wandall, hans – Københavns Universitet

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Hans H. Wandall

associate professor, MD, PhD

e-mail: hhw@sund.ku.dk
telephone: (+45) 23 84 01 56
room: 24.6.38

 

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 novel genome editing techniques with engineered nucleases, biochemistry, advanced cell culture systems, and proteomics, we search to understand the structure, location, and function of glycans in health and disease.

current research

Projects include characterization of the structure and location of specific glycans on proteins. Using advanced cell culture systems we examine how specific glycan structures are involved in an array of biological functions including the transformation of healthy epithelial cells to invasive cancer cells. In addition we explore the use of glycans as specific tumor biomarkers with a particular interest in colorectal carcinomas. Furthermore we use glycans to generate vaccine strategies for the treatment of cancer and allergies.

The use of a novel genome editing technology has the power to redesign most living organisms with exquisite precision, speed and cost-effectiveness. We have created the Copenhagen Consortium for Designer Organisms as a leading knowledge center on precise genetic engineering using nuclease-based technologies.
For more information please see http://www.cdo.ku.dk/

Production of APC Targeted Allergy Vaccines (APCGlyVac)
We hypothesize that recombinant allergy vaccines with defined carbohydrates will target APCs and enhance efficiency, induce tolerance at lower dosages, and possibly reduce side-effects. This proposal aims to explore the potential for enhancing efficiency of recombinant allergens vaccines against major allergens by targeting these to APCs through specific glycosylation patterns

Probing function of O-glycosylation by an organotypic skin model
This project is dedicated to the discovery and molecular dissection of functions of protein glycosylation with a particular emphasis on O-linked protein glycosylation.

cell lines expressing tailor made glycans We use novel genome editing techniques with engineered nucleases to create cell lines expressing glycan structures.

TEM micrographs of cross-sections of Drosophila melanogaster peripheral nerves from wild type (Left)

glycans in tissue development
and formation We use the combination of novel genome targeting techniques and complex mammalian cell systems to decipher the function of specific glycans in biological systems. In addition we use drosophila melanogaster in which the glycan biosynthetic pathways have been manipulated.

 

platelet glycobiology

Studies include analysis of platelet glycosyltransferases and the importance of surface glycans for the function 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:
UCPH Excellence Programme (2016 Funds), Danish Council for Science,
Danish Strategic Research Council,
Danish Medical Research Council,
The Lundbeck Foundation,
Novo Nordisk Foundation,
Danish National Research Foundation
The Danish Council for Strategic Research, as represented by the Programme Commission on Strategic Growth Technologies

 

collaborators

Sally Dabelsteen, Institute of Odontology.
Anders Woetmann and Niels Ødum, Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen.
Morten Frödin, BRIC,
Cord Brakebusch, BRIC,
Anders E. Pedersen, Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, 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.
Hans-Henrik Ipsen, ALK-Abello A/S
Bent Larsen Petersen, Department of Plant- and Environmental science, Plantglycobiology

selected publications

  • Johannes W. Pedersen, Aleksandra Gentry-Mahara, Evangelia-Ourania Fourkala, Anne Dawnay, Matthew Burnell, Alexey Zaikin, Anders E. Pedersen, Ian Jacobs, Usha Menon, and Hans H. Wandall Early detection of colorectal cancer in the general population - a blinded case control study of p53 auto-antibodies. Br J. Cancer. 2012. Jan 15.
  • Anne Louise Tølbøll Sørensen, Henrik Clausen, Hans H Wandall. Carbohydrate Clearance Receptors in Transfusion Medicine. (Review Article). BBA - General Subjects. 2012. Jul 27
  • Hans H. Wandall, Viktoria Rumjantseva2, Anne Louise Tølbøll Sørensen, Sunita Patel-Hett2, Emma C. Josefsson, Eric P. Bennett, Joseph E. Italiano Jr., Henrik Clausen, John H. Hartwig, and Karin M. Hoffmeister. The origin and function of platelet glycosyltransferases. Blood. 2012 Jul 120(3).
  • Katrine T-B. G. Schjoldager , Sergey Y Vakhrushev , Yun Kong , Catharina Steentoft , Aaron S Nudelman , Nis B Pedersen , Hans H Wandall , Ulla Mandel , Eric P Bennett , Steven B Levery , Henrik Clausen. Probing Isoform-specific Functions of Polypeptide GalNAc-Transferases Using Zinc Finger Nuclease Glycoengineered SimpleCells. Proc Natl Acad Sci U S A. 2012 Jun 19;109(25): Epub 2012 May 7.
  • Dahlgaard K, Jung A, Qvortrup K, Clausen H, Kjaerulff O*, Wandall HH*. Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. Proc Natl Acad Sci U S A. 2012 May 1;109(18)
  • 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.
  • 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.
  • 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
  • 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)
  • 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.