Division of Vascular Signaling and Cancer

Prof. Dr. Andreas Fischer

Fluorescence microscopy image of a tumor. Blood vessels are stained in green (endothelial cells) and red (mural cells), cell nuclei in blue.
© dkfz.de

Blood vessels supply almost every cell in the human body with oxygen and nutrients. However, blood vessels are not simple, passive tubes enabling the transport of blood, but also instruct tissue regeneration, stem cell renewal and differentiation, as well as tumor progression. In addition, there is increasing evidence that signaling pathways in endothelial cells actively control the transport of nutrients, hormones, immune and cancer cells across the vessel wall. As such, the endothelium appears to act as a communication platform that integrates numerous signals from blood and parenchymal cells to actively maintain homeostasis.

The Division of Vascular Signaling and Cancer studies signaling pathways that control blood vessel growth in cancer and the transport of nutrients, hormones, cancer cells and immune cells across the vessel wall. Our laboratory has identified Delta/Notch and Semaphorin/Neuropilin signaling in the endothelium as key players of angiogenesis, barrier control and metastasis. We aim at understanding how endothelial cells orchestrate the recruitment and differentiation of immune cells and how this alters inflammation and tumor progression. Secondly, we aim at understanding the roles of endothelial cells as organ-specific sensors of nutritional status and analyze how changes in plasma metabolite concentration alter the transcriptional landscape and the functions of the endothelium. We investigate how endothelial signaling pathways affect the transport of plasma metabolites and how this affects organ functions.

FUTURE OUTLOOK
Based on this research we will define innovative preclinical therapeutic strategies to interfere with the progression of metabolic diseases and cancer.

Contact

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

Selected Publications

  • Wieland, Rodriguez-Vita et al. (2017) Endothelial Notch1 facilitates metastasis. Cancer Cell, (3) 355-367.
  • Feldner A, et al., (2017) Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Mol Med. 9(7):890-905.
  • 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.
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