Recently, it was discovered that glycosylation of glucocorticoids reduces their side effects due to the activity of the enzyme GBA2 at sites of inflammation. I investigate the regulation of GBA2 and its role in the inflammatory response, using zebrafish. Furthermore, I screen novel glycosylated glucocorticoid drugs for their therapeutic potential.

More information about Hildert Bronkhorst

Research

Glucocorticoid drugs such as prednisolone and dexamethasone are widely used clinically to treat a variety of auto-immune and inflammatory diseases, such as rheumatoid arthritis, asthma, inflammatory bowel disease and eczema. They are among the most prescribed drugs worldwide, but their clinical use is severely limited by their side effects, which include osteoporosis, diabetes, obesity, muscle atrophy and depression. Over the last 50 years, an enormous effort has been made in both academia and industry to develop novel glucocorticoid therapies that retain the effective immune-suppressive activity, but show reduced side effects. However, this has not been successful and no such drug has reached the market yet.

Interestingly, in recent years a team from IBL has made an enormous breakthrough in this area. Inspired by the discoveries on the mechanism of action of compounds from the Chinese medicinal herb ginseng, a novel glucocorticoid that has virtually no side effects was developed. This was done by attaching two glucose moieties to the glucocorticoid drug prednisolone, thereby creating an inactive prodrug, that is selectively activated in inflamed tissue by the enzyme beta-glucosylceramidase 2 (GBA2). In my project, I proceed with this groundbreaking project in three directions. First, I perform basic biology research on the mechanism of action of the drugs and the regulation of GBA2 expression. Second, I investigate the pharmacokinetics of glycosylated glucocorticoids on cellular level, e.g. their dependence on glucose transporters. Third, I screen novel compounds for possible clinical use.

Brief biography

I obtained a bachelor degree in Molecular Life Sciences at Wageningen University & Research (2019). I specialized in chemical biology during the master Life Science & Technology at Leiden University (2022). I also studied theology on bachelor and master level and was a junior researcher at the Erasmus School of Philosophy. In 2023, I started as PhD-candidate in molecular biology at the IBL.

Publications