Parkinson’s UK Senior Research Fellow
My research interests are concerned with investigating mitochondria in neurodegenerative diseases, primarily focused on Parkinson’s Disease. This encompasses mitochondrial function, DNA, morphology and recycling. My research focuses on both trying to further the understanding of the causes of mitochondrial problems in neurodegenerative conditions and in vitro drug screening for molecules which rescue mitochondrial function in patient tissue.
- Drug re-purposing in Parkinson’s Disease
- LRRK2 and mitochondria
- What role does mitochondrial DNA have in neurodegeneration?
- Drug targeting of mitophagy
- Mitochondrial dysfunction in Alzheimer's Disease - mechanism and therapeutic target
- Patient derived models of Parkinson's Disease
Dr Mortiboys’ research is supported by Parkinson’s UK, Rosetree's trust, Alzheimer Research UK, Michael J Fox Foundation, Industrial Collaborators and the University of Sheffield.
- Aurelie Schwarzentruber, Research Assistant
- Camilla Boschian, Research Assistant
- Ruby Macdonald, PhD student
- Chris Hastings, PhD student
- Mohammed Karami PhD student
Simon Bell, Clinical Fellow
Katy Barnes, Research Assistant
1) Liao C, Ashley N, Diot A, Morten K, Phadwal K, Williams A, Fearnley I, Rosser L, Lowndes J, Fratter C, Ferguson DJ, Vay L, Quaghebeur G, Moroni I, Bianchi S, Lamperti C, Downes SM, Sitarz KS, Flannery PJ, Carver J, Dombi E, East D, Laura M, Reilly MM, Mortiboys H, Prevo R, Campanella M, Daniels MJ, Zeviani M, Yu-Wai-Man P, Simon AK, Votruba M, Poulton J. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology. 2017 Jan 10;88(2):131-142.
2) Mortiboys H. Screening for chemical modulators for LRRK2. Biochem Soc Trans. 2016 Dec 15;44(6):1617-1623.
3) Soman S, Keatinge M, Moein M, DaCosta M, Mortiboys H, Skupin A, Sugunan S, Bazala M, Kuznicki J, Bandmann O. Inhibition of the mitochondrial calcium uniporter (MCU) rescues dopaminergic neurons in pink1-/- zebrafish. Eur J Neurosci. 2016 Nov 12
4) Yealland G, Battaglia G, Bandmann O, Mortiboys H. Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes. Neurosci Lett. 2016 Jul 10;630:23-29. doi: 10.1016/j.neulet.2016.06.065.
5) Keatinge M, Bui H, Menke A, Chen YC, Sokol AM, Bai Q, Ellett F, Da Costa M, Burke D, Gegg M, Trollope L, Payne T, McTighe A, Mortiboys H, de Jager S, Nuthall H, Kuo MS, Fleming A, Schapira AH, Renshaw SA, Highley JR, Chacinska A, Panula P, Burton EA, O'Neill MJ, Bandmann O. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Hum Mol Genet. 2015 Dec 1;24(23):6640-52.
6) Mortiboys H, Furmston R, Bronstad G, Aasly J, Elliott C, Bandmann O. (2015) UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo. Neurology. 85(10):846-52.
7) Diot A, Hinks-Roberts A, Lodge T, Liao C, Dombi E, Morten K, Brady S, Fratter C, Carver J, Muir R, Davis R, Green CJ, Johnston I, Hilton-Jones D, Sue C, Mortiboys H, Poulton J. A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA. Pharmacol Res. 2015 Oct;100:24-35
8) Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E, Mortiboys H, Whitworth AJ (2014) The complex I subunit NDUFA10 selectively rescues Drosophila pink1 mutants through a mechanism independent of mitophagy. PLoS Genetics, 10(11):e:1004815.
9) Hickey FB, Corcoran JB, Griffin B, Bhreathnach U, Mortiboys H, Reid HM, Andrews D, Byrne S, Furlong F, Martin F, Godson C, Murphy M. IHG-1 increases mitochondrial fusion and bioenergetic function. Diabetes. 2014 Dec;63(12):4314-25
10) Allen SP, Rajan S, Duffy L, Mortiboys H, Higginbottom A, Grierson AJ, Shaw PJ. Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis. Neurobiol Aging. 2014 Jun;35(6):1499-509.
11) Flinn LJ, Keatinge M, Bretaud S, Mortiboys H, Matsui H, De Felice E, Woodroof HI, Brown L, McTighe A, Soellner R, Allen CE, Heath PR, Milo M, Muqit MM, Reichert AS, Köster RW, Ingham PW, Bandmann O. TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency. Ann Neurol. 2013 Dec;74(6):837-47.
12) Mortiboys H, Aasly J, Bandmann O (2013) Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease. Brain, 136(Pt10): 3038-50.
13) Mortiboys H, Cox A, Brock IW, Bandmann O (2013) The Parkinson’s Disease mutation LRRK2 G2019S is not increased in breast cancer patients in the absence of Parkinson’s disease. Journal of Neurology, 260(8):2177-8.
14) Richardson K, Allen S, Mortiboys H, Grierson AJ, Wharton SB, Ince PG, Shaw PJ, Heath PR (2013) The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress, and influence of mutation-type. PLOS One, 8(6):e68256.
15) Mortiboys H, Johansen KK, Aasly JO, Bandmann O (2010). Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology.75(22):2017-20.
16) Cox LE, Ferraiuolo L, Goodall EF, Heath PR, Higginbottom A, Mortiboys H, Hollinger HC, Hartley JA, Brockington A, Burness CE, Morrison KE, Wharton SB, Grierson AJ, Ince PG, Kirby J, Shaw PJ. Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS One. 2010 Mar 24;5(3):e9872.
17) Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ. (2009) Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci. 12(9):1129-35.
18) Flinn L, Mortiboys H, Volkmann K, Köster RW, Ingham PW, Bandmann O. (2009) Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish. Brain. 32(Pt 6):1613-23.
19) Mortiboys H, Thomas KJ, Koopman WJ, Klaffke S, Abou-Sleiman P, Olpin S, Wood NW, Willems PH, Smeitink JA, Cookson MR, Bandmann O. (2008) Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol. 64(5):555-65.
20) Osborne NN, Li GY, Ji D, Mortiboys HJ, Jackson S. Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies. J Neurochem. 2008 Jun;105(5):2013-28.
I was awarded my PhD from the International Max Planck PhD Program in Dresden Germany in 2006 with the grade summa cum laude; this project focused on the ‘Influence of mitochondrial energy metabolism on cellular function: implications for neurometabolic and neurodegenerative diseases.’ After which I worked in the Neurology department at the University Hospital Dresden as a research associate on an EU funded project investigating Co-enzyme Q deficiency in patient tissue.
I joined the Neuroscience department at the University of Sheffield in 2006 to set up mitochondrial investigations in models of Parkinson’s Disease working as a postdoctoral research associate with Prof. Oliver Bandmann.
I recently became a Parkinson’s UK Senior Research Fellow based within the Sheffield Institute for Translational Neuroscience (SITraN) to continue and expand this work setting up my own laboratory.
I teach in the MSc courses in Translational Neuroscience, Clinical Neurology and Molecular Medicine focussing on protein assay work and basic cell biology assays, the pathogenetic mechanisms involved in Parkinson’s Disease and critical review of the literature teaching. I also teach on the undergraduate Biomedical Science course on the module the Biological Basis of Brain Disease. I supervise MSc students during their research projects.