Research Focus

1.     The novel roles of aminoacyl tRNA synthetases, specifically seryl-tRNA synthetase (SerRS), in the regulation of the metabolic homeostasis of biological macromolecules beyond their canonical roles in protein biosynthesis.

2.     Identification of the metabolic features essential for metastasis, drug resistance and the recurrence of cancers by genome-scale gene knockout screen in the murine model of cancers.

3.     Develop herb-sourced small molecules targeting the novel metabolic features we identified for the therapy of cancers.

Education

Ph.D., Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Biochemistry and Molecular Biology, 2007

B.S., Nanjing University, Department of Biochemistry, 1997

Professional Experience

2016 – present Associate Professor, School of Medicine, Nankai University

2009-2015 Post Doctor and Staff Scientist, Department of Physical Chemistry, The Scripps Research Institute (La Jolla campus), USA

2007-2009 Assistant Professor, Department of Biochemistry and Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Selected Publications (*corresponding author, ^#first author)

[1]  Y. Zhao, S. Li, J. Lv, Y. Liu, Y. Chen, Y. Liu, X. Chen, J. Li, X. Qin, X. Wang, J. Shi, Y. Shi*, R. Xiang*, Generation of triacyl lipopeptide-modified glycoproteins by metabolic glycoengineering as the neoantigen to boost anti-tumor immune response, Theranostics 11(15) (2021) 7425-7438.

[2]  J. Zhao, H. Bai, X. Li, J. Yan, G. Zou, L. Wang, X. Li, Z. Liu, R. Xiang, X.L. Yang, Y. Shi*, Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer, Signal Transduct Target Ther 6(1) (2021) 303.

[3]  X. Qin, J. Li, S. Wang, J. Lv, F. Luan, Y. Liu, Y. Chen, X. Chen, Y. Zhao, J. Zhu, Y. Piao, W. Zhang, Y. Shi, R. Xiang, P. Qu, L. Wang, Serotonin/HTR1E signaling blocks chronic stress-promoted progression of ovarian cancer, Theranostics 11(14) (2021) 6950-6965.

[4]  J. Li, X. Qin, J. Shi, X. Wang, T. Li, M. Xu, X. Chen, Y. Zhao, J. Han, Y. Piao, W. Zhang, P. Qu, L. Wang, R. Xiang*, Y. Shi*, A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis, Elife 10 (2021).

[5]  X. Chen, Y. Lv, K. Xu, X. Wang, Y. Zhao, J. Li, X. Qin, Y. Shi, L. Wang, A. Chang, C. Huang, R. Xiang, DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma, Cancers (Basel) 13(6) (2021).

[6]  G. Zou, X. Zhang, L. Wang, X. Li, T. Xie, J. Zhao, J. Yan, L. Wang, H. Ye, S. Jiao, R*. Xiang*, Y. Shi*, Herb-sourced emodin inhibits angiogenesis of breast cancer by targeting VEGFA transcription, Theranostics 10(15) (2020) 6839-6853.

[7]  X. Zhang^#, G. Zou^#, X. Li^#, L. Wang, T. Xie, J. Zhao, L. Wang, S. Jiao, R. Xiang, H. Ye*, Y. Shi*, An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway, Cancer Biol Med 17(3) (2020) 693-706.

[8]  Y. Shi^#，*, Z. Liu, Q. Zhang, I. Vallee, Z. Mo, S. Kishi, X.L. Yang*, Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis, PLoS Biol 18(12) (2020) e3000991.

[9]  Y. Lv, X. Wang, X. Li, G. Xu, Y. Bai, J. Wu, Y. Piao, Y. Shi*, R. Xiang*, L. Wang*, Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway, PLoS Biol 18(11) (2020) e3000872.

[10] M. Li, C. Zhang, L. Zhou, S. Li, Y.J. Cao, L. Wang, R. Xiang, Y. Shi, Y*. Piao*, Identification and validation of novel DNA methylation markers for early diagnosis of lung adenocarcinoma, Mol Oncol 14(11) (2020) 2744-2758.

[11] Y. Fan, Z. Huang, X. Wang, Y. Ma, Y. Li, S. Yang, Y. Shi*, Discovery of 12O-A Novel Oral Multi-Kinase Inhibitor for the Treatment of Solid Tumor, Molecules 25(21) (2020).

[12] L. Zhao, L. Wang, C. Zhang, Z. Liu, Y. Piao, J. Yan, R. Xiang*, Y. Yao*, Y. Shi*, E6-induced selective translation of WNT4 and JIP2 promotes the progression of cervical cancer via a noncanonical WNT signaling pathway, Signal Transduct Target Ther 4 (2019) 32.

[13] W. Xu, M. Xu, L. Wang, W. Zhou, R. Xiang, Y. Shi*, Y. Zhang*, Y. Piao*, Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers, Signal Transduct Target Ther 4 (2019) 55.

[14] Y. Li, X. Li, M. Cao, Y. Jiang, J. Yan, Z. Liu, R. Yang, X. Chen, P. Sun, R. Xiang, L*. Wang*, Y. Shi*, Seryl tRNA synthetase cooperates with POT1 to regulate telomere length and cellular senescence, Signal Transduct Target Ther 4 (2019) 50.

[15] Z. Huang, B. Zhao, Z. Qin, Y. Li, T. Wang, W. Zhou, J. Zheng, S. Yang, Y. Shi*, Y. Fan*, R. Xiang*, Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis, Eur J Med Chem 181 (2019) 111541.

[16] R. Du, W. Shen, Y. Liu, W. Gao, W. Zhou, J. Li, S. Zhao, C. Chen, Y. Chen, Y. Liu, P. Sun, R. Xiang, Y. Shi*, Y. Luo*, TGIF2 promotes the progression of lung adenocarcinoma by bridging EGFR/RAS/ERK signaling to cancer cell stemness, Signal Transduct Target Ther 4 (2019) 60.

[17] Y. Song, H. Zhou, M.N. Vo, Y. Shi, M.H. Nawaz, O. Vargas-Rodriguez, J.K. Diedrich, J.R. Yates, S. Kishi, K. Musier-Forsyth, P. Schimmel, Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid, Nat Commun 8(1) (2017) 2281.

[18] Y. Shi^#，*, N. Wei, X.L. Yang*, Studying nuclear functions of aminoacyl tRNA synthetases, Methods 113 (2017) 105-110.

[19] Y. Song^#, Y. Shi^#, T.M. Carland, S. Lian, T. Sasaki, N.J. Schork, S.R. Head, S. Kishi, P. Schimmel*, p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish, Proc Natl Acad Sci U S A 113(30) (2016) 8460-5.

[20] Z. Mo, Q. Zhang, Z. Liu, J. Lauer, Y. Shi, L. Sun, P.R. Griffin, X.L. Yang, Neddylation requires glycyl-tRNA synthetase to protect activated E2, Nat Struct Mol Biol 23(8) (2016) 730-7.

[21] W. He^#, G. Bai^#, H. Zhou, N. Wei, N.M. White, J. Lauer, H. Liu, Y. Shi, C.D. Dumitru, K. Lettieri, V. Shubayev, A. Jordanova, V. Guergueltcheva, P.R. Griffin, R.W. Burgess, S.L. Pfaff, X.L. Yang*, CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase, Nature 526(7575) (2015) 710-4.

[22] N. Wei, Y. Shi, L.N. Truong, K.M. Fisch, T. Xu, E. Gardiner, G. Fu, Y.O. Hsu, S. Kishi, A.I. Su, X. Wu, X.L. Yang, Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage, Mol Cell 56(2) (2014) 323-332.

[23] Y. Shi, X. Xu, Q. Zhang, G. Fu, Z. Mo, G.S. Wang, S. Kishi, X.L. Yang*, tRNA synthetase counteracts c-Myc to develop functional vasculature, Elife 3 (2014) e02349.

[24] X. Xu, Y. Shi, X.L. Yang*, Crystal structure of human Seryl-tRNA synthetase and Ser-SA complex reveals a molecular lever specific to higher eukaryotes, Structure 21(11) (2013) 2078-86.

[25] X. Xu^#, Y. Shi^#, H.M. Zhang, E.C. Swindell, A.G. Marshall, M. Guo, S. Kishi, X.L. Yang*, Unique domain appended to vertebrate tRNA synthetase is essential for vascular development, Nat Commun 3 (2012) 681.

[26] G. Fu, T. Xu, Y. Shi, N. Wei, X.L. Yang, tRNA-controlled nuclear import of a human tRNA synthetase, J Biol Chem 287(12) (2012) 9330-4.

Projects

1. National Natural Science Foundation of China (#81772974), Mechanistic study of the abnormal glucose metabolism in breast cancer: the role of seryl-tRNA synthetase, 2018-2021

2. National Natural Science Foundation of China (#32070752), The role of SerRS in dysregulated lipid metabolism of triple-negative breast cancer and targeted interference, 2021-2024

Teaching

Biochemistry