Research in the Wang laboratory centers around interface of genetics, chemistry, biology, medicine and biotechnology investigations that explore the protein post-translational modifications (PTMs) and their networks. We are studying bacterial and eukaryotic systems in a multidisciplinary approach that includes expanding genetics codes, protein chemistry, enzymology and structural analysis. With knowledge of PTM studies, we are also seeking the applications in discovering new concepts of protein drug design.

My research currently focus on three subjects in coherence mode:

1. Synthesizing protein with PTMs, e.g., protein ubiquitin-like modifications, methylation and phosphorylation;
2. Biocatalysis: developing novel enzyme for in vivo protein modifications through click-type bioothogonal reactions;
3. Expanding genetic code studies: developing evolved protein translation system for incorporating multiple and different non-canonical amino acids into proteins in vivo.

Positions Held

• 2015 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2012 – 2015   Postdoctoral Associate, Department of Molecular Biophysics and Biochemistry, Medical School, Yale University, USA
• 2003 – 2007   Research Assistant, Institute of Chemistry, Academia Sinica

Degrees

• 2007 – 2012   Ph. D., Department of Chemistry, Texas A&M University, USA
• 1999 – 2001   M.S., Department of Chemistry, National Cheng-Kung University
• 1995 – 1999   B. S., Department of Chemistry, National Cheng-Kung University

1. Tseng HW, Baumann T, Sun H, (Wang YS), Ignatova Z, Budisa N  (2020-09)  Molecules  25(19), 4418  "Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids."
   
2. Jiang HK, Wang YH, Weng JH, Kurkute P, Li CL, Lee MN, Chen PJ, Tseng HW, Tsai MD, (Wang YS)*  (2020-06)  Biochemistry  59(24), 2205-2209  "Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues."
   
3. Jiang HK, Lee MN, Tsou JC, Chang KW, Tseng HW, Chen KP, Li YK, (Wang YS)*  (2020-04)  Frontiers in bioengineering and biotechnology  8, 235  "Linker and N-terminal domain engineering of pyrrolysyl-tRNA synthetase for substrate range shifting and activity enhancement"
   
4. Tateki S, Corwin M, Guo LT, Ho JML, Bryson DI, (Wang YS), Liu DR, Söll D*  (2017-12)  Nature Chemical Biology  13(12), 1261-1266  "Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase"
   
5. Englert M, Vargas-Rodriguez O, Reynolds NM, (Wang Y S), Söll D*, Umehara T*  (2017-11)  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS  1861(11 Pt B), 3009-3015  "A genomically modified Escherichia coli strain carrying an orthogonal E. coli histidyl-tRNA synthetase•tRNAHis pair."
   
6. Sharma V, (Wang YS), Liu WR*  (2016-11)  ACS Chemical Biology  11(12), 3305-3309  "Probing the catalytic charge-relay system in alanine racemase with genetically encoded histidine mimetic"
   
7. Amiram M, Haimovich AD, Fan CQ, (Wang YS), Aerni HR, Ntai I, Moonan DW, Ma NJ, Rovner AJ, Hong SH, Kelleher NL, Goodman AL, Jewett MC, Söll D*, Rinehart J*, and Isaacs FJ*  (2015-12)  Nature Biotechnology  33(12), 1272-1279  "Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids"
   
8. Englert M^†, Nakamura A^†, (Wang YS)^†, Eiler D, Söll D*, and Guo LT*  (2015-12)  Nucleic Acids Research  43 (22), 11061-11067  "Probing the active site tryptophan of Staphylococcus aureus thioredoxin with an analog"
   
9. Fan, C. Q.^†, Ho, J. M. H.^†, Chirathivat, N., Söll, D.* and (Wang, Y. S.)*  (2014)  ChemBioChem  15(12), 1805-1809  "Exploring the substrate range of wild-type aminoacyl-tRNA synthetases."
   
10. Tharp, J. M., (Wang, Y. S.), Lee, Y. J., Yang, Y., and Liu, W. R.*  (2014)  ACS Chemical Biology  9(4), 884-890  "Genetic incorporation of seven ortho-substituted phenylalanine derivatives."
    
11. Guo, L. T.^†, (Wang, Y. S.) ^†, Nakamura, A. ^†, Eiler, D. ^†, Kavran, J. M., Wong, M., Kiessling, L. L., Steitz, T. A., O’Donoghue, P.* and Söll, D.*  (2014)  Proceedings of the National Academy of Sciences of the United States of America  111(47), 16724-16729  "Polyspecific pyrrolysyl-tRNA synthetases from directed evolution."
    
12. Tuley, A., (Wang, Y. S.), Fang, X., Kurra, Y., Rezenom, Y. H., and Liu, W. R.*  (2014)  Chemical Communications  50(20), 2673-2675  "The genetic incorporation of thirteen novel non-canonical amino acids."
    
13. (Wang, Y. S.), Fang, X., Chen, H. Y., Wu, B., Wang, Z. U., Hilty, C., and Liu, W. R.*  (2013)  ACS Chemical Biology  8(2), 405-415  "Genetic incorporation of twelve meta-substituted phenylalanine derivatives using a single pyrrolysyl-tRNA synthetase mutant."
    
14. Ko, J. H. ^†, (Wang, Y. S.) ^†, Nakamura, A. ^†, Guo, L. T., Söll, D.*, and Umehara, T.*  (2013)  FEBS Letters  587(19), 3243-3248  "Pyrrolysyl-tRNA synthetase variants reveal ancestral aminoacylation function."
    
15. O'Donoghue, P. ^†, Ling, J. ^†, (Wang, Y. S.)^† and Söll, D.*  (2013)  Nature Chemical Biology  9(10), 594-598  "Upgrading protein synthesis for synthetic biology."
    
16. Wang, Z. ^†, (Wang, Y. S.) ^†, Pai, P. J., Russell, W. K., Russell, D. H. and Liu, R. W.*  (2012)  Biochemistry  51(26), 5232-5234  "A facile method to synthesize histones with posttranslational modification mimics."
    
17. (Wang, Y. S.), Fang, X., Wallace, A. L., Wu, B., and Liu, W. R.*  (2012)  Journal of the American Chemical Society  134(6), 2950-2953  "A rationally designed pyrrolysyl-tRNA synthetase mutant with a broad substrate spectrum."
    
18. Wan, W., (Wang, Y. S.), and Liu, R. W.*  (2012)  Organic Chemistry: Current Research  1(3), e111  "Genetically Encoding Bioorthogonal Functional Groups for Site-selective Protein Labeling."
    
19. Liu, W. R.*, (Wang, Y. S.), and Wan, W.  (2011)  Molecular Biosystems  7(1), 38-47  "Synthesis of proteins with defined posttranslational modifications using the genetic noncanonical amino acid incorporation approach."
    
20. (Wang, Y. S.), Russell, W. K., Wang, Z., Wan. W,, Dodd, L. E., Pai, P. J., Russell, D. H., and Liu, W. R.*  (2011)  Molecular Biosystems  7(3), 714-717  "The de novo engineering of pyrrolysyl-tRNA synthetase for genetic incorporation of L-phenylalanine and its derivatives."
    
21. (Wang, Y. S.), Wu, B., Wang, Z., Huang, Y., Wan, W., Russell, W. K., Pai, P. J., Moe, Y. N., Russell, D. H., and Liu, W. R.*  (2010)  Molecular Biosystems  6(9), 1557-1560  "A genetically encoded photocaged Nepsilon-methyl-L-lysine."
    
22. Ng, K. Y., Tu, L. C., (Wang, Y. S.), Chan, S. I., Yu, S. S.*  (2008)  ChemBioChem  9(7), 1116-1123  "Probing the hydrophobic pocket of the active site in the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) by variable stereoselective alkane hydroxylation and olefin epoxidation."
    
23. Whang, T. J., Wang, Y. T., Wu, Y. P., (Wang, Y. S.), Tsai, M. C., and Huang, D. S.*  (2005)  SAR and QSAR in Environmental Research  16(3), 247-262  "Assessment of baseline toxicity of mono-cyclic aromatic compounds by pseudomonas initial oxygen uptake assay."
    
24. Huang, D. S.*, Whang, T. J., Cheng, F. C., Wu, Y. P., Wang, Y. T., Luo, W. I., and (Wang, Y. S.)  (2005)  Environmental Toxicology and Chemistry  24(2), 253-260  "Toxicity assessment of mono-substituted benzenes and phenols using a Pseudomonas initial oxygen uptake assay."
    
25. Yu, S. S., Chen, K. H., Tseng, M. Y., (Wang, Y. S.), Tseng, C. F., Chen, Y. J., Huang, D. S., and Chan, S. I.*  (2003)  Journal of Bacteriology  185(20), 5915-5924  "Production of high-quality particulate methane monooxygenase in high yields from Methylococcus capsulatus (bath) with a hollow-fiber membrane bioreactor."
    
26. Huang, D. S., Wu, S. H., (Wang, Y. S.), Yu, S. S., and Chan, S. I.*  (2002)  ChemBioChem  3(8), 760-765  "Determination of the carbon kinetic isotope effects on propane hydroxylation mediated by the methane monooxygenases from Methylococcus capsulatus (Bath) by using stable carbon isotopic analysis."
    
27. Wu, S. H., (Wang, Y. S.), Fan, L. X., Chang, R. T. D. and Huang, D. S.*  (2002)  Journal of the Chinese Chemical Society  79(3), 315-317  "Hydrous Pyrolysis of Methylphenanthrenes – Degradation and Isomerization."