Prof. Zhao's research focuses on the development and application of mass spectrometry-based proteomics, combined with chemical biology and other biological approaches, to uncover and study previously undescribed cellular pathways. His current work emphasizes protein post-translational modifications (PTMs) and their roles in epigenetic regulation. Over the past 18 years, his laboratory has discovered 13 novel lysine acylation pathways closely linked to cellular metabolism and identified approximately 1,000 new histone marks—more than doubling the number known from the first four decades of chromatin biology. His team has also characterized the enzymatic machinery responsible for writing, erasing, and reading these modifications, including a new class of enzymes that generate short-chain acyl-CoAs used as cofactors for lysine acylation.These discoveries have revealed the fundamental importance of metabolite-derived PTMs in regulating gene expression, contributing to various inborn errors of metabolism, shaping the cellular microenvironment (e.g., hypoxia), and modulating immune cell functions.
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