Roberge, Michel

Professor Emeritus, Biochemistry and Molecular Biology
Faculty of Medicine

University of Sherbrooke, 1980, BSc (Biology)
University of Sherbrooke, 1982, MSc (Biology)
U. of Heidelberg, 1985, PhD (Biochemistry)

Office: Life Sciences Centre, 5401

Research Interest

Genetic disease drug discovery

There are more than 7,000 distinct rare human genetic diseases that collectively affect one in twelve people. Unfortunately, most have no treatments and about one third of patients die in childhood. The small number of patients with each disease (typically fewer than 1 in 2,000) makes it difficult to study disease biology and develop disease-specific therapies. However, about 10% of patients share a common mutation type: nonsense mutations. These mutations change an amino acid codon to a premature termination codon (PTC), resulting in truncated and non-functional protein. Nonsense mutations also account for about 10% of mutations in tumor suppressor genes in cancer. Restoring function of the mutated gene is a key treatment goal for rare genetic diseases and cancer.

Chemicals that enable translational bypass of a PTC, termed PTC readthrough, allow production of full-length protein and offer the possibility of using the same treatment for many patients with different genetic diseases or cancers. Our research is focused on discovering chemicals that induce or promote PTC readthrough and developing them into treatments.


Comprehensive List

Selected Publications

  1. Baradaran-Heravi, A., Niesser, J., Balgi, A. D., Choi, K., Zimmerman, C., South, A. P., Anderson, H. J., Strynadka, N. C., Bally, M. B. and Roberge, M. Gentamicin B1 is a minor gentamicin with major nonsense mutation suppression activity. Proc. Natl Acad. Sci USA 114:3479-3484 (2017)
  2. Morris, E. J., Kawamura, E., Gillespie, J. A., Muller, W. J., Roberge, M. and Dedhar, S. Stat3 regulates centrosome clustering via stathmin/PLK1 to maintain cancer stem cells. Nat. Commun. 8:15289. DOI: 10.1038/ncomms15289 (2017)
  3. Arns, S., Balgi, A.D., Shimizu, Y., Heller, M., Pfeifer, T., Kumar. K., Shidmoosavee, F., Jaquith, J. B., Bourque, E., Niikura, M., Roberge, M. Novel spirothiazamenthane inhibitors of the influenza A M2 proton channel. Eur. J. Med. Chem, 120:64-73 (2016)
  4. Baradaran-Heravi, A., Balgi, A. D., Zimmerman, C., Choi, K., Shidmoosavee, F. S., Tan, J. S., Bergeaud, C., Krause, A., Flibotte, S., Shimizu, Y., Anderson, H. J., Jan, E., Pfeifer, T., Jaquith, J. B., Roberge, M. Novel small molecules potentiate premature termination codon readthrough by aminoglycosides. Nucleic Acids Res. 44: 6583-6598 (2016)
  5. Mathew, M. D., Mathew, N. D., Miller, A., Simpson, M., Au, V., Garland, S., Gestin, M., Edgley, M. L., Flibotte, S., Balgi, A. D., Chiang, J., Giaever, G., Dean, P., Tung, A., Roberge, M., Roskelley, C. D., Forge, T., Nislow, C. and Moerman, D. Using C. elegans Forward and Reverse Genetics to identify new compounds with anthelmintic activity. PLOS Neglected Tropical Diseases DOI:10.1371 (28 pages) (2016).
  6. Huang, S., Balgi, A. D., Pan, Y., Li, M., Zhang, X., Du, L., Zhou, M., Roberge, M. and Li, X. Identification of methylosome components as negative regulators of plant immunity using chemical genetics. Mol. Plant 9:1620-1633 (2016)
  7. Klionsky, D. and many others, including Roberge, M. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy. Autophagy 12:1-122 (2016)
  8. Yang, Y. S. C., Vilin, Y. Y., Roberge, M., Kurata, H. T. and Johnson, J. D. Multi-parameter screening reveals a role for Na(+) channels in cytokine-induced beta-cell death. Mol. Endocrinol. 28: 406-417 (2014)
  9. Donohue, E., Balgi, A. D., Komatsu, M. and Roberge, M. Induction of covalently crosslinked p62 oligomers with reduced binding to polyubiquitinated proteins by the autophagy inhibitor verteporfin. PLOSONE 9(12):e114964 (2014)
  10. Tam, Y.Y., Chen, S., Zaifman, J., Tam, Y. K., Lin, P. J., Ansell, S., Roberge, M., Ciufolini, M. A. and Cullis, P. R. Small molecule ligands for enhanced intracellular delivery of nanoparticle formulations of SiRNA. Nanomedicine 9:665-674 (2013)
  11. Balgi, A. D., Wang, J., Cheng, D. Y. H., Ma, C., Pfeifer, T., Shimizu, Y., Anderson, H. J., Pinto, L. H., Lamb, R. A., DeGrado, W. F. and Roberge, M. Inhibitors of the influenza A virus M2 proton channel discovered using a yeast high-throughput growth restoration assay. PLoS ONE 8(2): e55271 (2013)
  12. Zimmerman, C., Austin, P., Khong, A., McLeod, S., Bean, B., Forestieri, R., Andersen, R. J., Jan, E., Roberge, M. and Roskelley, C. D. The small molecule genkwanine M induces single mode, mesenchymal tumor cell motility. Exp. Cell Res. 319:908-917(2013)
  13. Towle, K. M., Chaytor, J. L., Liu, H., Austin, P., Roberge, M., Roskelley, C. D. and Vederas, J. C. Synthesis and biological studies of neopetrosiamides as inhibitors of tumour cell invasion. Org. Biomol. Chem. 11:1476-1481 (2013)
  14. Austin, P., Freeman, S., Gray, C., Vogel, A., Andersen, R. J., Roberge, M. and Roskelley, CD. The invasion inhibitor sarasinoside A1 initiates E-cadherin-independent cell junction formation. Mol. Cancer Res. 11:530-540 (2013)
  15. Forestieri, R., Donohue, E., Balgi, A., Roberge, M. and Andersen, R. J. Synthesis of Clionamine B, An Autophagy Stimulating Aminosteroid Isolated from the Sponge Cliona celata. Org. Lett. 15:3918-3929 (2013)
  16. Donohue, E., Thomas, A., Maurer, N., Manisali, I., Zeisser, M., Zisman, N., Anderson, H. J., Ng, S. S. W., Webb, M., Bally, M. and Roberge, M. The autophagy inhibitor verteporfin moderately enhances the antitumor activity of gemcitabine in a pancreatic ductal adenocarcinoma model. J. Cancer. 4:585-596 (2013)
  17. Kawamura, E., Fielding, A. B., Kannan, N., Balgi, A., Eaves, C.J., Roberge, M. and Dedhar, S. Identification of novel small molecule inhibitors of centrosome clustering in cancer cells. Oncotargets 4:1763-1776 (2013)
  18. Dragowska, W. H., Weppler, S. A., Wang, J. C., Wong, L. Y., Kappanen, A. I., Rawji, . S., Warburton, C., Qadir, M. A., Donohue, E., Roberge, M., Gorski, S. M., Gelmon, K. A. and Bally, M. B. Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer. PLoSONE 8 e76503 (2013)