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Lai-Xi Wang

Contact Information
Office: IHV/UMD School of Medicine, 725 Lombard St.,
Phone: 410-706-4982
Wang CV
Lab Website

Professor

Ph.D. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences 1991; Post-Doctoral Johns Hopkins University 1994; Post-Doctoral Massachusetts Institute of Technology (MIT) 1997

Professional Interests

The Wang Lab is working in the areas of bioorganic chemistry, synthetic carbohydrate chemistry, glycobiology, and immunology. Current research in the group is centered on protein glycosylation, one of the most ubiquitous posttranslational modifications of proteins in eukaryotes. It is estimated that half of total human proteins are glycoproteins. Glycosylation adds a new level of structural and functional diversity of proteins and expands the biological information of an otherwise concise human genome. Students in Wang group combine synthetic organic chemistry, structural biology, and immunology to understand the functional roles of glycans and glycoproteins in biological system. Current research projects include: 1) Development of new chemoenzymatic methods for the synthesis of oligosaccharides and glycoproteins; 2) Structural and mechanistic study of endoglycosidases and glycosynthases; and 3) HIV glycobiology and vaccine design targeting the viral envelope glycoproteins.

 

  1. Huang, W., Giddens, J., Fan, S. Q., Toonstra, C., Wang, L. X., “Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions”, J. Am. Chem. Soc.134, 12308−12318 (2012).
  2. Cross, A.S., Hyun, S.W., Miranda-Ribera, A., Feng, C., Liu, A., Nguyen, C., Zhang, L., Luzina, I.G., Atamas, S.P., Twaddell, W.S., Guang, W., Lillehoj, E.P., Puche, A.C., Huang, W., Wang, L.X., Passaniti, A., Goldblum, S.E. “NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia. NEU1 restrains endothelial cell migration whereas NEU3 does not”, J. Biol. Chem., 287, 15966-15980 (2012).
  3. Fan, S., Huang, W., Wang, L. X. “Remarkable transglycosylation activity of glycosynthase mutants of Endo-D, an endo-β-N-acetylglucosaminidase from Streptococcus pneumonia”, J. Biol. Chem., 287, 11272–11281 (2012).
  4. Lillehoj, E.P., Hyun, S.W., Feng, C., Zhang, L., Liu, A., Guang, W., Nguyen, C., Luzina, I.G., Atamas, S.P., Passaniti, A., Twaddell, W.S., Puché, A.C., Wang, L.X., Cross, A.S., Goldblum, S.E. “NEU1 sialidase expressed in human airway epithelia regulates epidermal growth factor receptor (EGFR) and MUC1 protein signaling”, J. Biol. Chem., 287, 8214-8231 (2012).
  5. Wang, L. X., Lomino, J. V. “Emerging technologies for making glycan-defined glycoproteins”, ACS Chemical Biology, 7, 110-122 (2011).
  6. McLellan, J., Pancera, M., Carrico, C., Gorman, J., Julien, J. P., Khayat, R., Louder, R., Pejchal, R., Sastry, M., Dai, K., O’Dell, S., Patel, N., Shahzad-ul-Hussan, S., Yang, Y., Zhang, B., Zhou, T., Zhu, J., Boyington, J. C., Chuang, G. Y., Diwanji, D., Georgiev, I., Kwon, Y. D., Lee, D., Louder, M. K., Moquin, S., Schmidt, S. D., Yang, Z. Y., Bonsignori, M., Crump, J. A., Kapiga, S. H., Sam, N. E., Haynes, B. F., Burton, D. R., Koff, W. C., Walker, L. M., Phogat, S., Wyatt, R., Orwenyo, J., Wang, L. X., Arthos, J., Bewley, C. A., Mascola, J. R., Nabel, G. J., Schief, W. R., Ward, A. B., Wilson, I. A., Kwong, P. D., “Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9”, Nature, 480, 336-343 (2011).
  7. Zou, G., Ochiai, H., Huang, W., Yang, Q., Li, C., Wang, L. X., “Chemoenzymatic synthesis and Fcƒ× receptor binding of homogeneous glycoforms of antibody Fc domain. Presence of a bisecting sugar moiety enhances the affinity of Fc to FcgIIIa receptor”, J. Am. Chem. Soc., 133, 18975-18991 (2011).
  8. Amin, M. N., Huang, W., Mizanur, R. M., Wang, L. X., “Convergent synthesis of homogeneous Glc1Man9GlcNAc2-protein and derivatives as ligands of molecular chaperones in protein quality control”, J. Am. Chem. Soc.133, 14404–14417 (2011).
  9. Huang, W., Li, J., Wang, L. X., “Unusual transglycosylation activity ofFlavobacterium meningosepticum endoglycosidases enables convergent chemoenzymatic synthesis of core fucosylated complex N-glycopeptides”,ChemBioChem12, 932-941 (2011).
  10. Huang, W., Zhang, X., Ju, T., Cummings, R.D., Wang, L.X. “Expeditious chemoenzymatic synthesis of CD52 glycopeptide antigens”, Org. Biomol. Chem., 8, 5224-5233 (2010).
  11. Brooks, C.L., Schietinger, A., Borisova1, S.N., Kufer, P., Okon, M., Hirama, T., MacKenzie, C.R., Wang, L.X., Schreiber, H., Evans, S.V., “Antibody recognition of a novel tumor-specific glycopeptide antigen”, Proc. Natl. Acad. Sci. USA, 107, 10056-10061 (2010).
  12. Huang, W., Yang, Q., Umekawa, M., Yamamoto, K., Wang, L.X., “Arthrobacter endo-beta-N-acetylglucosaminidase shows transglycosylation activity on complex type N-glycan oxazolines. One-pot conversion of ribonuclease B to sialylated ribonuclease C”. ChemBioChem,11, 1350-1355 (2010).
  13. Yang, Q., Li, C., Wei, Y., Huang, W., Wang, L. X., “Expression, glycoform characterization, and antibody-binding of HIV-1 V3 glycopeptide domain fused with human IgG1-Fc”, Bioconjugate Chem., 21, 875-883 (2010).
  14. Schwarz, F., Huang, W., Li, C., Schulz, B. L., Lizak, C., Palumbo, A., Numao, S., Neri, D., Aebi, M., Wang, L. X. “A combined method for producing homogeneous glycoproteins with eukaryotic N-glycosylation”,Nat. Chem. Biol., 6, 264-266 (2010).
  15. Umekawa, M., Li,C., Higashiyama, T., Huang, W., Ashida, H., Yamamoto, K., Wang, L. X., “Efficient glycosynthase mutant derived from Mucor hiemalis endo-b-N-acetylglucosaminidase capable of transferring oligosaccharide from both sugar oxazoline and natural N-glycan”, J. Biol. Chem., 281, 511-521 (2010).
  16. Huang, W., Wang, D., Yamada, M., Wang, L. X., “Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters”,J. Am. Chem. Soc.131, 17963-17971 (2009).
  17. Huang, W., Li, C., Li, B., Umekawa, M., Yamamoto, K., Zhang, X., Wang, L. X., “Novel glycosynthases enable a highly efficient chemo-enzymatic synthesis of N-glycoproteins carrying intact natural N-glycans”, J. Am. Chem. Soc.131, 2214-2223 (2009).
  18. Zhu, X. Y., Holtz, B., Wang, Y., Wang, L. X., Orndorff, P. E., Guo, A., „Quantitative glycomics from fluidic glycan microarrays“, J. Am. Chem. Soc.131, 13646-13650 (2009).
  19. Wang, L. X., “Expanding the repertoire of glycosynthases”, Chem. Biol.,16, 1026-1027 (2009).
  20. Newsom-Davis, T. E., Wang, D., Steinman, L., Chen, P. F. T., Wang, L. X., Simon, A. K., Screaton, G. R., “Enhanced immune recognition of cryptic glycan markers in human tumors”, Cancer Research., 69, 2018-25 (2009).
  21. Wang, L. X., Huang, W., “Enzymatic transglycosylation for glycoconjugate synthesis”, Curr. Opin. Chem. Biol., 13, 592–600 (2009).
  22. Huang, W., Groothuys S., Heredia A., Kuijpers B.H., Rutjes F.P., van Delft F.L., Wang L.X., “Enzymatic glycosylation of triazole-linked GlcNAc/Glc-peptide: Synthesis, stability, and anti-HIV activity of triazole-linked HIV-1 gp41 glycopeptide C34 analogues”, ChemBioChem10, 1234-1242 (2009).
  23. Huang, W., Ochiai, H., Zhang, X., Wang, L. X., “Introducing N-glycans into natural products through a chemoenzymatic approach”, Carbohydr. Res.,343, 2903-2913 (2008).
  24. Wei, Y., Li, C., Huang, W., Li, B., Strome, S. E., Wang, L. X., “Glyco-engineering of human IgG1-Fc through combined yeast expression and in vitro chemoenzymatic glycosylation”, Biochemistry47, 10294-10304 (2008).
  25. Ochiai, H., Huang, W., Wei, Y., Wang, L. X., “Expeditious chemoenzymatic synthesis of homogeneous N-glycoproteins carrying defined oligosaccharide ligands”. J. Am. Chem. Soc., 130, 13790-13803 (2008).
  26. Li, C., Huang, W., Wang, L. X., “Chemoenzymatic synthesis of N-linked neoglycoproteins through a chitinase-catalyzed transglycosylation”,Bioorg. Med. Chem.,16, 8366-8372 (2008).
  27. Li, B., Takegawa, K., Suzuki, T., Yamamoto, K., Wang, L. X., “Synthesis and inhibitory activity of oligosaccharide thiazolines as a class of mechanism-based inhibitors for endo-beta-N-acetylglucosaminidases”,Bioorg. Med. Chem., 16, 4670-4675 (2008).
  28. Wang, L. X., “Chemoenzymatic synthesis of glycopeptides and glycoproteins through endoglycosidase-catalyzed transglycosylation”,Carbohydr. Res.343, 1509-22 (2008).
  29. Umekawa, M., Huang, W., Li, B., Fujita, K., Ashida, H., Wang, L. X., Yamamoto, K., “Mutants of Mucor hiemalis endo-beta-N-acetylglucosaminidase show enhanced transglycosylation and glycosynthase-like activities”, J. Biol. Chem., 283, 4469-4479 (2008).

 

Honors and Awards

  • 2008-2012, Chartered Member, NIH Synthetic and Biological Chemistry (SBCA) Study Section
  • 2005-2007, Ad Hoc Member, NIH Synthetic and Biological Chemistry (SBCA) Study Section
  • 2006-2008, Member, NIH BCMB Special Emphasis Panel
  • Member, Editorial Advisory Board, ‘Recent Patent Reviews on Anti-Infective Drug Discovery’
  • Executive Editor for special issues, Current Pharmaceutical Design (Bentham Science Publishers)
  • The 2004 Young Investigator Award in Carbohydrate Chemistry, The American Chemical Society
  • 2009- Member, Editorial Board of Carbohydrate Research

 

Funding

Active grants:

R01 GM096973-02 (NIGMS/NIH) PI: Lai-Xi Wang

07/01/2011 – 06/30/2015
Title: “Synthesis and Function of Antibody Fc Domain Glycoforms”
Role: Principal Investigator
R21 AI101035 (NIAID/NIH) PI: Lai-Xi Wang
07/05/2012 – 06/30/2014
Title: “Synthetic Variable Domain Glycopeptides for Neutralizing Epitope Characterization”
Role: Principal Investigator            
R01 AI102680-01(NIAID/NIH) PI: David Pauza
07/20/2012 – 06/30/2016
Title: “FcRn-targeted mucosal HIV vaccine”
Role: Co-Investigator                      
Pending grants:
R01 GM080374-06(NIGMS/NIH) PI: Lai-Xi Wang
04/01/2013-03/31/2017
Title: “Convergent chemoenzymatic synthesis of glycopeptides and glycoproteins”
Role: Principal Investigator
(Scientific review completed: Impact Score: 16; Percentile: 2.0)
 
Recently completed Grants
 
R01 GM080374-05(NIGMS/NIH) PI: Lai-Xi Wang
06/01/2007-05/31/2012
Title: “Convergent chemoenzymatic synthesis of glycopeptides and glycoproteins”
Role: Principal Investigator
R01 AI067111(NIAID/NIH) PI: Lai-Xi Wang
01/01/2006-12/31/2010
Title: “HIV-1 glycopeptides as immunogens”
Role: Principal Investigator
 
R01 GM073717(NIGMS/NIH) PI: Lai-Xi Wang
09/01/2006-08/31/2009
Title: “Enzymatic transglycosylation for N-glycopeptide synthesis”
Role: Principal Investigator

Courses Taught

  • CHEM 435: Biochemistry of Complex Carbohydrates