Primary Appointment

Microvascular endothelial cells play a critical role in the initiation and perpetuation of a number of pathophysiologic processes, including cancer. Studies have shown that tumor cells exploit cytokine-inducible endothelial cell glycoproteins to promote their retention in target organs of metastasis and then recruit resident endothelial cells to form new vascular networks (i.e., angiogenesis) in order to ensure tumor growth and survival. Because tumor cell arrest and angiogenesis are regarded as key, rate-limiting steps in metastasis, much of my research has focused on an improved understanding of the cellular and molecular interactions that take place between tumor cells and vascular endothelial cells. To advance our studies, we established a broad panel of microvascular endothelial cell lines from different tissues of the mouse. These cell lines have enabled us to define the molecular basis of therapy and to identify those growth factors most likely to stimulate endothelial cell division in different tissues. This type of information is valuable in that it can be used to predict which antiangiogenic strategy would be most beneficial for a given anatomic region. We have also been interested in developing in vitro models of the tumor-associated blood vasculature in order to identify new targets for anticancer therapy. To this end, we recently developed a methodology for generating constitutively active ligand-independent chimeric receptors and have shown that when this receptors are introduced into endothelial cells, the user can identify intracellular effectors that may serve as potential targets for therapy.

Last updated: 8/13/2009