Summary
Dr Chai is a Senior Research Fellow of the Glycosciences Laboratory and Wellcome Trust supported Carbohydrate Microarray Resource, Department of Medicine. As a trained chemist he 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.
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 the detection 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 the essential 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.
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Selected Publications
Journal Articles
Gao T, Yan J, Liu C-C, et al., 2019, Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope, Journal of the American Chemical Society, Vol:141, ISSN:0002-7863, Pages:19351-19359
Wu N, Silva LM, Liu Y, et al., 2019, Glycan Markers of Human Stem Cells Assigned with Beam Search Arrays., Molecular & Cellular Proteomics, Vol:18, ISSN:1535-9476, Pages:1981-2002
Yan J, Ding J, Jin G, et al., 2019, Profiling of Human Milk Oligosaccharides for Lewis Epitopes and Secretor Status by Electrostatic Repulsion Hydrophilic Interaction Chromatography Coupled with Negative-Ion Electrospray Tandem Mass Spectrometry, Analytical Chemistry, Vol:91, ISSN:0003-2700, Pages:8199-8206
Li Z, Chai W, 2019, Mucin <i>O</i>-glycan microarrays, Current Opinion in Structural Biology, Vol:56, ISSN:0959-440X, Pages:187-197
Sun S, Huang C, Wang Y, et al., 2018, Toward Automated Identification of Glycan Branching Patterns Using Multistage Mass Spectrometry with Intelligent Precursor Selection, Analytical Chemistry, Vol:90, ISSN:0003-2700, Pages:14412-14422
Chai W, Zhang Y, Mauri L, et al., 2018, Assignment by Negative-Ion Electrospray Tandem Mass Spectrometry of the Tetrasaccharide Backbones of Monosialylated Glycans Released from Bovine Brain Gangliosides, Journal of the American Society for Mass Spectrometry, Vol:29, ISSN:1044-0305, Pages:1308-1318
Yan J, Ding J, Jin G, et al., 2018, Profiling of sialylated oligosaccharides in mammalian milk using online solid phase extraction-hydrophilic interaction chromatography coupled with negative-ion electrospray mass spectrometry, Analytical Chemistry, Vol:90, ISSN:0003-2700, Pages:3174-3182
Mulloy B, Wu N, Gyapon-Quast F, et al., 2016, Abnormally high content of free glucosamine residues identified in a preparation of commercially available porcine intestinal heparan sulfate, Analytical Chemistry, Vol:88, ISSN:1520-6882, Pages:6648-6652
Gao C, Zhang Y, Liu Y, et al., 2015, Negative-Jon Electrospray Tandem Mass Spectrometry and Microarray Analyses of Developmentally Regulated Antigens Based on Type 1 and Type 2 Backbone Sequences, Analytical Chemistry, Vol:87, ISSN:1520-6882, Pages:11871-11878
Zhang H, Zhang S, Tao G, et al., 2013, Typing of Blood-Group Antigens on Neutral Oligosaccharides by Negative-Ion Electrospray Ionization Tandem Mass Spectrometry, Analytical Chemistry, Vol:85, Pages:5940-5949-5940-5949
Kaiser H-J, Orlowski A, Rog T, et al., 2011, Lateral sorting in model membranes by cholesterol-mediated hydrophobic matching, Proceedings of the National Academy of Sciences of the United States of America, Vol:108, ISSN:0027-8424, Pages:16628-16633
Childs RA, Palma AS, Wharton S, et al., 2009, Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray, Nat.biotechnol., Vol:27, Pages:797-799
Beeson JG, Andrews KT, Boyle M, et al., 2007, Structural basis for binding of <i>Plasmodium falciparum</i> erythrocyte membrane protein 1 to chondroitin sulfate and placental tissue and the influence of protein polymorphisms on binding specificity, Journal of Biological Chemistry, Vol:282, ISSN:0021-9258, Pages:22426-22436
Liu Y, Feizi T, Campanero-Rhodes MA, et al., 2007, Neoglycolipid probes prepared via oxime ligation for microarray analysis of oligosaccharide-protein interactions, Chem.biol., Vol:14, Pages:847-859
Palma AS, Feizi T, Zhang YB, et al., 2006, Ligands for the β-glucan receptor, Dectin-1, assigned using "designer" microarrays of oligosaccharide probes (neoglycolipids) generated from glucan polysaccharides, Journal of Biological Chemistry, Vol:281, Pages:5771-5779
Feizi T, Chai WG, 2004, Oligosaccharide microarrays to decipher the glyco code, Nature Reviews Molecular Cell Biology, Vol:5, ISSN:1471-0072, Pages:582-588
Fukui S, Feizi T, Galustian C, et al., 2002, Oligosaccharide microarrays for high-throughput detection and specificity assignments of carbohydrate-protein interactions, Nature Biotechnology, Vol:20, ISSN:1087-0156, Pages:1011-1017
Chai WG, Beeson JG, Lawson AM, 2002, The structural motif in chondroitin sulfate for adhesion of <i>Plasmodium falciparum</i>-infected erythrocytes comprises disaccharide units of 4-<i>O</i>-sulfated and non-sulfated <i>N</i>-acetylgalactosamine linked to glucuronic acid, Journal of Biological Chemistry, Vol:277, ISSN:0021-9258, Pages:22438-22446
Chai W, Pisvarev V, Lawson AM, 2001, negative-ion electrospray mass spectrometry of neutral underivatized oligosaccharides, Analytical Chemistry, Vol:73, ISSN:0003-2700, Pages:651-657
Beeson JG, Rogerson SJ, Cooke BM, et al., 2000, Adhesion of <i>Plasmodium falciparum</i>-infected erythrocytes to hyaluronic acid in placental malaria, Nature Medicine, Vol:6, ISSN:1078-8956, Pages:86-90
Chai WG, Yuen CT, Kogelberg H, et al., 1999, High prevalence of 2-mono- and 2,6-di-substituted Manol-terminating sequences among O-glycans released from brain glycopeptides by reductive alkaline hydrolysis, European Journal of Biochemistry, Vol:263, ISSN:0014-2956, Pages:879-888
Chai WG, Luo JL, Lim CK, et al., 1998, Characterization of heparin oligosaccharide mixtures as ammonium salts using electrospray mass spectrometry, Analytical Chemistry, Vol:70, ISSN:0003-2700, Pages:2060-2066