The largest human sensory organ is the subject of her research and medical care: the skin. For dermatologist Ulrike Raap, it is "an architectural masterpiece" whose building blocks she wants to understand even better in the service of new therapies.
On this summer evening, they float colourfully across the stage of the experimental lecture hall on the Wechloy campus. Soap bubbles. The youngest members of the audience at dermatologist Ulrike Raap's lecture "When the skin blisters" are responsible for this: her two sons. The 45-year-old has just given her inaugural lecture, but she has long since arrived - in Oldenburg, at the University Hospital, where she is Director of the University Clinic for Dermatology and Allergology, at the School of Medicine with its cross-border model study programme "European Medical School Oldenburg-Groningen".
This was evidenced not only by the packed lecture theatre - with new colleagues, students and staff from the School and clinic as well as long-time companions. Raap, who moved to Oldenburg with her whole family just one month after accepting her appointment at the university, has made the most of the time since taking up her post in autumn 2016. The first joint publication with her Groningen colleague and clinic director Marcel Jonkman has been produced, and a joint research project between the two on blistering skin diseases will be launched in January. Raap has changed processes and structures in her clinic, had a bathroom converted into an admission room, switched to electronic patient files and predominantly paper-free offices.
Dean Hans Gerd Nothwang calls the dermatologist a "power woman". Anyone who has a successful scientific career in medicine with two children and also runs marathons gives an idea of "the energy behind it". According to Nothwang, Raap's most important driving force is probably her great fascination for the skin.
Dynamics and dramatic events in the skin
Ulrike Raap's obvious enthusiasm for this largest human sensory organ - and the "up close and personal" contact with patients - was already evident in her first year of medical school, which she began in Lübeck and completed in her hometown of Hanover. In order to earn money during her studies, she worked as a temporary hospital assistant and was quickly assigned to the dermatology department in Lübeck on a permanent basis. "Even as a temp, I was quickly allowed to take on complicated wound care, which I really enjoyed and had a lot of fun doing," she recalls. The team was always very friendly and relaxed, which made a lasting impression on Raap. After her clinical traineeship, her colleagues in dermatology at Hannover Medical School (MHH) recruited her as a doctoral student. Her doctorate was followed by specialist training in dermatology.
Since then, Raap has been studying the subject in ever greater detail, skin layer by skin layer and cell type by cell type, and has also acquired proven immunological expertise following a one-year post-doctoral stay in neuroimmunology in Marburg. She has not only penetrated the molecular and cellular processes that take place in the body when recognising and fending off (actual or supposed) disruptive factors. She is also able to explain them clearly, even to laypeople. When the university lecturer talks about the skin, she refers to motorways and petrol stations, seething cells and arsenals of weapons - and it is possible to imagine the dynamics and sometimes dramatic events that take place beneath the surface.
These vivid descriptions are about the so-called eosinophil granulocytes, for example, which Raap wrote his doctoral thesis on at the Hannover Medical School (MHH) in 1999 and which "always look like they have sunglasses on" due to their double cell nucleus. These are mobile cells that are formed in the bone marrow and play a role in the defence against parasites in particular. "The eosinophils migrate to the inflammatory process, to where they are needed," says Raap. "So if someone has a parasite in their gut, for example, these guys receive a message signal, come marching up and bombard the parasite with oxygen radicals and cytokines, which are certain proteins." In the end, the parasite is excreted, virtually riddled with holes.
But the parasite fighters are also present in some skin diseases. "If someone has atopic dermatitis and you see that the eosinophil granulocytes are increased in the skin - with the arsenal of weapons they can release - then you know why the patient has such severe skin inflammation." The dermatologist and her team discovered that eosinophils can produce and release a nerve growth factor called BDNF, particularly in atopic dermatitis patients. The resulting, to a certain extent hyperactive nerve cells are therefore one reason why those affected often develop itching very quickly.
Ulrike Raap's portfolio also includes research into itching. She discovered that an itch-causing protein called interleukin-31, which was first identified by US scientists in 2004, correlates with the severity of the disease in atopic dermatitis patients. "Checking this was actually a very simple idea that occurred to me at the nappy-changing table at the time," recalls Raap. "We couldn't have imagined that my technical assistant and I would later place this project in one of the largest immunological journals."
As a result, another high-calibre - and highly awarded - publication was produced in which Raap, together with a colleague from Lübeck, took a close look at the interleukin-31 concentration in mastocytosis patients. Mastocytosis means an increased number of mast cells already present in the skin of every person, which release the messenger substance histamine and thus trigger itching. A serious disease, according to Raap: "If there is an increased number of mast cells in the intestine, patients may suffer from diarrhoea; if there is an increased number of mast cells in the bone marrow, this can lead to osteoporosis, for example." Together with her colleague, she found that interleukin-31 is also increasingly released in mastocytosis patients - and that the IL-31 concentration correlates with the progression of the disease.
When chewing gum does not provide enough support
It is now also clear that the itching protein IL-31 is in turn linked to the eosinophil granulocytes - the blood cells whose appearance is reminiscent of sunglasses. For example, in bullous pemphigoid, a blistering autoimmune disease of the skin. When it occurs, autoantibodies cause "the skin cells, which actually stick together like a strip of chewing gum, to soften and form a blister," says the dermatologist. Eosinophils are not only found in the skin and blood, but in the blister fluid almost in pure culture - "like a small nuclear power plant". These can produce IL-31, among other things, and are activated by it: a perpetual motion machine. "It's all connected," emphasises Raap.
Understanding the cellular processes behind skin diseases even better and being able to take countermeasures: This is the aim of the dermatologist's research. Among other things, she is leading a sub-project on bullous pemphigoid in the Clinical Research Unit Autoimmunity, which is funded by the German Research Foundation (DFG). In addition to eosinophils, the project is also focussing on basophil granulocytes, which play a role in allergic - including acute and potentially life-threatening - inflammations. Raap is involved in a project by a colleague from Münster on the subject of itching. From January, Raap and her Groningen colleague Jonkman will also be involved in a project funded by the faculty, in which they hope to establish a special skin model for blistering autoimmune diseases.
Detective work for unexpected allergies
Raap not only has to combine research, such as weekly laboratory meetings with her laboratory manager on the Wechloy campus, Bernhard Gibbs, with clinic management, including the private outpatient clinic and day clinic. She also teaches at the European Medical School. Raap likes to show the students what is possible in dermatology. Whether it's sexually transmitted diseases in the outpatient clinic, detective work for unexpected contact allergies, the most severe autoimmune diseases or plastic surgery for everything from groats to skin cancer: the wide range is "a real dream" for Raap.
As in the clinic, her research and teaching is always focussed on the patients, whose well-being is close to her heart. "We work on the patients, with the patients, and our aim is to develop new treatment options for them," emphasises Raap. To this end, her team uses the "entire repertoire" of immunological research: "No cells are safe from us". So that the skin - contrary to the title of her inaugural lecture - does not blister if possible.
