Research Summary

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.

Members of the laboratory:
Hilary Anderson
Aruna Balgi
Alireza Baradaran-Heravi
Kunho Choi
Mike Ferguson
Chloe Gerak
Carla Zimmerman


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


Khong, A., Forestieri, R., Williams, D.E., Patrick, B.O., Olmstead, A., Svinti, V., Schaeffer, E., Jean, F., Roberge, M., Andersen, R.J., and Jan, E., A Daphnane Diterpenoid isolated from Wikstroemia Polyantha induces an inflammatory response and modulates miRNA activity. PLoS ONE 7(6) e39621 (11 pages) (2012)

Carr, G., Williams, D.E., Ratnayake, R., Bandara, R., Wijesundara, S., Tarling, T., Balgi, A.D., Roberge. M., Andersen, R.J., and Karunaratne, V., Hortonones A to C new hydroazulenones from the genus Hortonia. J. Nat. Prod. 75:1189-1191 (2012)

Fonseca, B.D., Diering, G.H., Bidinosti, M.A., Dalal, K., Alain, T., Balgi, A.D., Forestieri, R., Nodwell, M., Rajadurai, C.V., Tee, A.R., Duong, F., Andersen, R.J., Orlowski. J., Numata, M., Soneberg, N., and Roberge, M., Structure-activity analysis of niclosamide reveals a potential role of cytoplasmic pH in the control of Mammalian target of rapamycin complex 1 (mTORC1) signaling. J. Biol. Chem. 287:17530-17535 (2012)

Lam, K.K.Y., Robeto Forestieri, R., Balgi, A.D., Zheng, X., Fonseca, B.D., Nodwell, M., Vollett, S., Anderson, H.J., Andersen, R.J., Av-Gay, Y., and Roberge, M. Nitazoxanide inhibits mTORC1 signaling, stimulates autophagy and inhibits the intracellular proliferation of Mycobacterium tuberculosis. PLoS Path. 8(5):e1002691 (15 pages) (2012)

Andersen, R.J., Li, D., Nodwell, M., Roberge M., Strangman, W., and Williams, D.E., Marine natural products that target microtubules. Handbook of marine natural products. Springer Science+Business Media, Fattorusso, E., Gerwick, W.H., Taglialatela-Scafati, O., Eds Chapter 20. Pp 1028-1064 (2012)

Onishi, I., Lin, P.J.C., Numata, Y., Austin, P., Cipollone, J., Roberge, M., Roskelley, C.D., and Numata, M., Organellar (Na+, K+)/H+ exchanger NHE7 regulates cell adhesion, invasion and anchorage-Independent growth of breast cancer MDA-MB-231 cells. Oncol. Rep. 27:311-317 (2012)

Balgi, A.D., Diering, G.H., Donohue, E., Lam, K.K.Y., Fonseca B.D., Zimmerman, C., Numata, M., and Roberge, M., Regulation of mTORC1 signaling by pH. PLoSONE 6:e21549 (2011)

Rocha, D.D., Balgi, A., Maia, A.I., Pessoa, O.D., Silveira, E.R., Costa-Lotufo, L.V., Roberge, M., and Pessoa, C., Cell cycle arrest through inhibition of tubulin polymerization by withaphysalin F, a bioactive compound isolated from Actinus arborescens. Invest. New Drugs 30:959-966 (2011)

Riffell, J.L., Janicke, R.U., and Roberge, M., Caspase-3-dependent mitotic checkpoint inactivation by the small molecule inducers of mitotic slippage SU5565 and geraldol. Mol. Cancer Ther. 10:839-849 (2011)

Ramon-Garcia, S., Ng, C., Anderson, H., Chao, J.D., Zheng, X., Pfeifer, T., Av-Gay, Y., Roberge, M., and Thompson, C.J., Synergistic drug combinations for tuberculosis therapy identified by a novel high throughput screen. Antimicrob. Agents Chemother. (2011)

Donohue, E., Tovey, A., Arns, S., Sternberg, E., Young, R.N., Dolphin, D., and Roberge, M., Inhibition of autophagosome formation by the benzoporphyrine derivative verteporfin. J. Biol. Chem. 286:7290-7300 (2011)

Gies, E., Wilde, I.B., Brack, M., Arias-Novoa, C., Aruna D. Balgi, A.D., Roberge, M., and Mayor, T., Niclosamide prevents the formation of large ubiquitin-containing aggregates caused by proteasome inhibition . PLoS ONE 5(12): e14410 (12 pages) (2010)

Nodwell, M., Zimmerman, C., Roberge, M., and Andersen, R.J., Synthetic analogues of the microtubule-stabilizing sponge alkaloid ceratamine A are more active than the natural product. J. Med. Chem. 53: 7843-7851 (2010)

Austin, P., Heller, M., Williams, D.E., McIntosh, L.P.,Vogel, A.W., Andersen, R.J., Roberge, M., and Roskelley, C.D., Drug-induced release of B1 integrin from the cell surface inhibits tumor cell invasion. PLoS ONE 5:e10836 (14 pages) (2010)

Liu, H., Boudreau, M.A., Zheng, J., Whittal, R.M., Dean, P., Roskelley, C.D., Roberge, M., Andersen, R.J. and Vederas, J.C., Chemical synthesis and biological activity of the neopetrosiamides and their analogues: revision of the disulfide bond connectivity. J. Am. Chem. Soc. 132:1486-1487 (2010)

Carr, G., Williams, D.E., Diaz-Marrero, A.R., Patrick, B.O., Bottriell, H., Balgi, A.D., Donohue, E., Roberge, M., and Andersen, R.J., Bafilomycins produced in culture by Streptomyces spp. Isolated from marine habitats are potent inhibitors of autophagy. J. Nat. Prod. 73:422-427 (2010)

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