Research in my laboratory is examining the cellular mechanisms of angiogenesis, vascular remodeling, and lymphangiogenesis in mouse models of cancer, chronic inflammation, and obesity. We use in-vivo cell-biological approaches to determine how abnormalities of blood vessels and lymphatics contribute to disease pathophysiology. Current interests include developing approaches for preventing, stopping, or reversing disease-related changes in blood vessels and lymphatics and learning the consequences of these actions. Related interests include the regulation of endothelial barrier function, downstream effects of altered plasma leakage and cellular trafficking, and control mechanisms of tissue fluid and cell clearance by lymphatics.
Projects in the laboratory use mouse models to dissect the role of key growth factors and receptors involved in growth and remodeling of blood vessels and lymphatics and related disease processes. VEGF-A, VEGF-C, angiopoietins, TNF-alpha, HGF and their receptors are of current interest. Signaling is manipulated in vivo by switchable transgenic overexpression, genetic deletion, viral vectors, or pharmacological agonists or inhibitors. Ongoing studies are using the models to examine factors that drive or modify remodeling of blood vessels and lymphatics in inflammatory conditions, with an emphasis on the airways, lungs, and adipose tissue. We are also studying favorable and potentially unfavorable effects of destroying blood vessels and/or lymphatics in tumors, reflected by tumor growth, invasion, and metastasis. The overall goal is to advance the understanding and development of strategies that can stop or reverse angiogenesis and lymphangiogenesis and to characterize the downstream benefits and consequences in cancer, inflammatory disease, and obesity.