VEGFRs in vascular development and disease

Research Angiogenesis and lymphangiogenesis involve the growth of new blood and lymphatic vessels from pre-existing vasculature, respectively. They are indispensable for physiological processes like embryonic development, but they also play a central role in several pathologies, like inflammatory and cardiovascular disorders. Understanding the molecular mechanisms underlying angiogenesis and lymphangiogenesis is crucial in order to translate these findings into the clinic aiming at the production of more efficient pro- and anti-angiogenesis treatments.

We are mainly interested in the role of Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) in blood and lymphatic vessel morphogenesis. VEGFR-3 is primarily expressed in lymphatic endothelial cells and has been mainly involved in lymphatic development and tumor metastasis. However our recent research has revealed important roles for VEGFR-3 also in angiogenesis. We have shown that VEGFR-3 is expressed in sprouting endothelial tip cells during development and in pathological settings as well, and that blocking VEGFR-3 signaling results in suppression of angiogenesis. Recently we were able to unravel some of the molecular mechanisms involved in VEGR-3 signaling, by discovering how VEGFR-3 activation results in the stabilization of newly formed branches in the developing vasculature of the mouse retina.

For our studies we employ several sophisticated genetic mouse models that allow us to manipulate receptor’s expression in vivo, with a great degree of precision. These transgenic mice permit spatial and temporal regulation of receptor’s genetic expression and are valuable tools for further elucidating the signaling properties of VEGFR-3 in the blood and lymphatic vasculature.

Selected publications

Tammela T, Zarkada G, Nurmi H, Jakobsson L, Heinolainen K, Tvorogov D, Zheng W, Franco CA, Murtomäki A, Aranda E, Miura N, Ylä-Herttuala S, Fruttiger M, Mäkinen T, Eichmann A, Pollard JW, Gerhardt H, Alitalo K. VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat Cell Biology, 13(10):1202-13 (2011)

Tammela T, Zarkada G, Murtomäki A, Wallgard E, Suchting S, Wirzenius M, Waltari M, Hellström M, Schomber T, Peltonen R, Freitas C, Duarte A, Isoniemi H, Laakkonen P, Christofori G, Ylä-Herttuala S, Eichmann A, Betsholtz C, and Alitalo K. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature, 454:656-60 (2008)

Contact

Georgia Zarkada, M.D., Georgia.Zarkada (at) Helsinki.fi
Kari Alitalo, Academy Professor, director of the Wihuri Research Institute, Kari.Alitalo (at) Helsinki.fi
Alitalo K in Pubmed ⊕ Opens in a new tab.

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Wihuri Research Institute

Biomedicum Helsinki
Haartmaninkatu 8
FI-00290 HELSINKI
Finland
Director: Kari Alitalo
 
Email: info [at] wri.fi
Tel: +358 9 191 25492 (PR Officer)
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