Research focus

Cell polarization is crucial for the development of multicellular organisms, and aberrant cell polarization contributes to various diseases. Seminal studies in invertebrates identified proteins that regulate various polarization processes including asymmetric cell division and epithelial cell polarization. Mammalian homologs have been shown to direct for instance neuronal polarization, polarized cell migration and immunological synapse formation. Polarity proteins may react to extrinsic polarity cues such as growth factor gradients or intrinsic polarity cues such as the microtubule cytoskeleton. By assembling multiprotein complexes, they induce downstream signaling to trigger the establishment of cellular asymmetry. Of the three described polarity protein complexes — partitioning defective-3 (Par3), Crumbs and Scribble — the Par3 complex has the broadest function. Furthermore, cross-talk between polarity proteins and Rho GTPase signaling components controls the establishment of cell-cell contacts and apico-basal polarity of epithelial cells. For decades, loss of apico-basal polarity has been considered a prerequisite for tumor formation and progression. However, the contribution of mammalian polarity proteins to these processes is currently unclear.

Research in our junior group addresses the function of polarity proteins in skin pathologies including cancer. In experimental skin tumor models, we have observed that mice with deregulated polarity signalling exhibit altered skin tumorigenesis. We investigate cell-autonomous and non-cell-autonomous functions of polarity proteins and study consequences of loss of polarity proteins on cellular architecture, survival mechanisms and cell death using cell culture techniques and different mouse models. Overall, we aim at a better understanding of polarity regulators in health and disease, which may reveal future directions for targeted therapies.