Department of Cell and Molecular Biology
Faculty, Graduate Program
The Yang laboratory studies cancer and neurodegenerative diseases through a multi-functional protein family.
Cancer and neurodegenerative diseases can be viewed as opposite consequences of disrupting the balanced degenerative versus survival and regenerative propensities of a healthy being. Such balance is maintained through homeostatic regulation of biosynthetic activities.
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. Aminoacyl-tRNA synthetases also have diverse regulatory functions in other important biological processes and response, for example, in blood vessel formation and oxidative stress response. Through their multi-functionality, tRNA synthetases can coordinate these processes and responses with protein synthesis, and therefore play a critical role in maintaining balanced cellular degenerative and regenerative activities.
Disrupting the role of tRNA synthetases in the homeostatic regulation, either by genetic or environmental factors, can lead to a diseased state. Indeed, mutations in several tRNA synthetases are causatively linked to axonal neuropathy; altered expression profile of tRNA synthetases is strongly associated with tumor progression and metastasis. Our research aims to reveal the homeostatic regulations of tRNA synthetases in healthy beings and how they are disrupted in the context of cancer and neurodegenerative diseases.
An “atom-to-animal” cross-disciplinary approach is used in our research. We integrate studies in animal models with 3D structural analysis, biophysical, biochemistry, and mammalian cell biology to reveal mechanistic insights and to provide therapeutic strategies. In addition to basic research, drug development programs targeting metastatic cancer and Charcot-Maria-Tooth disease (also known as Hereditary Motor and Sensory Neuropathy) are ongoing in the laboratory.
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, 2014-2017
Professor, Department of Molecular Medicine, The Scripps Research Institute, 2017-
Founding Chair, Translation Machinery in Health & Disease Gordon Research Conference, 2015
Sun L., Gomes, AC., He, W., Zhou, H., Wang, X., Pan, DW., Schimmel, P., Pan, T., Yang, X-L. (2016). Evolutionary Gain of Alanine Mischarging to Noncognate tRNAs with a G4:U69 Base Pair. J Am Chem Soc. 138(39): 12948-12955.
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. 23(8):730-7
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.
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)
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.
Dr. Yang's Complete Publication List: