Prof. Dr. rer. nat. Thomas M. Magin

Research profile

My major interest is to understand molecular mechanisms governing epithelial differentiation, regeneration and pathogenesis, using the function of the epithelial keratin cytoskeleton as a model system. This topic captured my interest during my PhD thesis work with Werner W. Franke at the German Cancer Research Center in the 1980ies. My lab follows the hypothesis that members of the keratin multigene family play a major role in the spatiotemporal regulation of the above epithelial functions, by acting as cell type-specific architectural and regulatory proteins. Through these functions keratins affect tissue regeneration, carcinogenesis and metastasis by regulating cell/tissue stiffness, cohesion, migration and invasion.

My postdoctoral education with David Melton at the ICMB, University of Edinburgh familiarized me with gene targeting and embryonic stem cell methodologies and enabled to me develop some of early keratin knockout mice. I returned to Germany in 1995, to take up a position as group leader at the Department of Genetics, University of Bonn. In 2001, I became full professor of Cell Biochemistry at the Institute of Biochemistry and Molecular Biology, University of Bonn. In 2010, I moved to the University of Leipzig (Translational Center of Reg. Med and Institute of Biology) to become full professor of Cell & Dev. Biology. Today, it is apparent that keratin dysfunction causes blistering, barrier and chronic inflammatory disorders, cell adhesion defects and impacts cell metabolism. In fact, mutations in 20 of the 54 keratin genes cause cell-specific epithelial disorders affecting predominantly the skin (e. g. Epidermolysis bullosa simplex).

The aim of our research is to elucidate molecular mechanisms by which keratin isotypes contribute to epidermal differentiation, cell adhesion, barrier function, metabolism, regeneration and disease. Understanding these mechanisms is necessary to resolve pathomechanisms underlying keratin-associated disorders as a major prerequisite for the development of molecular therapies, an aspect which we address in several projects.

To achieve our aims, we work with 3 model systems, namely genetically altered mice, Drosophila and cultured keratinocytes, in combination with a wide range of cell biological, biochemical and molecular genetics approaches. In addition to mice carrying deletion of individual keratin genes, we have established mice in which all 28 type I and 26 type II keratin genes are deleted conditionally, using cre-lox mediated genome engineering. Keratinocyte cell lines isolated from these mice form the basis for a strategy we called “delete and replace” to elucidate keratin function. Using these mice and keratinocytes derived therefrom, we have identified previously unknown roles of keratins in desmosome-based adhesion and in the control of keratinocyte-based inflammatory skin disorders. These discoveries were featured in special commentaries in the Journal of Cell Biology (2013) and the Journal of Cell Science (2012). Moreover, in collaboration with biophysicists, we showed that keratins are major determinants of cell stiffness and invasiveness (PNAS 2013). This finding has great relevance for tumor biology and tissue engineering