Dalia Barsyte-Lovejoy

Dalia Barsyte-Lovejoy

SGC Toronto

Barsyte-Lovejoy

Biography

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.

Research Areas

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.

2021

Protein arginine methylation: from enigmatic functions to therapeutic targeting.

Wu Q, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D

Nat Rev Drug Discov. 2021-3-19 . .doi: 10.1038/s41573-021-00159-8

PMID: 33742187

A First-in-Class, Highly Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 6.

Shen Y, Li F, Szewczyk MM, Halabelian L, Chau I, Eram MS, Dela Seña C, Park KS, Meng F, Chen H, Zeng H, McLeod D, Zepeda-Velázquez CA, Campbell RM, Mader MM, Watson BM, Schapira M, Arrowsmith CH, Al-Awar R, Barsyte-Lovejoy D, Kaniskan HÜ, Brown PJ, Vedadi M, Jin J

J Med Chem. 2021-2-16 . .doi: 10.1021/acs.jmedchem.0c02160

PMID: 33591753

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, Kushida MM, Cavalli FMG, Lee L, Rastegar N, Vu V, Sánchez-Osuna M, Coulombe-Huntington J, Kanshin E, Whetstone H, Durand M, Thibault P, Hart K, Mangos M, Veyhl J, Chen W, Tran N, Duong BC, Aman AM, Che X, Lan X, Whitley O, Zaslaver O, Barsyte-Lovejoy D, Richards LM, Restall I, Caudy A, Röst HL, Bonday ZQ, Bernstein M, Das S, Cusimano MD, Spears J, Bader GD, Pugh TJ, Tyers M, Lupien M, Haibe-Kains B, Artee Luchman H, Weiss S, Massirer KB, Prinos P, Arrowsmith CH, Dirks PB

Nat Commun. 2021-2-12 . 12(1):979 .doi: 10.1038/s41467-021-21204-5

PMID: 33579912

Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2.

Ferreira de Freitas R, Liu Y, Szewczyk MM, Mehta N, Li F, McLeod D, Zepeda-Velázquez C, Dilworth D, Hanley RP, Gibson E, Brown PJ, Al-Awar R, James LI, Arrowsmith CH, Barsyte-Lovejoy D, Min J, Vedadi M, Schapira M, Allali-Hassani A

J Med Chem. 2021-2-1 . .doi: 10.1021/acs.jmedchem.0c01768

PMID: 33522809

2020

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Szewczyk MM, Ishikawa Y, Organ S, Sakai N, Li F, Halabelian L, Ackloo S, Couzens AL, Eram M, Dilworth D, Fukushi H, Harding R, Dela Seña CC, Sugo T, Hayashi K, McLeod D, Zepeda C, Aman A, Sánchez-Osuna M, Bonneil E, Takagi S, Al-Awar R, Tyers M, Richard S, Takizawa M, Gingras AC, Arrowsmith CH, Vedadi M, Brown PJ, Nara H, Barsyte-Lovejoy D

Nat Commun. 2020-5-14 . 11(1):2396 .doi: 10.1038/s41467-020-16271-z

PMID: 32409666

Discovery of a First-in-class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor.

Shen Y, Li F, Szewczyk MM, Halabelian L, Park KS, Chau I, Dong A, Zeng H, Chen H, Meng F, Barsyte-Lovejoy D, Arrowsmith CH, Brown P, Liu J, Vedadi M, Jin J

J. Med. Chem.. 2020-5-5 . .doi: 10.1021/acs.jmedchem.0c00406

PMID: 32367723

Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment.

Criqui M, Qamra A, Chu TW, Sharma M, Tsao J, Henry DA, Barsyte-Lovejoy D, Arrowsmith CH, Winegarden N, Lupien M, Harrington L

Elife. 2020-4-16 . 9: .doi: 10.7554/eLife.47333

PMID: 32297856

2019

Discovery of a chemical probe for PRDM9.

Allali-Hassani A, Szewczyk MM, Ivanochko D, Organ SL, Bok J, Ho JSY, Gay FPH, Li F, Blazer L, Eram MS, Halabelian L, Dilworth D, Luciani GM, Lima-Fernandes E, Wu Q, Loppnau P, Palmer N, Talib SZA, Brown PJ, Schapira M, Kaldis P, O'Hagan RC, Guccione E, Barsyte-Lovejoy D, Arrowsmith CH, Sanders JM, Kattar SD, Bennett DJ, Nicholson B, Vedadi M

Nat Commun. 2019-12-17 . 10(1):5759 .doi: 10.1038/s41467-019-13652-x

PMID: 31848333

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers.

Lovejoy DA, Hogg DW, Dodsworth TL, Jurado FR, Read CC, D'Aquila AL, Barsyte-Lovejoy D

Front Endocrinol (Lausanne). 2019-11-30 . 10:730 .doi: 10.3389/fendo.2019.00730

PMID: 31781029

SETD7 at the heart of chromatin factor interplay.

Barsyte-Lovejoy D

Stem Cell Investig. 2019-9-29 . 6:20 .doi: 10.21037/sci.2019.06.01

PMID: 31559307