Brockhausen, Inka - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

The Brockhausen lab aims to understand the biochemical mechanisms underlying diseases such as inflammation, infections and cancer. Studies of the role of protein glycosylation in cell behaviour and cell death will reveal new mechanisms in cancer and inflammation. We also hope to develop novel therapeutic interventions based on our knowledge and inhibition of glycosyltransferase enzymes that glycosylate proteins in humans, and assemble the O-antigenic polysaccharides in pathogenic bacteria. Newly developed assays for glycosyltransferases help to characterize enzymes, reveal protein structure and function relationships, and design inhibitors which could 1. Reduce inflammation, 2. Reduce cancer metastasis and 3. Act as new antibiotics for Gram negative bacteria.

研究领域

Thousands of different structures of sugar chains are found on glycoproteins, however, the role of these glycans in health and disease is largely undefined. The longterm goal of our research is to obtain knowledge of the molecular mechanisms controlling the biosynthesis of glycoprotein-bound glycans, and to understand the role of glycans in cell growth, cell death and cell adhesion. These biological processes are important in inflammatory diseases such as rheumatoid arthritis, in cystic fibrosis, inflammatory bowel disease, cancer, and other diseases. Our Vision is to understand the biochemical mechanisms underlying the pathology of these diseases. We hope to develop novel therapeutic interventions based on the ability to re-engineer glycoprotein-bound glycans to normalize the biological functions of proteins. We are also interested in the biochemistry of O-antigenic polysaccharides in Gram negative bacteria. These complex carbohydrates function in the protection of microbes. We are developing specific biochemical assays for the enzymes involved in the biosynthesis of these polysaccharides in order to characterize the enzymes and to develop inhibitors as anti-biotic drug candidates.

近期论文

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Selected Reviews I Brockhausen, J Schutzbach, W Kuhns. Glycoproteins and their relationship to human disease. (1998) Acta Anat. 161: 36-78. I Brockhausen. Pathways of O-glycan biosynthesis in cancer cells. (1999) Biochim. Biophys. Acta, 1473: 67-95. I Brockhausen. The role of galactosyltransferases in cell surface functions and in the immune system. (2006) Drug News and Perspectives 19(7): 401-409. J Schutzbach, H Ankel, I Brockhausen. Synthesis of cell envelope glycoproteins of Cryptococcus laurentii. (2007) Carbohydr. Res. Glycobiology Protocols in Methods in Molecular Biology. I. Brockhausen Ed. (2006) Humana Press. I Brockhausen. Biochemical Aspects: Biosynthesis of O-glycans. In Comprehensive Glycosciences, From Chemistry to Systems Biology. (2007) Elsevier. I Brockhausen. Structure and function of glycosyltransferases specific for O-glycan processing. (2007) In Glycobiology, Scion Publ. Woodbury NY. J. Schutzbach, I Brockhausen. Inhibition of glycosyltransferase activities as the basis for drug development. (2009) Methods in Molecular Biology, Humana Press, Totowa, NY. 534: 1-15. I Brockhausen. biosynthesis of complex mucin-type O-glycans. (2009) Comprehensive Natural Products Chemistry II Volume 5, Carbohydrates, nucleosides and nucleic acids. G. Wang Ed. Elsevier. Selected papers I Brockhausen, J Yang, J Burchell, C Whitehouse, J Taylor-Papadimitriou. Mechanism underlying aberrant glycosylation of the MUC1 mucin in breast cancer cells. (1995) Eur. J. Biochem., 233: 607-617. C Whitehouse, J Burchell, S Gschmeissner, I Brockhausen, K Lloyd, J Taylor-Papadimitriou. A transfected sialyltransferase that is elevated in breast cancer and localizes to the medial/trans-Golgi apparatus inhibits the development of core 2-based O-glycans. (1997) J. Cell Biol., 137:1229-1241. I Brockhausen, J Yang, N Dickinson, S Ogata, S Itzkowitz. Enzymatic basis for sialyl-Tn expression in human colon cancer cells. (1998) Glycoconj. J., 15: 595-603. I Brockhausen, M Lehotay, J Yang, W Qin, D Young, J Lucien, J Coles, H Paulsen. Glycoprotein biosynthesis in porcine aortic endothelial cells and changes in the apoptotic cell population. (2002) Glycobiology, 12: 33-45. X Yang, W Qin, M Lehotay, D Toki, P Dennis, J Schutzbach, I Brockhausen. Soluble human core 2 beta6-GlcNAc-transferase requires its conserved Cys residues for full activity (2003) Biochim. Biophys. Acta, 1648:62-74. X Yang, M Lehotay, T Anastassiades, M Harrison, I Brockhausen. The effect of TNFalpha on glycosylation pathways in bovine synoviocytes. (2004) Biochemistry and Cell Biology, 82(5):559-568. DS McBride, I Brockhausen. FWK Kan. Detection of glycosyltransferases in the golden hamster (Mesocricetus auratus) oviduct and evidence forthe regulation of O-glycan biosynthesis during the estrus cycle. (2005) Biochim. Biophys. Acta, 1721:107-115. JG. Riley, M Menggad, P Montoya-Peleaz, WA. Szarek, CL Marolda, MA Valvano, JS Schutzbach, I Brockhausen. The wbbD gene of E. coli strain VW187 (O7:K1) encodes a UDP-Gal: GlcNAc(alpha)-pyrophosphate-R (beta)1,3-galactosyltransferase involved in the biosynthesis of O7-specific lipopolysaccharide. (2005) Glycobiology, 15: 605-613. I Brockhausen, M Benn, S Bhat, S Marone, JG, Riley J, P Montoya-Peleaz, JZ Vlahakis, H Paulsen, JS Schutzbach, W Szarek. UDP-Gal: GlcNAc-R beta1,4-Galactosyltransferase - a target enzyme for drug design. Acceptor specificity and inhibition of the enzyme. (2006) Glycoconj. J., 23: 523-539. X Yang, J Yip, T Anastassiades, M Harrison, I Brockhausen. The action of TNFalpha and TGFbeta include specific alterations of the glycosylation of bovine and human chondrocytes. (2006) Biochim. Biophys. Acta. Y Li, X Yang, A Nguyen, I Brockhausen. Requirement of N-glycosylation for the secretion of recombinant extracellular domain of human Fas in heLa cells. (2007) Internat. J. Biochem. Cell Biol. 39: 1625-1636. X Yang, J Yip, M Harrison, I Brockhausen. Primary human osteoblasts and bone cancer cells as models to study glycodynamics in bone. (2007) Internat. J. Biochem. Cell Biol. I Brockhausen, J Riley, M Joynt, X Yang, WA Szarek. Acceptor substrate specificity of UDP-Gal: GlcNAc-R b1,3-galactosyltransferase from Escherichia coli O7:K1. (2008) glycoconj. J. 25: 663-673. I Brockhausen, B Liu, B Ju, K Lau, W Szarek, L Wang, L Feng. Characterization of two UDP-GlcNAcNAc: b1,3-glucosyltranferases from the Escherichia coli serotypes O56 and O152. (2008) J. Bacteriol. 190: 4922-4932.