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.

2024

A chemical probe to modulate human GID4 Pro/N-degron interactions.

Owens DDG, Maitland MER, Khalili Yazdi A, Song X, Reber V, Schwalm MP, Machado RAC, Bauer N, Wang X, Szewczyk MM, Dong C, Dong A, Loppnau P, Calabrese MF, Dowling MS, Lee J, Montgomery JI, O'Connell TN, Subramanyam C, Wang F, Adamson EC, Schapira M, Gstaiger M, Knapp S, Vedadi M, Min J, Lajoie GA, Barsyte-Lovejoy D, Owen DR, Schild-Poulter C, Arrowsmith CH

Nat Chem Biol. 2024-5-21 . .doi: 10.1038/s41589-024-01618-0

PMID: 38773330

Probing the CRL4DCAF12 interactions with MAGEA3 and CCT5 di-Glu C-terminal degrons.

Righetto GL, Yin Y, Duda DM, Vu V, Szewczyk MM, Zeng H, Li Y, Loppnau P, Mei T, Li YY, Seitova A, Patrick AN, Brazeau JF, Chaudhry C, Barsyte-Lovejoy D, Santhakumar V, Halabelian L

PNAS Nexus. 2024-4-26 . 3(4):pgae153 .doi: 10.1093/pnasnexus/pgae153

PMID: 38665159

Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing.

Shen L, Ma X, Wang Y, Wang Z, Zhang Y, Pham HQH, Tao X, Cui Y, Wei J, Lin D, Abeywanada T, Hardikar S, Halabelian L, Smith N, Chen T, Barsyte-Lovejoy D, Qiu S, Xing Y, Yang Y

Nat Commun. 2024-4-1 . 15(1):2809 .doi: 10.1038/s41467-024-47107-9

PMID: 38561334

Chemical tools for the Gid4 subunit of the human E3 ligase C-terminal to LisH (CTLH) degradation complex.

Yazdi AK, Perveen S, Dong C, Song X, Dong A, Szewczyk MM, Calabrese MF, Casimiro-Garcia A, Chakrapani S, Dowling MS, Ficici E, Lee J, Montgomery JI, O'Connell TN, Skrzypek GJ, Tran TP, Troutman MD, Wang F, Young JA, Min J, Barsyte-Lovejoy D, Brown PJ, Santhakumar V, Arrowsmith CH, Vedadi M, Owen DR

RSC Med Chem. 2024-3-20 . 15(3):1066-1071 .doi: 10.1039/d3md00633f

PMID: 38516600

2023

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition.

Kimani SW, Perveen S, Szewezyk M, Zeng H, Dong A, Li F, Ghiabi P, Li Y, Chau I, Arrowsmith CH, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Halabelian L

Commun Biol. 2023-12-16 . 6(1):1272 .doi: 10.1038/s42003-023-05655-8

PMID: 38104184

Development of HC-258, a Covalent Acrylamide TEAD Inhibitor That Reduces Gene Expression and Cell Migration.

Fnaiche A, Chan HC, Paquin A, González Suárez N, Vu V, Li F, Allali-Hassani A, Cao MA, Szewczyk MM, Bolotokova A, Allemand F, Gelin M, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Guichou JF, Annabi B, Gagnon A

ACS Med Chem Lett. 2023-12-14 . 14(12):1746-1753 .doi: 10.1021/acsmedchemlett.3c00386

PMID: 38116405

Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations.

Alqazzaz MA, Luciani GM, Vu V, Machado RAC, Szewczyk MM, Adamson EC, Cheon S, Li F, Arrowsmith CH, Minden MD, Barsyte-Lovejoy D

Exp Hematol. 2023-12-10 . 104135 .doi: 10.1016/j.exphem.2023.11.009

PMID: 38072134

Development of LM-41 and AF-2112, two flufenamic acid-derived TEAD inhibitors obtained through the replacement of the trifluoromethyl group by aryl rings.

Fnaiche A, Mélin L, Suárez NG, Paquin A, Vu V, Li F, Allali-Hassani A, Bolotokova A, Allemand F, Gelin M, Cotelle P, Woo S, LaPlante SR, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Guichou JF, Annabi B, Gagnon A

Bioorg Med Chem Lett. 2023-9-26 . 129488 .doi: 10.1016/j.bmcl.2023.129488

PMID: 37770003

HiBiT Cellular Thermal Shift Assay (HiBiT CETSA).

Ramachandran S, Szewczyk M, Barghout SH, Ciulli A, Barsyte-Lovejoy D, Vu V

Methods Mol Biol. 2023-8-10 . 2706:149-165 .doi: 10.1007/978-1-0716-3397-7_11

PMID: 37558947