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Cambridge Cardiovascular



PhD Thesis Supervisor: Dr Thomas Krieg

Title: The investigation of mitochondrial function in ischaemia/reperfusion injury through the use of metabolomics and click chemistry

Abstract: Mitochondrial dysfunction and the production of reactive oxygen species (ROS) is a key component of ischaemia/reperfusion injury.

We hypothesise that during ischaemia there is a significant build-up of succinate and the generation of a maximal mitochondrial membrane potential, conditions which favour reverse electron transport through complex I during reperfusion and a large production of ROS.

My research will aim to characterise the metabolic profile of mouse cardiac tissue under various conditions in the isolated heart preparation and in vivo. It will also aim to investigate alterations in mitochondrial membrane potential in vivo through the validation and testing of a novel mitochondrial-targeted probe, MitoClick.


Key publications: 

Moving Forwards by Blocking Back-Flow: The Yin and Yang of MI Therapy. Pell VR, Chouchani ET, Murphy MP, Brookes PS, Krieg T. Circ Res. 2016 Mar 4;118(5):898-906.

A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury. Chouchani ET, Pell VR, James AM, Work LM, Saeb-Parsy K, Frezza C, Krieg T, Murphy MP. Cell Metab. 2016 Feb 9;23(2):254-63.

Assessing the Mitochondrial Membrane Potential in Cells and In Vivo using Targeted Click Chemistry and Mass Spectrometry. Logan A, Pell VR, Shaffer KJ, Evans C, Stanley NJ, Robb EL, Prime TA, Chouchani ET, Cochemé HM, Fearnley IM, Vidoni S, James AM, Porteous CM, Partridge L, Krieg T, Smith RA, Murphy MP. Cell Metab. 2016 Feb 9;23(2):379-85.

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord EN, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa AS, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP. Nature. 2014 Nov 5. doi: 10.1038/nature13909. [Epub ahead of print]

Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts. Methner C, Chouchani ET, Buonincontri G, Pell VR, Sawiak SJ, Murphy MP, Krieg T. Eur J Heart Fail. 2014 Jul;16(7):712-7.

Using exomarkers to assess mitochondrial reactive species in vivo. Logan A, Cochemé HM, Li Pun PB, Apostolova N, Smith RA, Larsen L, Larsen DS, James AM, Fearnley IM, Rogatti S, Prime TA, Finichiu PG, Dare A, Chouchani ET, Pell VR, Methner C, Quin C, McQuaker SJ, Krieg T, Hartley RC, Murphy MP. Biochim Biophys Acta. 2014 Feb;1840(2):923-30.

Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cochemé HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP. Nat Med. 2013 Jun;19(6):753-9.

Comparison of human ETA and ETB receptor signalling via G-protein and β-arrestin pathways. Maguire JJ, Kuc RE, Pell VR, Green A, Brown M, Kumar S, Wehrman T, Quinn E, Davenport AP. Life Sci. 2012 Oct 15;91(13-14):544-9.

Research Associate
Dr Victoria  Pell


Person keywords: 
ischaemic preconditioning
reperfusion injury