Professor Stuart Cobb

Personal profile

• 2017 - present: Simons Fellow, Reader and Professor in Translational Neuroscience, University of Edinburgh.
• 2002 - 2017: Lecturer, Sn. Lecturer, Reader, University of Glasgow.
• 1999 - 2002: RSE Caledonian Research Fellow, University of Glasgow.
• 1996 - 1999: RA, University of Edinburgh.
• 1993 - 1996: DPhil in Neuroscience, University of Oxford.

Research Themes

• Synapses, Circuits and Behaviour
• Genes and Development

Research

Abnormalities in brain development, once thought to be irreversible in adults, are assumed to underlie a range of autism, intellectual disability and epilepsy disorders. There is growing evidence that reversing the underlying molecular deficits can result in substantial improvements in function and this knowledge is in turn changing the way we view and envisage treating such disorders in the future.

The aim of my laboratory is to understand the tractability of neurodevelopmental disorders (NDDs) to therapeutic intervention. This includes gaining an understanding of those aspects of NDDs that genuinely result from aberrant early brain development to features that result from ongoing dysfunction within the mature nervous system. This is important not only for a fundamental understanding of the pathophysiology but also in terms of windows of opportunity for treatment.

A major focus of our efforts is to develop gene therapy for Rett Syndrome and related disorders. Our laboratory was the first to report the ameliorative effect of gene therapy in mice modelling the disorder. Projects going forward include:

1. A programme to develop next generation Rett syndrome gene therapy cassettes for enhanced efficacy and safety.
2. Developing RNA and splicing-based approaches to bypass disease-causing mutations in neurodevelopmental and epilepsy disorders (Rett syndrome, CDKL5 deficiency, Dravet syndrome).
3. Testing the reversibility of neurological dysfunction and testing classical gene transfer and editing approaches in other related neurological disorders.

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Funding

• Rett Syndrome Research Trust
• Simons Initiative for the Developing Brain
• Medical Research Council
• Neurogene

Team Members

• Kamal Gadalla, Postdoctoral Fellow
• Ralph Hector, Postdoctoral Fellow
• Paul Ross, Postdoctoral Fellow
• Sophie Thomson, Postdoctoral Fellow
• Jim Selfridge, Postdoctoral Fellow
• Noha Bahey, RA
• Stephanie Mearns, Research Technician
• Gwen Tsang, Research Technician
• Amanda Morris, Research Technician
• Elisa Hall-Ponsele, Research Technician
• Scott Noble, Research Technician
• Wonsuk Lee, Research Technician
• Sarah Giachetti, PhD student
• Laura Kaminioti-Dumont, PhD student
• Ceren Erdem, PhD student

Collaborations

• Professor Adrian Bird, University of Edinburgh 
• Professor Peter Kind, University of Edinburgh
• Professor Ian Duguid, University of Edinburgh 
• Dr Mark Bailey, University Glasgow
• Professor Victor Faundez, Emory University

Selected Publications

Hector, R.D., Kalscheuer V.M., Hennig, F., Leonard H., Downs J., Clarke A., Benke, T.A., Armstrong J., Pineda. M., Bailey M.E.S., Cobb S. (2017) CDKL5 variants: improving our understanding of a rare neurological disorder. Neurology genetics, 3 (6):e200. doi: 10.1212/NXG.0000000000000200.

Tillotson, R., Selfridge, J., Koerner, M.V., Gadalla, K.E., Guy, J., De Sousa, D., Hector, R.D., Cobb, S.R. and Bird, A. (2017) Radically shortened MeCP2 reverses Rett syndrome-like neurological defects. Nature, 550, 398-401.

Bahey, N.G., Gadalla, K.K.E., McGonigal, R., Bailey, M.E.S., Edgar, J.M., and Cobb, S.R. (2017) Reduced axonal diameter of peripheral nerve fibres in a mouse model of Rett syndrome. Neuroscience, 358, 261-8.

Gadalla, K.K., Vudhironarit, T., Hector, R.D., Sinnett, S.E., Bahey, N.G., Bailey, M.E.S., Gray, S.J. and Cobb, S.R. (2017) Development of a novel AAV gene therapy cassette with improved safety features and efficacy in a mouse model of Rett syndrome. Molecular therapy methods and clinical development. 5 :180-190. doi: 10.1016/j.omtm.2017.04.007.

Leonard, H., Cobb, S., and Downs, J. (2017) Clinical and biological progress over 50 years in Rett syndrome. Nature Reviews Neurology, 13(1), pp. 37-51. (doi:10.1038/nrneurol.2016.186) (PMID:27934853)

Ross, P.D., Guy, J., Selfridge, J., Kamal, B., Bahey, N., Tanner, E., Gillingwater, T., Jones, R., Loughrey, C.M., McCarroll, C.S., Bailey, M.E.S., Bird, A., Cobb, S.R. (2016) Tissue-specific reactivation of Mecp2 in mice reveals both brain and peripheral phenotypes. Human Molecular Genetics, (doi:10.1093/hmg/ddw269) (Early Online Publication)

Hector, R., Dando, O., Landsberger, N., Kilstrup-Nielsen, C., Kind, P., Bailey, M.E.S., Cobb, S. (2016) Characterisation of CDKL5 transcript isoforms in human and mouse. PLOS one. http://dx.doi.org/10.1371/journal.pone.0157758

Cobb, S. R. (2015) Cognitive disorders: deep brain stimulation for Rett syndrome. Nature, 526(7573), pp. 331-332. (doi:10.1038/526331a) (PMID:26469040)

Booker, S. A., Pires, N., Cobb, S., Soares-da-Silva, P., and Vida, I. (2015) Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors. Neuropharmacology, 93, pp. 103-115. (doi:10.1016/j.neuropharm.2015.01.019) (PMID:25656478)

Kamal, B., Russell, D., Payne, A., Constante, D., Tanner, K. E., Isaksson, H., Mathavan, N., and Cobb, S. R. (2015) Biomechanical properties of bone in a mouse model of Rett syndrome. Bone, 71, pp. 106-114. (doi:10.1016/j.bone.2014.10.008) (PMID:25445449) (PMCID:PMC4289916)

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here