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Molecular Medicine

Faculty

Xiang-Lei Yang, Ph.D.

Professor
Department of Molecular Medicine
California Campus
Laboratory Website
xlyang@scripps.edu
(858) 784-8976

Scripps Research Joint Appointments

Department of Cell and Molecular Biology
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.

Education

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

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.

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)

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:
https://www.ncbi.nlm.nih.gov/sites/myncbi/xiang-lei.yang.1/bibliography/40933959/public/?sort=date&direction=descending

Links

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

Scientists Find New Cancer Drug Target in Dual-Function Protein

Toward a Cure for Charcot-Marie-Tooth Disease

Spotlight on 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

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty