Restin: mutants, receptor cloning and signaling studies.

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Anti-angiogenic molecules have tremendous potential in the treatment of cancer. Anti-angiogenic therapy has several benefits over conventional chemotherapy as different tumors can be treated with less toxicity. Most significantly, drug resistance is unlikely. Despite these potential advantages, the utility of current anti-angiogenic agents is limited since the mechanism of action of these proteins is unknown. The PI?s long term objective is to study the mechanism of action of antiangiogenic proteins and to identify the cell surface molecules that interact with these proteins. This proposal focuses on Restin, a C-terminal fragment of the NC1 domain in human collagen XV. This fragment possesses antimigratory function against endothelial cells. This proposal plans to understand the mechanism of action of restin with the following specific aims: Specific Aim 1: To define the structure-function relationship of restin. Specific Aim 2: To determine the intracellular signaling events mediated by restin. Specific Aim 3: To identify and clone the cell surface binding partner(s) receptor for restin. We will use molecular biology and biochemical techniques to address these aims. Once the mechanism of restin?s action has been elucidated, we will understand better the utility of restin and similar agents as anti-cancer drugs.