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. 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

Our research group is towards this end

• examining the signaling interplay between endothelial cells, as well as interactions of endothelial cells with pericytes and tumor cells.
• investigate the role of Delta-Notch signaling and other genes, which are implicated in the formation of vascular malformations and vascular tumors.
• studying novel factors necessary for barrier functions of blood vessels, and how these control the passage of tumor cells and fluids through the vessel wall. An important research approach deals with the question how genetic alterations in the endothelium affect metabolism.

1. Jabs M,  Rose AJ, Lehmann LH, Taylor J, Moll I, Sijmonsma TP, Herberich SE, Sauer SW, Poschet G, Federico G, Mogler C, Weis EM, Augustin HG, Yan M, Gretz N, Schmid RM, Adams RH, Gröne HJ, Hell R, Okun JG, Backs J,  Nawroth PP, Herzig S, Fischer A. Inhibition of endothelial Notch signaling impairs fatty acid transport and leads to metabolic and vascular remodeling of the adult heart. Circulation, 2018 in press
2. Wieland E*, Rodriguez-Vita J*, Liebler SS, Mogler C, Moll I, Herberich SE, Espinet E, Herpel E, Menuchin A, Chang-Claude J, Hoffmeister M, Gebhardt C, Brenner H, Trumpp A, Siebel CW, Hecker M, Utikal J, Sprinzak D, Fischer A: Endothelial Notch1 Activity Facilitates Metastasis. Cancer Cell, 3:355-367, 2017.
3. Feldner A, Adam MG, Tetzlaff F, Moll I, Komljenovic D, Sahm F, Bäuerle T, Ishikawa H, Schroten H, Korff T, Hofmann I, Wolburg H, von Deimling A, Fischer A.  Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Mol Med. 2017; 9(7):890-905.
4. Yang W-J*, Hu J*, Uemura A, Tetzlaff F, Augustin HG, Fischer A.  Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit pathological angiogenesis. EMBO Mol Med. 2015, 7 (10):1267-1284.
5. Klose R*, Berger C*, Moll I, Adam MG, Schwarz F, Mohr K, Augustin HG, Fischer A: Soluble Notch ligand and receptor peptides act antagonistically during angiogenesis. Cardiovasc Res, 107:153-63, 2015.
6. Schulz GB, Wieland E, Wüstehube-Lausch J, Boulday G, Moll I, Tournier-Lasserve E, Fischer A: Cerebral cavernous malformation-1 protein controls DLL4-Notch3 signaling between the endothelium and pericytes. Stroke, 46:1337-43, 2015.
7. Adam MG, Berger C, Feldner A, Yang WJ, Wüstehube-Lausch J, Herberich SE, Pinder M, Gesierich S, Hammes HP, Augustin HG, Fischer A: Synaptojanin-2 binding protein stabilizes the notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circ Res, 113: 1206–18, 2013.
8. Wüstehube J*, Bartol A*, Liebler SS, Brütsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A: Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A, 107: 12640–5, 2010.
9. Brütsch R*, Liebler SS*, Wüstehube J*, Bartol A, Herberich SE, Adam MG, Telzerow A, Augustin HG, Fischer A: Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. Circ Res, 107: 592–601, 2010.
10. Fischer A, Steidl C, Wagner TU, Lang E, Jakob PM, Friedl P, Knobeloch KP, Gessler M: Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res, 100: 856–63, 2007.