Xiang-Lei Yang, PhD

Department of Molecular Medicine
California Campus


Scripps Research Joint Appointments

Faculty, Graduate Program

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.


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

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

Selected References

Sun. L.*, Wei, N.*, Kuhle, B., Blocquel, D., Novick, S., MatuszeK, Z., Zhou, H., He, W., Zhang, J., Weber, T., Horvath, R., Latour, P., Pan, T., Schimmel, P.#, Griffin, P., and Yang X-L.# (2021) CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS. Proc. Natl. Acad. Sci. U S A: 118 e2012898118 (*co-first author; #co-corresponding author)

Shi, Y.*, Liu, Z.*, Zhang, Q., Vallee, .I, Mo, Z., Kishi, S., and Yang, X.-L. (2020) Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis. PLOS Biol. 18(12):e3000991. (*co-first author)

Chen, M., Kuhle, B.#, Diedrich, J., Liu, Z., Moresco, J.J., Yates, J.R. III, Pan, T., and Yang, X.L.# (2020) Cross-editing by a tRNA synthetase allows vertebrates to abundantly express mischargeable tRNA without causing mistranslation. Nucleic Acids Res. 48(12):6445. (#co-corresponding author)

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.#, and Yang, X.L.# (2019) Transcriptional dysregulation by a nucleuslocalized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy. Nat Commun 10, 5045 doi:10.1038/s41467-019-12909-9 (*co-first author; #co-corresponding author)

Blocquel, D.*, Sun, L.*, Matuszek, Z., Li, S., Weber, T., Kuhle, B., Kooi, G., Wei, N., Baets, J., Pan, T., Schimmel, P.#, and Yang, X.-L. #(2019) CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells.  Proc. Natl. Acad. Sci. U S A. 116(39):19440-19448. (*co-first author; #co-corresponding author)

Wei, N., Zhang, Q., and Yang, X.-L. (2019) Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases. J. Biol. Chem. doi: 10.1074/jbc.REV118.002955.

Mo, Z., Zhao, X. Liu, H., Hu, Q., Chen, X., Pham, J., Wei, N., Liu, Z., Zhou, J., Burgess, R. W., Pfaff, S. L., Caskey, C. T., Wu, C., Bai, G., and Yang, X.-L. (2018) Aberrant GlyRS-HDAC6 interaction links to axonal transport deficit in Charcot-Marie-Tooth neuropathy. Nat. Commun. DOI:10.1038/s41467-018-03461-z

Blocquel, D., Li, S., Wei, N., Daub, H., Sajish, M., Erfurth, M-L., Kooi, G., Zhou, J., Bai, G., Schimmel, P., Jordanova, A., Yang, X.-L. (2017) Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.  Nucleic Acids Res. 45:8091-8104

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. 138:12948-12955.(#co-corresponding author)

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. 23:730-7

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; #co-corresponding 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)

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. U S A. 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.

Dr. Yang's Complete Publication List:


For the first time, potential treatment path becomes clear for subtype of Charcot-Marie-Tooth disease

'Relaxed' enzymes may be at the root of Charcot-Marie-Tooth disease

Asking the Hard Questions: A Profile of Xiang-Lei Yang

Spotlight on Charcot-Marie-Tooth Disease

Scientists Find New Cancer Drug Target in Dual-Function Protein

Toward a Cure for Charcot-Marie-Tooth Disease

Team Points to Cause of Debilitating Nerve Disease

TSRI Collaboration Finds Ancient Protein-Making Enzyme Moonlights as DNA Protector

Study Finds Molecular ‘Yin-Yang’ Regulates Blood Vessel Growth

Collaboration Unlocks Evolutionary Secret of Blood Vessels

Team Solves Mystery of Nerve Disease Genes

Scientists Crack Mystery of Protein's Dual Function

Analysis of Protein-Building Enzyme Sheds Light on Protein Evolution