Deciphering the role of soluble epoxide hydrolase in homeostasis with Chemical Biology tools

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The soluble epoxide hydrolase (sEH) is a bifunctional enzyme which is highly expressed in numerous tissues and is considered an emerging therapeutic target for various diseases. Our group previously characterized sEH as a key player in physiology and pathophysiology. However, the consequences of sEH inhibition inhibition or degradation in the resolution of inflammation in macrophages, the heart and in the brain are still unclear. Chemical probes are valuable tools to study the function of proteins under physiological and pathophysiological conditions which are complementary to genetic technologies. In this project, we will develop three chemical tools to investigate the role of sEH - proteolysis targeting chimeras (PROTACs), fluorescent ligands and fluorogenic substrates. Using these chemical tools we will investigate the role of sEH activity, localization and degradation in in macrophages, the heart and in the brain under physiological and pathophysiological conditions.