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Ischaemia-Reperfusion Injury

Ischaemia-Reperfusion Injury

A major theme in the Saeb-Parsy lab is investigation of the mechanisms of ischaemia-reperfusion injury (IRI) in transplantation and other disorders and development of novel therapeutic strategies. As part of the Mitochondrial Therapies Group, we have a long-standing collaboration with Dr Mike Murphy from the Cambridge MRC Mitochondrial Unit, Dr Christian Frezza from the MRC Cancer Unit, Dr Thomas Kreig from the Department of Medicine and  Prof Richard Hartley from University of Glasgow to study mitochondrial mechanisms of IRI and safety and efficacy of novel mitochondria-targeted therapeutics in transplantation, myocardial infarction and stroke.

Our fundamental approach is to simultaneously examine key IRI hypotheses using murine, porcine and human experimental models to enable accelerated translation. We utilise a comprehensive range of murine, porcine and human models of IRI, which include mouse heterotopic heart and kidney transplantation, and in close collaboration with Prof Mike Nicholson and Dr Sarah Hosgood from the Department of Surgery, ex vivo normothermic perfusion of porcine and human organs. We co-founded and coordinate the annual UK Ex Vivo Normothermic Perfusion Symposium, which aims to share expertise and encourage collaborations focused on the use of ex vivo organ perfusion in transplantation.

 

Selected Related Publications

  • Chouchani ET, Pell VR, Gaude E, Aksentijevic´ D, Sundier SY, Robb EL, Logan A, Nadtochiy AM, Ord ENJ, Smith AC, Eyassu F, Shirley R, Hu C-H, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa ASH, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 515(7527):431-5.
  • Chouchani ET, Pell VR, James AM, Work LM, Saeb-Parsy K, Frezza C, Kreig T, Murphy M (2016) A unifying mechanism for mitochondrial superoxide production during ischaemia-reperfusion injury. Cell Metabolism 23: 254-63.
  • Dare A, Logan A, PrimeT, Rogatti S, Goddard M, Bolton E, Bradley JA, Pettigrew GJ, Murphy M, Saeb-Parsy K (2015) The mitochondria-targeted antioxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. Journal of Heart and Lung Transplantation 34: 1471-80.
  • Barlow AD, Hamed MO, Mallon DH, Brais RJ, Gribble FM, Scott MA, Howat WJ, Bradley JA, Bolton EM, Pettigrew GJ, Hosgood SA, Nicholson ML, Saeb-Parsy K (2015) Use of ex vivo normothermic perfusion for quality assessment of discarded human donor pancreases. American Journal of Transplantation 15: 2475-82.
  • Dare AJ, Bolton EA, Pettigrew GJ, Bradley JA, Saeb-Parsy K, Murphy MP (2015) Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ. Redox Biology 5:163-168.
  • Arndt S, Baeza-Garza CD, Logan A, Rosa T, Wedmann R, Prime TA, Martin JL, Saeb-Parsy K, Krieg T, Filipovic MR, Hartley RC, Murphy MP (2017). Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA. Journal of Biological Chemistry 292(19):7761-7773.