Publications – University of Copenhagen

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CCG > Publications

Selected Publications 

A monoclonal antibody 5E5 developed by CCG towards a cancer specific glycopeptide has proven to be very effective in a new form of cancer immunotherapy called "Chimeric antigen receptor (CAR) T cell therapy".
In collaboration with one of the worlds leading  pioneers in this research area, Professor Carl June at University of Pennsylvania, the new 5E5 CAR therapy has been tested in mice with pancreatic cancer, and the results were so good that clinical trials may commence within the next two years.
Immunity 44(6): 1444–1454 (June, 2016)

Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. This knowledge enables dissection of specific functional roles of individual glycosites and provides a framework for design of glycoprotein vaccines with representative glycosylation.

J Biol Chem 291(23):12014-28. (June, 2016)

Dynamic interplay between catalytic and  domains of GalNAc-transferases modulates protein O-glycosylation. We present the first crystal structures of complexes of GalNAc-T2 with glycopeptides and demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Both a dynamic conformational landscape and a prominent role of compact structures of GalNAc-T2 are required for efficient catalysis. The results shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.
Nat Commun 6: 6937 (May, 2015)

A glycogene mutation map for discovery of diseases of glycosylation. Glycosylation of proteins and lipids involves over 200 known glycosyltransferases (GTs), and deleterious defects in many of the genes encoding these enzymes cause disorders collectively classified as congenital disorders of glycosylation (CDGs). Most known CDGs are caused by defects in glycogenes that affect glycosylation globally. Here, we constructed a draft of a functional mutational map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2000 Danes. We cataloged all missense mutations and used prediction algorithms, manual inspection and in case of carbohydrate-active enzymes family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP: http://glymap.glycomics.ku.dk

Glycobiology 25(2): 211-224 (February, 2015)

Glycoproteomic Analysis of Seven Major Allergenic Proteins Reveals Novel Post-translational Modifications. Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM1 characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. 

Mol Cell Proteomics 14: 191-204 (January, 2015)

Precision genome editing: A small revolution for glycobiology. Precise and stable gene editing in mammalian cell lines has until recently been hampered by the lack of efficient targeting methods. While different gene silencing strategies have had tremendous impact on many biological fields, they have generally not been applied with wide success in the field of glycobiology, primarily due to their low efficiencies, with resultant failure to impose substantial phenotypic consequences upon the final glycosylation products. Here, we review novel nuclease-based precision genome editing techniques enabling efficient and stable gene editing, including gene disruption, insertion, repair, modification and deletion.

Glycobiology 24(8): 663-680 (August, 2014)

High-efficiency genome editing

Genome editing using zinc finger nucleases or CRISPR/Cas9 nickase pairs is used for studying gene function and regulation. We have developed a method that increase editing efficiencies in standard routine genome manipulations combining co-expression of fluorescent protein followed by fluorescence-activated cell sorting which increase the genome editing rate.

Nucleic Acids Res 42(10): e84 (June, 2014)

A first map of the human O-glycoproteome

We have developed a genetic engineering approach using human cell lines to simplify O-glycosylation (SimpleCells) that enables proteome-wide discovery of O-glycan sites and implemented this on 12 human cell lines from different organs. Now we present a first map of the human O-glycoproteome with almost 3000 glycosites in over 600 O-glycoproteins as well as an improved NetOGlyc4.0 model for prediction of O-glycosylation.

EMBO J 32(10):1478-1488 (May, 2013)

Galnt11 modifies Notch

We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy, and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats.

Nature 504(7480):456-459 (December, 2013)