Speaker:

Professor Sean M Davidson

Professor Davidson obtained his PhD in Melbourne, Australia, then moved to Paris for a postdoctoral position, where he conducted research on the development of the heart. He moved to London in 1998 and is now Professor of Cardiovascular Research at the Hatter Cardiovascular Institute at University College London, where he investigates methods to protect the heart from myocardial infarction. A major focus of his interest lies in investigating the PI3Kinase pathway and how it can be harnessed to protect the heart. He is actively involved in the scientific community and is the current Secretary of the International Society for Heart Research – European Section (ISHR-ES). He is an associate editor of Cardiovascular Research and Cardiovascular Drugs and Therapy and is on the editorial board of Basic Research in Cardiology.

Title:

'A New Approach to Targeting PI3‐Kinase in ischaemia-reperfusion injury'

Abstract

The Hatter Cardiovascular Institute, University College London

Acute obstruction of a coronary artery causes ischaemia and can cause ST-elevation myocardial infarction (STEMI). Despite optimal reperfusion and medical therapy, mortality and morbidity remain high. However, clinical translation of cardioprotective strategies has been disappointing, partly due to the negative impact of common co-commodities such as diabetes and atherosclerosis. Improved methods to prevent infarction are vital. The alpha isoform of PI3-kinase (PI3Kα) plays a central role in many cardioprotective strategies. We therefore developed a novel, direct, allosteric activator of PI3Kα called UCL-TRO-1938. UCL-TRO-1938 significantly reduces infarct size in isolated perfused rat hearts subject to ischaemia and reperfusion (IR) and in an in vivo mouse model of IR. Importantly, since it bypasses cell surface receptors, UCL-TRO-1938 is able to activate the PI3K/AKT cardioprotective signalling pathway, even in the setting of insulin resistance. Furthermore, UCL-TRO-1938 was cardioprotective in a mouse model with coronary atherosclerosis. Studies are ongoing to use this novel compound as a tool to investigate the mechanism of protection by PI3Kα activation.

Host:

Dr Dan Bromage

Our series is open to the public and King’s staff and students are encouraged to attend.