Mara Pitulescu

Research topic

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.

Selected Publications

  • Luxan, G.§, Stewen, J.§, Diaz, N., Kato, K., Maney, S.K., Aravamudhan, A., Berkenfeld, F., Nagelmann, N., Drexler, H.C., Zeuschner, D., Faber, C., Schillers, H., Hermann, S., Wiseman, J., Vaquerizas, J.M., Pitulescu, M.E.*, and Adams, R.H.* (2019). Endothelial EphB4 maintains vascular integrity and transport function in adult heart. Elife 8. (§, *equal contribution)
  • Corada, M., Orsenigo, F., Bhat, G.P., Conze, L.L., Breviario, F., Cunha, S.I., Claesson-Welsh, L., Beznoussenko, G.V., Mironov, A.A., Bacigaluppi, M., Martino, G., Pitulescu, M.E., Adams, R.H., Magnusson, P., and Dejana, E. (2019). Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier. Circ Res 124, 511-525.
  • Del Monte-Nieto, G., Ramialison, M., Adam, A.A.S., Wu, B., Aharonov, A., D'Uva, G., Bourke, L.M., Pitulescu, M.E., Chen, H., de la Pompa, J.L., Shou, W., Adams, R.H., Harten, S.K., Tzahor, E., Zhou, B., and Harvey, R.P. (2018). Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation. Nature 557, 439-445.
  • 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., and 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.M., Enriquez-Gasca, R., Sivaraj, K.K., Kusumbe, A.P., Singh, A., Di Russo, J., Bixel, M.G., Zhou, B., Sorokin, L., Vaquerizas, J.M., and 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.G., Harding, K.G., Adams, R.H., Nobes, C.D., and Martin, P. (2015). Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization. Cell Rep 13, 1380-1395.
  • 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. (§ equal first author contribution)
  • 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. (*shared corresponding authorship)
  • Pitulescu, M.E., and Adams, R.H. (2010). Eph/ephrin molecules--a hub for signaling and endocytosis. Genes Dev 24, 2480-2492.