FG 1368

The combination of Duska Dragun and Wolf-Hagen Schunck brings together long-standing interest in the area of renal transplantation with in depth knowledge of the role of arachidonic acid metabolites. Dragun studies the vascular mechanisms involved in the pathogenesis of AKI in native and transplanted kidneys in experimental and clinical settings. In particular, the finding that agonistic autoantibody-mediated activation of angiotensin II-type 1 receptor induces pro-inflammatory downstream cascades in the vasculature and severe injury of the renal allograft with consecutive hypertension has received widespread attention. Schunck has recently demonstrated that cytochrome P450 (CYP) dependent 20-HETE generation and action is involved in the development of renal ischemia/reperfusion injury (I/RI).

Maik Gollasch's group has put forward new concepts in the paracrine control of the vasculature. He contributes to the Research Unit by his in-depth-knowledge of vascular smooth muscle patch clamping and microvascular imaging, with particular interest in TRP channels and cytochrome P450 products. Martin Tepel did pioneering work on new strategies to prevent CIN. His seminal paper on the role of N-acetylcysteine in the prevention of CIN forged the first link from oxidative stress in CIN to clinical application. Since then, the preventive application of N-acetylcysteine has been introduced in several national guidelines and has been confirmed in a number of subsequent studies and meta-analyses. Tepel is a Guest Professor at the Charité, and holds a faculty appointment at the University of Southern Denmark.

Dominik Müller specialises in molecular pathways of renal damage. Together with Ruth Schmidt-Ullrich, an expert in NF-κB, they have provided a new view on the role of NF-κBs role in renal failure. Inhibition of NF-κB markedly blunts renal inflammation and alleviates renal damage as caused by hypertension. Kai Schmidt-Ott, an Emmy Noether Fellow and Junior Professor, creates tubular-specific mouse models for investigating the role of the Wnt family of secreted glycoproteins that bind cell surface receptors and modulate the activity of specific intracellular effectors. Wnt-catenin is a fundamental molecular pathway in both renal embryogenesis and disease.

Thoralf Niendorf heads the Berlin Ultrahigh Field Facility of the ECRC on Campus Berlin-Buch. This facility houses human Magnetic Resonance Imaging (MRI) scanner (3.0 Tesla, 7.0 Tesla) and a 9.4 Tesla MRI scanner for imaging of mice and rats. Niendorf provides expertise in MRI methodology with a focus on new ways of non-invasive mapping and probing morphology, function, physiology and metabolism to advance renal MRI in conjunction with alternative tools established in physiology. Erdmann Seeliger participates by providing expertise in integrative physiology techniques; Uwe Hoff is junior faculty and contributes by implementing the I/R-model.

The Andreas Patzak/Pontus Persson group has long-standing experience in kidney function
and AKI as observed after contrast media exposure. The extensive work by this group comprises articles on adenosine and angiotensin II signalling in renal vasculature, focusing on central mechanisms of CIN, as well as a number of often-cited larger-scale studies on the pathophysiology of CIN. Patzak is specialised on the renal microcirculation.

Sebastian Bachmann and Christian Rosenberger unite experimental and clinical background, and will contribute considerable expertise in the mechanisms mediating hypoxic damage to renal tissue. Moreover they have profound expertise in the area of HIF research and fibrosis. Bachmann provides valuable expertise with regard to kidney morphology.

The group of Erdmann Seeliger/Bert Flemming/Pontus Persson contributes to the network by experience in renal hemodynamics and microcirculation. They assess various parameters of the renal microcirculation, a prerequisite for the understanding of AKI. Together with, e.g., Christian Rosenberger this group has underscored the importance of diminished medullary blood flow for the development of CIN. By their work on CIN, the importance of fluid viscosity for this form of AKI became widely accepted, and was confirmed clinically by a large-scalestudy comprising observations on over 57,000 patients.

Timm Westhoff provides experience in the isolation, identification and characterization of new physiological mediators. For example, he isolated a novel endocrine compound from human myocardium and has performed several clinical studies.