Molecular Dermatology

The focus of our research is the vascular endothelium, which lines the blood vessels. As an interface between blood and tissue, it plays important roles in oxygen and nutrient supply. In various tissues such as the skin, it also importantly contributes to inflammation and wound healing processes.

For example, in case of an infection, released inflammatory mediators such as TNF and IL-1 trigger the expression of endothelial adhesion molecules and chemotactically active messenger substances (chemokines), which in turn recruit white blood cells from the bloodstream to the site of infection. Some substances from the environment such as contact allergens can trigger endothelial activation thereby promoting inflammation. The endothelium is extraordinarily versatile and predestined to respond quickly to new environmental cues. While this is beneficial in physiological processes such as wound healing, its versatility can be detrimental in certain disease conditions, for example in tumor development. Various diseases such as Diabetes mellitus, Psoriasis vulgaris („psoriasis“), Hidradenits suppurativa (Acne inversa) or Lupus erythematosus are associated with serious complications of the vascular system and an increased risk of cardiovascular diseases. The main goal of our working group is a better understanding of the intracellular signaling pathways that control clinically relevant endothelial functions in order to be able to develop new therapeutic strategies to intervene in various disease situations.

One research focus in this effort is the investigation of the molecular recognition mechanisms through which common contact allergens for example the metal allergen nickel or drug allergens such as the human immunodeficiency virus (HIV)-inhibiting drug abacavir mediate their inflammatory effects on the endothelium and skin-associated immune cells. In this context we are particularly interested in the role of so-called „pattern recognition“ receptors, such as toll-like receptor 4 (TLR4) or NOD-like receptor 3 (NLRP3). These innate immune receptors serve the innate immune system as sensors of microbial structures and subsequently initiate defense against infection by stimulating inflammatory signaling pathways. Our own work showed that these also convey the inflammatory effect of certain metal and drug allergens and thus represent potential target structures for future therapeutic approaches for contact and drug allergies.

A second focus of our research is the investigation of the vasoprotective MEK5 / ERK5 / KLF2 / 4 signaling pathway in the context of various diseases. This mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in maintaining blood vessels and regulating vascular remodeling and inflammation processes in the endothelium. However, recent findings of our group show that it also serves an important protective function in other organ systems such as the bones. In addition, it contributes to tumorigenesis in malignant melanoma by mediating resistance to certain anticancer drugs. The investigation of the underlying molecular mechanisms is the subject of current investigations in which we evaluate the suitability of ERK5 as a target structure for novel treatment approaches for patients with therapy-resistant melanoma.