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Yang Xu

Research

Our laboratory is interested in understanding the signaling pathways involved in maintaining genetic stability in mammalian cells, particularly embryonic stem cells (ESCs). With their capability of unlimited self-renewal and pluripotency to differentiate into any cell types in the body, ESCs hold great promise for human cell replacement therapy. Therefore, it is critical to elucidate the mechanism to safeguard the genetic integrity of ESCs so that DNA damage will not be passed on to progeny. We are investigating the pathways that coordinate the DNA damage responses and self-renewal of ESCs and adult stem cells. We are testing the hypothesis that disruption of this coordination will induce genetic instability in adult stem cell population, leading to the generation of cancer stem cells. We are focusing on the roles of tumor suppressors such as ATM and p53, which are critical to maintaining genetic stability in somatic cells. To facilitate the studies of gene function in human ESCs, we recently developed technologies that allow efficient knock-out and knock-in through homologous recombination in hESCs.

Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, could provide unlimited autologous cells for human therapy. Since most of the reprogramming factors have oncogenic potential, we are investigating the genetic stability in iPSCs. In addition, we are developing strategies to address the bottlenecks that hinder the clinic development of human ESCs and iPSCs. For example, we are identifying the pathways that can be used to eliminate the teratomas risk associated with ESCs and iPSCs-based therapy. In the context of hESCs, we are investigating the options to induce immune tolerance to allogenic grafts derived from hESCs.

Select Publications

  • Zhao, T., Zhang, Z.N., Westenskow, P.D., Todorova, D., Hu, Z., Lin, T., Rong, Z., Kim, J., He, J., Wang, M., Clegg, D.O., Yang, Y.G., Zhang, K., Friedlander, M., & Xu, Y.* (2015). Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells. Cell Stem Cell 17(3):353-359.
  • Xiong, J., Todorova, D., Su, NY., Kim, J., Lee, PJ., Shen, Z., Briggs, SP., & Xu, Y.* (2015). Stemness factor Sall4 is required for DNA damage response in embryonic stem cells. J Cell Biol. 208(5):513-20.
  • Rong, Z., Wang, M., Hu, Z., Stradner, M., Zhu, S., Kong, H., Yi, H., Goldrath, A., Yang, YG., Xu, Y.,* and Fu, X.* (2014). An Effective Approach to Prevent Immune Rejection of Human ESC-Derived Allografts. Cell Stem Cell 14:121-30. (Co-corresponding author)
  • Zhao, T., Zhang, Z.N, Rong, Z. and Xu. Y. *(2011). The immunogenicity of the induced pluripotent stem cells. Nature 474: 212-215.
  • Liu, D., Ou, L., Clemenson Jr, G.D., Chao, C., Lutske, M.E., Zambetti, G.P., Gage, F.H. and Xu. Y.* (2010). Puma is required for p53-induced depletion of adult stem cells. Nat. Cell Biol. 12:993-8.
  • Moretto-Zita, M, Jin, H, Shen, Z., Zhao, T., Briggs, S.P. and Xu, Y. (2010). Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc. Natl. Acad. Sci. U S A 107:13312-13317.
  • Song, H., Chung, S.K. and Xu, Y.* (2010). Modeling disease in human ESCs using an efficient BACbased homologous recombination system. Cell Stem Cell 6, 180-89.
  • Song, H., Hollstein, M. and Xu, Y.* (2007). p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat. Cell. Biol. 9:573-80.
  • Xu, Y. (2006) DNA damage: a trigger of innate immunity but essential for adaptive immune homeostasis. Nat Reviews Immunol. 6:261-70.
  • Zhao, T. and Xu, Y. (2010). p53 and Stem cells: new developments and new concerns. Trends Cell Biol. 20:170-175.
  • Deng W. and Xu, Y. (2009). Genome integrity: linking pluripotency and tumorigenicity. Trends Genet. 25:425-427.
  • Song, H., Hollstein, M. and Xu, Y. (2007). p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat. Cell. Biol. 9:573-580.
  • Xu, Y. (2006) DNA damage: a trigger of innate immunity but essential for adaptive immune homeostasis. Nat Reviews Immunol. 6:261-70.
  • Lin, T., Chao, C., Saito, S., Muzar, S., Murphy, M., appella, E. and Xu, Y.* (2005). p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat. Cell Biol. 7, 165- 171.

Biography

Yang Xu received his Ph.D. from Harvard University. He conducted postdoctoral research at the Massachusetts Institute of Technology as a fellow of the Damon Runyon-Walter Winchell Cancer Research Fund.

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