HomeCentre Lead
Group Lead
Professor John Priestley MA (Cantab), DPhil (Oxon)
Academic staff
Research field
Staff in the unit have shown that nociceptive dorsal root ganglion (DRG) neurons can be divided into two main subpopulations depending on whether they contain neuropeptide transmitters, and that DRG neurons not only respond to target-derived growth factors but also make brain-derived neurotrophic factor (BDNF). This work is continuing, with further study of the functional and neurochemical properties of nociceptive DRG neurons, and their response to traumatic injury including peripheral nerve injury and root avulsion injury. This includes analysis of key transduction molecules and ion channels involved in pain signalling including the vanilloid receptor TRPV1, the cannabinoid receptor CB1, and the voltage gated sodium channel Nav1.9. A major programme of spinal injury studies is also underway, and has shown that fibronectin and silk biomaterial implants can be used to support axonal regeneration, and that omega-3 polyunsaturated fatty acids (PUFAs) are neuroprotective. Ongoing studies are examining the mechanism underlying this neuroprotection, including the role of retinoid signalling. In addition to the HEFCE-funded staff, senior postdoctoral staff include Dr. Min Liu and Dr. Von King.
Key research papers
1 Averill S, Michael GJ, Shortland PJ, Leavesley RC, King VR, Bradbury EJ, McMahon SB, Priestley JV (2004) NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury. Eur J Neurosci 19: 1437-1445.
2 Baker MD, Chandra SY, Ding Y, Waxman SG, Wood JN (2003) GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones. J Physiol 548: 373-382.
3 Bergerot A, Shortland PJ, Anand P, Hunt SP, Carlstedt T (2004) Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury. Exp Neurol 187: 359-366.
4 Bridges D, Rice AS, Egertova M, Elphick MR, Winter J, Michael GJ (2003) Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ hybridisation and immunohistochemistry. Neurosci 119: 803-812.
5 King VR, Henseler M, Brown RA, Priestley JV (2003) Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat. Exp Neurol 182: 383-398.
6 Liu M, Willmott NJ, Michael GJ, Priestley JV (2004) Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons. Neurosci 127: 659-672.
Academic staff
Research field
The neurosurgery group has a special interest in neuroimmune interactions, and the role that inflammatory cells and molecules have in neural regeneration.
Work by Professor Richardson has been key in identifying the "conditioning response", whereby the regenerative response of somatosensory neurons is augmented by a prior injury. One focus of ongoing work is the molecular basis for this response, including the role of cytokines and signalling via the NFkB transcription factor. Transgenic studies, including the generation of mice with modified NFkB signalling, are an important tool in this work. Another focus is therapies for neuronal regeneration based on cell transplants and lentiviral gene-delivery. This work is carried out in collaboration with Dr. Yi Zhang, a Wellcome Trust Research Career Development Fellow who is part of the unit.
Key research papers
1 Magoulas C, Fried M (2000) Isolation and genomic analysis of the human surf-6 gene: a member of the Surfeit locus. Gene 243: 115-123.
2 Subang MC, Richardson PM (2001) Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci 13: 521-528.
3 Zhang Y, Bo X, Schoepfer R, Holtmaat AJDG, Verhaagen J, Emson PC, Lieberman AR, Anderson PN (2005) GAP-43 and L1 act synergistically to promote regenerative regrowth of Purkinje cell axons in vivo. Proc Natl Acad Sci USA In press.
Neurology and Neuroimmunology Units
Group Leads
Academic Staff
Dr. Charles Cockerell PhD, MRCP
Dr Andrea Malaspina
Research field
Prof Giovannoni (Professor of Neurology) and Prof David Baker (Professor of Neuroimmunology) were recruited from the Institute of Neurology in Nov 2006. The main research and clinical interests of the unit focus on multiple sclerosis (MS) and other inflammatory disorders of the central nervous system. MS is characterised by extensive myelin loss, the result of diverse inflammatory events. Research at present is directed to myelin repair, as well as to understanding the molecular mechanisms of demyelination, in order that the myelinolytic process can be interrupted pharmacologically. Prof Giovannoni runs a MS clinical trials unit and is the principal investigator on several phase II and III MS trials. Prof Baker has been involved in understanding the involvement of the cannabinoid system in symptom control, neurodegeneration and immunity as they relate to MS and the development of agents for the treatment of chronic neurogeneration and symptom control. Other interests of the unit include biomarker discovery, both to study the pathogenesis of MS and to establish predictive testing; and antibody mediated autoimmune disorders of the central nervous system.
Under Professor Mike Swash, the previous Professor of Neurology, the neurology department established an international reputation for clinical studies on motoneuron disease. Work on motoneuron disease continues in the Neuroscience Centre, directed by Dr. Andrea Malaspina, Consultant Neurologist and honorary Non-Clinical Senior Lecturer. Other interests of the neurology unit include clinical studies of epilepsy, and the motor pathways that underlie the generation of tremor.
Key research papers
1 Pryce G, Ahmed Z, Hankey DRJ, Jackson SL, Croxford JL, Pocock JM, Ledent C, Petzhold A, Thompson AJ, Giovannoni G, Cuzner ML, Baker D (2003) Cannabinoids inhibit neurodegeneration in multiple sclerosis models. Brain 126: 2191-202.
2 Baker D, Pryce G, Davies WL, Hilley CR (2006). In silico patent searching identifies a new cannabinoid receptor? Trends Pharm Sci. 27:1-4
3 Petzold A, Eikelenboom MJ, Gveric D, Keir G, Chapman M, Lazeron RH, Cuzner ML, Polman CH, Uitdehaag BM, Thompson EJ, Giovannoni G (2002) Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 125: 1462-1473.
4 Dale RC, Church AJ, Surtees RA, Lees AJ, Adcock JE, Harding B, Neville BG, Giovannoni G (2004) Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Brain 127: 21-33.
5 Malaspina A, Kaushik N, de Belleroche J (2001) Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. J Neurochem 77: 132-145.
6 Malaspina A, de Belleroche J (2004) Spinal cord molecular profiling provides a better understanding of amyotrophic lateral sclerosis pathogenesis. Brain Res Rev 45: 213-229.
Group Lead
Professor Silvia Marino PhD, FMH-Path
Research field
Prof Marino was recruited to the Chair of Neuro-oncology in Jan 2006. The focus of her research group is on molecular mechanisms controlling the development of the central nervous system and on how these very same mechanisms can contribute to tumourigenesis when deregulated. The work is mainly centered on the biology of neural stem cells and neural progenitor cells, on the pathways and genes involved in control of their proliferation and differentiation, in particular the Sonic Hedgehog pathway and the Polycomb group genes. Moreover the group is investigating pathways and molecular mechanisms involved in the formation, development and progression of brain tumours in experimental models and in human tumour samples.
Key research papers
1 O. Shakhova, C. Leung, E. van Montfort, A. Berns and S. Marino (2006) Lack of Rb and p53 delays cerebellar development and predisposes to large cell anaplastic medulloblastzomas through amplification of N-Myc and Ptc2. Cancer Research 66: 5190-5200.
2 S. Bruggeman, M. Lingbeek, P. van der Stoop, J. Jacobs, K. Kieboom, E. Tanger, D. Hulsman, C. Leung, S. Marino and M. van Lohuizen (2005) Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1 deficient mice. Genes & Development 19:1438-1443
3 C. Leung, M. Lingbeek, O. Shakhova, J. Liu, E. Tanger, P. Saremaslani, M. van Lohuizen, S. Marino (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337-41.
4 S. Marino, D. Hoogervoorst, S. Brandner and A. Berns (2003) Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence. Development 130:3359-68.
Group Lead
Research field
Prof Sheer (Professor of Human Genetics) joined the Neuroscience Centre in Oct 2006, supported by Cancer Research UK . Her research is based on two inter-related themes. The first concerns the structure and functioning of human chromosomes and the nucleus. Prof Sheer's group recently identified distinct chromatin configurations that are dependent on gene density and transcriptional activity, and showed that the multi-functional PML bodies are organised in the nucleus close to genomic regions of high gene density and activity. The second theme concerns the contribution of genetic aberrations to the formation of brain tumours. The group recently conducted a high resolution study of the highly aggressive brain tumour glioblastoma multiforme, and is currently determining the genetic, epigenetic and expression profiles of a large series of paediatric astrocytic gliomas and correlating the findings with clinico-pathological variables.
Key research papers
1 Shiels C, Islam SA, Vatcheva R, Sasieni P, Sternberg MJE, Freemont PS, Sheer D. (2001) PML bodies associate with the MHC gene cluster. J Cell Sci. 114 (20): 3705-3716.
2 Donev R, Horton R, Beck S, Doneva T, Vatcheva R, Bowen WR, Sheer D. (2003) Recruitment of heterogeneous nuclear ribonucleoprotein A1 in vivo to the LMP/TAP region of the Major Histocompatibility Complex. J Biol Chem. 278(7):5214-26.
3 Wang J, Shiels C, Sasieni P, Wu PJ, Islam SA, Freemont PS, Sheer D. (2004) Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions. J Cell Biol. 164(4):515-526.
4 Mulholland PJ, Fiegler H, Mazzanti C, Gorman P, Sasieni P, Adams J, Jones TA, Babbage JW, Vatcheva R, Ichimura K, East P, Poullikas C, Collins VP, Carter NP, Tomlinson IPM, Sheer D. (2006) Genomic profiling identifies discrete deletions associated with translocations in glioblastoma multiforme. Cell Cycle 5(7):783-791.
