The purpose of this research project is to determine the roles of lysophospholipids in the regulation of angiogenesis. The function of S1P is pretty well understood, however there are some issues that are unclear. LPA involvement is currently in debate due to the ambiguity of the data that have been published. Both of these molecules act through activation of G-protein coupled receptors of the Endothelial Differentiation Gene (EDG) family. Some studies have demonstrated EDG-1 receptor to be involved in the regulation of angiogenesis, however, the function of other EDG receptors have not been completely elucidated. The goal of this proposal is to determine and understand the roles of S1P and LPA in the regulation of angiogenesis by studying activation and inhibition of their receptors using a library of selective compounds. First, in vitro models of angiogenesis (migration and proliferation assays) in Human Microvascular Endothelial Cells will be performed and then, in vivo assays in mice will be used to confirm in vitro data. With this information it would be easier to design selective pharmaceutical agents for the treatment of conditions, such as cancer, in which angiogenesis is involved. ? ?
