Departments and Institutes
Regulation of thrombosis in response to vascular injury
The balance between cell death and cell survival is essential to organism homeostasis and both must be tightly regulated. Cell death can be controlled by regulated death programs including apoptosis and several distinct regulated necrosis pathways.
Blood platelets are an essential element in the primary haemostatic system that prevents bleeding. Platelet count is a delicate balance between platelet production and platelet death. Platelet lifespan appears to be controlled by intrinsic apoptosis. In contrast, regulated necrosis and phosphatidylserine exposure in activated platelets may contribute to their roles in haemostasis and thrombosis. Platelet death pathways must therefore be tightly controlled to maintain a constant platelet count and normal haemostasis.
My research aim is to understand cell death signalling in platelets. What triggers different platelet death pathways? How are platelet death pathways controlled by intracellular signalling? What are the roles of different regulated death programs in platelet physiology and pathology?
platelets ; cell death ; phosphatidylserine exposure ; thrombosis ; thrombocytopenia
Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity. Harper MT, Poole AW. Cell Death Dis. 2013 Dec 19;4:e969.
Transient receptor potential channels function as a coincidence signal detector mediating phosphatidylserine exposure. Harper MT, Londoño JE, Quick K, Londoño JC, Flockerzi V, Philipp SE, Birnbaumer L, Freichel M, Poole AW. Sci Signal. 2013 Jun 25;6(281):ra50.
Bcl-xL-inhibitory BH3 mimetic ABT-737 depletes platelet calcium stores. Harper MT, Poole AW. Blood. 2012 May 3;119(18):4337-8.
Store-operated calcium entry and non-capacitative calcium entry have distinct roles in thrombin-induced calcium signalling in human platelets. Harper MT, Poole AW. Cell Calcium. 2011 Oct;50(4):351-8.
PKC inhibition markedly enhances Ca2+ signaling and phosphatidylserine exposure downstream of protease-activated receptor-1 but not protease-activated receptor-4 in human platelets. Harper MT, Poole AW. J Thromb Haemost. 2011 Aug;9(8):1599-607.
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