Chi-Huey Wong, PhD

Professor of Chemistry
Department of Chemistry
California Campus



Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Faculty, Graduate Program

Other Joint Appointments

Academia Sinica, Taipei, Taiwan

Research Focus

Research in the Wong lab encompasses a broad spectrum of bioorganic and synthetic chemistry. Development of small molecules targeting RNA and design and synthesis of inhibitors to enzymes and receptors are being performed to investigate how small molecules interact with biologically important molecules and in turn, learn more about the function of those molecules. Development of both synthetic and bioorganic strategies is also paramount to our research. Programmable one-pot reactions can be used for the synthesis of complex oligosaccharides and glycoarrays, and complement development of new enzymatic catalysts for glycoprotein synthesis and other organic reactions.


Education

Ph.D. (Organic Chemistry), Massachusetts Institute of Technology, 1982
M.S. (Biochemical Sciences), National Taiwan University, 1977
B.S. (Chemistry & Biochemical Sciences), National Taiwan University, 1970

Professional Experience

B.S. Chemistry/Biochemical Sciences 1966–1970 National Taiwan University
M.S. Biochemical Sciences 1975–1977 National Taiwan University
Ph.D. Organic Chemistry 1979–1982 MIT (with G.M. Whitesides)
Postdoctoral Fellow 1982–1983 Harvard University (with G.M.Whitesides)

2006-2016 President, Academia Sinica
1996-2006 Member, The Skaggs Institute for Chemical Biology, Scripps Research
1989-2006 Ernest W. Hahn Professor of Chemistry, Chemistry, Scripps Research
1989-2006 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences, Scripps Research
1991-1999 Head, Frontier Research Program on Glycotechnology, RIKEN: Institute of Physical and Chemical Research
1987-1989 Professor of Chemistry, Texas A&M University
1987-1989 Professor, Department of Biochemistry and Biophysics and the Institute of Biosciences and Technology, Texas A&M University
1986-1987 Associate Professor of Chemistry, Texas A&M University
1983-1986 Assistant Professor of Chemistry, Texas A&M University
1982-1983 Postdoctoral Fellow with G.M. Whitesides, Harvard University

Awards & Professional Activities

Searle Scholar Award in Biomedical Sciences, 1985; Presidential Young Investigator in Chemistry, 1986; ACS Arthur C. Cope Scholar Award, 1993; The IUPAC International Carbohydrate Award, 1994; Elected Member of Academia Sinica, Taipei 1994; Elected Member of the American Academy of Arts and Sciences, 1996; The ACS Harrison Howe Award in Chemistry, 1998; The ACS Claude S. Hudson Award in Carbohydrate Chemistry, 1999; The International Enzyme Engineering Award, 1999; Presidential Green Chemistry Award, 2000; The ACS Award for Creative Work in Synthetic Organic Chemistry, 2006; Humboldt Research Award for Senior Scientists, 2008; F. A. Cotton Medal for Excellence in Chemical Research, 2005;  The ACS Arthur C. Cope Award, 2012; The Wolf Prize in Chemistry, 2014; The Royal Society of Chemistry Robert Robinson Award, 2015; Elected Member of the National Academy of Science, 2002; American Academy of Arts and Sciences, 1996; and President of Academia Sinica, 2006-2016; Distinguished Research Fellow, The Genomics Research Center, Academia Sinica, Taipei, Taiwan, 2016-present

Selected References

All Publications

Koeller, K., Wong, C.-H. "Enzymes for chemical synthesis," Nature (2001) 409, 232.

Sears, P., Wong, C.-H. "Toward automated synthesis of oligosaccharides and glycoproteins," Science (2001) 291, 2344.

Danishefsky, S.J., Shue, Y.-K., Chang, M.N., Wong, C.-H. "Development of Globo-H Cancer Vaccine," Acc. Chem. Res. (2015) 48, 643.

Shivatare, S.S., Chang, S.-H., Tsai, T.-I., Tseng, S.Y., Lin, Y.-S., Cheng, Y.-Y., Ren, C.-T., Pawar, S., Tsai, C.-S., Shi, H.-W., Zeng, Y.-F., Liang, C.-H., Kwong, P.D., Burton, D.R., Wu, C.-Y., Wong, C.-H. "Modular Synthesis of N-glycans and Arrays for the Hetero-ligand Binding Analysis of Antibodies," Nature Chem. (2016) doi:10.1038/nchem.2463.

G. B. E. Stewart-Jones, C. Soto, T. Lemmin, G.-Y. Chuang, A. Druz, R. Kong, P. V. Thomas, K. Wagh, T. Zhou, A.-J. Behrens, T. Bylund, C. W. Choi, J. R. Davison, I. S. Georgiev, M. G. Joyce, Y. D. Kwon, M. Pancera, J. Taft, Y. Yang, B. Zhang, S. S. Shivatare, V. S. Shivatare, C.-C. D. Lee, C.-Y. Wu, C. A. Bewley, D. R. Burton, W. C. Koff, M. Connors, M. Crispin, B. T. Korber, C.-H. Wong, J. R. Mascola and P. D. Kwong, “Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G”, Cell,165, 813-826, (2016)

P.-C. Wang, J.-M. Fang, K.-C. Tsai, S.-Y. Wang, W.-I. Huang, Y.-S. Cheng, R. C., C.-H. Wong, “Peramivir phosphonate derivatives as influenza neuraminidase inhibitors”, J. Med. Chem., 59 (11), 5297-5310, (2016)

L. Krasnova and C.-H. Wong, “Understanding the chemistry and biology of glycosylation with glycan synthesis”, Annual Review of Biochemistry, 85, 599-630, (2016)

L. Krasnova and C.-H. Wong, “Exploring human glycosylation for better therapies”, Molecular Aspects of Medicine, S0098-2997 (16), 30013-30019, (2016)

S.-C. Yeh, P.-Y. Wang, Y.-W. Lou, K.-H. Khoo, M. Hsiao, T.-L. Hsu, C.-H. Wong“Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity”,Proc. Nat. Acad. Sci. U.S.A., 113 (20), 5592-5597, (2016)

T.-C. Kuo, L.-W. Li, S.-H. Pan, J.-M. Fang, J.-H. Liu, T.-R. Cheng, C.-J. Wang, P.-F. Hung, H.-Y. Chen, T.-M. Hong, Y.-L .Hsu, C.-H. Wong, P.-C. Yang, “Purine-type compounds induce microtubule fragmentation and lung cancer cell death through interaction with katanin”, J. Med. Chem., 59 (18), 8521-34, (2016)

C.-H. Hsu, S. Park, D. E. Mortenson, B. L. Foley, X. Wang, R. J. Woods, D. A. Case, E. T. Powers, C.-H. Wong, H. J. Dyson, J. W. Kelly, “The dependence of carbohydrate-aromatic interaction strengths on the structure of the carbohydrate”, J. Am. Chem. Soc., 138 (24), 7636-7648, (2016)

D. Sok, M. Pauthner, B. Briney, J.-H. Lee, K. L. Saye-Francisco, J. Hsueh, A. Ramos, K.-M. Le, M. Jones, J. G. Jardine, R. Bastidas, A. Sarkar, C.-H. Liang, S. S. Shivatare, C.-Y. Wu, W. R. Schief, C.-H. Wong, I. A. Wilson, A. B. Ward, J. Zhu, P. Poignard, D. R. Burton, “A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans”, Immunity, 45 (1), 31-45, (2016)

D. T. MacLeod, N. M. Choi, B. Briney, F. Garces, L. S. Ver, E. Landais, B. Murrell, T. Wrin, W. Kilembe, C.-H. Liang, A. Ramos, C.-B. Bian, L. Wickramasinghe, L. Kong, K. Eren, C.-Y. Wu, C.-H. Wong, S. L. Kosakovsky Pond, I. A. Wilson, D. R. Burton, P. Poignard, “Early antibody lineage diversification and independent limb maturation lead to broad HIV-1 neutralization targeting the env high-mannose patch”, Immunity, 44 (5), 1215-1226, (2016).

S. Y. Tseng, W.-H. Cho, J. Su, S.-H. Chang, D. Chiang, C.-Y. Wu, C.-N. Hsiao, C.-H. Wong, “Preparation of aluminum oxide-coated glass slides for glycan microarray”, ACS Omega, 1 (5), 773–783, (2016).

T.-N. Wu, K.-H. Lin, Y.-T. Wu, J.-R. Huang, J.-T. Hung, J.-C. Wu, C.-Y. Chen, K.-C. Chu, N.-H. Lin, A. L. Yu, C.-H. Wong, “Phenyl glycolipids with different glycosyl groups exhibit marked differences in murine and human iNKT cell activation”, ACS Chem. Biol., 11 (12), 3431-3441, (2016)

Y.-L. Lo, G.-G. Liou, C.-H. Lu, M. Hsiao, T.-L. Hsu, C.-H. Wong, “Dengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complex”, PLOS ONE,11 (11), e0166474, (2016)

Y. Kizuka, S. Funayama, H. Shogomori, M. Nakano, K. Nakajima, R. Oka, S. Kitazume, Y. Yamaguchi, M. Sano, H. Korekane, T.-L. Hsu, H.-Y. Lee, C.-H. Wong and N. Taniguchi, “High sensitivity and low toxicity fucose probe for glycan imaging and biomarker discovery”, Cell Chem. Biol., 23 (7), 782-792, (2016)

C.-Y. Wu, C.-W. Lin, T.-L. Tsai, C.-C. D. Lee, H.-Y. Chuang, J.-B. Chen, M.-H. Tsai, B.-R. Chen, P.-W. Lo, C.-P. Liu, V. S. Shivatare and C.-H. Wong, “Influenza A surface glycosylation and vaccine design”, Proc. Nat. Acad. Sci. U.S.A., 114 (2), 280-285, (2017).

T.-I. Tsai, S.-T. Li, C.-P. Liu, K. Chen, S. S. Shivatare, C.-W. Lin, S.-F. Liao, C.-W. Lin, T.-L. Hsu, Y.-T. Wu, M.-H. Tsai, M-Y. Lai, N.-H. Lin, C.-Y. Wu, C.-H. Wong, “An effective bacterial fucosidase for glycoprotein remodeling”, ACS Chemical Biology, 12 (1), 63-72, (2017)

J.-J. Shie, Y.-C. Liu, J.-C. Hsiao, J.-M. Fang, C.-H. Wong, “A Cell-Permeable and Triazole-forming fluorescence probe for glycoconjugate imaging in live cells”,ChemComm,53 (9), 1490-1493, (2017).

W. Yang, D. Punyadarsaniya, R. Lambertz, D. Lee, C.-H. Liang, D. Höper, S. Leist, A. Hernandez-Caceres, J. Stech, M. Beer, C.-Y. Wu, C.-H. Wong, K. Schughart, F. Meng, and G. Herrler, “Mutations during the adaptation of H9N2 avian influenza virus to the respiratory epithelium of pigs enhance the sialic acid binding activity and the virulence in mice”, Journal of Virology, 91 (8),pii: e02125-16, (2017)

C.-L. Chen, J.-C. Hsu, C.-W. Lin, C.-H. Wang, M.-H. Tsai, C.-Y. Wu, C.-H. Wong, C. Ma, “Crystal structure of a homogeneous IgG-Fc glycoform with the N-glycan designed to maximize the antibody dependent cellular cytotoxicity”, ACS Chemical Biology, 12 (5), 1335-1345, (2017)

A. M. Stax, J. Tuengel, E. Girardi, N. Kitano, L. L. Allan, J. I. Alvarez, V. Li, D. Zheng, W. J. Panenka, C.-H. Wong, S. van Calenbergh, D. M. Zajonc, P. van den Elzen, “Autoreactivity to sulfatide by human invariant NKT cells”, Journal of Immunology, 199 (1), 97-106, (2017)

T. H. Tseng, T.-W. Lin, C.-Y. Chen, C.-H. Chen, J.-L. Lin, T.-L. Hsu, C.-H. Wong, “Substrate preference and interplay of fucosyltransferase 8 and N-acetylglucosaminyltransferases”, J. Am. Chem. Soc., 139 (28), 9431-9434, (2017).

Y.-W. Huang, H.-I. Yang, Y.-T. Wu, T.-L. Hsu, T.-W. Lin, J. Kelly, C.-H. Wong, “Residues comprising the enhanced aromatic sequon influence protein N-glycosylation efficiency”, J. Am. Chem. Soc., 139 (37), 12947-12955, (2017).

C.-Y. Ting, Y.-W. Lin, C.-Y. Wu, C.-H. Wong, “Design of disaccharide modules for the programmable one-pot synthesis of building blocks with LacNAc repeats for asymmetric N-glycans”, Asian Journal of Organic Chemistry, 6 (12),1800–1807, (2017)

L.-Y. Huang, S.-C. Wang, T.-J. R. Cheng, C.-H. Wong “Undecaprenyl phosphate phosphatase activity of undecaprenol kinase regulates the lipid pool in Gram-positive bacteria”, Biochemistry, 56 (40), 5417-5427, (2017).

Y. Kizuka, M.Nakano, Y. Yamaguchi, K.Nakajima, R. Oka, K. Sato, C.-T.Ren, T.-L.Hsu, C.-H.Wong, N. Taniguchi,“An alkynyl-fucose halts hepatoma cell migration and invasion by inhibiting GDP-fucose-synthesizing enzyme FX, TSTA3”Cell Chem Biol.,24 (12),1467-1478, (2017). 

R. Andrabi, C.-Y.Su, C.-H.Liang, S.-S.Shivatare, B. Briney, J.E.Voss, S. K.Nawazi, C.-Y.Wu, C.-H.Wong, D. R.Burton“Glycans function as anchors for antibodies and help drive HIV broadly neutralizing antibody development”Immunity,47 (3), 524-537,(2017)

H.-W. Cheng, R.-J. Chein, T.-J. Cheng, P.-S. Wu, H.-Y. Wu, P.-F. Hung, C.-J. Wang, Y.-L. Hsu, J.-M. Wong, A. Yuan, C.-H. Wong, P.-C. Yang, S.-H. Pan, “2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction”, Cancer Science, 109 (3), 832-842, (2018)

C.-P. Liu, T.-I Tsai, T. Cheng, V. S. Shivatare, C.-Y. Wu, C.-Y. Wu, C.-H. Wong, “Glycoengineering of antibody (Herceptin) through yeast expression and in vitroenzymatic glycosylation”, Proc. Nat. Acad. Sci. U.S.A., 115 (4), 720-725, (2018).

S. S. Shivatare, V. S. Shivatare, C.-Y. Wu, C.-H. Wong, “Chemo-Enzymatic Synthesis of N-Glycans for array development and HIV antibodies profiling”, Journal of Visualized Experiments, 132, (2018)

W.-S. Wu, W.-C. Cheng, T.-R. Cheng, C.-H. Wong, “Affinity-based screen for inhibitors of bacterial transglycosylase”, J. Am. Chem. Soc., 140 (8), 2752-2755, (2018)

C.-F. Huang, K. S. Liang, T.-L. Hsu, T.-T. Lee, Y.-Y. Chen, S.-M. Yang, H.-H. Chen, S.-H. Huang, W.-H. Chang, T.-K. Lee, P. Chen, K.-E. Peng, C.-C. Chen, C.-Z. Shi, Y.-F. Hu, G. Margaritondo, T. Ishikawa, C.-H. Wong and Y. Hwu, “Free-electron-laser coherent diffraction images individual drug-carrying liposome particles in solution”, Nanoscale, 10 (6), 2820-2824, (2018)

V. S. Shivatare, S. S. Shivatare, C.-C. Lee, C.-H. Liang, K.-S. Liao, Y.-Y. Cheng, G. Saidachary, C.-Y. Wu, N.-H. Lin, P. D. Kwong, D. Burton, C.-Y. Wu, C.-H. Wong, “Unprecedented role of hybrid N-glycans as ligands for HIV-1 broadly neutralizing antibodies”, J. Am. Chem. Soc., 140 (15), 5202-5210, (2018).

T. Zhou, A. Zheng, U. Baxa, G.-Y. Chuang, I. S. Georgiev, R. Kong, S. O’Dell, S. Shahzad-ul-Hussan, C.-H. Shen, Y. Tsybovsky, R. T. Bailer, S. K. Gift, M. K. Louder, K. McKee, R. Rawi, C. H. Stevenson, G. B. E. Stewart-Jones, J. D. Taft, E. Waltari, Y. Yang, B. Zhang, S. S. Shivatare, V. S. Shivatare, C.-C. D. Lee, C.-Y. Wu, NISC Comparative Sequencing Program, J. C. Mullikin, C. A. Bewley, D. R. Burton, V. R. Polonis, L. Shapiro, C.-H. Wong, J. R. Mascola, P. D. Kwong, and X. Wu, “Structural basis of recognition by an antibody targeting the silent face of HIV envelope”, Immunity, 48 (3), 500-513, (2018).

X. Wang, L. Krasnova, K. B. Wu, W.-S. Wu, T.-J. Cheng, C.-H. Wong, “Towards new antibiotics targeting bacterial transglycosylase: synthesis of a lipid II analog as stable transition-state mimic inhibitor”, Bioorg. Med. Chem. Lett., pii: S0960-894X (18), 30228-2, (2018).

P.-W.Lo, J.-J.Shie, C.-H.Chen, C.-Y.Wu, T.-L.Hsu, C.-H.Wong,O-GlcNAcylation regulates the stability and enzymatic activity of the histone methyltransferase EZH2”,Proc. Nat. Acad. Sci. U.S.A., 115 (28), 7302-7307, (2018)

S. S. Shivatare, L.-Y. Huang, Y.-F. Zeng, J.-Y. Liao, T.-H. You, S.-Y. Wang, T. Cheng, C.-W. Chiu, P. Chao, L.-T. Chen, T.-I. Tsai, C.-C. Huang, C.-Y. Wu, N.-H. Lin, and C.-H. Wong, “Development of Endo-S2 mutants for the synthesis of homogeneous antibody glycoforms to elucidate effector functions”, Chem, Comm., 54 (48), 6161-6164, (2018)

S. Dey and C.-H. Wong, “Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives”, Chemical Science, 9 (32), 6685-6691, (2018)

S. Dey, S. O. Bajaj, T.-I. Tsai, H.-J. Lo, K. Wu, and C.-H. Wong, “Synthesis of modular building blocks using glycosyl phosphate donors for the construction of asymmetric N-Glycans”, Tetrahedron, 74 (41), 6003-6011, (2018)

S.-C. Wang, H.-Y. Liao, J.-Y. Zhang, T.-J. R. Cheng, C.-H. Wong, “Development of a universal influenza vaccine using hemagglutinin stem protein produced from Pichia pastoris”, Virology, 526 (2), 125-137, (2018)

C.-W. Cheng, Y. Zhou, W.-H. Pan, S. Dey, C.-Y. Wu, W.-L. Hsu, and C.-H. Wong, “Hierarchical and programmable one-pot synthesis of oligosaccharides”, Nature Communications, in press, (2018)


Links

The Skaggs Institute for Chemical Biology

Molecules Caught in the Act-- Scientists at TSRI Solve Elusive Enzyme Mechanism

The Skaggs Institute Scientific Report

Antivirals, Anti-Cancers, and Antibiotics in One Pot