Dr Paul Heath
Senior Scientific Officer
Sheffield Institute for Translational Neuroscience
University of Sheffield
385a Glossop Road
Telephone: +44 (0)114 222 2254
Fax: +44 (0)114 226 1201
- 2007 Senior Scientific Officer, Manager of Affymetrix microarray core facility, University of Sheffield, UK
- 2001–2007 Postdoctoral Research Associate. Academic Neurology Unit, University of Sheffield.
- 1998-2001 Associate programmer, HSBC Bank, Griffin House, Silver Street Head, Sheffield.
- 1994-1998 Postdoctoral Research Associate, Department of Biomedical Science, University of Sheffield.
- 1990-1994 Research Assistant, Department of Biomedical Science, University of Sheffield.
- Jan 1990–Jun 1990 Experimental Officer, Biotechnology, I.C.I. Pharmaceuticals, Alderley Park, Macclesfield, Cheshire.
- 1987-1989 Experimental Officer, I.C.I. Diagnostics, Gadbrook Park, Northwich, Cheshire.
- January to October 1987. Visiting Research Scientist, Department of Microbiology and Molecular Genetics, University of California, Irvine, California,
- 1982-1986 Molecular Biologist / Clinical Cytogeneticist,Centre for Human Genetics, Langhill, 117, Manchester Road, Sheffield.
- 1979-1982 Research Scientist, University Department of Haematology, Royal Hallamshire Hospital, Sheffield.
The role of GluR2 editing in motor neuron disease.
The AMPA receptor subunit GluR2 controls calcium entry to the motor neurone. During development it undergoes post transcriptional RNA editing giving rise to a mature form which blocks the receptor pore. There is evidence which suggests that in some forms of motor neurone disease this process is faulty giving rise to a receptor that becomes calcium permeable. In collaboration with colleagues in Edinburgh I am investigating this evidence in our own material.
Selective vulnerability to neurodegeneration of motor neuron populations.
In motor neuron disease there is a loss of motor neurons from the spinal cord and motor cortex but the motor neurons controlling eye movement (oculomotor) and the pelvic floor are spared. I am currently involved with a project to examine the gene expression profiles of both the spinal cord and oculomotor motor neurons in order to determine what mechanisms might be involved in the differential vulnerability of the two groups.
Microarray analysis of RNA extracted from formalin-fixed paraffin embedded samples.
There is a large archive of tissue samples collected for histological analysis that are formalin fixed and then embedded in paraffin. I have begun a project to develop a reliable methodology to unlock the RNA from these samples and make it available for microarray studies. This will enable us to carry out gene expression studies of some valuable samples in a number of areas.
Principal Funding Sources
- Sheffield Hospitals Charitable Trust
J.E. Simpson, O. Hosny El-Sayed, S. B. Wharton, P. R. Heath, H. Holden, M. S. Fernando, F. Matthews, G. Forster, J. T. O´Brien MD, R. Barber MD, R. N. Kalaria, C. Brayne, P. J. Shaw, C. E. Lewis, P. G. Ince; on behalf of the MRC Cognitive Function and Ageing Study Neuropathology Group. Stroke (in press) Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways
Avery, K., Avery, S., Shepherd, J., Heath P.R., Moore, H., Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation and pluripotency in human embryonic stem cells (2008) Stem Cells Dev.(epub)
Kirby, J., Heath, P.R., Shaw, P.J., Hamdy, F.C., Gene Expression Assays. (2007) Adv Clin Chem. 44 (247-292).
Ferraiuolo, L., Heath, P.R., Holden,H., Kasher, P., Kirby, J., Shaw, P.J., Microarray analysis of the cellular pathways involved in the adaptation to and progression of the motor neuron injury in the SOD1 G93A mouse model of familial ALS. J. Neurosci. (2007) 27 (9201-9219).
Baker, D.E.,, Harrison, N.J.,, Maltby, E., Smith, K., Moore, H.D., Shaw PJ, Heath, P.R., Holden, H., Andrews, P.W. Nature Biotechnology. (2007) 25(2):207-15. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo.
Wood-Allum, C.A., Barber, S.C., Kirby, J, Heath, P.R, Holden, H., Mead, R., Higginbottom, A., Allen, S., Beaujeux, T., Alexson, S.A., Ince, P.G. & Shaw, P.J. Brain (2006) 129 (7) 1693-1609. Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen
Pamphlett, R., Heath, P.R., Holden, H., Ince, P.G., Shaw, P.J. J. Neurosci Methods. (2005) 147 (1) 65-67
Detection of mutations in whole genome-amplified DNA from laser-microdissected neurons
Kirby, J., Halligan, E., Baptista, M.J., Allen S., Heath, P.R., Holden, H., Barber, S.C., Loynes, C.A., Wood-Allum, C.A., Lunec, J. & Shaw, P.J. Brain. (2005) 128 (7) 1686-1706. Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS.
S. Allen, P.R.Heath, J.Kirby, S.B.Wharton, M.R.Cookson, F.M.Menzies, R.E.Banks and P.J.Shaw.J. Biol. Chem. (2003) 278 (8) 6371-6383. Analysis of the cytosolic proteome in a cell-culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defences and nitric oxide synthetic pathways.
P.R.Heath, J.Tomkins, P.G.Ince and P.J.Shaw. Neuroreport (2002) 13 (1753-1757).
Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by LCM.