Dr John Mitcheson

I moved to the University of Leicester to establish my research group in 2000. I was promoted to Reader/Assistant professor in 2006. My research focusses on voltage gated potassium channels, with a particular emphasis on their function and regulation in the heart and in certain types of cancer. I have been fortunate to work with some excellent young research scientists, supervising more than 12 PhD students to completion and 7 postdoctoral research assistants and technicians. My research has been funded by the MRC, BBSRC and British Heart Foundation as well as by Pharmaceutical and Biotechnology companies. I make a substantial contribution to the delivery of Physiology and Pharmacology teaching in the School of Biological Sciences.

Early Career
I graduated from Kings College London with a BSc in Physiology and Biochemistry in 1991. My research career started in the Department of Physiology at the University of Bristol, first as a Wellcome Trust Research Assistant then as an MRC funded PhD student (1992 - 1995) and subsequently as a BHF Postdoctoral research assistant (1995 - 1998). My research at Bristol was focussed on cardiac ion channels, excitation-contraction coupling and pacemaker activity. In 1998 I successfully applied for a Wellcome Trust Prize Travelling Research Fellowship that enabled me to move to Salt Lake City and work with Prof Mike Sanguinetti on ion channel structure,  function, and pharmacology. It was after this I moved to Leicester to start my research group and contribute to teaching in the School of Biological Sciences.

My lab use a combination of electrophysiology, molecular biology, protein biochemistry and structure biology techniques to study the role of voltage gated potassium channels in healthy and diseased tissues. I have a long-standing interest in the role of potassium channels particularly hERG (Kv11) in cardiac repolarization and how dysfunction and ion channel remodelling leads to arrhythmias and sudden cardiac death. My group have a well-established collaboration with Prof Andre Ng (Department of Cardiovascular Sciences) and have recently been awarded a joint BHF 5 year programme grant to study mechanisms of increased vulnerability to ventricular fibrillation and sudden death with heart failure.

Other interests include the role of hEAG (Kv10) a close relative of hERG in cancer. hEAG channels are aberrantly over-expressed in many human cancers and inhibition of hEAG channel function decreases the proliferation of tumour cells and the size of tumours. On-going studies are working out the molecular mechanisms linking hEAG channel function to proliferation. 

Selected publications

Burton M, Cresser-Brown, Thomas M, Portolano N, Basran J, Freeman SL, Kwon H, Bottrill AR, Llansola-Portoles MJ, Pascal AA, Jukes-Jones R, Chernova T, Schmid R, Davies NW, Storey NM, Dorlet P, Moody PCE, Mitcheson JS & Raven EL. (2020) Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel J Biol Chem. 2020 Sep 18; 295(38): 13277–13286.

Bate N, Caves RE, Skinner SP, Goult BT, Basran J, Mitcheson JS, & Vuister GW. (2018). A Novel Mechanism for Calmodulin-Dependent Inactivation of Transient Receptor Potential Vanilloid 6.. Biochemistry. doi:10.1021/acs.biochem.7b01286

Kapetanaki SM, Burton MJ, Basran J, Uragami C, Moody PCE, Mitcheson JS, Schmid R, Davies NW, Dorlet P, Vos MH, Storey NM, Raven, E. (2018). A mechanism for CO regulation of ion channels. NATURE COMMUNICATIONS, 9, 10 pages. doi:10.1038/s41467-018-03291-z 

Lorinczi E, Helliwell M, Finch A, Stansfeld PJ, Davies NW, Mahaut-Smith M, Muskett FW, Mitcheson JS. Calmodulin Regulates Human Ether à Go-Go 1 (hEAG1) Potassium Channels through Interactions of the Eag Domain with the Cyclic Nucleotide Binding Homology Domain. J Biol Chem. 2016 Aug 19;291(34):17907-18. doi: 10.1074/jbc.M116.733576. 
 
Burton MJ, Kapetanaki SM, Chernova T, Jamieson AG, Dorlet P, Santolini J, Moody PC, Mitcheson JS, Davies NW, Schmid R, Raven EL, Storey NM. A heme-binding domain controls regulation of ATP-dependent potassium channels. Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):3785-90. doi: 10.1073/pnas.1600211113 

Melgari D, Brack KE, Zhang C, Zhang Y, El Harchi A, Mitcheson JS, Dempsey CE, Ng GA, Hancox JC. hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine. J Am Heart Assoc. 2015 Apr 24;4(4). pii: e001813. doi: 10.1161/JAHA.115.001813.  

Gasparoli L, D’Amico M, Masselli M, Pillozzi S, Caves R, Khuwaileh R, Tiedke W, Mugridge K, Pratesi A, Mitcheson JS, Basso G, Becchetti A and Arcangeli A. The new pyrimido-indole compound CD-160130 preferentially inhibits the Kv 11.1B isoform and produces antileukemic effects without cardio-toxicity. Mol Pharmacol. 2015 Feb;87(2):183-96. doi: 10.1124/mol.114.094920. 

Pier DM, Shehatou GS, Giblett S, Pullar CE, Tresize DJ, Pritchard CA, Challiss J, Mitcheson JS. Long-term Channel Block is Required to Inhibit Cellular Transformation by Human Ether-a-go-go-related Gene (hERG1) Potassium Channels. Mol Pharmacol. 2014 Aug;86(2):211-21. doi: 10.1124/mol.113.091439. 

Muskett FW, Thouta S, Thomson SJ, Bowen A, Stansfeld PJ, Mitcheson JS. Mechanistic insight into human ether-Ã -go-go-related gene (hERG) K+ channel deactivation gating from the solution structure of the EAG domain. J Biol Chem. 2011 Feb 25;286(8):6184-91. doi: 10.1074/jbc.M110.199364. 

Ion channel physiology

Ion channel pharmacology

Potassium channel structure and function

Cardiac physiology

Cardiac pharmacology

Ion channels and cancer

Degree streams I teach on include Medical Physiology Biological Sciences (Physiology and Pharmacology) Neuroscience and Natural Sciences

Modules

BS1060 - Multicellular Organisation - an introduction to Physiology Pharmacology and Neuroscience

BS2013 - Physiology and Pharmacology

BS2015 - Physiology of Excitable Cells

BS2014 - Exercise Physiology and Pharmacology

MB3057 - Current and future therapeutics

BS3056 - Cellular Physiology of the Cardiovascular System

BS3X00 - Third year projects

NS1004 - Biophysics Physiology and Metabolism

Cardiac physiology

Ion channel related diseases

Senior Fellow of the Higher Education Academy

PhD Cardiac myocyte electrophysiology University of Bristol BSc (Hons)

Physiology and Biochemistry Kings College London