Raymond Hui

Principal Investigator

University of Toronto

Since 2004, Ray’s group has become the world leader in the expression, purification, crystallization and chemical screening of parasite proteins. The goal of this research is to produce tools to support anti-parasitic drug discovery as well as to enable other parasitologists in their quest to understand parasite biology and host invasion. The tools produced by Ray’s team include purified recombinant parasite proteins, inhibitors of these proteins and their crystallographic structures, all of which are readily shared with parasitology labs around the world.

Research Areas

Malaria, toxoplasmosis, cryptosporidiosis, Chagas disease, African Sleeping Disease and visceral leishmaniasis are diseases resulting from infection by protozoan parasites. For some of these diseases, such as malaria, existing drugs face the threat of resistance. For others, such as cryptosporidiosis, there is no effective chemotherapy. At SGC in Toronto, Raymond Hui leads the Structural and Chemical Parasitology group to study proteins of protozoan parasites. Structural parasitology is the study of structures of parasite proteins. Chemical parasitology involves the identification and use of chemical probes to investigate the functions of these proteins.

Group Members

  • Majida El Bakkouri
  • Linda Lin
  • Khan Osman
  • Mehrnaz Amani
  • Dunquan Jiang
  • David Hou
  • Andrew Bognar
  • Kodjo Ayi
Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from Plasmodium parasites.
Artz JD, Wernimont AK, Dunford JE, Schapira M, Dong A, Zhao Y, Lew J, Russell RG, Ebetino FH, Oppermann U, Hui R
J. Biol. Chem.. 2011 286(5):3315-22. doi: 10.1074/jbc.M109.027235
PMID: 21084289

The Cryptosporidium parvum kinome.
Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P, Hutchinson A, Chau I, von Delft F, MacKenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R
BMC Genomics. 2011 12:478. doi: 10.1186/1471-2164-12-478
PMID: 21962082

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium.
Wernimont AK, Artz JD, Finerty P, Lin YH, Amani M, Allali-Hassani A, Senisterra G, Vedadi M, Tempel W, Mackenzie F, Chau I, Lourido S, Sibley LD, Hui R
Nat. Struct. Mol. Biol.. 2010 17(5):596-601. doi: 10.1038/nsmb.1795
PMID: 20436473

Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma.
Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD
Nature. 2010 465(7296):359-62. doi: 10.1038/nature09022
PMID: 20485436

Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis.
Sibley LD, Qiu W, Fentress S, Taylor SJ, Khan A, Hui R
Eukaryotic Cell. 2009 8(8):1085-93. doi: 10.1128/EC.00107-09
PMID: 19465561

2017

Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor.
Osman KT, Ye J, Shi Z, Toker C, Lovato D, Jumani RS, Zuercher W, Huston CD, Edwards AM, Lautens M, Santhakumar V, Hui R
Bioorg. Med. Chem.. 24.01.2017 . doi: 10.1016/j.bmc.2017.01.036
PMID: 28162900

2016

Discovery of a PCAF Bromodomain Chemical Probe.
Moustakim M, Clark PG, Trulli L, Fuentes de Arriba AL, Ehebauer MT, Chaikuad A, Murphy EJ, Mendez-Johnson J, Daniels D, Hou CD, Lin YH, Walker JR, Hui R, Yang H, Dorrell L, Rogers CM, Monteiro OP, Fedorov O, Huber KV, Knapp S, Heer J, Dixon DJ, Brennan PE
Angew. Chem. Int. Ed. Engl.. 14.12.2016 . doi: 10.1002/anie.201610816
PMID: 27966810

Using a Genetically Encoded Sensor to Identify Inhibitors of Toxoplasma gondii Ca2+ Signalling.
Sidik SM, Hortua Triana MA, Paul AS, El Bakkouri M, Hackett CG, Tran F, Westwood NJ, Hui R, Zuercher WJ, Duraisingh MT, Moreno SN, Lourido S
J. Biol. Chem.. 29.04.2016 . doi: 10.1074/jbc.M115.703546
PMID: 26933036

Identification of small molecule inhibitors that block the Toxoplasma gondii rhoptry kinase ROP18.
Simpson C, Jones NG, Hull-Ryde EA, Kireev D, Stashko M, Tang K, Janetka J, Wildman SA, Zuercher WJ, Schapira M, Hui R, Janzen W, Sibley LD
ACS Infect Dis. 11.03.2016 2(3):194-206. doi: 10.1021/acsinfecdis.5b00102
PMID: 27379343

Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against 14,000 Cell-Active Compounds.
Crowther GJ, Hillesland HK, Keyloun KR, Reid MC, Lafuente-Monasterio MJ, Ghidelli-Disse S, Leonard SE, He P, Jones JC, Krahn MM, Mo JS, Dasari KS, Fox AM, Boesche M, El Bakkouri M, Rivas KL, Leroy D, Hui R, Drewes G, Maly DJ, Van Voorhis WC, Ojo KK
PLoS ONE. 02.03.2016 11(3):e0149996. doi: 10.1371/journal.pone.0149996
PMID: 26934697

2015

Identification of small molecule inhibitors that block the Toxoplasma gondii rhoptry kinase ROP18
Simpson C, Jones N, Hull-Ryde E, Kireev D, Stashko M, Tang K, Janetka J, Wildman S, Zuercher W, Schapira M, Hui R, Janzen W, Sibley LD.
ACS Infect. Dis.. 28.12.2015 2(3):194-206. doi: 10.1021/acsinfecdis.5b00102
PMID:

Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans.
Hui R, El Bakkouri M, Sibley LD
Trends Pharmacol. Sci.. 05.07.2015 . doi: 10.1016/j.tips.2015.04.011
PMID: 26002073

Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c) from Plasmodium falciparum.
Buchko GW, Yee A, Semesi A, Myler PJ, Arrowsmith CH, Hui R
Acta Crystallogr F Struct Biol Commun. 18.04.2015 71(Pt 5):514-21. doi: 10.1107/S2053230X1402799X
PMID: 25945703

Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design.
Mohanty S, Kennedy EJ, Herberg FW, Hui R, Taylor SS, Langsley G, Kannan N
Biochim. Biophys. Acta. 03.04.2015 . doi: 10.1016/j.bbapap.2015.03.012
PMID: 25847873

2013

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design.
Pizarro JC, Hills T, Senisterra G, Wernimont AK, Mackenzie C, Norcross NR, Ferguson MA, Wyatt PG, Gilbert IH, Hui R
PLoS Negl Trop Dis. 17.10.2013 7(10):e2492. doi: 10.1371/journal.pntd.0002492
PMID: 24147171

2012

Structural insights into the inactive subunit of the apicoplast-localized caseinolytic protease complex of Plasmodium falciparum.
El Bakkouri M, Rathore S, Calmettes C, Wernimont AK, Liu K, Sinha D, Asad M, Jung P, Hui R, Mohmmed A, Houry WA
J. Biol. Chem.. 28.11.2012 . doi: 10.1074/jbc.M112.416560
PMID: 23192353

Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase.
Bandini G, Mariño K, Güther ML, Wernimont AK, Kuettel S, Qiu W, Afzal S, Kelner A, Hui R, Ferguson MA
Mol. Microbiol.. 12.07.2012 85(3):513-34. doi: 10.1111/j.1365-2958.2012.08124.x
PMID: 22676716

Novel insights into the regulation of malarial calcium-dependent protein kinase 1.
Ahmed A, Gaadhe K, Sharma GP, Kumar N, Neculai M, Hui R, Mohanty D, Sharma P
FASEB J.. 25.04.2012 26(8):3212-21. doi: 10.1096/fj.12-203877
PMID: 22539638

Crystal structures from the Plasmodium peroxiredoxins: new insights into oligomerization and product binding.
Qiu W, Dong A, Pizarro JC, Botchkarsev A, Min J, Wernimont AK, Hills T, Hui R, Artz JD
BMC Struct. Biol.. 19.03.2012 12:2. doi: 10.1186/1472-6807-12-2
PMID: 22429898

Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium geranylgeranyl diphosphate synthase (GGPPS) and exhibit potent antimalarial activity.
No JH, de Macedo Dossin F, Zhang Y, Liu YL, Zhu W, Feng X, Yoo JA, Lee E, Wang K, Hui R, Freitas-Junior LH, Oldfield E
Proc. Natl. Acad. Sci. U.S.A.. 13.03.2012 109(11):4058-63. doi: 10.1073/pnas.1118215109
PMID: 22392982

2011

Target highlights in CASP9: Experimental target structures for the critical assessment of techniques for protein structure prediction.
Kryshtafovych A, Moult J, Bartual SG, Bazan JF, Berman H, Casteel DE, Christodoulou E, Everett JK, Hausmann J, Heidebrecht T, Hills T, Hui R, Hunt JF, Seetharaman J, Joachimiak A, Kennedy MA, Kim C, Lingel A, Michalska K, Montelione GT, Otero JM, Perrakis A, Pizarro JC, van Raaij MJ, Ramelot TA, Rousseau F, Tong L, Wernimont AK, Young J, Schwede T
Proteins. 21.10.2011 79 Suppl 10:6-20. doi: 10.1002/prot.23196
PMID: 22020785

The Cryptosporidium parvum kinome.
Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P, Hutchinson A, Chau I, von Delft F, MacKenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R
BMC Genomics. 30.09.2011 12:478. doi: 10.1186/1471-2164-12-478
PMID: 21962082

Characterization of 14-3-3 proteins from Cryptosporidium parvum.
Brokx SJ, Wernimont AK, Dong A, Wasney GA, Lin YH, Lew J, Vedadi M, Lee WH, Hui R
PLoS ONE. 11.08.2011 6(8):e14827. doi: 10.1371/journal.pone.0014827
PMID: 21853016

Characterization of a new phosphatase from Plasmodium.
Hills T, Srivastava A, Ayi K, Wernimont AK, Kain K, Waters AP, Hui R, Pizarro JC
Mol. Biochem. Parasitol.. 13.06.2011 179(2):69-79. doi: 10.1016/j.molbiopara.2011.06.001
PMID: 21689687

Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from Plasmodium parasites.
Artz JD, Wernimont AK, Dunford JE, Schapira M, Dong A, Zhao Y, Lew J, Russell RG, Ebetino FH, Oppermann U, Hui R
J. Biol. Chem.. 04.02.2011 286(5):3315-22. doi: 10.1074/jbc.M109.027235
PMID: 21084289

2010

Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.
Fentress SJ, Behnke MS, Dunay IR, Mashayekhi M, Rommereim LM, Fox BA, Bzik DJ, Taylor GA, Turk BE, Lichti CF, Townsend RR, Qiu W, Hui R, Beatty WL, Sibley LD
Cell Host Microbe. 16.12.2010 8(6):484-95. doi: 10.1016/j.chom.2010.11.005
PMID: 21147463

Structures of parasitic CDPK domains point to a common mechanism of activation.
Wernimont AK, Amani M, Qiu W, Pizarro JC, Artz JD, Lin YH, Lew J, Hutchinson A, Hui R
Proteins. 03.12.2010 79(3):803-20. doi: 10.1002/prot.22919
PMID: 21287613

The Clp chaperones and proteases of the human malaria parasite Plasmodium falciparum.
El Bakkouri M, Pow A, Mulichak A, Cheung KL, Artz JD, Amani M, Fell S, de Koning-Ward TF, Goodman CD, McFadden GI, Ortega J, Hui R, Houry WA
J. Mol. Biol.. 03.12.2010 404(3):456-77. doi: 10.1016/j.jmb.2010.09.051
PMID: 20887733

The crystal structure of Toxoplasma gondii pyruvate kinase 1.
Bakszt R, Wernimont A, Allali-Hassani A, Mok MW, Hills T, Hui R, Pizarro JC
PLoS ONE. 14.09.2010 5(9):e12736. doi: 10.1371/journal.pone.0012736
PMID: 20856875

Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma.
Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD
Nature. 20.05.2010 465(7296):359-62. doi: 10.1038/nature09022
PMID: 20485436

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium.
Wernimont AK, Artz JD, Finerty P, Lin YH, Amani M, Allali-Hassani A, Senisterra G, Vedadi M, Tempel W, Mackenzie F, Chau I, Lourido S, Sibley LD, Hui R
Nat. Struct. Mol. Biol.. 02.05.2010 17(5):596-601. doi: 10.1038/nsmb.1795
PMID: 20436473

Structure and function of a G-actin sequestering protein with a vital role in malaria oocyst development inside the mosquito vector.
Hliscs M, Sattler JM, Tempel W, Artz JD, Dong A, Hui R, Matuschewski K, Schüler H
J. Biol. Chem.. 09.04.2010 285(15):11572-83. doi: 10.1074/jbc.M109.054916
PMID: 20083609

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.
Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG
Nature. 01.04.2010 464(7289):728-32. doi: 10.1038/nature08893
PMID: 20360736

2009

Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide.
Alag R, Bharatham N, Dong A, Hills T, Harikishore A, Widjaja AA, Shochat SG, Hui R, Yoon HS
Protein Sci.. 20.08.2009 18(10):2115-24. doi: 10.1002/pro.226
PMID: 19691130

Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis.
Sibley LD, Qiu W, Fentress S, Taylor SJ, Khan A, Hui R
Eukaryotic Cell. 22.05.2009 8(8):1085-93. doi: 10.1128/EC.00107-09
PMID: 19465561

Buffer optimization of thermal melt assays of Plasmodium proteins for detection of small-molecule ligands.
Crowther GJ, Napuli AJ, Thomas AP, Chung DJ, Kovzun KV, Leibly DJ, Castaneda LJ, Bhandari J, Damman CJ, Hui R, Hol WG, Buckner FS, Verlinde CL, Zhang Z, Fan E, van Voorhis WC
J Biomol Screen. 21.05.2009 14(6):700-7. doi: 10.1177/1087057109335749
PMID: 19470714

Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.
Qiu W, Wernimont A, Tang K, Taylor S, Lunin V, Schapira M, Fentress S, Hui R, Sibley LD
EMBO J.. 08.04.2009 28(7):969-79. doi: 10.1038/emboj.2009.24
PMID: 19197235

2008

Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.
Artz JD, Dunford JE, Arrowood MJ, Dong A, Chruszcz M, Kavanagh KL, Minor W, Russell RG, Ebetino FH, Oppermann U, Hui R
Chem. Biol.. 22.12.2008 15(12):1296-306. doi: 10.1016/j.chembiol.2008.10.017
PMID: 19101474

Protein production and purification.
Gräslund S, Nordlund P, Weigelt J, Hallberg BM, Bray J, Gileadi O, Knapp S, Oppermann U, Arrowsmith C, Hui R, Ming J, dhe-Paganon S, Park HW, Savchenko A, Yee A, Edwards A, Vincentelli R, Cambillau C, Kim R, Kim SH, Rao Z, Shi Y, Terwilliger TC, Kim CY, Hung LW, Waldo GS, Peleg Y, Albeck S, Unger T, Dym O, Prilusky J, Sussman JL, Stevens RC, Lesley SA, Wilson IA, Joachimiak A, Collart F, Dementieva I, Donnelly MI, Eschenfeldt WH, Kim Y, Stols L, Wu R, Zhou M, Burley SK, Emtage JS, Sauder JM, Thompson D, Bain K, Luz J, Gheyi T, Zhang F, Atwell S, Almo SC, Bonanno JB, Fiser A, Swaminathan S, Studier FW, Chance MR, Sali A, Acton TB, Xiao R, Zhao L, Ma LC, Hunt JF, Tong L, Cunningham K, Inouye M, Anderson S, Janjua H, Shastry R, Ho CK, Wang D, Wang H, Jiang M, Montelione GT, Stuart DI, Owens RJ, Daenke S, Schütz A, Heinemann U, Yokoyama S, Büssow K, Gunsalus KC
Nat. Methods. 01.02.2008 5(2):135-46. doi: 10.1038/nmeth.f.202
PMID: 18235434

2007

In situ proteolysis for protein crystallization and structure determination.
Dong A, Xu X, Edwards AM, Chang C, Chruszcz M, Cuff M, Cymborowski M, Di Leo R, Egorova O, Evdokimova E, Filippova E, Gu J, Guthrie J, Ignatchenko A, Joachimiak A, Klostermann N, Kim Y, Korniyenko Y, Minor W, Que Q, Savchenko A, Skarina T, Tan K, Yakunin A, Yee A, Yim V, Zhang R, Zheng H, Akutsu M, Arrowsmith C, Avvakumov GV, Bochkarev A, Dahlgren LG, Dhe-Paganon S, Dimov S, Dombrovski L, Finerty P, Flodin S, Flores A, Gräslund S, Hammerström M, Herman MD, Hong BS, Hui R, Johansson I, Liu Y, Nilsson M, Nedyalkova L, Nordlund P, Nyman T, Min J, Ouyang H, Park HW, Qi C, Rabeh W, Shen L, Shen Y, Sukumard D, Tempel W, Tong Y, Tresagues L, Vedadi M, Walker JR, Weigelt J, Welin M, Wu H, Xiao T, Zeng H, Zhu H
Nat. Methods. 04.11.2007 4(12):1019-21. doi: 10.1038/nmeth1118
PMID: 17982461

A potent, covalent inhibitor of orotidine 5'-monophosphate decarboxylase with antimalarial activity.
Bello AM, Poduch E, Fujihashi M, Amani M, Li Y, Crandall I, Hui R, Lee PI, Kain KC, Pai EF, Kotra LP
J. Med. Chem.. 08.03.2007 50(5):915-21. doi: 10.1021/jm060827p
PMID: 17290979

2006

Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms.
Vedadi M, Lew J, Artz J, Amani M, Zhao Y, Dong A, Wasney GA, Gao M, Hills T, Brokx S, Qiu W, Sharma S, Diassiti A, Alam Z, Melone M, Mulichak A, Wernimont A, Bray J, Loppnau P, Plotnikova O, Newberry K, Sundararajan E, Houston S, Walker J, Tempel W, Bochkarev A, Kozieradzki I, Edwards A, Arrowsmith C, Roos D, Kain K, Hui R
Mol. Biochem. Parasitol.. 13.11.2006 151(1):100-10. doi: 10.1016/j.molbiopara.2006.10.011
PMID: 17125854

Screening for ligands using a generic and high-throughput light-scattering-based assay.
Senisterra GA, Markin E, Yamazaki K, Hui R, Vedadi M, Awrey DE
J Biomol Screen. 07.11.2006 11(8):940-8. doi: 10.1177/1087057106294699
PMID: 17092916

Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination.
Vedadi M, Niesen FH, Allali-Hassani A, Fedorov OY, Finerty PJ, Wasney GA, Yeung R, Arrowsmith C, Ball LJ, Berglund H, Hui R, Marsden BD, Nordlund P, Sundstrom M, Weigelt J, Edwards AM
Proc. Natl. Acad. Sci. U.S.A.. 24.10.2006 103(43):15835-40. doi: 10.1073/pnas.0605224103
PMID: 17035505

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