Carien M Niessen - C 10

Regulation of cell and tissue architecture in skin homeostasis, regeneration and degeneration

Abstact

Cytoskeletal rearrangements, altered cell polarity and cell adhesion defects are observed in a wide range of human diseases ranging from degenerative diseases to inflammatory disorders and cancer. We propose that alterations in key regulators of cell- and tissue architecture underlie a broad range of these diseases. We recently demonstrated in mouse skin epidermis that E-cadherin-dependent control of suprabasal EGFR activity orchestrates the polarized, tissue-level organization of junctions, tension, and the cytoskeleton, which is crucial for vivo skin barrier function. These studies also indicate a mechanistic role for EGFR at tight junctions (TJs), potentially explaining why EGFR inhibitors compromise skin barrier function in human cancer patients. Furthermore, we showed that the polarity kinase atypical kinase C (aPKC) integrates regulation of cell fate with control of the structural and immunological skin barrier. The goal of the current proposal is to address how cadherins and aPKCs cooperate to spatiotemporally coordinate the formation and maintenance of a functional multi-layered epithelial barrier with the explicit aim to identify novel therapy targets for a range of (inflammatory) skin barrier related diseases.

Clinical/medical relevance and sustainability in disease understanding

Inflammatory and degenerative skin diseases, such as psoriasis, atopic dermatitis and non- healing wounds, are highly prevalent. However, specific treatments are still mostly lacking due to a poor understanding of the underlying molecular causes. A dysfunctional skin barrier is considered to be one major contributor to disease. The two main components that build up the skin barrier are the outermost dead stratum corneum and the tight junctions in the uppermost viable stratum granulosum. This project addresses the molecular mechanisms that coordinate the formation and maintenance of these two epidermal barriers and explores their therapeutic potential in dysfunctional skin barrier related diseases.


Prof. Dr. rer. nat. Carien M Niessen

Dept. of Dermatology

Prof. Dr. rer. nat. Carien Niessen

Principal Investigator C 10
Executive Board Member

carien.niessen@uni-koeln.de

Work +49 221 478 89512

Fax (Work) +49 221 478 6360

Dept. of Dermatology
Joseph-Stelzmann-Str. 26
50931 Cologne

Publications - Carien M Niessen

Link to PubMed

Group Members

Dr. Oana Persa (MD)
Dr. Susanne Vorhagen (Postdoc)
Jabiz Nafisi (PhD Student)
Frederik Tellkamp (PhD Student)
Julia Stinn (Technician)