Our research

Investigating glycosylation pathways in health

Our team uncovers how cell-surface sugars guide the immune system, combining cutting-edge mass spectrometry with molecular biology to better understand cancer and infectious diseases.

Learn more about our main research themes and associated projects below.

Blood glycobiology

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 eg corticosteroid binding globulin (CBG), acute phase glycoproteins eg alpha-1-antitrypsin (A1AT) and key leukocyte factors eg 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.

• Serum N-glycomics stratifies bacteremic patients infected with different pathogens
• Structural and functional diversity of neutrophil glycosylation in innate immunity and related disorders
• Protein paucimannosylation is an enriched N‐glycosylation signature of human cancers
• Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase
• Micro- and macroheterogeneity of N-glycosylation yields size and charge isoforms of human sex hormone binding globulin circulating in serum
• N-glycans modulate the function of human corticosteroid-binding globulin

Cancer glycobiology

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.

• Trends in oligomannosylation and α1, 2-mannosidase expression in human cancers
• The complexity and dynamics of the tissue glycoproteome associated with prostate cancer progression
• Distinct urinary glycoprotein signatures in prostate cancer patients
• In-depth N-glycome profiling of paired colorectal cancer and non-tumorigenic tissues reveals cancer-, stage- and EGFR-specific protein N-glycosylation
• Rapid and individual-specific glycoprofiling of the low abundance N-glycosylated protein tissue inhibitor of metalloproteinases-1

Glycoproteomics and glycomics

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)
• enabling a more confident assignment of mass spectral data of intact glycans and glycopeptides (higher confidence and automation).

• Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis
• Glycomics & glycoproteomics: from analytics to function
• Post-column make-up flow (PCMF) enhances the performance of capillary-flow PGC-LC-MS/MS-based glycomics
• Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease
• Utilizing ion-pairing hydrophilic interaction chromatography solid phase extraction for efficient glycopeptide enrichment in glycoproteomics

Infection and immuno-glycobiology

With a focus on understanding basic molecular mechanisms in innate glycoimmunology and using advanced glycoproteomics and glycomics technologies and methods in molecular and cellular glycobiology. we are currently exploring:

• various acquired infectious diseases eg tuberculosis and HIV
• inherited immune-related diseases eg cystic fibrosis
• rare lysosomal diseases eg Tay-Sachs/Sandhoff diseases

Deciphering the glycobiological processes existing within and between neutrophils and macrophages are of particular interest.

• Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells
• Hyper-truncated Asn355-and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase
• N-acetyl-β-D-hexosaminidases mediate the generation of paucimannosidic proteins via a putative noncanonical truncation pathway in human neutrophils
• Glycan analysis of human neutrophil granules implicates a maturation-dependent glycosylation machinery
• High-resolution longitudinal N- and O-glycoprofiling of human monocyte-to-macrophage transition
• Human protein paucimannosylation: cues from the eukaryotic kingdoms
• Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions
• Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and Their Microparticles
• Emerging roles of protein mannosylation in inflammation and infection
• Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum