Department of Immunology, Genetics and Pathology, Uppsala University
Lena Claesson-Welsh is professor in medical biochemistry at Uppsala University since 1997. She was a group leader at the Ludwig Institute for Cancer Research. She has served as the national co-director for the Science for Life Laboratories. She is a member of the Royal Academy of Sciences and the EMBO organization. The main focus of her lab is on the role of blood and lymphatic vessels in physiology and pathology. She is supported by the Knut and Alice Wallenberg foundation, the Leducq Foundation, the Cancer Society and the Research Council.
Vascular endothelial growth factors (VEGFs) control a range of vascular functions through the receptor tyrosine kinase VEGFR2. VEGFR2 is essential as it transduces signals regulating endothelial survival, proliferation, migration, polarity and vascular leakage. VEGFR2 signaling is suppressed through formation of multiprotein complexes including protein tyrosine phosphatases, at endothelial junctions. VEGFR2 activation induces junctional destabilization, allowing signal transduction to be initiated. Junctional destabilization eventually results in a break-down of the vascular barrier, resulting in transient passage of molecules and cells across the vessel wall. We have identified the VEGFR2-induced signaling pathway regulating junctional destabilization and vascular leakage. Using several recombinant mouse models for different components in the pathway we show how it can be suppressed to seal junctions in normal vessels as well vessels in pathologies, suppressing hematogenic and lymphatic metastatic spread in cancer and ocular edema in retinopathy.
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