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.

2023

Discovery and Characterization of a Chemical Probe Targeting the Zinc-Finger Ubiquitin-Binding Domain of HDAC6.

Harding RJ, Franzoni I, Mann MK, Szewczyk MM, Mirabi B, Ferreira de Freitas R, Owens DDG, Ackloo S, Scheremetjew A, Juarez-Ornelas KA, Sanichar R, Baker RJ, Dank C, Brown PJ, Barsyte-Lovejoy D, Santhakumar V, Schapira M, Lautens M, Arrowsmith CH

J Med Chem. 2023-7-27 . .doi: 10.1021/acs.jmedchem.3c00314

PMID: 37499118

Discovery of a Potent and Selective Targeted NSD2 Degrader for the Reduction of H3K36me2.

Hanley RP, Nie DY, Tabor JR, Li F, Sobh A, Xu C, Barker NK, Dilworth D, Hajian T, Gibson E, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Herring LE, Wang GG, Licht JD, Vedadi M, Arrowsmith CH, James LI

J Am Chem Soc. 2023-3-28 . .doi: 10.1021/jacs.3c01421

PMID: 36976643

Discovery of Nanomolar DCAF1 Small Molecule Ligands.

Li ASM, Kimani S, Wilson B, Noureldin M, González-Álvarez H, Mamai A, Hoffer L, Guilinger JP, Zhang Y, von Rechenberg M, Disch JS, Mulhern CJ, Slakman BL, Cuozzo JW, Dong A, Poda G, Mohammed M, Saraon P, Mittal M, Modh P, Rathod V, Patel B, Ackloo S, Santhakumar V, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Marcellus R, Guié MA, Keefe AD, Brown PJ, Halabelian L, Al-Awar R, Vedadi M

J Med Chem. 2023-3-22 . .doi: 10.1021/acs.jmedchem.2c02132

PMID: 36948210

Reference compounds for characterizing cellular injury in high-content cellular morphology assays.

Dahlin JL, Hua BK, Zucconi BE, Nelson SD, Singh S, Carpenter AE, Shrimp JH, Lima-Fernandes E, Wawer MJ, Chung LPW, Agrawal A, O'Reilly M, Barsyte-Lovejoy D, Szewczyk M, Li F, Lak P, Cuellar M, Cole PA, Meier JL, Thomas T, Baell JB, Brown PJ, Walters MA, Clemons PA, Schreiber SL, Wagner BK

Nat Commun. 2023-3-13 . 14(1):1364 .doi: 10.1038/s41467-023-36829-x

PMID: 36914634

Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.

Göricke F, Vu V, Smith L, Scheib U, Böhm R, Akkilic N, Wohlfahrt G, Weiske J, Bömer U, Brzezinka K, Lindner N, Lienau P, Gradl S, Beck H, Brown PJ, Santhakumar V, Vedadi M, Barsyte-Lovejoy D, Arrowsmith CH, Schmees N, Petersen K

J Med Chem. 2023-2-20 . .doi: 10.1021/acs.jmedchem.2c01933

PMID: 36802665

2022

Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.

Hogg DW, Reid AL, Dodsworth TL, Chen Y, Reid RM, Xu M, Husic M, Biga PR, Slee A, Buck LT, Barsyte-Lovejoy D, Locke M, Lovejoy DA

Front Physiol. 2022-12-17 . 13:1031264 .doi: 10.3389/fphys.2022.1031264

PMID: 36523555

Combinatorial Anticancer Drug Screen Identifies Off-Target Effects of Epigenetic Chemical Probes.

Barghout SH, Mann MK, Aman A, Yu Y, Alteen MG, Schimmer AD, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D

ACS Chem Biol. 2022-9-9 . .doi: 10.1021/acschembio.2c00451

PMID: 36084291

Enzymatic nucleosome acetylation selectively affects activity of histone methyltransferases in vitro.

Trush VV, Feller C, Li ASM, Allali-Hassani A, Szewczyk MM, Chau I, Eram MS, Jiang B, Luu R, Zhang F, Barsyte-Lovejoy D, Aebersold R, Arrowsmith CH, Vedadi M

Biochim Biophys Acta Gene Regul Mech. 2022-7-27 . 194845 .doi: 10.1016/j.bbagrm.2022.194845

PMID: 35907431

Chemical biology and pharmacology of histone lysine methylation inhibitors.

Barghout SH, Machado RAC, Barsyte-Lovejoy D

Biochim Biophys Acta Gene Regul Mech. 2022-6-23 . 194840 .doi: 10.1016/j.bbagrm.2022.194840

PMID: 35753676