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Visiting Faculty, Hannover Medical School, Germany
Membrane Biology
M.D., Free University of Berlin, 1982
Professor of Medicine,
Dean of Medical Education,
Hannover Medical School
The goal of our research is to understand the mechanisms of the endothelium. Endothelial cells line all blood vessels and play an important role in acute and chronic vascular diseases such as inflammation, hypertension, and atherosclerosis. They play an important role in the formation of new blood vessels, regulate vasodilation and the adhesion of inflammatory cells, and control the permeability of the vessel wall. Increased capilary permeability results in proteinuria, a hallmark of renal and vascular disease.
We use zebrafish as a research model to understand how endothelial cells contribute to proteinuria and to find new therapeutic targets. Targeted deletion of unknown genes by morpholino and antisense strategies, and the use of confocal and electron microscopy allows us to find novel mechanisms of endothelial function. In addition to proteinuria, we are looking for developmental changes in the kidney vasculature.
We are especially interested in is the protein kinase C (PKC) family. We have found that PKC isoforms play an importnat role in diabetic nephropathy, transplantation, and inflammation. We are now analyzing the role of PKC epsilon, theta, and zeta in our zebrafish model.
To further analyze novel therapuetic targets for renal disease, we are collaborating with Ron Korstanje and his lab group at the Jackson Laboratory. This collaboration allows us to use mice as a second animal model as a translational tool for the development of novel therapies.
We are also studying the effects of environmental toxins on proteinuria in the zebrafish model.
Testing of novel genes of endothelial function
Environmental toxins and proteinuria
Students will learn to handle zebrafish and zebrafish embryos. They will use microinjection into fish eggs and embryonic vasculature. For further analysis, they will use confocal microscopy and prepare tissue samples for electron microscopy.
Members of the Haller lab:
Lynn Staggs, technician
Mario Schiffer, MD
Jessica Wortmann, MD
Hermann Haller, MD
Mechanisms of proteinuria – podocytes and endothelium
Our research group works on mechanisms of proteinuria. Proteinuria is a hallmark of renal and cardiovascular disease and indicates acute and chronic damage to the vasculature. At MDIBL we use zebrafish as an animal model
(1) to analyze the molecular mechanisms of capillary permeability and
(2) to identify novel therapeutic targets to prevent proteinuria.
Zebrafish are an ideal model to test gene deletion by using morpholino or antisense strategies. Originally, the zebrafish model was used as a platform for the study of developmental biology. Recent work with the zebrafish model, however, has extended its application to a wide variety of experimental studies relevant to human disease. We have recently developed a model where kidney and vascular function can be assessed in the zebrafish embryo. This method allows us to screen for novel molecules in the pathogenesis of renal and vascular disease. We also can use this model to identify novel targets for drug development. To further analyze the molecular mchanisms of proteinuria we use transgenic GFP-zebrafish, cell culture, confocal microscopy and elctron microscopy.
Our lab works in close collaboration with the Jackson lab to use other animal models for translational research.