Non-clinical Professor in Neurogenetics
My research interests are the genetics of MND and how gene expression profiling can be used to investigate the pathogenic mechanisms of neurodegeneration and to identify diagnostic and prognostic biomarkers. MND is genetically heterogeneous, with over 30 genes identified for the most common form of the disease, amyotrophic lateral sclerosis (ALS), which in some patients can also be associated with frontotemporal dementia (FTD). The use of next generation sequencing, both whole exome and whole genome sequencing has significantly increased the identification of new genes.
Since individuals with known genetic variants of MND are generally indistinguishable from sporadic patients in the clinical setting, the disease is thought to progress along common pathways which result in the death of the motor neurones. Therefore, by understanding the pathogenic mechanisms in the genetic variants of the disease, it is hoped that the results will be widely applicable to other cases where the cause is currently unknown.
My research therefore focuses on obtaining gene expression profiles from experimental models of the disease and from patient and control samples, in order to both elucidate the reasons why the motor neurones are dying and to identify useful biomarkers of ALS, including micro RNAs and other non-coding RNAs. More recently, as part of a large clinical trial, I am assessing the impact of therapeutic treatments on the blood transcriptome to help understand the mechanisms of action of low dose interleukin-2.
- Determining the transcriptional response in blood to riluzole and low dose interleukin-2 (IMODALS and MIROCALS Clinical Trials)
- Identification of novel genetic causes of ALS using next generation sequencing technology
- Elucidation of genotype / phenotype correlations in newly identified genetic variants of ALS
- Isolating motor neurones from MND and control post-mortem spinal cord to look for changes in gene expression specific to genetic and disease variants of MND
- Elucidation of age-related changes in RNA expression profiles of the spinal cord
- Establishing a gene signature of fast and slow disease progression in biosamples from ALS patients
- Elucidation of distinct ALS subgroups through large scale gene expression profiling of lymphoblastoid cell lines, with a specific focus on identifying signatures associated with genetic variants and disease progression.
- Establishing biomarkers for diagnosis and monitoring progression of the disease by detecting miRNAs in the serum and CSF of patients and controls
Constanza I Marin Marquez (second supervisor)
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Beer A, Robins H, Fox I, Niedermoser I, Van Damme P, Moisse M, Robberecht W, Hardiman O, Panades MP, Assialioui A, Mora JS, Basak AN, Morrison KE, Shaw CE, Al-Chalabi A, Landers JE, Wyles M, Heath PR, Higginbottom A, Walsh T, Kazoka M, McDermott CJ, Hautbergue GM, Kirby J, Shaw PJ. Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis. Cell Rep. 2019;26(9):2298-306 e5
Waller R, Goodall EF, Milo M, Cooper-Knock J, Da Costa M, Hobson E, Kazoka M, Wollff H, Heath PR, Shaw PJ, Kirby J. Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS). Neurobiol Aging. 2017;55:123-31.
Stopford MJ, Higginbottom A, Hautbergue GM, Cooper-Knock J, Mulcahy PJ, De Vos KJ, Renton AE, Pliner H, Calvo A, Chio A, Traynor BJ, Azzouz M, Heath PR, Italsgen Consortium NC, Kirby J, Shaw PJ. C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Hum Mol Genet. 2017;26(6):1133-45
Bayatti, N., J. Cooper-Knock, J. J. Bury, M. Wyles, P. R. Heath, J. Kirby, and P. J. Shaw. (2014) "Comparison of Blood RNA Extraction Methods Used for Gene Expression Profiling in Amyotrophic Lateral Sclerosis." PLoS One 9: e87508 10.1371/journal.pone.0087508.
Kirby, J., K. Ning, L. Ferraiuolo, P. R. Heath, A. Ismail, S. W. Kuo, C. F. Valori, L. Cox, B. Sharrack, S. B. Wharton, P. G. Ince, P. J. Shaw, and M. Azzouz. (2011) "Phosphatase and Tensin Homologue/Protein Kinase B Pathway Linked to Motor Neuron Survival in Human Superoxide Dismutase 1-Related Amyotrophic Lateral Sclerosis." Brain 134: 506-17 10.1093/brain/awq345.
- Peer review of grant applications for funding bodies including MRC, Wellcome Trust & Motor Neurone Disease Association (MNDA)
- Peer review of submitted articles for high impact journals including Brain, Human Molecular Genetics and Neurology
- Current or past member of MNDA (UK), Agenzia di Ricercaper la Sclerosci Laterale Amiotrophica (Italy) and ALS Canada Grant Review Boards
- Member of the Editorial Board for Journal of Neuropathology and Applied Neurobiology
- Member of Ethics Review Panel for School of Medicine
I first came to the University of Sheffield as an undergraduate, graduating with a First Class Honours in Genetics and the Alan Roper (Panlabs) Prize for Genetics. I then went on to complete my PhD in Genetics at the MRC Human Biochemical Genetics Unit, University College London. I subsequently joined the Motor Neurone Disease Research Group at the University of Newcastle-upon-Tyne, headed by Prof Pamela Shaw. During the intervening years, first at Newcastle and now at the University of Sheffield, I have focused on the genetic and transcriptomic analysis of ALS, in order to understand the molecular basis of this complex disorder and identify prognostic and diagnostic biomarkers. I was awarded a New Blood Lectureship in the Academic Neurology Unit and having followed the academic track, I am currently a Reader in Neurogenetics. I am also Deputy Head of Department for Learning and Teaching.
- 1992 Alan Roper (Panlabs) Prize for Genetics, University of Sheffield
- 2003 New Blood Lectureship, University of Sheffield
- 2010 Senate Award for Excellence in Learning & Teaching, University of Sheffield
I am currently the Faculty Director of Postgraduate Teaching, and within the Department of Neuroscience, I am Director of Learning and Teaching, as well as Deputy Head for L&T. I chair the Faculty PGT Committee and Neuroscience L&T Committee.
I was instrumental in developing and delivering the MSc in Translational Neuroscience and more recently the MSc in Genomic Medicine programmes at the University of Sheffield. I am currently co-lead of the Genomic Medicine programme, as well as module lead for several of the taught modules and the Research Project. I am also a module lead for two modules on our new MSc in Advanced Cell and Gene Therapies.
I previously led the MSc Translational Neuroscience, which covers basic neurobiology and molecular biology, through to neuroimaging and applied clinical practise. I am the co-module leader for the Molecular Neuroscience and Research Project modules on this course. I also contribute to delivery of other PGT courses, including MSc Translational Neuropathology and MSc Clinical Neurology as well as our distance learning programme Neuroscience and Neurodegeneration.
Sheffield Institute for Translational Neuroscience
University of Sheffield
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MSc Translational Neuroscience Course Administrator:
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