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Michael Tropak

TitleResearch Associate-RI
InstitutionThe Hospital for Sick Children
DepartmentGenetics and Genome Biology
Address555 University Avenue
Toronto ON M5G 1X8
Phone416-813-1500
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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Karumuthil-Melethil S, Nagabhushan Kalburgi S, Thompson P, Tropak M, Kaytor MD, Keimel JG, Mark BL, Mahuran D, Walia JS, Gray SJ. Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease. Hum Gene Ther. 2016 07; 27(7):509-21. PMID: 27197548.
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    2. Tropak MB, Yonekawa S, Karumuthil-Melethil S, Thompson P, Wakarchuk W, Gray SJ, Walia JS, Mark BL, Mahuran D. Construction of a hybrid ß-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo. Mol Ther Methods Clin Dev. 2016; 3:15057. PMID: 26966698.
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    3. Tropak MB, Zhang J, Yonekawa S, Rigat BA, Aulakh VS, Smith MR, Hwang HJ, Ciufolini MA, Mahuran DJ. Pyrimethamine Derivatives: Insight into Binding Mechanism and Improved Enhancement of Mutant ß-N-acetylhexosaminidase Activity. J Med Chem. 2015 Jun 11; 58(11):4483-93. PMID: 25984755.
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    4. Siragam V, Cui X, Masse S, Ackerley C, Aafaqi S, Strandberg L, Tropak M, Fridman MD, Nanthakumar K, Liu J, Sun Y, Su B, Wang C, Liu X, Yan Y, Mendlowitz A, Hamilton RM. TMEM43 mutation p.S358L alters intercalated disc protein expression and reduces conduction velocity in arrhythmogenic right ventricular cardiomyopathy. PLoS One. 2014; 9(10):e109128. PMID: 25343256.
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    5. Siriwardena A, Sonawane DP, Bande OP, Markad PR, Yonekawa S, Tropak MB, Ghosh S, Chopade BA, Mahuran DJ, Dhavale DD. Synthesis of 1,5-dideoxy-1,5-iminoribitol C-glycosides through a nitrone-olefin cycloaddition domino strategy: identification of pharmacological chaperones of mutant human lysosomal ß-galactosidase. J Org Chem. 2014 May 16; 79(10):4398-404. PMID: 24735108.
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    6. Merlocco AC, Redington KL, Disenhouse T, Strantzas SC, Gladstone R, Wei C, Tropak MB, Manlhiot C, Li J, Redington AN. Transcutaneous electrical nerve stimulation as a novel method of remote preconditioning: in vitro validation in an animal model and first human observations. Basic Res Cardiol. 2014 May; 109(3):406. PMID: 24604614.
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    7. Leung CH, Wang L, Nielsen JM, Tropak MB, Fu YY, Kato H, Callahan J, Redington AN, Caldarone CA. Remote cardioprotection by transfer of coronary effluent from ischemic preconditioned rabbit heart preserves mitochondrial integrity and function via adenosine receptor activation. Cardiovasc Drugs Ther. 2014 Feb; 28(1):7-17. PMID: 24018748.
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    8. Surendra H, Diaz RJ, Harvey K, Tropak M, Callahan J, Hinek A, Hossain T, Redington A, Wilson GJ. Interaction of d and ? opioid receptors with adenosine A1 receptors mediates cardioprotection by remote ischemic preconditioning. J Mol Cell Cardiol. 2013 Jul; 60:142-50. PMID: 23608604.
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    9. Rigat BA, Tropak MB, Buttner J, Crushell E, Benedict D, Callahan JW, Martin DR, Mahuran DJ. Evaluation of N-nonyl-deoxygalactonojirimycin as a pharmacological chaperone for human GM1 gangliosidosis leads to identification of a feline model suitable for testing enzyme enhancement therapy. Mol Genet Metab. 2012 Sep; 107(1-2):203-12. PMID: 22784478.
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    10. Babajani G, Tropak MB, Mahuran DJ, Kermode AR. Pharmacological chaperones facilitate the post-ER transport of recombinant N370S mutant ß-glucocerebrosidase in plant cells: evidence that N370S is a folding mutant. Mol Genet Metab. 2012 Jul; 106(3):323-9. PMID: 22592100.
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    11. Michelsen MM, Støttrup NB, Schmidt MR, Løfgren B, Jensen RV, Tropak M, St-Michel EJ, Redington AN, Bøtker HE. Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor. Basic Res Cardiol. 2012 May; 107(3):260. PMID: 22426795.
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    12. Goddard-Borger ED, Tropak MB, Yonekawa S, Tysoe C, Mahuran DJ, Withers SG. Rapid assembly of a library of lipophilic iminosugars via the thiol-ene reaction yields promising pharmacological chaperones for the treatment of Gaucher disease. J Med Chem. 2012 Mar 22; 55(6):2737-45. PMID: 22360565.
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    13. Redington KL, Disenhouse T, Strantzas SC, Gladstone R, Wei C, Tropak MB, Dai X, Manlhiot C, Li J, Redington AN. Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors. Basic Res Cardiol. 2012 Mar; 107(2):241. PMID: 22231674.
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    14. He X, Galpin JD, Tropak MB, Mahuran D, Haselhorst T, von Itzstein M, Kolarich D, Packer NH, Miao Y, Jiang L, Grabowski GA, Clarke LA, Kermode AR. Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants. Glycobiology. 2012 Apr; 22(4):492-503. PMID: 22061999.
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    15. Rempel BP, Tropak MB, Mahuran DJ, Withers SG. Tailoring the specificity and reactivity of a mechanism-based inactivator of glucocerebrosidase for potential therapeutic applications. Angew Chem Int Ed Engl. 2011 Oct 24; 50(44):10381-3. PMID: 21915968.
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    16. Hill T, Tropak MB, Mahuran D, Withers SG. Synthesis, kinetic evaluation and cell-based analysis of C-alkylated isofagomines as chaperones of ß-glucocerebrosidase. Chembiochem. 2011 Sep 19; 12(14):2151-4. PMID: 21751327.
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    17. Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR, McCrindle BW, Wells GD, Redington AN. Remote preconditioning improves maximal performance in highly trained athletes. Med Sci Sports Exerc. 2011 Jul; 43(7):1280-6. PMID: 21131871.
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    18. Fröhlich RF, Furneaux RH, Mahuran DJ, Saf R, Stütz AE, Tropak MB, Wicki J, Withers SG, Wrodnigg TM. 1-Deoxy-D-galactonojirimycins with dansyl capped N-substituents as ß-galactosidase inhibitors and potential probes for GM1 gangliosidosis affected cell lines. Carbohydr Res. 2011 Sep 06; 346(12):1592-8. PMID: 21645885.
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    19. Tropak MB, Shi H, Li J, Dai X, Redington AN, Askalan R. Potent neuroprotection induced by remote preconditioning in a rat model of neonatal cerebral hypoxic-ischemic injury. J Thorac Cardiovasc Surg. 2011 Jul; 142(1):233-5. PMID: 21555139.
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    20. Li J, Xuan W, Yan R, Tropak MB, Jean-St-Michel E, Liang W, Gladstone R, Backx PH, Kharbanda RK, Redington AN. Remote preconditioning provides potent cardioprotection via PI3K/Akt activation and is associated with nuclear accumulation of ß-catenin. Clin Sci (Lond). 2011 May; 120(10):451-62. PMID: 21143191.
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    21. Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN. Crystal structure of ß-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone. J Med Chem. 2011 Mar 10; 54(5):1421-9. PMID: 21265544.
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    22. Maj M, Sriskandarajah N, Hung V, Browne I, Shah B, Weadge A, Jamieson NL, Tropak M, Cameron JM, Addis JB, Robinson BH. Identification of drug candidates which increase cytochrome c oxidase activity in deficient patient fibroblasts. Mitochondrion. 2011 Mar; 11(2):264-72. PMID: 21050896.
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    23. Schitter G, Steiner AJ, Pototschnig G, Scheucher E, Thonhofer M, Tarling CA, Withers SG, Fantur K, Paschke E, Mahuran DJ, Rigat BA, Tropak MB, Illaszewicz C, Saf R, Stütz AE, Wrodnigg TM. Fluorous iminoalditols: a new family of glycosidase inhibitors and pharmacological chaperones. Chembiochem. 2010 Sep 24; 11(14):2026-33. PMID: 20715263.
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    24. Clarke JT, Mahuran DJ, Sathe S, Kolodny EH, Rigat BA, Raiman JA, Tropak MB. An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants). Mol Genet Metab. 2011 Jan; 102(1):6-12. PMID: 20926324.
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    25. Steensrud T, Li J, Dai X, Manlhiot C, Kharbanda RK, Tropak M, Redington A. Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral preconditioning by remote limb ischemia or intra-arterial adenosine. . 2010 Nov; 299(5):H1598-603. PMID: 20802131.
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    26. Fröhlich RF, Furneaux RH, Mahuran DJ, Rigat BA, Stütz AE, Tropak MB, Wicki J, Withers SG, Wrodnigg TM. 1-Deoxynojirimycins with dansyl capped N-substituents as probes for Morbus Gaucher affected cell lines. Carbohydr Res. 2010 Jul 02; 345(10):1371-6. PMID: 20471633.
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    27. Schitter G, Scheucher E, Steiner AJ, Stütz AE, Thonhofer M, Tarling CA, Withers SG, Wicki J, Fantur K, Paschke E, Mahuran DJ, Rigat BA, Tropak M, Wrodnigg TM. Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors. Beilstein J Org Chem. 2010 Mar 01; 6:21. PMID: 20502610.
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    28. Tropak MB, Bukovac SW, Rigat BA, Yonekawa S, Wakarchuk W, Mahuran DJ. A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates. Glycobiology. 2010 Mar; 20(3):356-65. PMID: 19917668.
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    29. Shimizu M, Tropak M, Diaz RJ, Suto F, Surendra H, Kuzmin E, Li J, Gross G, Wilson GJ, Callahan J, Redington AN. Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. Clin Sci (Lond). 2009 Aug 03; 117(5):191-200. PMID: 19175358.
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    30. Maegawa GH, Tropak MB, Buttner JD, Rigat BA, Fuller M, Pandit D, Tang L, Kornhaber GJ, Hamuro Y, Clarke JT, Mahuran DJ. Identification and characterization of ambroxol as an enzyme enhancement agent for Gaucher disease. J Biol Chem. 2009 Aug 28; 284(35):23502-16. PMID: 19578116.
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    31. Steiner AJ, Schitter G, Stütz AE, Wrodnigg TM, Tarling CA, Withers SG, Mahuran DJ, Tropak MB. 2-Acetamino-1,2-dideoxynojirimycin-lysine hybrids as hexosaminidase inhibitors. Tetrahedron Asymmetry. 2009 May 01; 20(6-8):832-835. PMID: 22328804.
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    32. Kornhaber GJ, Tropak MB, Maegawa GH, Tuske SJ, Coales SJ, Mahuran DJ, Hamuro Y. Isofagomine induced stabilization of glucocerebrosidase. Chembiochem. 2008 Nov 03; 9(16):2643-9. PMID: 18932186.
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    33. Tropak MB, Kornhaber GJ, Rigat BA, Maegawa GH, Buttner JD, Blanchard JE, Murphy C, Tuske SJ, Coales SJ, Hamuro Y, Brown ED, Mahuran DJ. Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry. Chembiochem. 2008 Nov 03; 9(16):2650-62. PMID: 18972510.
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    34. Steiner AJ, Schitter G, Stütz AE, Wrodnigg TM, Tarling CA, Withers SG, Fantur K, Mahuran D, Paschke E, Tropak M. 1-Deoxygalactonojirimycin-lysine hybrids as potent D-galactosidase inhibitors. Bioorg Med Chem. 2008 Dec 15; 16(24):10216-20. PMID: 18996021.
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    35. Wang L, Oka N, Tropak M, Callahan J, Lee J, Wilson G, Redington A, Caldarone CA. Remote ischemic preconditioning elaborates a transferable blood-borne effector that protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest. J Thorac Cardiovasc Surg. 2008 Aug; 136(2):335-42. PMID: 18692639.
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    36. Tropak MB, Mahuran D. Lending a helping hand, screening chemical libraries for compounds that enhance beta-hexosaminidase A activity in GM2 gangliosidosis cells. FEBS J. 2007 Oct; 274(19):4951-61. PMID: 17894780.
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    37. Tropak MB, Blanchard JE, Withers SG, Brown ED, Mahuran D. High-throughput screening for human lysosomal beta-N-Acetyl hexosaminidase inhibitors acting as pharmacological chaperones. Chem Biol. 2007 Feb; 14(2):153-64. PMID: 17317569.
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    38. Maegawa GH, Tropak M, Buttner J, Stockley T, Kok F, Clarke JT, Mahuran DJ. Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis. J Biol Chem. 2007 Mar 23; 282(12):9150-61. PMID: 17237499.
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    39. Maegawa GH, Stockley T, Tropak M, Banwell B, Blaser S, Kok F, Giugliani R, Mahuran D, Clarke JT. The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported. Pediatrics. 2006 Nov; 118(5):e1550-62. PMID: 17015493.
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    40. Fan X, Zhang H, Zhang S, Bagshaw RD, Tropak MB, Callahan JW, Mahuran DJ. Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C). Am J Hum Genet. 2006 Oct; 79(4):738-44. PMID: 16960811.
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    41. Sinici I, Zarghooni M, Tropak MB, Mahuran DJ, Ozkara HA. Comparison of HCMV IE and EF-1 promoters for the stable expression of beta-subunit of hexosaminidase in CHO cell lines. Biochem Genet. 2006 Apr; 44(3-4):173-80. PMID: 16645900.
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    42. Zarghooni M, Bukovac S, Tropak M, Callahan J, Mahuran D. An alpha-subunit loop structure is required for GM2 activator protein binding by beta-hexosaminidase A. Biochem Biophys Res Commun. 2004 Nov 19; 324(3):1048-52. PMID: 15485660.
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    43. Tropak MB, Reid SP, Guiral M, Withers SG, Mahuran D. Pharmacological enhancement of beta-hexosaminidase activity in fibroblasts from adult Tay-Sachs and Sandhoff Patients. J Biol Chem. 2004 Apr 02; 279(14):13478-87. PMID: 14724290.
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    44. Sinici I, Tropak MB, Mahuran DJ, Ozkara HA. Assessing the severity of the small inframe deletion mutation in the alpha-subunit of beta-hexosaminidase A found in the Turkish population by reproducing it in the more stable beta-subunit. J Inherit Metab Dis. 2004; 27(6):747-56. PMID: 15505380.
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    45. Foussias G, Taylor SM, Yousef GM, Tropak MB, Ordon MH, Diamandis EP. Cloning and molecular characterization of two splice variants of a new putative member of the Siglec-3-like subgroup of Siglecs. Biochem Biophys Res Commun. 2001 Jun 22; 284(4):887-99. PMID: 11409877.
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    46. Schnaar RL, Collins BE, Wright LP, Kiso M, Tropak MB, Roder JC, Crocker PR. Myelin-associated glycoprotein binding to gangliosides. Structural specificity and functional implications. Ann N Y Acad Sci. 1998 Jun 19; 845:92-105. PMID: 9668345.
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    47. Collins BE, Kiso M, Hasegawa A, Tropak MB, Roder JC, Crocker PR, Schnaar RL. Binding specificities of the sialoadhesin family of I-type lectins. Sialic acid linkage and substructure requirements for binding of myelin-associated glycoprotein, Schwann cell myelin protein, and sialoadhesin. J Biol Chem. 1997 Jul 04; 272(27):16889-95. PMID: 9201997.
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    48. Tropak MB, Roder JC. Regulation of myelin-associated glycoprotein binding by sialylated cis-ligands. J Neurochem. 1997 Apr; 68(4):1753-63. PMID: 9084450.
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    49. Shpitz B, Stern H, Sandhu JS, Reilley RM, Tropak MB, Jansz G, Xu J, Gallinger S. Cytotoxicity of B72.3XOKT3 bispecific antibody recognizing human colon cancer. J Surg Res. 1996 Feb 15; 61(1):134-8. PMID: 8769955.
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    50. Tropak MB, Jansz GF, Abramow-Newerly W, Roder JC. Conservation of functionally important epitopes on myelin associated glycoprotein (MAG). Comp Biochem Physiol B Biochem Mol Biol. 1995 Oct; 112(2):345-54. PMID: 7584863.
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    51. Meyer-Franke A, Tropak MB, Roder JC, Fischer P, Beyreuther K, Probstmeier R, Schachner M. Functional topography of myelin-associated glycoprotein. II. Mapping of domains on molecular fragments. J Neurosci Res. 1995 Jun 15; 41(3):311-23. PMID: 7563224.
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    52. Li C, Tropak MB, Gerlai R, Clapoff S, Abramow-Newerly W, Trapp B, Peterson A, Roder J. Myelination in the absence of myelin-associated glycoprotein. Nature. 1994 Jun 30; 369(6483):747-50. PMID: 7516497.
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    53. Tropak MB, Roder JC. High-resolution mapping of GenS3 and B11F7 epitopes on myelin-associated glycoprotein by expression PCR. J Neurochem. 1994 Mar; 62(3):854-62. PMID: 7509375.
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    54. Almazan G, Tropak M, Roder J. Myelin associated glycoproteins confer heterophilic adhesion properties to an immortalized optic nerve derived cell line. Cell Struct Funct. 1992 Dec; 17(6):407-15. PMID: 1284234.
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    55. Dulac C, Tropak MB, Cameron-Curry P, Rossier J, Marshak DR, Roder J, Le Douarin NM. Molecular characterization of the Schwann cell myelin protein, SMP: structural similarities within the immunoglobulin superfamily. Neuron. 1992 Feb; 8(2):323-34. PMID: 1739462.
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    56. Johnson PW, Abramow-Newerly W, Seilheimer B, Sadoul R, Tropak MB, Arquint M, Dunn RJ, Schachner M, Roder JC. Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function. Neuron. 1989 Sep; 3(3):377-85. PMID: 2484339.
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    57. D'Agostaro G, Bendiak B, Tropak M. Cloning of cDNA encoding the membrane-bound form of bovine beta 1,4-galactosyltransferase. Eur J Biochem. 1989 Jul 15; 183(1):211-7. PMID: 2502398.
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    58. Attia J, Tropak M, Johnson PW, Newerly-Abranow W, Pawson T, Roder JC, Dunn RJ. Modulated adhesion: a proposal for the role of myelin-associated glycoprotein in myelin wrapping. Clin Chem. 1989 May; 35(5):717-20. PMID: 2655996.
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    59. Tropak MB, Johnson PW, Dunn RJ, Roder JC. Differential splicing of MAG transcripts during CNS and PNS development. Brain Res. 1988 Sep; 464(2):143-55. PMID: 2464408.
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    60. Arpaia E, Dumbrille-Ross A, Maler T, Neote K, Tropak M, Troxel C, Stirling JL, Pitts JS, Bapat B, Lamhonwah AM, et al. Identification of an altered splice site in Ashkenazi Tay-Sachs disease. Nature. 1988 May 05; 333(6168):85-6. PMID: 3362213.
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    61. Oshima A, Kyle JW, Miller RD, Hoffmann JW, Powell PP, Grubb JH, Sly WS, Tropak M, Guise KS, Gravel RA. Cloning, sequencing, and expression of cDNA for human beta-glucuronidase. Proc Natl Acad Sci U S A. 1987 Feb; 84(3):685-9. PMID: 3468507.
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    62. Quan F, Korneluk RG, Tropak MB, Gravel RA. Isolation and characterization of the human catalase gene. Nucleic Acids Res. 1986 Jul 11; 14(13):5321-35. PMID: 3755525.
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    63. Korneluk RG, Mahuran DJ, Neote K, Klavins MH, O'Dowd BF, Tropak M, Willard HF, Anderson MJ, Lowden JA, Gravel RA. Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease. J Biol Chem. 1986 Jun 25; 261(18):8407-13. PMID: 3013851.
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    64. Soltyk A, Tropak M, Friesen JD. Isolation and characterization of the RNA2+, RNA4+, and RNA11+ genes of Saccharomyces cerevisiae. J Bacteriol. 1984 Dec; 160(3):1093-100. PMID: 6094499.
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    65. Friesen JD, Tropak M, An G. Mutations in the rpIJ leader of Escherichia coli that abolish feedback regulation. Cell. 1983 Feb; 32(2):361-9. PMID: 6186394.
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