Research

Analysis of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)-mediated signal transduction to investigate the molecular, physiological and pathophysiological mechanisms of this signalling pathway e.g. in the cardiovascular, renal, gastrointestinal and immunological system. Thereby, cellular and transgenic mouse models are used.	? ??????????????? NO/NP/cGMP Signal transduction
Ligands, Kinases and Kinase substrates are analysed with heterologous expression systems and primary cell cultures to measure changes in the intracellular calcium, of the cytoskeleton and the proliferation. cGMP-dependent protein kinases I and II are expressed (in SF9-insect cells) and kinase-activators and –inhibitors are tested. Using murine models, functions in the cardiovascular, renal and haematological system are analysed.
? ?????????? Immunocytochemical analysis in vascular smooth muscle cells (VSMC)
? ? ? ? Defect thrombosis suppression by NO in IRAGΔ12 mouse mutant
? ? Upon sepsis-induction (by lipopolysaccharides) the blood pressure (MAP, measured by telemetry) is not lowered in IRAG-KO mice

Model for inhibition of renal fibrosis by NO/cGMP/cGKI. The NO-donor ISDN (isosorbid-dinitrate) or soluble guanylyl cyclase (sGC) activator YC1 stimulates cGKIα which suppresses the transforming growth factor β (TGFβ) signaling by inhibition of the profibrotic RhoA/ROCK (Rho-associated kinase) pathway. [Y27632: ROCK-inhibitor; FSP-1: fibroblast-specific protein-1; EMT: epithelial mesenchymal transition] (Figure from: Schinner et al., Kidney International 2013, doi: 10.1038/ki.2013.219)

Techniques and expertise:

Kinase assays, receptor binding assays, G-protein assays, immunoblotting, protein purification, immunoprecipitation, affinity chromatography, FPLC, HPLC, molecular biology, fluorescence microscopy, calcium imaging, timelapse microscopy, immunohistochemistry, cell culture, myography, aggregometry, microtome, transgenic mice, in vivo pharmacology (inter alia telemetry, kidney fibrosis)

Cooperations in research and teaching:

Universities: Hofmann (TU München): cardiovascular analysis, transgenic mice models; Massberg (TU München): thromobosis models; Kurtz (Regensburg): kidney function of cGMP; Seifert (Hannover): function of pyrimidinic nucleotides; Steegborn (Bayreuth): x-ray structure analysis
Companies: Bayer Health Care; Novartis; Merck

Scientific cooperative grants (Graduate School; Sonderforschungsbereich):

Project in: SFB699 “Structural, physiological and molecular basis of renal function”