skip to primary navigationskip to content
 

Dr Thomas Krieg

Dr Thomas Krieg

University Lecturer in Clinical Pharmacology

Honorary Consultant Physician


Office Phone: 01223 762584

Research themes

Stem Cells:

Research Interests

Cardiovascular Ischaemia/Reperfusion Injury

A heart attack occurs when a blood clot forms in a coronary artery depriving blood flow from a region of the heart, a condition termed ischaemia. Current therapy is to reopen the artery but blood flow is seldom restored before a significant amount of the heart muscle has died. Because lost heart muscle cannot be regenerated the patient is left with a weakened heart and heart failure often occurs.

Our research is directed toward identifying therapies that prevent cell death in ischaemic heart. We have found that both population of G-coupled adenosine receptors and activation of the nitric oxide-PKG pathway just before the restoration of blood flow (reperfusion) makes the heart very resistant to cell death.

Our current research is directed at understanding the complex signal transduction pathways involved. We study these pathways using a model mirroring the pathophysiological events during an acute heart attack where we measure tissue death after a standardised ischemic insult as an end-point. We can then use pharmacological tools to both trigger and block the protection at specific points in the given pathway.

Secondly, we study isolated heart muscle cells as well as isolated mitochondria where protection can be analysed with certain techniques and the chemical signals can be measured directly using protein chemistry.

Keywords

myocardial ischaemia ; mitochondria ; reperfusion injury

Key Publications

More recent publications are available through PubMed:

cGMP-Elevating Compounds and Ischemic Conditioning Provide Cardioprotection Against Ischemia and Reperfusion Injury via Cardiomyocyte-Specific BK Channels. Frankenreiter S, Bednarczyk P, Kniess A, Bork N, Straubinger J, Koprowski P, Wrzosek A, Mohr E, Logan A, Murphy MP, Gawaz M, Krieg T, Szewczyk A, Nikolaev VO, Ruth P, Lukowski R. Circulation. 2017 Oct 19. [Epub ahead of print]

MitoNeoD: A Mitochondria-Targeted Superoxide Probe. Shchepinova MM, Cairns AG, Prime TA, Logan A, James AM, Hall AR, Vidoni S, Arndt S, Caldwell ST, Prag HA, Pell VR, Krieg T, Mulvey JF, Yadav P, Cobley JN, Bright TP, Senn HM, Anderson RF, Murphy MP, Hartley RC. Cell Chem Biol. 2017 Oct 19;24(10):1285-1298.e12.

Identification and quantification of protein S-nitrosation by nitrite in the mouse heart during ischemia. Chouchani ET, James AM, Methner C, Pell VR, Prime TA, Erickson BK, Forkink M, Lau GY, Bright TP, Menger KE, Fearnley IM, Krieg T, Murphy MP. J Biol Chem. 2017 Sep 1;292(35):14486-14495.

Assessment of H2S in vivo using the newly developed mitochondria-targeted mass spectrometry probe MitoA. 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. J Biol Chem. 2017 May 12;292(19):7761-7773.

Functional assessment and transplantation of the donor heart after circulatory death. Messer SJ, Axell RG, Colah S, White PA, Ryan M, Page AA, Parizkova B, Valchanov K, White CW, Freed DH, Ashley E, Dunning J, Goddard M, Parameshwar J, Watson CJ, Krieg T, Ali A, Tsui S, Large SR. J Heart Lung Transplant. 2016 Dec;35(12):1443-1452.

Succinate metabolism: a new therapeutic target for myocardial reperfusion injury. Pell VR, Chouchani ET, Frezza C, Murphy MP, Krieg T. Cardiovasc Res. 2016 Jul 15;111(2):134-41.

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 20;515(7527):431-5.

Turning on cGMP-dependent pathways to treat cardiac dysfunctions: boom, bust, and beyond. Lukowski R, Krieg T, Rybalkin SD, Beavo J, Hofmann F. Trends Pharmacol Sci. 2014 Aug;35(8):404-13.

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.

Adenosine receptor activation improves microcirculation in experimental intestinal ischemia/reperfusion. Zhou J, Zimmermann K, Krieg T, Soltow M, Pavlovic D, Cerny V, Lehmann C. Clin Hemorheol Microcirc. 2014 Jun 2.

Functional assessment of the mouse heart by MRI with a 1-min acquisition. Buonincontri G, Methner C, Krieg T, Carpenter TA, Sawiak SJ. NMR Biomed. 2014 Jun;27(6):733-7.

Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy. Chouchani ET, Methner C, Buonincontri G, Hu CH, Logan A, Sawiak SJ, Murphy MP, Krieg T. PLoS One. 2014 Apr 4;9(4):e94157.

Riociguat reduces infarct size and post-infarct heart failure in mouse hearts: insights from MRI/PET imaging. Methner C, Buonincontri G, Hu CH, Vujic A, Kretschmer A, Sawiak S, Carpenter A, Stasch JP, Krieg T. PLoS One. 2013 Dec 31;8(12):e83910.

MRI and PET in mouse models of myocardial infarction. Buonincontri G, Methner C, Carpenter TA, Hawkes RC, Sawiak SJ, Krieg T. J Vis Exp. 2013 Dec 19;(82):e50806.

Cambridge Cardiovascular logo - transparent

Logo design by Dr Ana-Mishel Spiroski and Dr Sarah Morgan.

 

We connect cardiovascular researchers in Cambridge.

Please follow us on Twitter for local news about research, events, funding calls, and open positions.

For inquiries about our research or the website, please contact Dr Katja Kivinen.