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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).
J Med Chem. 2021 . doi: 10.1021/acs.jmedchem.0c02160
PMID: 33591753
Nucleic Acids Res. 2020 . doi: 10.1093/nar/gkaa1176
PMID: 33313896
Nat Commun. 2020 11(1):2396. doi: 10.1038/s41467-020-16271-z
PMID: 32409666
J. Med. Chem.. 2020 . doi: 10.1021/acs.jmedchem.0c00406
PMID: 32367723
Nat. Struct. Mol. Biol.. 2019 . doi: 10.1038/s41594-019-0246-6
PMID: 31235913
Mol. Cell. 2019 . doi: 10.1016/j.molcel.2019.10.031
PMID: 31806351
Nat Commun. 2019 10(1):5759. doi: 10.1038/s41467-019-13652-x
PMID: 31848333
Nat Commun. 2018 9(1):3411. doi: 10.1038/s41467-018-05646-y
PMID: 30143613
Nucleic Acids Res.. 2018 . doi: 10.1093/nar/gky1192
PMID: 30462309
2024
Nat Commun. 01.04.2024 15(1):2809. doi: 10.1038/s41467-024-47107-9
PMID: 38561334
Nat Chem Biol. 08.03.2024 . doi: 10.1038/s41589-024-01570-z
PMID: 38459278
J Med Chem. 19.02.2024 . doi: 10.1021/acs.jmedchem.3c01795
PMID: 38372781
EMBO Rep. 23.01.2024 . doi: 10.1038/s44319-024-00059-z
PMID: 38263329
2023
Commun Biol. 16.12.2023 6(1):1272. doi: 10.1038/s42003-023-05655-8
PMID: 38104184
J Med Chem. 23.11.2023 . doi: 10.1021/acs.jmedchem.3c01471
PMID: 37996079
J Med Chem. 02.10.2023 . doi: 10.1021/acs.jmedchem.3c01192
PMID: 37782247
J Chem Inf Model. 23.06.2023 . doi: 10.1021/acs.jcim.3c00082
PMID: 37350740
J Med Chem. 22.03.2023 . doi: 10.1021/acs.jmedchem.2c02132
PMID: 36948210
2022
Nat Chem Biol. 08.06.2022 . doi: 10.1038/s41589-022-01059-7
PMID: 35676539
2021
Cell Discov. 28.12.2021 7(1):122. doi: 10.1038/s41421-021-00344-4
PMID: 34961760
Nucleic Acids Res. 28.10.2021 . doi: 10.1093/nar/gkab934
PMID: 34718722
J Mol Biol. 16.10.2021 433(23):167294. doi: 10.1016/j.jmb.2021.167294
PMID: 34662547
Life (Basel). 30.07.2021 11(8):. doi: 10.3390/life11080768
PMID: 34440512
ChemMedChem. 23.06.2021 . doi: 10.1002/cmdc.202100432
PMID: 34164919
Nat Biotechnol. 01.03.2021 . doi: 10.1038/s41587-021-00836-4
PMID: 33649568
J Med Chem. 16.02.2021 . doi: 10.1021/acs.jmedchem.0c02160
PMID: 33591753
2020
Nucleic Acids Res. 11.12.2020 . doi: 10.1093/nar/gkaa1176
PMID: 33313896
Nat Commun. 14.05.2020 11(1):2396. doi: 10.1038/s41467-020-16271-z
PMID: 32409666
J. Med. Chem.. 05.05.2020 . doi: 10.1021/acs.jmedchem.0c00406
PMID: 32367723
2019
Nat Commun. 17.12.2019 10(1):5759. doi: 10.1038/s41467-019-13652-x
PMID: 31848333
Mol. Cell. 15.11.2019 . doi: 10.1016/j.molcel.2019.10.031
PMID: 31806351
Front Plant Sci. 18.10.2019 10:1105. doi: 10.3389/fpls.2019.01105
PMID: 31620147
Frontiers in Plant Science. 16.09.2019 10:1105-. doi: 10.3389/fpls.2019.01105
PMID: 31620147
Nat. Struct. Mol. Biol.. 24.06.2019 . doi: 10.1038/s41594-019-0246-6
PMID: 31235913
2018
Nucleic Acids Res.. 20.11.2018 . doi: 10.1093/nar/gky1192
PMID: 30462309
Nucleic Acids Research. 20.11.2018 :-. doi: 10.1093/nar/gky1192
PMID: 30462309
Nat Commun. 24.08.2018 9(1):3411. doi: 10.1038/s41467-018-05646-y
PMID: 30143613