B.S., 1995, Biochemistry, Fudan University, China
M.S., 1997, Institute of Genetics, Fudan University, China
Ph.D., 2002, Molecular Genetics and Microbiology, Rutgers University and UMDNJ, Piscataway, NJ
Postdoctoral research: UMDNJ, Piscataway, NJ and Princeton University, Princeton, NJ
My lab is interested in elucidation of signaling pathways related to cancer using multi-disciplinary biophysics and biochemical approaches, including structural biology and proteomics, in combination with cell biology. We focus on signaling pathways that affect cancer cell metabolism and cancer cell genome integrity.
Protein phosphatase 2A (PP2A) is involved in many essential cellular functions. Deregulation of PP2A function is frequently linked to multiple types of cancer. The importance of PP2A function also resides in its crosstalk with the Tor signaling pathway, which has broad effects on cell growth and metabolism. PP2A also interacts with PML, a major component of PML-nuclear body (PML-NB) that is missing in later stage of tumors. PML is considered an important tumor suppressor and has important functions in genome integrity and as an antiviral. Structural biology in combination with biochemistry and proteomics will provide powerful tools for elucidation of the structure and function of the key components in the regulation of PP2A, Tor and PML, as well as the crosstalk among them. Results from these aspects of our research will have a direct impact on the design of therapeutics against cancer.
Seok SH, Lee W, Jiang L, Molugu K, Zheng A, Li Y, Park S, Bradfield CA, Xing Y. Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex. Proc Natl Acad Sci U S A. 2017 May 23;114(21):5431-5436. doi: 10.1073/pnas.1617035114. Epub 2017 Apr 10. PubMed PMID: 28396409; PubMed Central PMCID: PMC5448172.
Kong G, Chang YI, Damnernsawad A, You X, Du J, Ranheim EA, Lee W, Ryu MJ, Zhou Y, Xing Y, Chang Q, Burd CE, Zhang J. Loss of wild-type Kras promotes activation of all Ras isoforms in oncogenic Kras-induced leukemogenesis. Leukemia. 2016 Jul;30(7):1542-51. doi: 10.1038/leu.2016.40. PubMed PMID: 27055865; PubMed Central PMCID: PMC5316475.
Wlodarchak N, Xing Y. PP2A as a master regulator of the cell cycle. Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):162-84. doi: 10.3109/10409238.2016.1143913. Epub 2016 Feb 24. PubMed PMID: 26906453; PubMed Central PMCID: PMC4905575.
Guo, F., Stanevich, V., Wlodarchak, N., Sengupta, R., Jiang, L., Satyshur, K. A., and Xing, Y. Structural Basis of PP2A Activation by PTPA, an ATP-dependent Activation Chaperone. Cell Res., 24(2): 190-203, 2014.
Guo, F., Wan, L., Zheng, A., Stanevich, V., Wei, Y., Satyshur, K. A., Shen, M., Lee, W., Kang, Y., and Xing, Y. Structural Insights Into the Tumor-Promoting Function of the MTDH-SND1 Complex. Cell Rep., 8(6): 1704-1713, 2014.
Kim, H., Guo, F., Brahma, S., Xing, Y ., and Burkard, M. E. Centralspindlin Assembly and 2 Phosphorylations on MgcRacGAP by Polo-like Kinase 1 Initiate Ect2 Binding in Early Cytokinesis. Cell Cycle, 13(18): 2952-2961, 2014.
Kotlo, K., Xing, Y., Lather, S., Grillon, J. M., Johnson, K., Skidgel, R. A., Solaro, R. J., and Danziger, R. S. PR65A Phosphorylation Regulates PP2A Complex Signaling. PLoS ONE, 9(1):e85000, 2014.
Stanevich, V., Zheng, A., Guo, F., Jiang, L., Wlodarchak, N., and Xing, Y. Mechanisms of the Scaffold Subunit in Facilitating Protein Phosphatase 2A Methylation. PLoS ONE, 9(1):e86955, 2014.
Wan, L., Lu, X., Yuan, S., Wei, Y., Guo, F., Shen, M., Yuan, M., Chakrabarti, R., Hua, Y., Smith, H. A., Blanco, M. A., Chekmareva, M., Wu, H., Bronson, R. T., Haffty, B. G., Xing, Y., and Kang, Y. MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors. Cancer Cell, 26(1): 92-105, 2014.
Jiang, L., Stanevich, V., Satyshur, K. A., Kong, M., Watkins, G. R., Wadzinski, B. E., Sengupta, R., and Xing, Y. Structural Basis of Protein Phosphatase 2A Stable Latency. Nat. Commun., 4:1699, 2013.
Wlodarchak, N., Guo, F., Satyshur, K. A., Jiang, L., Jeffrey, P. D., Sun, T., Stanevich, V., Mumby, M. C., and Xing, Y. Structure of the Ca2+-Dependent PP2A Heterotrimer and Insights into Cdc6 Dephosphorylation. Cell Res., 23(7): 931-946, 2013.
Mezrich, J. D., Nguyen, L. P., Kennedy, G., Nukaya, M., Fechner, J. H., Zhang, X., Xing, Y., and Bradfield, C. A. SU5416, a VEGF Receptor Inhibitor and Ligand of the AHR, Represents a New Alternative for Immunomodulation. PLoS One, 7(9):e44547, 2012.
Xing, Y., Nukaya, M., Satyshur, K. A., Jiang, L., Stanevich, V., Korkmaz, E. N., Burdette, L., Kennedy, G. D., Cui, Q., and Bradfield, C. A. Identification of the Ah-Receptor Structural Determinants for Ligand Preferences. Toxicol. Sci., 129: 86-97, 2012.