Angiogenesis; cancer; chronic inflammation; endothelial cells; vascular remodeling
Our laboratory is studying the cellular mechanisms of angiogenesis, vascular remodeling, and plasma leakage in mouse models of chronic inflammation and cancer. We are also studying cellular changes in lymphatic vessels in disease models. The goal is use novel in vivo cell biological approaches to identify abnormalities of blood and lymphatic vasculature that can serve as the basis of novel treatments. In one area of research, we are examining the mechanism of the action of VEGF, angiopoietins, and other factors on blood vessel growth, remodeling, and leakiness. Other experiments include exploring the mechanism and reversibility of vascular remodeling and angiogenesis and examining the cellular actions of inhibitors of angiogenesis and lymphangiogenesis in tumors and inflammatory disease. We are also studying the cellular mechanisms of plasma leakage in disease. Here, the mechanism of plasma leakage from tumor vessels, due to a defective endothelial monolayer, contrasts with leakage in inflammation, where intercellular gaps form in seconds and reseal spontaneously. Multiple different disease models in wild-type, transgenic, and knockout mice are being used in combination with novel therapeutic agents to identify the cells and growth factors that drive angiogenesis and vascular remodeling and to understand the mechanism of reversibility of vascular changes in inflammation and cancer.