Dr. Levon Halabelian, PhD is an Assistant Professor at the Department of Pharmacology and Toxicology, UofT, and Principal Investigator in structural biology at the SGC-Toronto. His research focuses on using x-ray crystallography and chemical biology tools to uncover the structures, functions, and therapeutic potential of the human WD-repeat (WDR) domain-containing proteins, one of the largest human protein families and highly enriched in disease-associated proteins. He is involved in structure-guided chemical probes and drug discovery efforts including the novel revolutionary PROTAC drug modality. Many of these projects are in collaboration with the pharmaceutical industry and AI-based drug-discovery groups from academia and industry. Dr. Halabelian is also the interim leader of SGC’s new open science TEP program in Women’s and Children’s Health funded by the Bill & Melinda Gates Foundation.
My group is interested in using the structural and chemical biology tools to uncover the structures and functions of human WD-repeat (WDR) proteins that are often associated with diverse human diseases, including neurodegenerative diseases and cancer. WDR domains comprise an emerging class of druggable protein modules and we seek to develop chemical biology tools to elucidate the function and therapeutic potential of select members of this family, such as LRRK2 and WDR41, which are associated with Parkinson’s disease and amyotrophic-lateral sclerosis (ALS), respectively. We are also interested in targeting key components of the ribosomal biogenesis pathway (WDR12, WDR55) for cancer therapy, which is becoming more attractive as promising findings emerge. Furthermore, many WDRs constitute the substrate recognition domain of E3-ligases, and we are interested in identifying small-molecule handles for the development of proteolysis-targeting chimeras (PROTACs) for targeted protein degradation. My team has also actively contributed to the characterization of other human proteins including DNA-repair proteins (HMCES), tRNA-modifying enzymes (PUS7), protein Arginine methyltransferases (PRMTs) involved in epigenetic regulation and ubiquitin-specific proteases (USP9X).
Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K, Subramaniam S, Halabelian L, Arrowsmith CH, Bénard F
Nat Chem Biol. 2022-6-8 . .doi: 10.1038/s41589-022-01059-7
PMID: 35676539Delaney K, Tan M, Zhu Z, Gao J, Dai L, Kim S, Ding J, He M, Halabelian L, Yang L, Nagarajan P, Parthun MR, Lee S, Khochbin S, Zheng YG, Zhao Y
Cell Discov. 2021-12-28 . 7(1):122 .doi: 10.1038/s41421-021-00344-4
PMID: 34961760Guegueniat J, Halabelian L, Zeng H, Dong A, Li Y, Wu H, Arrowsmith CH, Kothe U
Nucleic Acids Res. 2021-10-28 . .doi: 10.1093/nar/gkab934
PMID: 34718722Saraon P, Snider J, Schormann W, Rai A, Radulovich N, Sánchez-Osuna M, Coulombe-Huntington J, Huard C, Mohammed M, Lima-Fernandes E, Thériault B, Halabelian L, Chan M, Joshi D, Drecun L, Yao Z, Pathmanathan S, Wong V, Lyakisheva A, Aboualizadeh F, Niu L, Li F, Kiyota T, Subramanian R, Joseph B, Aman A, Prakesch M, Isaac M, Mamai A, Poda G, Vedadi M, Marcellus R, Uehling D, Leighl N, Sacher A, Samaržija M, Jakopović M, Arrowsmith C, Tyers M, Tsao MS, Andrews D, Al-Awar R, Stagljar I
J Mol Biol. 2021-10-16 . 433(23):167294 .doi: 10.1016/j.jmb.2021.167294
PMID: 34662547Halabelian 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: 34164919Sugata K, Matsunaga Y, Yamashita Y, Nakatsugawa M, Guo T, Halabelian L, Ohashi Y, Saso K, Rahman MA, Anczurowski M, Wang CH, Murata K, Saijo H, Kagoya Y, Ly D, Burt BD, Butler MO, Mak TW, Hirano N
Nat Biotechnol. 2021-3-1 . .doi: 10.1038/s41587-021-00836-4
PMID: 33649568Shen 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: 33591753Zhu Z, Han Z, Halabelian L, Yang X, Ding J, Zhang N, Ngo L, Song J, Zeng H, He M, Zhao Y, Arrowsmith CH, Luo M, Bartlett MG, Zheng YG
Nucleic Acids Res. 2020-12-11 . .doi: 10.1093/nar/gkaa1176
PMID: 33313896Szewczyk 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