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Integrated chemical biology approach to study cellular redox signaling and its associated diseases


School of Biomedical Sciences

About the Project

Redox-active compounds, which can undergo oxidation/reduction readily, were once classified as detrimental compounds in biology and known to contribute to serious diseases such as cancer, obesity, diabetes and neurodegenerative disorders. Recently, these redox-active molecules are found to be essential to life and when they are produced in a controllable fashion, they can serve as important signaling molecules and mediate specific redox signaling to regulate essential cellular processes including autophagy, cell migration, circadian rhythm, neurogenesis and stem cell proliferation. Therefore, understanding molecular mechanisms on initiation, transduction and regulation of redox signaling, as well as the identity of proteins involved in the signaling process would be critical for developing new therapy against redox-associated diseases and for dissecting complicated signaling pathways in living systems. However, all these remain insufficiently understood so far. This is mainly because unlike other cellular signaling which involves protein phosphorylation/de-phosphorylation that are quite stable modifications, redox signaling is mediated by reversible oxidation/reduction, and these unstable modifications is difficult to be detected/visualized by conventional biochemical/biological experiments.

Our lab is interested in developing new chemical tools and an innovative chemical biology platform to study cellular redox signaling. Through specific chemical reactions, our probes can convert the “unstable redox modifications” into “permanent covalent tag” on the protein(s) involved in redox signaling, thus enabling in-depth study of redox signaling and how it is initiated, transduced and regulated. We can also real-time monitor the dynamic redox signaling by trapping redox modification into a permanent tag labelled with fluorophores. All these new tools and technology should help to identify new proteins involved in redox signaling which are important targets for promoting health and developing new therapy.

Supervisor
Dr. Clive Chung received first-class honors BSc degree in chemistry at The University of Hong Kong (HKU) in 2008. He then worked in Prof Vivian Wing-Wah Yam’s research group for a PhD degree from 2008 to 2013, focusing on the development of luminescence platinum(II) complexes and supramolecular assemblies for biosensing, live-cell imaging and functioning as stimuli-responsive materials. In 2014, he worked as a postdoctoral fellow of Prof Chi-Ming Che at HKU, in which he investigated anti-cancer properties of inorganic medicines and nano-formulations based on self-assembly properties of amphiphilic metal complexes. In 2016, Dr Chung received Croucher Postdoctoral Fellowship and joined Prof Christopher J. Chang’s research group, working on molecular imaging of reactive oxygen species (ROS) and copper ion to identify elevated H2O2 level in liver tissues of murine model of non-alcoholic fatty liver disease (NAFLD) and unravel roles of copper ion in biology, particularly in cancer and neuroscience. In 2018, Dr Chung moved to Novartis-Berkeley Center for Proteomics and Chemistry Technologies in UC Berkeley, working with Prof Daniel K. Nomura on chemoproteomics and mass spectrometry (MS) for discovering activity-based compounds that can modulate autophagy and mTORC1 signaling. In May 2020, Dr Chung joined the School of Biomedical Sciences and Department of Pathology, HKU, as an Assistant Professor. His current research is highly interdisciplinary, with the focus on applying new chemistry to investigate cellular signaling as well as to develop new drug modalities using advance mass spectrometry (MS)-platforms.

Faculty information, funding opportunities and application deadlines: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

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