Senior Lecturer - Biomedical and Forensic Sciences
Platelets are the principal cellular determinants of haemostasis and pathological thrombus formation leading to myocardial infarction and stroke. Following adhesion to sites of vascular damage, platelets undergo primary activation leading to shape change, upregulation of integrin activity and secretion of alpha and dense granules. Granule release introduces bioactive molecules into the immediate environment of a growing thrombus. Such molecules include adhesion proteins, coagulation factors and soluble platelet agonists, such as ADP, ATP, thromboxane and zinc. Zinc has long been known to be a regulator of haemostatic responses, influencing both coagulation and platelet aggregation. However, the role of mechanism by which zinc influences platelets is not well understood.
My principal research aims are to examine the mechanism by which zinc acts as an extracellular and intracellular mediator of platelet behaviour. Other interests include the analysis of platelet receptor activity in in vitro models of thrombosis.
platelets ; thrombosis
Collaborators outside this directory
- Professor Martyn Mahaut-Smith - http://www2.le.ac.uk/departments/cpp/staff/mahaut-smith
Dynamic analysis of platelet deposition to resolve platelet adhesion receptor activity in whole blood at arterial shear rate. Pugh N, Bihan D, Perry DJ, Farndale RW. Platelets. 2014 Mar 28. [Epub ahead of print]
Identification of platelet function defects by multi-parameter assessment of thrombus formation. de Witt SM, Swieringa F, Cavill R, Lamers MM, van Kruchten R, Mastenbroek T, Baaten C, Coort S, Pugh N, Schulz A, Scharrer I, Jurk K, Zieger B, Clemetson KJ, Farndale RW, Heemskerk JW, Cosemans JM. Nat Commun. 2014 Jul 16;5:4257.
Pericellular Ca(2+) recycling potentiates thrombin-evoked Ca(2+) signals in human platelets. Sage SO, Pugh N, Farndale RW, Harper AG. Physiol Rep. 2013 Oct;1(5):e00085.
Constitutive dimerization of glycoprotein VI (GPVI) in resting platelets is essential for binding to collagen and activation in flowing blood. Jung SM, Moroi M, Soejima K, Nakagaki T, Miura Y, Berndt MC, Gardiner EE, Howes JM, Pugh N, Bihan D, Watson SP, Farndale RW. J Biol Chem. 2012 Aug 24;287(35):30000-13.
The properties conferred upon triple-helical collagen-mimetic peptides by the presence of cysteine residues. Slatter DA, Bihan DG, Jarvis GE, Stone R, Pugh N, Giddu S, Farndale RW. Peptides. 2012 Jul;36(1):86-93.
Mapping of potent and specific binding motifs, GLOGEN and GVOGEA, for integrin α1β1 using collagen toolkits II and III. Hamaia SW, Pugh N, Raynal N, Némoz B, Stone R, Gullberg D, Bihan D, Farndale RW. J Biol Chem. 2012 Jul 27;287(31):26019-28.
Crosslinking and composition influence the surface properties, mechanical stiffness and cell reactivity of collagen-based films. Grover CN, Gwynne JH, Pugh N, Hamaia S, Farndale RW, Best SM, Cameron RE. Acta Biomater. 2012 Aug;8(8):3080-90.
A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1). Jarvis GE, Bihan D, Hamaia S, Pugh N, Ghevaert CJ, Pearce AC, Hughes CE, Watson SP, Ware J, Rudd CE, Farndale RW. J Thromb Haemost. 2012 Feb;10(2):268-77.
The impact of factor Xa inhibition on axial dependent arterial thrombus formation triggered by a tissue factor rich surface. Pugh N, Jarvis GE, Koch A, Sakariassen KS, Davis B, Farndale RW. J Thromb Thrombolysis. 2012 Jan;33(1):6-15.
OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. Barrow AD, Raynal N, Andersen TL, Slatter DA, Bihan D, Pugh N, Cella M, Kim T, Rho J, Negishi-Koga T, Delaisse JM, Takayanagi H, Lorenzo J, Colonna M, Farndale RW, Choi Y, Trowsdale J. J Clin Invest. 2011 Sep;121(9):3505-16.
Monitoring the intracellular store Ca2+ concentration in agonist-stimulated, intact human platelets by using Fluo-5N. Sage SO, Pugh N, Mason MJ, Harper AG. J Thromb Haemost. 2011 Mar;9(3):540-51.
Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood. Pugh N, Simpson AM, Smethurst PA, de Groot PG, Raynal N, Farndale RW. Blood. 2010 Jun 17;115(24):5069-79.