Stefan Rose-John - Biography#

Stefan Rose-John studied Biology, Chemistry and Physics at the University of Heidelberg. After his doctorate, he worked as a postdoc at the Michigan State University in the USA. He became a group leader at the German Cancer Research Center in Heidelberg, Germany. After moving to the RWTH Aachen, he was habilitated in Biochemistry. He became Associate Professor of Pathophysiology at the University of Mainz. In 2000, he moved to the University of Kiel where he became full Professor and Director of the Institute of Biochemistry.

His laboratory is focused on understanding the molecular biology of cytokines. Using structure-function analysis approaches, he has defined the binding sites of Interleukin-6 (IL-6) and its two receptor subunits, Interleukin-6-receptor (IL-6R) and gp130. This has enabled him to build the first molecular model of the IL-6R complex and it was the starting point for the construction of various designer cytokines with considerably higher specific biologic activity than the natural cytokines. A second aspect of his work started with the discovery of a naturally occurring proteolytic cleavage of the IL-6R, which leads to the generation of a soluble IL-6R (sIL-6R). He discovered that the complex of sIL-6R and IL-6 stimulates cells, which express the signal transducing receptor subunit gp130 but not the ligand binding subunit IL-6R. In the absence of the sIL-6R such cells do not respond to IL-6. He has called this process 'trans-signaling' and he has shown that 'trans-signaling' is important for the regulation of cellular differentiation and of apoptosis and has a prominent role in inflammation, neuronal survival, hematopoiesis, and tumor defense. He has developed the concept that IL-6 'trans-signaling' is an emergency reaction of the human immune system and that disruption of 'trans-signaling' can be used therapeutically for the treatment of chronic inflammatory diseases and cancer. Indeed, he generated a specific IL-6 'trans-signaling' antagonist, which – in animal models – has proven effective in blocking chronic inflammatory diseases such as Crohn’s diseases, Rheumatoid Arthritis and inflammatory colon cancer. This protein under the WHO name 'Olamkicept' has successfully finished Phase II clinic trials in patients with inflammatory bowel disease and is on its way to Phase III clinic trials.