Platelets (small circulating blood cells) are involved in blood clotting to prevent excessive bleeding, however, their inappropriate activation under pathological conditions leads to thrombosis resulting in major cardiovascular diseases such as heart attack and stroke. Our recent achievements in platelet research include the discovery of a new phenomenon of intercellular communication between platelets through gap junctions and its importance for the synchronised functions of these cells within blood clots. Furthermore, we have investigated the significance of Eph-ephrin mediated contact-dependent and -independent signalling in the regulation of initial platelet activation and the architecture of thrombus. Although platelets play an important role in the maintenance of haemostasis and thrombosis, due to their high numbers in the circulation, they act as sentinels through controlling inflammatory responses. Therefore, we are currently investigating the orchestrated functions of a range of surface receptors present on the blood cells such as platelets, monocytes and neutrophils, and endothelial cells on the inner lining of blood vessels in the regulation of multicellular interactions and their significance in the progression of inflammatory responses.
Furthermore, with the support of specialists in the field of pharmaceutical chemistry, we are involved in the isolation and characterisation of therapeutically valuable constituents from herbal plants to modulate platelet reactivity under pathological conditions. Likewise, we also apply synthetic chemistry to generate cell-target specific molecules in order to control thrombosis and inflammatory responses.
Overall, a project is available within our laboratory either to determine the functions of a receptor and elucidate its signalling mechanisms within platelets, or to isolate/synthesise and functionally characterise therapeutically valuable components to control the cellular functions under various pathophysiological settings. The PhD student will have splendid opportunities to learn a broad spectrum of techniques in the field of cell and molecular biology, biochemistry, pharmacology and pharmaceutical chemistry.
Vaiyapuri S, Sage T, Rana RH, Schenk MP, Ali MS, Unsworth AJ, Jones CI, Stainer AR, Kriek N,
Moraes LA, Gibbins JM (2015) EphB2 regulates contact-dependent and independent signalling to
control platelet function. Blood 125(4): 720-30.
Vaiyapuri S, Roweth H, Ali MS, Amanda UJ, Stainer AR, Flora GD, Crescente M, Jones CI,
Moraes LA, Gibbins JM (2015) Pharmacological actions of nobiletin in the modulation of platelet
function. British Journal of Pharmacology 172(16): 4133-45.
Vaiyapuri S, Flora GD, Gibbins JM (2015) Gap junctions and connexin hemichannels in the
regulation of haemostasis and thrombosis. Biochemical Society Transactions 43(3): 489-94.
Vaiyapuri S, Moraes LA, Sage T, Ali MS, Lewis KR, Mahaut-Smith MP, Oviedo-Orta E, Simon
AM, Gibbins JM (2013) Connexin40 regulates platelet function. Nature Communications 4: 2564.
Vaiyapuri S, Ali MS, Moraes LA, Sage T, Lewis KR, Jones CI, Gibbins JM (2013) Tangeretin
regulates platelet function through inhibition of phosphoinositide 3-kinase and cyclic nucleotide
signalling. Arteriosclerosis, Thrombosis and Vascular Biology 33(12): 2740-9.
Vaiyapuri S, Jones CI, Sasikumar P, Moraes LA, Munger SJ, Wright JR, Ali MS, Sage T, Kaiser
WJ, Tucker KL, Stain CJ, Bye AP, Jones S, Oviedo-Orta E, Simon AM, Mahaut-Smith MP, Gibbins
JM (2012) Gap junctions and connexin hemichannels underpin haemostasis and thrombosis.
Circulation 125(20): 2479-91.
Vaiyapuri S, Hutchinson EG, Ali MS, Dannoura A, Stanley RG, Harrison RA, Bicknell AB, Gibbins
JM (2012) Rhinocetin, a venom-derived integrin-specific antagonist inhibits collagen-induced
platelet and endothelial cell functions. Journal of Biological Chemistry 287(31): 26235-44.