Professor of Neurology, University of Newcastle upon Tyne (1990-present) HEFCE funded
Honorary Consultant Neurologist, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne
Director Wellcome Trust Centre for Mitochondrial Research
National lead of the National Highly Specialised Services for Rare Mitochondrial Diseases of Children and Adults. This involves 3 centres (Newcastle, London and Oxford) and provides diagnostic and specialist clinical services for patients with mitochondrial diseases.
Director, Newcastle University Centre for Brain Ageing and Vitality sponsored by BBSRC, EPSRC, ESRC and MRC.
I began my research as a junior doctor when I became interested in why a patient developed muscle pain on exercise. This led me to start my studies on mitochondria and disease which have continued to fascinate me to this day. My PhD studies focused on understanding the molecular mechanisms in mitochondrial disease “Mitochondrial Cytopathies: Clinical and Experimental Studies”. At the same time I completed an MD which focused on the anticonvulsant drug sodium valproate but I was particularly interested in the toxicity of sodium valproate which involves mitochondria “Sodium Valproate: Clinical and Biochemical Studies”.
On completion of my research degrees I became a Lecturer in Experimental Neurology and continued my research into mitochondrial disease. In 1990 I became Professor of Neurology at Newcastle University and this allowed me to develop my clinical and molecular studies of mitochondrial disease. One of the great strengths of working in the UK is the ability to link clinical studies to basic research and this highlight my main research interest and expertise. Building upon research which started over two decades ago we have been able to build the Wellcome Trust Centre for Mitochondrial Research along with a world class clinical service for patients.
Director Wellcome Trust Centre for Mitochondrial Research
This was a strategic award from the Trust and was officially opened in September 2012 by Sir Mark Walport. I am the Director of the Centre. The Centre focuses on improving the lives of patients with mitochondrial disease. To achieve these strategic aims we are integrating basic and clinical research, training exceptional young researchers and addressing the public and policy engagement issues around our research. The research is focused on four main areas: mitochondrial gene expression and related diseases, preventing transmission of mitochondrial DNA disease, understanding and treating the consequences of mitochondrial disease on the nervous system and determining the role of mitochondrial DNA in common chronic human diseases. I have also been working extensively with the Trust on the public engagement and policy issues around this research. Our work on preventing transmission of mitochondrial disease has been the subject of a public consultation exercise by the Human Fertilisation and Embryology Authority (HFEA) and will be considered by the Department of Health in March 2013 after the HFEA reports. If this research is to lead to more reproductive choices to women at risk then it will require a change in the HFE Act.
National lead for the NHS National Highly Specialised Services for Rare Mitochondrial Diseases of Children and Adults
This service is for all patients with mitochondrial disease in the UK. The service was originally designated in April 2007 and involves 3 centres (Newcastle, London and Oxford). The service provides diagnostic investigations for patients suspected of mitochondrial disease which includes biochemical, histochemical and molecular genetic studies. We provide a multidisciplinary clinical service for our patients including medical, specialist nurse, physiotherapy, speech and language therapy and welfare rights. The clinic is accessible for all patients and those unable to travel we have a telephone clinic. This service is unique internationally and highlights one of the great strengths of the NHS, the ability to focus on the best of care for all. The service also provides a wonderful opportunity to combine with clinical research since we have large cohorts of patients and the vast majority of them delighted to consent for research studies. We have a number of clinical research studies on-going using interventions such as exercise. I also have a major role in the MRC Centre for Neuromuscular Diseases at UCL and Newcastle which is a translational research centre and provides the infrastructure for clinical studies as well as supporting the MRC Mitochondrial Disease Cohort.
Director, Newcastle University Centre for Brain Ageing and Vitality
The Lifelong Health and Wellbeing programme was launched as one of the major cross research council grand challenges. Three ‘lifelong health and wellbeing’ research Centres were funded by the BBSRC, EPSRC, ESRC and MRC in 2008 and I am Director of the Newcastle University Centre for Brain Ageing and Vitality. Our Centre focuses on understanding mechanisms underlying the ageing process, with a particular emphasis on the brain, and developing interventions which will promote healthy ageing. In addition, our Centre has played a very major role in capacity building in the area of Lifelong Health. One of the most important initiatives has been to develop a new research area within the Centre around exercise and activity. Funded in part by a strategic award by the MRC we have developed an exercise training laboratory and developing interventions for both normal ageing individuals and patients with several age related diseases.
I have a long standing interest in research training for both clinical and basic scientists. I have supported 10 clinical training fellows and currently sponsor two Wellcome Trust Senior Clinical Fellows (Professor Timothy Griffiths and Professor Patrick Chinnery). I have chaired the Wellcome Trust Clinical Interest Group and the NIHR Fellowship Committee. I have supervised in total 35 PhD students and currently supervising 10 PhD students. Research training and mentorship is a major component of my current activity.
Recent Key Publications
Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 2010; 465:82-5
Trevelyan AJ, Kirby DM, Smulders-Srinivasan TK, Nooteboom M, Acin-Perez R, Enriquez JA, Whittington MA, Lightowlers RN, Turnbull DM. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain 2010; 133: 787-96.
Greaves LC, Elson JL, Nooteboom M, Grady JP, Taylor GA, Taylor RW, et al. Comparison of mitochondrial mutation spectra in ageing human colonic epithelium and disease: absence of evidence for purifying selection in somatic mitochondrial DNA point mutations. PLoS Genet 2012; 8: e1003082.
Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, et al. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain 2012; 135: 1736-50.
Lax NZ, Whittaker RG, Hepplewhite PD, Reeve AK, Blakely EL, Jaros E, et al. Sensory neuronopathy in patients harbouring recessive polymerase gamma mutations. Brain 2011; 135: 62-71.
Key Historical Publications
Krishnan KJ, Reeve AK, Samuels DC, Chinnery PF, Blackwood JK, Taylor RW, Wanrooij S, Spelbrink JN, Lightowlers RN, Turnbull DM. What causes mitochondrial DNA deletions in human cells? Nat Genet. 2008 Mar;40(3):275-9.
Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet. 2006 May;38(5):515-7. Epub 2006 Apr 9.
McFarland R, Clark KM, Morris AA, Taylor RW, Macphail S, Lightowlers RN, Turnbull DM. Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation. Nat Genet. 2002 Feb;30(2):145-6.
Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999 Oct;23(2):147.
Clark KM, Bindoff LA, Lightowlers RN, Andrews RM, Griffiths PG, Johnson MA, Brierley EJ, Turnbull DM. Reversal of a mitochondrial DNA defect in human skeletal muscle. Nat Genet. 1997 Jul;16(3):222-4.
Awards, honours and professional service
Prizes and awards
Goulstonian Lecturer Royal College of Physicians 1992
Jean Hunter Prize, Royal College of Physicians 2003
Sims Royal College of Physicians Lecturer 2004
Membership of Research Committees
Wellcome Trust Panels/Committees
Neuroscience Panel (1992-1997)
Genetics Interest Group (1992-1995)
Innovations Grants Panel (1998-1999)
ALSPAC steering committee (2000-2003)
Clinical Interest Group (2003-6)
Chair Clinical Interest Group (2006-2007)
Chair of Molecular and Cellular Neuroscience Panel (2007-2011)
NIHR Senior Fellow (2011-present)
NIHR Fellowship programme (2005-6)
Vice-chair of NIHR Fellowship Programme (2006-2007)
Chair of NIHR Fellowship programme (2007- 2010)
Current Lab members
Mitochondria in ageing