We are interested in understanding how posttranslational modifications, particularly protein arginine methylation, control diverse cellular processes, and how their dysregulations lead to cancers, and finally to develop small molecule inhibitors targeting these aberrant events for cancer therapy. A range of complementary approaches are used in the lab, including biochemistry, molecular and cellular biology, multi-omics, and mouse models.
Research Information
Research Interests
Genome sequencing revealed that there are approximately 20,000 protein-coding genes in the human genome. However, one million proteins with distinct functions are predicted in the human proteome. Post-translational modification (PTM) is a major source conferring the proteomic diversity. Notably, protein arginine methylation is emerging as one of the most common PTMs. It plays a critical role in many fundamental cellular processes by controlling protein stability, protein-protein interactions, enzymatic activity, and localization.
The Gan’s laboratory is interested in addressing the outstanding questions and gaps in the field of arginine methylation. How is the activity and expression of arginine methyltransferases regulated? Are there specific arginine demethylases? What are the readers for numerous of arginine methylated proteins? How arginine methylation contributes to human cancers? How to target arginine methylation for cancer therapy? Our goals are to mechanically understand this modification and to develop novel therapies for cancer patients.
Publications
Yin S, Brobbey C, Ball LE, Fu T, Sprague DJ, Gan W. (2025). BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling. Science Advances, 11(17):eads6385. PMID: 40279411 PMCID: PMC12024519.
Brobbey, C., Yin, S., Liu, L., Ball, L.E., Howe, P.H., Delaney, J.R. & Gan, W. (2023). Autophagy dictates sensitivity to PRMT5 inhibitor in breast cancer. Scientific Reports 13(1):10752. PMID: 37400460 PMCID: PMC10318021.
Yin, S., Liu, L., Ball, L. E., Wang, Y., Bedford, T. M., Duncan, A. S., Wang, H. & Gan, W. (2023). CDK5-PRMT1-WDR24 signaling cascade promotes mTORC1 signaling and tumor growth. Cell Reports 42(4):112316. PMID: 36995937.
Liu, L.*, Lin, B.*, Yin, S., Ball, L. E., Delaney, J., Long, D. T.# & Gan, W#. (2022). Arginine methylation of BRD4 by PRMT2/4 governs transcription and DNA repair. Science Advances, 8(49):eadd8928. PMID: 36475791 PMCID: PMC9728970.
Liu, L.*, Dai, X.*, Yin, S., Liu, P., Hill, E. G., Wei, W.#, & Gan, W#. (2022). DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway. Science Signaling, 15(715):eabh2290. PMID: 34982576, PMCID: PMC8992387.
Yin, S.*, Liu, L.*, Brobbey, C., Palanisamy, V., Ball, L. E., Olsen, S. K., Ostrowski, M. C., & Gan, W. (2021). PRMT5-mediated arginine methylation activates AKT kinase to govern tumorigenesis. Nature Communications, 12(1):3444. PMID: 34103528, PMCID: PMC8187744.
Gan, W.*#, Dai, X.*, Dai, X., Xie, J., Yin, S., Zhu, J., Wang, C., Liu, Y., Guo, J., Wang, M., Liu, J., Hu, J., Quinton, R. J., Ganem, N. J., Liu, P., Asara, J. M., Pandolfi, P. P. P., Yang, Y., He, Z., Gao, G., & Wei, W#. (2020). LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control. Nature Cell Biology, 22(2):246-256. PMID: 32015438, PMCID: PMC7076906.