Professor Janine Kirby

PhD

Department of Neuroscience

Professor in Neurogenetics

j.kirby@sheffield.ac.uk
+44 114 222 2247
+44 114 222 2296 (MSc Courses Administrator: Helen Hickson)

Full contact details

Professor Janine Kirby
Department of Neuroscience
Room B47
385a Glossop Road
Sheffield
S10 2HQ
Profile

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 completed 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 I am now Professor of Neurogenetics. I am Deputy Head of Department for Learning and Teaching and the Faculty Director of Postgraduate Teaching.

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 over 25 loci identified for the most common form of the disease, ALS, and the causative genes have been identified at most of these through the application of next generation sequencing.

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. More recently, I am looking at the impact of therapeutic treatments on the blood transcriptome.


Current projects

  1. Determining the transcriptional response in blood to riluzole and low dose interleukin-2 (IMODALS and MIROCALS Clinical Trials)
  2. Identification of novel genetic causes of ALS using next generation sequencing technology
  3. Elucidation of genotype / phenotype correlations in newly identified genetic variants of ALS
  4. 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
  5. Elucidation of age-related changes in RNA expression profiles of the spinal cord
  6. Establishing a gene signature of fast and slow disease progression in biosamples from ALS patients
  7. 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.
  8. Establishing biomarkers for diagnosis and monitoring progression of the disease by detecting miRNAs in the serum and CSF of patients and controls
Publications

Journal articles

Chapters

Conference proceedings papers

  • (2016) Nottingham Pathology 2016. 9th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 28 June - 1 July 2016. The Journal of Pathology, Vol. 240 (pp S1-S48) View this article in WRRO RIS download Bibtex download
  • Lorente-Pons A, Wood JD, Shaw PJ, Ince PG, Cooper-Knock J, Ramachandran A, Kirby J & Highley JR (2016) Investigating the mechanisms underlying oligodendrocyte dysfunction in C9ORF72 ALS. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 42(S1) (pp 28-28), 2 March 2016 - 4 March 2016. View this article in WRRO RIS download Bibtex download
  • Lorente-Pons A, Wood JD, Shaw PJ, Ince PG, Cooper-Knock J, Ramachandran A, Kirby J & Highley JR (2015) Investigating the mechanisms underlying oligodendrocyte dysfunction in C9ORF72 ALS. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 41 (pp 26-27) RIS download Bibtex download
  • Beer A, Cooper-Knock J, Higginbottom A, Robin Highley J, Wharton SP, Milano A, Jones A, Al-Chalabi A, Kirby J & Shaw PJ (2014) AMYOTROPHIC LATERAL SCLEROSIS ASSOCIATED WITH AN INTERMEDIATE LENGTH GGGGCC REPEAT EXPANSION HAS DISTINCT NEUROPATHOLOGY COMPARED TO PATIENTS WITH LARGER EXPANSIONS. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 85(10) (pp e4.130-e4) RIS download Bibtex download
  • Highley JR, Cooper-Knock J, Frolov A, Charlesworth G, Kirby J, Wharton SB, Ince PG, Shaw PJ, Wood N & Bandman O (2013) A pathological basis for the association of parkinsonism and amyotrophic lateral sclerosis. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 39 (pp 51-51) RIS download Bibtex download
  • Cooper-Knock J, Highley JR, Hartley J, Milano A, Sawcer S, Compston A, Frolov A, Charlesworth G, Wood N, Bandmann O , McDermott CJ et al (2013) Neurodegeneration caused by intronic expansions of C9ORF72 is a clinically heterogeneous but pathologically distinct disease. LANCET, Vol. 381 (pp 32-32) RIS download Bibtex download
  • Ferraiuolo L, Higginbottom A, Heath PR, Barber S, Greenald D, Kirby J & Shaw PJ (2012) DYSREGULATION OF THE CROSS-TALK WITH ASTROCYTES AS A CONTRIBUTORY FACTOR TO MOTOR NEURON INJURY IN MOTOR NEURON DISEASE. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 83(3) RIS download Bibtex download
  • Smith BN, Topp S, Barwell J, Al-Chalabi A, Kirby J, Shaw PJ, Paul H, Morrison KE, de Jong V, Baas F , Lewis CM et al (2012) Age-dependent penetrance and anticipation in ALS+/-FTLD kindreds due to C9ORF72 hexanucleotide intronic repeat expansion mutations (C9HIREM). DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, Vol. 33 (pp 282-282) RIS download Bibtex download
  • Smith BN, Topp S, Barwell J, Al-Chalabi A, Kirby J, Shaw PJ, Paul H, Morrison KE, de Jong V, Baas F , Lewis CM et al (2012) Age-dependent penetrance and anticipation in ALS+/-FTLD kindreds due to C9ORF72 hexanucleotide intronic repeat expansion mutations (C9HIREM). DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, Vol. 33 (pp 36-37) RIS download Bibtex download
  • Highley R, Kirby J, Jansweijer JA, Heath PR, Shaw PJ & Ince PG (2011) TARDBP mutations, amyotrophic lateral sclerosis and alternative splicing. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 37 (pp 20-20) RIS download Bibtex download
  • Hosny O, Kirby J, Simpson J & Ince P (2008) Iron metabolism pathways in white matter lesions in the elderly. JOURNAL OF NEURAL TRANSMISSION, Vol. 115(12) (pp 1717-1718) RIS download Bibtex download
  • Hosny O, Kirby J, Ince PG & MRC Cognitive Function & Ageing (2008) HFE gene polymorphisms and risk of brain white matter lesions (WML). NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 34 (pp 32-32) RIS download Bibtex download
  • Highley JR, Smith O, Brockington A, Kirby J, Wharton SB, Spillantini M, Lowe JS, Layfield R, Shaw PJ & Ince PG (2007) Extra-motor manifestations of motor neurone disease and the role of TDP43 in ALS variants. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 33(2) (pp 264-265) RIS download Bibtex download
  • McDermott CJ, Burness CE, Rao G, Kirby J, Shaw PJ & Spastin HSP Consortium Neurologist (2006) Further insights into HSP and spastin: Severe complicated phenotypes and evidence of lower motor neurone dysfunction. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 77(1) (pp 137-137) RIS download Bibtex download
  • Wood-Allum C, Barber S, Kirby J, Heath P, Holden H, Beaujeux T, Allen S, Alexson S, Ince P & Shaw P (2005) Impaired mitochondrial anti-oxidant defence in SOD1-related familial amyotrophic lateral sclerosis (FALS). JOURNAL OF THE NEUROLOGICAL SCIENCES, Vol. 238 (pp S56-S56) RIS download Bibtex download
  • Wood-Allum C, Barber S, Kirby J, Heath P, Ince PG, Allen S & Shaw P (2005) Perturbation of mitochondrial anti-oxidant defence in a cell-culture model of SOD1-related familial amyotrophic lateral sclerosis. JOURNAL OF NEUROLOGY, Vol. 252 (pp 18-19) RIS download Bibtex download
  • McDermott CJ, Dayaratne RK, Tomkins J, Johnson MA, Casari G, Turnbull DM, Bushby K & Shaw PJ (2000) Hereditary spastic paraparesis with amyotrophy and OXPHOS muscle defect associated with a deletion in the paraplegin (SPG7) gene with apparent autosomal dominant transmission. NEUROLOGY, Vol. 54(7) (pp A425-A425) RIS download Bibtex download
  • Shaw PJ, Tomkins J, Ince PG, Slade JY, Usher P, Curtis A & Bushby K (1997) Cu/Zn superoxide dismutase (SOD1) mutations in amyotrophic lateral sclerosis (ALS) CNS tissue: Exclusion of somatic mutations and correlations with molecular pathology. NEUROLOGY, Vol. 48(3) (pp 49005-49005) RIS download Bibtex download

Datasets

Research group

Research Technician 

Alex Daniel

PhD Students 

Ilaria Giovanelli 

Shaila Haque 

Tobias Moll (second supervisor)

Teaching activities

I was instrumental in developing and delivering the MSc in Genomic Medicine at the University of Sheffield. I am co-lead of this programme, as well as module lead for several of the taught modules and the Research Project. I previously led the MSc Translational Neuroscience, which covers basic neurobiology and molecular biology, through to neuroimaging and applied clinical practise.

I am the module leader for the Research Projects 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 course Translational Neuroscience and Neurodegeneration.

In terms of L&T leadership, I am 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.

Professional activities
  • 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