The development of new blood vessels from pre-existing vessels (angiogenesis) is essential for normal wound healing and is often inadequate in poorly healing wounds. On the other hand solid tumor growth and metastases can be facilitated by angiogenesis. Thus understanding how to accelerate or impair angiogenesis has broad clinical relevance. We have been focusing on how endothelial cells coordinately regulate expression of genes for extracellular matrix proteins, matrix degrading proteinases, and cellular adhesion molecules, which are essential in the development of new capillaries. In particular we are investigating the role of Homeobox (Hox) master transcriptional factors that appear to control expression of many of these genes associated with matrix remodeling during angiogenesis. We have identified Hox genes that can either promote angiogenesis, or those that appear to inhibit this process. Furthermore using gene transfer, we can manipulated Hox expression to either accelerate deficient wound or to impair angiogenesis associated with solid tumor growth and dissemination. In addition we are identifying promoters which are direct downstream transcriptional targets of Hox genes as well as investigating Hox functions which are independent of DNA binding.