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Investigation of the critical roles of platelets at the interface between thrombosis and inflammation in order to develop improved therapeutic strategies for the treatment and/or prevention of cardiovascular/inflammatory diseases


School of Pharmacy

About the Project

"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. Due to their high number in the circulation, platelets also act as sentinels through controlling immune/inflammatory responses. 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 inflammatory receptors such as FPRs and TLRs, and inflammatory molecules including LL37, fMLF and Lipoxin A4 on the regulation of platelet activation and signalling during various pathophysiological settings. We are currently investigating the orchestrated functions of a range of inflammatory receptors present on the blood cells such as platelets, monocytes and neutrophils on the regulation of multicellular interactions and their significance in the progression of inflammatory/cardiovascular responses.

Furthermore, with the support of specialists in the field of pharmaceutical and medicinal 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 platelet function 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, pharmacology, biochemistry, physiology, biophysics and pharmaceutical/medicinal chemistry. "

Funding Notes

Students with their own financial support are welcome to contact us anytime.

References

"1. Salamah, M. F., Ravishankar, D., Vaiyapuri, R., Moraes, L. A., Patel, K., Perretti, M., Gibbins, J. M. and Vaiyapuri, S. (2019) The formyl peptide fMLF primes platelet activation and augments thrombus formation. Journal of Thrombosis and Haemostasis, 17 (7). pp. 1120-1133.

2. Salamah, M. F., Ravishankar, D., Kodji, X., Moraes, L. A., Williams, H. F., Vallance, T. M., Albadawi, D. A., Vaiyapuri, R., Watson, K., Gibbins, J. M., Brain, S. D., Perretti, M. and Vaiyapuri, S. (2018) The endogenous antimicrobial cathelicidin LL37 induces platelet activation and augments thrombus formation. Blood Advances, 2 (21). pp. 2973-2985.

3. Ravishankar, D., Salamah, M., Attina, A., Pothi, R., Vallance, T. M., Javed, M., Williams, H. F., Alzahrani, E. M. S., Kabova, E., Vaiyapuri, R., Shankland, K., Gibbins, J., Strohfeldt, K., Greco, F., Osborn, H. M. I. and Vaiyapuri, S. (2017) Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy. Scientific Reports, 7. 5738.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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."

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