Our group is interested in the molecular mechanisms controlling stem cell maintenance, lineage commitment and differentiation in self-renewing systems such as the hematopoietic system, the skin and the gut. The basic principle of self-renewing tissues is that they constantly produce cells from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate and migrate to the correct compartment. These processes have to be under stringent control to ensure life-long homeostasis. In recent years a substantial body of evidence has accumulated to support the notion that signaling pathways known to be important during embryonic development (such as e.g. Shh, Wnt and Notch) play important roles in regulating self-renewing tissues. Moreover, the same pathways are often deregulated during tumorigenesis due to mutations of key elements of these pathways. The general concept is that a better understanding of the mechanisms controlling stem maintenance versus differentiation may lead to the identification of novel therapeutic targets, as well as improving strategies for influencing these players during tumorigenesis. Currently, attention is being focused on the evolutionarily conserved Notch signaling pathway, which plays pleiotropic roles in different self-renewing tissues and cancer.
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