Pharmacology and Toxicology

Faculty: Matthieu Schapira, PhD

Matthieu Schapira, PhDMatthieu Schapira, PhD
Associate Professor

General Research Area: Computational Chemistry.

Matthieu holds a M.Sc degree in chemistry from the National Superior Chemistry School, Nancy, France, and a Ph.D in biochemistry from Ecole Normale Superieure, Paris. After graduating in 1995, he completed a couple post-docs in protein crystallography and computational chemistry at New York University Medical Center. In 2000, he joined Molsoft, a San-Diego based biotech, as senior research scientist. In 2003, he moved to Lyon, France, to lead structure-based drug design at Aptanomics/Imaxio, a drug discovery start-up. In 2007, he joined the SGC (Structural Genomics Consortium) as head of research informatics. Matthieu holds an Associate Professor cross-appointment with the Department of Pharmacology and Toxicology at University of Toronto, and an adjunct Associate Professor position with the Department of Pharmacology at New York University.

SGC Toronto’s Research Informatics group has three distinct roles. (1) Research: we apply computational chemistry tools to analyze protein structures and support the development of chemical inhibitors. We also analyze cancer genomics data. (2) Tools: we develop web interfaces, such as Chromohub, to easily navigate structural, chemical and genomic data. (3) Databases: we manage the wealth of biological and chemical data generated at SGC-Toronto.


Pubmed

Selected Publications:

Open laboratory notebooks: good for science, good for society, good for scientists
Schapira M, The Open Lab Notebook Consortium, Harding R
F1000Research. 2019 . doi: 10.12688/f1000research.17710.1

Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors.
Ferreira de Freitas R, Harding RJ, Franzoni I, Ravichandran M, Mann MK, Ouyang H, Lautens M, Santhakumar V, Arrowsmith CH, Schapira M
J. Med. Chem. 2018. doi: 10.1021/acs.jmedchem.8b00258
PMID: 29741882

WD40 repeat domain proteins: a novel target class?
Schapira M, Tyers M, Torrent M, Arrowsmith CH
Nat Rev Drug Discov. 2017 . doi: 10.1038/nrd.2017.179
PMID: 29026209

Disease Association and Druggability of WD40 Repeat Proteins.
Song R, Wang ZD, Schapira M
J. Proteome Res.. 2017 . doi: 10.1021/acs.jproteome.7b00451
PMID: 28956604

Chemical Inhibition of Protein Methyltransferases.
Schapira M
Cell Chem Biol. 2016 . doi: 10.1016/j.chembiol.2016.07.014
PMID: 27569753

Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening.
Ferreira de Freitas R, Eram MS, Smil D, Szewczyk MM, Kennedy S, Brown PJ, Santhakumar V, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M
J. Med. Chem. 2016. doi: 10.1021/acs.jmedchem.6b00668
PMID: 27390919

Discovery of a Potent Class I Protein Arginine Methyltransferase Fragment Inhibitor.
Ferreira de Freitas R, Eram MS, Szewczyk MM, Steuber H, Smil D, Wu H, Li F, Senisterra G, Dong A, Brown PJ, Hitchcock M, Moosmayer D, Stegmann CM, Egner U, Arrowsmith C, Barsyte-Lovejoy D, Vedadi M, Schapira M
J. Med. Chem. 2016. doi: 10.1021/acs.jmedchem.5b01772
PMID: 26824386

Probing the epigenome.
Huston A, Arrowsmith CH, Knapp S, Schapira M
Nat. Chem. Biol. 2015. 11(8):542-5. doi: 10.1038/nchembio.1871
PMID: 26196765

Discovery of a Dual PRMT5-PRMT7 Inhibitor.
Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M
ACS Med Chem Lett. 2015 6(4):408-12. doi: 10.1021/ml500467h
PMID: 25893041

Structural Chemistry of Human RNA Methyltransferases.
Schapira M
ACS Chem. Biol. 2015. doi: 10.1021/acschembio.5b00781
PMID: 26566070

STRUCTURAL BIOLOGY. Chromatin complex, crystal clear.
Schapira M
Science. 2015 350(6258):278-9. doi: 10.1126/science.aad5203
PMID: 26472895

Structural diversity of the epigenetics pocketome.
Cabaye A, Nguyen KT, Liu L, Pande V, Schapira M
Proteins. 2015 . doi: 10.1002/prot.24830
PMID: 25974248

Structural biology and chemistry of protein arginine methyltransferases.
Schapira M, Ferreira de Freitas R
Medchemcomm. 2014 5(12):1779-1788. doi: 10.1039/c4md00269e
PMID: 26693001

A global assessment of cancer genomic alterations in epigenetic mechanisms.
Shah MA, Denton EL, Arrowsmith CH, Lupien M, Schapira M
Epigenetics Chromatin. 2014 7(1):29. doi: 10.1186/1756-8935-7-29
PMID: 25484917

Strategy to Target the Substrate Binding site of SET Domain Protein Methyltransferases.
Nguyen KT, Li F, Poda G, Smil D, Vedadi M, Schapira M
J Chem Inf Model. 2013 . doi: 10.1021/ci300596x
PMID: 23410263

ChromoHub V2: Cancer Genomics.
Shah MA, Denton EL, Liu L, Schapira M
Bioinformatics. 2013 . doi: 10.1093/bioinformatics/btt710
PMID: 24319001

Bromo-deaza-SAH: A potent and selective DOT1L inhibitor.
Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH, Vedadi M, Brown PJ, Schapira M
Bioorg. Med. Chem.. 2013 21(7):1787-94. doi: 10.1016/j.bmc.2013.01.049
PMID: 23433670

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.
Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M
Nat Commun. 2012 3:1288. doi: 10.1038/ncomms2304
PMID: 23250418

Epigenetic protein families: a new frontier for drug discovery.
Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M
Nat Rev Drug Discov. 2012 11(5):384-400. doi: 10.1038/nrd3674
PMID: 22498752

ChromoHub: a data hub for navigators of chromatin-mediated signalling.
Liu L, Zhen XT, Denton E, Marsden BD, Schapira M
Bioinformatics. 2012 28(16):2205-6. doi: 10.1093/bioinformatics/bts340
PMID: 22718786

Druggability of methyl-lysine binding sites.
Santiago C, Nguyen K, Schapira M
J. Comput. Aided Mol. Des.. 2011 25(12):1171-8. doi: 10.1007/s10822-011-9505-2
PMID: 22146969

Structural biology of human metal-dependent histone deacetylases.
Schapira M
Handb Exp Pharmacol. 2011 206:225-40. doi: 10.1007/978-3-642-21631-2_10
PMID: 21879452

Structural Chemistry of Human SET Domain Protein Methyltransferases.
Schapira M
Curr Chem Genomics. 2011 5(Suppl 1):85-94. doi: 10.2174/1875397301005010085
PMID: 21966348

Structural chemistry of the histone methyltransferases cofactor binding site.
Campagna-Slater V, Mok MW, Nguyen KT, Feher M, Najmanovich R, Schapira M
J Chem Inf Model. 2011 51(3):612-23. doi: 10.1021/ci100479z
PMID: 21366357

Structural genomics of histone tail recognition.
Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M
Bioinformatics. 2010 26(20):2629-30. doi: 10.1093/bioinformatics/btq491
PMID: 20739309

Finding Inspiration in the Protein Data Bank to Chemically Antagonize Readers of the Histone Code.
Campagna-Slater V, Schapira M
Mol Inform. 2010 29(4):322-31. doi: 10.1002/minf.201000018
PMID: 27463059

Pharmacophore screening of the protein data bank for specific binding site chemistry.
Campagna-Slater V, Arrowsmith AG, Zhao Y, Schapira M
J Chem Inf Model. 2010 50(3):358-67. doi: 10.1021/ci900427b
PMID: 20112952

Structural biology of human H3K9 methyltransferases.
Wu H, Min J, Lunin VV, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M
PLoS ONE. 2010 5(1):e8570. doi: 10.1371/journal.pone.0008570
PMID: 20084102

Evaluation of virtual screening as a tool for chemical genetic applications.
Campagna-Slater V, Schapira M
J Chem Inf Model. 2009 49(9):2082-91. doi: 10.1021/ci900219u
PMID: 19702241


Contact:
Structural Genomics Consortium
101 College St. , South Tower, Rm 713
Toronto, Ontario
M5G 1L6
Phone: 416-978-3092
Email: matthieu.schapira@utoronto.ca