Staff Profile:Professor Jon Gibbins

Name:

Professor Jon Gibbins

Job Title:

Academic/Deputy Head of School/Director, ICMR, Hopkins building

Responsibilities:

Director of the Institute for Cardiovascular and Metabolic Research

Currently holds a Visiting Professor position at King Saud University.

Areas of Interest:

Platelets play a vital role in the prevention of bleeding on damage to blood vessels. The carefully balanced regulation of platelet function ensures that platelets are normally only activated when they are exposed to extra-cellular matrix proteins such as sub-endothelial collagens or by factors that are generated at sites of tissue damage. The importance of these complex control systems is highlighted in conditions where these go wrong. This can lead to excessive bleeding, or perhaps more commonly thrombosis (causing heart attacks and strokes). The focus of the research in this group is to increase our understanding of the molecular mechanisms that positively and negatively regulate platelet function.  As described below, this is currently divided into a number of areas of interest.

A major focus of the laboratory is understanding immune-like signalling mechanisms regulate the balance between platelet activation and inhibition.  This includes platelet activation via the collagen receptor GPVI, and the inhibition of platelet function by the adhesion receptor PECAM-1. 

The ability of activated platelets to form a thrombus is mediated by receptors of the integrin family, the affinity of which for their ligands becomes increased during platelet activation (commonly called inside-out signalling). In this way integrins support platelet-platelet interactions and adhesion to components of the damaged vascular wall.  We are currently investigating the bi-directional signalling mechanisms employed by platelet integrins.  This includes the role of thiol isomerases that we have shown to be recruited to the platelet surface during activation, and their roles in conformational changes that are associated with integrin affinity modulation.

We have recently discovered new positive feedback regulatory mechanisms in platelets that are mediated by members of the tachykinin family of peptides that are secreted from platelets during activation.  We are currently determining their mechanisms of action and physiologic importance.

Through collaboration with the Nutrition Group at the University of Reading we investigate the ability of dietary components to modulate platelet function and signal transduction.  Using  in vitro and in vivo techniques in humans we have made substantial progress in understanding the effects of some compounds at the molecular level.

The University of Reading has developed state of the art proteomics facilities, and we are using these to take a more global perspective on the signalling mechanisms that regulate platelet function.  Our strategies are designed to home in on the protein-protein interactions that are essential for platelet function. 

The driving factor behind our research is the clinical need to prevent and treat thrombosis more effectively. A greater understanding of the molecular mechanisms that regulate platelet function and the specific molecules that are involved will aid in the development of more effective and specific strategies to prevent and treat thrombosis.  Our work is supported by research grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the British Heart Foundation and the Wellcome Trust.

Research groups / Centres:

Cardiovascular biology

Institute for Cardiovascular & Metabolic Research

Publications:

Y

Jump to: 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003

Number of items: 49.

2012

• 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 hemostasis and thrombosis. Circulation, 125 (20). pp. 2479-2491. ISSN 0009-7322
• 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. Journal of Thrombosis and Haemostasis, 10 (2). pp. 278-288. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2011.04593.x
• Coxon, C. H., Lewis, A. M., Sadler, A. J., Vasudevan, S. R., Thomas, A., Dundas, K. A., Taylor, L., Campbell, R.D., Gibbins, J. M., Churchill, G. C. and Tucker, K. L. (2012) NAADP regulates human platelet function. Biochemical Journal, 441 (1). pp. 435-442. ISSN 0264-6021 doi: 10.1042/BJ20111175
• Bertling, A., Niemann, S., Hussain, M., Holbrook, L., Stanley, R. G., Brodde, M. F., Pohl, S., Schifferdecker, T., Roth, J., Jurk, K., Müller, A., Lahav, J., Peters, G., Heilmann, C., Gibbins, J. M. and Kehrel, B. E. (2012) Staphylococcal extracellular adherence protein induces platelet activation by stimulation of thiol isomerases. Arteriosclerosis Thrombosis and Vascular Biology. ISSN 1079-5642

2011

• Wright, B., Stanley, R. G., Kaiser, W. J., Mills, D. J. and Gibbins, J. M. (2011) Analysis of protein networks in resting and collagen receptor (GPVI)-stimulated platelet sub-proteomes. Proteomics, 11 (23). pp. 4588-4592. ISSN 1615-9853 doi: 10.1002/pmic.201100410
• Vaiyapuri, S., Wagstaff, S. C., Harrison, R. A., Gibbins, J. M. and Hutchinson, G. (2011) Evolutionary analysis of novel serine proteases in the venom gland transcriptome of Bitis gabonica rhinoceros. PloS ONE, 6 (6). e21532. ISSN 1932-6203 doi: 10.1371/journal.pone.0021532
• Spyridon, M., Moraes, L. A., Jones, C. I., Sage, T., Sasikumar, P., Bucci, G. and Gibbins, J. M. (2011) LXR as a novel antithrombotic target. Blood, 117 (21). pp. 5751-5761. ISSN 1528-0020 doi: 10.1182/blood-2010-09-306142
• Stanley, R., Tucker, K., Barrett, T. and Gibbins, J. (2011) Platelets and their role in thrombotic and cardiovascular disease: the impact of proteomic analysis. In: Garcia, A. and Senis, Y. (eds.) Platelet Proteomics: Principles, Analysis and Applications. Mass Spectrometry . Wiley, pp. 3-26. ISBN 9780470463376
• Tucker, K. L., Sage, T. and Gibbins, J. M. (2011) Clot retraction. In: Gibbins, J. M. and Mahaut-Smith, M. P. (eds.) Platelets and Megakaryocytes. vol. 3, Additional Protocols and Perspectives. Methods in Molecular Biology, vol. 788. Humana Press, pp. 101-108. ISBN 9781617793066
• Jones, C. I., Barrett, T. E., Moraes, L. A., Gibbins, J. M. and Jackson, D. E. (2011) Endogenous inhibitory mechanisms and the regulation platelet function. In: Gibbins, J. and Mahaut-Smith, M. (eds.) Platelets and Megakaryocytes. vol. 3, Additional Protocols and Perspectives. Methods in Molecular Biology, vol. 788. Humana Press, pp. 341-366. ISBN 9781617793066
• Jones, C., Moraes, L. and Gibbins, J. (2011) Regulation of platelet biology by platelet endothelial cell adhesion molecule-1. Platelets. ISSN 0953-7104 (print), 1369-1635 (electronic) doi: 10.3109/09537104.2011.626091 (In Press)

2010

• Moraes, L. A., Barrett, N. E., Jones, C., Holbrook, L. M., Spyridon , M., Sage, T., Newman, D. K. and Gibbins, J. M. (2010) Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells. Journal of Thrombosis and Haemostasis, 8 (11). pp. 2530-2541. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2010.04025.x
• Glen, A., Evans, C. A., Gan, C. S., Cross, S. S., Hamdy, F. C., Gibbins, J., Lippitt, J., Eaton, C. L., Noirel, J., Wright, P. C. and Rehman, I. (2010) Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: an exploratory study. The Prostate, 70 (12). pp. 1313-1332. ISSN 1097-0045 doi: 10.1002/pros.21167
• Vaiyapuri, S., Wagstaff, S. C., Watson, K. A., Harrison, R. A., Gibbins, J. M. and Hutchinson, E. G. (2010) Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros. PLoS Neglected Tropical Diseases, 4 (8). e796. ISSN 1935-2735 doi: 10.1371/journal.pntd.0000796
• Wright, B., Gibson, T. , Spencer, J. , Lovegrove, J. A. and Gibbins, J. M. (2010) Platelet-mediated metabolism of the common dietary flavonoid, quercetin. PloS ONE, 5 (3). e9673. ISSN 1932-6203 doi: DOI:10.1371/journal.pone.0009673
• Moraes, L. A., Spyridon, M., Kaiser, W. J., Jones, C., Sage, T., Atherton, R. E. and Gibbins, J. M. (2010) Non-genomic effects of PPARgamma ligands: inhibition of GPVI-stimulated platelet activation. Journal of Thrombosis and Haemostasis, 8 (3). pp. 577-587. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2009.03732.x
• Vaiyapuri, S., Harrison, R. A., Bicknell, A., Gibbins, J. M. and Hutchinson, E. G. (2010) Purification and functional characterisation of Rhinocerase, a novel serine protease from the venom of Bitis gabonica rhinoceros. PloS ONE, 5 (3). e9687. ISSN 1932-6203 doi: 10.1371/journal.pone.0009687
• Wright, B., Moraes, L. A., Kemp, C. F., Mullen, W., Crozier, A., Lovegrove, J. A. and Gibbins, J. M. (2010) A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids. British Journal of Pharmacology, 159. pp. 1312-1325. ISSN 1476-5381 doi: 10.1111/j.1476-5381.2009.00632.x
• Holbrook, L. M., Watkins, N. A., Simmonds, A. D., Jones, C., Ouwehand, W. H. and Gibbins, J. M. (2010) Platelets release novel thiol isomerase enzymes which are recruited to the cell surface following activation. British Journal of Haematology, 148 (4). pp. 627-637. ISSN 0007-1048 doi: 10.1111/j.1365-2141.2009.07994.x

2009

• Jones, C. I., Garner, S. F., Moraes, L. A., Kaiser, W. J., Rankin, A., Bloodomics Consortium, , Ouwehand, W. H., Goodall, A. H. and Gibbins, J. M. (2009) PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways. FEBS Letters, 583 (22). pp. 3618-3624. ISSN 0014-5793 doi: 10.1016/j.febslet.2009.10.037
• Tucker, K. L., Kaiser, W. J., Bergeron, A. L., Hu, H. B., Dong, J. F., Tan, T. H. and Gibbins, J. M. (2009) Proteomic analysis of resting and thrombin-stimulated platelets reveals the translocation and functional relevance of HIP-55 in platelets. Proteomics, 9 (18). pp. 4340-4354. ISSN 1615-9853 doi: 10.1002/pmic.200900024
• Gibbins, J. M. (2009) Tweaking the gain on platelet regulation: The tachykinin connection. Atherosclerosis, 206 (1). pp. 1-7. ISSN 0021-9150 doi: 10.1016/j.atherosclerosis.2008.12.010
• Kaiser, W. J., Holbrook, L. M., Tucker, K. L., Stanley, R. G. and Gibbins, J. M. (2009) A functional proteomic method for the enrichment of peripheral membrane proteins reveals the collagen binding protein Hsp47 is exposed on the surface of activated human platelets. Journal of Proteome Research, 8 (6). pp. 2903-2914. ISSN 1535-3893 doi: 10.1021/pr900027j

2008

• Barrett, N. E., Holbrook, L., Jones, S., Kaiser, W. J., Moraes, L. A., Rana, R., Sage, T., Stanley, R. G., Tucker, K. L., Wright, B. and Gibbins, J. M. (2008) Future innovations in anti-platelet therapies. British Journal of Pharmacology, 154 (5). pp. 918-939. ISSN 0007-1188 doi: 10.1038/bjp.2008.151
• Jones, S., Tucker, K. L., Sage, T., Kaiser, W. J., Barrett, N. E., Lowry, P. J., Zimmer, A., Hunt, S. P., Emerson, M. and Gibbins, J. M. (2008) Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation. Blood, 111 (2). pp. 605-612. ISSN 0006-4971 doi: 10.1182/blood-2007-07-103424
• Tucker, K. L., Sage, T., Stevens, J. M., Jordan, P. A., Jones, S., Barrett, N. E., St-Arnaud, R., Frampton, J., Dedhar, S. and Gibbins, J. M. (2008) A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion. Blood, 112 (12). pp. 4523-4531. ISSN 0006-4971 doi: 10.1182/blood-2008-03-148502
• Jones, S. and Gibbins, J. M. (2008) The neurokinin 1 receptor: a potential new target for anti-platelet therapy? Current Opinion in Pharmacology, 8 (2). pp. 114-119. ISSN 1471-4892 doi: 10.1016/j.coph.2008.01.004

2007

• Guerrero, J. A., Navarro-Nunez, L., Lozano, M. L., Martinez, C., Vicente, V., Gibbins, J. M. and Rivera, J. (2007) Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells. British Journal of Clinical Pharmacology, 64 (2). pp. 133-144. ISSN 0306-5251 doi: 10.1111/j.1365-2125.2007.02881.x
• Gumireddy, K., Sun, F. X., Klein-Szanto, A. J., Gibbins, J. M., Gimotty, P. A., Saunders, A. J., Schultz, P. G. and Huang, Q. H. (2007) In vivo selection for metastasis promoting genes in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 104 (16). pp. 6696-6701. ISSN 0027-8424 doi: 10.1073/pnas.0701145104
• Moraes, L. A., Bishop-Bailey, D. and Gibbins, J. M. (2007) Non-genomic signalling of the retinoic X receptor through inhibition of Gq signalling in human platelets. Heart, 93 (11). pp. 371-374. ISSN 1355-6037
• Moraes, L. A., Swales, K. E., Wray, J. A., Damazo, A., Gibbins, J. M., Warner, T. D. and Bishop-Bailey, D. (2007) Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets. Blood, 109 (9). pp. 3741-3744. ISSN 0006-4971 doi: 10.1182/blood-2006-05-022566

2006

• Jordan, P. A. and Gibbins, J. M. (2006) Extracellular disulfide exchange and the regulation of cellular function. Antioxidants & Redox Signaling, 8 (3-4). pp. 312-324. ISSN 1523-0864
• Hubbard, G. P., Wolffram, S., de Vos, R., Bovy, A., Gibbins, J. M. and Lovegrove, J. A. (2006) Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. British Journal of Nutrition, 96 (3). pp. 482-488. ISSN 0007-1145 doi: 10.1079/bjn20061831
• Falati, S., Patil, S., Gross, P. L., Stapleton, M., Merrill-Skoloff, G., Barrett, N. E., Pixton, K. L., Weiler, H., Cooley, B., Newman, D. K., Newman, P. J., Furie, B. C., Furie, B. and Gibbins, J. M. (2006) Platelet PECAM-1 inhibits thrombus formation in vivo. Blood, 107 (2). pp. 535-541. ISSN 0006-4971 doi: 10.1182/blood-2005-04-1512
• Patel, B., Sharifi, M., Milward, A. D., Oberprieler, N. G., Gibbins, J. M., Parkin, S. and Naseem, K. M. (2006) Platelet nitric oxide synthase is activated by tyrosine dephosphorylation: possible role for SHP-1 phosphatase. Journal of Thrombosis and Haemostasis, 4 (11). pp. 2423-2432. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2006.02160.x

2005

• Jordan, P. A., Stevens, J. M., Hubbard, G. P., Barrett, N. E., Sage, T., Authi, K. S. and Gibbins, J. M. (2005) A role for the thiol isomerase. protein ERP5 in platelet function. Blood, 105 (4). pp. 1500-1507. ISSN 0006-4971 doi: 10.1182/blood-2004-02-0608

2004

• Hubbard, G.P., Wolffram, S., Lovegrove, J.A. and Gibbins, J. M. (2004) Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. Journal of Thrombosis and Haemostasis, 2 (12). pp. 2138-2145. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2004.01067.x
• Coffey, M.J., Jarvis, G.E., Gibbins, J. M., Coles, B., Barrett, N.E., Wylie, O.R.E. and O'Donnell, V.B. (2004) Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple signaling pathways in agonist control of H(P)ETE synthesis. Circulation Research, 94 (12). pp. 1598-1605. ISSN 0009-7330 doi: 10.1161/01.RES.0000132281.78948.65
• Gibbins, J. M. (2004) Platelet adhesion signalling and the regulation of thrombus formation. Journal of Cell Science, 117 (16). pp. 3415-3425. ISSN 0021-9533 doi: 10.1242/jcs.01325
• Jones, M. L., Craik, J. D., Gibbins, J. M. and Poole, A. W. (2004) Regulation of SHP-1 tyrosine phosphatase in human platelets by serine phosphorylation at its C terminus. The Journal of Biological Chemistry, 279 (39). pp. 40475-40483. ISSN 1083-351X doi: 10.1074/jbc.M402970200
• Batuwangala, T., Leduc, M., Gibbins, J. M., Bon, C. and Jones, E. Y. (2004) Structure of the snake-venom toxin convulxin. Acta Crystallographica Section D- Biological Crystallography, 60 (1). pp. 46-53. ISSN 0907-4449 doi: 10.1107/s0907444903021620
• Gibbins, J. M. (2004) Study of tyrosine kinases and protein tyrosine phosphorylation. Methods in Molecular Biology, 273. pp. 153-168. ISSN 1064-3745 doi: 10.1385/1-59259-783-1:153
• Graham, G. J., Stevens, J. M., Page, N. M., Grant, A. D., Brain, S. D., Lowry, P. J. and Gibbins, J. M. (2004) Tachykinins regulate the function of platelets. Blood, 104 (4). pp. 1058-1065. ISSN 0006-4971 doi: 10.1182/blood-2003-11-3979
• Gibbins, J. M. (2004) Techniques for analysis of proteins by SDS-polyacrylamide gel electrophoresis and Western blotting. Methods in Molecular Biology, 273. pp. 139-152. ISSN 1064-3745 doi: 10.1385/1592597831
• Stevens, J. M., Jordan, P. A., Sage, T. and Gibbins, J. M. (2004) The regulation of integrin-linked kinase in human platelets: evidence for involvement in the regulation of integrin alpha(2)beta(1). Journal of Thrombosis and Haemostasis, 2 (8). pp. 1443-1452. ISSN 1538-7933 doi: 10.1111/j.1538-7836.2004.00870.x

2003

• Polanowska-Grabowska, R., Gibbins, J. M. and Gear, A. R. L. (2003) Platelet adhesion to collagen and collagen-related peptide under flow. Roles of the alpha(2)beta(1) integrin, GPVI, and Src tyrosine kinases. Arteriosclerosis Thrombosis and Vascular Biology, 23 (10). pp. 1934-1940. ISSN 1079-5642 doi: 01.ATV.0000086937.46974.70v1
• Hubbard, G.P., Stevens, J.M., Cicmil, M., Sage, T., Jordan, P.A., Williams, C.M., Lovegrove, J.A. and Gibbins, J.M. (2003) Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. Journal of Thrombosis and Haemostasis, 1 (5). pp. 1079-1088. ISSN 1538-7933 doi: 10.1046/j.1538-7836.2003.00212.x
• Barry, F. A., Graham, G. J., Fry, M. J. and Gibbins, J. M. (2003) Regulation of glycogen synthase kinase 3 in human platelets: a possible role in platelet function? FEBS Letters, 553 (1-2). pp. 173-178. ISSN 0014-5793 doi: 10.1016/s0014-5793(03)01015-9
• Hubbard, G. P., Wolffram, S., Lovegrove, J. A. and Gibbins, J. M. (2003) The role of polyphenolic compounds in the diet as inhibitors of platelet function. Proceedings of the Nutrition Society, 62 (2). pp. 469-478. ISSN 0029-6651 doi: 10.1079/pns2003253

This list was generated on Thu May 24 17:28:40 2012 BST.

 

 

 

 

 

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