Inflammatory signaling pathways need to be tightly regulated in order to avoid chronic inflammation and the development of inflammatory pathology One of the regulatory proteins responsible for such control is OTULIN, a deubiquitinating enzyme which specifically cleaves linear ubiquitin chains generated by the linear ubiquitin chain assembly complex

We have generated keratinocyte-specific OTULIN knockout mice which develop a severe inflammatory skin condition and exhibit markedly enhanced epidermal stem cell activation In this project, we will investigate the molecular pathways that are affected by the lack of OTULIN in the epithelial cells of the skin, in order to understand how OTULIN regulates inflammatory signaling and cell death responses in the skin Skin harbors many well-characterized stem cell populations and therefore represents an ideal model system to study the intercellular crosstalk between immune cells and stem cells The results of this research will identify crucial mediators of stem cell activation and this knowledge may lay the grounds for novel therapeutic approaches in the treatment of inflammatory skin disorders