Our Platelet Research Group has a strong interest in the behaviour of platelets during normal haemostasis, and during thrombosis leading to heart attacks and strokes.
Current research projects involve the investigation of the role of zinc in platelet behaviour. We hypothesise that zinc acts as both an extracellular platelet agonist, and as an intracellular second messenger. This research is funded by the British Heart Foundation.
We also have an interest in quantifying thrombus formation in vitro in whole blood laminar flow systems. We have developed a protocol to quantify platelet behaviour, providing information on platelet activation in real time.
The group is led by Associate Professor Nicholas Pugh. We are actively seeking collaborations, particularly with groups who could apply Nick's protocols to quantify platelet behaviour in perfusion based systems.
We are also able to supply laminar flow chambers for mounting on microscopes to image cell behaviour under flow conditions in real time. Please get in contact if you are considering setting up such a system in your lab.
For more information, email Nick at [email protected]
Nick recently gave a talk, 'Zinc is a secondary messenger in platelets', for the Blood and Bone Seminar Series.
We organised the Platelet UK 2019 conference at the University of Cambridge, and held the 14th Zinc-Net meeting in 2019, having previously hosted it in 2015.
Lopes-Pires, M. E., Ahmed, N. S., Vara, D., Gibbins, J. M., Pula, G., Pugh, N., 2020. Zinc regulates reactive oxygen species generation in platelets. Platelets, Apr 5:1-10. doi: 10.1080/09537104.2020.1742311
Ahmed, N. S., Lopes Pires, M.E., Taylor, K. A., Pugh, N., 2019. Agonist-Evoked Increases in Intra-Platelet Zinc Couple to Functional Responses. Thromb Haemost, Jan;119(1):128-139. doi: 10.1055/s-0038-1676589
Burzynski, L. C., Pugh, N., Clarke, M. C., 2019. Platelet Isolation and Activation Assays. Bio-protocol, 9(20): e3405. doi: 10.21769/BioProtoc.3405
Iegre, J., Ahmed, N. S., Gaynord, J. S., Wu, Y., Herlihy, K. M., Tan, Y. S., Lopes-Pires, M. E., Jha, R., Lau, Y. H., Sore, H. F., Verma, C., O' Donovan, D. H., Pugh, N., Spring, D. R., 2018. Stapled peptides as a new technology to investigate protein-protein interactions in human platelets. Chem Sci, Apr 25;9(20):4638-4643. doi: 10.1039/c8sc00284c
Rosini, S., Pugh, N., Bonna, A. M., Hulmes, D. J. S., Farndale, R. W., Adams, J. C., 2018. Thrombospondin-1 promotes matrix homeostasis by interacting with collagen and lysyl oxidase precursors and collagen cross-linking sites. Sci Signal, May 29;11(532):eaar2566. doi: 10.1126/scisignal.aar2566
Howes J. M., Pugh, N., Hamaia, S. W., Jung, S. M., Knäuper, V., Malcor, J. D., Farndale, R. W., 2018. MMP-13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation. Res Pract Thromb Haemost, Mar 25;2(2):370-379. doi: 10.1002/rth2.12088
Misra, A., Prakash, P., Aggarwal, H., Dhankani, P., Kumar, S., Pandey, C. P., Pugh, N., Bihan, D., Barthwal, M. K., Farndale, R. W., Dikshit, D. K., Dikshit, M., 2018. Anti-thrombotic efficacy of S007-867: Pre-clinical evaluation in experimental models of thrombosis in vivo and in vitro. Biochem Pharmacol, Feb;148:288-297. doi: 10.1016/j.bcp.2018.01.013
Taylor, K. A., Wilson, D. G. S., Harper, M. T., Pugh, N., 2018. Extracellular chloride is required for efficient platelet aggregation. Platelets, Jan;29(1):79-83. doi: 10.1080/09537104.2017.1332367
Pugh, N., Maddox, B. D., Bihan, D., Taylor, K. A., Mahaut-Smith, M. P., Farndale, R. W., 2017. Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions. Thromb Haemost, Jul 26;117(8):1588-1600. doi: 10.1160/TH16-12-0906
Taylor, K. A., Pugh, N., 2016. The contribution of zinc to platelet behaviour during haemostasis and thrombosis. Metallomics, Feb;8(2):144-55. doi: 10.1039/c5mt00251f
Watson, B. R., White, N. A., Taylor, K. A., Howes, J. M., Malcor, J. D., Bihan, D., Sage, S. O., Farndale, R. W., Pugh, N., 2016. Zinc is a transmembrane agonist that induces platelet activation in a tyrosine phosphorylation-dependent manner. Metallomics, Jan;8(1):91-100. doi: 10.1039/c5mt00064e
Howes, J. M., Pugh, N., Knäuper, V., Farndale, R. W., 2015. Modified platelet deposition on matrix metalloproteinase 13 digested collagen I. J Thromb Haemost, Dec;13(12):2253-9. doi: 10.1111/jth.13166
Pugh, N., Bihan, D., Perry, D. J., Farndale, R. W., 2015. Dynamic analysis of platelet deposition to resolve platelet adhesion receptor activity in whole blood at arterial shear rate. Platelets, 26(3):216-9. doi: 10.3109/09537104.2014.893289
de Witt, S. M., Swieringa, F., Cavill, R., Lamers, M. M., van Kruchten, R., Mastenbroek, T., Baaten, C., Coort, S., Pugh, N., Schulz, A., Scharrer, I., Jurk, K., Zieger, B., Clemetson, K. J., Farndale, R. W., Heemskerk, J. W., Cosemans, J. M., 2014. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nat Commun, Jul;16;5:4257. doi: 10.1038/ncomms5257