Curry Group: Endothelial regulation of haemostasis in health and disease
We study the mechanisms by which vascular endothelial cells regulate haemostasis in health and in acquired bleeding disorders, namely trauma-induced coagulopathy, to better understand disease pathogenesis and identify novel therapeutic targets.
Trauma-induced coagulopathy (TIC) is a major, preventable cause of mortality in patients with severe traumatic injuries, and its clinical management remains suboptimal.
TIC is a recently coined term that describes the spectrum of clotting abnormalities seen in trauma patients, encompassing increased clot lysis in the early stages (within 6 hours of injury) as well as widespread clot formation in the late stages (>24 hours after injury).
Normally functioning vascular endothelial cells (ECs) serve to protect intact vessels against unwanted coagulation while promoting the formation of stable, localised fibrin clots (coagulation) that are resistant to lysis (fibrinoloysis) when vessels are injured to prevent excessive bleeding. Following traumatic injury, however, ECs become dysfunctional not only to enhance the lysis of clots that have formed at the site of injury, resulting in potentially fatal bleeding, but also to promote the widespread formation of clots within uninjured vessels even after the bleeding has been mechanically controlled, leading to multiple organ failure and subsequently death. This EC dysfunction that leads to aberrations in clotting in trauma patients is aptly termed endotheliopathy of trauma (EoT).
Our understanding of the mechanisms that underpin EoT and its contribution to TIC is in its infancy due to the scarcity of basic science research in the field. The Curry Group is working to better understand the molecular mechanisms underlying endothelial dysfunction in both the early and late stages of trauma to aid in the identification of novel drug targets for the treatment of TIC.
Internal Collaborators
- Dr Naveed Akbar, Associate Professor of Cardiovascular Science, Division of Cardiovascular Medicine
- Prof Robin Choudhury, Professor of Cardiovascular Medicine, Division of Cardiovascular Medicine
- Prof Simon Stanworth, Professor of Haematology and Transfusion Medicine, Nuffield Division of Clinical Laboratory Sciences
- Dr Paul Holloway, Principal Investigator, Investigative Medicine Division
- Dr David Metcalfe, Kadoorie Associate Professor of Emergency Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
EXTERNAL COLLABORATORS
- Dr Gael Morrow, Chancellor's Fellow, Robert Gordon University, Aberdeen, United Kingdom
- Prof Stavroula Balabani, Professor of Fluid Mechanics, University College London, London, United Kingdom
- Prof Karim Brohi, Professor of Trauma Sciences, Queen Mary University of London, London, United Kingdom
- Dr Ross Davenport, Senior Lecturer in Trauma Sciences, Queen Mary University of London, London, United Kingdom
- Dr Paul Armstrong, Lecturer in Pharmacology, Queen Mary University of London, London, United Kingdom
FUNDERS
- Medical Research Council
- John Fell Fund
- British Geriatric Society/Dunhill Medical Trust