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.

2025

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID.

Shrestha S, Maitland MER, Jing L, Duan S, Nie DY, St-Germain J, Kanaris M, Barsyte-Lovejoy D, Arrowsmith CH, Raught B

Nat Commun. 2025-8-31 . 16(1):8089 .doi: 10.1038/s41467-025-63357-7

PMID: 40883309

OICR-41103 as a chemical probe for the DCAF1 WD40 domain.

Kimani SW, Noureldin M, Wilson B, Hoffer L, Green SR, Szewczyk MM, González-Álvarez H, Mohammed M, Chan M, Krausser C, Li ASM, Hajian T, Tucker S, Joshi D, Saraon P, Thériault B, Kim JS, Santhakumar V, Loppnau P, Li Y, Seitova A, Dong A, Kiyota T, Hammann T, Gehrtz P, Patel B, Rathod V, Vala A, Rout B, Jagodra P, Brown PJ, Aman A, Ramnauth J, Poda G, Uehling D, Arrowsmith CH, Barsyte-Lovejoy D, Marcellus R, Ackloo S, Mamai A, Al-Awar R, Halabelian L

Commun Biol. 2025-7-20 . 8(1):1076 .doi: 10.1038/s42003-025-08491-0

PMID: 40683980

PRMT1 inhibitor MS023 suppresses RNA splicing to sensitize small cell lung cancer to DNA damaging agents.

Aparnathi MK, Ul Haq S, St-Germain J, Nixon KCJ, Walton J, Song L, Majeed S, Patel PS, Subramaniam R, Philip V, Marcellus R, Barsyte-Lovejoy D, Al-Awar R, Hakem R, Arrowsmith CH, Ailles L, Raught B, Lok BH

Neoplasia. 2025-5-26 . 66:101176 .doi: 10.1016/j.neo.2025.101176

PMID: 40413955

PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites.

Yadav M, AlQazzaz MA, Ciamponi FE, Ho JC, Maron MI, Sababi AM, MacLeod G, Ahmadi M, Bullivant G, Tano V, Langley SR, Sánchez-Osuna M, Sachamitr P, Kushida M, Bardile CF, Pouladi MA, Kurtz R, Richards L, Pugh T, Tyers M, Angers S, Dirks PB, Bader GD, Truant R, Massirer KB, Barsyte-Lovejoy D, Shechter D, Harding RJ, Arrowsmith CH, Prinos P

Nucleic Acids Res. 2025-4-30 . 53(8): .doi: 10.1093/nar/gkaf347

PMID: 40304179

Potent and selective SETDB1 covalent negative allosteric modulator reduces methyltransferase activity in cells.

Uguen M, Shell DJ, Silva M, Deng Y, Li F, Szewczyk MM, Yang K, Zhao Y, Stashko MA, Norris-Drouin JL, Waybright JM, Beldar S, Rectenwald JM, Mordant AL, Webb TS, Herring LE, Arrowsmith CH, Ackloo S, Gygi SP, McGinty RK, Barsyte-Lovejoy D, Liu P, Halabelian L, James LI, Pearce KH, Frye SV

Nat Commun. 2025-2-25 . 16(1):1905 .doi: 10.1038/s41467-025-57005-3

PMID: 39994194

2024

Interplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex.

Maitland MER, Onea G, Owens DDG, Gonga-Cavé BC, Wang X, Arrowsmith CH, Barsyte-Lovejoy D, Lajoie GA, Schild-Poulter C

Commun Biol. 2024-12-20 . 7(1):1668 .doi: 10.1038/s42003-024-07371-3

PMID: 39702571

Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.

Mabanglo MF, Wilson B, Noureldin M, Kimani SW, Mamai A, Krausser C, González-Álvarez H, Srivastava S, Mohammed M, Hoffer L, Chan M, Avrumutsoae J, Li ASM, Hajian T, Tucker S, Green S, Szewczyk M, Barsyte-Lovejoy D, Santhakumar V, Ackloo S, Loppnau P, Li Y, Seitova A, Kiyota T, Wang JG, Privé GG, Kuntz DA, Patel B, Rathod V, Vala A, Rout B, Aman A, Poda G, Uehling D, Ramnauth J, Halabelian L, Marcellus R, Al-Awar R, Vedadi M

Nat Commun. 2024-11-24 . 15(1):10165 .doi: 10.1038/s41467-024-54500-x

PMID: 39580491

A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.

Ackloo S, Li F, Szewczyk M, Seitova A, Loppnau P, Zeng H, Xu J, Ahmad S, Arnautova YA, Baghaie AJ, Beldar S, Bolotokova A, Centrella PA, Chau I, Clark MA, Cuozzo JW, Dehghani-Tafti S, Disch JS, Dong A, Dumas A, Feng JA, Ghiabi P, Gibson E, Gilmer J, Goldman B, Green SR, Guié MA, Guilinger JP, Harms N, Herasymenko O, Houliston S, Hutchinson A, Kearnes S, Keefe AD, Kimani SW, Kramer T, Kutera M, Kwak HA, Lento C, Li Y, Liu J, Loup J, Machado RAC, Mulhern CJ, Perveen S, Righetto GL, Riley P, Shrestha S, Sigel EA, Silva M, Sintchak MD, Slakman BL, Taylor RD, Thompson J, Torng W, Underkoffler C, von Rechenberg M, Walsh RT, Watson I, Wilson DJ, Wolf E, Yadav M, Yazdi AK, Zhang J, Zhang Y, Santhakumar V, Edwards AM, Barsyte-Lovejoy D, Schapira M, Brown PJ, Halabelian L, Arrowsmith CH

J Med Chem. 2024-11-4 . .doi: 10.1021/acs.jmedchem.4c02010

PMID: 39495097

A high-throughput approach to identify BRCA1-downregulating compounds to enhance PARP inhibitor sensitivity.

Sellars E, Savguira M, Wu J, Cancelliere S, Jen M, Krishnan R, Hakem A, Barsyte-Lovejoy D, Hakem R, Narod SA, Kotsopoulos J, Salmena L

iScience. 2024-7-19 . 27(7):110180 .doi: 10.1016/j.isci.2024.110180

PMID: 38993666

Recruitment of FBXO22 for targeted degradation of NSD2.

Nie DY, Tabor JR, Li J, Kutera M, St-Germain J, Hanley RP, Wolf E, Paulakonis E, Kenney TMG, Duan S, Shrestha S, Owens DDG, Maitland MER, Pon A, Szewczyk M, Lamberto AJ, Menes M, Li F, Penn LZ, Barsyte-Lovejoy D, Brown NG, Barsotti AM, Stamford AW, Collins JL, Wilson DJ, Raught B, Licht JD, James LI, Arrowsmith CH

Nat Chem Biol. 2024-7-4 . .doi: 10.1038/s41589-024-01660-y

PMID: 38965384