Mechanisms of the Pathologies of the Cutaneous Inflammation
The principal research topic of our group is the pathophysiology of cutaneous inflammation, using psoriasis as a model disease. The research laboratory focuses on three main research lines:
- IL-17E: Recent investigations have highlighted the important role of the Th17/IL-23 pathway in psoriasis, and identified IL-17A as a critical effector cytokine in this disease. Our laboratory has recently demonstrated that IL-17E, another IL-17 isoform, is highly up-regulated in psoriatic skin and may represent an important mediator of the cross-talk between resident and infiltrating (inflammatory) cells in the skin. This project aims to further determine the role of IL-17E in the skin with respect to the function of immune cells and keratinocytes, and to elucidate the cellular and molecular mechanisms by which IL-17E exerts its effects.
- Lrig1: Lrig1 is a member of the leucin-rich and immunoglobulin-like domains family of proteins that negatively regulates several receptor tyrosine kinases. Recent studies indicate that Lrig1 plays an important role in cutaneous homeostasis by regulating epidermal stem cell activity. In mice, loss of Lrig1 leads to the development of chronic inflammatory symptoms resembling psoriasis. The aim of this project is to identify the functional link between Lrig1 and the induction of chronic inflammation.
- Mechanotransduction: Recent studies have indicated that the mechanical environment exerts a dominant influence on the way in which epithelial cells respond to other stimuli, such as biochemical factors or inflammatory cytokines. Aberrant activation of components of the mechanotransduction cascade has been linked to abnormal cell fate decisions in epithelial cells, resulting in perturbed homeostasis, impaired wound healing, and the promotion of diseases such as cancer. The aim of this project is to understand how extracellular matrix components are altered in chronic cutaneous inflammatory diseases such as psoriasis, and how this subsequently influences mechanotransduction.
To address the aims outlined above, we employ a variety of in vitro and in vivo approaches using human clinical samples and animal models of disease, respectively. Our laboratory is supported in part by the Swiss National Foundation (SNF).