Helmholtz University Junior Research Group Vascular Signaling and Cancer
PD Dr. Andreas Fischer
Blood vessels are a prerequisite for the maintenance of all organ functions. Embryogenesis is dependent on the development and outgrowth of blood vessels, which provide the organism with oxygen and nutrients. Sprouting angiogenesis occurs rarely in the adult organism but can be observed for example during wound healing and also in cancer. Thus, a detailed knowledge about factors regulating angiogenesis and genetic networks, which provide a functional quiescent vascular bed, is highly desirable.
Besides the formation of new blood vessels, maintenance of existing blood vessels is essential as well. Endothelial cells provide the inner lining of all blood vessels. Disturbed endothelial cell functions are implicated in the pathogenesis of several cardiovascular diseases. Importantly, tumor growth and metastasis are strictly dependent on vascular growth and remodeling.
Our research group investigates signaling pathways that keep blood vessels in a resting but fully functional state. We examine the signaling interplay between endothelial cells as well as interactions of endothelial cells with pericytes and tumor cells. By using cell culture and animal models, our research will help to better understand how genetic factors coordinate angiogenesis in the adult organism. We investigate the role of Delta-Notch signaling and other genes, which are implicated in the formation of vascular malformations and vascular tumors. Other projects in our group focus on barrier functions of blood vessels which are essential to control the passage of tumor cells and fluids through the vessel wall. A novel research approach deals with the question how genetic alterations in the endothelium affect metabolism and are implicated in the pathogenesis of cardiovascular diseases.
Our research work aims at identifying critical molecular and cellular mechanisms of cardiovascular diseases and tumor progression. These findings will help to lay the foundation for the development of innovative pharmacological strategies.
Wüstehube J, Bartol A, Liebler SS, Brütsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A. (2010). Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A., 28, 12640-5.
Brütsch R, Liebler SS, Wüstehube J, Bartol A, Herberich SE, Adam MG, Telzerow A, Augustin HG, Fischer A. (2010). Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. Circ Res., 5, 592-601.
Adam MG, Berger C, Feldner A, Yang WJ, Wüstehube-Lausch J, Herberich SE, Pinder M, Gesierich S, Hammes HP, Augustin HG, Fischer A. (2013) Synaptojanin-2 binding brotein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circ Res., ePub Sep. 11.
Yang WJ, Hu J, Uemura A, Tetzlaff F, Augustin HG, Fischer A. (2015) Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit pathological angiogenesis. EMBO Mol Med., ePub July 20