We make use of microarray analysis to examine the transcriptional changes associated with stress responses and aging disorders. With this approach, we can identify sentinel proteins that can serve as reporters for high-throughput hazard assesment of toxic chemicals. In addition to high throughput screening, we also use a functional genomic approach to perform detailed analyses of stress signalling pathways in embryonic stem cells.

We use a combination of transgenic mouse models, three-dimensional in vitro organoid culture, transcriptomics and functional genomics to unravel the mechanisms of toxicity in the liver and kidney - organs which are particularly susceptible to adverse drug reactions. The role of signalling by Toll-Like Receptors (TLRs) and the immune response in stress responses in the kidney are of specific interests here. From a mechanistic viewpoint, there are similarities in the responses observed in kidney epithelial cells during ischemia-reperfusion injury. We are studying the role of cell adhesion in the modulation of ischemic stress responses and cytotoxicity and more specifically at the role of the tyrosine kinase FAK in knockout mose models of ischemia.

We use a combination of different approaches to unravel the role of protein tyrosine kinases in the development of breast cancer and the onset of metastasis. Our main interest is on focal adhesion kinase (FAK), Src kinase, epidermal growth factor receptor (EGFR) and their downstream targets. The role of these proteins in mammary gland development and the early steps in mammary tumorigenesis is determined by three-dimensional cell culture and MEC transplantation and experimental metastasis models.  Their role in metastasis is determined via migration and invasion assays as well as in vivo lung metastasis models. To identify novel drug targets we use different high-throughput microscopy-based RNA interference screens. Such screens are combined with different read-outs, such as cell migration, focal adhesion turnover, and Fluorescence Resonance Energy Transfer (FRET) imaging.

Interactions between cancer cells and their microenvironment modulate tumor growth and progression. Connections with the extracellular matrix are mediated by transmembrane receptors termed “integrins”. These receptors, together with associated cytoplasmic proteins are organized into large multi-protein aggregates, termed “cell-matrix adhesions”. We study the dynamics of such cell matrix adhesions in relation to cell migration and we study how different integrins transmit different signals through Rho GTPases that cause distinct types of motile behavior. The importance of identified pathways is explored in in vivo metastasis models. In addition, we study the cross talk between oncogenes such as Src and Ras and different types of integrins in relation to tumor growth. Finally, dynamic interactions between epithelial cells and 3D extracellular matrices are studied in an in vitro morphogenesis model.