Regulation of blood vessel formation
Our projects are focused on angiogenesis, formation of new blood vessels. Growth of tissues requires angiogenesis, both in physiological processes such as embryonic development, wound healing and in the female reproductive system, and in disease processes, such as cancer, psoriasis, retinopathies and inflammatory diseases. Our work aims to understand how angiogenesis is induced, but also how angiogenesis can be suppressed.
Vascular endothelial growth factors (VEGF) are essential regulators of blood vessel formation, angiogenesis, and survival of existing blood vessels. VEGF was originally denoted VPF, vascular permeability factor (VPF), reflecting another essential function of VEGF. Angiogenesis is initiated by binding of VEGF to receptor tyrosine kinases, VEGFR1 and VEGFR2, on endothelial cells. VEGFR2 is the most important receptor for VEGF; activation of VEGFR2 by VEGF is essential for establishment of the vasculature during embryogenesis and for regulation of angiogenesis in physiological and pathological processes.
We employ in vivo models to study VEGF signal transduction in healthy organs, in tumors and in other disease models such as retinopathy and myocardial infarction. Our particular interest is to identify signal transduction pathways regulating i) vascular morphogenesis to create functional vessels that lead blood, and ii) vascular permeability, the process where fluid, molecules and cells leave the blood and extravasate into the surrounding tissue. We furthermore study the biology of the heparin-binding plasma protein histidine-rich glycoprotein (HRG), which acts on inflammatory cells and indirectly, on blood vessels. Treatment with HRG normalizes tumor vessels, and decreases metastatic dissemination. One important goal of our research is to exploit our findings for therapeutic applications.