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About Sickkids
About SickKids

Don Mahuran, PhD

Research Institute
Senior Scientist Emeritus
Genetics & Genome Biology

University of Toronto
Department of Laboratory Medicine and Pathobiology

Phone: 416-813-6161
Fax: 416-813-8700
Email: hex@sickkids.ca

Brief Biography

Dr. Don Mahuran received his PhD from the University of Windsor, in Windsor, Ontario, Canada in 1976.  The title of his thesis was "Characterization of Fumarylacetoacetate Fumarylhydrolase" (the enzyme defective in the French Canadian variant of Tyrosinemia). From 1977 to 1980, he completed his postdoctoral training with Dr. “Sandy” Lowden, the head of the Division of Neurosciences at The Hospital for Sick Children (SickKids) at that time.  He then spent one year working with Dr. John Hopwood in the Chemical Pathology Department at Adelaide Children's Hospital in Adelaide, South Australia, before returning to a position at SickKids.  

During his postdoctoral training he developed his long-term interest in the molecular and cellular biology of lysosomal storage diseases, with a particular focus on GM2-gangliosidosis (Tay-Sachs and Sandhoff disease, and the AB-variant form).  His work initially focused on purification and characterization of the defective isozymes (β-hexosaminidase A and/or B), which lead into the cloning of their cDNAs in 1985-86 for genotype/ phenotype correlations and structure/ function studies.

Research Interests

The basic research carried out worldwide over the last 40 years has made possible the development of novel therapeutic approaches for the treatment of several of lysosomal storage diseases.  At the present time the most widely used approach is enzyme replacement therapy (ERT), which is very expensive and not fully effective. Recently small molecule-based substrate reduction and enzyme enhancement therapies have been introduced and/ or proposed for some forms of these diseases, which potentially have many benefits as either a substitute for or adjunct to ERT.  Dr. Mahuran has turned his research focus towards these small-molecule based therapies.  He currently coordinates a group of eight Canadian researches funded in 2007-2012 by a Team Grant from the Canadian Institutes of Health Sciences, whose goals are to develop and expand these therapeutic approaches for lysosomal storage diseases.

External Funding

2009 - 2014: CIHR Emerging Team Grant in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): From Genes to Proteins, Cells, Tissues and Patients.

2007 - 2012: CIHR Team Grant in Lysosomal Storage Disease Pharmaco Therapeutics

2010 - 2012: The Sanfilippo Children's Research Foundation


K.S. Bateman, M.M. Cherney, D.J. Mahuran, M. Tropak & M.N. James. Crystal Structure of beta-Hexosaminidase B in Complex with Pyrimethamine, a Potential Pharmacological Chaperone. Journal of Medicinal Chemistry 54 (2011) 1421-1429

J.T.R. Clarke, D.J. Mahuran, S. Sathe, E.H. Kolodny, B.A. Rigat, J.A. Raiman, M.B. Tropak.  Open-label Phase I/II clinical trial of pyrimethamine for the treatment of chronic GM2 gangliosidosis, Molecular Genetics and Metabolism 102 (2011) 6-12.

R.F. Frohlich, R.H. Furneaux, D.J. Mahuran, B.A. Rigat, A.E. Stutz, M.B. Tropak, J. Wicki, S.G. Withers, T.M. Wrodnigg.  1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines, Carbohydr Res 345 (2010) 1371-1376.

R. Khanna, E.R. Benjamin, L. Pellegrino, A. Schilling, B.A. Rigat, R. Soska, H. Nafar, B.E. Ranes, J. Feng, Y. Lun, A.C. Powe, D.J. Palling, B.A. Wustman, R. Schiffmann, D.J. Mahuran, D.J. Lockhart, K.J. Valenzano. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta-glucosidase, FEBS J 277 (2010) 1618-1638.

H. Zhang, D.J. Mahuran, J.W. Callahan, Identification of proteins in the ceroid-like autofluorescent aggregates from liver lysosomes of Beige, a mouse model for human Chediak-Higashi syndrome, Mol Genet Metab 99 (2010) 389-395.

G. Schitter, A.J. Steiner, G. Pototschnig, E. Scheucher, M. Thonhofer, C.A. Tarling, S.G. Withers, K. Fantur, E. Paschke, D.J. Mahuran, B.A. Rigat, M.B. Tropak, C. Illaszewicz, R. Saf, A.E. Stütz, T.M. Wrodnigg, Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones, ChemBioChem 11 (2010) 2026-2033

M.B. Tropak, S.W. Bukovac, B.A. Rigat, S. Yonekawa, W.  Wakarchuk and D.J. Mahuran.  A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates. Glycobiology 20 (2010) 356-365

B. Rigat, H. Yeger, D. Shehnaz, and D. Mahuran.  GM2 activator protein inhibits platelet activating factor signaling in rats. Biochem. Biophys. Resear. Commun. 385 (2009) 576-580

B. Rigat and D. Mahuran.  Diltiazem, a L-type Ca2+ Channel Blocker, also acts as a Pharmacological Chaperone in Gaucher Patient Cells.  Mol Genet Metab 96, 225-232 (2009).

M. B. Tropak, G. J. Kornhaber, B.A. Rigat, G. H. Maegawa,  J. Buttner, J. E. Blanchard, C. Murphy, S. J. Tuske, S. J. Coales, Y. Hamuro, E. Brown, and D. J. Mahuran.  Identification of Pharmacological Chaperones for Gaucher Disease and Characterization of Their Effects on β-Glucocerebrosidase by Hydrogen/Deuterium Exchange Mass Spectrometry.  ChemBiochem 9, 2650-2662 (2008).

Intellectual Property

  • Episomal Cassettes for Gene Therapy
  • Products and Methods for Gaucher's Disease Therapy