The aim of our group is to understand the regulation and function of Ras-like small GTPases. Ras is the paradigm of the family and mutated in 15% of all human cancers. Rap is a very close relative that functions in among others cell adhesion, integrity of cell junctions, cell migration, cell polarity and secretion. The group has used biochemical, cell biological, and proteomic approaches to study the spatial and temporal control and the molecular mechanism of the function of Ras and Rap.
Central in these studies have been the Epac proteins identified in our lab as a cAMP-regulated guanine nucleotide exchange factor for Rap in 1998. Due to development of a selective cAMP analog 8-CPT-2'OMe-cAMP or as we call it 007, many process in which Epac plays a role have been eluded and currently the protein is one of the centerpieces in cAMP research.
Recently the group has adopted the organoid culture system developed by Hans Clevers as a model system to study signal transduction in cell complexes. This includes the development of systems to perform high-end live-imaging of signalling events. Using these organoids we are currently exploring the mechanism of resistance and possible solutions of mutant Ras tumors for targeted drugs.