My lab is focused on studying how endothelial cell phenotypes are differentially regulated from site of the vascular tree to another. We employ a series of in vitro assays (co-culture, 3D cultures, transient and stable transfections) and in vivo assays (transgenic mice, homologous recombination, transplantation, systemic growth factor delivery, tumor xenografts) to elucidate the molecular mechanisms of endothelial cell heterogeneity. One of the questions we are actively pursuing is how endothelial cell gene expression is differentially regulated in tumor angiogenesis. We have identified a novel marker of tumor endothelium, termed endothelial cell specific molecule-1 (SEM-1). In contrast to most markers of tumor blood vessels, ESM-1 is not expressed in the developing vasculature of embryos. We have also identified promoter fragments of endothelial cell-specific genes that contain information for tumor endothelial cell-specific expression in transgenic mouse models. We are currently delineating the responsible regulatory DNA elements with the ultimate goal of developing novel targeting strategies for delivering biologically active genes to tumor endothelium.