Identification of membrane targets for lipid species containing esterified EETs (ELS)

• Applicants: Professor Dr. Stefan Offermanns; Professor Dr. Eugen Proschak
• Subject Area: Pharmacy
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560019833

This research project focuses on understanding the physiological and therapeutic potential of epoxyeicosatrienoic acids (EETs), lipid molecules derived from arachidonic acid. EETs have been shown to exhibit beneficial effects, such as anti-inflammatory, cardioprotective, and vasodilatory actions. However, the molecular mechanisms underlying these effects remain elusive, especially regarding the identification of a specific receptor for EETs, which could significantly advance therapeutic applications. The project aims to explore whether the membrane lipid species containing esterified EETs (ELS) may be responsible for the biological effects attributed to free EETs. It hypothesizes that identifying proteins interacting with ELS and EETs could clarify their physiological role and open new pathways for disease treatment. Previous studies suggested that EETs interact with G-protein coupled receptors (GPCRs) and might act through receptor binding, but a clear molecular target has not been confirmed. Building on the research expertise of the involved labs, the team will synthesize different ELS and EET derivatives and use three complementary approaches to identify their potential receptors: screening against GPCR libraries, photoaffinity labeling, and biotinylation techniques. These methods aim to pinpoint specific receptors involved in EET signaling, validate their physiological relevance using in vitro and in vivo models, and explore the therapeutic potential of modulating these pathways for conditions like cardiovascular and metabolic diseases.

• DFG Programme: Reinhart Koselleck Projects