We focus primarily on the highly conserved Wnt signaling pathway and intersected pathways, forkhead/p53 transcription factors, and the biogenesis of RNA-binding proteins. Distortions in these proteins and pathways lead to a plethora of diseases, including cancers, neurological and metabolic disorders, and are linked to ageing. Our group aims to reveal the molecular mechanisms underlying interactions of disordered proteins to provide insight into the intricate link between their function, regulation, and human diseases. We explore our mechanistic/structural discoveries in a drug discovery approach to provide novel routes for disease therapy.

We use NMR-based metabolic phenotyping to obtain systemic insight into the molecular outcome of distortions in signaling pathways in cell-based assays, in vivo model systems, and patients. This allows to bridge the gap between atom and patient and vice versa and to obtain new insights into disease mechanisms and diagnosis. More specifically, we are focusing on metabolic changes in cellular senescence, ageing, and the link between metabolism, signaling, liquid-liquid phase separation and human diseases on the level of post-translational modifications (i.e. arginine methylation).

To be able to study large and dynamic biomolecular complexes involved in signal transduction, we employ and develop integrated structure determination protocols in which we combine NMR spectroscopy, SAXS/SANS, complementary techniques (i.e. XRD, MS, cryo-EM, FRET, ITC, fluorescence polarization, SPR), and modeling strategies. Next to molecular dynamics programs widely used in the NMR community, our computational focus is on the integration of novel techniques in the Rosetta and AlphaFold de novo structure prediction framework. Several approaches were developed and applied by us to challenging biological systems in the last few years.