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Physiology profile

Associate Professor Pete Jones

PositionAssociate Professor
DepartmentDepartment of Physiology
QualificationsBSc(Hons) PhD
Research summaryMolecular mechanisms underlying heart disease, arrhythmia and skeletal muscle disease

Research

My principal research interest is in how calcium cycling is controlled in cardiac myocytes. In particular, my focus is on the mechanisms by which calcium release from intra-cellular stores (sarcoplasmic reticulum, SR) is controlled by the cardiac ryanodine receptor (RyR2). The aim of my research is to characterize how the activity of RyR2 is altered both physiologically and in disease. This is achieved using a broad spectrum of assays from molecular biology and single channel recordings, through to isolated cardiac myocytes and ultimately whole animal models.

Publications

Gardner, R. J. M., Crozier, I. G., Binfield, A. L., Love, D. R., Lehnert, K., Gibson, K., … Jones, P. P., … Kennedy, M. A., & Skinner, J. R. (2019). Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy. Molecular Genetics & Genomic Medicine, 7(1), e00476. doi: 10.1002/mgg3.476

Pearson, J. T., Collie, N., Lamberts, R. R., Inagaki, T., Yoshimoto, M., Umetani, K., … Wilkins, G., Jones, P. P., … Schwenke, D. O. (2018). Ghrelin preserves ischemia-induced vasodilation of male rat coronary vessels following beta-adrenergic receptor blockade. Endocrinology, 159(4), 1763-1773. doi: 10.1210/en.2017-03070

Chakraborty, A. D., Gonano, L. A., Munro, M. L., Smith, L. J., Thekkedam, C., Staudacher, V., Gamble, A. B., … Jones, P. P. (2018). Activation of RyR2 by class I kinase inhibitors. British Journal of Pharmacology. Advance online publication. doi: 10.1111/bph.14562

Daniels, L. J., Wallace, R. S., Nicholson, O. M., Wilson, G. A., McDonald, F. J., Jones, P. P., Baldi, J. C., Lamberts, R. R., & Erickson, J. R. (2018). Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats. Cardiovascular Diabetology, 17, 89. doi: 10.1186/s12933-018-0732-x

Jones, P. P., MacQuaide, N., & Louch, W. E. (2018). Dyadic plasticity in cardiomyocytes. Frontiers in Physiology, 9, 1773. doi: 10.3389/fphys.2018.01773

Journal - Research Article

Gardner, R. J. M., Crozier, I. G., Binfield, A. L., Love, D. R., Lehnert, K., Gibson, K., … Jones, P. P., … Kennedy, M. A., & Skinner, J. R. (2019). Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy. Molecular Genetics & Genomic Medicine, 7(1), e00476. doi: 10.1002/mgg3.476

Pearson, J. T., Collie, N., Lamberts, R. R., Inagaki, T., Yoshimoto, M., Umetani, K., … Wilkins, G., Jones, P. P., … Schwenke, D. O. (2018). Ghrelin preserves ischemia-induced vasodilation of male rat coronary vessels following beta-adrenergic receptor blockade. Endocrinology, 159(4), 1763-1773. doi: 10.1210/en.2017-03070

Daniels, L. J., Wallace, R. S., Nicholson, O. M., Wilson, G. A., McDonald, F. J., Jones, P. P., Baldi, J. C., Lamberts, R. R., & Erickson, J. R. (2018). Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats. Cardiovascular Diabetology, 17, 89. doi: 10.1186/s12933-018-0732-x

Chakraborty, A. D., Gonano, L. A., Munro, M. L., Smith, L. J., Thekkedam, C., Staudacher, V., Gamble, A. B., … Jones, P. P. (2018). Activation of RyR2 by class I kinase inhibitors. British Journal of Pharmacology. Advance online publication. doi: 10.1111/bph.14562

Gonano, L. A., & Jones, P. P. (2017). FK506-binding proteins 12 and 12.6 (FKBPs) as regulators of cardiac Ryanodine Receptors: Insights from new functional and structural knowledge. Channels, 11(5), 415-425. doi: 10.1080/19336950.2017.1344799

Waddell, H. M. M., Zhang, J. Z., Hoeksema, K. J., McLachlan, J. J., McLay, J. C., & Jones, P. P. (2016). Oxidation of RyR2 has a biphasic effect on the threshold for store overload-induced calcium release. Biophysical Journal, 110(11), 2386-2396. doi: 10.1016/j.bpj.2016.04.036

Diong, C., Jones, P. P., Tsuchimochi, H., Gray, E. A., Hughes, G., Inagaki, T., Bussey, C. T., … Schwenke, D. O. (2016). Sympathetic hyper-excitation in obesity and pulmonary hypertension: Physiological relevance to the 'obesity paradox'. International Journal of Obesity, 40, 938-946. doi: 10.1038/ijo.2016.33

Zhang, J. Z., Waddell, H. M. M., Wu, E., Dholakia, J., Okolo, C. A., McLay, J. C., & Jones, P. P. (2016). FKBPs facilitate the termination of spontaneous Ca2+ release in wild-type RyR2 but not CPVT mutant RyR2. Biochemical Journal, 473(14), 2049-2060. doi: 10.1042/bcj20160389

Xiao, Z., Guo, W., Sun, B., Hunt, D. J., Wei, J., Liu, Y., … Jones, P. P., … Chen, S. R. W. (2016). Enhanced cytosolic Ca2+ activation underlies a common defect of central domain cardiac ryanodine receptor mutations linked to arrhythmias. Journal of Biological Chemistry, 291(47), 24528-24537. doi: 10.1074/jbc.M116.756528

Thaung, H. P. A., Baldi, J. C., Wang, H.-Y., Hughes, G., Cook, R. F., Bussey, C. T., Sheard, P. W., Bahn, A., Jones, P. P., Schwenke, D. O., & Lamberts, R. R. (2015). Increased efferent cardiac sympathetic nerve activity and defective intrinsic heart rate regulation in type 2 diabetes. Diabetes, 64(8), 2944-2956. doi: 10.2337/db14-0955

Liu, Y., Sun, B., Xiao, Z., Wang, R., Guo, W., Zhang, J. Z., … Jones, P. P., … Chen, S. R. W. (2015). Roles of the NH2-terminal domains of cardiac ryanodine receptor in Ca2+ release activation and termination. Journal of Biological Chemistry, 290(12), 7736-7746. doi: 10.1074/jbc.M114.618827

Mi, T., Xiao, Z., Guo, W., Tang, Y., Hiess, F., Xiao, J., … Zhang, J. Z., … Jones, P. P., & Chen, S. R. W. (2015). Role of Cys3602 in the function and regulation of the cardiac ryanodine receptor. Biochemical Journal, 467(1), 177-190. doi: 10.1042/BJ20141263

Bussey, C. T., Hughes, G., Saxena, P., Galvin, I. F., Bunton, R. W., Noye, M. K., Coffey, S., Williams, M. J. A., Baldi, J. C., Jones, P. P., & Lamberts, R. R. (2015). Chamber-specific changes in calcium-handling proteins in the type 2 diabetic human heart with preserved ejection fraction. International Journal of Cardiology, 193, 53-55. doi: 10.1016/j.ijcard.2015.05.053

Thaung, H. P. A., Yao, Y., Bussey, C. T., Hughes, G., Jones, P. P., Bahn, A., Sammut, I. A., & Lamberts, R. R. (2015). Chronic bilateral renal denervation reduces cardiac hypertrophic remodelling but not β-adrenergic responsiveness in hypertensive type 1 diabetic rats. Experimental Physiology, 100(6), 628-639. doi: 10.1113/EP085021

Chen, W., Wang, R., Chen, B., Zhong, X., Kong, H., Bai, Y., … Jones, P. P., … Chen, S. R. W. (2014). The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias. Nature Medicine, 20(2), 184-192. doi: 10.1038/nm.3440

Lamberts, R. R., Lingam, S. J., Wang, H.-Y., Bollen, I. A. E., Hughes, G., Galvin, I. F., Bunton, R. W., Bahn, A., Katare, R., Baldi, J. C., Williams, M. J. A., Saxena, P., Coffey, S., & Jones, P. P. (2014). Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovascular Diabetology, 13, 72. doi: 10.1186/1475-2840-13-72

Zhang, J. Z., McLay, J. C., & Jones, P. P. (2014). The arrhythmogenic human HRC point mutation S96A leads to spontaneous Ca2+ release due to an impaired ability to buffer store Ca2+. Journal of Molecular & Cellular Cardiology, 74, 22-31. doi: 10.1016/j.yjmcc.2014.04.019

Bai, Y., Jones, P. P., Guo, J., Zhong, X., Clark, R. B., Zhou, Q., … Chen, S. R. W. (2013). Phospholamban knockout breaks arrhythmogenic Ca2+ waves and suppresses catecholaminergic polymorphic ventricular tachycardia in mice. Circulation Research, 113, 517-526. doi: 10.1161/circresaha.113.301678

Liu, Y., Kimlicka, L., Heiss, F., Tian, X., Wang, R., Zhang, L., Jones, P. P., … Chen, S. R. W. (2013). The CPVT-associated RyR2 mutation G230C enhances store overloadinduced Ca2+ release and destabilizes the N-terminal domains. Biochemical Journal, 454(1), 123-131. doi: 10.1042/BJ20130594

Wang, R., Zhong, X., Meng, X., Koop, A., Tian, X., Jones, P. P., … Chen, S. R. W. (2011). Localization of the dantrolene-binding sequence near the FK506-binding protein-binding site in the three-dimensional structure of the ryanodine receptor. Journal of Biological Chemistry, 286(14), 12202-12212. doi: 10.1074/jbc.M110.194316

Zhou, Q., Xiao, J., Jiang, D., Wang, R., Vembaiyan, K., Wang, A., … Jones, P. P., … Chen, S. R. W. (2011). Carvedilol and its new analogs suppress arrhythmogenic store overload—induced Ca2+ release. Nature Medicine, 17, 1003-1009. doi: 10.1038/nm.2406

Beca, S., Helliwell, P. B., Simpson, J. A., Zhao, D., Farman, G. P., Jones, P. P., … Backx, P. H. (2011). Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and cardiac contractility, independently of L-Type Ca2+ current. Circulation Research, 109(9), 1024-1030. doi: 10.1161/CIRCRESAHA.111.250464

Jiang, D., Jones, P. P., Davis, D. R., Gow, R., Green, M. S., Birnie, D. H., … Gollob, M. H. (2010). Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia. Channels, 4(4), 12666. doi: 10.4161/chan.4.4.12666

Mufti, R. E., Brett, S. E., Tran, C. H. T., El-Rahman, R. A., Anfinogenova, Y., El-Yazbi, A., … Jones, P. P., … Welsh, D. G. (2010). Intravascular pressure augments cerebral arterial constriction by inducing voltage-insensitive Ca2+ waves. Journal of Physiology, 588(20), 3983-4005. doi: 10.1113/jphysiol.2010.193300

Jones, P. P., Jiang, D., Bolstad, J., Hunt, D. J., Zhang, L., Demaurex, N., & Chen, S. R. W. (2008). Endoplasmic reticulum Ca2+ measurements reveal that the cardiac ryanodine receptor mutations linked to cardiac arrhythmia and sudden death alter the threshold for store-overload-induced Ca2+ release. Biochemical Journal, 412, 171-178. doi: 10.1042/BJ20071287

Kong, H., Jones, P. P., Koop, A., Zhang, L., Duff, H. J., & Chen, S. R. W. (2008). Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor. Biochemical Journal, 414, 441-452. doi: 10.1042/BJ20080489

Jiang, D., Chen, W., Xiao, J., Wang, R., Kong, H., & Jones, P. P. (2008). Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia. Journal of Biological Chemistry, 283(30), 20813-20820. doi: 10.1074/jbc.M801944200

Jones, P. P., Meng, X., Xiao, B., Cai, S., Bolstad, J., Wagenknecht, T., … Chen, S. R. W. (2008). Localization of PKA phosphorylation site, Ser2030, in the three-dimensional structure of cardiac ryanodine receptor. Biochemical Journal, 410, 261-270. doi: 10.1042/BJ20071257

Hunt, D. J., Jones, P. P., Wang, R., Chen, W., Bolstad, J., Chen, K., … Chen, S. R. W. (2007). K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association. Biochemical Journal, 404, 431-438. doi: 10.1042/BJ20070135

Xiao, B., Tian, X., Xie, W., Jones, P. P., Cai, S., Wang, X., … Chen, S. R. W. (2007). Functional consequence of protein kinase A-dependent phosphorylation of the cardiac ryanodine receptor: Sensitization of store overload-induced Ca2+ release. Journal of Biological Chemistry, 282(41), 30256-30264. doi: 10.1074/jbc.M703510200

Xiao, J., Tian, X., Jones, P. P., Bolstad, J., Kong, H., Wang, R., … Chen, S. R. W. (2007). Removal of FKBP12.6 does not alter the conductance and activation of the cardiac ryanodine receptor or the susceptibility to stress-induced ventricular arrhythmias. Journal of Biological Chemistry, 282(48), 34828-34838. doi: 10.1074/jbc.M707423200

Jones, P. P., Bazzazi, H., Kargacin, G. J., & Colyer, J. (2006). Inhibition of cAMP-dependent protein kinase under conditions occurring in the cardiac dyad during a Ca2+ transient. Biophysical Journal, 91, 433-443. doi: 10.1529/biophysj.106.083931

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Journal - Research Other

Jones, P. P., MacQuaide, N., & Louch, W. E. (2018). Dyadic plasticity in cardiomyocytes. Frontiers in Physiology, 9, 1773. doi: 10.3389/fphys.2018.01773

Jones, P. P., Guo, W., & Chen, S. R. W. (2017). Control of cardiac ryanodine receptor by sarcoplasmic reticulum luminal Ca2+. Journal of General Physiology, 149(9), 867-875. doi: 10.1085/jgp.201711805

Jones, P. P., & Braun, A. P. (2009). Store operated Ca2+ entry (SOCE) [Commentary]. Channels, 3(1), 1-2. doi: 10.4161/chan.3.1.7983

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