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The Translation Laboratory

 

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School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.

For more information:

FANG group recruitment

WANG group recruitment

About TTLab

TTLab stands for The Translation Laboratory, because research groups in TTLab are concerned with facilitating the practical application of scientific discoveries from basic research to the development of new ways to prevent, diagnose, and treat human diseases.

TTLab can also be interpreted by Transcription-Translation Laboratory, since transcription and translation are our two major research directions.

In the translation aspect, the FANG group is focused on aminoacyl-tRNA synthetases. The enzymes catalyze the attachments of amino acids to their cognate tRNAs. This is the first reaction of protein synthesis, and it establishes the algorithm of the genetic code. The research group investigates synthetases in their role as catalysts of aminoacylation and how it can be intervened to treat human diseases. Synthetases in mammalian cells are also known to have expanded functions, including activities in signal transduction pathways, such as those for angiogenesis and inflammation. These activities also provide opportunities for anticipated therapeutic applications.

The second direction is focused on the Mi (MITF/TFE/USF) family of transcription factors. This family includes several important proteins that are critical for innate immune responses, autophagy, and tumor genesis. The WANG group investigates the cellular regulation pathways that lead to the activation of the Mi family. Development of drugs to target the Mi family for human disease treatment is another goal of the WANG group.

For all of these works, a cross-disciplinary approach is used. Methods and logic of biochemistry and molecular and cell biology are merged with genetics, x-ray crystallography, evolutionary analysis, and high throughput drug screening.

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Principal Investigators

Pengfei Fang, Ph.D.

Professor

State Key Laboratory of Bioorganic and Natural Products Chemistry

Shanghai Institute of Organic Chemistry

Chinese Academy of Sciences

FangPengfei@@sioc.ac.cn   

https://orcid.org/0000-0002-3448-5494

Jing Wang, Ph.D.

Professor

State Key Laboratory of Bioorganic and Natural Products Chemistry

Shanghai Institute of Organic Chemistry

Chinese Academy of Sciences

JWang@@sioc.ac.cn

https://orcid.org/0000-0002-7566-1212

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Principal Investigators

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Joining TTLab

Available Positions for Postdoctoral Fellows

Location:

School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.

For more information:

FANG group recruitment

WANG group recruitment

We welcome interested students to join our laboratory after being admitted to SIOC graduate program.

We encourage inquiries to be sent directly to Dr. Fang (fangpengfei@@sioc.ac.cn) or Dr. Wang (jwang@@sioc.ac.cn).

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>> Publications from Professor Jing Wang

¡¤       Publications from Professor Pengfei Fang:

46.   Cheng Y, Yi X, Zhang Y, He Q, Chen D, Cao W, Fang P, Liu W. Oxidase Heterotetramer Completes 1-Azabicyclo[3.1.0]hexane Formation with the Association of a Nonribosomal Peptide Synthetase.  J Am Chem Soc. doi: 10.1021/jacs.2c12507. (2023).

45.   Qiao H, Xia M, Cheng Y, Zhou J, Zheng L, Li W, Wang J, Fang P. Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion.  Commun Biol. 6(1):107. (2023).

44.   Zeng QY, Zhang F, Zhang JH, Hei Z, Li ZH, Huang MH, Fang P, Wang ED, Sun XJ, Zhou XL. Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development.  J Biol Chem. doi: 10.1016/j.jbc.2023.104704. (2023).

43.   Lin Y, Yu B, Fang P, Wang J. Inhibiting autophagy before it starts. Autophagy. doi: 10.1080/15548627.2023.2197364. (2023).

42.   Lin Y, Shi Q, Yang G, Shi F, Zhou Y, Wang T, Xu P, Li P, Liu Z, Sun H, Zhao Z, Ding K, Wang Z, Feng H, Yu B, Fang P, Wang J. A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB. Proc Natl Acad Sci USA, 120(7):e2213670120 (2023).

41.   Liu Z, Chen K, Dai J, Xu P, Sun W, Liu W, Zhao Z, Bennett SP, Li P, Ma T, Lin Y, Kawakami A, Yu J, Wang F, Wang C, Li M, Chase P, Hodder P, Spicer TP, Scampavia L, Cao C, Pan L, Dong J, Chen Y, Yu B, Guo M, Fang P, Fisher DE, Wang J. A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy. Cell Research, 33(1):55-70 (2023).

40.   Liu Y, Chen Y, Jiang J, Chu X, Guo Q, Zhao L, Feng F, Liu W, Zhang X, He S, Yang P, Fang P, Sun H. Development of highly potent and specific AKR1C3 inhibitors to restore the chemosensitivity of drug-resistant breast cancer. European Journal of Medicinal Chemistry, 247:115013 (2023).

39.   Hei Z, Fang P. Sequential magnesium binding facilitates lysyl-tRNA synthetase to recognize ATP. Biochemistry and Biophysics Reports, 33:101426 (2023).

38.   Yu T, Zhang Y, Zheng WQ, Wu S, Li G, Zhang Y, Li N, Yao R, Fang P, Wang J, Zhou XL. Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease. Nucleic Acids Research, 50(20):11755-11774 (2022).

37.   Cao X, Du X, Jiao H, An Q, Chen R, Fang P, Wang J, Yu B. Carbohydrate-based drugs launched during 2000-2021. Acta Pharmaceutica Sinica B, 12(10):3783-3821 (2022).

36.   Zhong B, Peng W, Du S, Chen B, Feng Y, Hu X, Lai Q, Liu S, Zhou ZW, Fang P, Wu Y, Gao F, Zhou H, Sun L. Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease. Small Science, 2, 2100124 (2022).

35.   Wu S, Zheng L, Hei Z, Zhou JB, Li G, Li P, Wang J, Ali H, Zhou XL, Wang J, Fang P. Human lysyltRNA synthetase evolves a dynamic structure that can be stabilized by forming complex. Cellular and Molecular Life Sciences, 79, 128 (2022).

34.   Yang G, Li P, Liu Z, Wu S, Zhuang C, Qiao H, Zheng L, Fang P, Lei C, Wang J. Structural basis for the dimerization mechanism of human transcription factor E3. Biochemical and Biophysical Research Communications, 569, 41-46 (2021).

33.   Wu S, Hei Z, Zheng L, Zhou J, Liu Z, Wang J, Fang P. Structural analyses of a human lysyl-tRNA synthetase mutant associated with autosomal recessive nonsyndromic hearing impairment. Biochemical and Biophysical Research Communications, 554, 83-88 (2021).

32.   Hei Z, Wu S, Zheng L, Zhou J, Liu Z, Wang J, Fang P. Crystal structures reveal a novel dimer of the RWD domain of human general control nonderepressible 2. Biochemical and Biophysical Research Communications, 549, 165-170 (2021).

31.   Zhou J, Huang Z, Zheng L, Hei Z, Wang Z, Yu B, Jiang L, Wang J, Fang P. Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an Anaplastic Lymphoma Kinase Inhibitor. Nucleic Acids Research, 48, 11566-11576 (2020).

30.   Zhou J, Zheng L, Hei Z, Li W, Wang J, Yu B, Fang P. Atomic resolution analyses of isocoumarin derivatives for inhibition of lysyl-tRNA synthetase. ACS chemical biology, 15, 1016-1025 (2020).

29.   Wang Y, Zhou JB, Zeng QY, Wu S, Xue MQ, Fang P, Wang ED, Zhou XL. Hearing impairment-associated KARS mutations lead to defects in aminoacylation of both cytoplasmic and mitochondrial tRNA(Lys). Science China. Life sciences, 63, 1227-1239 (2020).

28.   Yu J, Liu Z, Liang Y, Luo F, Zhang J, Tian C, Motzik A, Zheng M, Kang J, Zhong G, Liu C, Fang P, Guo M, Razin E, Wang J. Second Messenger Ap4A Polymerizes Target Protein HINT1 to Transduce Signals in Fc¦ÅRI-activated Mast Cells. Nature communications 10, 4664 (2019).

27.   Zhou XL, Chen Y, Zeng QY, Ruan ZR, Fang P, Wang ED. Newly acquired N-terminal extension targets threonyl-tRNA synthetase-like protein into the multiple tRNA synthetase complex. Nucleic acids research, 47, 8662-8674 (2019). 

26.   Hei Z, Wu S, Liu Z, Wang J, Fang P. Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex. The Journal of biological chemistry 294, 4775-4783 (2019). 

25.   Kong J, Fang P, Madoux F, Spicer TP, Scampavia L, Kim S, et al. High-Throughput Screening for Protein Synthesis Inhibitors Targeting Aminoacyl-tRNA Synthetases. SLAS discovery : advancing life sciences R & D 23, 174-182 (2018). 

24.   Wang J, Fang P, Chase P, Tshori S, Razin E, Spicer TP, et al. Development of an HTS-Compatible Assay for Discovery of Melanoma-Related Microphthalmia Transcription Factor Disruptors Using AlphaScreen Technology. SLAS discovery : advancing life sciences R & D 22, 58-66 (2017). 

23.   Tao Y, Fang P, Kim S, Guo M, Young NL, Marshall AG. Mapping the contact surfaces in the Lamin A:AIMP3 complex by hydrogen/deuterium exchange FT-ICR mass spectrometry. PloS one 12, e0181869 (2017). 

22.   Fang P, Guo M. Structural characterization of human aminoacyl-tRNA synthetases for translational and nontranslational functions. Methods 113, 83-90 (2017). 

21.   Slade DJ, Fang P, Dreyton CJ, Zhang Y, Fuhrmann J, Rempel D, et al. Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design. ACS chemical biology 10, 1043-1053 (2015). 

20.   Rachmin I, Amsalem E, Golomb E, Beeri R, Gilon D, Fang P, et al. FHL2 switches MITF from activator to repressor of Erbin expression during cardiac hypertrophy. International journal of cardiology 195, 85-94 (2015). 

19.   Park H, Gonzalez AL, Yildirim I, Tran T, Lohman JR, Fang P, et al. Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10). Biochemistry 54, 3851-3859 (2015). 

18.   Mirando AC, Fang P, Williams TF, Baldor LC, Howe AK, Ebert AM, et al. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. Scientific reports 5, 13160 (2015). 

17.   Fang P, Yu X, Jeong SJ, Mirando A, Chen K, Chen X, et al. Structural basis for full-spectrum inhibition of translational functions on a tRNA synthetase. Nature communications 6, 6402 (2015). 

16.   Fang P, Han H, Wang J, Chen K, Chen X, Guo M. Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor. Chemistry & biology 22, 734-744 (2015). 

15.   Fang P, Guo M. The Nature's Clever Trick for Making Cyclic Dinucleotide. Structure 23, 801-802 (2015). 

14.   Fang P, Guo M. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification. Life 5, 1703-1725 (2015). 

13.   Kim DG, Lee JY, Kwon NH, Fang P, Zhang Q, Wang J, et al. Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. Nat Chem Biol 10, 29-34 (2014). 

12.   Zhu Y, Dai J, Zhang T, Li X, Fang P, Wang H, et al. Structural insights into the neutralization mechanism of monoclonal antibody 6C2 against ricin. The Journal of biological chemistry 288, 25165-25172 (2013). 

11.   Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, et al. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol Cell 49, 30-42 (2013). 

10.   Wang J, Fang P, Schimmel P, Guo M. Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. The journal of physical chemistry B 116, 6798-6805 (2012). 

9.     Jones JE, Slack JL, Fang P, Zhang X, Subramanian V, Causey CP, et al. Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors. ACS chemical biology 7, 160-165 (2012). 

8.     Xing L, Zhu Y, Fang P, Wang J, Zeng F, Li X, et al. Crystallization and preliminary crystallographic studies of UbiG, an O-methyltransferase from Escherichia coli. Acta crystallographica Section F, Structural biology and crystallization communications 67, 727-729 (2011). 

7.     Wang J, Gossing M, Fang P, Zimmermann J, Li X, von Mollard GF, et al. Epsin N-terminal homology domains bind on opposite sides of two SNAREs. Proc Natl Acad Sci U S A 108, 12277-12282 (2011). 

6.     Kumar A, Park H, Fang P, Parkesh R, Guo M, Nettles KW, et al. Myotonic dystrophy type 1 RNA crystal structures reveal heterogeneous 1 x 1 nucleotide UU internal loop conformations. Biochemistry 50, 9928-9935 (2011). 

5.     Kumar A, Fang P, Park H, Guo M, Nettles KW, Disney MD. A crystal structure of a model of the repeating r(CGG) transcript found in fragile X syndrome. Chembiochem : a European journal of chemical biology 12, 2140-2142 (2011). 

4.     Fang P, Zhang HM, Shapiro R, Marshall AG, Schimmel P, Yang XL, et al. Structural context for mobilization of a human tRNA synthetase from its cytoplasmic complex. Proc Natl Acad Sci U S A 108, 8239-8244 (2011). 

3.     Fang P, Li X, Wang J, Xing L, Gao Y, Niu L, et al. Crystal structure of the protein L-isoaspartyl methyltransferase from Escherichia coli. Cell biochemistry and biophysics 58, 163-167 (2010). 

2.     Fang P, Li X, Wang J, Niu L, Teng M. Structural basis for the specificity of the GAE domain of yGGA2 for its accessory proteins Ent3 and Ent5. Biochemistry 49, 7949-7955 (2010). 

1.     Fang P, Wang J, Li X, Guo M, Xing L, Cao X, et al. Crystallization and preliminary X-ray analysis of Escherichia coli RNase G. Acta crystallographica Section F, Structural biology and crystallization communications 65, 586-588 (2009).

¡¤       Publications from Professor Jing Wang:

27.   Lin Y, Yu B, Fang P, Wang J. Inhibiting autophagy before it starts. Autophagy. doi: 10.1080/15548627.2023.2197364. (2023).

26.   Lin Y, Shi Q, Yang G, Shi F, Zhou Y, Wang T, Xu P, Li P, Liu Z, Sun H, Zhao Z, Ding K, Wang Z, Feng H, Yu B, Fang P, Wang J. A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB. Proc Natl Acad Sci USA, 120(7):e2213670120 (2023).

25.   Qiao H, Xia M, Cheng Y, Zhou J, Zheng L, Li W, Wang J, Fang P. Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion.  Commun Biol. 6(1):107. (2023).

24.   Liu Z, Chen K, Dai J, Xu P, Sun W, Liu W, Zhao Z, Bennett SP, Li P, Ma T, Lin Y, Kawakami A, Yu J, Wang F, Wang C, Li M, Chase P, Hodder P, Spicer TP, Scampavia L, Cao C, Pan L, Dong J, Chen Y, Yu B, Guo M, Fang P, Fisher DE, Wang J. A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy. Cell Research, 33(1):55-70 (2023).

23.   Hou W, Wang M, Wang J, Cao X, Xu P, Yu B. Collective Synthesis and Cytotoxicities of Wentilactone Type Norditerpenoid Dilactones. Asian Journal of Organic Chemistry, e202200646 (2022).

22.   Cao X, Du X, Jiao H, An Q, Chen R, Fang P, Wang J, Yu B. Carbohydrate-based drugs launched during 2000-2021. Acta Pharmaceutica Sinica B, 12(10):3783-3821 (2022).

21.   Wu S, Zheng L, Hei Z, Zhou JB, Li G, Li P, Wang J, Ali H, Zhou XL, Wang J, Fang P. Human lysyltRNA synthetase evolves a dynamic structure that can be stabilized by forming complex. Cellular and Molecular Life Sciences, 79, 128 (2022).

20.   Yang Q, Wang W, Lin Y, Lin Y, Tang Z, Wang J, Tao J, Tang W, Liu W. Characterization of a carboxyl methyltransferase in Fusarium graminearum provides insights into the biosynthesis of fusarin A. Organic & Biomolecular Chemistry, 19, 6638-6643 (2021).

19.   Yang G, Li P, Liu Z, Wu S, Zhuang C, Qiao H, Zheng L, Fang P, Lei C, Wang J. Structural basis for the dimerization mechanism of human transcription factor E3. Biochemical and Biophysical Research Communications, 569, 41-46 (2021).

18.   Ye F, Zhao J, Xu P, Liu X, Yu J, Shangguan W, Liu J, Luo X, Li C, Ying T, Wang J, Yu B, Wang P. Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies. Angewandte Chemie International Edition. 60, 12904-12910 (2021).

17.   Wu S, Hei Z, Zheng L, Zhou J, Liu Z, Wang JFang P. Structural analyses of a human lysyl-tRNA synthetase mutant associated with autosomal recessive nonsyndromic hearing impairment. Biochemical and Biophysical Research Communications, 554, 83-88 (2021).

16.   Hei Z, Wu S, Zheng L, Zhou J, Liu Z, Wang JFang P. Crystal structures reveal a novel dimer of the RWD domain of human general control nonderepressible 2. Biochemical and Biophysical Research Communications, 549, 165-170 (2021).

15.   Zhou J, Huang Z, Zheng L, Hei Z, Wang Z, Yu B, Jiang L, Wang J, Fang P. Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an Anaplastic Lymphoma Kinase Inhibitor. Nucleic Acids Research, 48, 11566-11576 (2020).

14.   Zhou J, Zheng L, Hei Z, Li W, Wang J, Yu B, Fang P. Atomic resolution analyses of isocoumarin derivatives for inhibition of lysyl-tRNA synthetase. ACS chemical biology, 15, 1016-1025 (2020).

13.   Yu J, Liu Z, Liang Y, Luo F, Zhang J, Tian C, Motzik A, Zheng M, Kang J, Zhong G, Liu C, Fang P, Guo M, Razin E, Wang J. Second Messenger Ap4A Polymerizes Target Protein HINT1 to Transduce Signals in Fc¦ÅRI-activated Mast Cells. Nature communications 10, 4664 (2019).

12.   Hei Z, Wu S, Liu Z, Wang J, Fang P. Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex. The Journal of biological chemistry 294, 4775-4783 (2019). 

11.   Wang J, Fang P, Chase P, Tshori S, Razin E, Spicer TP, et al. Development of an HTS-Compatible Assay for Discovery of Melanoma-Related Microphthalmia Transcription Factor Disruptors Using AlphaScreen Technology. SLAS discovery : advancing life sciences R & D 22, 58-66 (2017). 

10.   Motzik A, Amir E, Erlich T, Wang J, Kim BG, Han JM, et al. Post-translational modification of HINT1 mediates activation of MITF transcriptional activity in human melanoma cells. Oncogene 36, 4732-4738 (2017). 

9.     Fang P, Han H, Wang J, Chen K, Chen X, Guo M. Structural Basis for Specific Inhibition of tRNA Synthetase by an ATP Competitive Inhibitor. Chemistry & biology 22, 734-744 (2015). 

8.     Kim DG, Lee JY, Kwon NH, Fang P, Zhang Q, Wang J, et al. Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction. Nat Chem Biol 10, 29-34 (2014). 

7.     Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, et al. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol Cell 49, 30-42 (2013). 

6.     Wang J, Fang P, Schimmel P, Guo M. Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. The journal of physical chemistry B 116, 6798-6805 (2012). 

5.     Xing L, Zhu Y, Fang P, Wang J, Zeng F, Li X, et al. Crystallization and preliminary crystallographic studies of UbiG, an O-methyltransferase from Escherichia coli. Acta crystallographica Section F, Structural biology and crystallization communications 67, 727-729 (2011). 

4.     Wang J, Gossing M, Fang P, Zimmermann J, Li X, von Mollard GF, et al. Epsin N-terminal homology domains bind on opposite sides of two SNAREs. Proc Natl Acad Sci U S A 108, 12277-12282 (2011). 

3.     Fang P, Li X, Wang J, Xing L, Gao Y, Niu L, et al. Crystal structure of the protein L-isoaspartyl methyltransferase from Escherichia coli. Cell biochemistry and biophysics 58, 163-167 (2010). 

2.     Fang P, Li X, Wang J, Niu L, Teng M. Structural basis for the specificity of the GAE domain of yGGA2 for its accessory proteins Ent3 and Ent5. Biochemistry 49, 7949-7955 (2010). 

1.     Fang P, Wang J, Li X, Guo M, Xing L, Cao X, et al. Crystallization and preliminary X-ray analysis of Escherichia coli RNase G. Acta crystallographica Section F, Structural biology and crystallization communications 65, 586-588 (2009).

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Li Zheng, Lab Manager/Research Associate

Zhoufei Hei - Postdoc

Jintong Zhou - Postdoc

Yuqi Lin - Graduate Student

Yiyuan Cheng - Graduate Student

Chen Zhuang - Graduate Student

Guang Yang - Graduate Student

Hang Qiao - Graduate Student

Chao Huang - Graduate Student

Mingyu Xia - Graduate Student

Jiheng Jiang - Graduate Student

Hanyin Sun - Graduate Student

Former Lab Members

Zaizhou Liu - Ph.D. 2022

Peifeng Li - Ph.D. 2022

Siqi Wu - Ph.D. 2021

  • Zhiyong Wang
  • Jing Yu
  • Jie Zhang
  • Zhixin Zhao
  • Jiayuan Wang
  • Yuanyuan Liang
  • Yangyang Zhu
  • Qiang Li
  • Hongqiang Li

 

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Email: lizheng2016y@@sioc.ac.cn
Tel: 021-54925
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