McDonald Lab Research

Angiogenesis and Microvascular Remodeling in Chronic Inflammation and Cancer

The McDonald laboratory is studying the cellular mechanisms of angiogenesis, vascular remodeling, and plasma leakage in animal models of chronic inflammation and cancer. The goal is to identify abnormalities of the vasculature that can be used as the basis of novel treatments. In one area of research, we are identifying novel targets on blood vessels in normal organs and tumors by using probes that bind to specific molecular addresses identified using random peptide phage libraries. Another research area concerns the cellular mechanisms of plasma leakage in disease. Here, the leakage from tumor vessels, due to a defective endothelial monolayer, contrasts with leakage in inflammation, where intercellular gaps form in seconds and reseal spontaneously. We are also studying the mechanism of the effects of angiopoietins on vessel leakiness following our discovery that angiopoietin-1 reduces leakage. A third area of interest is the mechanism and reversibility of vascular remodeling, angiogenesis, and lymphangiogenesis in chronic inflammation and tumors. We are using Mycoplasma pulmonis infection of the airways of normal, transgenic, and knockout mice to identify the cells and growth factors that mediate vascular remodeling in chronic inflammation and are using the abnormal vasculature as a therapeutic target. Finally, we are examining the mechanism of action and cellular effects of angiogenesis inhibitors in cancer.