Our projects

Our projects

Infection and Immuno-Glycobiology

Front cover of Mol Cell Proteomics, August 2017
(from Loke et al., Mol Cell Proteomics. 16(8):1507-1527. 2017)

With a focus on understanding basic molecular mechanisms in innate glycoimmunology, we are currently exploring various acquired infectious diseases e.g. tuberculosis and HIV, inherited immune-related diseases e.g. cystic fibrosis and rare lysosomal diseases e.g. Tay-Sachs/Sandhoff diseases using advanced glycoproteomics and glycomics technologies and methods in molecular and cellular glycobiology. Deciphering the glycobiological processes existing within and between neutrophils and macrophages are of particular interest.

Disease/Physiology of interest:

Tuberculosis, cystic fibrosis, HIV, Tay-Sachs disease, Sandhoff disease

Keywords:

Neutrophil, macrophage, host-pathogen interaction, innate immunology, myeloperoxidase, glycoimmunology, granule biology, biosynthesis, carbohydrate binding protein (lectin), paucimannose, β-hexosaminidase, lysosome, extracellular vesicle, cell-cell communication

Representative publications:
  1. H Hinneburg, J L Pedersen, N J Bokil, A Pralow, F Schirmeister, R Kawahara, E Rapp, B M Saunders, M Thaysen-Andersen. High-resolution longitudinal N- and O-glycoprofiling of human monocyte-to- macrophage transition. Glycobiology. 2020.
  2. Loke I, Østergaard O, Heegaard NHH, Packer NH, Thaysen-Andersen M. Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions. Mol Cell Proteomics. 16(8):1507-1527. 2017.
  3. Hare NJ, Lee LY, Loke I, Britton WJ, Saunders BM, Thaysen-Andersen M. Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and Their Microparticles. J Proteome Res. 16(1):247-263. 2016.
  4. Loke I, Kolarich D, Packer NH, Thaysen-Andersen M. Emerging roles of protein mannosylation in inflammation and infection. Mol Aspects Med. 51:31-55. 2016.
  5. Thaysen-Andersen M, Venkatakrishnan V, Loke I, Laurini C, Diestel S, Parker BL, Packer NH. Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum. J Biol Chem. 290(14):8789-802. 2015.

Blood Glycobiology

From Sumer-Bayraktar et al., J Biol Chem. 291(34):17727. 2016.

Decoding the glycobiology of the many highly glycosylated proteins circulating in blood is key to an improved understanding of human health and disease. We are exploring the immune-modulatory roles of central hepatic glycoproteins e.g. corticosteroid binding globulin (CBG), acute phase glycoproteins e.g. alpha-1-antitrypsin (A1AT) and key leukocyte factors e.g. neutrophil elastase (NE) and their involvement in the regulation of pathogen-triggered and sterile systemic and local inflammation via the delivery of anti-inflammatory cortisol and related innate immune processes.

Disease/physiology of interest:

Sepsis, bacteremia, pregnancy, blood stream infections

Keywords:

Corticosteroid binding globulin, corticosteroids, acute phase proteins, oral contraception, serum glycoproteomics, blood cell biology, blood infections, proteolysis, systemic inflammation.

Representative publications:
  1. Sumer-Bayraktar Z, Grant OC, Venkatakrishnan V, Woods RJ, Packer NH, Thaysen-Andersen M. Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase. J Biol Chem. 291(34):17727-42. 2016.
  2. Sumer-Bayraktar Z, Nguyen-Khuong T, Jayo R, Chen DD, Ali S, Packer NH, Thaysen-Andersen M. Micro- and macroheterogeneity of N-glycosylation yields size and charge isoforms of human sex hormone binding globulin circulating in serum. Proteomics. 12(22):3315-27. 2012.
  3. Sumer-Bayraktar Z, Kolarich D, Campbell MP, Ali S, Packer NH, Thaysen-Andersen M. N-glycans modulate the function of human corticosteroid-binding globulin. Mol Cell Proteomics. 10(8):M111.009100. 2011.

Cancer Glycobiology

Front cover of Glycobiology, 2016
(from Sethi et al., Glycobiology. 25(10):1064-78. 2015.)

Tumour micro-environments comprise extremely heterogeneous populations of cells and biomolecules in the extracellular matrix that communicate via glycoprotein-lectin interactions to facilitate pro- and anti-cancerous processes. We are using advanced mass spectrometry in conjunction with methods in biochemistry and molecular and cellular biology to understand the roles of the aberrant glycoproteome in the tumour micro-environment. Understanding the glycobiology of the immune component of tumour development and progression is of particular interest.

Disease/physiology of interest:

Prostate cancer, colorectal cancer, pan-cancer

Keywords:

Lysosomes, tumour micro-environment, tumour associated neutrophil, tumour associated macrophage, M6P-glycosylation, paucimannose, glycoproteomics, extracellular vesicle, glycosylation machinery, hydrolase.

Representative publications:
  1. Kawahara R, Ortega F, Rosa-Fernandes L, Guimarães V, Quina D, Nahas W, Schwämmle V, Srougi M, Leite KRM, Thaysen-Andersen M, Larsen MR, Palmisano G. Distinct urinary glycoprotein signatures in prostate cancer patients. Oncotarget. 9(69):33077-33097. 2018.
  2. Sethi MK, Kim H, Park CK, Baker MS, Paik YK, Packer NH, Hancock WS, Fanayan S, Thaysen-Andersen M. In-depth N-glycome profiling of paired colorectal cancer and non-tumorigenic tissues reveals cancer-, stage- and EGFR-specific protein N-glycosylation. Glycobiology. 25(10):1064-78. 2015.
  3. Thaysen-Andersen M, Thøgersen IB, Nielsen HJ, Lademann U, Brünner N, Enghild JJ, Højrup P. Rapid and individual-specific glycoprofiling of the low abundance N-glycosylated protein tissue inhibitor of metalloproteinases-1. Mol Cell Proteomics. 6(4):638-47. 2007.

Glycoproteomics and Glycomics

From Hinneburg et al., Analytical Chemistry, 91(7):4559-67. 2019.

Much of our research is conducted using advanced mass spectrometry-based glycomics and glycoproteomics. We continue to work towards improving the performance and applicability of these powerful ‘omics technologies by optimising the sample handling and processing (less bias, more automation), improving the LC-MS/MS-based separation and detection (more structural information, and a higher accuracy and glyco(proteo)me coverage) and enabling a more confident assignment of mass spectral data of intact glycans and glycopeptides (higher confidence and automation).

Keywords:

Enrichment, HILIC, TiO2, SPE, derivatisation, post-column makeup flow, LC-MS/MS, isotopic labelling, multiplexing, glycan, glycopeptide, dissociation methods, acquisition strategies, informatics tools, Human Glycoproteomics Initiative (HGI).

Representative publications:
  1. Hinneburg H, Chatterjee S, Schirmeister F, Nguyen-Khuong T, Packer NH, Rapp E, Thaysen-Andersen M. Post-Column Make-up Flow (PCMF) Enhances the Performance of Capillary-Flow PGC-LC-MS/MS-Based Glycomics. Anal Chem. 2019. doi: 10.1021/acs.analchem.8b05720. [Epub ahead of print]
  2. Thaysen-Andersen M, Packer NH, Schulz BL. Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease. Mol Cell Proteomics. 15(6):1773-90. 2016.
  3. Mysling S, Palmisano G, Højrup P, Thaysen-Andersen M. Utilizing ion-pairing hydrophilic interaction chromatography solid phase extraction for efficient glycopeptide enrichment in glycoproteomics. Anal Chem. 82(13):5598-609. 2010.
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