Angiogenesis is the formation of new blood vessels from pre-existing ones and is involved in different physiological and pathological processes such as cancer and ischemia. Tyrosine phosphorylation is a reversible process, mediated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). Although the role of PTKs in angiogenesis is well established, little is known about the function of specific PTPs in this process. In collaboration with Dr. H. Augustin, (Heidelberg, Germany) we found that the expression of several PTPs changes when spheroids of endothelial cells embedded in 3D matrices are exposed to angiogenic stimuli. To investigate the role of PTPs in angiogenesis, we generated a tetracycline-inducible shRNA library for targeting PTPs. We are also generating lentiviral vectors expressing inducible cDNAs of all the human PTPs. I propose to investigate the biological role of PTPs in angiogenesis by loss- and gain of function experiments in endothelial cells, using different in vitro and in vivo angiogenesis assays. My studies will determine the role of PTPs in developmental and pathological angiogenesis and test their merits as targets of angiogenic therapy.