My broad research interests are in the field of ubiquitin signaling, protein engineering, targeted protein degradation, genome stability, and cancer therapeutics. In the past four years, my lab has been working on development of synthetic biology approaches to manipulate human cell signal transduction cascades to identify new molecular mechanisms and innovative therapeutic strategies. So far, we have published 35 papers in high impact journals and filed 3 patents (2 granted, 1 pending).
I greatly appreciate the following agencies currently providing funding support to my laboratory: Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Cancer Society, Cancer Research Society, Canadian Foundation for Innovation (CFI), Ontario Research Fund, and the Early Researcher Awards program funded by the Ontario Ministry of Colleges & Universities. I am also appointed in the Canadian Institute for Advanced Research (CIFAR) Humans & The Microbiome program as an Azrieli Global Scholar.
BSc – School of Life Sciences, Beijing Normal University
PhD – Department of Molecular Genetics, University of Toronto
Postdoctoral Fellow - The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
In the Zhang lab, we create synthetic probes modulating protein-protein interactions to: 1) accelerate understanding of biology, and 2) facilitate development of novel therapeutics. For example, we systematically generated inhibitors and activators for E3 ubiquitin ligases to discover new enzyme catalytic mechanism and new E3 substrates: Zhang et al. Molecular Cell 2016; Gabrielsen et al. Molecular Cell 2017 We also create molecular tools to increase CRISPR-Cas9 genome-editing efficiency: Canny et al. Nature Biotechnology 2018 Finally, we showed that structure-based protein engineering enables development of anti-viral reagents for Middle East respiratory syndrome (MERS) coronavirus:Zhang et al. PLoS Pathogens 2017. Please check here for the complete list of publications.
Currently, we are interested in the following research projects:
Developing synthetic proteins to manipulate ubiquitin signaling for cancer therapeutics
Engineering protein-protein interactions to probe and rewire DNA damage reponse
Creating new molecules to recruit E3 ligases for targeted protein degradation
#: Co-first authors; name in bold: Zhang lab members
Aminu B#, Fux J#, Mallette E, Petersen N, Zhang W. (2022) Targeted Degradation of 53BP1 Using Ubiquitin Variant Induced Proximity. Biomolecules 12, 479.
Guo Y#, Liu Q#, Mallette E#, Caba C, Hou F, Fux J, LaPlante G, Dong A, Zhang Q, Zheng H, Tong Y, Zhang W. (2021) Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1. Journal of Biological Chemistry 297, 101107.
Roscow O, Zhang W. (2021) Using phage display to develop ubiquitin variant modulators for E3 ligases. Journal of Visualized Experiments 174, e62950.
LaPlante G, Zhang W. (2021) Targeting the ubiquitin-proteasome system for cancer therapeutics by small-molecule inhibitors. Cancers 13, 3079.
Liang CT#, Roscow O#, Zhang W. (2021) Recent developments in engineering protein-protein interactions using phage display. Protein Engineering, Design and Selection 34, 1-13.
Liu Q#, Aminu B#, Roscow O, Zhang W. (2021) Targeting the ubiquitin signaling cascade in tumor microenvironment for cancer therapy. International Journal of Molecular Sciences 22, E791.
LeBlanc N#, Mallette E#, Zhang W. (2021) Targeted modulation of E3 ligases using engineered ubiquitin variants. The FEBS Journal 288, 2143-2165.
Veggiani G#, Gerpe MCR#, Sidhu SS, Zhang W. (2019) Emerging drug development technologies targeting ubiquitination for cancer therapeutics. Pharmacology & Therapeutics 119, 139-154.
Gabrielsen M, Buetow L, Nakasone MA, Ahmed SF, Sibbet GJ, Smith BO, Zhang W*, Sidhu SS*, Huang DT*. (2017) A general strategy for discovery of inhibitors and activators of RING and U-box E3 ligases with ubiquitin variants. Molecular Cell 68, 456-470. (*Co-corresponding authors)
Zhang W, Ben-David M, Sidhu SS. (2017) Engineering cell signaling modulators from native protein-protein interactions. Current Opinion in Structural Biology 45, 25-35.
Zhang W, Bailey-Elkin BA, Knaap RCM, Khare B, Dalebout TJ, Johnson G, van Kasteren PB, McLeish N, Gu J, He W, Kikkert M, Mark BL, Sidhu SS. (2017) Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants. PLoS Pathogens 13(5): e1006372. https://doi.org/10.1371/journal.ppat.1006372
Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS. (2016) System-wide modulation of HECT E3 ligases with selective ubiquitin variant probes. Molecular Cell 62, 121-36.