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 angiogenesis and survival of the existing vascular bed. VEGFs stimulate endothelial cells to secrete proteases, and to migrate, proliferate and differentiate to form a new lumen-containing vessel. We study these processes using tissue culture models such as primary endothelial cells and advanced embryonic stem cell models (embryoid bodies). We use in vivo angiogenesis models such as subcutaneous matrigel plugs, tumor models in wild type and transgenic mice, and human biobank tissues. In addition, we study retinal vascularization during development and in disease models.
We employ these models in our studies on regulation of VEGF receptor kinase activity and signal transduction in formation of the 3D vascular tube. An important focus is to use in vivo models to determine VEGF-induced signal transduction in vascular permeability. We furthermore study the effect of histidine-rich glycoprotein (HRG) that was identified by us as an angiogenic regulator, and which is of potential clinical relevance. One project concerns the involvement of the VEGF co-receptor neuropilin in tumor growth and vascularization. We also investigate the role of the endothelial-specific phosphatase vascular endothelial (VE) PTP in angiogenesis.