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Summer School Molecular Medicine / Program 2024 / Module Complex II / Module II/3
Prof. Dr. Regine Heller
Institute of Molecular Cell Biology,
Center for Molecular Biomedicine (CMB),
Jena University Hospital
Hans-Knöll-Str. 2
07745 Jena

phone: +49 3641 9395633
The figure shows blood vessel formation in Matrigel plugs in mice in response to basic fibroblast growth factor. Matrigel plugs were fixed in Zinc fixative and embedded in paraffin. 5 µm sections were prepared and stained for the endothelial marker protein CD31.
The figure shows blood vessel formation in Matrigel plugs in mice in response to basic fibroblast growth factor. Matrigel plugs were fixed in Zinc fixative and embedded in paraffin. 5 µm sections were prepared and stained for the endothelial marker protein CD31.

Angiogenesis, the growth of blood vessels, is an essential biological process under both physiologic and pathologic conditions. It requires the tight coordination of endothelial cell proliferation, differentiation, migration, of matrix degradation and of cell-cell signaling processes. Angiogenesis is controlled by a variety of growth factors with Vascular Endothelial Growth Factor (VEGF) being one of the most important molecules.

Our interest focuses on the characterization of signalling pathways in endothelial cells in response to proangiogenic stimuli, in particular to VEGF. We are especially interested to understand how signals initiated or controlled by oxidative or metabolic stress affect endothelial cell functions. In this context, we investigate the role of the energy sensor AMP-activated kinase (AMPK) and of oxidant-sensitive signaling molecules such as protein tyrosine phosphatases. Recently, we found that AMPKα1 plays an essential role in VEGF-induced angiogenesis in vitro and in vivo and characterized the VEGF/AMPK/GFAT* pathway as one of the responsible mechanisms  (* GFAT - glutamine fructose-6-phosphate amidotransferase; Stahmann N et al. J Biol Chem. 285:10638-52, 2010, Zibrova D et al. Biochem J 474:983-1001, 2017).

The course will provide hands-on training in preparing primary endothelial cells of human or mice origin and in performing different migration and angiogenesis assays (transwell migration, wound healing assays, spheroid assays, matrigel assays). These tests involve cellular fluorescence microscopy and the ECIS (Electric Cell-Substrate Impedance Sensing) technology. Further, the students will get familiar with RNA interference techniques and shRNA lentiviral transduction in primary cells to investigate the role of selected molecules in angiogenesis.

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