Dr Stephen Gilbert
PhD Nov 2008 MRCVS BSc(Hons) BVMS(Hons) MRes
MRC Special Training Fellow in Biomedical Informatics
Institute of Membrane and Systems Biology
Background: BSc 1999 (Molecular Biology, Glasgow, UK), BVMS(Hons) 2001 (Glasgow, UK), MRes 2005(Bioinformatics and Computational Biology, Leeds,UK), PhD, 2008 (Leeds, UK).
Office: Garstang 7.53
Phone: +44(0) 113 34 31869
Email: s.h.gilbert@leeds.ac.uk
Centre membership: The Multidisciplinary Cardiovascular Research Centre (MCRC)
Research Interests
Integrative computational approach to the role of myocardial structure in myocardial function and dysfunction
I will explore the role of local myocardial structure in cardiac excitation and arrhythmia.
The arrangement of the ventricular myocytes is controversial. In a leading model myocytes are arranged as regularly helically coursing fibres running through sheets. Structural studies show that sheets belong to two populations (of positive or negative orientation), have a complex distribution, vary in form between individuals and have localised regions of sudden orientation change. Ventricular electrophysiological propagation is significantly influenced by both by fibre orientation and local sheet structure, and these and other heterogeneities are believed to play a role in the success or failure of defibrillation. Detailed understanding of normal and deranged cardiac excitation requires the integration of knowledge of individual myocyte electrophysiology, cell interconnectivity, the 3D structural arrangement of myocytes and the of the purkinje system.
I will acquire structural and functional data from experimental studies of selected regions of the normal rabbit myocardium, at high spatial resolution. This will be extended to the whole left ventricle, at lower spatial resolution. These data will be built into an integrative structural computational model (virtual tissue). Electrophysiological propagation will be simulated, based upon experimental recordings and using the virtual tissue. Structural changes in the diseased myocardium will be incorporated by manipulation of the normal model, based on published rabbit studies and from our exploration of canine cardiomyopathy. This will also allow the exploration of interspecies differences in the normal and diseased heart.
Structure will be analysed using DT-MRI and three-dimensional histology. The distribution of gap junctions and ion channels (as a marker of myocyte sub-type) will be mapped using immunohistochemistry and in situ hybridisation. These data will be complemented by recording the monophasic action potential and optical recording using voltage sensitive dyes. A multi-layered and detailed virtual tissue will be constructed and then used for the simulation of normal and abnormal electrical propagation. We will explore the roles of the anatomic distribution of fibres, sheets, gap junctions and cell types in electrical propagation. Electrophysiology recording will be used to refine the model, and the model will be used to redirect the recording studies.
The outputs will be i) detailed structural data, ii) a structural and simulation model, and iii) the knowledge from electrophysiological recording and simulation. These will add to the scientific understanding of the mechanisms of arrhythmia which will, in turn, facilitate development of therapies. Specifically the results may find application in clinical defibrillation studies.
Overseas collaborators: Professor Bruce Smaill (New Zealand), Dr Lisbeth Olsen (Denmark).
More information: Holden and Bernus
Personal Research Fellowship (Commenced November 2008)
Medical Research Council, Special Research Training Fellowships in Biomedical Informatics, £422,714.
Responsibilities
MRC Special Training Fellow in Biomedical Informatics
Publications
Gilbert SH; Benoist D; Benson AP; White E; Tanner SF; Holden AV; Dobrzynski H; Bernus O; Radjenovic A Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 302 H287-H298, 2012
DOI:10.1152/ajpheart.00824.2011
Benoist D; Stones R; Drinkhill MJ; Benson AP; Yang Z; Cassan C; Gilbert SH; Saint DA; Cazorla OF; Steele DS; Bernus O; White E Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension. Am J Physiol Heart Circ Physiol -, 2012
DOI:10.1152/ajpheart.01084.2011
Gilbert SH; Benson AP; Walton RD; Bernus O; IEEE Slowed Propagation Across the Compacta-Trabeculata Interface: A Consequence of Fiber and Sheet Anisotropy 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) 1688-1692, 2011
Benson AP; Bernus O; Dierckx H; Gilbert SH; Greenwood JP; Holden AV; Mohee K; Plein S; Radjenovic A; Ries ME; Smith GL; Sourbron S; Walton RD Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology INTERFACE FOCUS 1 101-116, 2011
DOI:10.1098/rsfs.2010.0005
Aslanidi OV; Al-Owais M; Benson AP; Colman M; Garratt CJ; Gilbert SH; Greenwood JP; Holden AV; Kharche S; Kinnell E; Pervolaraki E; Plein S; Stott J; Zhang H Virtual tissue engineering of the human atrium: Modelling pharmacological actions on atrial arrhythmogenesis European Journal of Pharmaceutical Sciences -, 2011
Aslanidi O; Atia J; Benson AP; van den Berg HA; Blanks AM; Choi C; Gilbert SH; Goryanin I; Hayes-Gill BR; Holden AV; Li P; Norman JE; Shmygol A; Simpson NAB; Taggart MJ; Tong WC; Zhang H Towards a computational reconstruction of the electrodynamics of premature and full term human labour Progress in Biophysics and Molecular Biology -, 2011
Walton RD; Benoist D; Hyatt CJ; Gilbert SH; White E; Bernus O Dual excitation wavelength epifluorescence imaging of transmural electrophysiological properties in intact hearts HEART RHYTHM 7 1843-1849, 2010
DOI:10.1016/j.hrthm.2010.08.019
Holden AV; Gilbert SH; Benson AP Is Geometry or Dynamics More Important in Cardiac Arrhythmogenesis?, 2010
DOI:10.1007/978-3-642-12110-4_53
Gilbert SH; McConnell FJ; Holden AV; Sivananthan MU; Dukes-McEwan J The potential role of MRI in veterinary clinical cardiology VETERINARY JOURNAL 183 124-134, 2010
DOI:10.1016/j.tvjl.2008.11.018
Dierckx H; Benson AP; Gilbert SH; Ries ME; Holden AV; Verschelde H; Bernus O Intravoxel Fibre Structure of the Left Ventricular Free Wall and Posterior Left-Right Ventricular Insertion Site in Canine Myocardium Using Q-Ball Imaging, 2009
Gilbert SH; Bernus O; Holden AV; Benson AP A Quantitative Comparison of the Myocardial Fibre Orientation in the Rabbit as Determined by Histology and by Diffusion Tensor-MRI, 2009
Benson AP; Lawrenson JA; Gilbert SH; Holden AV Quantifying effects of class I anti-arrhythmic drugs in human virtual cardiac tissues BIOMEDICAL SIMULATION, PROCEEDINGS 5104 203-208, 2008
Stones R; Gilbert SH; Benoist D; White E Inhomogeneity in the response to mechanical stimulation: Cardiac muscle function and gene expression PROGRESS IN BIOPHYSICS&MOLECULAR BIOLOGY 97 268-281, 2008
DOI:10.1016/j.pbiomolbio.2008.02.01
Benson AP; Gilbert SH; Li P; Newton SM; Holden AV Reconstruction and Quantification of Diffusion Tensor Imaging-Derived Cardiac Fibre and Sheet Structure in Ventricular Regions used in Studies of Excitation Propagation MATHEMATICAL MODELLING OF NATURAL PHENOMENA 3 101-130, 2008
DOI:10.1051/mmnp:2008083
Gilbert SH; Benson AP; Li P; Holden AV Regional localisation of left ventricular sheet structure: integration with current models of cardiac fibre, sheet and band structure EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 32 231-249, 2007
DOI:10.1016/j.ejcts.2007.03.032
Gilbert SH; Benson AP; Li P; Holden AV Visualisation of dog myocardial structure from diffusion tensor magnetic resonance imaging: The paradox of uniformity and variability Functional Imaging and Modeling of the Heart, Proceedings 4466 403-412, 2007
Humphreys S; Rowley G; Stevenson A; Anjum MF; Woodward MJ; Gilbert S; Kormanec J; Roberts M Role of the two-component regulator CpxAR in the virulence of Salmonella entetica serotype typhimurium INFECTION AND IMMUNITY 72 4654-4661, 2004
DOI:10.1128/IAI.72.8.4654-4661.2004
