Hans H. Wandall

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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.

 

Primary fields of research

• 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

Current research

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.

Precise Cancer Targeting of Cancer Associated Glycans Changes in protein and lipid glycosylation are one of the most consistent alterations in human cancers. We use the next generation of genetically engineered 3D tissue models to systematically address the effect of cancer associated glycans in cancer biology and to develop cancer specific treatments. We have identified O-linked glycosylation signatures on proteins and developed a series of cancer specific mAbs to exploit O-glycan signatures for the precise targeting of cancer.

GlycoVirology: Probing the Functions of Glycosylation in Viral Biology  This project aims to 1) characterize glycans on enveloped viruses using mass spectrometry and 2) to examine the glycan functions in virus biology using our comprehensive library of genetically engineered cells. We particularly focus on the importance of site-specific O-glycosylation. We have demonstrated that HSV-1 and other herpesviruses are heavily O-glycosylated and that this type of glycosylation is important for virus propagation and early immune sensing. The project will expand our knowledge on glycosylation in virus biology and help develop antivirals and vaccines. The project is heading by Assistant Professor Dr. Ieva Bagdonaite.

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 continuously implement the novel precise genetic engineering technologies.

Our work has been funded by the following agencies:

UCPH 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, Danish National Research Program "Sapere Aude – Project leader”, European Research Council - "ERC Consolidator Grant", NEYE Foundation,

Collaborators

• 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.

Highlights

GlycoSkin

• Development of a glycoengineered organotypic epithelial tissue model
• A systematic interrogation of glycan functions in human tissue formation and homeostasis
• Combined with mass spectrometry the model is a resource for further identification of glycan molecular functions.
• Aim is to examine the potential link between changes in glycans structures and stemness, tissue rejuvenation, cellular stress, cancer, and aging

Dabelsteen, S, Pallesen, EM,……Wandall HH
Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model. Developmental Cell. 2020. 

Bagdonaite I, Pallesen EM, ….. Wandall HH.
O-glycan initiation directs distinct biological pathways and controls epithelial differentiation. EMBO Rep. 2020 

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.

Possible conflicts of interest

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.