Professor  |  Principal Investigator; Vice Chair, Department of Molecular Genetics

Peter Roy

Department of Molecular Genetics - Canada Research Chair in Chemical Genetics

PhD

Address
Room 1202
Research Interests
Drug Discovery, Preclinical Drug Discovery, New Drug Target Discovery, Environmentally Friendly Pesticide Discovery, C. elegans, Models of Disease, Liver Disease, Amyloids
Appointment Status
Primary

Qualification

  • Stanford University, Stanford, CA, U.S., Beckman Fellow in Developmental Biology and Genetics, 2001-2002.
  • Stanford University, Stanford, CA, U.S., Research Fellow in Developmental Biology and Genetics, 1999-2001.
  • University of Toronto, PhD in Molecular and Medical Genetics, 1999.
  • Dalhousie University, Halifax, BSc in Biology and Neuroscience, 1993.

MY RESEARCH OVERVIEW (GO TO SCIENTIFIC OVERVIEW)

Peter’s lab at the University of Toronto is focused on developing new drug leads and environmentally-safe pesticide lead molecules. Briefly, their projects include:

PEXIL™ Technology

Peter’s group has recently developed a new, high-throughput, massively paralleled drug and pesticide screening technology called PEXIL™.

Parasitic Prodrugs

The Roy Lab has discovered a suite of antiparasitic small molecule scaffolds that are bioconverted by the parasites into lethal products.

Novel Neuromodulatory Nematicides

The Roy Lab has developed a new pipeline that reveals small molecule disruptors of motor behaviour in nematodes. One scaffold that resulted from this pipeline is Nementin™, which induces convulsions, paralysis and death though massive synaptic vesicle release in nematodes.

Candidate Drugs to Treat PFIC3 Liver Disease

Peter’s lab has established a new nematode model of PFIC3 disease and have identified candidate drugs that suppress the worm’s defects. Work is on-going to understand how these molecules suppress the PFIC3 model and their utility in treating a mouse model of the disease.

Amyloid Disruptors

Over 50 human diseases have amyloid formation as their root cause, including Parkinson’s, ALS, scrapie, and Huntington’s. Peter’s group has developed a nematode-based pipeline that yields molecules capable of disrupting amyloid formation.

A NEMATODE WORM ILLUMINATED WITH FLUORESCENT MARKERS
A NEMATODE WORM ILLUMINATED WITH FLUORESCENT MARKERS

SCIENTIFIC RESEARCH OVERVIEW

PEXIL™ Technology

The world is in desperate need of new drugs to combat drug-resistant pathogens, parasites and crop pests. To help accelerate drug discovery, Peter’s group has recently developed a new, high-throughput, massively paralleled drug/pesticide screening technology called PEXIL™. PEXIL’s advantages over traditional phenotypic screens using single pathogens or agricultural pests include: i) targeting of 100s of pathogens or pests simultaneously; ii) the delivery of new pesticide targets that enables medicinal chemistry optimization of new pesticide-leads, and, iii) the ability to target pests that are simply un-screenable in high-throughput fashion (i.e. schistosomes, cestodes, insects, plant parasitic nematodes etc). The group is actively looking for partners to commercialize this technology.

Parasitic Prodrugs

Parasitic nematodes are estimated to destroy over $150B USD worth of crop every year. Towards developing nematicides to improve global food security, the Roy Lab has discovered a suite of small molecule scaffolds that are active against plant parasitic nematodes. These molecules are bioconverted within nematodes into lethal products. The bioconversion of one of these scaffolds, which they call Selectivin™, is restricted to nematodes. The Roy Lab uncovered the details of how Selectivin™ works and show demonstratable utility against some of the world’s most destructive plant parasitic nematodes in green house-based assays. The group has patents pending on Selectivin™, and IP is being generated for other scaffolds that have come out of this project. Roy Lab members are seeking industrial partners to help further develop the utility of these compounds. A manuscript describing Selectivin™ is currently in review.

Novel Neuromodulatory Nematicides

The Roy Lab has developed a drug-screening pipeline that reveals small molecule disruptors of motor behaviour in nematodes. Nementin™ is one scaffold revealed by this screen. Nementin™ induces convulsions, paralysis and death though massive synaptic vesicle release. Nementin™ also dramatically enhances the activity of organophosphate and carbamate pesticides that are used kill nematodes. Hence, Nementin™ may have utility in reducing the amount of these non-specific pesticides that are used in agriculture. Roy Lab members are seeking industrial partners to help further develop the utility of Nementin™.  A manuscript describing Nementin™ will soon be submitted for peer review.

Candidate Drugs to Treat PFIC3 Liver Disease

PFIC3 is a rare liver disease that manifests in early childhood and often requires liver transplantation. The disease is caused by defects in the liver’s ABCB4 lipid pump. By knocking out an ABCB4 homolog in the worm, Peter’s lab has established a new PFIC3 nematode model. They used this model to identify 30 FDA-approved compounds that suppress the worm’s defects associated with loss of the presumptive lipid pump. Exploiting C. elegans forward genetic screens, the group showed that these FDA compounds likely upregulate alternative pumps to make up for the loss of the ABCB4 homolog. Together with collaborators, Peter’s group is testing whether these FDA compounds can successfully treat a mouse model of PFIC3.

 

SELECT PUBLICATIONS

  • Burns, A.R., Ross, R., Kitner, M., Volpatti, J., Vaidya, A. S., Puumala, E., Palmeira, B.M., Redman, E.M., Snider, J., Marwah, S., Chung, S., MacDonald, M.H., Tiefenbach, J., Hu, C., Xiao, Q., Finney, C.A.M., Krause, H.M., MacParland, S.A., Stagljar, I., Gilleard, J.S., Cowen, L.E., Meyer, S., Cutler, S.R., Dowling, J.J., Lautens, M., Zasada, I., Roy, P.J. Selective Control of Parasitic Nematodes Using Bioactivated Nematicides. In review.
  • Harrington, S., Knox, J. Pyche, J., Ross, R., Loon-Choo, K., Kim, Y., R. Burns, A.R., Kitner, M., Haeberli, C., D’Amato, C., Au, A., Volpatti, J., Guiliani, M., Snider, J., Palmeira, B.M., Redman, E.M., Scott, I., Gilleard, J., Stagljar, I., Dowling, J., Yip, C., Keiser, J., Lautens, M., Zasada, I., and Roy. P.J. A Nematode-Selective Potentiator of Organophosphate and Carbamate Agrochemicals. Manuscript in preparation.
  • 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