The goal of our lab centers on uncovering the previously unrecognized functions of epigenetic modification during normal and pathological bioprocesses, and decoding the potential crosstalk between epigenetics and epitranscriptomics.
One of our current research interests is to discover the novel noncanonical roles of histone methyltransferase EZH2 during prostate cancer progression. In parallel, my lab dedicates to investigate the dysregulation of various RNA modifications in cancer and unveil the underlying mechanisms. In the past few years, we have reported a number of novel EZH2 functions beyond its canonical role as a transcription repressor (Science Advances, 2020; Clinical Translational Medicine, 2021; Oncogene, 2022). In particular, we were the first to report that EZH2 could upregulate rRNA 2′-O methylation via its direct interaction with rRNA methyltransferase FBL. This work further proved that the crosstalk between EZH2 and rRNA 2′-O methylation promotes the translation process globally in cancer cells (Nature Cell Biology, 2021). In another project, we identified thousands of new 2′-O methylation sites on human mRNAs. More importantly, we confirmed FBL as a mRNA 2′-O methyltransferase and observed a positive effect of FBL-mediated 2′-O methylation on mRNA stability (Molecular Cell, 2024). Besides 2′-O methylation, my research interest also falls into m6A methylation, the most prevalent modification type in eukaryotic RNAs. For instance, we established a novel model for m6A marks around start codon of mRNA splicing factors in mediating nonsense-mediated mRNA decay (NMD) of these splicing factors. Via this signaling, the m6A methyltransferase METTL3 modulates alternative splicing of cancer-related regulators to facilitate tumor outgrowth and self-renewal (Cancer research, 2019). As compared with housekeeping genes, cell identity genes tend to be expressed in a cell- or lineage-specific manner and thus require more precise regulation. By conjoint analyses of RNA stability and chromatin state datasets in multiple cell types, we revealed a significant enrichment of super enhancers and broad H3K4me3 domains at the gene loci of cell identity gene transcripts (Nucleic Acids Research, 2023a). Our data suggest a run-and-brake model, where cell identity genes undergo both frequent transcription and fast RNA decay to achieve precise regulation. In another back-to-back paper, we found a preferential deposition of m6A modification on mRNAs of tumor suppressors (Nucleic Acids Research, 2023b). The m6A-mediated fast decay of tumor suppressor mRNAs was further enhanced in cancer cells relative to normal cells, indicating a strong post-transcriptional expression regulatability. In 2025, we reported an interplay between EZH2 and m6A methylation which promotes prostate cancer progression through modulating an m6A autoregulation pathway (Journal of Clinical Investigation, 2026). In 2026, we show that EZH2 controls selective RNA editing by ADAR1 through remodeling its interactome and nuclear transport, thereby promoting MDM2 expression and prostate cancer progression (Nature Communications, 2026).
