Wengang CHAI
As a trained chemist Dr Wengang Chai became interested in the structural aspects of carbohydrate molecules of biomedical importance. After a period of work at the Institute of Chemistry, Chinese Academy of Sciences (Beijing) and the Department of Pharmaceutical Chemistry & NIH National Bio-Organic Biomedical Mass Spectrometry Resource Center, University of California at San Francisco, he joined the Glycosciences Laboratory at the MRC Clinical Research Centre in 1988, which later became part of the Imperial College London. He has been an ‘Lvka Visiting Professor’ of OUC since 2005. His research programme has been aimed at characterizing the sequences and understanding the roles of oligosaccharide chains of glycoproteins, glycolipids and polysaccharides in recognition systems of biological and medical importance, including: i) the design and application of integrated strategies to tackle the difficult area of structure and function assignments of oligosaccharides, and ii) the development of methods for structural analysis of bioactive oligosaccharides, using mass spectrometry as the principal technique, and their application in different biological settings.
His main achievement has been the establishment, together with colleagues, of the first oligosaccharide microarray system in the world, which has found many important applications in the fields of infection and immunity. He has also developed various mass spectrometric strategies, particularly negative-ion electrospray tandem mass spectrometry, for sequence determination of bioactive oligosaccharides, and as a result many oligosaccharides with novel sequences have been isolated from different natural sources. Highlights include thedetection of natural killer cell marker HNK-1 epitope on O-glycans with a novel O-mannosyl core in brain and demonstration of the high prevalence (30%) of the ‘yeast-type’ 2- and 2,6-linked O-mannosylated sequences among the O-glycans; and identification of sulphated Lewis a/x oligosaccharides as novel ligands for E-selectin.In collaboration with James Beeson (WEHI, Melbourne), he has defined theessential structural motif on chondroitin sulphate A and hyaluronic acid for adhesion of P. falciparum-infected erythrocytes and the key structural requirements on heparan sulphate-like molecules which can block P. falciparum merozoite invasion of erythrocytes.
SELECTED KEY PUBLICATIONS
1. Chai, W., Luo, L., Lim, C.-K. & Lawson, A.M., Characterisation of Heparin Oligosaccharide Fractions as Ammonium Salts Using Electrospray Mass Spectrometry, Anal. Chem., 1998,70, 2060-2066.
2. Chai, W., Yuen, C.-T., Kogelberg, H., Carruthers, R.A., Feizi, T. & Lawson, A.M., High Prevalence of 2-Substituted and 2,6-Di-substituted Mannitol-Terminating Sequences among Oligosaccharides Released from Brain Glycopeptides by Reductive Alkaline Hydrolysis, Eur. J. Biochem., 1999,263, 879-888.
3. Beeson, J.G., Rogerson, S.J., Cooke, B.M., Reeder, J.C., Chai, W., Lawson, A.M., Molyneux, M.E. & Brown, G.V., Adhesion of Plasmodium falciparum-Infected Erythrocytes to Hyaluronic Acid in Placental Malaria, Nature Medicine, 2000,6, 86-90.
4. Chai, W., Pisvarev, V. & Lawson, A.M., Negative-Ion Electrospray Mass Spectrometry of Neutral Underivatized Oligosaccharides, Anal. Chem., 2001,73, 651-657.
5. Chai, W., Beeson, J.G. & Lawson, A.M., The Structural Motif in Chondroitin Sulfate for Adhesion of Plasmodium falciparum-Infected Erythrocytes Comprises Disaccharide Units of 4-O-Sulfated and Non-Sulfated N-Acetylgalactosamine Linked to Glucuronic Acid, 2002,J. Biol. Chem., 277, 22438-22446.
6. Fukui, S., Feizi, T., Galustian, C., Lawson, A.M. & Chai, W.,Oligosaccharide Microarrays toward High-Throughput Detection and Specificity Assignments of Carbohydrate-Protein Interactions, Nature Biotechnol., 2002,20, 1011-1017.
7. Feizi, T. & Chai, W., Oligosaccharide Microarray to Decipher the Glyco Code, Nature Reviews Mol. Cell Biol., 2004,5, 582-588.
8. Palma, A.S., Feizi, T., Zhang, Y., Stoll, M.S., Lawson, A.M., Díaz-Rodríguez, E., Campanero-Rhodes, M.A., Costa, J., Gordon, S., Brown, G.D. & Chai, W., Ligands for the b-Glucan Rec eptor, Dectin-1, Assigned using ‘Designer’ Microarrays of Oligosaccharide Probes (Neoglycolipids) Generated from Glucan Polysaccharides, J. Biol. Chem., 2006,281, 5771-5779.
9. Beeson, J.G., Andrews, K.T., Boyle, M., Duffy, M.F., Choong, E.K., Byrne, T.J., Chesson, J.M., Lawson, A.M. & Chai, W., Structural Basis for Binding of Plasmodiumfalciparum Erythrocyte Membrane Protein 1 to Chondroitin Sulfate and Placental Tissue and the Influence of Protein Polymorphism, J. Biol. Chem., 2007,282, 22426-22436.
10. Liu, Y., Feizi,T., Campanero-Rhodes,M.A., Childs, R.A., Zhang, Y., Mulloy,B., Evans, P.G., Osborn, H.M.I., Otto, D., Crocker, P.R. & Chai, W., Novel Neoglycolipid Probes Prepared via Chemoselective Oxime-Ligation for Microarray Analysis of Oligosaccharide-Protein Interactions, Chem. Biol., 2007,14, 847-859.
11. Liu, Y., Chai, W., Campanero-Rhodes, M.A., Zhang, Y., Eickmann, M., Kiso, M., Hay, A., Matrosovich, M. & Feizi, T., Experimental Determination of the Receptor Binding Specificity of the Pandemic Influenza A (H1N1) 2009 Virus by Carbohydrate Microarray Analyses, Childs, R.A., Palma, A.S., Wharton, S., Matrosovich, T., Nature Biotechnol., 2009,27, 797-799.
12. Yu, G., Zhang, Y., Zhang, Z., Song, L., Wang, P. & Chai, W., The Effect and Limitation of Excess Ammonium on the Release of O-Glycans in Reducing Forms from Glycoproteins under Mild Alkaline Conditions for Glycomic and Functional Analysis, Anal. Chem., 2010,82, 9534-9542.
13. Kaiser, H.-J., Orłowski, A., Rog, T., Nyholm, T.K.M., Chai, W., Feizi, T., Lingwood, D., Vattulainen, I. & Simons, K., Sorting in Model Membranes by Cholesterol-Mediated Hydrophobic Matching, Proc. Natl. Acad. Sci. USA, 2011,108,16628-16633.
14. Zhang, H., Zhang, S., Tao, G., Zhang, Y., Mulloy, B., Zhan, X. & Chai, W., Typing of Blood-Group Antigens on Neutral Oligosaccharides by Negative-Ion Electrospray Ionization Tandem Mass Spectrometry, Anal. Chem., 2013,85, 5940-5949.
15. Palma, A., Feizi, T., Childs, R.A.,Chai, W. & Liu, Y., The Neoglycolipid (NGL)-Based Oligosaccharide Microarray SystemPoised toDecipher the Meta-Glycome, Curr. Opin. Chem. Biol., 2014,in press.