You are here

Home > For Scientists > SGC Sites and Groups > Toronto > Biophysics

Biophysics

Group Site: 
toronto
Group Leader: 

Masoud Vedadi Ph.D. McGill University (1997)

Group Info

Research Areas

Masoud and his team characterize proteins produced by the SGC scientists in Toronto and also focus on developing new high throughput biophysical and biochemical characterization techniques. By screening proteins against customized chemical libraries, they identify ligands that promote crystallization and improve crystal quality. They also screen for buffer conditions that reduce protein aggregation and enable them to further concentrate problematic proteins. Creating and comparing chemical profiles for members of each family of protein along with functional studies, they investigate the structure-function relationship and identify unique inhibitors that can discriminate among members of each family of protein. Identifying human SNPs that affect human health by employing high throughput screening techniques is also an ongoing project in his group.

Group Members
Masoud Vedadi, Principal Investigator

Masoud received his Ph.D. from McGill University (1997) and worked as a postdoctoral fellow in the Department of Biochemistry in Concordia University, Canada, focusing on structural and functional studies of enzymes (1997-1999).

Masoud then joined Affinium Pharmaceuticals where he worked as Associate Director of Protein Science. There, he and his team were involved in purifying, characterizing and crystallizing hundreds of proteins as well as developing novel methods of protein purification and characterization (1999-2003). He later joined the Structural Genomics Consortium in 2003 as head of the Molecular Biophysics group.

Gregory Wasney, B.Sc., Laboratory Technician

 

After graduating with a B.Sc. in Biochemistry from the University of Manitoba in 1997, Greg worked at the University of British Columbia researching the roles of various chemokines until 2000 when he began to work at Sunnybrook Hospital in Toronto studying the mechanism of MRSA infection as well as evaluating the role of human kallikreins at Mount Sinai Hospital in Toronto. He joined the Structural Genomics Consortium in 2003.

Abdellah Allali-Hassani, Ph.D., Team Leader-Enzymatic Assays (Sr. RA)

 

Abdellah received his Ph.D. from UAB University, Barcelona, Spain (1997) and was engaged in postdoctoral studies in the Department of Biochemistry at Purdue University, Indiana, USA, focusing on the enzymology and molecular biology of ALDH family of proteins (1998-2000). He completed a second postdoctoral in Dr. Eric Brown’s laboratory at McMaster University (2001-2004) focusing on characterization and HTS of bacterial proteins with unknown function. Abdellah joined the Molecular Biophysics at SGC Toronto in 2005.

Guillermo Senisterra, Ph.D., Research Associate

 

Guillermo graduated with a Ph.D. degree in Biophysics from Facultad de Ciencias Exactas, National University of La Plata. Argentina. He later worked as a Post-Doctoral Fellow in the Department of Biochemistry, McMaster University and as a research associate in Department of Physics, University of Waterloo Canada. In 2000 he joined Affinium Pharmaceuticals Inc. as a senior scientist and was involved in inventing the StarGazerTM (DSLS screening). Guillermo later joined the Molecular Biophysics group in 2006.

Irene Chau, M.Sc., Laboratory Technician

 

Irene has been with the Molecular Biophysics group in SGC Toronto since November 2006 after graduating from University of Toronto with M.Sc. in Medical and Molecular Genetics.

Alena Siarheyeva, Ph.D., Research Associate

 

Alena has been with the Molecular Biophysics group in SGC Toronto since 2008. She graduated with a PhD degree in Biochemistry from the Institute of Biophysical Chemistry, University of Frankfurt, Germany in 2006. Her PhD was dedicated to Solid State NMR investigation on Multidrug Transporter LmrA. She later moved to the University of Guelph, where she spent almost 3 years working as a postdoctoral fellow, exploring mechanisms of multidrug resistance.

Taraneh Hajian, M.Sc., Laboratory Technician

 

Taraneh has been with the Molecular Biophysics group since 2009. She graduated from Tehran University with M.Sc. degree in virology.

Fengling Li, Ph.D., Research Associate

Fengling completed her Ph.D. in Plant Molecular Biology at the Institute of Plant Physiology & Ecology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, China. Following her doctoral studies, she worked in Dr. Ray Wu’s lab in Cornell University (1999-2003); the NRC Plant Biotechnology Institute in Saskatoon (2003-2006),  and  the University of British Columbia as a research associate (2006-2011). In 2011, she joined Molecular Biophysics group in Toronto.

Ekaterina Kuznetsova, Ph.D., Research Associate

 

Kate graduated from University of Toronto, Department of Medical Biophysics with a Ph.D. degree in 2009. She joined SGC Stockholm, Karolinska Institutet as a postdoctoral fellow and moved to SGC Toronto in September 2011.

Alisha Griffith, Student

 

Alisha is a Biotechnology student at Canadore College, Canada. She is completing her research project in Molecular Biophysics group. 

Tracy Tiefenbach , Ph.D., Post Doctoral Fellow

Tracy received her PhD from McMaster University in 2011 in Biochemistry & Biomedical research.  Her research focused on characterizing enzymes required for DNA interstrand crosslinking repair.  She began her postdoctoral work at the Structural Genomics Consortium in 2012.

Publications

Masoud Vedadi, Dalia Barsyte-Lovejoy, Feng Liu, Sylvie Rival-Gervier, Abdellah Allali-Hassani, Viviane Labrie, Tim J. Wigle, Peter A. DiMaggio, Gregory A. Wasney, Alena Siarheyeva, Aiping Dong, Wolfram Tempel1, Sun-Chong Wang, Xin Chen, Irene Chau, Thomas J. Mangano, Xi-ping Huang, Catherine D. Simpson, Samantha G. Pattenden, Jacqueline L. Norris, Dmitri B. Kireev, Ashutosh Tripathy, Aled Edwards, Bryan L. Roth, William P. Janzen, Benjamin A. Garcia, Arturas Petronis, James Ellis, Peter J. Brown, Stephen V. Frye, Cheryl H. Arrowsmith & Jian Jin (2011) A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. PMID:21743462.

Derek F. Ceccarelli, Xiaojing Tang, Benoit Pelletier, Stephen Orlicky, Weilin Xie, Veronique Plantevin, Dante Neculai, Yang-Chieh Chou, Abiodun Ogunjimi,1 Abdallah Al-Hakim, Xaralabos Varelas, Joanna Koszela, Gregory A. Wasney, Masoud Vedadi, Sirano Dhe-Paganon, Sarah Cox, Shuichan Xu, Antonia Lopez-Girona, Frank Mercurio, Jeff Wrana, Dan Durocher, Sylvain Meloche, David R. Webb, Mike Tyers and Frank Sicheri (2011) An Allosteric Inhibitor of the Human Cdc34 Ubiquitin-Conjugating Enzyme. Cell. PMID:21683433.

Abdellah Allali-Hassani, Gregory A Wasney, Alena Siarheyeva, Taraneh Hajian, Cheryl H. Arrowsmith and Masoud Vedadi (2011) Fluorescence-based methods for screening writers and readers of histone methyl marks. J. Biomol. Screen,PMID:21972038.

Guillermo Senisterra, Irene Chau and Masoud Vedadi (2011) Thermal Denaturation Assays in Chemical Biology. ASSAY and Drug Development Technologies,PMID:22066913

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 Jr, 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. (2011) The Cryptosporidium parvum Kinome. BMC Genomics. 12(1):478.

Brokx SJ, Wernimont AK, Dong A, Wasney GA, Lin YH, Lew J, Vedadi M, Lee WH, Hui R. (2011) Characterization of 14-3-3 Proteins from Cryptosporidium parvum.PLoS One. PMID:21853016.

Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold M, Chen X, Yates CM, Frye SV, Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J. (2011) Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines. J Med Chem. PMID:21780790

Herold JM, Wigle TJ, Norris JL, Lam R, Korboukh VK, Gao C, Ingerman LA, Kireev DB, Senisterra G, Vedadi M, Tripathy A, Brown PJ, Arrowsmith CH, Jin J, Janzen WP, Frye SV. (2011) Small-Molecule Ligands of Methyl-Lysine Binding Proteins. J Med Chem. PMID: 21417280

Kaustov L, Quyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney G, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH. (2010) Recognition and specificity determinants of the human Cbx chromodomains. J Biol Chem. PMID: 21047797.

Melanie A. Adams-Cioaba, Yahong Guo, ChuanBing Bian, Maria F. Amaya, Robert Lam, Gregory A. Wasney, Masoud Vedadi, Chao Xu, Jinrong Min (2010) Structural Studies of the Tandem Tudor Domains of Fragile X Mental Retardation Related Proteins FXR1 and FXR2. PLoS One.5(11):e13559. PMID: 21072162.

Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G, Chau I, Siarheyeva A, Norris JL, Kireev DB, Jadhav A, Herold JM, Janzen WP, Arrowsmith CH, Frye SV, Brown PJ, Simeonov A, Vedadi M, Jin J. (2010) Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines. J Med Chem. PMID: 20614940

Masoud Vedadi, Cheryl H. Arrowsmith, Abdellah Allali-Hassani, Guillermo Senisterra and Gregory A. Wasney (2010) Biophysical Characterization of Recombinant Proteins: A key to higher structural genomics success. J. Struct. Biol. PMID: 20466062.

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

Hong BS, Allali-Hassani A, Tempel W, Finerty PJ Jr, Mackenzie F, Dimov S, Vedadi M, Park HW. (2010) Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: Single amino acid near the active site influences inhibitor sensitivity. J. Biol. Chem. PMID: 20299452

Guillermo A. Senisterra, Hamed Ghanei, Galina Khutoreskaya, Elena Dobrovetsky, Aled M. Edwards, Gilbert G. Privé and Masoud Vedadi (2010) Assessing the stability of membrane proteins to detect ligand binding using differential static light scattering. J. Biomol. Screen. 15:314-320. PMID: 20150591.

Amy Quinn, Abdellah Allali-Hassani, Masoud Vedadi, Anton Simeonov (2010) A Chemiluminescence-based Method for Identification of Histone Lysine Methyltransferase Inhibitors. Molecular BioSystems. PMID: 20567762.

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. (2010) Structural biology of human H3K9 methyltransferases. PLoS One. 11;5(1):e8570. PMID: 20084102.

Tim J. Wigle, J. Martin Herold, Guillermo Senisterra, Masoud Vedadi, Dmitri B. Kireev, Cheyl H. Arrowsmith, Stephen V. Frye, and William P. Janzen. (2010) Screening for Inhibitors of Low-Affinity Epigenetic Peptide-Protein Interactions: An AlphaScreen™-Based Assay for Antagonists of Methyl-Lysine Binding Proteins. J. Biomol. Screen. 15(1):62-71.

Feng Liu, Xin Chen, Abdellah Allali-Hassani, Amy Quinn, Gregory Wasney, Aiping Dong, Dalia Barsyte, Ivona Kozieradzki, Guillermo Senisterra, Irene Chau, Alena Siarheyeva, Dmitri Kireev, Ajit Jadhav, Martin Herold, Stephen Frye, Cheryl Arrowsmith, Peter Brown, Anton Simeonov, Masoud Vedadi, Jian Jin. (2009) Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a. J. Med. Chem. 52(24):7950-3.

Abdellah Allali-Hassani, Gregory A. Wasney, Irene Chau, Bum Soo Hong, Guillermo Senisterra, Peter Loppnau, Zhen Shi, John Moult, Aled M. Edwards, Cheryl H. Arrowsmith, Hee Won Park, Matthieu Schapira and Masoud Vedadi (2009) A survey of proteins encoded by non-synonymous SNPs reveals a significant fraction with altered stability and activity. Biochem. J. 424(1):15-26

Eryilmaz J, Pan P, Amaya MF, Allali-Hassani A, Dong A, Adams-Cioaba MA, Mackenzie F, Vedadi M, Min J. (2009) Structural studies of a four-MBT repeat protein MBTD1. PLoS One. Oct 20;4(10):e7274.

Min T, Vedadi M, Watson D, Wasney G, Munger C, Cygler M, Matte A, Young N. (2009) Specificity of the Campylobacter jejuni Adhesin PEB3 for Phosphates and Structural Differences among its Ligand Complexes. Biochemistry. 48(14):3057-67

Guo Y, Nady N, Qi C, Allali-Hassani A, Zhu H, Pan P, Adams-Cioaba MA, Amaya MF, Dong A, Vedadi M, Schapira M, Read RJ, Arrowsmith CH, Min J. (2009) Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2. Nucleic Acids Res. 37(7):2204-10.

Huang X, Finerty P Jr, Walker JR, Butler-Cole C, Vedadi M, Schapira M, Parker SA, Turk BE, Thompson DA, Dhe-Paganon S. (2008) Structural insights into the inhibited states of the Mer receptor tyrosine kinase. J Struct Biol. 165:88-96.

Guillermo A. Senisterra, Bum Soo Hong, Hee-Won Park and Masoud Vedadi (2008) Application of high throughput isothermal denaturation to assess protein stability and screen for ligands. J Biomol Screen. 13(5):337-42.

Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH (2008) L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Mol Biol.14(12):1229-30.

Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. (2008) Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem. 283(17):11355-63.

Niesen F, Berglund H, and Vedadi M. (2007) The use of Differential Scanning Fluorimetry to detect ligand interactions that promote protein stability. Nature Protocols. 2(9):2212-21.

Hong BS, Senisterra G, Rabeh WM, Vedadi M, Leonardi R, Zhang YM, Rock CO, Jackowski S, Park HW (2007) Crystal structures of human pantothenate kinases. Insights into allosteric regulation and mutations linked to a neurodegeneration disorder. J Biol Chem. 282(38):27984-93.

Allali-Hassani A, Pan PW, Dombrovski L, Najmanovich R, Tempel W, Dong A, Loppnau P, Martin F, Thornton J, Edwards AM, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. (2007) Structural and Chemical Profiling of the Human Cytosolic Sulfotransferases. PLoS Biology. 5(5): e97.

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. (2007) Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms. Mol Biochem Parasitol. 151(1):100-10.

Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A,Loppnau P, Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN. (2007) Structural Basis of Inhibition of the Human NAD(+)-Dependent Deacetylase SIRT5 by Suramin. Structure. 15(3):377-89.

Wu H, Horton JR, Battaile K, Allali-Hassani A, Martin F, Zeng H, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Cheng X. (2007) Structural basis of allele variation of human thiopurine-S-methyltransferase. Proteins. 67(1):198-208.

Lorca GL, Ezersky A, Lunin VV, Walker JR, Altamentova S, Evdokimova E, Vedadi M, Bochkarev A, Savchenko A.(2007) Glyoxylate and pyruvate are antagonistic effectors of the Escherichia coli IclR transcriptional regulator. J Biol Chem. 282:16476-91.

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 Jr, 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. (2007) In situ proteolysis for protein crystallization and structure determination. Nat Methods. 4:1019-21.

Najmanovich RJ, Allali-Hassani A, Morris RJ, Dombrovsky L, Pan PW, Vedadi M, Plotnikov AN, Edwards A, Arrowsmith C, Thornton JM. (2007) Analysis of binding site similarity, small-molecule similarity and experimental binding profiles in the human cytosolic sulfotransferase family. Bioinformatics. 15;23(2):e104-9.PMID: 17237076

Vedadi M, Niesen FH, Allali-Hassani A, Fedorov OY, Finerty PJ Jr, Wasney GA, Yeung R, Arrowsmith C, Ball LJ, Berglund H, Hui R, Marsden BD, Nordlund P, Sundstrom M, Weigelt J, Edwards AM. (2006) Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination. Proc Natl Acad Sci U S A. 103 (43):15835-40.

Schuetz A, Allali-Hassani A, Martin F, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Arrowsmith CH, Min J. (2006) Structural basis for molecular recognition and presentation of histone H3 by WDR5. EMBO J. 25(18):4245-52.

Senisterra GA, Markin E, Yamazaki K, Hui R, Vedadi M and Awrey DE (2006) Screening for ligands using a generic and high-throughput light-scattering-based assay. J Biomol Screen; 11(8): 940-8

Kimber MS, Martin F, Lu Y, Houston S, Vedadi M, Dharamsi A, Fiebig KM, Schmid M, Rock CO (2004) The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa. J Biol Chem. 279:52593-602

Kimber, M, Vallee, F, Houston, S, Necakov, A, Skarina, T, Evdokimova, E, Beasley, S, Christendat, D, Savchenko, A, Arrowsmith, C, Vedadi, M, Gerstein, M, and Edwards, A. (2003) Data mining crystallization databases: Knowledge-based approaches to optimise protein crystal screens. PROTEINS: Structure, Function and Genetics. 51:562-568.

Khamessan,A, Naghibalhossaini F, Vedadi,M,and Johnstone,R.M. (2001) Mutated gama-actin restores growth to a yeast amino acid transport defective mutant. J Cell Physiol.186: 124-35.

Edwards AM, Arrowsmith CH, Christendat D, Dharamsi A, Friesen JD, Greenblatt JF, Vedadi M. (2000) Protein production: feeding the crystallographers and NMR spectroscopists. Nat Struct Biol. l:970-2

Ahvazi B, Coulombe R, Delarge M, Vedadi M,Zhang L, Meighen E, and Vrielink, A. (2000) Crystal structure of the NADP+ dependant aldehyde dehydrogenase from Vibrio harveyi. : structural implications for cofactor specificity and affinity. Biochem J. 349:853-61.

Vedadi M, Barriault D, Sylvestre, M and Powlowski, J (2000) Active site residues of cis-2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase from Comamonas testosteroni strain B-356. Biochemistry. 39:5028-34.

Barriault D, Vedadi M, Powlowski J,and Sylvestre M (1999) Cis-2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase and cis-1,2-dihydro-1,2-dihydroxynaphthalene dehydrogenase catalyze dehydrogenation of the same range of substrates. Biochem. Biophys. Res. Commun. 260:181-7.

Vedadi M, Vrielink A, Meighen E (1997) Involvement of conserved glycine residues, 229 and 234, of V. harveyi aldehyde dehydrogenase in activity and nucleotide binding. Biochem. Biophys. Res. Commun. 238(2), 448-451.

Vedadi M, Croteau N, Delarge M, Vrielink A, Meighen E (1997) Structural and functional studies of an NADP+-specific aldehyde dehydrogenase from the luminescent marine bacterium V. harveyi. Adv.Exp.Med.Biol. 414,269-275.

Vedadi M, Meighen E (1997) Critical glutamic acid residues affecting the mechanism and nucleotide specificity of V. harveyi aldehyde dehydrogenase. Eur.J.Biochem.246, 698-704.

Vedadi M and Meighen. (1995) Is fatty aldehyde dehydrogenase expression under similar control as the bioluminescent system in V. harveyi in Bioluminescence and Chemiluminescence.[Campbell,A, Kricka,LJ, Stanley,PE. (Ed)] pp 556-559, John Wiley & Sons, New York.

Vedadi M, Szittner R, Smillie L, and Meighen E(1995) Involvement of cysteine 289 in the catalytic activity of an NADP+-specific aldehyde dehydrogenase from V. harveyi. Biochemistry. 34,16725-16732.

Contact
Masoud Vedadi, Ph.D.
Principal Investigator, Molecular Biophysics
Structural Genomics Consortium,
University of Toronto,

MaRS Centre, South tower
101 College St.7 Floor,Room 714
Toronto ON M5G 1L7

Tel: 416 946 0897
Cel: 416 432 1980
e-mail:mvedadi[at]uhnres [dot] utoronto [dot] ca
Landing Page