Leena Bruckner-Tuderman from the Department of Dermatology at the University Medical Centre in Freiburg has just been awarded the Eva Luise Köhler Research Prize for Rare Diseases.
She has not only made a decisive contribution to the clarification of the molecular causes of the skin disease “dystrophic epidermolysis bullosa”, but has also begun focusing on potential clinical therapies. Prof. Dr. Leena Bruckner-Tuderman from Finland has worked at many different institutes around the world. And although she has often found it rather difficult to organise her private life, she always found her work worth it.
Rare diseases – this does not really sound like a world-shaking problem. So why are physicians interested in such diseases? For Prof. Dr. Leena Bruckner-Tuderman, head of the Department of Dermatology and Venerology at the Freiburg University Medical Centre and director of the School of Life Sciences at the Freiburg Institute for Applied Studies (FRIAS), there are many reasons for such interest. The term rare disease means that only one in two thousand people suffer from it. This is why research into rare diseases is neglected. Physicians are often unable to come up with a correct diagnosis, and only a handful of specialists are able to help. Patients with rare diseases often have severe symptoms, but feel ignored because nobody really knows what they are suffering from. More than a thousand rare diseases are known, affecting more than several million people worldwide. There is a huge need for therapies. “And then there is also the scientific aspect,” said Bruckner-Tuderman. “These rare diseases are caused by a single gene defect. Therefore, it is very interesting to look into the molecular effects of these gene defects and find out more about the normal function of the affected tissue.”
A good decision
For Leena Kaarina Bruckner-Tuderman, born in the Finnish city of Oulu in 1952, the combination of clinical and scientific interests has always been her driving force. She chose to study medicine because it offered her a wide variety of subjects, including pathology, nephrology and radiology. Another important reason for choosing medicine was the potential to work as both physician and researcher. She studied at the University of Oulu from 1971 to 1976 and did an experimental doctoral thesis in molecular medicine, dealing with the biosynthesis of connective tissue. In 1977, she continued her postdoctoral studies in Piscataway close to New York, where she focused on the molecular causes of human connective tissue disease at the Rutgers Medical School. In the USA, she met her husband, a Swiss biochemist. “Getting married meant that I became one half of a ‘dual career couple’. And this made it difficult to plan the next step,” said Bruckner-Tuderman. “Our best offer was from Switzerland.” In 1980, Bruckner-Tuderman accepted a position at the Biocentre in Basel where she continued her research with great enthusiasm until 1983. “The modern and highly interdisciplinary institute showed me the possibilities offered by cell and molecular biology,” said Bruckner-Tuderman. “And this has had an influence on my later career.”
At first, she also wanted to work as a physician and so in 1987 she decided to move on to the Hospital of Dermatology at the University of Zurich and do specialist training in dermatology. This was an excellent decision because her chief physician at the time, Prof. Dr. Urs Schnyder, was interested in the different types of dystrophic epidermolysis bullosa, a genetic skin disease characterised by blisters, wounds and severe pain, with a fatal outcome in some cases. Bruckner-Tuderman’s expertise in molecular biology methods and her knowledge of the molecular processes in the connective tissue turned out to be very useful. The scientists were the first group in the world to show that the rare skin disease was the result of a single molecular defect. Their research showed that the gene for the protein collagen VII was either defective or completely missing in all dystrophic epidermolysis bullosa patients. This protein is a component of the extracellular matrix between the cells of the upper (epidermis) and lower skin (dermis). This layer plays an important role in strengthening and stabilising the skin. Collagen VII is the main component of structures (anchoring fibrils) which anchor the epidermis to the underlying dermis. When type VII collagen is abnormal or missing, the two skin layers become separated. This separation leads to the formation of blisters, which can cause scarring and wounds.
Between basic research and clinical research
In 1995, Bruckner-Tuderman’s husband became the head of a department at the University of Münster in Germany. She joined him, accepting a position at the University’s Skin Hospital. She received a SCORE grant from the Swiss National Science Foundation (SNF) followed by a Heisenberg professorship from the DFG, which enabled her to continue her research. In 1998, she took a research post in Hong Kong, followed by another at the Harvard Medical School in Boston between 2000 and 2001. In 2003, she became head of the Department of Dermatology and Venerology at the University Medical Centre in Freiburg where she has been active as researcher and physician ever since. “Sometimes it is quite difficult to be a professor and be married to another professor. We have very little time to ourselves; every weekend, either my husband or I travel to Münster,” said the 57-year-old. “But as we are both professors this also helps us to understand each other’s problems and triumphs; we know what it means to discover something new; we are happy and share our happiness together.” Bruckner-Tuderman finds the work in Freiburg very fulfilling and rewarding. At present, she has no plans to go back to Finland, although she travels to her home country twice a year to visit her family and act as advisor and sit on the boards of a range of Finnish universities. Since 2007, she has been a director at FRIAS where she exchanges information with top class colleagues, as well as working with them to develop new ideas. And this is another reason for her to remain in Freiburg for the time being.
Nowadays, her research is more than ever situated at the interface between basic discipline and clinical application. She and her team, along with international cooperation partners, are still investigating how the individual defects of the gene coding for collagen VII lead to the different types of dystrophic epidermolysis bullosa. The researchers are focusing on the molecular interactions in skin tissue. “At the same time, we are also thinking about molecular therapies to treat the disease,” said Bruckner-Tuderman.
The scientists have a knock-out mouse model which lacks the collagen VII gene. They are trying to inject healthy skin cells, which are able to produce the important protein, under the skin of the animals. At some point in the future this might also be a potential treatment for humans suffering from the disease. A range of control experiments still need to be carried out. For example, the body rejects foreign cells and the researchers need to find ways to prevent this immunological reaction. Stem cell therapy is another, relatively modern approach to treat the disease. As part of a BMBF project carried out in cooperation with the Universities of Tübingen, Marburg and Cologne, the researchers will soon start experiments involving the transplantation of bone marrow stem cells into the skin of the animals. Bruckner-Tuderman is still fascinated with her work. “I have always been interested in complex problems,” said the scientist. “And this is what my job offers me.”