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primary research areas

overview
A dense layer (glycocalyx) of glycoproteins, glycolipids, and proteoglycans cover the surface of cells. The individual glycoconjugates participate in a wide variety of biological phenomena in both health and disease, such as cell differentiation, proliferation, migration, and morphogenesis. This variety of biological impact is mediated by the interaction of glycoconjugates to growth factors, enzymes, and extracellular matrix proteins. Such interactions are partly determined by the structure and binding properties of the polysaccharide chains (glycans) of the various classes of glycoconjugates. The assembly of these molecules involves multiple glycosyltransferases. Using chemistry, biochemistry and genetics we search to understand the structure and function of glycans in health and disease.

current research

cancer biology
Projects include studies of the importance of glycans in the generation of autologous anti-tumor responses. In collaboration with Henrik Clausen, Ola Blixt, and Eric P. Bennett we use micro array strategies searching for tumor specific biomarkers. This group has a particular focus on gastro-intestinal-, CNS-, and lung cancer. Furthermore we study the use of glycosphingolipids and O-linked glycans to generate vaccine strategies for the treatment of cancer.

assembly of glycans
Studies include analysis of the large family of polypeptide GalNAc-transferases that initiate O-linked glycosylation.

glycolipids in development

Projects include studies of development of the neural systems in drosophila melanogaster in which the glycosphingolipid biosynthetic pathway has been manipulated. Furthermore we aim to understand how glycosphingolipids impinge on receptor signaling in vivo.

Confocal immunofluorescence image of a Drosophila melanogaster stage 8 egg chamber mutant for brainiac, showing a strong accumulation of truncated glycosphingolipids (red staining) in follicle cells (marked by the absence of green fluorescent protein staining). Nuclei are stained blue. Glycosphingolipid synthesis is arrested in follicle cell mutants for the glycosyltransferase gene brainiac.
 

platelet glycobiology
In collaboration with Dr. Karin Hoffmeister (Brigham and Women’s Hospital, Boston) studies include analysis of platelet glycosyltransferases and the importance of surface glycans for the clearance of platelets. 

Megakaryocyte under differentiation with green Golgi, red alpha-granules, and blue Nucleus.

work in the lab has been funded by the following agencies:

Danish Council for Science, Technology and Innovation & Danish Medical Research Council & The Lundbeck Foundation & Novo Nordisk Foundation & Danish Cancer Research Foundation

collaborators

Henrik Clausen, Dept. of Cellular and Molecular Medicine, Copenhagen University
Ola Blixt, Dept. of Cellular and Molecular Medicine, Copenhagen University
Eric P. Bennett, Institute of Odontology - Section Y
Anders E. Pedersen, Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen
Steen S. Poulsen, Endocrinology Research Section, University of Copenhagen 
Ole Kjærulff, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen
Usha Menon & Aleksandra Gentry-Maharaj, Institute for Women's Health, University College London, UK 
Karin M. Hoffmeister, Brigham and Women's Hospital, Harvard University
Steven M Cohen, Temasek Life Sciences Laboratory, Singapore

selected publications

• Catharina Steentoft, Sergey Y. Vakhrushev, Malene B. Vester-Christensen, Katrine T-B. G. Schjoldager, Yun Kong, Eric Paul Bennett, Ulla Mandel, Hans H. Wandall, Steven B. Levery, and Henrik Clausen.
  A method to mine the elusive O-glycoproteome using Zinc finger nuclease glycoengineered SimpleCells. Nature Methods. 2011 Oct 9. doi: 10.1038/nmeth.1731. [Epub ahead of print]

• Pedersen JW, Bennett EP, Schjoldager KT, Meldal M, Holmer AP, Blixt O, Clo E, Levery SB, Clausen H, Wandall HH.
  Lectin domains of polypeptide GalNAc-transferases exhibit glycopeptide binding specificity. J Biol Chem. 2011 Jul 15.

• Johannes W. Pedersen, Ola Blixt, Eric P. Bennett, Mads A. Tarp, Imran Dar, Ulla Mandel1,2, Steen S. Poulsen, Anders E. Pedersen4, Susanne Rasmussen, Per Jess, Henrik Clausen, and Hans H. Wandall
  Seromic profiling of colorectal cancer patients with novel glycopeptide microarray. Int. J. Cancer. 2010. Nov.

• Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U, Ragupathi G, Livingston PO, Hollingsworth MA, Taylor-Papadimitriou J, Burchell J, Clausen H.
  Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010 Feb 1. Epub 2010 Feb 2.

• Viktoria Rumjantseva, Prabhjit K. Grewal, Hans H. Wandall, Emma C. Josefsson, Sara Neyeb-Hashemi, Goran Larson, Jamey D. Marth, John H. Hartwig, Karin M. Hoffmeister.
  Dual roles for lectin receptors in the clearance of chilled platelets. Nature Medicine. Published online: 27 September 2009 | 10.1038/nm.2030

• Anne Louise Sørensen, Viktoria Rumjantseva, Sunita Patel-Hett1, Jennifer Richardson1, Joseph E. Italiano Jr, John H. Hartwig, Hans H. Wandall*, and Karin M. Hoffmeister*.
  Role of sialic acid for platelet lifespan: exposure of βgalactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. Blood. 2009 Jun 11. * Corresponding authors

• Anne Louise Sørensen, Karin M. Hoffmeister, and Hans H. Wandall*.
  Glycans and glycosylation of platelets: current concepts and implications for transfusion. (2008) Current Opinion in Hematology. Review. Nov;15(6).

• Wandall HH, Hoffmeister KM, Sorensen AL, Rumjantseva V, Clausen H, Hartwig JH, Slichter SJ (2008)
  Galactosylation does not prevent the rapid clearance of long-term 4°C stored platelets. Blood. 111(6):3249-56.

• Wandall HH, Irazoqui F, Tarp MA, Bennett EP, Mandel U, Takeuchi H, Kato K, Irimura T, Suryanarayanan G, Hollingsworth MA, Clausen H (2007).
  The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate binding specificity for GalNAc: Lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation. Glycobiology 17:374-87.

• Wandall HH, Pizette S, Pedersen JW, Eichert H, Levery SB, Mandel U, Cohen SM, Clausen H (2005)
  Egghead and brainiac are essential for glycosphingolipid biosynthesis in vivo. J Biol Chem 280:4858-63.

• Wandall HH, Pedersen JW, Park C, Levery SB, Pizette S, Cohen SM, Schwientek T, Clausen H. (2003)
  Drosophila egghead encodes a β1,4mannosyltransferase predicted to form the immediate precursor glycosphingolipid substrate for Brainiac. J Biol Chem 278:1411-4

• Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H (1997) Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem 272:23503-14.