Professur für Experimentelle Gefäßmedizin und Transplantationsforschung
Vascular Medicine Research: How Blood Vessels Regulate Inflammation
PI Univ.-Prof. Dr. med. Florian P. Limbourg
In clinic, we see patients who suffer from hypertension and cardiovascular or renal diseases. From a clinical point of view, one major problem in these patients is vascular dysfunction and impaired regenerative capacity of blood vessels and organs, but also chronic low-grade inflammation, which promotes further dysfunction. In fact, the two seem very much interconnected. Certainly chronic inflammation triggers vascular dysfunction, however, vascular dysfunction per se seems to be a major factor triggering inflammation. This is the major focus of our current research efforts.
We were among the first to show that blood vessels influence monocyte and macrophage cell fate, which is regulated by Notch signaling, an evolutionary conserved signaling mechanisms working by direct cell-cell contact. Distinct endothelial cell populations express a Notch ligand from the Delta-like (Dll) family in specialized niches, which in turn activates Notch signaling in monocytes and controls homeostatic monocyte differentiation. The same process also promotes monocyte maturation into healing macrophages during ischemia, while conditional deletion of the ligand in endothelial cells impairs normal monocyte differentiation, which results in enhanced inflammation and impairs vessel regeneration after ischemia. This work has opened a new aspect on the concept of endothelial dysfunction and shown another important function of blood vessel independent of blood flow. However, how distinct myeloid or lymphoid cell populations respond to endothelial cells during inflammatory challenges and how their function and fate is regulated by Notch signaling is still unclear.
Publications: see Pubmed
If you are a motivated MD student not afraid of bench work and looking for a structured experimental MD thesis project, please contact us. Ideal is participation in the StrucMed program.
We are also looking for PhD students for a basic inflammation research project.
Methods: advanced multicolor flow cytometry analysis and FACS sorting of cell populations, cell culture techniques, tissue and organ analysis by histology and laser scanning confocal microscopy, advanced genetic mouse models, gene expression and protein analyses.