Faculty: Peter Roy, PhD
Professor, Department of Molecular Genetics and Department of Pharmacology & Toxicology
Canada Research Chair in Chemical Genetics
General Research Areas: neurodegeneration, anthelmintics, nematicides, drug discovery, pharmacological interactions with amyloids and intrinsically disordered proteins
Dr. Roy has pioneered the use of the nematode C. elegans to discover useful small molecule tools and potential drug leads. He is currently leading projects in the following areas:
Pharmacological Interactions with Intrinsically Disordered Proteins and their Relationship to Neurodegeration: Dr. Roy’s group discovered that select small molecules form crystals within the head of C. elegans. At least two cuticle components are required for this phenomenon; intrinsically disordered proteins (IDPs; see below) and polar lipids. Molecules that are known to prevent human amyloid formation disrupt crystal formation in the IDP-rich cuticle. Dr. Roy’s group is exploiting this system to identify novel small molecules that disrupt amyloid formation and develop them as candidate treatments of amyloid-based diseases such as Alzheimer’s.
Parasitic Prodrugs: Dr. Roy’s group has discovered a suite of small molecules that are bioactivated within nematodes into lethal products. Focusing on ‘nemactivin’, they have shown its bioactivation is restricted to nematodes and that it has real-world utility against plant parasitic nematodes. They are: i) further developing nemactivin as a nematicide with industrial partners; ii) developing additional nematicide prodrugs, and iii) building a system to identify otherwise innocuous small molecules that can be metabolically converted into lethal products within any targeted organism.
Nematicidal Neuromodulators: Dr. Roy’s group has developed a pipeline to identify small molecule disruptors of motor behaviour in nematodes. They discovered a scaffold called ‘nementin’ that induces convulsions, paralysis and death though massive synaptic vesicle release. They are further developing nementin with industrial partners and working to better understand its mechanism of action.
- Knox, J., Joly. N., Linossi, E. M., Carmona-Negrón, J.A., Jura, N., Pintard, L., Zuercher, W., and Roy, P.J§. A Survey of the Kinome Pharmacopeia Reveals Multiple Scaffolds and Targets for the Development of Novel Anthelmintics. Scientific Reports. In press.
- Volpatti, J., Endo, Y., Knox, J., Groom, L., Brennan, S., Noche, R., Noche, R., Zuercher, W., Roy, P., Dirksen, R. T., and Dowling, J.J.§ 2020. Identification of drug modifiers for RYR1 related myopathy using a multi-species discovery pipeline. eLife 2020;9:e57481 DOI: 10.7554/eLife.57481
- Kamal, M., Moshiri, H., Magomedova, L., Han, D., Nguyen, K.C.Q., Yeo, M., Knox, J., Bagg, R., Won, A.M., Szlapa, K., Yip, C., Cummins, C.L., Hall, D.H., and Roy, P.J.§ 2019. The Marginal Cells of the Caenorhabditis elegans Pharynx Scavenge Cholesterol and Other Hydrophobic Small Molecules. Nature Communications. 10, 1-16. https://doi.org/10.1038/s41467-019-11908-0
- Otten, C., Knox, J., Boulday, G., Eymery, M., Haniszewski, M., Neuenschwander,M., Radetzki, S., Vogt, I, Hähn, T., De Luca, C., Cardoso, C., Hamad, S., Gil, C., I., Roy, P., Albiges-Rizo, C., Faurobert, C., von Kries, J.P., Campillos, M., Tournier-Lasserve, E., Derry, W.B., and Abdelilah-Seyfried, S.§. 2018. Novel molecular pathways involved in cerebral cavernous malformations uncovered by systematic pharmacological suppression. EMBO Mol Medicine, 10(10). pii: e9155. doi: 10.15252/emmm.201809155. PMID: 30181117
- Burns, A.R.*, Bagg, R., Yeo, M., Luciani, G.M., Schertzberg, M., Fraser, A.G., and Roy, P.J.§. 2017. The Novel Nematicide wact-86 Interacts with Aldicarb to Kill Nematodes. PLoS Neglected Tropical Diseases. http://dx.doi.org/10.1371/journal.pntd.0005502
- Tharmalingam, S., Burns, A. R., Roy, P.J., and Hampson, D.R. 2012. Orthosteric and Allosteric Drug Binding Sites in the C. elegans mgl-2 Metabotropic Glutamate Receptor. Neuropharmacology 63, p667-674. PMID: 22652059
- Burns, A., and Roy, P. 2012. To Kill a Mocking Worm: Strategies to Improve Caenorhabditis elegans as a Model System for use in Anthelmintic Discovery. A chapter in the book, “Parasitic Helminths: Targets, Drugs and Vaccines”. Eds. Caffrey, C. , Selzer, P., Wiley VCH, Publishers.
- Burns, A.R.*, Luciani, G.M., Musso, G., Bagg, R., Yeo, M., Zhang, Y., Rajendran, L., Glavin, J., Hunter, R., Redman, E., Stasiuk, S., Schertzberg, M., McQuibban, G.A., Caffrey, C.R., Cutler, S., R., Tyers, M., Giaever, G., Nislow, C., Fraser, A.G., MacRae, C. A., Gilleard, J. and Roy, P.J.§. 2015. Caenorhabditis elegans is a useful model for Anthelmintic Discovery. Nature Communications. 6:7485 | DOI: 10.1038/ncomms8485
- Luciani, G.M., Magomedova, L., Puckrin, R., Urbanus, M., L., Wallace, I.M., Giaever, G., Nislow, C., Cummins, C.L. §, and Roy, P.J.§. 2011. Dafadine Inhibits DAF-9 to Promote Dauer-Formation and Longevity of Caenorhabditis elegans. Nature Chemical Biology 7, 891-893. doi: 10.1038/nchembio.698. PMID: 22057127
- Burns, A.R., Wallace, I.M., Wildenhain, J., Tyers, M., Giaever, G., Bader, G., Nislow, C., Cutler, S.R., and Roy, P.J.§. 2010. A Predictive Model for Drug Bioaccumulation and Bioactivity in Caenorhabditis elegans. Nature Chemical Biology, 6, p549-557 (doi: 10.1038/nchembio.380).
- Hui, K.*, Kwok, T.C.Y.*, Kostelecki, W., Leen, J., Roy, P.J.§, and Feng, Z.P.§. 2009. Differential sensitivities of CaV1.2 IIS5-S6 mutants to 1,4-dihydropyridine analogs. European Journal of Pharmacology, 602, p255-261. PMID:19068212
- Kwok, T.C.Y.*, Hui, K.*, Kostelecki, W., Selman, G., Ricker, N., Feng, Z.P.§, and Roy, P.J.§. 2008. A Screen for Dihydropyridine (DHP)-Resistant Worms Reveals a Mechanism for DHP-Blockage of Mammalian Calcium Channels. PLoS Genetics, 4(5):e1000067.
- Kwok, T., Ricker, N., Fraser, R., Chan, A., Burns, A., Stanley, E.F., McCourt, P., Cutler, S., and Roy, P.J.§ 2006. A Small Molecule Screen in C. elegans Yields a New Calcium Channel Antagonist. Nature. 441, 91-95. PMID: 16672971
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