Research program
Angiopoietin growth factorsThe angiopoietin growth factors (Ang, ANGPT) and their Tie receptors are key signaling molecules in controlling the various functions of the vasculature. Scientists at WRI have identified growth factor mechanisms regulating signaling via the Ang-Tie system, and unraveled how this system may be modulated to inhibit tumor metastasis.
Structure of vascular growth factor-receptor complexesVascular endothelial growth factor (VEGF) receptors are among the major mediators of both angiogenesis and lymphangiogenesis in development and in disease. Scientists at WRI have determined the crystal structures of the VEGF-C – VEGFR-2 complex and of the VEGF-D growth factor, revealing structural determinants mediating specificity of ligand-receptor interactions.
VEGFRs in vascular development and diseaseVascular Endothelial Growth Receptors (VEGFRs) are principal regulators of embryonic, postnatal and pathological angiogenesis. Using state of the art genetic models, scientists at WRI have identified novel functions for VEGFR-3 in blood vessel development and have elucidated some of the mechanisms by which VEGFR-3 controls angiogenic signaling.
Vascular growth factors regulating coronary artery growthVascular endothelial growth factor B (VEGF-B) is one of the less well understood endothelial growth factors that specifically binds to VEGF receptor-1 (VEGFR-1). Scientists at WRI have recently found that the VEGF-B growth factor can induce hypertrophy, and the growth of coronary blood vessels, thus opening possibilities for therapeutic use of VEGF-B in cardiovascular diseases.
Lymphatic vessels in obesity and cardiovascular diseaseScientists at WRI have made seminal and clinically translatable discoveries in the field of lymphatic biology. Recent discoveries unexpectedly link lymphatic vessel malfunction to obesity and cardiovascular disease processes, such as thrombosis and atherosclerosis.
Lipoprotein particles and their modificationChronic inflammation is the major driving force in atherogenesis. In the arterial wall, modified LDL particles trigger and maintain inflammation, while HDL particles exert anti-atherogenic actions. Among the inflammatory cells in atherosclerotic lesions, activated mast cells are found. The mast cells secrete a vast array of critical proinflammatory mediators. Expand
The scientists at the WRI have uncovered mechanisms by which activated mast cells participate in the development of the lesions. In addition, they have delineated the roles of several types of modified LDL and HDL in the initiation and progression of atherogenesis. They also proposed novel pathways in the molecular pathogenesis of aortic stenosis to lay scientific foundations for clinical success of future pharmacotherapies of this disease.
