Présentation

Sujets de recherche

Antivirals, Cancer Diagnosis and Detection, Cardiovascular Diseases, Infectious Diseases.

Disciplines de recherche

Pharmacology.

Mots-clés

Biochemistry/Enzymes, Cell biology, Infectious diseases, Influenza virus, Molecular biology, Neuropeptides, Pharmacology, Proprotein convertases, Prostate Cancer, Proteomics.

Intérêts de recherche

Precursor proteins of the secretory pathways are activated via a catalytic cleavage mediated by the proprotein convertases. The proprotein convertases are now regarded as a choice target in various diseases, such as cancer and infectious diseases. Our interest is to develop selective inhibitors for each convertase.

Centre de recherche

Centre de recherche du CHUS

Langues parlées et écrites

Anglais, Français

Prix et distinctions

• (2010) Prix Étienne-Le Bel. (Distinction).
• (2010) Prix Rayonnement. (Distinction).

Publications

Articles de revue

• Duhamel M, Rodet F, Delhem N, Vanden Abeele F, Kobeissy F, Nataf S, Pays L, Desjardins R, Gagnon H, Wisztorski M, Fournier I, Day R, Salzet M. (2015). Molecular consequences of proprotein convertase 1/3 inhibition in macrophages for application to cancer immunotherapy: a proteomic study. Mol Cell Proteomics, (In Press).
• Couture F, Ly K, Levesque C, Kwiatkowska A, Ait-Mohand S, Desjardins R, Guérin B, Day R. (2015). Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity. Biomed Res Int, 2015, 824014.
• Couture F, Kwiatkowska A, Dory Y, Day R. (2015). Therapeutic uses of furin and its inhibitors: a patent review. Expert Opinion on Therapeutic Patents, 7, 1-18.
• Semaan W, Desbiens L, Houde M, Labonté J, Gagnon H, Yamamoto D, Takai S, Laidlaw T, Bkaily G, Schwertani A, Pejler G, Levesque C, Desjardins R, Day R, D'Orléans-Juste P. (2015). Chymase inhibitor-sensitive synthesis of endothelin-1 (1-31) by recombinant mouse mast cell protease 4 and human chymase. Biochem Pharmacol, 94(2), 91-100.
• Quanico J, Franck J, Gimeno JP, Sabbagh R, Salzet M, Day R, Fournier I. (2015). Parafilm-assisted microdissection: a sampling method for mass spectrometry-based identification of differentially expressed prostate cancer protein biomarkers. Chem Commun (Camb), 51(22), 4564-7.
• Levesque C, Couture F, Kwiatkowska A, Desjardins R, Guérin B, Neugebauer WA, Day R. (2015). PACE4 inhibitors and their peptidomimetic analogs block prostate cancer tumor progression through quiescence induction, increased apoptosis and impaired neovascularisation. Oncotarget, 6(6), 3680-93.
• Kara I, Poggi M, Bonardo B, Govers R1, Landrier JF, Tian S, Leibiger I, Day R, Creemers JW, Peiretti F. (2015). The paired basic amino acid-cleaving enzyme 4 (PACE4) is involved in the maturation of insulin receptor isoform B: an opportunity to reduce the specific insulin receptor-dependent effects of insulin-like growth factor 2 (IGF2). J Biol Chem, 290(5), 2812-21.
• F. Couture, C. Levesque, V. Dumulon-Perreault, S. Ait-Mohand, F. D’Anjou, R. Day, B. Guérin. (2014). PACE4-Based Molecular Targeting of Prostate Cancer Using an Engineered 64Cu-Radiolabeled Peptide Inhibitor. Neoplasia, 16, 634-643.
• Ly K, Saavedra YG, Canuel M, Routhier S, Desjardins R, Hamelin J, Mayne J, Lazure C, Seidah NG, Day R. (2014). Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9. J Biol Chem, 289, 17732-46.
• R. Longuespée, C. Tastet, A. Desmons, O. Kerdraon, R. Day, I. Fournier, Michel Salzet. (2014). HFIP extraction followed by 2D CTAB-SDS PAGE separation: A new procedure for protein identification from tissue sections after MALDI mass spectrometry profiling for personalized medicine research. OMICS, 18, 374-384.
• R. Longuespée, F. Couture, C. Levesque, A. Kwiatkowska, R. Desjardins, S. Gagnon, D. Vergara, M. Maffia, I. Fournier, M. Salzet, R. Day. (2014). Implications of Proprotein Convertases in Ovarian Cancer Cell Proliferation and Tumor Progression: Insights for PACE4 as a Therapeutic Target. Translational Oncology, 7(3), 410-419.
• D'Anjou F , Couture F , Desjardins R , Day R. (2014). Knockdown strategies for the study of proprotein convertases and proliferation in prostate cancer cells. Methods Mol Biol, 1103, 67-82.
• Wetsel WC , Rodriguiz RM , Guillemot J , Rousselet E , Essalmani R , Kim IH , Bryant JC , Marcinkiewicz J , Desjardins R , Day R , Constam DB , Prat A , Seidah NG. (2013). Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. Proc Natl Acad Sci U S A, 110(43), 17362-7.
• Kay P , Wagner RJ , Gagnon H , Day R , Klarskov K. (2013). Modification of Peptide and Protein Cysteine Thiol Groups by Conjugation with a Degradation Product of Ascorbate. Chem Res Toxicol, 26(9), 1333-9.
• Franck J , Quanico J , Wisztorski M , Day R , Salzet M , Fournier I. (2013). Quantification Based Mass Spectrometry Imaging of Proteins by Parafilm Assisted Microdissection. Anal Chem, 85(17), 8127-34.
• Longuespée R , Gagnon H , Boyon C , Strupat K , Dauly C , Kerdraon O , Ighodaro A , Desmons A , Dupuis J , Wisztorski M , Vinatier D , Fournier I , Day R , Salzet M. (2013). Proteomic analyses of serous and endometrioid epithelial ovarian cancers: cases studies :molecular insights of a possible histological etiology of serous ovarian cancer. Proteomics Clin Appl, 7(5-6), 337-54.
• Quanico J , Franck J , Dauly C , Strupat K , Dupuy J , Day R , Salzet M , Fournier I , Wisztorski M. (2013). Development of liquid microjunction extraction strategy for improving protein identification from tissue sections. J Proteomics, 79, 200-18.
• Gagnon H , Refaie S , Gagnon S , Desjardins R , Salzet M , Day R. (2013). Proprotein Convertase 1/3 (PC1/3) in the Rat Alveolar Macrophage Cell Line NR8383: Localization, Trafficking and Effects on Cytokine Secretion. PloS One, 8(4), e61557.
• Sun X , Essalmani R , Day R , Khatib AM , Seidah NG , Prat A. (2012). Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver. Neoplasia (New York, N.Y.), 14(12), 1122-31.
• Saavedra YG , Day R , Seidah NG. (2012). The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. The Journal of biological chemistry, 287(52), 43492-501.
• Levesque C , Fugère M , Kwiatkowska A , Couture F , Desjardins R , Routhier S , Moussette P , Prahl A , Lammek B , Appel JR , Houghten RA , D'Anjou F , Dory YL , Neugebauer W , Day R. (2012). The Multi-Leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells. Journal of medicinal chemistry, 55(23), 10501-11.
• Couture F , D'Anjou F , Desjardins R , Boudreau F , Day R. (2012). Role of proprotein convertases in prostate cancer progression. Neoplasia (New York, N.Y.), 14(11), 1032-42.
• Gagnon H , Franck J , Wisztorski M , Day R , Fournier I , Salzet M. (2012). Targeted mass spectrometry imaging: specific targeting mass spectrometry imaging technologies from history to perspective. Prog Histochem Cytochem, 47(3), 133-74.
• Longuespée R , Boyon C , Castellier C , Jacquet A , Desmons A , Kerdraon O , Vinatier D , Fournier I , Day R , Salzet M. (2012). The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling. Histochemistry and cell biology, 138(1), 141-54.
• Becker GL , Lu Y , Hardes K , Strehlow B , Levesque C , Lindberg I , Sandvig K , Bakowsky U , Day R , Garten W , Steinmetzer T. (2012). Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases. The Journal of biological chemistry, 287(26), 21992-2003.
• Longuespée R , Boyon C , Desmons A , Vinatier D , Leblanc E , Farré I , Wisztorski M , Ly K , D'Anjou F , Day R , Fournier I , Salzet M. (2012). Ovarian cancer molecular pathology. Cancer metastasis reviews, 31(3-4), 713-32.
• Refaie S , Gagnon S , Gagnon H , Desjardins R , D'Anjou F , D'Orléans-Juste P , Zhu X , Steiner DF , Seidah NG , Lazure C , Salzet M , Day R. (2012). Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion. The Journal of biological chemistry, 287(18), 14703-17.
• Couture F , D'Anjou F , Day R. (2011). On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications. Biomolecular concepts, 2(5), 421-438.
• Susan-Resiga D , Essalmani R , Hamelin J , Asselin MC , Benjannet S , Chamberland A , Day R , Szumska D , Constam D , Bhattacharya S , Prat A , Seidah NG. (2011). Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10. The Journal of biological chemistry, 286(26), 22785-94.
• Bonnel D , Longuespee R , Franck J , Roudbaraki M , Gosset P , Day R , Salzet M , Fournier I. (2011). Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: application to prostate cancer. Analytical and bioanalytical chemistry, 401(1), 149-65.
• D'Anjou F , Routhier S , Perreault JP , Latil A , Bonnel D , Fournier I , Salzet M , Day R. (2011). Molecular Validation of PACE4 as a Target in Prostate Cancer. Translational oncology, 4(3), 157-72.
• Bournival V , Desjardins R , Campbell S , Roberge C , Doueik A , Gendron L , Payet MD , Gallo-Payet N , Day R , Praud JP. (2011). Presence of task-1 channel in the laryngeal mucosa in the newborn lamb. Experimental lung research, 37(4), 205-11.
• Lei X , Shi F , Basu D , Huq A , Routhier S , Day R , Jin W. (2011). Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity. The Journal of biological chemistry, 286(18), 15747-56.
• Wardman JH , Zhang X , Gagnon S , Castro LM , Zhu X , Steiner DF , Day R , Fricker LD. (2010). Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics. Journal of neurochemistry, 114(1), 215-25.
• El Ayed M , Bonnel D , Longuespée R , Castelier C , Franck J , Vergara D , Desmons A , Tasiemski A , Kenani A , Vinatier D , Day R , Fournier I , Salzet M. (2010). MALDI imaging mass spectrometry in ovarian cancer for tracking, identifying, and validating biomarkers. Medical science monitor : international medical journal of experimental and clinical research, 16(8), BR233-45.
• Becker GL , Sielaff F , Than ME , Lindberg I , Routhier S , Day R , Lu Y , Garten W , Steinmetzer T. (2010). Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. Journal of medicinal chemistry, 53(3), 1067-75.
• Remacle AG , Gawlik K , Golubkov VS , Cadwell GW , Liddington RC , Cieplak P , Millis SZ , Desjardins R , Routhier S , Yuan XW , Neugebauer WA , Day R , Strongin AY. (2010). Selective and potent furin inhibitors protect cells from anthrax without significant toxicity. The international journal of biochemistry & cell biology, 42(6), 987-95.
• Stauber J , El Ayed M , Wisztorski M , Day R , Fournier I , Salzet M. (2009). Polymerase chain reaction and immunoassay--matrix assisted laser desorption mass spectrometry using tag-mass technology: new tools to break down quantification limits and multiplexes. Analytical chemistry, 81(22),

Chapitres de livre

• (2012). Knockdown strategies for the study of proprotein convertases and proliferation in prostate cancer cells. Therapeutic Applications of Ribozymes and Riboswitches: Methods and Protocols Springer Science+Business Media. (Submitted).
• (2012). MALDI-MSI and ovarian cancer biomarkers. Advances in Cancer Management InTech. (Published).
• (2010). Design, synthesis and stability studies of potent inhibitors of pro-protein convertases (PCs). J Peptide Science (16, (S1), P374-314). Peptides 2010, Proc 31st European Peptide Symposium. (Published).
• (2010). Solid-phase synthesis C-terminus chloromethyl ketone peptides. J Peptide Science (16, (S1), P024-199). Peptides 2010, Proc 31st European Peptide Symposium. (Published).
• (2010). Solid-phase synthesis substituted peptide amides on aryl hydrazine resin. J Peptide Science (16, (S1), P023-198). Peptides 2010, Proc 31st European Peptide Symposium. (Published).
• (2009). Proopiomelanocortin. Encyclopedia of Neuroscience (3rd ed) (7:1139-41). Oxford: Academic Press. (Published).
• (2008). Furin. Encyclopedia of Cancer, 2nd Edition Springer, Berlin-Heidelberg-New York. (Published).

Articles de conférence

• (2012). Development of new anti-prostate cancer agents through SAR studies of potent PACE4 inhibitor (ML peptide). 32ND European Peptide Symposium 2012, Megaron, Athens, Greece. (Accepted).
• (2012). Development of small molecule inhibitors of PCSK9 by SP-SPCL and rational design. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2012). Multi-Leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2012). Role of proprotein convertases (PCs) in prostate cancer. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2012). Structure-Activity relatioship studies of a potent PACE4 inhibitor (Multi-Leu peptide): promising lead structure for the development of anti-prostate cancer agents. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA, July 15-20 2012. (Accepted).
• (2012). Le projet Influenza A H5N1 : Conception et synthèse de peptidomimétiques inhibiteurs de proprotéines convertases. Conférence mensuelle de l'IPS, Institut de pharmacologie de Sherbrooke, Sherbrooke, Qc, Canada, Février 2012. (Accepted).
• (2011). Recherche de nouveaux biomarqueurs des cancers épithéliaux de l’ovaire par imagerie MALDI. Journées Francophones de Recherche en Obstétrique et Gynécologie (JFROG), France, Paris. (Accepted).
• (2011). Étude du rôle de PACE4 dans le cancer de la prostate. Journée Scientifique du département de Chirurgie, Université de Sherbrooke, 2 décembre 2011. (Accepted).
• (2011). Conception rationnelle d'inhibiteurs macrocycliques de la furine. Journée Phare. Hotel le Sheribourg, Orford, Qc, Canada. (Accepted).
• (2011). Rôle de PC1/3 dans l’immunité innée : Une approche protéomique. Journée Phare, Orford, Canada. (Accepted).
• (2011). Strategies to develop peptide-based PCSK9 inhibitors. Journée Phare, Orford, Canada. (Accepted).
• (2011). Synthesis and biological activity of proprotein convertases inhibitors. Journée Phare, Orford, Canada. (Accepted).
• (2011). The multi-Leu peptide targets PACE4 to inhibit DU145 proliferation. Journée Phare, Orford, Canada. (Accepted).
• (2011). The multi-leu peptide targets PACE4 to inhibit DU145 proliferation. Journée Phare 2011, Rencontre interuniversitaire de pharmacologie, Hôtel Chéribourg, Orford. (Accepted).
• (2011). Validation moléculaire des proprotéines convertases en tant que cibles pharmacologies dans le cancer de la prostate. Journée Phare 2011, Rencontre interuniversitaire de pharmacologie, Hôtel Chéribourg, Orford. (Accepted).
• (2011). MALDI MSI for ovarian cancer biomarkers research: latest developments of the technology for screening and tracking. 53rd Symposium of the Society for Histochemistry, Munich, Germany. (Accepted).
• (2011). MALDI MSI for the screening of ovarian cancer biomarkers: new insight of the technology for new issues in pharmacology. . Human Proteome 10th World Congress, Geneva, Switzerland. (Accepted).
• (2011). MALDI Mass Spectrometry Imaging for the Screening of Epithelial Ovarian Cancer Biomarkers. 17th International Meeting of the European Society of Gynecological Oncology (ESGO), Milan, Italy. (Accepted).
• (2011). Molecular assesment of proprotein convertases as potential pharmacological targets in prostate cancer using an shRNA knockdown approach. Journée scientifique de la Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Qc, Canada. (Accepted).
• (2011). Molecular histology for epithelial ovarian cancers biomarker hunting: new issues for biology and pharmacology. Société de Spectrométrie de Masse et d’Analyses Protéomiques (SMAP), Avignon, France. (Accepted).
• (2011). Tissue Proteomics of Epithelial Ovarian Cancers. European Society of Gynecological Oncology (ESGO), Milan, Italy. (Accepted).
• (2011). Molecular histology for epithelial ovarian cancers biomarker hunting: new issues for biology and pharmacology. European Molecular Biology Organization (EMBO), Cancer Proteomics, Dublin, Ireland. (Accepted).
• (2011). Tissue proteomics of ovarian epithelial cancers. 4th European Symposium on Ovarian Cancer (ESOC), Reims, France. (Accepted).
• (2011). Études ab-initio et semi-empirique des intéractions moléculaires enzyme-ligant de la furine. Symposium de Chimie Médicinale de l'ACFAS. Université de Sherbrooke, Sherbrooke, Qc, Canada. (Accepted).
• (2010). Design, synthesis and stability studies of potent inhibitors of pro-protein convertases (PCs). 31st Europ. Pept. Symp. Copenhagen, Denmark. (Accepted).
• (2010). Solid phase synthesis substituted peptides amides on aryl hydrazine resin. 31st Europ. Pept. Symp. Copenhagen, Denmark. (Accepted).
• (2010). The role of PACE4 in the proliferation of the HT1080 fibrosarcoma cell line validated with proprotein convertase shRNAs. 5e Journée Scientifique de la FMSS, Université de Sherbrooke, Sherbrooke, Qc, Canada. (Accepted).
• (2010). Characterization of Recombinant human PCSK9 purified from Drosophila Schneider 2 cells. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2010). Rational design and synthesis of proprotein convertase inhibitors using click chemistry. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2010). Role of PACE4 in prostate cancer: genomic and proteomic studies with DU145 human cell line. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2010). Role of PACE4 in the proliferaiton of HT1080 fibrosarcoma cell lines validated with proprotein convertase shRNAs. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).
• (2010). The multi-leu peptide targets intracellular PACE4 to inhibit cell proliferation. Gordon Research Conferences: Proprotein Processing, Trafficking & Secretion. Colby-Sawyer College, New London, NH, USA. (Accepted).

Propriétés intellectuelles

Patents

• Mammalian pro-hormone convertase PC7. WO/1997/005256. (Completed).
• Multi-Leu peptides and analogues thereof as selective PACE4 inhibitors and effective antiproliferative agents. WO/2010/003231. (Completed).
• Proprotein converting enzyme. WO/1998/004686. (Completed).
• Stable peptide-based PACE4 inhibitor. PCT/CA2012/050601. (Completed).
• Stable peptide-based furin inhibitor. PCT/CA2012/050603. (Completed).
• Stable peptide-based proprotein convertase inhibitors. Provisional Patent USA no. 61/530,478. (Completed).
• Targeting host proteinases as a therapeutic strategy against viral and bacterial pathogens. WO/2009/023306. (Completed).
• Zis-SR nucleic acid and amino acid sequences involved in the regulated secretory pathway and/or the regulation of the neuroendocrine phenotype (NEP). WO/2002/061082. (Completed).

Autres contributions

Gestion d'évènements

• Funds raising committee: Gordon Research Conference. Gordon Research Conference - Protein Processing, Trafficking and Secretion. (Conference).
• Chair Gordon Research Conference GRC. Gordon Research Conference -Protein Processing, Trafficking and Secretion. (Conference).
• Vice-Chair: Gordon Research Conference. Gordon Research Conference - Protein Processing, Trafficking and Secretion. (Conference).

Présentations

• (2012). PCs and prostate cancer. Invited speaker: Gordon Research Conference - Protein Processing, Trafficking and Secretion. New London.
• (2011). Proprotein Convertases in prostate cancer. Invited speaker: Montreal General Hospital Research Institute, McGill U. Montreal.
• (2010). The Proprotein Convertases: Are They Potential Therapeutic Targets. Invited speaker: University Gdansk. Gdansk.