Tissue-scale cell-cell communication and roles of polarity networks in homeostasis and disease
Plasticity in cyto-architecture is essential for the homeostasis, function and repair of tissues and for effective adaptation to organismal constraints. How changes in cell shape and intercellular communication are coordinated in a continuously self-renewing tissue like the skin epidermis remains an intriguing open question. The key goal of our research is to unravel molecular mechanisms underlying the control of cell-cell adhesion and tissue architecture in health and disease. We study functions of different conserved polarity proteins and their interacting proteins in mammalian tissue morphogenesis, homeostasis, stress responses and malignancy. Moreover, we study molecular and cellular mechanisms that control homo- as well as heterotypic cell-cell communication in complex epithelial tissues.
Our aims and approaches
Our ongoing research aims at understanding how different cell types, or cells of different fate, communicate, synergize or compete with each other at tissue scale, how polarity networks impinge on these dynamic interactions, and how these processes fail in the disease context. These studies should help identify basic principles of development and tissue homeostasis as well as pathophysiological mechanisms linked to disturbed cell polarity.
We combine mouse genetics and animal disease models with cell and molecular biology, biophysics, imaging technologies and protein biochemistry to acquire new knowledge about mechanisms that drive cell and tissue polarization, from subcellular details towards the tissue and organismal context. This way, we aim at understanding how polarity, cell adhesion, growth and mechanical signaling are coordinated to ensure proper tissue function. We further develop and improve simple and complex in vitro (co)culture systems to complement the in vivo models used. Together with our clinical collaborators we combine these with analyses of human (patient) datasets and specimen to test the significance of our findings for human disease and to explore translational directions for disease prevention and control.