420 Washington Avenue SE
Minneapolis, MN 55455
Our long-term goal is to discover and characterize novel posttranslational modification (PTM) pathways that are involved in protein homeostasis, cellular signaling and epigenetic regulation. To achieve this goal, we develop and apply mass spectrometry-based quantitative and chemical proteomics technology as well as bioinformatic analysis tools for system-wide characterization of protein modification networks. Our study employs both cellular and animal-based models that involve diverse biological applications including cancer, metabolic diseases, nutrition and aging.
Covalent posttranslational modifications (PTMs) of proteins represent one of the fundamental regulatory mechanisms in the cell with enzyme families encoded by more than 5% of the genome in higher eukaryotes. Extensive studies in the past twenty years established the functional roles of some well-known PTMs, including protein phosphorylation, glycosylation, ubiquitination, lysine acetylation and methylation in signal transduction, cell cycle, protein-protein interactions and epigenetic memories.
We have developed highly efficient mass-spectrometry based technology for system-wide identification and quantification of PTM sites and established the bioinformatics platform for understanding the functional relevance of the PTMs in protein structure and cellular physiology.
Our future research aims to develop and apply powerful proteomic technologies in combination with biochemistry, cell biology and computational analysis to understand the dynamic profiles of the PTM networks in various diseases, and reveal the correlation between cellular metabolism and diverse PTM pathways.
Li, Y., Evers, J., Luo, A., Erber, L., Postler, Z. & Chen, Y. A Quantitative Chemical Proteomics Approach for Site-specific Stoichiometry Analysis of Ubiquitination. Angew Chem Int Ed Engl. 58(2):537-541 (2019)
Erber, L., Luo, A. & Chen, Y. Targeted and Interactome Proteomics Revealed the Role of PHD2 in Regulating BRD4 Proline Hydroxylation. Mol. Cell. Proteomics 18(9):1772-1781 (2019).
Zhou, T., Erber, L., Liu, B., Gao, Y., Ruan, H.B. & Chen, Y. Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells. Oncotarget 7, 79154-79169 (2016).
Zhou, T., Chung, Y., Chen, J. & Chen, Y. Site-specific Identification of Lysine Acetylation Stoichiometries in Mammalian Cells. J Proteome Res 15, 1103-1113. (2016)
Park, J.*, Chen, Y.*, Tishkoff, D.X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B.M.M., Skinner, M.E., Lombard, D.B. & Zhao, Y. Sirt5-mediated Lys desuccinylation regulates diverse metabolic pathways. Mol Cell 50, 919-930 (2013)
Chen, Y., Zhao, W., Yang, J.S., Cheng, Z., Luo, H., Lu, Z., Tan, M., Gu, W. & Zhao, Y. Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways. Mol Cell Proteomics 11, 1048-1062 (2012).
Chen, Y., Chen, W., Cobb, M.H. & Zhao, Y. PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A 106, 761-766 (2009).
Tang, Y., Zhao, W., Chen, Y., Zhao, Y. & Gu, W. Acetylation is indispensable for p53 activation. Cell 133, 612-626 (2008).
Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S.C., Falck, J.R., Peng, J., Gu, W. & Zhao, Y. Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics 6, 812-819 (2007).
Kim, S.C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N.V., White, M., Yang, X.J. & Zhao, Y. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23, 607-618 (2006).
Chen, Y., Kwon, S.W., Kim, S.C. & Zhao, Y. Integrated approach for manual evaluation of peptides identified by searching protein sequence databases with tandem mass spectra. J Proteome Res 4, 998-1005 (2005).