Janine Kirby

Dr. Janine Kirby PhD

Reader in Neurogenetics

Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B47
385a Glossop Road
S10 2HQ

Telephone: +44 (0)114 22 22247
Fax: +44 (0)114 22 22290
Email: j.kirby@sheffield.ac.uk

Secretary: Bev Carter
Tel: +44 (0)114 22 22295
Email: bev.carter@sheffield.ac.uk

MSc Courses Administrator: Helen Hickson
Tel: +44 (0)114 2222296
Email: h.hickson@sheffield.ac.uk



I first came to the University of Sheffield as an undergraduate and graduated with a First Class Honours in Genetics and the Alan Roper (Panlabs) Prize for Genetics. I went on to complete my PhD in Genetics at the MRC Human Biochemical Genetics Unit, University College London, graduating in 1996.  I subsequently joined the Motor Neurone Disease Research Group at the University of Newcastle-upon-Tyne, headed by Prof Pamela Shaw. During the intervening 20 years, first at Newcastle and subsequently at the University of Sheffield, I have provided genetic input to the research strategy of investigating the molecular basis of this complex disorder.

In 2003, I was awarded a New Blood Lectureship in the Academic Neurology Unit. Having followed the academic track, I am currently a Reader in Neurogenetics.

Research Interests

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 at least 25 loci for the most common form of the disease, ALS, of which the causative genes have been identified at 22 loci. 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.

Teaching Interests

I am the course leader on the MSc in Translational Neuroscience, which brings together expertise from the Departments of Neuroscience, Psychology and Biomedical Science. This course covers basic neurobiology and molecular biology, through to neuroimaging and applied clinical practise. As well as Course Lead, I am the module leader for the Molecular & Developmental Neuroscience and Genetics & Modelling of Neurodegenerative Diseases modules. I am the Director of Teaching (PGT) for Neuroscience. 

I am also the Co-Lead  for the MSc Genomic Medicine.  This is a programme of study provided in conjunction with Health Education England, to provide biomedical and healthcare researchers with an understanding of the scope and application of genomics within clinical practise and biomedical research.

Research Team

Post-doctoral Research Associates

  • Dr Rachel Waller
  • Dr Nadhim Bayatti

PhD Students

  • Afnan Al Sultan
  • Matthew Stopford
Professional Activities
  • Peer review of grant applications for funding bodies including MRC, Wellcome Trust & Motor Neurone Disease Association
  • Peer review of submitted articles for high impact journals including Neurology, Annals of Neurology and Human Molecular Genetics
  • Evaluated MND Research Proposals as a Member of the Motor Neurone Disease Association Biomedical Research Advisory Board UK (2010-2014) and Agenzia di Ricercaper la Sclerosci Laterale Amiotrophica, Italy (2011-2013; Reappointed 2016)
  • Ethics Reviewer for School of Medicine
Current Projects
  1. 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
  2. Establishing biomarkers for diagnosis and monitoring progression of the disease by detecting miRNAs in the serum and CSF of patients and controls
  3. 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 rapid and slow disease progression.
  4. Determining the crosstalk between in astrocytes and motor neurones in animal models and post-mortem ALS material.
  5. Investigating the mechanisms of how the GGGGCC repeat expansion in C9ORF72 leads to motor neurone death through generation and characterisation of a cellular model in NSC34 cells
  6. Elucidation of genotype / phenotype correlations in newly identified genetic variants of ALS
  7. Identification of novel genetic causes of ALS using next generation sequencing technology
  8. Elucidation of age-related changes in RNA expression profiles of the spinal cord

Key Publications

 Baker DJ, Blackburn DJ, Keatinge M, Sokhi D, Viskaitis P, Heath PR, Ferraiuolo L, Kirby J and Shaw PJ. (2015) "Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the Sod1 (G93A) mouse model of Amyotrophic Lateral Sclerosis." Front Cell Neurosci 9: 410

 Bury JJ, Highley JR, Cooper-Knock J, Goodall EF, Higginbottom A, McDermott CJ, Ince PG, Shaw PJ, and Kirby J. (2015) "Oligogenic inheritance of optineurin (OPTN) and C9orf72 mutations in ALS highlights localisation of OPTN in the TDP-43-negative inclusions of C9orf72-ALS." Neuropathology 10.1111/neup.12240 (E-pub)

Cooper-Knock J, Bury JJ, Heath PR, Wyles M, Higginbottom A, Gelsthorpe C, Highley JR, Hautbergue G, Rattray M, Kirby J, Shaw PJ (2015) C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis. PLoS One;10:e0127376.

Cooper-Knock J*, Kirby J*, Highley R, Shaw PJ (2015) The Spectrum of C9orf72-mediated Neurodegeneration and Amyotrophic Lateral Sclerosis. Neurotherapeutics;12:326-39. (*Joint first authors)

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.

Highley JR*, Kirby J*, Jansweijer JA, Webb PS, Hewamadduma CA, Heath PR, Higginbottom A, Raman R, Ferraiuolo L, Cooper-Knock J, McDermott CJ, Wharton SB, Shaw PJ, Ince PG (2014) Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones. Neuropathol Appl Neurobiol;40:670-85. (*Joint first authors)

Kirby, J., J. R. Highley, L. Cox, E. F. Goodall, C. Hewitt, J. A. Hartley, H. C. Hollinger, M. Fox, P. G. Ince, C. J. McDermott, and P. J. Shaw. (2013) "Lack of Unique Neuropathology in Amyotrophic Lateral Sclerosis Associated with p.K54E Angiogenin (Ang) Mutation." Neuropathol Appl Neurobiol;39:562-71.