We are interested on mechanisms that control endothelial cell (EC) behavior and functional specialization. The endothelium forms the inner lining of blood vessels, which are arranged in complex, tree-like networks that extend almost into every organ of the vertebrate body. Blood vessels and ECs show distinct morphological and functional properties, depending on the vascular bed (arteries, veins and capillaries), the organ where they reside, mechanical stress, or the regulation through specific transcriptional programs. Recently, we demonstrated using mouse retina as a model system that some endothelial tip cells, specialized ECs at the distal end of vascular sprouts, are arterial progenitors and incorporate into growing arteries (Pitulescu M.E. et al., 2017). Within this CRC, we investigate this new mechanism of artery formation in mouse central nervous system (CNS), namely in retina and brain. Better understanding of this process might also lead to new therapeutical approaches in cardiovascular diseases. Furthermore, to understand endothelial cell heterogeneity in murine CNS, we are studying the transcriptional regulation of EC behavior during vascular morphogenesis. To address our questions, we use powerful mouse genetics, state-of-the-art-microscopy techniques, in vitro models, and different sequencing techniques.
- Pitulescu M.E. *, Schmidt I., Giaimo B.D., Antoine T., Berkenfeld F., Ferrante F., Park H., Ehling M., Biljes D., Rocha S.F., Langen U.H., Stehling M., Nagasawa T., Ferrara N., Borggrefe T., Adams R.H. * (2017). Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nat Cell Biol. 19, 915-927. (*shared corresponding authorship)
- Langen, U.H., Pitulescu M.E., Kim, J., Enríquez-Gasca, R., Sivaraj, K., Kusumbe, A., Singh, A., Di Russo, J., Bixel, G., Zhou, B., Sorokin, L., Vaquerizas, J., Adams, R.H.(2017). Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat Cell Biol 19, 189-201.
- Nunan, R., Campbell, J., Mori, R., Pitulescu, M.E., Jiang, W., Harding, K., Adams, R.H., Nobes, C, Martin, P. (2015). Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization. Cell Rep 13, 1380-95.
- Xu, C., Hasan, S., Schmidt, I., Rocha, S., Pitulescu, M.E., Bussmann, J., Meyen, D., Raz, E., Adams, R.H., Siekmann, A. (2014). Arteries are formed by vein-derived endothelial tip cells. Nat Commun 5, 5758.
- Pitulescu, M.E. and Adams RH. (2014). Regulation of signaling interactions and receptor endocytosis in growing blood vessels. Cell Adh Migr 8, 366-77.
- Corada, M., Orsenigo, F., Morini, M.F., Pitulescu, M.E., Bhat, G., Nyqvist, D., Breviario, F., Conti, V., Briot, A., Iruela-Arispe, M.L., Adams, R.H., and Dejana, E. (2013). Sox17 is indispensable for acquisition and maintenance of arterial identity. Nat Commun 4, 2609.
- Wang, Y.*, Nakayama, M.*, Pitulescu, M.E.*, Schmidt, T.S.*, Bochenek, M.L., Sakakibara, A., Adams, S., Davy, A., Deutsch, U., Luthi, U., Barberis, A., Benjamin, L.E., Makinen, T., Nobes, C.D., and Adams, R.H. (2010). Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 465, 483-486. (* shared first authorship)
- Sawamiphak, S., Seidel, S., Essmann, C. L., Wilkinson, G.A., Pitulescu, M.E., Acker, T., and Acker-Palmer, A. (2010). Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465, 487-491.
- Pitulescu, M.E., Schmidt, I., Benedito, R., and Adams, R.H. (2010). Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice. Nat Protoc 5, 1518-1534.
- Pitulescu, M.E. and Adams, R.H. (2010). Eph/ephrin molecules-a hub for signaling and endocytosis. Genes Dev 24, 2480-2492.