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Department of Biochemistry


Molecular pathophysiology of cardiac arrhythmias

Our research programme focuses on characterising the properties of the heart that provide the ‘substrate’ for arrhythmias.  The central hypothesis is that the determinants of arrhythmic risk including atrial and ventricular fibrillation lie within the heart itself and that much of this risk is genetic.  Our core activities are therefore concerned with linking genetic alterations determining fibrillation syndromes to arrhythmogenic phenotypes through the use of GM mouse and human iPS cell-derived models.  We have a strong group of collaborators facilitating these aspects of the programme.  My clinical research involves electrophysiological phenotyping and is firmly based on the laboratory models.  A large, wide ranging referral base allows the efficient delivery of this translational limb of the program.  I have also developed links with industry based on translational (‘cell-to-bedside’) principles that provide novel and even ‘disruptive’ approaches (drugs and devices) for patient management largely based on the insights obtained through the pre-clinical programmes.

Lab members: Laila Guzadhur, Christopher Huang, Jeremy Skepper, Gary Tse

Key publications:

1.  SaumarezRC, Pytkowski M, Chojnowska L, Sterlinski M, Sadoul N, Clague J, Connelly D, McLeod K,Morgan J, Cobbe SA, GriffithMJ, Bourke J, Huang C. L-H, Grace AA. (2008): Paced ventricular electrogram fractionation predicts sudden death in hypertrophic cardiomyopathy, European Heart Journal. 29:1653-1661

2.  LiuM, Sanyal S, Gao G, GurungIS, Zhu X, Gaconnet G, Kerchner LJ, ShangLL, Huang C L-H, GraceAA, London B, Dudley SC. (2009):  Cardiac Na+ Current Regulation by Pyridine Nucleotides: A Possible Explanation of Glycerol-3-Phosphate Dehydrogenase-Linked Brugada Syndrome. Circulation Research. 105:737-745

3..  Bardy GH, Smith WM, Hood MA, Crozier IG, Melton IC, Jordaens L, Theuns D, Park RE, Wright DJ, Connelly DT, Fynn SP, Murgatroyd FD, Sperzel J, Neuzner J, Spitzer SG, Ardashev AV, Oduro A, Boersma L, Maas AH, Van Gelder IC, Wilde AA, van Dessel PF, Knops RE, Lupo P, Cappato R, Grace AA. (2010): The Subcutaneous only Implantable Cardioverter Defibrillator. New England Journal of Medicine. 363:36-44

4.  Martin CA, Grace AA, Huang CL (2011): Spatial and temporal heterogeneities are localized to the right ventricular outflow tract in a heterozygotic Scn5a mouse model. American Journal of Physiology (Heart and Circulatory Physiology 300:H605-16