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Xiang-Lei Yang, PhD

Professor

Department of Integrative Structural and Computational Biology

Ernest W. Hahn Endowed Chair

Xiang-Lei Yang, PhD

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.

Select Publications

  • Liu, Ze*; Wang, Justin*; Shi, Yi; Yee, Brian A.; Terrey, Markus; Zhang, Qian; Lee, Jenq-Chang; Lin, Kuo-I; Wang, Andrew H.; Ackerman, Susan; Yeo, Gene W.; Cui, Haissi#; Yang, Xiang-Lei# Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery. Nucleic Acids Research 2023, In Press.

  • Jones, Julia* A.; Wei, Na*; Cui, Haissi; Shi, Yi; Fu, Guangsen; Rauniyar, Navin; Shapiro, Ryan; Morodomi, Yosuke; Berenst, Nadine; Dumitru, Calin D.; Kanaji, Sachiko; Yates, John R.; Kanaji, Taisuke; Yang, Xiang- L. Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response". Cell Reports 2023, 42, 112632.

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  • Kanaji, Sachiko*; Chen, Wenqian*; Morodomi, Yosuke; Shapiro, Ryan; Kanaji, Taisuke; Yang, Xiang- L. Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome. Trends in Biochemical Sciences 2023, 48, 288-302.

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  • Shi, Yi*; Liu, Ze*; Zhang, Qian; Vallee, Ingrid; Mo, Zhongying; Kishi, Shuji; Yang, Xiang-lei Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis. PLoS Biol. 2020, 18, e3000991.

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  • Bervoets, Sven*; Wei, Na*; Erfurth, Maria- L.; Yusein-Myashkova, Shazie; Ermanoska, Biljana; Mateiu, Ligia; Asselbergh, Bob; Blocquel, David; Kakad, Priyanka; Penserga, Tyrone; Thomas, Florian P.; Guergueltcheva, Velina; Tournev, Ivailo; Godenschwege, Tanja; Jordanova, Albena#; Yang, Xiang-Lei# Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy. Nature Communications 2019, 10, 5045.

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  • He, Weiwei*; 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, Patrick R.; Burgess, R. W.; Pfaff, S.# L.; Yang, Xiang-Lei# CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature 2015, 526, 710-714.

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News, Events & Media
From left, professor Xiang-Lei Yang and postdoctoral associate Huimin Zhang.
News

A double “off-switch” helps cells respond to stress

Integrative Structural & Computational Biology
Scripps Research’s Skaggs Graduate School awards doctoral degrees to 33rd graduating class
News

Scripps Research’s Skaggs Graduate School awards doctoral degrees to 33rd graduating class

The ceremony represented the largest graduating class since the doctoral program’s inception in 1989.

Graduate Program Institute News Education
Scripps Research’s Skaggs Graduate School awards doctoral degrees to 32nd graduating class
News

Scripps Research’s Skaggs Graduate School awards doctoral degrees to 32nd graduating class

Skaggs family also honored at commencement ceremony as first recipients of Scripps Research Presidential Medal

Graduate Program Institute News Education
Three faculty members honored with endowed chairs
News

Three faculty members honored with endowed chairs

Donna Blackmond, Marisa Roberto and Xiang-Lei Yang have been honored with endowed chairs in recognition of their scientific leadership and impactful discoveries.

Translational Medicine Integrative Structural & Computational Biology Chemistry
Enzyme discovery is missing piece in understanding how to rein in blood vessels that fuel cancer
News

Enzyme discovery is missing piece in understanding how to rein in blood vessels that fuel cancer

The findings may enable better cancer treatments and new interventions for heart disease.

Integrative Structural & Computational Biology
For the first time, potential treatment path becomes clear for subtype of Charcot-Marie-Tooth disease
News

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

An unexpected finding from Scripps Research has illuminated a promising strategy for treating the inherited neurological disease Charcot-Marie-Tooth, for which there is no approved medicine today.

Integrative Structural & Computational Biology
‘Relaxed’ enzymes may be at the root of Charcot-Marie-Tooth disease
News

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

Scripps Research scientists make a key discovery into the underpinnings of a complex disease that damages patients' peripheral nervous system. 

Integrative Structural & Computational Biology
Doctors may be able to enlist a mysterious enzyme to stop internal bleeding
News

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

"This opens up new options for treating diseases of the blood."

Molecular & Cellular Biology Integrative Structural & Computational Biology
Groundbreaking Science.
Life-changing Medicine.