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From Bedside to Bench

Clinical research is challenging scientific work that requires a good deal of creativity. It also has a fundamental impact on our molecular understanding of various diseases. As a result, this kind of research requires a strong background in both clinical and scientific training.

I gained my training in medicine at the medical schools of the Universities of Göttingen and Tübingen. Work for my doctoral thesis, which described the influence of different surface activators on intrinsic coagulation pathways in high dose aprotinin therapy, was at the Department of Heart and Vascular Surgery at the University Hospital in Tübingen. This work enabled me for the first time to study clinically relevant problems in the laboratory. After finishing my internship at the Department of Gastroenterology, Hepatology, and Infectious Diseases at the University Hospital, I joined the laboratory of Professor Klaus Schulze-Osthoff, who has an outstanding scientific reputation especially in the field of apoptosis. In 1999, we moved from Tübingen to the University of Münster, where I am presently working as a postdoctoral fellow in the Department of Immunology and Cell Biology. Especially during the last few years, I have gained a broad scientific and methodological background in cell biology, protein chemistry, and molecular biology.

During my postdoctoral training, I have developed a great enthusiasm for signalling pathways, which have become more and more relevant to the understanding of pathological processes occurring in inflammatory and infectious diseases. Among the various pathophysiological pathways, apoptosis--or ?programmed cell death?--has a tremendous impact on our understanding of a multitude of diseases. This kind of cell death particularly serves to eliminate unwanted cells from the organism, including those infected with bacteria or viruses. Although apoptosis is causally implicated in various diseases, the molecular mechanisms leading to cell death, as well as the role of caspases (the proteases that are the main executioners of apoptosis), are unknown in most cases.

When I started working in the research laboratory, I first established novel tools that became important in analysing apoptotic events in patients? tissue biopsies and blood samples and that therefore provided new insights into the role of apoptosis in various diseases. Recently, my colleagues Dr. R. Jänicke and Dr. B. Sinha and I clearly defined the signalling pathway used in Staphylococcus aureus-induced cytotoxicity (Bantel et al., Journal of Cell Biology 155, 637-647 [2001]). S. aureus is one of the most common gram-positive bacterial pathogens and plays a role in nosocomial infections as well as in serious clinical complications, such as septic and toxic shock syndromes. Our findings open promising insights into how S. aureus mediates apoptosis in T-lymphocytes, which may also explain immune cell death during sepsis. These data therefore provide a molecular rationale for future diagnostic and therapeutic interventions in bacterial infections.

In addition to my interest in bacterial infections, I am also fascinated by molecular research on virus-mediated signalling pathways. In my recent study published in Hepatology (34, 758-767 [2001]), I demonstrated for the first time that caspases are indeed activated in liver biopsies of patients with chronic hepatitis C virus (HCV) infection. Surprisingly, I was able to detect active caspases in a high percentage of liver cells (7%-20%). Most interestingly, activation of caspases correlated significantly with the inflammatory activity in chronic HCV infection. This observation is of high clinical relevance as it opens up challenging new possibilities for monitoring disease activity and therapeutic efficacy in chronic HCV infection.

My studies were supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University of Münster, an institution that emphasizes a strong connection between various basic and clinical research laboratories. For my work, I was recently awarded the Freundlich-Preis and the Young Investigator Award in clinical microbiology and infectious diseases (provided by the European Society of Clinical Microbiology and Infectious Diseases).

Overall, clinical research is important because it has a fundamental impact on our pathophysiological understanding of various diseases and provides a molecular rationale for the development of new diagnostic and therapeutic interventions in these diseases. However, investigating clinically relevant problems at the molecular level requires both medical and scientific expertise. The application of basic research to problems concerning patients? health makes this job so exciting. Moreover, the simultaneous involvement in basic and clinical research activities is of great advantage because it opens up challenging career possibilities in both university institutions and the pharmaceutical industry.