Harmer, Stephen

Stephen Harmer

Steve Harmer graduated with a B.Sc. (Hons) in Molecular Biology in 2002 from the University of Reading. He then undertook a Ph.D. in Molecular Endocrinology at the University of Reading with Professor Philip Lowry and Dr Andrew Bicknell to determine whether specific pro-opiomelanocortin (POMC) derived peptides have novel roles in the periphery. This work led to the award of a doctoral thesis entitled ‘An investigation into the actions of gamma-MSH peptides in the periphery’ in April 2006. After his Ph.D. training Steve joined University College London (UCL) where he did post-doctoral research investigating disease mechanisms in the Long QT syndrome (LQTS) with Professor Andrew Tinker. In October 2011, he moved with Professor Andrew Tinker to the William Harvey Heart Centre (QMUL). In November 2012 Steve was awarded a British Heart Foundation (BHF) Intermediate Basic Science Research Fellowship (IBSRF).

Summary of Research

Sudden death due to cardiac causes (SCD) is a major clinical problem and the Long QT syndrome (LQTS) is an important cause of SCD in young people. LQTS is characterised by a prolongation of the QT interval as visualised on an electrocardiogram (ECG). This prolongation can lead to the development of torsade-de-pointes, a characteristic irregular wave pattern on the ECG, and in turn ventricular fibrillation. LQTS can be an inherited syndrome or acquired, usually as a result of drug therapy. Of the hereditary forms of LQTS that have been identified approximately half of all cases are associated with mutations in KCNQ1 or KCNE1. These two proteins assemble to form a heteromultimeric channel complex, composed of a tetramer of KCNQ1 α-subunits and between one and four KCNE1 β-subunits, which produces a potassium selective current in ventricular myocytes called IKs. The IKs current is critical for repolarisation of the human cardiac action potential and mutations in either of these ion channel subunits can cause LQTS. In detail, mutations in KCNQ1 underlie LQTS type 1 (LQT1) whilst mutations in KCNE1 account for LQT5. In recent years it has become apparent that, in addition to their functional effects on current properties, mutations in either KCNQ1 or KCNE1 can also act to disrupt the trafficking of the channel complex to its site of action at the cell surface. Although it is now clear that defective channel trafficking plays a major role in LQT1 disease pathogenesis the molecular mechanisms that underlie this process remain poorly understood. Dr Steve Harmer’s research interests include:

  • Characterisation of the molecular mechanisms that underlie the defective trafficking of LQT1 mutant channel complexes.
  • The use of inducible pluripotent stem cell (iPSc) technology to generate cardiac cells from patients with LQT1 that can be used as model systems in which to study the mechanisms that underlie this disease.
  • The development of therapeutic strategies that could rescue the function of disease causing LQT1 mutations and ultimately prevent sudden death in these patients.

Key Publications

For a full list of publist publications click here

Harmer SC, Mohal JS, Kemp D, Tinker A. Readthrough of long-QT syndrome type 1 nonsense mutations rescues function but alters the biophysical properties of the channel. Biochemical Journal. 2012 May; 443(3): 635-42.

Thomas AM, Harmer SC, Khambra T, Tinker A. Characterization of a binding site for anionic phospholipids on KCNQ1. Journal of Biological Chemistry. 2011 Jan; 286(3): 2088-100.

Tinker A, Harmer SC. K+ channels in the heart: new insights and therapeutic implications. Expert Reviews in Clinical Pharmacology. 2010 May; 3(3): 305-19.

Mashanov GI, Nobles M, Harmer SC, Molloy JE, Tinker A. Direct observation of individual KCNQ1 potassium channels reveals their distinctive diffusive behavior. Journal of Biological Chemistry. 2010 Feb; 285(6): 3664-75.

Harmer SC, Wilson AJ, Aldridge R, Tinker A. Mechanisms of disease pathogenesis in long QT syndrome type 5. American Journal of Physiology - Cell Physiology. 2010 Feb; 298(2): C263-73.

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