK9 are involved in the regulation of T-cell activation with the aim of developing new therapies targeting the two convertases in cancer/metastasis of various tumors.
The candidate will utilize a range of cellular and molecular biology techniques to elucidate the functions of these PCSKs in cancer development and immune regulation. Preferentially, the candidate should have experience and/or willing to master essential methods such as gene editing (CRISPR-Cas9), RNA interference, cell culture, flow cytometry, immunoprecipitation, immunoblotting, advanced microscopy techniques and the use of genetically engineered mouse models. The project will also involve transcriptomic and proteomic analyses to study gene expression profiles, post-translational modifications, and protein-protein interactions related to PCSK7 and PCSK9.
Expertise in immuno-oncology, mouse handling and surgery will be highly valued.
Additionally the candidate should:
- Participate in writing scientific articles and presenting findings at national/international conferences.
- Conduct experiments using cellular and animal models to study biological and pathological mechanisms.
- Contribute to laboratory meetings and knowledge exchange within the team.
Financial support and duration of contract
- The salary is to be discussed.
- The contract duration is negotiable with the research director.
Qualifications required
PhD in Biochemistry, Molecular and Cellular Biology, or a related field (obtained within the last 2 years):
- At least two manuscripts published or in preparation (e.g., bioRxiv, MedRxiv) as first author.
- Experience in handling mice is an asset.
- Independence, critical thinking, and productivity in laboratory experiments. The candidate is expected to be up to date with the scientific literature and come up with novel research hypotheses.
- Excellent written and oral communication skills.
- Ability to work collaboratively within a team and manage research projects efficiently.
- Fluency in English is required; knowledge of French is an asset.
How to apply
Please send your CV, a cover letter, and contact details for three references to Dr. Nabil G. Seidah at seidahn@ircm.qc.ca and a copy to Jisca Borgela at jisca.borgela@ircm.qc.ca
The IRCM at a glance
The IRCM is located near downtown Montreal and the “Plateau Mont-Royal”. The IRCM is an autonomous, not-for-profit research institution, affiliated with the Université de Montréal and associated with McGill University. Located in the heart of Montreal's academic community, the IRCM attracts the best researchers. Every year, more than a hundred master's and doctoral students, as well as some fifty postdoctoral fellows, supervised by experienced researchers in various fields of biomedical research, come to improve and/or polish their scientific training at the Institute.
The training of students, trainees and employees is an integral mission of IRCM and of Seidah Laboratory, and we aim to attract and retain the best scientists. IRCM's Code of Collegial Conduct clearly specifies that respect for people and gender equality is a core value of our institution, and we recognize diversity as a strength and a source of richness. IRCM and the Seidah Laboratory strives to provide an environment that promotes and supports the inclusion and fair representation of women, members of the LGBTQ+ community, people living with disabilities and people from ethnic, cultural, and religious minorities.
