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Dr CHUNG, Yik Sham Clive 鍾亦琛 (joint appointment with Department of Pathology)

Dr CHUNG, Yik Sham Clive 鍾亦琛 (joint appointment with Department of Pathology)

  • BSc, PhD (HKU)
  • Assistant Professor
L1-53, Laboratory Block, 21 Sassoon Road, Hong Kong
+852 3917 9172
+852 2855 1254
  • Chemical biology
  • Organic synthesis of novel functional tools and drug lead compounds for biological studies and disease therapy
  • Chemoproteomics and mass spectrometry (MS)
  • Molecular imaging of cellular signaling molecules
  • Postdoctoral fellow, Novartis-Berkeley Center for Proteomics and Chemistry Technologies, UC Berkeley (2018-2020); Supervisor: Prof. Daniel K. Nomura
  • Postdoctoral fellow, Department of Chemistry, UC Berkeley (2016-2017); Supervisor: Prof. Christopher J. Chang
  • Postdoctoral fellow, Department of Chemistry, HKU (2014-2015); Supervisor: Prof. Chi-Ming Che
  • Research Associate, Department of Chemistry, HKU (2012-2014); Supervisor: Prof. Vivian Wing-Wah Yam
  • PhD, Department of Chemistry, HKU (2008-2012); Supervisor: Prof. Vivian Wing-Wah Yam
  • BSc(Chemistry; first class honors), Department of Chemistry, HKU (2005-2008)

Chemical biology: application of synthetic chemicals and chemistry techniques to study and manipulate biological systems

Understanding functions and activities of biomolecules at molecular level are crucial, as this can significantly increase our knowledge on physiology and pathology which can facilitate development of effective diagnosis and therapy for diseases. Yet, complex biological environments make studies on specific target or signaling event very challenging. Chemical compounds can be valuable tools for tackling this challenge, as generally they can be synthesized in large scale and high purity with good characterization, as compared to biological modalities. More importantly, by good design on their chemical structures, these compounds can be readily functionalized for serving specific purpose to study, image or profile target biomolecules, or even modulate activities of the targets and exhibit therapeutic effects.

Integrated chemical biology approach, spanning from synthetic chemistry, molecular imaging and proteomics, to molecular and cell biology for studying cellular signaling events and diseases

Our lab develops new chemical tools for studying diseases and cellular signaling events, particularly those related to or mediated by reversible redox modifications. These redox modifications are known to be essential to life and mounting evidences indicate that they can regulate important biological processes including cell migration, circadian rhythm, neurogenesis and stem cell proliferation. Yet, the identity of most proteins/biomolecules involved in these redox signaling events are still unknown, mainly because of the difficulties in studying these unstable and transient redox modifications (unlike traditional stable phosphorylation/de-phosphorylation of proteins).

Our chemical probes show specific reactions with signaling molecules/proteins of interest, and this enables us to trap “reversible redox modification” into “permanent covalent tag”, thus allowing us to identify these target(s) by proteomics and mass spectrometry (MS)-based platforms. We can also real-time visualize these signaling events by using a fluorescent tag, and this approach is more advantageous than imaging by conventional fluorescent probes because we can preserve spatial resolution of the target(s).

After identifying biomolecules/proteins involved in redox signaling pathways, we will further investigate molecular and cell biology of these biomolecules/proteins, particularly their roles on cellular signaling and disease development and propagation.

Cellular event

High-throughput screening coupled with activity-based protein profiling (ABPP) for discovery of new therapeutic agents

Redox-active species have been found to show correlations with serious diseases such as cancer, aging, obesity, diabetes and neurodegenerative diseases. Therefore, the protein targets identified by our chemical probes can be of great therapeutic values, as modulating activities of these proteins can be an effective way to tackle the diseases.

Our lab develops a library of activity-based compounds with unique chemical structures and physiochemical properties, and occupying a large three-dimensional chemical spaces. These activity-based compounds can covalently bind onto reactive sites on the proteins, and in many cases these bindings can alter functions and activities of the proteins. Through high-throughput screening and ABPP experiments, activity-based compounds with high binding affinity and selectivity toward protein targets in live cells as well as in vivo can be identified. More importantly, ABPP allows us to identify/validate the exact binding sites of the compounds on the proteins, thus facilitating our understanding of the mechanism of actions of the compounds in biological systems. This also accelerates lead optimization for the development of new therapeutic agents.

ABPP

  1. Activity-Based Sensing with a Metal-Directed Acyl Imidazole Strategy Reveals Cell Type-Dependent Pools of Labile Brain Copper. 

    S. Lee, C. Y. S. Chung, P. Liu, L. Craciun, Y. Nishikawa, K. J. Bruemmer, I. Hamachi, K. Saijo, E. W. Miller and C. J. Chang, J. Am. Chem. Soc., in press, doi: 10.1021/jacs.0c05727. (These authors contributed equally)

  2. Nidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1.

    X. Mao, S. K. Tey, C. L. S. Yeung, E. M. L. Kwong, Y. M. E. Fung, C. Y. S. Chung, L.‐Y. Mak, D. K. H. Wong, M.‐F. Yuen, J. C. M. Ho, H. Pang, M. P. Wong, C. O.‐N. Leung, T. K. W. Lee, V. Ma, W. C.‐S. Cho, P. Cao, X. Xu, Y. Gao and J. W. P. Yam, Adv. Sci., in press, doi: 10.1002/advs.202002157. (These authors contributed equally)

  3. Activity-Based Ratiometric FRET Probe Reveals Oncogene-Driven Changes in Labile Copper Pools Induced by Altered Glutathione Metabolism
    C. Y. S. Chung, J. M. Posimo, S. Lee,† T. Tsang, J. M. Davis, D. C. Brady# and C. J. Chang,# Proc. Natl. Acad. Sci. U. S. A., 2019, 116, 18285. (These authors contributed equally; #co-corresponding authorship)
  4. Covalent Targeting of the Vacuolar H+-ATPase activates autophagy via mTORC1 inhibition (featured in News and Views in Nat. Chem. Biol., 2019, 15, 760)
    C. Y. S. Chung, H. R. Shin, C. A. Berdan. B. Ford, C. C. Ward, J. A. Olzmann, R. Zoncu# and D. K. Nomura,# Nat. Chem. Biol., 2019, 15, 776. (These authors contributed equally; #co-corresponding authorship)
  5. Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications
    C. C. Ward, J. I. Kleinman, S. M. Brittain, P. S. Lee, C. Y. S. Chung, K. Kim, Y. Petri, J. R. Thomas, J. A. Tallarico, J. M. McKenna, M. Schirle and D. K. Nomura, ACS Chem. Biol., 2019, 14, 2430.
  6. Versatile Histochemical Approach to Detection of Hydrogen Peroxide in Cells and Tissues Based on Puromycin Staining
    C. Y. S. Chung, G. A. Timblin, K. Saijo and C. J. Chang, J. Am. Chem. Soc., 2018, 140, 6109.
  7. A Modular Trigger for the Development of Selective Superoxide Probes
    Z. H. Yu, C. Y. S. Chung, F. K. Tang, T. F. Brewer and H. Y. Au-Yeung, Chem. Commun., 2017, 53, 10042. ( These authors contributed equally)
  8. Amphiphilic oligo(ethylene glycol)- and poly(ethyleneoxide)-block-poly(propylene oxide)-block-poly-(ethylene oxide)-containing cyclometalated alkynylgold(III) complexes: From basic photophysics to self-assembly and stimuli-responsive properties
    S. K. L. Siu, C. Y. S. Chung and V. W. W. Yam, J. Organomet. Chem., 2017, 845, 177.
  9. Simple and versatile preparation of luminescent amphiphilic platinum(II)–containing polystyrene complexes with transformable nanostructures assisted by Pt···Pt and π–π interactions
    H. K. Cheng, C. Y. S. Chung, K. Zhang and V. W. W. Yam, Chem. Asian J., 2017, 12, 1509.
  10. A multi-functional PEGylated gold(III) compound: Potent anti-cancer properties and self-assembly into nanostructures for drug co-delivery
    C. Y. S. Chung, S. K. Fung, K. C. Tong, P. K. Wan, C. N. Lok, Y. Huang, T. Chen and C. M. Che, Chem. Sci., 2017, 8, 1942.
  11. Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression
    T. T. H. Fong, C. N. Lok, C. Y. S. Chung, Y. M. E. Fung, P. K. Chow, P. K. Wan and C. M. Che, Angew. Chem. Int. Ed., 2016, 55, 11935.
  12. Highly luminescent palladium(II) complexes with sub-millisecond blue to green phosphorescent excited states. Photocatalysis and highly efficient PSF-OLEDs
    P. K. Chow, G. Cheng, G. S. M. Tong, C. Ma, W. M. Kwok, W. H. Ang, C. Y. S. Chung, C. Yang, F. Wang and C. M. Che, Chem. Sci., 2016, 7, 6083.
  13. Synthesis and Electrochemical, Photophysical, and Self-Assembly Studies on Water-Soluble pH-Responsive Alkynylplatinum(II) Terpyridine Complexes
    C. Y. S. Chung, S. P. Y. Li, K. K. W. Lo and V. W. W. Yam, Inorg. Chem., 2016, 55, 4650.
  14. Metal−Metal and π−π Interactions Directed End-to-End Assembly of Gold Nanorods
    F. C. M. Leung, S. Y. L. Leung, C. Y. S. Chung and V. W. W. Yam, J. Am. Chem. Soc., 2016, 138, 2989.
  15. Stable luminescent iridium(III) complexes with bis(N-heterocyclic carbene) ligands: photostability, excited state properties, visible-light driven radical cyclization and CO2 reduction, and cellular imaging
    C. Yang, F. Mehmood, T. L. Lam, S. L.-F. Chan, Y. Wu, C.-S. Yeung, X. Guan, K. Li, C. Y. S. Chung, C.-Y. Zhou, T. Zou and C.-M. Che, Chem. Sci., 2016, 7, 3123.
  16. Parallel folding topology-selective label-free detection and monitoring of conformational and topological changes of different G-quadruplex DNAs by emission spectral changes via FRET of mPPE-Ala–Pt(II) complex ensemble
    K. Chan, C. Y. S. Chung and V. W. W. Yam, Chem. Sci., 2016, 7, 2842.
  17. Conjugated Polyelectrolyte-Induced Self-Assembly of Alkynylplatinum(II) 2,6-Bis(benzimidazol-2ˈ-yl)pyridine Complexes
    K. Chan, C. Y. S. Chung and V. W. W. Yam, Chem.–Eur. J., 2015, 21, 16434.
  18. Supramolecular Assembly of Achiral Alkynylplatinum(II) Complexes and Carboxylic β-1,3-Glucan into Different Helical Handedness Stabilized by Pt···Pt and/or π – π Interactions
    C. Y. S. Chung, S.-i. Tamaru, S. Shinkai and V. W. W. Yam, Chem.–Eur. J., 2015, 21, 5447.
  19. Induced Self-Assembly of Platinum(II) Alkynyl Complexes through Specific Interactions between Citrate and Guanidinium for Proof-of-Principle Detection of Citrate and an Assay of Citrate Lyase
    C. Y. S. Chung and V. W. W. Yam, Chem.–Eur. J., 2014, 20, 13016.
  20. Dual pH- and Temperature-Responsive Metallosupramolecular Block Copolymers with Tunable Critical Micelle Temperature via Modulation of Self-Assembly of NIR Emissive Alkynylplatinum(II) Complexes Induced by Changes in Hydrophilicity and Electrostatic Effects
    C. Y. S. Chung and V. W. W. Yam, Chem.–Eur. J., 2013, 19, 13182.
  21. Induced Self-Assembly and Disassembly of Water-Soluble Alkynylplatinum(II) Terpyridyl Complexes with “Switchable” Near-Infrared (NIR) Emission Modulated by Metal-Metal Interactions Over Physiological pH: Demonstration of pH-Responsive NIR Luminescent Probes in Cell-Imaging Studies
    C. Y. S. Chung, S. P. Y. Li, M. W. Louie, K. K. W. Lo and V. W. W. Yam, Chem. Sci., 2013, 4, 2453.
  22. Selective Label-Free Detection of G-Quadruplex Structure of Human Telomere by Emission Spectral Changes in Visible-and-NIR Region under Physiological Condition through the FRET of a Two-Component PPE-SO3−−Pt(II) Complex Ensemble with Pt∙∙∙Pt, Electrostatic and π–π Interactions
    C. Y. S. Chung and V. W. W. Yam, Chem. Sci., 2013, 4, 377.
  23. Reversible thermo-responsive luminescent metallo-supramolecular triblock copolymers based on platinum(II) terpyridyl chromophores with unusual aggregation behaviour and red-near-infrared (NIR) emission upon heating
    Y. Hu, K. H. Y. Chan, C. Y. S. Chung and V. W. W. Yam, Dalton Trans., 2011, 40, 12228.
  24. Induced Self-Assembly and Förster Resonance Energy Transfer Studies of Alkynylplatinum(II) Terpyridine Complex Through Interaction With Water-Soluble Poly(phenylene ethynylene sulfonate) and the Proof-of-Principle Demonstration of this Two-Component Ensemble for Selective Label-Free Detection of Human Serum Albumin
    C. Y. S. Chung and V. W. W. Yam, J. Am. Chem. Soc., 2011, 133, 18775.
  25. “Proof-of-principle” concept for label-free detection of glucose and α-glucosidase activity through the electrostatic assembly of alkynylplatinum(II) terpyridyl complexes
    C. Y. S. Chung, K. H. Y. Chan and V. W. W. Yam, Chem. Commun., 2011, 47, 2000.
  26. Reversible pH- and solvent-responsive micelle-mediated self-assembly of platinum(II) terpyridyl-based metallo-supramolecular diblock copolymers.
    V. W. W. Yam, Y. Hu, K. H.Y. Chan and C. Y. S. Chung, Chem. Commun., 2009, 6216.

Croucher Postdoctoral Fellowship (2016-18)
Best poster presentation in Gordon Research Conference - Hybrid Electronic & Photonic Materials and Phenomena (2014)
G. T. Byrne Memorial Prize in Chemistry, HKU (2007/08)
Rayson Huang Scholarship in Chemistry, HKU (2006-08)
Douglas Payne Prizes in Chemistry, HKU (2005/06)

  1. mTORC1 inhibitors for activating autophagy
    D. K. Nomura, R. Zoncu, C. Y. S. Chung and H. Shin, U.S. Patent Application No. 62/791,655.
  2. Activity-based FRET probe for Copper detection
    C. J. Chang, C. Y. S. Chung and S. Lee, U.S. Patent Application No. 62/845,108.
  3. mTORC1 modulators
    D. K. Nomura, R. Zoncu, A. M. Roberts, K. F. Cho, C. Y. S. Chung, H. Shin and B. Croze, U.S. Patent Application No. 62/639,431
  4. Puromycin-based probes and methods of use thereof
    C. J. Chang and C. Y. S. Chung, U.S. Patent Application No. 62/647,481.
  5. Gold porphyrin-PEG conjugates and method of use
    C. M. Che and C. Y. S. Chung, US 2017/0157261 A1; PCT/CN2016/109051.
  6. Metal-Directed Acyl Imidazole Strategy
    S. Lee, C. Y. S. Chung and C. J. Chang, U.S. Patent Application No. 63/020,014.