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The generation and action of enzymatically-oxidised phospholipids (eoxPL) in vascular inflammation

November 27 @ 12:00 pm - 1:00 pm

Professor Valerie O’Donnell
Director, Division of Infection and Immunity, Cardiff
University; Co-Director of Systems Immunity Research Institute

Enzymatically-oxidized phospholipids (eoxPL) are generated through regulated processes, by attaching eicosanoids or prostaglandins to phospholipids (PL) in immune cells, following acute agonist activation. These lipids comprise structurally diverse families of biomolecules, and it is becoming increasingly clear that they possess significant immunoregulatory roles in both health and disease. The idea that oxidized PL (oxPL) can form via enzymatic pathways and signal biologically in their own right has only recently been realized. eoxPL form through the co-ordinated actions of cellular lipoxygenases, cyclooxygenases, and Land’s cycle enzymes. They display emerging roles in cellular events that include ferroptosis, apoptosis and blood clotting, and diseases such as arthritis, diabetes and cardiovascular disease. In our lab, we used several mass spectrometry approaches (precursor scanning, untargeted) to map eoxPL in human blood cells, including platelets, neutrophils and monocytes, both in isolation and during formation of a static clot. Platelets generate over 100 molecular species on thrombin activation, and mice that lack the ability to generate these show a consumptive coagulopathy and are protected against atherosclerosis and aortic aneurysm. Our recent studies have characterized the biophysical mechanisms by which eoxPL promote blood clotting, and in this talk, our recent stucies on their role(s) in vascular inflammation and hemostasis will be presented.

Valerie O’Donnell is Director of Division of Infection and Immunity at Cardiff University, and Co-Director of Systems Immunity Research Institute which she co-founded in 2016. She is Strategic Management lead of the LIPID MAPS Gateway (www.lipidmaps.org), a Wellcome Trust funded bioresource jointly led with UCSD and Babraham, and with over 1M users annually. She is an ERC Advanced Investigator and lipid biochemist whose research is focused on using mass spectrometry for discovery and characterization of new lipid mediators of inflammation. For the last 10 yrs she has studied how specialized lipids generated by circulating vascular cells regulate inflammation, wound healing and thrombosis, with a particular focus on around 150 molecular species of lipids termed enzymatically-oxidized phospholipids (eoxPL). These were discovered, characterized and chemically synthesized in her group, and then analyzed in vitro and in vivo in human clinical samples and mouse models, for their biological and pathophysiological actions.

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November 27
12:00 pm - 1:00 pm
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Centenary Institute Lecture Theatre