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Center for excellence "fragile skin"| Genodermatoses | Autoimmune | Lymphology

Center for Excellence "Fragile Skin" 

Director : Prof. Dr.Leena Bruckner-Tuderman, MD leena.bruckner-tuderman@uniklinik-freiburg.de +49-761-270-67160

Clinical Investigators:
PD Dr. Cristina Has, MD
Prof. Dr. Silke Hofmann, MD
Dr. Dr. Johannes Kern, MD, PhD
Dr. Dimitra Kiritsi, MD
Dr. Agnes Schwieger-Briel, MD
Prof. Dr. Hauke Schumann, MD (external collaboration partner)

The Center of Excellence “Fragile Skin” combines clinical patient care, molecular diagnostics and experimental research. The term “Fragile Skin” was coined for disorders of the skin and mucous membranes, which manifest with blister formation, easy bruisability or tearing, slow or disturbed wound healing, and reduced resistance against external mechanical forces. The Center is hosted by the Department of Dermatology, University Medical Center Freiburg. Its functions are based on intensive interactions of research and clinical medicine and encompass the following:

•  high standards in interdisciplinary medical care and nursing
•  modern molecular diagnostics of skin fragility disorders
•  internationally competitive experimental research
•  development of novel molecular and cellular therapeutic strategies.

The lab members are an international group comming from Germany, Finland, Greece, Italy, Poland, Romania, Sweden, China, India, and Japan. The center participates in several international networks for basic and clinical research. Below, the different areas of research in the center are introduced:

Genodermatoses and Biology of the Dermo-Epidermal Junction Zone

Prof. Dr. Cristina Has, MD
cristina.has@uniklinik-freiburg.de
+49-761-270-67850

Our work is focused on the molecular diagnostics and mechanisms of inherited skin fragility disorders like the Kindler syndrome and Epidermolysis bullosa. The Kindler syndrome is an autosomal recessive genodermatosis characterized by skin blistering in the childhood. Skin atrophy develops progressively leading to generalized poikiloderma in adults. We identified multiple abnormalities in kindlin-1 deficient skin and cultivated basal keratinocytes: cell polarity is lost, proliferation is strongly reduced and adhesion is decreased. These findings may explain the pathogenesis of skin blistering and atrophy in patients with the Kindler syndrome.

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Dr. Dr. Johannes Kern, MD, PhD                               Dr. Stefan Löckerman, MD
johannes.steffen.kern@uniklinik-freiburg.de                stefan.loeckermann@uniklinik-freiburg.de
+49-761-270-67850                                                  +49-761-270-67210

In a translational research effort we are testing molecular therapy approaches for dystrophic epidermolyis bullosa in a preclinical model. We are using an immune-competent transgenic mouse to evaluate the feasibility, efficacy and potential adverse effects of cell and protein therapies. The goal of these efforts is to find suitable therapeutic regimens of patient

Dr. Venugopal R. Mittapalli, PhD
venugopal.rao.mittapalli@uniklinik-freiburg.de
+49-761-270-67210

In previous studies from our lab, my colleagues have generated a hypomorphic mouse (a mice model that produces only 10% of collagen VII than in normal mice) that shows almost all the symptoms occur in DEB patient. Currently, it is of great interest for us to understand the susceptibility of mice to induced tumor development and also to elucidate the possible molecular mechanism(s) leading to the development of squamous cell carcinomas of the skin. Our studies may help to understand the development of SCC associated with RDEB and may help to provide efficient therapeutic strategies in future.

Patients with RDEB often develop partial or total mitten deformities of the hands and feet and also develop squamous cell carcinoma of the skin, which is rather aggressive and often leads to death.

Our work is focused on understanding the development of squamous cell carcinoma in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a severe form of dystrophic epidermolysis bullosa (DEB), an inherited severe skin fragility disorder that occurs due to absence of collagen VII. Collagen VII is one of the major proteins that stabilize the dermal-epidermal junctions by forming anchoring fibrils.

Autoimmune Skin Diseases

PD Dr. Silke Hofmann, MD                                         Prof. Dr. Cassian Sitaru, MD
silke.hofmann@uniklinik-freiburg.de                             cassian.sitaru@uniklinik-freiburg.de
                                                                                +49-761-270-69920

Helper T (Th) cell-regulated development of antigen-specific B and plasma cells resulting in the production of pathogenic autoantibodies underpins the pathology of several autoimmune diseases. These include pemphigus, pemphigoid, myasthenia gravis, Guillan-Barre syndrome, autoimmune hemolytic anemia, immune thrombocytopenia, autoimmune dilative cardiomyopathy, Goodpasture’s syndrome, systemic lupus erythematosus, anti-phospholipid syndrome, and rheumatoid arthritis. Our research focuses on the mechanisms governing the coupling of autoantibody specificity to effector cell response, with special emphasis on autoantibodies against structural skin proteins in autoimmune blistering diseases. These diseases are clinically and immunopathologically well-defined entities where both the autoantigen and the pathogenic autoantibodies are well characterized. However, the complex pathogenic and regulatory mechanisms of pathogenic autoantibody production and several aspects of blister formation are still poorly understood. A major focus of our research is to investigate these pathogenetic mechanisms using in vitro and in vivo models of autoimmunity against structural skin proteins. In parallel projects, we study the structure and function of skin proteins, including collagens VII and XVII of the dermoepidermal junction such as collagen XVII (BP180) or p200, which are targets of the autoimmune response in a group of acquired blistering diseases. Ongoing patient-centered studies address the pathogenesis of pemphigus, a severe bullous dermatosis with intraepidermal blistering, with the aim of improving diagnosis and therapy.

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