Research
The research carried out in our department is focused on the molecular aspects of cellular stress and regulation of glycosylation in the context of inflammation and autoimmunity
Characterization and function of autoantigens
Patients suffering from autoimmune diseases produce antibodies to self-proteins, which are referred to as autoantigens. In general, such autoantigens are macromolecules which have important cellular functions. We study the structure and function of autoantigens involved in the synthesis and degradation of RNA and proteins.
We also address the question why tolerance to self-proteins is lost in autoimmunity. Our studies are based on the hypothesis that unusual posttranslational modifications play a role in the generation of autoreactive antibodies, and we believe that such modifications play an important role in the initiation of autoimmunity. The knowledge obtained on the structure and modifications of autoantigenic molecules is used for the development of autoimmune diagnostics.
Dissecting cellular glycosylation in health and disease
Next to nucleic acids, proteins and lipids, glycans are major molecular building blocks of the cell. Glycans are composed of different sugar molecules that are assembled inside the cell into a staggering repertoire of highly diverse structures – the glycome. Glycans regulate the biochemical properties and functions of glycoproteins and glycolipids and mediate numerous molecular recognition events at the cell surface. Altered glycosylation is found in every major disease including inflammation, autoimmunity, and cancer. We study how glycosylation contributes to the normal functions of a cell and how it is altered during molecular stress and in disease. Special focus is on the regulation of glycosylation in the intestine, glycan interactions with the microbiome, and roles in inflammation and autoimmunity. Insights from this research inspire the development of glycan-focused therapeutics for the treatment of inflammatory diseases and autoimmunity.
Projects
- The human ribonuclease RNase MRP and RNase P: from structural similarity to functional diversity
- Agglutination assay for rheumatoid arthritis biomarkers
- Detection and characterization of autoreactive B cells
- Subcellular accumulation of autoantigens
- Epithelial glycosylation in the human colon and cross-talk with the microbiome
- Genetic and chemical engineering of sialoglycoproteins in human cells
- Sialoglycan recognition by glycan-binding proteins
- Are glycans crucial determinants of autoantibody reactivity in multiple sclerosis?