Wandall Group

Modeling Glycobiology

Glycans decorate most proteins and cover all our cell membranes, yet our understanding of how glycans influence the lives of cells and organisms is limited.

We use gene editing, organotypic tissue models, and sophisticated mass spectrometry to decipher glycan functions. The genetically engineered cells and organotypic tissue model have provided evidence of the importance of glycans in tissue differentiation, cancer, and host-pathogen interactions.

We now use organotypic tissue models for broad discovery and dissection of the specific structure-function relationships by which glycans drive normal epithelial formation, transformation and interaction with viruses and the microbiome.

We aim to exploit this knowledge for new and targeted treatments for inflammation, cancer, tissue regeneration, and the development of novel viral vaccine strategies.

• Glycan functions in tissue homeostasis, stem cell biology, and regenerative medicine
• Glycans in host-pathogen interactions (Bacteria, Virus, and parasites)
• Creation of disease models
• Impact of glycans on inflammation, cancer, and degenerative diseases

GlycoSkin. Our understanding of how glycans influence the life of cells and organisms is limited, and only few functions have been molecularly dissected. We will use step-by-step genetic deconstruction of glycosylation capacities in organotypic tissue models for broad discovery and dissection of specific structure-function relationships driving normal epithelial formation, cancer transformation and interaction between the host and the microbiome.

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.

Copenhagen as the next generation leader in precise genome engineering: 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.

Novel proteome-wide discovery strategy for O-glycosylation sites on viral envelope proteins using herpes simplex virus type 1 (HSV-1) as a model. We identified 74 O-linked glycosylation sites on 8 out of the 12 HSV-1 envelope proteins. With the use of precise gene editing, we further demonstrate that elongated O-glycans are essential for HSV-1 in human HaCaT keratinocytes.

Bagdonaite I, Nordén R, Joshi HJ, Dabelsteen S, Nyström K, et al. (2015) A Strategy for O-Glycoproteomics of Enveloped  Viruses—the O-Glycoproteome of Herpes Simplex Virus Type 1. PLoS Pathog 11(4): e1004784.

Uncovering the function of cancer associated glycan changes using simplified cells and simplified tissues. We demonstrate, with the use of well-defined cell systems generated by precise gene editing, that the aberrant O-glycophenotype by itself induces oncogenic features with enhanced growth and invasion.

Truncation of O-linked glycans down regulate intercellular adhesion and promote invasion of keratinocytes in organotypic cultures

See comment in Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14009-10. Not so sweet malignant transformation. Baenziger JU.

Our work has been funded by the following agencies:

• CPH Excellence Programme (2016 ,Facul 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

Genetic engineering, simple cells, and simplified skin tissues:

• Radhakrishnan P, Dabelsteen S, Madsen FB, Francavilla C, Kopp KL, Steentoft C, Vakhrushev SY, Olsen JV, Hansen L, Bennett EP, Woetmann A, Yin G, Chen L, Song H, Bak M, Hlady RA, Peters SL, Opavsky R, Thode C, Qvortrup K, Schjoldager TBG, Clausen H, Hollingsworth MA, and Wandall, HH Immature truncated O-glycophenotype of cancer directly induces oncogenic features. Proc Natl Acad Sci USA 2014, August 11.
  
  
• 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 USA 2012 May 1;109(18)
  
  
• 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 USA. 2012 Jun 19;109(25): Epub 2012 May 7.
  
  
• 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.

 Glycans in Immunity, Virology, and Cancer:

• Bagdonaite I, Nordén R, Joshi HJ, Dabelsteen S, Nyström K, Vakhrushev SY, Olofsson S, Wandall HH. A Strategy for O-Glycoproteomics of Enveloped Viruses-the O-Glycoproteome of Herpes Simplex Virus Type 1.PLoS Pathog. 2015 Apr 1
  
  
• 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.
  
  
• 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. 2011, Apr 128(8). Epub 2011 Jan 12.
  
  
• Pedersen JW, Gentry-Maharaj A, Nøstdal A, Fourkala EO, Dawnay A, Burnell M, Zaikin A, Burchell J, Papadimitriou JT, Clausen H, Jacobs I, Menon U, Wandall HH. Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Int J Cancer. 2013 Oct 11.
  
  
• 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.
  
  
• Caroline B. Madsen, Anders E. Pedersen and Hans H. Wandall. Glycan-mediated modification of the immune response. OncoImmunology. Volume 2, Issue 4   April 2013

Glycans and Glycosyltransferases in hematology:

• 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).
  
  
• 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)

• ALK-Abello A/S
• Cord Brakebusch, BRIC,
• Sally Dabelsteen, Department of Odontology of Health Sciences, University of Copenhagen.
• Morten Frödin, BRIC,
• Michael Hollingsworth, University of Nebraska, Omaha, NE
• Usha Menon & Aleksandra Gentry-Maharaj, Institute for Women's Health, University College London, UK.
• Sigvard Olofsson, University of Gothenburg
• Anders E. Pedersen, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen.
• Bent Larsen Petersen, Department of Plant- and Environmental science, Plant Glycobiology
• Søren Skov, Department of Veterinary Disease Biology, University of Copenhagen.
• Steffen Thiel, Department of Biomedicine, Aarhus
• Anders Woetmann and Niels Ødum, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen.

• Consultant for and founder of GO-therapeutics focusing on development of antibodies for immunotherapy of cancer (http://gotherapeutics.com). 

• Co-founder and consultant for early stage biotech initiative for the development of antibodies to various non-glycosylated targets (Ebumab Aps & Hemab Aps). 

• Established Wandall ApS to control consultant activities. 

The Danish Council for Strategic Research, as represented by the Programme Commission on Strategic Growth Technologies

Danish National Research Program "Sapere Aude – Project leader”

European Research Council - "ERC Consolidator Grant"