Research

Mass-spectrometry proteomics, arguably the most poweful strategy to study posttranslational modifications!

Profiling protein long chain S-acylation by mass-spectrometry proteomicss

Acyl-biotin exchange (ABE) and lipid metabolic labelling (LML), both coupled with mass spectrometry proteomics, are indirect but powerful methods for analyzing protein long chain S-acylation. However, these methods are prone to false positive identifications, which can compromise the accuracy of S-palmitoylation analysis. To overcome this limitation, we use the orthogonality of both ABE and LML, and use both approaches in parallel to study bona fide S-palmitoylated proteins and sites. Furthermore, we continuously optimize and refine these proteomics strategies to better understand the role of S-palmitoylation in neurodegenerative disorders and cancer.

S-palmitoylation profiling of SH-SY5Y cells during RA-induced neuronal differentiation

Acyl-protein thioesterase substrate identification

In recent years, several depalmitoylating enzymes beyond APT1 and APT2 have been discovered, including ABHD17a-c and ABHD10. These enzymes have been found to be crucial in the regulation of long chain S-acylation dynamics. However, the specific substrates of these acyl-protein thioesterases remain largely unknown. To address this gap in knowledge, our aim is to develop novel strategies for identifying acyl-protein thioesterase substrates

Bioorthogonal ligation and activity-based protein profiling

We are interested in the development of new enrichment strategies for the selective enrichment of posttranslational modifications and chemically tagged proteins.

We are working on the development of IMAC-enrichable affinity tags (PhosID) that are compatible with ABPP studies.
Phosphonate handles enable identification of the exact drug binding sites on proteins.
We use detailed insight in the fragmentation behavior of ABPs to identify their protein binding sites.