My research looks to use Drosophila melanogaster (fruit flies) as a powerful genetic model organism to dissect the molecular mechanisms contributing to neurodegenerative diseases including dementia, motor neurone disease and Parkinson’s disease. My primary research focuses on two overlapping neurodegenerative disorders, Frontotemporal Dementia (FTD) and Motor Neurone Disease (MND). I am particularly interested in how dipeptide-repeats associated with the disease causing hexanucleotide expansion within the C9orf72 gene contribute towards neurodegeneration. In the lab we have a number of Drosophila models of both FTD and MND including C9orf72 related DPRs, C9orf72 pure repeat models and models of CHMP2B, VCP and TDP-43 related disease. I am also interested in how we can use Drosophila as part of a translational pipeline both to understand the molecular mechanisms of disease and as part of a drug-screening strategy.
- Dissecting the role of POSH as a JNK Scaffold in Frontotemporal Dementia
- How physiologically relevant repeat length dipeptide-repeats interact in vivo to mediate neurodegeneration
- UDCA as a Neuroprotective compound in Drosophila models of Neurodegeneration
- Drosophila as a model for Drug Screens in Neurodegenerative Diseases
Sharpe JL, Harper NS, West RJH. Identification and Monitoring of Nucleotide Repeat Expansions Using Southern Blotting in Drosophila Models of C9orf72 Motor Neuron Disease and Frontotemporal Dementia. Bio-protocol 12(10): e4424. 2022 May
Sharpe JL, Harper NS, Garner DR, West RJH. Modeling C9orf72-Related Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Drosophila. Front Cell Neurosci. 2021 Oct 21;15:770937.
Ugbode C, West RJH. Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiol Dis. 2021 Jan;147:105144.
West RJH, Sharpe JL, Voelzmann A, Munro AL, Hahn I, Baines RA, Pickering-Brown S. Co-expression of C9orf72 related dipeptide-repeats over 1000 repeat units reveals age- and combination-specific phenotypic profiles in Drosophila. Acta Neuropathol Commun. 2020 Sep 7;8(1):158.
West RJH, Ugbode C, Fort-Aznar L, Sweeney ST. Neuroprotective activity of ursodeoxycholic acid in CHMP2BIntron5 models of frontotemporal dementia. Neurobiol Dis. 2020 Oct;144:105047. doi: 10.1016/j.nbd.2020.105047. Epub 2020 Aug 13.
Lu Y, West RJH, Pons M, Sweeney ST, Gao FB. Ik2/TBK1 and Hook/Dynein, an adaptor complex for early endosome transport, are genetic modifiers of FTD-associated mutant CHMP2B toxicity in Drosophila. Sci Rep. 2020 Aug 26;10(1):14221. doi: 10.1038/s41598-020-71097-5.
West RJH, Lu Y, Marie B, Gao FB, Sweeney ST.Rab8, POSH, and TAK1 regulate synaptic growth in a Drosophila model offrontotemporal dementia. J Cell Biol. 2015 Mar 30;208(7):931-47. doi: 10.1083/jcb.201404066. Epub 2015 Mar 23. PubMed PMID: 25800055; PubMed Central PMCID: PMC4384727.
West RJH, Ugbode C, Gao FB, Sweeney ST.The pro-apoptotic JNK scaffold POSH/SH3RF1 mediates CHMP2BIntron5-associated toxicity in animal models of frontotemporal dementia. Hum Mol Genet. 2018 Apr 15;27(8):1382-1395. doi: 10.1093/hmg/ddy048. PubMed PMID: 29432529.
West RJH, Elliott CJ, Wade AR.Classification of Parkinson's Disease Genotypes in Drosophila Using Spatiotemporal Profiling ofVision. Sci Rep. 2015 Nov 24;5:16933. doi: 10.1038/srep16933. PubMed PMID: 26597171; PubMed Central PMCID: PMC4657034.
West RJH, Furmston R, Williams CA, Elliott CJ.Neurophysiology of Drosophila models of Parkinson's disease.Parkinsons Dis.2015;2015:381281. doi: 10.1155/2015/381281. Epub 2015 Apr 20. Review. PubMed PMID: 25960916; PubMed Central PMCID: PMC4414211.
Oswald MC, Brooks PS, Zwart MF, Mukherjee A, West RJH, Giachello CN, Morarach K, Baines RA, Sweeney ST, Landgraf M. Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila. Elife. 2018 Dec 17;7. pii: e39393. doi: 10.7554/eLife.39393.
Vilidaite G, Norcia AM, West RJH, Elliott CJH, Wade AR, Baker DH. Autism sensory dysfunction in an evolutionarily conserved system. Proc Biol Sci. 2018 Dec 19;285(1893):20182255. doi: 10.1098/rspb.2018.2255.
West RJH, Briggs L, Perona Fjeldstad M, Ribchester RR, Sweeney ST.Sphingolipids regulate neuromuscular synapse structureand function in Drosophila. J Comp Neurol. 2018 Sep 1;526(13):1995-2009. doi: 10.1002/cne.24466. Epub 2018 Aug 2. PubMed PMID: 29761896; PubMed Central PMCID: PMC6175220.
Himmelberg MM, West RJH, Elliott CJH, Wade AR. Abnormal visual gain control and excitotoxicity in early-onset Parkinson's disease Drosophila models. J Neurophysiol. 2018 Mar 1;119(3):957-970. doi: 10.1152/jn.00681.2017. Epub 2017 Nov 15. PubMed PMID: 29142100; PubMed Central PMCID: PMC5899316.
Himmelberg MM, West RJH, Wade AR, Elliott CJH. A perceptive plus in Parkinson's disease. Mov Disord. 2018 Feb;33(2):248. doi: 10.1002/mds.27240. Epub 2018 Jan 14. PubMed PMID: 29333617; PubMed Central PMCID: PMC5838541.
Oswald MC, West RJH, Lloyd-Evans E, Sweeney ST. Identification of dietary alanine toxicity and trafficking dysfunction in a Drosophila model of hereditary sensory and autonomic neuropathy type 1. Hum Mol Genet. 2015 Dec 15;24(24):6899-909. doi: 10.1093/hmg/ddv390. Epub 2015 Sep 22. PubMed PMID: 26395456; PubMed Central PMCID: PMC4654049.
West RJH, Eyeing up Drosophila models of frontotemporal dementia: Identifying conserved mechanisms in disease pathology.Future Neurology. 2015 Nov 10(6):507-510. 10.2217/fnl.15.30
Katzemich A, West RJH, Fukuzawa A, Sweeney ST, Gautel M, Sparrow J, Bullard B. Binding partners of the kinase domains in Drosophila obscurin and their effect on the structure of the flight muscle. J Cell Sci. 2015 Sep 15;128(18):3386-97. doi: 10.1242/jcs.170639. Epub 2015 Aug 6. PubMed PMID: 26251439; PubMed Central PMCID: PMC4582401.
Biography & Awards
2019 – Present: SITraN Fellow and Alzheimer’s Society Fellow (SITraN, University of Sheffield)
2018 – 2019: Alzheimer’s Society Junior Fellow (University of Manchester)
2015 – 2018: Postdoctoral Research Associate (University of York)
2013-2015: Centre for Chronic Diseases and Disorders Wellcome Trust funded “Discipline hopping” Fellow (University of York)
Following an Industrial placement year at Eli Lilly, working on murine models of Parkinson’s Disease I moved to York in 2010 to do my PhD in the lab of Sean Sweeney, characterising a Drosophila model of Frontotemporal Dementia associated with the CHM2BIntron5 mutation. After my PhD I remained in York as Wellcome trust funded “discipline hopping” fellow looking at visual disturbances in Parkinson’s disease and then as a post-doc continuing my work on CHMP2B and the role of POSH as a JNK scaffold in FTD. In 2017 I was awarded an Alzheimer’s Society Fellowship and moved to Manchester in 2018. At the end of October 2019, I moved to SITraN to continue my Alzheimer’s Society Fellowship and take up a position as a SITraN Fellow. Here I am establishing Drosophila facilities within SITraN and continuing my work on Drosophila models of neurodegeneration.
Department of Neuroscience
University of Sheffield
385a Glossop Road
T: +44 (0)114 2222239
Joanne Sharpe (Manchester, Joint with Stuart-Pickering Brown): Drosophila Models of C9orf72 Related Dipeptide-Repeats
Nikki Harper (Manchester, Joint with Stuart-Pickering Brown): Interaction between Ataxin2 and C9orf72 related Dipeptide-Repeat Proteins
Duncan Garner (Dipeptide Repeat Interactions In Drosophila Models of C9orf72 Frontotemporal Dementia and Motor Neurone Disease)