Helmholtz University Junior Research Group Vascular Signaling and Cancer

PD Dr. Andreas Fischer

Small blood vessels of the ret...
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Blood vessels play an essential role in the maintenance of all organ functions, because they provide oxygen and nutrients. Tumors cannot grow beyond a certain size without the recruitment or the growth of new blood vessels (angiogenesis). Therefore, therapies have been developed to interfere with angiogenesis. Recent research have shown that blood vessels are not simple passive tubes for the transport of blood, but that they also instruct tissue regeneration and differentiation. Moreover, there is increasing evidence that signaling pathways in endothelial cells actively control the transport of nutrients and immune cells across the vessel wall.

FUTURE OUTLOOK
Our research group investigates signaling pathways that control blood vessel growth and the transport of nutrients, cancer cells and immune cells across the vessel wall. We have identified Delta-Notch and Semaphorin-Neuropilin signaling pathways as key players of pathological angiogenesis and metastasis. Based on this, our research aims at identifying critical molecular and cellular mechanisms of tumor progression driven by these signaling pathways. We developed innovative tools to interfere with Notch signaling, and we are currently testing them in preclinical cancer models. The fact that Notch signaling is also active in normal blood vessels might complicate the therapeutic use of such compounds. Therefore, we are also investigating how Notch signaling activity is modified under physiological conditions and how it controls the integrity and function of the vascular barrier. Our data indicates that blocking Notch signaling might be a powerful strategy to interfere with several steps of the metastatic cascade. However, such treatment also interferes with the proper flux of nutrients and hormones across the vessel wall. We are currently investigating the molecular mechanisms responsible and are developing strategies to circumvent this.

Contact

PD Dr. Andreas Fischer
Vascular Signaling and Cancer (A270)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg

Selected Publications

  • Klose R. et al. (2015). Soluble Notch ligand and receptor peptides act antagonistically during angiogenesis. Cardiovasc Res., 107(1), 153-163.
  • Yang W.J. et al. (2015). Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit pathological angiogenesis. EMBO Mol Med., 7(10), 1267-1284.
  • Adam M.G. et al. (2013). Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circ Res., 113(11), 1206–1218.
  • Wüstehube J. et al. (2010). Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A., 107(28), 12640–12645.?
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