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The regulation of platelet function - towards new strategies to prevent thrombosis

School of Biological Sciences

About the Project

Platelets perform a pivotal role in the regulation of haemostasis, a physiological response to injury that prevents excessive bleeding. They also play a central role in thrombosis, the inappropriate formation of blood clots in the circulation that lead to heart attacks and strokes. Considerable progress has been made in increasing our understanding of the signal transduction mechanisms that positively regulate the function of these cells at sites of tissue damage, and negatively regulate their function in the undamaged circulation. A particular interest of the host laboratory is understanding the complex interplay between activatory and inhibitory signalling mechanisms in platelets. It is believed that the fine balance between these dynamic mechanisms regulates the threshold stimulus strength required for thrombus formation, and limits the size of a developing thrombus, thereby localising platelet function to sites of injury where sub-endothelial collagen is exposed.

A PhD project is available to study a newly discovered cell communication mechanism that is utilised by platelets to regulate haemostasis and is also implicated in thrombotic disease. This study will focus on the signals that are present in the damaged and undamaged circulation, the receptors that they bind to on platelets and related cells, he channel-like proteins that through which the newly discovered communication mechanisms work, and the signal transduction mechanisms that ultimately control the functions of these cells in health and disease. This PhD will be in a clinically important area of biomedical research and will provide specialist training in cardiovascular biology, a broad training in cell biology approaches and the translation of fundamental biomedical science into new preventative or therapeutic strategies.


Crescente, M., Pluthero, F.G., Li, L., Lo, R.W., Walsh, T.G., Schenk, M.P., Holbrook, L.M., Louriero, S., Ali, M.S., Vaiyapuri, S., Falet, H., Jones, I.M., Poole, A.W., Kahr, W.H.A., and Gibbins, J.M. (2016) Intracellular trafficking, localization and mobilization of platelet-borne thiol isomerases. Arterioscler Thromb Vasc Biol. In press

Bye, A.P., A.J. Unsworth, S. Vaiyapuri, A.R. Stainer, M.J. Fry, and J.M. Gibbins. (2015) Ibrutinib inhibits platelet integrin αIIbβ3 outside-in signaling and thrombus stability but not adhesion to collagen. Arterioscler Thromb Vasc Biol, 35, 2326-35.

Vaiyapuri, S., Roweth, H., Ali, M.S., Unsworth, A.J., Stainer, A.R., Flora, G.D., Crescente, M., Jones, C.I., Moraes, L.A., Gibbins, J.M. (2015) Pharmacological actions of nobiletin in the modulation of platelet function. Brit J Pharmacol. 43, 489-94.

Vaiyapuri, S., Sage, T., Rana, R.H., Schenk, M.P., Ali, M.S., Unsworth, A.J., Jones, C.I., Stainer, A.R., Kriek, N., Moraes, L.A., Gibbins, J.M. (2015) EphB2 regulates contact-dependent and independent signalling to control platelet function. Blood. 125, 720-730.

Jones, C.I., Sage, T., Moraes, L.A., Vaiyapuri, S., Hussain, U., Tucker, K.L., Barrett, N.E. and Gibbins, J.M. (2014) PECAM-1 inhibits platelet response to thrombin and VWF by regulating the internalisation of GPIb via AKT/GSK-3/Dynamin and integrin αIIbβ3. Arterioscl. Thromb. Vasc. Biol. 34, 1968-1976.

Jones, C.I., Tucker, K.L., Sasikumar, P., Sage, T., Kaiser, W.J., Moore, C., Emerson, M. and Gibbins, J.M. (2014) Integrin linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi. J Throm Haemost, 12, 1342-52.

Vaiyapuri, S., Moraes, L.A., Sage, T., Ali, M.S., Lewis, K.R., Mahaut-Smith, M.P., Oviedo-Orta, E., Simon, A.M., Gibbins, J.M. (2013) Cx40 Regulates Platelet Function. Nat Comm, 4, 2564.
Moraes, L.A., Vaiyapuri, S., Sasikumar, P., Ali, M.S., Kriek, N., Sage, T. and Gibbins, J.M. (2013) Antithrombotic actions of statins involve PECAM-1 signalling. Blood, 122, 3188-3196.
Vaiyapuri, S., Jones, C.I., Sasikumar, P., Moraes, L.A., Munger, S.J., Wright, J.R., Ali, M.S., Sage, T., Kaiser, W.J., Tucker, K.L., Stain, C.J., Bye, A.P., Jones, S., Oviedo-Orta, E., Simon, A.M., Mahaut-Smith, M.P., and Gibbins, J.M. (2012) Gap Junctions and Connexin Hemichannels Underpin Haemostasis and Thrombosis. Circulation. 125, 2479-2491.

Holbrook, L-M, Sasikumar, P., Stanley, R.G., Simmonds, A.D., Bicknell, A.B., and Gibbins, J.M. (2012) The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function. J Thromb Haemost, 10, 278-88.

Spyridon, M., Moraes, L.A., Jones, C.I., Sage, T., Bucci, G., and Gibbins, J.M. (2011) LXR as a novel antithrombotic target. Blood, 117, 5751-5761.

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