Prof Paul McMahan Mattews

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Professor Paul McMahan Matthews

PhD
Visiting Professor (Honorary)
Email: p.matthews@ntu.edu.sg
Principal Investigator

Translational Neuroscience and Therapeutics and Head of the Division of Brain Sciences in the Department of Medicine of Imperial College London.  Prior to this appointment, he was a Vice President in Pharmaceuticals Research and Development for GlaxoSmithKline, where he led their Clinical Imaging Centre, Discovery Clinical Genetics and a medicine development programme.  Before that, he was MRC Clinical Research Professor and Head of the Department of Clinical Neurology in the University of Oxford.  Through these roles, he became the founding Director of the Oxford Centre for Functional Magnetic Resonance of the Brain (FMRIB) and founding Head of the GSK Clinical Imaging Centre in London (now known as Imanova, Ltd.).

Early work as a post-graduate student and post-doctoral fellow provided a foundation for Blood Oxygenation Leven Dependent (BOLD) functional imaging with a quantitative model for the dependence of the in vivo MRI signal on blood oxygenation with Keith Thulborn and John Waterton.  In Professor Sir George Radda’s Oxford laboratory, Prof Matthews, along with Doug Arnold , also conducted amongst the first in vivo phosphorus magnetic resonance spectroscopy (MRS) studies.  After moving to McGill University in his first faculty position, Prof Matthews and Doug Arnold later led in establishing MRS for the diagnosis and monitoring of mitochondrial diseases.  

They also demonstrated the substantial, widespread axonal degeneration and loss in patients with multiple sclerosis (MS) using proton MRS methods. In a series of subsequent reports over several years, Prof Matthews’ group (at that time in the Department of Neurology in Oxford) confirmed it neuropathologically and demonstrated that the damage extends outside of lesions into the conventionally “normal appearing” white matter, progresses through the disease course and is a primary mechanism of disability.  They extended these observations of axonal pathology with novel evidence for early and progressive neurodegeneration, and the selective vulnerability of specific populations of neurons. These discoveries have contributed influentially to the new focus on neuroprotective and reparative therapies for this and related neuroinflammatory diseases.

To explain the potential for clinically complete recovery of patients in the relapsing-remitting phase of MS despite irreversible neuroaxonal loss, Prof Matthews proposed that intrinsic brain plasticity enables brain functional adaptation to damage and provided first demonstrations of underlying mechanisms using functional MRI (fMRI).  He then showed how both pharmacological and behavioural interventions can modulate this both in MS and after subcortical ischaemic stroke. This work has contributed to a fundamental paradigm shift in MS and other white matter diseases, shifting attention from focal lesions to the integrity of the preserved brain.

To enable these discoveries, Prof Matthews led the FMRIB group with Steve Smith and his colleagues who made major methodological contributions with development of automated methods for precise assessment of brain atrophy (SIENA), white matter connectivity (probabilistic tractography, TBSS, FLIRT) and connectivity-based parcellation of grey matter, as well as robust paradigms for the analysis and interpretation of fMRI data, particularly in the resting state.  These tools are part of the FSL software package from FMRIB, now perhaps the most widely used image analysis software “toolbox” world-wide.

Subsequent work has pioneered applications of imaging in therapeutics development.  Over the last few years, he has worked to promote research imaging data harmonisation and sharing, and large population imaging.  Contributing to this, Prof Matthews serves in several external leadership roles, including as Steering Committee Member and Chair of the Imaging Work Group for the UK Biobank, Executive Member and Chair of the Dementias Platform UK MRI-PET Network, and one of the UK representatives for the Interim Board of Euro-Bioimaging.

He has been a member of the Nuffield Council of Bioethics Biological and Health Data Working Party, chaired or served on MRC, Canadian Institutes of Healthcare Research, Finnish Academy of Science and other grants councils.  Amongst honours received, in 1997, Prof Matthews was made a Fellow by Special Election in St Edmund Hall, Oxford, in 2008, Prof Matthews was awarded an OBE for services to neuroscience and, in 2014, he was elected as a Fellow of the Academy of Medical Sciences.

Research Focus

Research in Prof Matthews’ laboratory focuses on understanding mechanisms by which inflammatory processes promote and protect the brain from neurodegeneration.  This work includes the development and exploitation of molecular imaging of innate immune responses in people with multiple sclerosis or early Alzheimer’s disease, as well as experimental medicine studies of innate immune responses using a range of ‘omics methods.  A specific focus has been on understanding mechanisms by which the 18kD mitochondrial translocator protein modulates microglial immune responses.   Tools include in vivo MRI and PET imaging, along with transcriptomics and metabolomics of accessible cell populations.  Increasing emphasis is being placed on inter-disciplinary work with data scientists to develop approaches for quantitative analyses and for molecular epidemiological study of these phenomena in large populations.

Key publications
Thulborn KR, Waterton JC, Matthews PM, Radda GK. 1982.  Oxygenation     dependence of the transverse relaxation time of water protons in whole blood at high   field. Biochim Biophys Acta. 714(2):265‑270.

Arnold DL, Matthews PM, Radda GK. 1984.  Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn Reson. Med 1(3):307‑315.

Arnold DL, Matthews PM, Francis G., Antel J. 1990.   Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 14(1):154-159.

DeStefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis G, Antel J, Arnold DL.1998.  Axonal damage correlates with disability in patients with relapsing- remitting multiple sclerosis.  Results of a longitudinal magnetic resonance spectroscopy study. Brain. 121(Pt 8):1469-7
7.

E
vangelou N, Esiri MM, Smith S, Palace J, Matthews PM. 2000.  Quantitative pathological evidence for axonal loss in normal-appearing white matter in multiple sclerosis. Ann Neurol. 47(3):391-395.

Cifelli Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J. Matthews PM.
2002.  Thalamic neurodegeneration in multiple sclerosis.  Ann Neurol. 52(5):650-653.

Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM. 2000.  The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.  Ann Neurol. 47(5):606-13.

Johansen-Berg H, Rushworth MFS, Bogdanovic MD, Kischka U, Wimalaratna S, Matthews PM.  2002.  The role of ipsilateral premotor cortex in hand movement after stroke.  Proc Natl Acad Sci. 
99(22):14518-23.

Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE.  2006.  Tract-based spatial statistics:  voxelwise analysis of multi-subject diffusion data.  Neuroimage. 31(4):1487-505. 

Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, Stjean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP.  2012.  An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 32(1):1-5. 

External Links:
http://www.imperial.ac.uk/people/p.matthews
https://www.seh.ox.ac.uk/users/paulmatthews
and http://www.acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/professor-paul-matthews/