The Gui lab @SU
The Gui lab focus on innovative drug discovery to target the traditional “undruggable” proteome. We are mining molecular glues from DNA encoded OBOC libraries to manipulate the intracellular protein homeostasis
Our Research
In human proteome, around 85% proteins remain “undruggable” by traditional occupancy driven pharmacology. Chemical induced proximity by recruiting an effector protein (EP) to the target protein (TP) is emerging as a powerful tool to target “undruggable” targets. The most successful case is targeted protein degradation by recruiting E3 ubiquitin ligases.
In my lab, we have two projects. Project 1: Screening non-inhibitory ligands and molecular glues for deubiquitinating enzymes (DUBs) from DNA encoded one bead one compound (OBOC) libraries through a functional platform. Another project we focus on is screening activator and molecular glues for 20S proteasome to degrade intrinsically disorerder proteins.
Our, ultimate gole is push the molecules into clinic and improve the quality of our life.
Project 1
Screening for non-inhibitory ligands and molecular glues for DUBs
Project 2:
Mining activators and molecular glues for 20S proteasome.
Publications
Prior to SU:
Gui., W., Goss., A., & Kodadek, T. (2025). A Functional Assay for Mining Noninhibitory Enzyme Ligands from One Bead One Compound Libraries: Application to E3 Ubiquitin Ligases. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.5c07307
Gui, W., & Kodadek, T. (2023). Facile Synthesis of Homodimeric Protein Ligands. ChemBioChem, 24(18), e202300392. https://doi.org/10.1002/cbic.202300392
Gui, W., Giardina, S., Balzarini, M., Barany, F., & Kodadek, T. J. (2023). Reversible Assembly of Proteolysis Targeting Chimeras. ACS Chemical Biology, 18(7), 1582–1593. https://doi.org/10.1021/acschembio.3c00199
Gui, W., & Kodadek, T. (2022). Applications and Limitations of Oxime-Linked “Split PROTACs”. ChemBioChem, 23(18), e202200275. https://doi.org/10.1002/cbic.202200275
Gui, W., Davidson, G. A., & Zhuang, Z. H. (2021). Chemical methods for protein site-specific ubiquitination. RSC Chemical Biology, 2(2), 450–467. https://doi.org/10.1039/d0cb00215a
Gui, W., Shen, S. Q., & Zhuang, Z. H. (2020). Photocaged Cell-Permeable Ubiquitin Probe for Temporal Profiling of Deubiquitinating Enzymes. Journal of the American Chemical Society, 142(46), 19493–19501. https://doi.org/10.1021/jacs.9b12426
Gui, W., Paudel, P., & Zhuang, Z. (2020). Activity-Based Ubiquitin Probes for Investigation of Deubiquitinases. Comprehensive Natural Products III, 589–602. https://doi.org/10.1016/B978-0-12-409547-2.14672-4
Gui, W.#; Ott, C. A.#; Yang, K.; Chung, J. S.; Shen, S.; Zhuang, Z., Cell-Permeable Activity-Based Ubiquitin Probes Enable Intracellular Profiling of Human Deubiquitinases. (# co-first author), J. Am. Chem. Soc. 2018, 140 (39), 12424-12433. https://doi.org/10.1021/jacs.8b05147.
Our Team
wgui03@syr.edu
jparambe@syr.edu
Graduate Student, 2024 sshahria@syr.edu
Graduate Student, 2025 kyoung18@syr.edu
Graduate Student, 2025 hhkandam@syr.edu
News
Dec 12th, 2025. Welcome first year graduate student Vitoria Fernandes Ferro, Hiruni Kandambi and Kate Young joins our lab.
Nov 1st, 2025. Welcom second year graduate student Janitha Parambe Gedara and Saimon Shahriar joins our lab.
Aug 27th, 2025
The Gui lab is officially open at SU!
We are hiring
We are hiring graduate students, postdoctoral, visiting schoolar, and undergraduate students. We especially encourage candidates with expertise and intrest in chemical biology, medicinal chemistry, biochemistry to apply. Please send your CV and research summary to wgui03@syr.edu
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