Source: Interfolio F180

Xiang-Lei Yang

Ernest W. Hahn Endowed Chair
Department of Molecular Medicine


Research Focus

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.


Ph.D. (Biophysics and Computational Biology), University of Illinois at Urbana-Champaign, 2000
B.S. (Biomedical Engineering), Capital Institute of Medical Sciences, Beijing, 1993

Professional Experience

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

Awards & Professional Activities

2021 Ernest W. Hahn Chair
1999 Harley J. Van Cleave Fellowship, School of Life Sciences, University of Illinois at Urbana-Champlain

Selected Publications

Liu, Z.; Wang, J.; Shi, Y.; Yee, B. A.; Terrey, M.; Zhang, Q.; Lee, J.; Lin, K.; Wang, A. H.; Ackerman, S.; Yeo, G. W.; Cui, H.; Yang, X. Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery. Nucleic Acids Research 2023, In Press.

Jones, J. A.; Wei, N.; Cui, H.; Shi, Y.; Fu, G.; Rauniyar, N.; Shapiro, R.; Morodomi, Y.; Berenst, N.; Dumitru, C. D.; Kanaji, S.; Yates, J. R.; Kanaji, T.; Yang, X. L. Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response". Cell Reports 2023, 42, 112632.

Kanaji, S.; Chen, W.; Morodomi, Y.; Shapiro, R.; Kanaji, T.; Yang, X. L. Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome. Trends in Biochemical Sciences 2023, 48, 288-302.

Shi, Y.; Liu, Z.; Zhang, Q.; Vallee, I.; Mo, Z.; Kishi, S.; Yang, X. Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis. PLoS Biol. 2020, 18, e3000991.

Bervoets, S.; Wei, N.; Erfurth, M. L.; Yusein-Myashkova, S.; Ermanoska, B.; Mateiu, L.; Asselbergh, B.; Blocquel, D.; Kakad, P.; Penserga, T.; Thomas, F. P.; Guergueltcheva, V.; Tournev, I.; Godenschwege, T.; Jordanova, A.; Yang, X. Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy. Nature Communications 2019, 10, 5045.

He, W.; Bai, G.; Zhou, H.; Wei, N.; White, N. M.; 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.; Yang, X. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature 2015, 526, 710-714.