Research Focus

Our laboratory centers on the translation machinery of the central dogma. By integrating multidisciplinary approaches, we investigate the biological functions and engineered modifications of tRNA and proteins. We are committed to developing next-generation biopharmaceuticals for the diagnosis and treatment of major diseases and rare genetic disorders.

Background

Life processes depend on precisely orchestrated signal transduction networks, which are largely mediated by the dynamic post-translational modifications (PTMs) of proteins. PTMs expand the functional diversity of the proteome through the covalent attachment of chemical groups. To date, hundreds of distinct PTM types have been identified in intracellular proteins—including phosphorylation, acetylation, methylation, glycosylation, ubiquitination, and lipidation. These modifications regulate protein function by altering structure, subcellular localization, and molecular interactions. Each PTM is tightly controlled by dedicated writer enzymes (that install the modification), eraser enzymes (that remove it), and reader proteins (that decode it), creating a sophisticated and dynamic regulatory network. Consequently, protein PTMs influence nearly every aspect of cellular physiology and play central roles in the onset and progression of major diseases. Studying and modulating PTMs is therefore fundamental to deciphering the mechanisms of life processes and disease pathology.

Research Directions

The laboratory pursues the following directions:

(1) Using interdisciplinary strategies, we investigate the dynamic changes in protein PTMs during the onset and progression of major diseases, and elucidate the molecular mechanisms and biological functions of PTMs on key regulatory proteins.

(2) We develop precise in vivo protein modification toolkits that enable the site-specific installation of natural PTMs or their mimics into target proteins in living systems, providing powerful platforms to decode the functions of protein PTMs.

(3) Leveraging our in vivo protein modification platform in combination with chemical proteomics, we discover novel intracellular PTMs and explore their functions, regulatory mechanisms, and therapeutic potential in cell signaling pathways and major disease processes.

(4) We explore the biological roles of tRNA during protein translation and, for a range of rare genetic disorders, develop protein-based therapeutics and gene therapies based on tRNA engineering technologies.

Website： https://person.zju.edu.cn/en/0017079