Yingming Zhao, Ph.D.

Cellular interactions, Proteomics, Systems Biology, and Protein Post-Translational Modifications

Research Summary

Post-translational modifications (PTMs) represent a major vehicle to diversify a cellular proteome, the inventory of all protein species in an organism. PTMs have critical roles in all the major cellular pathways and diseases. A protein can be potentially modified by more than 300 types of post-translational modifications, which are catalyzed by enzymes encoded by more than 5% of the genome in higher eukaryotes. A combination of a dozen PTM sites in a substrate protein could lead to more than a million possible protein structures with potentially different functions. Given the high abundance and diversities of PTMs, they are likely the most complex regulatory mechanisms in cells. Despite their critical roles in cells, little is known about their biology, except several most extensively studied PTMs. Functional characterizations of PTMs at the molecular level have been slow, largely due to a lack of suitable information infrastructure and technology infrastructure.

Our research aims to develop novel proteomics technologies, and to use them to dissect PTM pathways. We are developing new mass spectrometry and bioinformatics tools for reliable, sensitive, and comprehensive analysis of proteins and PTMs. We are interested in dynamics analysis of diverse PTMs in order to understand their functions. We are using proteomics approach to characterize lysine acetylation, lysine propionylation, lysine butyrylation pathways, and novel protein methylations, the last three of which were recently discovered by us. We have begun applying a new bioinformatics tool, PTMap, also recently developed by us, to investigate PTM cross-talks. We also use powerful proteomics technologies in conjunction with biochemistry, molecular biology, and cell biology to decode PTM networks that have major implications for human health and are not amenable to conventional techniques.

Selected Papers

Chen, Y., Kai, Z. and Zhao, Y., PTMap, a new software to identify all the possible post translational modifications with high speed and high accuracy. Proc Natl Acad Sci U S A, 2009. 106(3):p.761-766.

Zhang, J., Sprung, R., Pei, J., Tan, X., Kim, S., Zhe, H., Liu, C.F., Grishin, N.V. and Zhao, Y., Abundant, evolutionarily conserved, DNA-independent substrate proteins of lysine acetylation in E. coli. Molecular and Cellular Proteomics, 2009. 8(2): p.215-225.

Sprung, R., Chen, Y., Zhang, K., Cheng, D., Zhang, T., Peng, J. and Zhao, Y., Identification and validation of eukaryotic aspartate and glutamate methylation in proteins. J Proteome Res, 2008. 7(3): p. 1001-6.

Tang, Y., Zhao, W., Chen, Y., Zhao, Y. and Gu, W., Acetylation is indispensable for p53 activation. Cell, 2008. 133(4): p. 612-26.

Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S.C., Falck, J.R., Peng, J., Gu, W. and Zhao, Y., Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics, 2007. 6(5): p. 812-9.

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. and Zhao, Y., Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell, 2006. 23(4): p. 607-18.

Chien, Y., Kim, S., Bumeister, R., Loo, Y.M., Kwon, S.W., Johnson, C.L., Balakireva, M.G., Romeo, Y., Kopelovich, L., Gale, M., Jr., Yeaman, C., Camonis, J.H., Zhao, Y. and White, M.A., RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell, 2006. 127(1): p. 157-70.

Qiu, Y., Zhao, Y., Becker, M., John, S., Parekh, B.S., Huang, S., Martinez, E.D., Chen, Y., Lu, H., Adkins, N.L., Georgel, P.T., Schiltz, P.L. and Hager, G.L., HDAC1 Acetylation is Linked to Progressive Modulation of Steroid Receptor Induced Gene Transcription. Mol Cell, 2006. 22(5): p. 669-679.