中央研究院 生物化學研究所

Posttranslational modification of proteins by ubiquitin (Ub) is a crucial regulatory mechanism in various cellular processes. Ubiquitin-mediated pathways are being rapidly discovered in different aspects of cell biology. Human deubiquitinases (DUBs) are an emerging class of therapeutic targets for drug discovery against cancer and neurodegenerative diseases. Activity-based DUB probes are powerful tools for identifying new DUB functions, understanding DUB catalysis and specificity, and developing DUB inhibitors. My lab has developed protein- and polyubiquitin-based DUB probes that helped identify DUBs targeting specific proteins, and elucidate the mode of ubiquitin chain recognition and cleavage by human ubiquitin-specific protease (USP). We have also worked on cell-permeable DUB probes that enable DUB profiling in live cells and inhibitor discovery. These chemical biology approaches offer insights into various cellular processes that involve protein ubiquitination and deubiquitination, laying the groundwork for future development of therapeutics that modulate DUBs.-Dr. Zhihao Zhuang