Principal Investigator – Junior Research Group Leader, CECAD Cologne
Dr. Sandra Iden
The Iden laboratory investigates mechanisms underlying cell and tissue polarization, and how molecular regulators of cell polarity control tissue homeostasis and skin cancer. Using mouse genetics and disease models, the scientists assess the impact of impaired cyto-architecture on oncogenic processes. Next to elucidating basic principles of cancer biology, a major goal is to develop new diagnostic and therapeutic approaches to skin cancers and eventually other types of cancer.
Our research: The Iden laboratory studies the phenomenon of cell polarity. The team aims to decrypt how cell polarity is regulated during the development and homeostasis of epithelial tissues, as well as in pathological conditions of the skin. For this, different in vivo and in vitro models are applied to manipulate polarity signaling and to assess the consequences on cell architecture, skin homeostasis, regeneration, and cancer.
Our successes: Using animal disease models, the team has shown that altered expression of polarity proteins impacts on the development and progression of different epidermal skin cancers. The group established a novel mouse tumor model for investigation of a common skin tumor relevant to human pathology. This and other models now serve to identify molecular mechanisms underlying tumor formation and to develop new therapeutic strategies for skin cancer patients.
Our goals: Current efforts aim at the identification of molecular mechanisms that link cell polarization, growth and differentiation, in the context of a functional skin barrier and various types of skin cancer. Different disease models are used to unravel potential similarities and differences in the way polarity signals contribute to specific skin tumors, and results are compared with normal and malignant human tissues. The aim is to resolve molecular processes that drive skin cancer and to identify new translational approaches to skin cancer diagnosis and therapy.
Our methods/techniques: We combine various in vitro techniques with analysis of genetic mouse models. Simplified, easy-to-manipulate cell culture systems serve for the initial investigation of molecular and cellular processes, as well as oncogenic signaling. Data are then translated into animal (disease) models to test their physiological relevance. Close collaboration with clinician scientists is crucial to connect the findings to human disease. The combination of protein biochemistry, cell culture assays, mouse models, and patient material, will deliver new insights into the role of cell polarity in mammalian tissue homeostasis and disease.
If you are interested in joining the research group of Sandra Iden for an internship, a Master student or a PhD student project, please send an e-mail to Sandra Iden.
Figure 1: Dual role of Par3 in skin tumorigenesis. Papilloma formation and growth is reduced, and aPKC and components of the Ras pathway are mislocalized when Par3 is lost. In contrast, Par3 KO mice develop significantly more keratoacanthomas, suggesting that Par3 has a tumor-suppressive function in this context (see Iden et al., Cancer Cell 2012).
Figure 2: Polarity protein signaling impinges on central cascades that influence tumor formation and progression. Left: In epidermal keratinocytes, Par3 serves to recruit aPKC and Ras signaling components to the plasma membrane, resulting in efficient downstream signaling towards Ras/Raf/MEK/ERK, promoting proliferation and growth of skin papillomas. Right: Par3 and aPKC promote cell survival by the stimulation of PI3K-Akt signaling, thereby counteracting oncogene-induced apoptosis.