Professor Derek Steele

Profile

BSc (Glasgow), PhD (Glasgow), Postdoctoral research at Glasgow. Lecturer (1996-2000); Senior Lecturer (2000-2006); Reader in Cellular Physiology (2006-2011); Cardiovascular Group Leader, Institute of Membrane & Systems Biology (2005-2011); Research Director, School of Biomedical Sciences (2011-2014); Professor of Cell Physiology (2011-present)

Research interests

My research addresses the molecular and cellular events that underlie excitation-contraction coupling in both cardiac and skeletal muscle and how these processes are modified by physiological adaptations or disease. Live cell confocal imaging and electrophysiology underpin much of my work and current projects in the cardiac field include studies that address remodeling of local Ca signaling in heart failure, the role of the Golgi apparatus as a Ca signaling organelle and novel mechanisms underlying arrhythmias.  In recent years my work has been underpinned by 2 consecutive BHF programme grants.

Selected research highlights:

2001- First demonstration that ATP depletion inhibits SR Ca sparks in cardiac cells and that re-introduction causes a synchronized burst of Ca release, which can act as a pro-arrhythmic substrate (1).
2002- First demonstration that the Na/Ca exchanger is localised in the t-tubules in cardiac cells, with consequent effects on cell function (2).
2005- First description of prolonged Ca release events originating at the nuclear poles in adult cardiac myocytes. Highlighted on front cover of Circulation Research (3)
2006- Demonstration that the RyR2 peptide DPc10 can mimic the disease phenotype associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) by disrupting interaction of specific RyR2 channel domains (4)
2010- First evidence that store-operated Ca entry contributes to malignant hyperthermia in humans (5). This work was the outcome of a 4 year study with clinicians based at the national screening centre for malignant hyperthermia, St James’s University Hospital, Leeds.
2010- First description of a novel mechanism by which the drug flecainide prevents CPVT arrhythmias by acting directly on the cardiac ryanodine receptor to alter Ca spark mass (6).  
2012-First demonstration that sub-lethal concentrations of carbon monoxide cause cardiac arrhythmias by activating the late sodium current, secondary to nitrosylation of Nav1.5 (7). It addition, it was shown that the drug ranolazine, a selective inhibitor of the late sodium current, blocks the pro-arrhythmic effects of CO in both cells and animals.
2014- Release of xySpark, an image analysis program written in Java and distributed as a plugin for ImageJ, which allows automatic analysis of Ca sparks in 2D image stacks. (8)
2015- First evidence that the Golgi apparatus operates as a Ca signaling organelle that is functionally distinct from the SR in adult cardiac myocytes (9)
2017- The first demonstration that inhibition of the Epac pathway increases mitochondrial ROS production and arrhythmia susceptibility via activation of the late Na current (10)

1. Yang Z and Steele DS Effects of cytosolic ATP on Ca sparks and SR Ca content in permeabilized cardiac myocytes. Circ.Res. 89:526-533, 2001.
2. Yang Z et al Na/Ca exchange activity is localized in the T-tubules of rat ventricular myocytes. Circ.Res. 91:315-322, 2002.
3. Yang Z and Steele DS. Characteristics of prolonged Ca release events associated with the nuclei in adult cardiac myocytes. Circ.Res. 96:82-90, 2005.
4. Yang Z et al. The RyR2 central domain peptide DPc10 lowers the threshold for spontaneous Ca release in permeabilized cardiomyocytes. Cardiovasc.Res. 70:475-485, 2006.
5. Duke AM et al. Store operated Ca entry in malignant hyperthermia-susceptible human skeletal muscle. J.Biol.Chem., 285:25645-53, 2010
6. Hilliard FA et al. Flecainide inhibits arrhythmogenic Ca waves by open state block of ryanodine receptor Ca release channels and reduction of Ca spark mass. J.Mol.Cell Cardiol. 48:293-301, 2010.
7. Dallas,M.L et al., Carbon monoxide induces cardiac arrhythmia via induction of the late Na+ Current. Am J Respir Crit Care Med 186:7 648-656, 2012.
8. Steele, E.M. & Steele D.S. Automated detection and analysis of Ca sparks in x-y image stacks using a thresholding algorithm implemented within the open-source image analysis platform, ImageJ Biophysical Journal, 106: 556-576, 2014  See web page for program download: www.fbs.leeds.ac.uk/staff/steele/xySpark/
9. Yang, Z. et al., The Golgi apparatus is a functionally distinct Ca store regulated by the PKA and Epac branches of the β1-adrenergic signaling pathway Science Signaling 8: 1-11, 2015.
10. Yang Z et al., Epac2-Rap1 Signaling Regulates Reactive Oxygen Species Production and Susceptibility to Cardiac Arrhythmias. Antioxid Redox Signal 27 117-132, 2017

• Abnormal calcium homeostasis as a mechanism of acute diaphragm weakness in sepsis

Qualifications

• B.Sc. Physiology (Hons 1st Class) Glasgow, 1986
• Ph.D. Glasgow, Cardiac Physiology, 1990

Professional memberships

• Physiological Society
• Biophysical Society

Student education

Studentship information

See also:

• Faculty Graduate School
• FindaPhD Project details:
  • Project 33877
  • Project 37220

Research groups and institutes

• Cardiovascular

Current postgraduate researchers

• Miriam Hurley