Stefan Neubauer MD, FRCP, FACC, FMedSci
Clinical Director, University of Oxford Centre Clinical Magnetic Resonance Research (OCMR), Co-Director, Oxford BHF Experimental Magnetic Resonance Unit
- Cardiovascular Science
Selected Cardiac Energetics Publications
- Aksentijevic Dunja, Lygate Craig A, Makinen Kimmo, Zervou Sevasti, Sebag-Montefiore Liam, Medway Debra, Barnes Hannah, Schneider Jurgen E, and Neubauer Stefan (2010) High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes. Eur J Heart Fail, 12(12):1282-9.
- Lygate Craig A, Hunyor Imre, Medway Debra, de Bono Joe P, Dawson Dana, Wallis Julie, Sebag-Montefiore Liam, and Neubauer Stefan (2009) Cardiac phenotype of mitochondrial creatine kinase knockout mice is modified on a pure C57BL/6 genetic background. J Mol Cell Cardiol, 46(1):93-9.
- Lygate Craig A, Fischer Alexandra, Sebag-Montefiore Liam, Wallis Julie, ten Hove Michiel, and Neubauer Stefan (2007) The creatine kinase energy transport system in the failing mouse heart. J Mol Cell Cardiol, 42(6):1129-36.
- Neubauer Stefan (2007) The failing heart--an engine out of fuel. N Engl J Med, 356(11):1140-51.
- Wallis Julie, Lygate Craig A, Fischer Alexandra, ten Hove Michiel, Schneider Jurgen E, Sebag-Montefiore Liam, Dawson Dana, Hulbert Karen, Zhang Wen, Zhang Mei H, Watkins Hugh, Clarke Kieran, and Neubauer Stefan (2005) Supranormal myocardial creatine and phosphocreatine concentrations lead to cardiac hypertrophy and heart failure: insights from creatine transporter-overexpressing transgenic mice. Circulation, 112(20):3131-9.
Selected Imaging Publications
- Schneider Jurgen E, Lanz Titus, Barnes Hannah, Stork Lee-Anne, Bohl Steffen, Lygate Craig A, Ordidge Roger J, and Neubauer Stefan (2011) Accelerated cardiac magnetic resonance imaging in the mouse using an eight-channel array at 9.4 Tesla. Magn Reson Med, 65(1):60-70.
- Karamitsos Theodoros D, Francis Jane M, Myerson Saul, Selvanayagam Joseph B, and Neubauer Stefan (2009) The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol, 54(15):1407-24.
- Rider Oliver J, Francis Jane M, Ali Mohammed K, Petersen Steffen E, Robinson Monique, Robson Matthew D, Byrne James P, Clarke Kieran, and Neubauer Stefan (2009) Beneficial cardiovascular effects of bariatric surgical and dietary weight loss in obesity. J Am Coll Cardiol, 54(8):718-26.
- Petersen Steffen E, Selvanayagam Joseph B, Wiesmann Frank, Robson Matthew D, Francis Jane M, Anderson Robert H, Watkins Hugh, and Neubauer Stefan (2005) Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol, 46(1):101-5.
- Selvanayagam Joseph B, Jerosch-Herold Michael, Porto Italo, Sheridan David, Cheng Adrian SH, Petersen Steffen E, Searle Nick, Channon Keith M, Banning Adrian P, and Neubauer Stefan (2005) Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment. Circulation, 112(21):3289-96.
University of Oxford Centre for Clinical Magnetic Resonance at the John Radcliffe Hospital
BHF Molecular Cardiology Laboratory and BHF Experimental MR Unit, Henry Wellcome Building of Genomic Medicine
Cardiac Energy Metabolism in Ischaemia and Heart Failure
Basic science work in this area is co-led by Dr Craig Lygate and funded by a British Heart Foundation programme grant. We are studying the influence of cardiac energy homeostasis on ischaemic heart disease and chronic heart failure, and the potential benefits of therapies that modulate cardiac metabolism.
The heart has very high energy requirements, cycling through more than 20 times its own weight in ATP every day, and maintaining energy production and transport is fundamental to normal cardiac function. Impairment of these mechanisms plays an important role in acute ischaemic heart disease and in chronic heart failure, both major killers worldwide.
Our hypothesis is that the failing heart is energy-starved, and in the search for new therapeutic strategies we have projects encompassing aspects of substrate utilisation, phosphotransfer mechanisms, and adenine nucleotide recycling, with a major emphasis of the creatine kinase system and the creatine transporter.
Our lab employs a wide range of molecular and biochemical techniques, high-throughput cell-based assays, global gene expression profiling and live cell imaging through confocal microscopy. Functional consequences of altered gene expression are studied at the level of the mitochondria, and at the whole organ level. We have particular expertise in assessing in vivo function in the intact organism, using cutting edge methodologies and state-of-the-art facilities, e.g. high-frequency echocardiography, left ventricular pressure measurements, and in close collaboration with Dr Jürgen Schneider we have pioneered techniques for experimental Magnetic Resonance Imaging and Spectroscopy.
Clinical science work in this area uses cardiac MR spectroscopy (31P and 1H) and MR imaging to investigate cardiac energetics, lipid metabolism and cardiac function in patients with hypertrophy and heart failure, including assessment of novel forms of metabolic therapy in clinical trials.
Development and Application of Magnetic Resonance Techniques for Phenotyping of Cardiovascular Disease
Clinical research in this area is carried out on 1.5 and 3T Siemens MR systems at the University of Oxford Centre for Clinical Magnetic Resonance Research (link), where we employ state-of-the-art cardiovascular magnetic resonance methods to assess aspects of cardiac function and physiology currently inaccessible to conventional imaging methods. Examples include tissue characterization methods (e.g. T1 mapping), myocardial oxygenation (BOLD), 4D flow and 7 Tesla human imaging (7T system installed 9/11). We also apply established CMR techniques to study novel scientific hypotheses, e.g. in patients with cardiomyopathies, ischemic heart disease and heart valve disease. Examples include the development of diagnostic criteria for left ventricular non-compaction, perfusion abnormalities in hypertrophic cardiomyopathy, or assessment of irreversible myocardial injury associated with revascularization (PCI or CABG). Our clinical science programme is closely integrated with the clinical cardiac CMR service (link) for the ORH NHS Trust, providing a truly translational research environment.
State-of-the-art methods for experimental Magnetic Resonance Imaging and Spectroscopy, to non-invasively characterize experimental models, are being developed at the BHF experimental MR unit (BMRU), co-led by Dr Jürgen Schneider, using a 9.4T high-field Agilent MR system.
Basic science group leadership: Dr. Dunja Aksentijevic, Dr. Craig Lygate, Dr. Juergen Schneider, Dr. Sevasti Zervou
Clinical science group leadership: Jane Francis, Dr. Cameron Holloway, Dr. Theo Karamitsos, Dr. Saul Myerson, Dr Matthew Robson.
Local collaborators: Prof. Hugh Watkins, Prof. Barbara Casadei, Prof. Kieran Clarke, Dr Damian Tyler, Dr. Angela Russell, Prof. Keith Channon, Prof. Adrian Banning, Prof. Robin Choudhury, Prof. Shoumo Bhattacharya, Dr. Ben Davies, Dr. Houman Ashrafian, Prof. John Stradling, Prof. John Wass, Prof. Sarah Darby, Prof. Paul Wordsworth, Dr Rajesh Kharbanda, Prof. David Taggart
National/International collaborators: Prof Dirk Isbrandt, Hamburg; Prof. Michael Jerosch-Herold, Boston; Prof. Juergen Henning, Freiburg; Prof. Michael Markl, Chicago; Prof. Axel Haase, Munich; Prof. Robert Balaban, NHLBI; Prof. Harald Becher, Edmonton; Prof. Meinrad Beer, Wuerzburg; Prof. Joseph Selvanayagam, Adelaide; Prof. Matthias Friedrich, Montreal; Prof. Thomas Vaughn, Minneapolis; Prof. Kamil Ugurbil, Minneapolis; Prof. Markus von Kienlin, Basel; Dr. Steffen Petersen, London;
Training: DPhil and DM students in our group can experience a wide, fully translational, spectrum of scientific studies and methods, from molecular/basic to clinical research. In recent years, many of our students have won national/international research prizes, such as from the American Heart Association, the International Society for Heart Research, the British Cardiovascular Society and the Society for Cardiovascular Magnetic Resonance.
Prof. Stefan Neubauer is a Professor of Cardiovascular Medicine, Clinical Director of the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), and Co-Director of the BHF Experimental MR Unit (Henry Wellcome Building of Genomic Medicine), at the Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. Prof. Neubauer’s work over the past 25 years has been devoted to two areas, the development and application of Cardiovascular Magnetic Resonance (CMR) imaging and spectroscopy, and the role of cardiac energy metabolism in ischemia and heart failure. He has published >300 original research articles and currently leads a group of ~40 co-workers. Editorial positions and contributions to scientific bodies include his involvement with the Society for Cardiovascular Magnetic Resonance (President 2006-2008), Chairman of the British Society of Cardiovascular Magnetic Resonance (2008-2010), Associate Editor of the European Heart Journal and of the Journal of Cardiovascular Magnetic Resonance, Co-Editor of Magnetic Resonance Materials. Awards and Honours include the American Heart Association Paul Dudley White International Lectureship Award 2005 and the British Cardiovascular Society Thomas Lewis Lecture 2008. He is a fellow of the UK Academy of Medical Sciences. He is also the leader of the Heart Theme for the Oxford NIHR Biomedical Research Centre.