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).
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: 39580491Li F, Ackloo S, Arrowsmith CH, Ban F, Barden CJ, Beck H, Beránek J, Berenger F, Bolotokova A, Bret G, Breznik M, Carosati E, Chau I, Chen Y, Cherkasov A, Corte DD, Denzinger K, Dong A, Draga S, Dunn I, Edfeldt K, Edwards A, Eguida M, Eisenhuth P, Friedrich L, Fuerll A, Gardiner SS, Gentile F, Ghiabi P, Gibson E, Glavatskikh M, Gorgulla C, Guenther J, Gunnarsson A, Gusev F, Gutkin E, Halabelian L, Harding RJ, Hillisch A, Hoffer L, Hogner A, Houliston S, Irwin JJ, Isayev O, Ivanova A, Jacquemard C, Jarrett AJ, Jensen JH, Kireev D, Kleber J, Koby SB, Koes D, Kumar A, Kurnikova MG, Kutlushina A, Lessel U, Liessmann F, Liu S, Lu W, Meiler J, Mettu A, Minibaeva G, Moretti R, Morris CJ, Narangoda C, Noonan T, Obendorf L, Pach S, Pandit A, Perveen S, Poda G, Polishchuk P, Puls K, Pütter V, Rognan D, Roskams-Edris D, Schindler C, Sindt F, Spiwok V, Steinmann C, Stevens RL, Talagayev V, Tingey D, Vu O, Walters WP, Wang X, Wang Z, Wolber G, Wolf CA, Wortmann L, Zeng H, Zepeda CA, Zhang KYJ, Zhang J, Zheng S, Schapira M
J Chem Inf Model. 2024-11-5 . .doi: 10.1021/acs.jcim.4c01267
PMID: 39499532Ackloo 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: 39495097Münzker L, Kimani SW, Fowkes MM, Dong A, Zheng H, Li Y, Dasovich M, Zak KM, Leung AKL, Elkins JM, Kessler D, Arrowsmith CH, Halabelian L, Böttcher J
Commun Biol. 2024-7-24 . 7(1):901 .doi: 10.1038/s42003-024-06584-w
PMID: 39048679Eguida M, Bret G, Sindt F, Li F, Chau I, Ackloo S, Arrowsmith C, Bolotokova A, Ghiabi P, Gibson E, Halabelian L, Houliston S, Harding RJ, Hutchinson A, Loppnau P, Perveen S, Seitova A, Zeng H, Schapira M, Rognan D
J Chem Inf Model. 2024-6-25 . .doi: 10.1021/acs.jcim.4c00601
PMID: 38916159Yong D, Ahmad S, Mabanglo MF, Halabelian L, Schapira M, Ackloo S, Perveen S, Ghiabi P, Vedadi M
Biochemistry. 2024-5-10 . .doi: 10.1021/acs.biochem.4c00044
PMID: 38729622Righetto 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: 38372781