
Yr Athro Gary F. Baxter
Dirprwy Is-Ganghellor Coleg y Gwyddorau Biofeddygol a Bywyd
- baxtergf@cardiff.ac.uk
- +44 (0)29 2068 8544
- Ty'r Coleg, King George V Drive East, Heath Park, Caerdydd, CF14 4EP
Trosolwg
Originally qualifying in pharmacy at the University of Nottingham (B.Pharm.) and The Royal London Hospital (M.R.Pharm.S.), I undertook research training in experimental pharmacology (M.Sc., Ph.D.).
My Ph.D. was awarded for studies on modulation of ischaemia- and reperfusion-induced arrhythmias in hypertrophied myocardium.
At the end of 2008, I was awarded the higher doctorate (DSc) from my alma mater, Nottingham University.
Bywgraffiad
I originally qualified in pharmacy at the University of Nottingham (B.Pharm.) and The Royal London Hospital (M.R.Pharm.S.). After a short period spent in clinical practice in hospitals in East Anglia, I undertook research training in experimental pharmacology in London and Leicester (M.Sc., Ph.D.). My Ph.D., undertaken in the laboratory of Professor Basil Northover, was awarded for studies on modulation of ischaemia- and reperfusion-induced arrhythmias in hypertensive left ventricular hypertrophy. In 2009, the higher doctorate (D.Sc.) was conferred by the University of Nottingham for a body of published works on protective actions of autacoid mediators in ischaemic and reperfused myocardium.
I was previously British Heart Foundation intermediate research fellow, at the Hatter Cardiovascular Institute and the Department of Physiology, UCL, mentored by Professor Derek Yellon.
After periods spent in the laboratory of Dr Jim Downey and Dr Michael Cohen at the University of South Alabama Medical College, USA, and with Professor Lionel Opie at the Ischaemic Heart Disease Research Unit in Cape Town, South Africa, I was appointed Senior Lecturer in the Department of Medicine at UCL (2000-2001). I was then promoted to Reader in Cardiovascular Biology at the Royal Veterinary College, University of London (2002-2007) prior to moving to Cardiff University as Professor of Pharmacology in April 2007.
In January 2009, I was appointed Director of Research in the School of Pharmacy and Pharmaceutical Sciences before succeeding Professor Stephen Denyer as Head of School in August 2010.
And finally... When I am not working, I am an organ anorak and am either playing the organ, listening to one, or dreaming about pipes, pistons and drawstops. So here are some links related to my passion for the "Wondrous Machine":
Anrhydeddau a Dyfarniadau
- British Pharmacological Society's Bowman Prize, 1996
- Naranjan Dhalla Prize of the International Academy of Cardiovascular Sciences, 2011
Aelodaethau proffesiynol
Learned and professional societies to which I belong and who support me as a scientist:
- Fellowship of the American Heart Association
- Fellowship of the American Physiological Society
- Fellowship of the British Pharmacological Society
- Fellowship of the Institute of Biology
- British Cardiac Society
- British Society for Cardiovascular Research
- European Society of Cardiology
- International Society for Heart Research
- Research Defence Society
Committee roles
- European Secretary of the International Society for Heart Research, 2003 to 2009
- served on the council of the European Society of Cardiology's Working Group on the Cellular Biology of the Heart, 2004-2009
- previously a member of the College of Experts for the Physiological Systems and Clinical Sciences panel of the Medical Research Council.
Editorial roles
I have previously served on the editorial boards of several international journals including British Journal of Pharmacology (2000-2003), Pharmacology & Therapeutics (1999-2009), Journal of Molecular & Cellular Cardiology (2008-2010) and currently serve on:
Cyhoeddiadau
2018
- Karwi, Q. G., Bice, J. S. and Baxter, G. F. 2018. Pre- and postconditioning the heart with hydrogen sulfide (H2S) against ischemia/reperfusion injury in vivo: a systematic review and meta-analysis. Basic Research in Cardiology 113(1), article number: 6. (10.1007/s00395-017-0664-8)
2017
- Jonas, K. C.et al. 2017. Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes. Cell and Tissue Research 369(3), pp. 567-578. (10.1007/s00441-017-2624-x)
- Karwi, Q. G.et al. 2017. Ap39, a mitochondria-targeting hydrogen sulfide (H2 s) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling. British Journal of Pharmacology 174(4), pp. 287-301. (10.1111/bph.13688)
2016
- Karwi, Q. G.et al. 2016. Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137. Pharmacological Research 111, pp. 442-451. (10.1016/j.phrs.2016.06.028)
- Bice, J. S.et al. 2016. Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: a systematic review of experimental and clinical studies. Basic Research in Cardiology 111(2), article number: 23. (10.1007/s00395-016-0540-y)
2015
- Bice, J. S. and Baxter, G. F. 2015. Postconditioning signalling in the heart: mechanisms and translatability. British Journal of Pharmacology 172(8), pp. 1933-1946. (10.1111/bph.12976)
2014
- Ferdinandy, P.et al. 2014. Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacological Reviews 66(4), pp. 1142-1174. (10.1124/pr.113.008300)
- Bice, J. S., Burley, D. and Baxter, G. F. 2014. Novel approaches and opportunities for cardioprotective signaling through 3',5'-cyclic muanosine monophosphate manipulation. Journal of Cardiovascular Pharmacology and Therapeutics 19(3), pp. 269-282. (10.1177/1074248413518971)
- Bice, J. S.et al. 2014. NO-independent stimulation or activation of soluble guanylyl cyclase during early reperfusion limits infarct size. Cardiovascular Research 101(2), pp. 220-228. (10.1093/cvr/cvt257)
- Thompson, I. R.et al. 2014. Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes. Cell and Tissue Research 355(2), pp. 425-436. (10.1007/s00441-013-1763-y)
- Burley, D.et al. 2014. Natriuretic peptides modulate ATP-sensitive K+ channels in rat ventricular cardiomyocytes. Basic Research in Cardiology 109, article number: 402. (10.1007/s00395-014-0402-4)
2012
- Burley, D. S.et al. 2012. P541: Natriuretic peptide inhibition of sarcolemmal atp-sensitive potassium channel in rat cardiomyocytes [Abstract]. Cardiovascular Research 93(S1), pp. S105-S106. (10.1093/cvr/cvr336)
2010
- Ovize, M.et al. 2010. Postconditioning and protection from reperfusion injury: where do we stand? Position Paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovascular Research 87(3), pp. 406-423. (10.1093/cvr/cvq129)
- Elsey, D., Fowkes, R. C. and Baxter, G. F. 2010. L-cysteine stimulates hydrogen sulfide synthesis in myocardium associated with attenuation of ischemia-reperfusion injury. Journal of Cardiovascular Pharmacology and Therapeutics 15(1), pp. 53-59. (10.1177/1074248409357743)
- Hamid, S. A.et al. 2010. Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium. Basic Research in Cardiology 105(2), pp. 257-266. (10.1007/s00395-009-0058-7)
- Elsey, D., Fowkes, R. C. and Baxter, G. F. 2010. Regulation of cardiovascular cell function by hydrogen sulfide (H2S). Cell Biochemistry and Function 28(2), pp. 95-106. (10.1002/cbf.1618)
- Gorbe, A.et al. 2010. Role of cGMP-PKG signaling in the protection of neonatal rat cardiac myocytes subjected to simulated ischemia/reoxygenation. Basic Research in Cardiology 105(5), pp. 643-650. (10.1007/s00395-010-0097-0)
- Hausenloy, D. J.et al. 2010. Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Research in Cardiology 105(6), pp. 677-686. (10.1007/s00395-010-0121-4)
- Rautureau, Y.et al. 2010. C-type natriuretic peptide regulation of guanosine-3′,5′-cyclic monophosphate production in human endothelial cells. Autonomic and Autacoid Pharmacology 30(3), pp. 185-192. (10.1111/j.1474-8673.2009.00449.x)
2009
- Giricz, Z.et al. 2009. Hyperlipidaemia induced by a high-cholesterol diet leads to the deterioration of guanosine-3',5'-cyclic monophosphate/protein kinase G-dependent cardioprotection in rats. British Journal of Pharmacology 158(6), pp. 1495-1502. (10.1111/j.1476-5381.2009.00424.x)
- Burley, D. S. and Baxter, G. F. 2009. Pharmacological targets revealed by myocardial postconditioning. Current Opinion in Pharmacology 9(2), pp. 177-188. (10.1016/j.coph.2008.11.009)
2008
- Burley, D.et al. 2008. Evidence for serca and BKCa activation in BNP protection of reperfused myocardium [Abstract]. Journal of Molecular and Cellular Cardiology 44(4), pp. 717. (10.1016/j.yjmcc.2008.02.015)
- Gorbe, A.et al. 2008. Role of NO-cGMP-PKG signalling in the protection of cardiac myocytes subjected to hypoxia/reoxygenation [Abstract]. Journal of Molecular and Cellular Cardiology 44(4), pp. 808., article number: 231. (10.1016/j.yjmcc.2008.02.232)
- Kleinz, M. J. and Baxter, G. F. 2008. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regulatory Peptides 146(1-3), pp. 271-277. (10.1016/j.regpep.2007.10.002)
- Baxter, G. F. and Burley, D. S. 2008. Reperfusion and calculated RISKs: pharmacological postconditioning of human myocardium. British Journal of Pharmacology 153(1), pp. 1-3. (10.1038/sj.bjp.0707498)
- Hamid, S. A.et al. 2008. Rho-kinase mediates reoxygenation-induced cardiomyocyte death and promotes mitochondrial transition pore opening. Journal of Molecular and Cellular Cardiology 44(4), pp. 791-792.
2007
- Burley, D. S. and Baxter, G. F. 2007. Activation of particulate guanylate cyclase during early reperfusion limits infarct size in the rat isolated heart. Journal of Molecular and Cellular Cardiology 42(6(S)), pp. S209. (10.1016/j.yjmcc.2007.03.633)
- Elsey, D., Fowkes, R. C. and Baxter, G. F. 2007. H2S production in myocardial ischaemia and reperfusion. Journal of Molecular and Cellular Cardiology 42(6), pp. S197-S198. (10.1016/j.yjmcc.2007.03.600)
- Giricz, Z.et al. 2007. Activation of cyclic GMP/PKG pathway fails to limit infarct size in hearts from hyperlipidaemic rats. Journal of Molecular and Cellular Cardiology 42(6), pp. S214-S214. (10.1016/j.yjmcc.2007.03.647)
- Gorbe, A.et al. 2007. NO-cGMP-PKG signalling pathway involved in the protection of cardiac myocytes during hypoxia/reoxygenation. Journal of Molecular and Cellular Cardiology 42(6(S1)), pp. 48-S49. (10.1016/j.yjmcc.2007.03.137)
- Hamid, S. A.et al. 2007. NO/cGMP pathway in adrenomedullin mediated cardioprotection in mouse. Journal of Molecular and Cellular Cardiology 42(6), pp. S195. (10.1016/j.yjmcc.2007.03.592)
- Kleinz, M. J. and Baxter, G. F. 2007. Apelin reduces myocardial reperfusion injury independent of PI3K/Akt and P70S6K [Abstract]. Journal of Molecular and Cellular Cardiology 42(6, S1), pp. S203. (10.1016/j.yjmcc.2007.03.616)
- Baxter, G. F., Bower, H. and Hamid, S. 2007. Rho-kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium. American Journal of Physiology - Heart and Circulatory Physiology 292(6), pp. H2598-H2606. (10.1152/ajpheart.01393.2006)
- Burley, D. S. and Baxter, G. F. 2007. B-type natriuretic peptide at early reperfusion limits infarct size in the rat isolated heart. Basic Research in Cardiology 102(6), pp. 529-541. (10.1007/s00395-007-0672-1)
- Burley, D. S., Ferdinandy, P. and Baxter, G. F. 2007. Cyclic GMP and protein kinase-G in myocardial ischaemia-reperfusion: opportunities and obstacles for survival signaling. British Journal of Pharmacology 152(6), pp. 855-869. (10.1038/sj.bjp.0707409)
- Burley, D. S., Hamid, S. A. and Baxter, G. F. 2007. Cardioprotective actions of peptide hormones in myocardial ischemia. Hear Failure Reviews 12(3-4), pp. 279-291. (10.1007/s10741-007-9029-y)
- Ferdinandy, P., Schulz, R. and Baxter, G. F. 2007. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacological Reviews 59(4), pp. 418-458. (10.1124/pr.107.06002)
- Ebrahim, Z., Yellon, D. M. and Baxter, G. F. 2007. Ischemic preconditioning is lost in aging hypertensive rat heart: Independent effects of aging and longstanding hypertension. Experimental Gerontology 42(8), pp. 807-814. (10.1016/j.exger.2007.04.005)
- Ebrahim, Z., Yellon, D. M. and Baxter, G. F. 2007. Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy. Pharmacological Research 55(1), pp. 42-48. (10.1016/j.phrs.2006.10.004)
- Hamid, S. A., Bower, H. S. and Baxter, G. F. 2007. Rho kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium. American Journal of Physiology - Heart and Circulatory Physiology 292(6), pp. H2598-H2606. (10.1152/ajpheart.01393.2006)
2003
- Baxter, G. F., Kis, A. and Yellon, D. 2003. Second window of protection following myocardial preconditioning: an essential role of PI3 kinase and p70S6 kinase. Journal of Molecular and Cellular Cardiology 35(9), pp. 1063-1071. (10.1016/S0022-2828(03)00208-6)
- D'Souza, S. P.et al. 2003. B-type natriuretic peptide limits infarct size in rat isolated heart via KATP channel opening. American Journal of Physiology - Heart and Circulatory Physiology 284(5), pp. H1592-H1600. (10.1152/ajpheart.00902.2002)
- Baxter, G. F., Kis, A. and Yellon, D. 2003. Role of nuclear factor-kB activation in acute ischaemia-reperfusion injury in myocardium. British Journal of Pharmacology 138(5), pp. 894-900. (10.1038/sj.bjp.0705108)
Addysgu
I hold a postgraduate certificate in teaching and learning in higher education (PGCHE, Open University) and am a Fellow of the Higher Education Academy.
Teaching profile:
- PH1122 The role of the pharmacist in professional practice
- PH1124 Human body systems
- PH2110 Clinical & professionalpharmacy
- PH2113 Diseases and drugs I
- PH3110 Optimisation of pharmaceutical care
- PH3202 Research methodology
- PH4116 Pharmacy research or scholarship project
External teaching
Kings College London, module JM0325 Experimental Cardiovascular Pharmacology: lectures on molecular basis of myocardial infarction, ischaemic preconditioning and postconditioning
Member of the School's Pharmacology & Physiology research discipline.
Research interests
- Myocardial and coronary vascular biology, with a special emphasis on the pathophysiology of acute myocardial infarction
- Cellular basis of ischaemia-reperfusion injury and mechanisms of cardioprotection
For several decades, ischaemic heart disease has been a leading cause of morbidity and mortality in the industrialised nations. While in the UK and USA there are trends towards a reduction in mortality from ischaemic heart disease, the condition is predicted to become the leading cause of death worldwide by 2030, outstripping death due to infectious or neoplastic disesases. Ischaemic heart disease therefore represents a significant and ongoing medical and scientific challenge.
Our group aims to integrate physiological, pharmacological, biochemical and molecular biological techniques to study basic aspects of cardiac biology relating to the pathophysiology and treatment of myocardial ischaemia. Understanding the principal molecular mechanisms that result in cell death during ischaemia-reperfusion is the basis for developing rational effective therapies for the early management of acute myocardial infarction. The group works with experimental models of ischaemia-reperfusion injury including coronary artery occlusion in vivo and ex vivo. Considerable effort is now being directed towards the paradox of reperfusion injury and the intracellular signalling mechanisms that control cellular responses to reperfusion.
The group has had a long-standing interest in the roles of autacoid factors and their associated signal transduction mechanisms as potentially tractable therapeutic targets that might modulate responses to myocardial ischaemia-reperfusion. Our recent foci of attention include cardiovascular peptides, including bradykinin, adrenomedullin and natriuretic peptides.
Current research projects
RhoA-dependent kinase activation as an injury signal in ischaemia-reperfusion
RhoA-dependent kinase (ROCK) is a serine-threonine protein kinase which regulates a wide variety of cellular processes. In the cardiovascular system, ROCK signalling is implicated in cytoskeletal actin assembly, cardiac myocyte hypertrophy, vascular smooth muscle contraction, and smooth muscle cell proliferation and migration. At the Royal Veterinary College, Mr Hugo Bower and Dr Shabaz Hamid showed that selective pharmacological inhibition of ROCK during ischaemia and reperfusion protected myocardium from necrosis and suggest that the deleterious effects of ROCK activation are mediated specifically during early reperfusion. This work is now being continued by Dr Dwaine Burley, supported by a British Heart Foundation grant.
The primary aim of this project is to understand the patterns of activation and potentially injurious roles of ROCK in post-ischaemic reperfusion. Specific objectives are:
- to obtain a detailed characterisation of ROCK activation in ischaemic and reperfused myocardium and the role of reactive oxygen species in the activation of ROCK
- to investigate the ability of ROCK to inhibit PI3-kinase/Akt activation at reperfusion as an injury-promoting mechanism during reperfusion
- to explore ROCK inhibition as a mechanism of postconditioning
We hypothesise that ROCK activation during early reperfusion inhibits a key survival signal, PI3-kinase/Akt, thus promoting the development of lethal reperfusion injury. In acute myocardial infarction, the ability of myocardium to withstand ischaemia and subsequent reperfusion is dependent on the critical balance of pro-survival and injury-promoting signals. Hopefully, these studies will furnish an understanding of the ROCK signalling pathway as a basis for the rational treatment of reperfusion injury.
Serotonin associated injury and survival signalling in myocardium: Receptor dependant and non receptor targets for cytoprotection
- Funder: British Heart Foundation
- Value: £141,823
- Duration: three years
Role of hydrogen sulphide signalling in ischaemia-reperfusion
Hydrogen sulphide (H2S) has been identified as an endogenous gaseous mediator, produced by a regulated enzyme pathway and exerting cardiovascular actions. Mr David Johansen (visiting student from the University of Tromso, Norway) demonstrated that exogenous H2S limited experimental infarct size via a mechanism involving opening of KATP channels. Mr David Elsey is currently supported by the British Heart Foundation to undertake PhD studies to explore the potential actions of endogenous H2S produced within the heart and coronary vessels. The project is characterising the expression of H2S generating enzymes within myocardium and the production of H2S under ischaemic and reperfusion conditions. We are also exploring the potential for exogenously-applied H2S and –SH donors to protect against ischaemia-reperfusion injury and the signal transduction mechanisms involved.
Cytoprotective regulation of intracellular calcium in myocardium by particulate and soluble guanylate cyclases
Mr Justin Bice has recently been appointed to undertake PhD studies to further examine the role of cGMP signalling in protection against ischaemia-reperfusion (work initiated by his predecessor Dr Dwaine Burley). cGMP is an intracellular second messenger derived from GTP through the action of particulate and soluble guanylate cyclases (pGCs and sGC). pGCs are membrane-associated receptors for natriuretic peptides whereas sGC is activated physiologically by nitric oxide (NO). Our previous work has identified that elevation of intracellular cGMP via activation of pGC by B-type natriuretic peptide (BNP) confers a marked cytoprotective effect on myocardium under the cytotoxic conditions of ischaemia-reperfusion. Preliminary evidence suggests that this protective effect of pGC is at least partially mediated through mechanisms related to sarcoplasmic reticulum ATPase activation which would promote sarcoplasmic reticulum Ca2+ uptake and decrease cytoplasmic Ca2+ overload, likely through activation of protein kinase G. Whether activation of sGC by NO exerts similar effects on Ca2+ handling is unclear. There is increasing evidence that cGMP from pGC and sGC may be differently compartmentalised within cells and exert different physiological actions.
The aim of this project is to characterise the effects of pGC and sGC activation on sarcoplasmic reticulum Ca2+ handling in cardiac myocytes. The general hypothesis is that activation of pGC and sGC results in the generation of differently compartmentalised cGMP pools, resulting in different patterns of intracellular Ca2+ regulation in myocardium subjected to ischaemia-reperfusion insult. The work is being co-supervised by Dr Ken Wann (Welsh School of Pharmacy) whose laboratory provides electrophysiological expertise, and Dr Chris George (Wales Heart Research Institute) who contributes sophisticated Ca2+ imaging techniques.
Other recent research projects
- Dr Dwaine Burley was funded by Heart Research UK to undertake his PhD investigating the role of the cGMP/PKG signalling pathway as a pro-survival (salvage) pathway in reperfusion. He showed that the protective phenomenon called "postconditioning" is mediated by activation of the cGMP/PKG pathway in reperfusion and explored the roles of NO and natriuretic peptides as activators of this protective response. His work pointed to differences between soluble gunaylate cyclase and particulate guanylate cyclase-derived cGMP in mediating cytoproetctive responses. This work is now being continued in the PhD studies conducted by Justin Bice.
- The laboratory has an ongoing interest in the phenomenon of ischaemic preconditioning. In collaboration with Dr Peter Ferdinandy (University of Szeged, Hungary), Dr Zoltan Giricz and Dr Aniko Gorbe were funded under the Wellcome Trust Collaborative Research Initiative to investigate the role of cGMP/PKG signalling in mediating preconditioning and cardioprotection and its modification by hyperlipidaemia.
- Work funded by the British Heart Foundation has identified a critical role of adrenomedullin in influencing myocardial responses to ischaemia-reperfusion (Dr Shabaz Hamid). A focus has been the ability of adrenomedullin to mediate protection particularly during post-ischaemic reperfusion through recruitment of pro-survival (salvage) kinase pathways, including NO/cGMP signalling. Some of this work was undertaken in collaboration with Dr Tienush Rassaf and colleagues at the University Hospital of Aachen
- Work undertaken in collaboration with Dr Matthias Kleinz (formerly Royal Veterinary College) assessed the cardiac actions of apelin/APJ signalling in myocardial ischaemia-reperfusion.
- Dr Yohann Rautureau (now at the Institut de Recherche Cardiovasculaire, University of Montreal, Canada) was supported by Heart Research UK to examine how natriuretic peptide/guanylate cyclase signalling influences coronary vascular cell function, including endothelial cell signalling pathways and proliferative responses in coronary vascular smooth muscle cells.
Current research opportunities
Projects are currently available for self-funded or independently-sponsored PhD students in the field of cardiac and coronary vascular physiology/pharmacology. PhD registration fees for candidates from EU countries are currently £3100 per annum. Please contact Professor Baxter for further information.
Current research students
- Outuba Karwi
Current post doctoral research associates
- Justin S Bice BSc PhD
Recent research students, visiting students and associates
- Dwaine Burley BSc PhD (2011)
- Dmitra Andreou (Erasmus Scholar, University of Athens, 2011)
- Paolo Strazzacappa (Erasmus Scholar, University of Padova, 2009-2010)
Currently active research collaborations
- Dr William Ford (School of Pharmacy and Pharmaceutical Sciences, Cardiff University)
- Dr Chris George (Wales Heart Research Institute, Cardiff University)
- Dr Ken Wann (School of Pharmacy and Pharmaceutical Sciences, Cardiff University)
- Dr Robert C Fowkes (Royal Veterinary College)
- Professor Derek Yellon and Dr Sean Davidson (University College London)
- Professor Peter Ferdinandy (University of Szeged, Hungary)
- Dr Tienush Rassaf (University of Aachen, Germany)