Understanding how blood clotting and thrombosis is affected by blood fats

Role of zinc in controlling histidine-rich glycoprotein complex formation: implications for the development of thrombotic complications

Dr Alan Stewart is studying the processes involved in blood clotting and identifying what happens when this process goes awry. People with diabetes or cancer, or those who are obese, have higher blood fat levels, and are at greater risk of abnormal blood clotting. Histidine-rich glycoprotein (HRG) is a protein in the blood that controls clotting by binding to and preventing the natural anti-clotting protein, heparin, from working. A molecule called zinc boosts HRG-heparin binding, and normally most zinc is bound to another protein called human serum albumin (HSA). Dr Stewart believes that high levels of blood fats in obesity, diabetes and cancer disrupt zinc binding to HSA, allowing more zinc to bind to and activate HRG, promoting abnormal blood clotting. In this project, Dr Stewart will work out exactly how zinc interacts with heparins and HRG, and determine how this affects blood clotting. He will work out whether fat levels in the blood impact on zinc’s role in blood clotting by comparing blood from healthy individuals and people with diabetes. This project could reveal new ways to prevent and treat potentially fatal blood clots and may help doctors predict which anti-clotting drugs are most likely to work in certain patients.