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Stroke Peter Kirkpatrick leads translational research into the pathophysiology of cerebrovascular disease using non-invasive assessments of cerebral haemodynamics to improve outcome from cerebrovascular neurosurgical procedures, and to develop new therapies for acute cerebral ischaemia. Elizabeth Warburton studies inflammation and atheroma in carotid plaques; and uses serial studies of individual patients to investigate plasticity in the motor, visual and language domains using fMRI and behavioural measures of deficit. Brain imaging is used to suggest strategies for manipulating pathophysiological processes and determine clinical recovery through serial study after ischaemic stroke. Hugh Markus leads a programme on cerebral small vessel disease and vascular cognitive impairment using multimodal MRI to characterise mechanism of cognitive impairment, and develop new treatment approaches. With Stephen Bevan he also works on identifying genetic variants for polygenic ischaemic stroke, and has identified the first novel independent locus, HDAC9. Neuro-oncology Research led by Colin Watts investigates how genetic and clonal heterogeneity evolves in response to treatment in patients with glioblastoma, including the impact of spatial and temporal diversity on the emergence of treatment resistance, with the aim of developing tumour sampling techniques and cancer stem cell derivation strategies to establish patient-specific in vitro and in vivo models of disease. Stephen Price is developing a research programme using MR and PET imaging to understand heterogeneity in brain tumours and the biology of glioma invasion. Dementia and neurodegeneration Research in behavioural neurology addresses neuropsychology and imaging assessments of cognitive deficits in patients with Alzheimer’s disease, fronto-temporal dementia, progressive supranuclear palsy and Huntington’s disease. James Rowe investigates behavioural disorders associated with neurodegenerative disease and focal brain injury using structural and functional magnetic resonance imaging and magnetoencephalography. The focus is on restoring function in the brain networks that enable the cognitive control of actions in neurodegeneration, especially Parkinson’s disease, frontotemporal dementia and progressive supranuclear palsy. Maria-Grazia Spillantini has provided molecular classifications for disorders characterised by intracellular aggregates of microtubule-associated proteins and studies mechanisms of intracellular protein aggregation in human brain tissue and transgenic mice in the context of disorders such as Parkinson’s disease and dementia with Lewy bodies (alpha-synuclein) and Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration and hereditary forms of frontotemporal dementia (tauopathies). Peter St George-Hyslop studies the genetics of Alzheimer’s and related disorders and is using structural biology to develop novel molecules for inhibiting the formation

of intracellular protein aggregates that destroy nerve cells. Giovanna Mallucci works on mechanisms of neurotoxicity in neurodegenerative diseases; she recently identified the role of the unfolded protein response in mediating the toxic effects of protein misfolding in prion disease and manipulated this pharmacologically to prevent neurodegeneration. This work is now being applied in other neurodegenerative disorders with an emphasis on neuroprotection in the early stages of neuronal and synaptic regeneration dysfunction. Roger Barker conducts clinical work that improves prediction across the spectrum of clinical deficits in Parkinson’s and Huntington’s disease using biomarkers for the natural history and heterogeneity of these disorders in epidemiological studies of cohorts studied for clinical and imaging phenotypes, and genomics. He studies abnormalities in adult neural stem cell turnover and differentiation in transgenic models of neurodegeneration, work that has implications for the development of novel therapies including the use of cell-based therapies for Parkinson’s and Huntington’s disease. Dennis Chan leads research on translational and clinical research into early Alzheimer’s disease, focusing on the study of altered brain function through clinical studies involving behavioural outcomes and functional MRI complemented by research on hippocampal function in mouse models of Alzheimer’s disease. Plasticity and brain repair James Fawcett works on recovery of function through adaptation, plasticity regeneration and repair of the injured brain and spinal cord. Chondroitinase and other compounds are being used to modify the inhibitory proteoglycan perineuronal net structures that normally prevent plasticity and limit the success of rehabilitation. Engineering of integrins is being developed to promote axon regeneration in the adult nervous system. Nanotech nerve interfaces have been developed to enable control of the bladder and limb prostheses. The work also has implications for neurodegenerative disease. Keith Martin studies the mechanisms of visual loss in glaucoma, and is currently investigating the integration of stem cells into the retina in experimental glaucoma, and studying the role of axonal transport dysfunction associated with glaucomatous retinal ganglion cell death. Stefano Pluchino studies the physiology of neural stem cells and their application in cell therapies for repair of the central nervous system, including the role of nanotechnology in delivering therapeutic agents. He also models the role of stem cells in modulating the fate of inflammatory and degenerative lesions. Demyelinating disease As a member of the International Multiple Sclerosis Genetics Consortium (IMSGC), Stephen Sawcer has helped to identify 110 susceptibility genes that demonstrate a genetic basis for the primary role of T and B cell-mediated adaptive immune mechanisms in the pathogenesis of multiple sclerosis. Alastair Compston has, with Alasdair Coles, also led the successful development of Alemtuzumab (Lemtrada)

CLINICAL NEUROSCIENCE

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School of Clinical Medicine Research Directory 2012-2014  

The Directory provides a description, department by department, of the main areas of our research together with a small number of key public...

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