Dr. Dalia Barsyte-Lovejoy, PhD, is an Associate Professor at the Department of Pharmacology and Toxicology, University of Toronto, Principal Investigator at the SGC-Toronto, and Affiliate Scientist at the Princess Margaret Cancer Center. Dr. Barsyte-Lovejoy did her undergraduate training at Vilnius University and her graduate degree in molecular biology at the University of Manchester, UK. She went on to do postdoctoral training at the Ontario Cancer Institute in cancer biology and transcriptional regulation. Dr. Barsyte-Lovejoy's research has been recognized by the prestigious CIHR Young Cancer Researcher award.
Dr. Barsyte-Lovejoy’s research focuses on understanding posttranslational modifications associated with splicing, epigenetic regulation, and proteostasis. Working on enzymes responsible for these modifications, we seek to identify cancer vulnerabilities, disease mechanisms, and therapeutic targets, and to develop novel small-molecule inhibitor chemical probe tools.
We are interested in understanding the mechanisms by which posttranslational modifications control cancer cell growth, differentiation, and therapeutic response. Protein lysine and arginine methyltransferases regulate transcription, genome stability, splicing, RNA metabolism, and other cell processes dictated by which substrates these enzymes methylate. Lysine methyltransferases such as EZH2 and NSD2 primarily methylate histones to establish repressive and active chromatin. In contrast, arginine methyltransferases have a broad substrate range, including histones, signaling molecules, enzymes, and structural proteins. Protein methylation, along with other modifications such as ubiquitylation, also plays important roles in splicing, protein-protein interactions, and cellular signaling and stress response, which cancer cells hijack to escape cell death and acquire drug resistance. Our work seeks to understand how these posttranslational modifications are misregulated in cancer and identify new therapeutic targets.
Through multidisciplinary research spanning cell and chemical biology, protein structural biology, and numerous collaborations with colleagues across industry and academia, the SGC chemical probes project has generated an extensive set of chemical probes for methyltransferases, ubiquitin ligases, and deubiquitylases. We are currently using these chemical probes to explore the cellular pathways in poor-prognosis acute myeloid leukemia, pancreatic, lung, and breast cancer.
Wu Q, Nie DY, Ba-Alawi W, Ji Y, Zhang Z, Cruickshank J, Haight J, Ciamponi FE, Chen J, Duan S, Shen Y, Liu J, Marhon SA, Mehdipour P, Szewczyk MM, Dogan-Artun N, Chen W, Zhang LX, Deblois G, Prinos P, Massirer KB, Barsyte-Lovejoy D, Jin J, De Carvalho DD, Haibe-Kains B, Wang X, Cescon DW, Lupien M, Arrowsmith CH
Nat Chem Biol. 2022-5-16 . .doi: 10.1038/s41589-022-01024-4
PMID: 35578032Vu V, Szewczyk MM, Nie DY, Arrowsmith CH, Barsyte-Lovejoy D
Annu Rev Biochem. 2022-4-1 . .doi: 10.1146/annurev-biochem-032620-105344
PMID: 35363509Srour N, Villarreal OD, Hardikar S, Yu Z, Preston S, Miller WH, Szewczyk MM, Barsyte-Lovejoy D, Xu H, Chen T, Del Rincón SV, Richard S
Cell Rep. 2022-3-29 . 38(13):110582 .doi: 10.1016/j.celrep.2022.110582
PMID: 35354055Szewczyk MM, Luciani GM, Vu V, Murison A, Dilworth D, Barghout SH, Lupien M, Arrowsmith CH, Minden MD, Barsyte-Lovejoy D
Redox Biol. 2022-3-11 . 51:102282 .doi: 10.1016/j.redox.2022.102282
PMID: 35305370Dilworth D, Hanley RP, Ferreira de Freitas R, Allali-Hassani A, Zhou M, Mehta N, Marunde MR, Ackloo S, Carvalho Machado RA, Khalili Yazdi A, Owens DDG, Vu V, Nie DY, Alqazzaz M, Marcon E, Li F, Chau I, Bolotokova A, Qin S, Lei M, Liu Y, Szewczyk MM, Dong A, Kazemzadeh S, Abramyan T, Popova IK, Hall NW, Meiners MJ, Cheek MA, Gibson E, Kireev D, Greenblatt JF, Keogh MC, Min J, Brown PJ, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, James LI, Schapira M
Nat Chem Biol. 2021-11-15 . .doi: 10.1038/s41589-021-00898-0
PMID: 34782742Szewczyk MM, Vu V, Barsyte-Lovejoy D
J Vis Exp. 2021-8-7 . .doi: 10.3791/62418
PMID: 34424246Halabelian L, Barsyte-Lovejoy D
Life (Basel). 2021-7-30 . 11(8): .doi: 10.3390/life11080768
PMID: 34440512Gagnon A, Mélin L, Abdullayev S, Fnaiche A, Vu V, Gonzalez Suarez N, Zeng H, Szewczyk M, Li F, Sinisterra G, Allali-Hassani A, Chau I, Dong A, Woo S, Annabi B, Halabelian L, LaPlante S, Vedadi M, Barsyte-Lovejoy D, Santhakumar V
ChemMedChem. 2021-6-23 . .doi: 10.1002/cmdc.202100432
PMID: 34164919Gradl S, Steuber H, Weiske J, Szewczyk MM, Schmees N, Siegel S, Stoeckigt D, Christ CD, Li F, Organ S, Abbey M, Kennedy S, Chau I, Trush V, Barsyte-Lovejoy D, Brown PJ, Vedadi M, Arrowsmith C, Husemann M, Badock V, Bauser M, Haegebarth A, Hartung IV, Stresemann C
SLAS Discov. 2021-6-21 . 24725552211019409 .doi: 10.1177/24725552211019409
PMID: 34154424Dölle A, Adhikari B, Krämer A, Weckesser J, Berner N, Berger LM, Diebold M, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Gebel J, Löhr F, Dötsch V, Eilers M, Heinzlmeir S, Kuster B, Sotriffer C, Wolf E, Knapp S
J Med Chem. 2021-5-13 . .doi: 10.1021/acs.jmedchem.1c00146
PMID: 33980013