Sheffield Institute for
Translational Neuroscience

Dr Heather Mortiboys PhD

Senior Lecturer in Translational Neuroscience


Research Interests

The main focus of my lab is mitochondria in neurodegenerative diseases, primarily focused on Parkinson’s Disease. This encompasses mitochondrial function, DNA, morphology and recycling as well as links with other cellular pathways.

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.

The lab has also recently become interested in investigating these mitochondrial abnormalities in Alzheimer’s Disease and Motor Neuron Disease patient derived cells. It is interesting to investigate the differing mitochondrial phenotypes between neurodegenerative diseases and the mechanisms by which they occur and potentially drive neuronal vulnerability.

Grants

My research is currently funded by Parkinson’s UK, Parkinson’s UK Virtual Biotech, MRC, several industrial partners including Nanna Therapeutics, Verge Analytics, NZP UK Ltd, and the White Rose Consortium.

Current Projects

  • Targeting mitochondrial dysfunction with novel small molecules in Parkinson’s Disease and Alzheimer’s Disease
  • Repurposing of compounds for the treatment of Parkinson’s Disease
  • LRRK2 and mitochondria – what is the connection?
  • Differing types of mitophagy in neurons
  • Targeting mitophagy with small molecules in Parkinson’s Disease
  • What are the metabolic abnormalities in Alzheimer’s Disease
  • Mitochondrial morphological abnormalities in patient derived models of Alzheimer’s Disease

Research Collaborations

Within Sheffield: Dr Laura Ferraiuolo, Prof Oliver Bandmann, Prof Kurt De Vos, Dr Suman De and Prof Val Gillet

Outside of Sheffield: Prof Sylvie Urbe (University of Liverpool), Prof Mike Clague (University of Liverpool), Dr Liz New (University of Sydney), Prof Joanna Poulton (University of Oxford), Dr Alex Whitworth (University of Cambridge)

Research Team

Postdoctoral Research Associates

  • Dr Elizabeth Stephen
  • Dr Naomi Hartopp
  • Dr Anastasia Thoma
  • Dr Emma Green
  • Dr Christopher Hastings
  • Dr David Carter
  • Dr Francesco Capriglia

Research Assistants

  • Tom Leah
  • Laura Ellis
  • Emily Mossman
  • Pauline Fleuren
  • Alicja Olejnik

PhD students

  • Katy Barnes
  • Rachel Hughes
  • James Lee
  • Toby Burgess

Publications

Journal articles

Frison M, Faccenda D, Abeti R, Rigon M, Strobbe D, England-Rendon BS, Cash D, Barnes K, Sadeghian M, Sajic M , Wells LA et al (2021) The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicityMolecular PsychiatryView this article in WRRO 

Leah T, Vazquez-Villaseñor I, Ferraiuolo L, Wharton S & Mortiboys H (2021) A Parkinson’s disease-relevant mitochondrial and neuronal morphology high-throughput screening assay in LUHMES cellsBio-protocol, 11(1). 

Gatto N, Dos Santos Souza C, Shaw AC, Bell SM, Myszczynska MA, Powers S, Meyer K, Castelli LM, Karyka E, Mortiboys H , Azzouz M et al (2020) Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and diseaseAging CellView this article in WRRO 

Bell SM, De Marco M, Barnes K, Shaw P, Ferraiuolo L, Blackburn DJ, Mortiboys H & Venneri A (2020) Do deficits in mitochondrial spare respiratory capacity contribute to neuropsychological changes seen in Alzheimer’s disease?Alzheimer's & Dementia, 16(S6). 

Bell SM, Burgess T, Lee J, Blackburn DJ, Allen SP & Mortiboys H (2020) Peripheral glycolysis in neurodegenerative diseasesInternational Journal of Molecular Sciences, 21(23). 

Schwartzentruber A, Boschian C, Lopes FM, Myszczynska MA, New EJ, Beyrath J, Smeitink J, Ferraiuolo L & Mortiboys H (2020) Oxidative switch drives mitophagy defects in dopaminergic parkin mutant patient neuronsScientific Reports, 10(1). 

Rusilowicz-Jones EV, Jardine J, Kallinos A, Pinto-Fernandez A, Guenther F, Giurrandino M, Barone FG, McCarron K, Burke CJ, Murad A , Martinez A et al (2020) USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylationLife Science Alliance, 3(8). View this article in WRRO 

Bell SM, De Marco M, Barnes K, Shaw PJ, Ferraiuolo L, Blackburn DJ, Mortiboys H & Venneri A (2020) Deficits in mitochondrial spare respiratory capacity contribute to the neuropsychological changes of alzheimer’s diseaseJournal of Personalized Medicine, 10(2). View this article in WRRO 

Carling PJ, Mortiboys H, Green C, Mihaylov S, Sandor C, Schwartzentruber A, Taylor R, Wei W, Hastings C, Wong S , Lo C et al (2020) Deep phenotyping of peripheral tissue facilitates mechanistic disease stratification in sporadic Parkinson’s diseaseProgress in Neurobiology, 187. 

Allen SP, Hall B, Woof R, Francis L, Gatto N, Shaw AC, Myszczynska M, Hemingway J, Coldicott I, Willcock A , Job L et al (2019) C9orf72 expansion within astrocytes reduces metabolic flexibility in amyotrophic lateral sclerosisBrain, 1-20. View this article in WRRO 

López KLR, Simpson JE, Watson LC, Mortiboys H, Hautbergue GM, Bandmann O & Highley JR (2019) TIGAR inclusion pathology is specific for Lewy body diseasesBrain Research, 1706, 218-223. View this article in WRRO 

Bell SM, Barnes K, Clemmens H, Al-Rafiah AR, Al-ofi EA, Leech V, Bandmann O, Shaw PJ, Blackburn DJ, Ferraiuolo L & Mortiboys H (2018) Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with either Sporadic or Familial Alzheimer's DiseaseJournal of Molecular Biology, 430(21), 3942-3953. View this article in WRRO 

Ratcliffe LE, Vázquez Villaseñor I, Jennings L, Heath PR, Mortiboys H, Schwartzentruber A, Karyka E, Simpson JE, Ince PG, Garwood CJ & Wharton SB (2018) Loss of IGF1R in human astrocytes alters complex I activity and support for neurons.Neuroscience, 390, 46-59. View this article in WRRO 

Macdonald R, Barnes K, Hastings C & Mortiboys H (2018) Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?Biochemical Society Transactions, 46(4), 891-909. View this article in WRRO 

Mortiboys H, Macdonald R, Payne T, Sassani M, Jenkins T & Bandmann O (2018) Translational approaches to restoring mitochondrial function in Parkinson's diseaseFEBS Letters, 592(5), 776-792. View this article in WRRO 

Carling P, Mortiboys H, Mihaylov S, Clemmens H, Schwartzenhuber A, Wade-Martins R, Talbot K, Hu M & Bandmann O (2017) PO076 Disease stratification in sporadic parkinson’s diseaseJournal of Neurology, Neurosurgery & Psychiatry, 88(Suppl 1), A31.4-A32. 

Bell SM, Clemmens H, Blackburn DJ, Bandmann O, Ferraiuolo L & Mortiboys H (2017) [P4-034]: MITOCHONDRIAL ABNORMALITIES ARE FOUND IN FIBROBLASTS FROM SPORADIC ALZHEIMER's DISEASE PATIENTS: RECOVERY WITH URSODOXYCHOLIC ACID TREATMENTAlzheimer's & Dementia, 13(7S_Part_26), P1269-P1269. 

Dombi E, Mortiboys H & Poulton J (2017) Modulating mitophagy in mitochondrial disease.Curr Med ChemView this article in WRRO 

Soman S, Keatinge M, Moein M, DaCosta M, Mortiboys H, Skupin A, Sugunan S, Bazala M, Kuznicki J & Bandmann O (2017) Inhibition of the mitochondrial calcium uniporter (MCU) rescues dopaminergic neurons in pink1-/- zebrafishEuropean Journal of Neuroscience, 45(4), 528-535. View this article in WRRO 

Liao C, Ashley N, Diot A, Morten K, Phadwal K, Williams A, Fearnley I, Rosser L, Lowndes J, Fratter C , Ferguson DJ et al (2017) Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutationsNeurology, 88(2), 131-142. View this article in WRRO 

Mortiboys H (2016) Screening for chemical modulators for LRRK2.Biochemical Society Transactions, 44(6), 1617-1623. View this article in WRRO 

Yealland G, Battaglia G, Bandmann O & Mortiboys H (2016) Rescue of mitochondrial function in parkin-mutant Fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomesNeuroscience Letters, 630, 23-29. View this article in WRRO 

Keatinge M, Bui H, Menke A, Chen Y-C, Sokol AM, Bai Q, Ellett F, Da Costa M, Burke D, Gegg M , Trollope L et al (2015) 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 deathHuman Molecular Genetics, 24(23), 6640-6652. View this article in WRRO 

Diot A, Hinks-Roberts A, Lodge T, Liao C, Dombi E, Morten K, Brady S, Fratter C, Carver J, Muir R , Davis R et al (2015) 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 mtDNAPharmacological Research, 100, 24-35. 

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 vivoNeurology, 85(10), 846-852. 

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 MitophagyPLoS Genetics, 10(11). View this article in WRRO 

Hickey FB, Corcoran JB, Griffin B, Bhreathnach U, Mortiboys H, Reid HM, Andrews D, Byrne S, Furlong F, Martin F , Godson C et al (2014) IHG-1 increases mitochondrial fusion and bioenergetic function.Diabetes, 63(12), 4314-4325. 

Hinks-Roberts A, Dombi E, Diot A, Liao C, Morten K, Carver J, Lodge T, Mortiboys H & Poulton J (2014) P33 Do modulators of mitophagy select pathogenic mtDNA mutations?Neuromuscular Disorders, 24, S15-S15. 

Allen SP, Rajan S, Duffy L, Mortiboys H, Higginbottom A, Grierson AJ & Shaw PJ (2014) Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis.Neurobiol Aging, 35(6), 1499-1509. 

Mortiboys H, Aasly J & Bandmann O (2013) Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease.Brain, 136(Pt 10), 3038-3050. 

Flinn LJ, Keatinge M, Bretaud S, Mortiboys H, Matsui H, De Felice E, Woodroof HI, Brown L, McTighe A, Soellner R , Allen CE et al (2013) TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency.Ann Neurol, 74(6), 837-847. View this article in WRRO 

Richardson K, Allen SP, Mortiboys HJ, 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, 6(8), e68256-e68256. View this article in WRRO 

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), 2017-2020. 

Bandmann O, Flinn L & Mortiboys H (2010) POMD08 Zebrafish models for early onset Parkinson's disease.J Neurol Neurosurg Psychiatry, 81(11), e59. 

Bandmann O, Flinn L & Mortiboys H (2010) A PINK1 Mutant Zebrafish Model of Early Onset Parkinson's Disease. MOVEMENT DISORD, 25, S631-S631. 

Cox LE, Ferraiuolo L, Goodall EF, Heath PR, Higginbottom A, Mortiboys H, Hollinger HC, Hartley JA, Brockington A, Burness CE , Morrison KE et al (2010) Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).PLoS One, 5(3), e9872. View this article in WRRO 

Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O & Whitworth AJ (2009) Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss.Nature Neuroscience, 12(9), 1129-1135. View this article in WRRO 

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 (Danio rerio).Brain, 132(Pt 6), 1613-1623. 

Mortiboys H, Thomas KJ, Koopman WJH, Klaffke S, Abou-Sleiman P, Cookson MR & Bandmann O (2009) 7. Mitochondrial function and morphology are impaired in parkin mutant fibroblastsMitochondrion, 9(1), 63-63. 

Mortiboys H, Thomas KJ, Koopman WJH, Klaffke S, Abou-Sleiman P, Olpin S, Wood NW, Willems PHGM, Smeitink JAM, Cookson MR & Bandmann O (2008) Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts.Ann Neurol, 64(5), 555-565. 

Osborne NN, Li G-Y, Ji D, Mortiboys HJ & Jackson S (2008) Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies.J Neurochem, 105(5), 2013-2028. 

Mortiboys HJ, Schaefer J, Reichmann H & Jackson S (2007) Mitochondrial dysfunction in Parkinson's disease--revisited.. Neurol Neurochir Pol, 41(2), 150-159. 

Schaefer J, Mortiboys H, Navas P, Weinhold M, Reichmann H & Jackson S (2006) Primärer Coenzym Q10-Mangel bei einem ErwachsenenAktuelle Neurologie, 33(S 1). 

Schaefer J, Mortiboys H, Reichmann H & Jackson S () Defekte der mitochondrialen Atmungskette bei idiopathischem Parkinson-SyndromAktuelle Neurologie, 32(S 4). 

Mortiboys HJ, Cox A, Brock IW & Bandmann O () The common PARK8 mutation LRRK2 G2019S is not a risk factor for breast cancer in the absence of Parkinson's disease.. Journal of Neurology

Sassani M, Alix J, McDermott C, Baster K, Hoggard N, Wild J, Mortiboys H, Shaw P, Wilkinson I & Jenkins T () Magnetic resonance spectroscopy reveals mitochondrial dysfunction in amyotrophic lateral sclerosis. Brain

Bell SM, Barnes K, De Marco M, Shaw PJ, Ferraiuolo L, Blackburn DJ, Venneri A & Mortiboys H () Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?Biomedicines, 9(1), 63-63. 

Conference proceedings papers

Keatinge M, Trollope L, Mortiboys H & Bandmann O (2018) Acid sphingomyelinase deficiency rescues mitochondrial dysfunction in gba-/- zebrafish (Danio rerio). MOVEMENT DISORDERS, Vol. 33 (pp S615-S615) 

Oliver B, Solman S, Keatinge M, DaCosta M, Mortiboys H, Sugunan S & Kuznicki J (2016) Inhibition of the mitochondrial calcium uniporter (MCU) rescues dopaminergic neurons in pink1-/- zebrafish. MOVEMENT DISORDERS, Vol. 31 (pp S209-S209) 

Liao C, Diot A, Ashley N, Morten K, Fratter C, Moroni I, Bianchi S, Lamperti C, Dombi E, Downes S , Sitarz K et al (2015) Dysregulated mitophagy and mitochondrial transport in sensori-motor neuropathy due to “Dominant Optic Atrophy” plus with OPA1 (Optic Atrophy 1) mutationsNeuromuscular Disorders, Vol. 25 (pp S185-S186) 

Bandmann O, Johansen KK, Aasly JO & Mortiboys H (2010) Mitochondrial Impairment in Manifesting LRRK2-G2019S Carriers. NEUROLOGY, Vol. 74(9) (pp A255-A255) 

Flinn L, Mortiboys H, Volkmann K, Koester RW, Ingham PW & Bandmann O (2009) Complex I deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio). MOVEMENT DISORDERS, Vol. 24 (pp S135-S135) 

Bandmann O, Klaffke S, Sleiman P, Wood NW & Mortiboys HJ (2008) Abnormal mitochondrial function and morphology in fibroblasts of patients with early onset Parkinson's disease and two parkin mutations. NEUROLOGY, Vol. 70(11) (pp A485-A485) 

Mortiboys H, Thomas K, Klaffke S, Koopman W, Cookson M & Bandmann O (2008) Mitochondrial function and morphology in parkin mutant fibroblasts. MOVEMENT DISORDERS, Vol. 23(1) (pp S49-S49) 

Datasets

Gatto N, Souza CDS, Bell S, Shaw A, Myszczynska M, Powers S, Meyer K, Heath P, Castelli L, Karyka E , Mortiboys H et al Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease.

 

Professional Activities

I am a member of the Parkinson’s UK college of experts as well as the Patient Public Involvement Steering Group. I also sit on the Cure Parkinson’s Trust Review Panel.

I am lead external examiner for MRes courses at University of Newcastle. I regularly review for several funding bodies including MRC, Parkinson’s UK, BBSRC, Motor Neuron Disease Association, EU, ARUK and many others.

Biography

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 started my own lab when I became a Parkinson’s UK Senior Research Fellow in September 2013 based within the Sheffield Institute for Translational Neuroscience (SITraN).

I am currently a Senior Lecturer in Translational Neuroscience.

Teaching Interests

I teach on the MSc courses in Translational Neuroscience, Translational Neuropathology, 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 enjoy training and supervising MSc and BMedSci students during their research projectsand usually host 2-3 students per year. In addition we host multiple medical students from the MBChB course for short projects per year.

Contact Details

Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B50
385a Glossop Road
Sheffield
S10 2HQ

T: +44 (0)114 2222259
E: h.mortiboys@shef.ac.uk

Administrator:
Rebecca Brown
T: +44 (0)114 2222261
E: rebecca.brown@sheffield.ac.uk