Dr David Greensmith
Lecturer in Biomedical Science; Programme Leader for Human Biology and Infectious Diseases
I graduated from The University of Salford in 2005 having completed a BSc Biological Sciences. I went on to do my PhD with Dr Mahesh Nirmalan and Professor David Eisner in the School of Medicine, University of Manchester. The main focus of my work was to investigate the effects of reactive oxygen species (ROS) and proinflammatory cytokines on calcium handling in ventricular myocytes.
Following the award of my PhD in 2009, I took a Post Doctoral position as a cardiac, cellular electrophysiologist with Professor David Eisner and Professor Andrew Trafford in the Institute of Cardiovascular Sciences, University of Manchester. Here, I helped to develop a fluorescent microscopy technique where cells are co-loaded with multiple calcium indicators. This allows the simultaneous, real-time measurement of calcium from multiple sub-cellular compartments. Using this technique, in combination with single cell patch-clamping, I contributed to the understanding of how cardiac intracellular calcium handling is regulated in health, and how this regulation becomes dysfunctional in disease states such as heart failure.
I took up my current position as a Lecturer in Biomedical Science at the University of Salford in September 2014.
I teach across the Biomedical Science Programme on various aspects of human physiology and pathophysiology.
Disease in which heart failure is implicated accounts for 160,000 annual deaths in the UK. To develop effective therapies which prevent, treat and cure heart disease, it essential that we understand the cellular mechanisms of cardiac function.
My particular focus investigates how calcium handling is regulated at the level of the individual cardiac myocyte, and, how this regulation becomes dysfunctional in various disease states. Many diseases are associated with elevations in reactive oxygen species (ROS) and proinflammatory cytokines, so I am particularly interested in how these mediators affect cardiac cellular function.
My experimental expertise lie in real-time fluorescent imaging using epifluorescent and confocal microscopy combined with electrophysiological techniques such as single cell patch-clamping.
Qualifications and Memberships
BSc (Hons) Biological Sciences, University of Salford, 2005
PhD, University of Manchester, 2009
Member of the Physiological Society
Member of the Society of Biology
Member of the European Society of Cardiology (European Working Group For Cardiac Cellular Electrophysiology)
Member of the British Society For Cardiovascular Research
Member of the Biophysical Society
Honorary Lecturer, University of Manchester
Sankaranarayanan R, Kistamas K, Greensmith DJ, Venetucci LA and Eisner DA. (2017). Systolic [Ca2+]i regulates diastolic levels in rat ventricular myocytes. Journal of Physiology. In press and awaiting citation. DOI: 10.1113/JP274366
Scotcher J, Prysyazhna O, Boguslavskyi A, Kistamas K, Hadgraft N, Martin E, Worthington J, Rudyk O, Cutillas PR, Cuello F, Shattock M, Marber M, Conte M, Greenstein A, Greensmith DJ, Venetucci L, Timms J and Eaton P (2016). Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response. Nature Communications, 7, 13187.
Sankaranarayanan R, Li, Y, Greensmith DJ, Eisner D and Venetucci L (2016). Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak. The Journal of Physiology, 594(3), 611-623.
Miller L*, Greensmith DJ*, Sankaranarayanan R, O’Neil S and Eisner D (2015). The effect of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) on intracellular Ca2+ handling in rat ventricular myocytes. Cell Calcium, 58, 208-214 *Equal contribution
Clarke JD, Caldwell JL, Horn MA, Bode EF, Richards MA, Hall MC, Graham HK, Briston SJ, Greensmith DJ, Eisner DA, Dibb KM and Trafford AW (2015). Perturbed atrial calcium handling in an ovine model of heart failure: Potential roles for reductions in the L-type calcium current. Journal of Molecular and Cellular Cardiology 79, 169-179.
Dubuis E, Thompson V, Leite MI, Blaes F, Maihöfner C, Greensmith DJ, Vincent A, Shenker N, Kuttikat A, Leuwer M and Goebel A (2014). Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors. PAIN, 155(11), 2408-2417.
Greensmith DJ, Galli G, Trafford AW and Eisner DA (2014) Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions. Cardiovascular Research 103, 554-563.
Greensmith DJ (2014). Ca analysis: an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis. Computer Methods and Programs in Biomedicine 113, 241-250.
Greensmith DJ and Nirmalan M (2013). The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes. Physiological Reports 1, e00093.
Johnson DM, Heijman J, Bode EF, Greensmith DJ, van der Linde H, Abi-Gerges N, Eisner DA, Trafford AW, and Volders PG (2013). Diastolic spontaneous calcium release from the sarcoplasmic reticulum increases beat-to-beat variability of repolarization in canine ventricular myocytes after beta-adrenergic stimulation. Circulation Research 112, 246-256.
Horn MA, Graham HK, Richards MA, Clarke JD, Greensmith DJ, Briston SJ, Hall MCS, Dibb KM, and Trafford AW (2012). Age-related divergent remodeling of the cardiac extracellular matrix in heart failure: Collagen accumulation in the young and loss in the aged. Journal of Molecular and Cellular Cardiology 53, 82-90.
Briston SJ, Caldwell JL, Horn MA, Clarke JD, Richards MA, Greensmith DJ, Graham HK, Hall MC, Eisner DA, Dibb KM, and Trafford AW (2011). Impaired β-adrenergic responsiveness accentuates dysfunctional excitation contraction coupling in an ovine model of tachypacing induced heart failure. Journal of Physiology (London) 589, 1367-1382.
Greensmith DJ, Eisner DA, and Nirmalan M (2010). The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte. Cell Calcium 48, 341-351.