The skin is the largest organ in the human body. It is not known why the immune system sometimes forms autoantibodies against it. This process can lead to blistering diseases such as pemphigus or bullous pemphigoid. Dr. Silke Hofmann from the Department of Dermatology at the University of Freiburg is investigating the molecular mechanisms that lead to such diseases. As she finds dermatology a very fascinating subject, she does not restrict herself to clinical work, but also manages to find the time to carry out research. Her research activities have led to informative insights into skin diseases.
The skin is the largest and functionally most versatile organ in human beings. It consists of three layers: the outermost skin layer (epidermis), the dermis beneath the epidermis and the hypodermis (subcutis) which lies below the dermis. The epidermal cells firmly "glue" to each other by way of structural proteins and protect the organism against environmental influences. It is still not known why the human immune system occasionally forms antibodies that are directed against these structural proteins (antigens). The antibodies bind to these proteins and attract other immune system cells which in turn degrade the structural proteins. This leads to the separation of the cells and to the creation of hollow spaces containing tissue fluid. Blisters form on the skin. Such processes can result in different types of blistering diseases, depending on the area of skin where an inflammation develops and on the structural proteins affected.
“At present we are only able to treat our patients according to the watering-can principle,” said Dr. Silke Hofmann, physician and researcher at the Department of Dermatology in Freiburg. The common treatment of skin diseases such as pemphigus or bullous pemphigoid involves the administration of drugs that suppress the defective action of the immune system,” said Hofmann going on to add that “it is our goal to develop therapies that are able to specifically inhibit the mechanisms that lead to a particular skin disease.” This is the aim of the research that she carries out in the time available when she is not pursuing her main role as medical specialist. “I am a doctor first and foremost,” said Hofmann. “And this leaves me with little time for research.” The fact that she nevertheless spends a lot of her spare time on research is because she is so enthusiastic about it.
Silke Hofmann, who was born in Erlangen in 1977, did some practical dermatological work during her medical studies at the University of Erlangen, which is when she discovered her interest for this particular discipline. She enjoys having to deal with a broad range of different patients and diseases. She explains that many skin diseases can be diagnosed from information provided by the patients themselves along with a close inspection of the affected skin areas. This often makes time-consuming investigations unnecessary.
She decided to do her doctoral thesis at the Erlangen Skin Hospital on bullous pemphigoid caused by defects of the structural proteins located in the layer between the epidermis and the dermis (basal lamina). In 2003, she moved to the Department of Dermatology (Freiburg University Medical Centre) in Freiburg where she became assistant doctor in 2004 and medical specialist in 2007.
In her laboratory, Silke Hofmann is looking for areas on structural skin proteins that represent excellent targets (epitopes) for antibodies. Her goal is to find out whether certain epitopes correlate with a higher disease activity and therefore require more intensive treatments to be put in place. The researcher is also interested in finding out how new antibody targets develop. One such example is the development of antibody targets in a disease known as IgA dermatosis where such targets are created through an enzymatic process. Hofmann and her team carried out numerous experiments and eventually found an enzyme that mediates this process. This protein (plasmin), which is found in human blood, cleaves a structural protein of the epidermis (collagen XVII), thereby leading to a shorter protein fragment that is attacked by IgA antibodies. This process leads to IgA dermatosis.
In another project, Hofmann succeeded in characterising in more detail the previously unknown p200 protein. This protein is the antigen of a specific form of pemphigoid (p200 pemphigoid). Prior to her investigations, hardly anything was known about the molecule. Only the weight of the molecule was known (200 kD), which also led to the specific designation of the protein.
Although Silke Hofmann was unable to identify the protein using protein biochemistry methods and immunofluorescence, she nevertheless succeeded in determining the cell types that synthesise the protein. In addition, she also showed that the p200 protein forms calcium-dependent complexes. Last year, a Japanese group of researchers identified the sought-after molecule (the laminin gamma 1 chain).
"It took our Japanese colleagues fifteen years before they were able to identify the molecule," said Hofmann. Since she only has limited time for her research, it is very difficult to compete with other groups. "Nevertheless, the project was very exciting," said Hofmann.
Hofmann’s research on blistering diseases has also led to a concrete project. Working in collaboration with researchers from the University of Lund (Sweden), Hofmann produced a monoclonal antibody against epidermal collagen XVII. This antibody is an important tool for research focusing on epidermal diseases and is now marketed by the company Covance.
In the meantime, Hofmann has directed her attention to peptides produced by the human body that are able to fend off bacteria and fungi. All human beings possess such molecules, which enable the human body to produce antibiotics that prevent infections caused by microorganisms. “Do patients suffering from skin infections have fewer antimicrobial peptides?” asks Hofmann who finds it a shame that she does not have enough time for her research. But she is pleased that she studied medicine because this has given her the chance to work with people. She would not like to focus entirely on laboratory research, and gains a great deal of satisfaction from her complementary roles as doctor and researcher.
Further information:Dr. med. Silke Hofmann Freiburg University Medical CentreDepartment of DermatologyHauptstr. 7 79104 FreiburgTel.: +49-(0)761/270-6701 Fax : +49-(0)761/270-6829E-mail: silke.hofmann(at)uniklinik-freiburg.de