Department of Cell and Molecular Biology
Faculty, Graduate Program
The Yang laboratory investigates regulatory functions of human tRNA synthetases beyond their classic enzymatic role in translation. These regulatory functions are critical in the development and homeostasis of higher organisms and, when dysregulated, are linked to cancer, inflammatory and neurodegenerative disorders.
Known as an essential component of the translational apparatus, aminoacyl-tRNA synthetase family catalyzes the first step reaction in protein synthesis, that is, to specifically attach each amino acid onto its cognate tRNA. While preserving this essential aminoacylation function, tRNA synthetases developed other important roles during evolution. Mammalian tRNA synthetases, in particular, have diverse regulatory functions in important biological processes such as inflammation, vascular development, and DNA damage response. The functional diversity is further illustrated in the association with various diseases through genetic mutations on tRNA synthetases that do not affect aminoacylation.
The primary goal of our research is to elucidate the physiological role of tRNA synthetases in mammalian organisms and in the context of human diseases. A cross-disciplinary approach is used for our research, with a strong emphasis on molecular genetic approaches from our own expertise and through world-wide collaborations. The genetic approach is complemented by our long-term expertise in 3D structural analysis, biochemistry, and mammalian cell biology to reveal mechanistic insights and to provide strategies for therapeutic applications.
B.S., Biomedical Engineering, Capital Institute of Medical Sciences, Beijing, 1993
Ph.D., Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 2000
Postdoc, Department of Molecular Biology, The Scripps Research Institute, 2000-2005
Assistant Professor, Department of Molecular Biology, The Scripps Research Institute, 2005-2008
Associate Professor, Department of Molecular Biology, The Scripps Research Institute, 2008-2011
Visiting Fellow, Institute for Advanced Study, Hong Kong University of Science and Technology, 2008-present
Associate Professor, Department of Chemical Physiology, The Scripps Research Institute, 2011-2014
Professor, Department of Chemical Physiology, The Scripps Research Institute, 2014-present
Founding Chair, Translation Machinery in Health & Disease Gordon Research Conference, 2015
Mo, Z., Zhang, Q., Liu, Z., Lauer, J., Shi, Y., Sun, L., Griffin, P. R., and Yang, X.-L. (2016). Neddylation requires glycyl-tRNA synthetase to protect activated E2. Nat. Struct. Mol. Biol. DOI: 10.1038/nsmb.3250.
He, W.*, Bai, G.*, Zhou, H., Wei, N., White, M. N., Lauer, J., Liu, H., Shi, Y., Dumitru, C. D., Lettieri, K., Shubayev, V., Jordanova, A., Guergueltcheva, V., Griffin, P. R., Burgess, R. W., Pfaff, S. L., and Yang, X.-L. (2015). CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature 526: 710-714 (*co-first author)
Wei, N., Shi, Y., Truong, L. N., Fisch, K. M., Xu, T., Gardiner, E., Fu, G., Hsu, Y. S., Kishi, S., Su, A. I., Wu, X., and Yang, X.-L. (2014). Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage. Mol. Cell 56: 323-332.
Shi, Y., Xu, X., Zhang, Q., Fu, G., Mo, Z., Wang, G. S., Kishi, S., and Yang, X.-L. (2014). tRNA synthetase counteracts c-Myc to develop functional vasculature. eLIFE 3:e02349. DOI: 10.7554/eLife.02349.
Yang, X.-L. (2013). Structural disorder in expanding the functionome of aminoacyl-tRNA synthetases. Chem. Biol. 20:1093-1099.
Xu, X.*, Shi, Y.*, Zhang, H.-M., Swindell, E. C., Marshall, A. G., Guo, M., Kishi, S. and Yang, X.-L. (2012). Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat. Commun. 3: 681. DOI: 10.1038/ncomms1686. (*co-first author)
Fu, G., Xu, T., Shi, Y., Wei, N., and Yang, X.-L. (2012). tRNA controlled nuclear import of a human tRNA synthetase. J. Biol. Chem. 287: 9330-9334. (Chosen as “Paper of the Week”).
He, W.*, Zhang, H.-M.*, Chong, Y. E., Guo, M., Marshall, A. G., and Yang, X.-L. (2011). Dispersed disease-causing neomorphic mutations on a single protein promote the same localized conformational opening. Proc. Natl. Acad. Sci. USA 108: 12307-12312. (*co-first author)
Guo, M., Yang, X.-L., and Schimmel, P. (2010). New functions of aminoacyl tRNA synthetases beyond translation. Nat. Rev. Mol. Cell. Biol. 11: 668-674.
Zhou, Q., Kapoor, M., Guo, M., Belani, R., Xu, X., Kiosses, W. B., Hanan, M., Park, C., Armour, E., Do, M.-H., Nangle, L. A., Schimmel, P., and Yang, X.-L. (2010). Orthogonal use of a human tRNA synthetase active site to achieve multi-functionality. Nat. Struct. Mol. Biol. 17: 57-61.