Dr. Alitalo discovered vascular growth factors that regulate growth of lymphatic vessels (lymphangiogenesis), and characterized the involved receptors and signaling mechanisms. He isolated and characterized the arterial endothelial tyrosine kinase Bmx and endothelial receptor tyrosine kinase Tie1, which together with Tie2 forms the receptor complex for angiopoietins involved regulation of vascular stability, inflammation, angiogenesis and lymphangiogenesis. He also isolated and cloned the vascular endothelial growth factor (VEGF) receptor-3, purified and cloned its ligand, the first lymphangiogenic growth factor, VEGF-C. Together with Dr. Marc Achen and Steven Stacker he characterized VEGF-D, another VEGFR3 ligand, and together with Dr. Ulf Eriksson, VEGF-B, a growth factor for coronary and adipose vasculature. Studies in his laboratory have demonstrated VEGF-C induced tumor angiogenesis and lymphangiogenesis, intralymphatic tumor growth, VEGF-C association with tumor metastasis and its inhibition by blocking the VEGFR-3 signal transduction pathway. Inhibitors of this pathway from his laboratory have been subject to phase 2 clinical trials in age-related macular degeneration and diabetic macular edema. He demonstrated mechanisms of lymphedema, and developed growth factor therapy for lymphedema, which has now undergone a phase 2 clinical trial. His recent findings include the discovery of meningeal lymphatic vessels, a molecular model of angiopoietin-Tie receptor complex at endothelial cell-cell junctions, and characterization of angiopoietin-2 mutations in human lymphedema.
Translational insights into vascular endothelial growth factorsKari Alitalo, Helsinki FI