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).
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: 38665159Shen 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: 38561334Schapira M, Halabelian L, Arrowsmith CH, Harding RJ
Nat Chem Biol. 2024-3-8 . .doi: 10.1038/s41589-024-01570-z
PMID: 38459278Gilleran JA, Ashraf K, Delvillar M, Eck T, Fondekar R, Miller EB, Hutchinson A, Dong A, Seitova A, De Souza ML, Augeri D, Halabelian L, Siekierka J, Rotella DP, Gordon J, Childers WE, Grier MC, Staker BL, Roberge JY, Bhanot P
J Med Chem. 2024-2-19 . .doi: 10.1021/acs.jmedchem.3c01795
PMID: 38372781Ipas H, Gouws EB, Abell NS, Chiou PC, Devanathan SK, Hervé S, Lee S, Mercado M, Reinsborough C, Halabelian L, Arrowsmith CH, Xhemalçe B
EMBO Rep. 2024-1-23 . .doi: 10.1038/s44319-024-00059-z
PMID: 38263329Kimani 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: 38104184Ahmad S, Xu J, Feng JA, Hutchinson A, Zeng H, Ghiabi P, Dong A, Centrella PA, Clark MA, Guié MA, Guilinger JP, Keefe AD, Zhang Y, Cerruti T, Cuozzo JW, von Rechenberg M, Bolotokova A, Li Y, Loppnau P, Seitova A, Li YY, Santhakumar V, Brown PJ, Ackloo S, Halabelian L
J Med Chem. 2023-11-23 . .doi: 10.1021/acs.jmedchem.3c01471
PMID: 37996079Shell DJ, Foley CA, Wang Q, Smith CM, Guduru SKR, Zeng H, Dong A, Norris-Drouin JL, Axtman M, Hardy PB, Gupta G, Halabelian L, Frye SV, James LI, Pearce KH
J Med Chem. 2023-10-2 . .doi: 10.1021/acs.jmedchem.3c01192
PMID: 37782247Kimani SW, Owen J, Green SR, Li F, Li Y, Dong A, Brown PJ, Ackloo S, Kuter D, Yang C, MacAskill M, MacKinnon SS, Arrowsmith CH, Schapira M, Shahani V, Halabelian L
J Chem Inf Model. 2023-6-23 . .doi: 10.1021/acs.jcim.3c00082
PMID: 37350740Li 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