Professor Guillaume Hautbergue

FRSB, PhD, PGCertHE, FHEA

Neuroscience, School of Medicine and Population Health

Professor of Translational RNA Biology

Head of the RNA Biology Laboratory

MBChB Research SSC Academic Lead for the Medical School

Founding Director of Crucible Therapeutics

g.hautbergue@sheffield.ac.uk
+44 114 222 2252

+44 114 222 2278 (Administrator: Heather Cartledge)

Sheffield Institute for Translational Neuroscience (SITraN)

Full contact details

Professor Guillaume Hautbergue
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ

Profile

Professor of Translational RNA Biology: January 2023 - present

Senior Lecturer in Translational RNA Biology January 2019 -December 2022

Lecturer in Translational Biology December 2012 - December 2018
Dr Hautbergue was recruited to the Sheffield Institute for Translational Neuroscience in August 2012 to set up the laboratory of RNA Molecular Biology, which is aimed at understanding the cause of gene expression dysregulation in neurodegenerative diseases, particularly focusing on ALS/MND, for the development of novel therapeutic strategies of neuroprotection.

Senior Experimental Officer March 2010 – November 2012

SITraN, University of Sheffield, U.K. August – November 2012. Setting up the RNA biology laboratory and my research group in SITraN to apply my scientific skills in RNA biology research to the understanding of RNA processing dysregulation in ALS/MND. Department of Molecular Biology and Biotechnology, University of Sheffield, U.K. March 2010 – July 2012

Structural and molecular mechanisms of human and viral mRNA nuclear export. Characterisation of ribonucleo-protein complexes. Expression, purification and solubility of proteins. Supervision of students/staff from other laboratories across Faculties. Module coordinator of undergraduate level 2 practical classes (MBB220, MBB226).

Qualifications

Post-Doctoral Research Associate January 2002 – February 2010
Department of Molecular Biology and Biotechnology, University of Sheffield, and Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, U.K.
Principal Investigator: Prof Stuart A. Wilson
The development of a general method to solubilise proteins led to the structure/function analysis of known and uncharacterised mRNA export adaptors establishing the presently accepted model for the molecular mechanisms of human mRNA nuclear export.

Ph.D. of Molecular and Cellular Biology (Very Best Commendation with Honour)
Université Pierre et Marie Curie Paris VI, Paris, France. August 1997 – September 2001
Department of Biochemistry and Molecular Genetics, Commissariat à l'Energie Atomique, Saclay, and Laboratory of Molecular Genetics, CNRS URA-1302, Ecole Normale Supérieure, Paris, France. Principal Investigator: Dr Valérie Goguel
Function of the yeast CTD Kinase I and atypical ubiquitin-mediated regulation of its activity.

French National Service October 1996 – July 1997
Sergeant (“Maréchal des Logis”) of the French Ground Armed Material Forces. Lead management training, First Help Training Certificate – Awarded a French National Defence bronze medal.

Molecular and Cellular Biology Advanced Studies Diploma June 1996
Université Pierre et Marie Curie Paris VI, Paris, France. Ranked in the top 3 for a Ph.D. fellowship.

M.Sc. Biochemistry (With Distinction) June 1995
Université Denis Diderot Paris VII, Paris, France.

Biochemistry Higher Technological Certificate (Best Commendation) June 1993
Ecole Nationale de Chimie Physique Biologie (ENCPB), Paris, France.

First National Prize in Biochemistry June 1990
France and French Overseas Countries in the competitive examination "Concours Général"

Biochemistry Baccalauréat (Best Commendation) June 1990
Lycée Pierre et Marie Curie, Sens, France

Research interests

Our research focuses on identifying pathophysiological alterations of gene expression in neurodegeneration for the development of novel therapeutic strategies using viral and non-viral gene therapy approaches.

Widespread dysregulation of the RNA metabolism has been recognised as a key pathological component causing multiple neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS), also known as motor neurone disease (MND, spinal muscular atrophy (SMA), Huntington’s disease (HD) and spinocerebellar ataxias (SCAs). Widespread alterations of transcriptomes have also been reported during physiological ageing of the brain while many neurodegenerative disorders are progressive late adult-onset diseases.

Although some genetic causes of often-fatal neurodegenerative diseases are known, the multifactorial molecular mechanisms governing pathogenesis and progression are still poorly understood. Genome-wide studies from cell or animal models and human post-mortem brains extensively described large alterations of transcriptomes at all levels of the RNA metabolism including RNA biogenesis and processing, axonal transport and translation. Thousands of changes were reported in multiple cellular pathways with dysregulation reaching up to one third of the TDP-43 linked ALS transcriptomes. Since it is not feasible to separately investigate all individual changes, it remains challenging to distinguish alterations that are causing neurodegeneration from those which are consequences of initial RNA dysregulation – a bottleneck for the development of novel therapies.

In fact, the functional outcomes of widespread RNA dysregulation in neurodegeneration and ageing remain largely uncharacterised at the protein level, which is ultimately linked to neuronal survival or death. Beyond our investigation of altered RNA/protein expression levels and the development of neuroprotective strategies, we also aim at answering challenging scientific questions concerning RNA dysregulation in neurodegeneration and ageing: Proportion and identities of abnormally processed RNA molecules that escape the safeguarding mechanisms of nuclear retention? Which abnormal proteins are synthesised from incorrectly processed RNAs? Roles of long intergenic non-coding (linc) RNAs that exhibit similar features to protein-coding genes?

Current Projects

Research in the laboratory currently focuses on the mechanisms of neurodegeneration and the identification of therapeutic strategies of neuroprotection in Amyotrophic Lateral Sclerosis (ALS) and Fragile X Tremor and Ataxia Syndrome (FXTAS). In particular, we aim to identify RNA changes that cause neurodegeneration and understand whether these involve converging mechanisms of altered RNA metabolism in different variants of diseases. We are also interested in investigating how these relate to sporadic ALS.

We use a combination of in vitro and in vivo models of diseases (mammalian cells, patient-derived neurons and astrocytes, Drosophila and mice) as well as molecular & cellular biology, biochemistry, structural/functional and OMICS investigations in association with the development of novel experimental methodologies to uncover molecular mechanisms of gene expression that cause and can rescue the neurodegeneration process.

Generation of non-neuronal and neuron-like inducible cell models of neurodegeneration to characterise early changes in gene expression and spread of dysregulation over time, in combination with studies in animal models and in astrocytes and motor neurons differentiated from induced neuronal progenitor cells (iNPCs) derived from patient fibroblasts. Whenever possible, we try validating our in vitro and in vivo results in human post mortem CNS tissues. We have access to one of the world largest collection of brain biosamples (Sheffield Brain Tissue Bank).

Functional and structural studies to identify the molecular mechanisms driving the nuclear export and the repeat-associated non-AUG (RAN) translation in C9ORF72-ALS/FTD and FXTAS

Molecular mechanisms of TDP-43 proteinopathy, which involves the nuclear loss and cytoplasmic aggregation of TDP-43.

Functional analysis of the master energy homeostasis co-transcriptional activator PGC-1alpha in neuronal ageing and models of senescence.

Genome-wide identification of transcriptomes and translatomes.

Founding Director of Crucible Therapeutics, a University of Sheffield biotech spinout company, developing novel therapeutic strategies of neuroprotection. Our technology involves granted patents and new applications for the use of gene therapy approaches in the potential treatment of neurodegenerative disorders - with a current focus on C9ORF72-ALS/FTD.

Publications

Journal articles

Webster CP, Hall B, Crossley OM, Dauletalina D, King M, Lin Y-H, Castelli LM, Yang Z-L, Coldicott I, Kyrgiou-Balli E , Higginbottom A et al (2025) RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD. Life Science Alliance, 8(2), e202402757-e202402757.
Hodgson RE, Rayment JA, Huang W-P, Avila AS, Ellis BCS, Lin Y-H, Soni N, Hautbergue GM & Shelkovnikova TA (2024) C9orf72 poly-PR forms anisotropic condensates causative of nuclear TDP-43 pathology. iScience, 110937-110937.
Burrows DJ, McGown A, Abduljabbar O, Castelli LM, Shaw PJ, Hautbergue GM & Ramesh TM (2024) RAN translation of C9orf72-related dipeptide repeat proteins in zebrafish recapitulates hallmarks of amyotrophic lateral sclerosis and identifies hypothermia as a therapeutic strategy. Annals of Neurology. View this article in WRRO
Allen SP, Al Sultan A, Kabucho Kibirige E, Tonkiss E, Hamer KJ, Castelli LM, Lin Y-H, Roscoe S, Stefanidis N, Mead RJ , Highley JR et al (2023) A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations. Frontiers in Aging Neuroscience, 15.
Moll T, Odon V, Harvey C, Collins MO, Peden A, Franklin J, Graves E, Marshall JN, Dos Santos Souza C, Zhang S , Castelli L et al (2023) Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication.. Life Sci Alliance, 6(1).
Bauer CS, Webster CP, Shaw AC, Kok JR, Castelli LM, Lin Y-H, Smith EF, Illanes-Álvarez F, Higginbottom A, Shaw PJ , Azzouz M et al (2022) Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation. Frontiers in Cellular Neuroscience, 16.
Marchi PM, Marrone L, Brasseur L, Coens A, Webster CP, Bousset L, Destro M, Smith EF, Walther CG, Alfred V , Marroccella R et al (2022) C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons.. Life Sci Alliance, 5(9).
Castelli LM, Benson BC, Huang W-P, Lin Y-H & Hautbergue GM (2022) RNA helicases in microsatellite repeat expansion disorders and neurodegeneration. Frontiers in Genetics, 13. View this article in WRRO
Karyka E, Berrueta Ramirez N, Webster CP, Marchi PM, Graves EJ, Godena VK, Marrone L, Bhargava A, Ray S, Ning K , Crane H et al (2022) SMN-deficient cells exhibit increased ribosomal DNA damage. Life Science Alliance, 5(8), e202101145-e202101145.
Benson BC, Shaw PJ, Azzouz M, Highley JR & Hautbergue GM (2021) Proteinopathies as Hallmarks of Impaired Gene Expression, Proteostasis and Mitochondrial Function in Amyotrophic Lateral Sclerosis. Frontiers in Neuroscience, 15.
Hautbergue GM, Cleary JD, Guo S & Ranum LPW (2021) Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia. Current Opinion in Neurology.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Lin Y-H, Myszczynska MA, Heath PR, Livesey MR, Ning K , Azzouz M et al (2021) SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export : genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 16(1).
Castelli LM, Huang W-P, Lin Y-H, Chang K-Y & Hautbergue GM (2021) Mechanisms of repeat-associated non-AUG translation in neurological microsatellite expansion disorders. Biochemical Society Transactions.
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 disease. Aging Cell.
De Marco M, Manca R, Kirby J, Hautbergue G, Blackburn DJ, Wharton S & Venneri A (2020) The association between polygenic hazard scores and clinical markers of Alzheimer’s disease following stratification for APOE genotype. Alzheimer's & Dementia, 16(S4).
De Marco M, Manca R, Kirby J, Hautbergue GM, Blackburn DJ, Wharton SB & Venneri A (2020) The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype. Current Alzheimer Research, 17.
Myszczynska MA, Ojamies PN, Lacoste AMB, Neil D, Saffari A, Mead R, Hautbergue GM, Holbrook JD & Ferraiuolo L (2020) Applications of machine learning to diagnosis and treatment of neurodegenerative diseases. Nature Reviews Neurology, 16, 440-456. View this article in WRRO
Allen S, Hall B, Castelli L, Frances L, Woof R, Siskos A, Kouloura E, Gray E, Thompson A, Talbot K , Higginbottom A et al (2019) Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis. Brain, 142(3), 586-605. 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 diseases. Brain Research, 1706, 218-223. View this article in WRRO
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Beer A, Robins H, Fox I, Niedermoser I, Van Damme P, Moisse M , Robberecht W et al (2019) Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis. Cell Reports, 26(9), 2298-2306.e5. View this article in WRRO
Ferraiuolo L, Varcianna AE, Myszczynska MA, Castelli LM, O'Neill B, Kim Y, Talbot J, Nyberg S, Nymali I, Heath PR , Stopford MJ et al (2019) Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.. EBioMedicine, 40, 626-635. View this article in WRRO
Shaw MP, Higginbottom A, Mcgown A, Castelli LM, James E, Hautbergue GM, Shaw PJ & Ramesh TM (2018) Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features. Acta Neuropathologica Communications, 6(1). View this article in WRRO
Iannitti T, Scarrott J, Likhite S, Coldicott IRP, Lewis KE, Heath PR, Higginbottom A, Myszczynska MA, Milo M, Hautbergue GM , Meyer K et al (2018) Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS. Molecular Therapy : Nucleic Acids, 12, 75-88. View this article in WRRO
Morgan SV, Garwood CJ, Jennings L, Simpson JE, Castelli LM, Heath PR, Mihaylov SR, Vaquéz-Villaseñor I, Minshull TC, Ince PG , Dickman MJ et al (2018) Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes. European Journal of Neuroscience, 47(12), 1444-1456. View this article in WRRO
Rust A, Shah S, Hautbergue G & Davletov B (2018) Burkholderia Lethal Factor 1, a Novel Anti-Cancer Toxin, Demonstrates Selective Cytotoxicity in MYCN-Amplified Neuroblastoma Cells. Toxins, 10(7), 261-261. View this article in WRRO
Castelli LM, Lin YH, Ferraiuolo L, Sanchez-Martinez A, Ning KE, Azzouz M, Whitworth A, Shaw PJ & Hautbergue GM (2018) SRSF1-dependent nuclear export of C9ORF72 repeat transcripts: targeting toxic gain-of-functions induced by protein sequestration as a selective therapeutic strategy for neuroprotection. Therapeutic Targets for Neurological Diseases, 4. View this article in WRRO
Cooper-Knock J, Robins H, Niedermoser I, Wyles M, Heath PR, Higginbottom A, Walsh T, Kazoka M, Ince PG, Hautbergue GM , McDermott CJ et al (2017) Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype. Frontiers in Molecular Neuroscience, 10, 370-370. View this article in WRRO
Chandran JS, Sharp PS, Karyka E, Aves-Cruzeiro JMDC, Coldicott I, Castelli L, Hautbergue G, Collins MO & Azzouz M (2017) Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome. Scientific Reports, 7(1). View this article in WRRO
Hautbergue GM (2017) RNA Nuclear Export: From Neurological Disorders to Cancer. Adv Exp Med Biol, 1007, 89-109. View this article in WRRO
Walker C, Herranz-Martin S, Karyka E, Liao C, Lewis K, Lukashchuk V, Chiang S-C, Ray S, Mulcahy PJ, Jurga M , Tsagakis I et al (2017) C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 20, 1225-1235. View this article in WRRO
Hautbergue GM, Castelli LM, Ferraiuolo L, Sanchez-Martinez A, Cooper-Knock J, Higginbottom A, Lin YH, Bauer CS, Dodd JE, myszczynska MA , Alam SM et al (2017) SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature Communications, 8. View this article in WRRO
Stopford M, Higginbottom A, Hautbergue , Cooper-Knock , Mulcahy , De Vos K, Renton A, Pliner H, Calvo A, Chio A , Traynor B et al (2017) C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Human Molecular Genetics, 26(6), 1133-1145. View this article in WRRO
Webster CP, Smith EF, Bauer CS, Moller A, Hautbergue GM, Ferraiuolo L, Myszczynska MA, Higginbottom A, Walsh MJ, Whitworth AJ , Kaspar BK et al (2016) The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO Journal, 35(15), 1656-1676. View this article in WRRO
Hautbergue GM (2016) Widespread RNA dysregulation in neurodegeneration: Challenges and Opportunities. Austin Neurology, 1(1). View this article in WRRO
Rust A, Hassan HHA, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T & Davletov B (2015) Two complementary approaches for intracellular delivery of exogenous enzymes. Scientific Reports, 5, 12444-12444. View this article in WRRO
Cooper-Knock J, Higginbottom A, Stopford MJ, Highley JR, Ince PG, Wharton SB, Pickering-Brown S, Kirby J, Hautbergue GM & Shaw PJ (2015) Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy. Acta Neuropathologica, 130(1), 63-75. View this article in WRRO
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(5), e0127376-e0127376. View this article in WRRO
Tazzyman S, Hautbergue G, Khurram A, Bryan M, Chantry A & Fragiadaki M (2015) The application of antibotoxsome, a novel cytotoxic conjugate, in cell death in in vitro models of pancreatic, liver, breast, cervical cancer, and myeloma.. Journal of Clinical Oncology, 33(15_suppl), e12018-e12018.
Snijders AP, Hautbergue GM, Bloom A, Williamson JC, Minshull TC, Phillips HL, Mihaylov SR, Gjerde DT, Hornby DP, Wilson SA , Hurd PJ et al (2015) Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA. RNA, 21(3), 347-359. View this article in WRRO
Walsh MJ, Cooper-Knock J, Dodd JE, Stopford MJ, Mihaylov SR, Kirby J, Shaw PJ & Hautbergue GM (2015) Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art. Neuropathology and Applied Neurobiology, 41(2), 109-134. View this article in WRRO
Caballero-Lima D, Hautbergue GM, Wilson SA & Sudbery PE (2014) In C andida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles. Molecular Microbiology, 94(4), 828-842. View this article in WRRO
Cooper-Knock J, Walsh MJ, Higginbottom A, Robin Highley J, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J , Hautbergue GM et al (2014) Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(Pt 7), 2040-2051. View this article in WRRO
Cooper-Knock J, Walsh M, Higginbottom A, Highley JR, Bury J, Dickman M, Rattray M, Heath P, Wyles M, Ince P , Wharton S et al (2014) GGGGCC Repeat Expansion of C9ORF72 Is Toxic Via Sequestration Of RNA Binding Proteins And Consequent Disruption Of RNA Splicing (S56.004). Neurology, 82(10_supplement).
Cooper-Knock J, Walsh M, Higginbottom A, Highley JR, Bury J, Dickman M, Rattray M, Heath P, Wyles M, Ince P , Wharton S et al (2014) GGGGCC Repeat Expansion of C9ORF72 Is Toxic Via Sequestration Of RNA Binding Proteins And Consequent Disruption Of RNA Splicing (1II-2.005). Neurology, 82(10_supplement).
Tunnicliffe RB, Hautbergue GM, Wilson SA, Kalra P & Golovanov AP (2014) Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF. PLoS Pathogens, 10(2). View this article in WRRO
Walsh MJ, Dodd JE & Hautbergue GM (2013) Ribosome-inactivating proteins. RNA Biology, 10(12), 1760.
Walsh MJ, Dodd JE & Hautbergue GM (2013) Ribosome-inactivating proteins: potent poisons and molecular tools.. Virulence, 4(8), 774-784.
Chang C-T, Hautbergue GM, Walsh MJ, Viphakone N, van Dijk TB, Philipsen S & Wilson SA (2013) Chtop is a component of the dynamic TREX mRNA export complex.. EMBO J, 32(3), 473-486.
Viphakone N, Hautbergue GM, Walsh M, Chang CT, Holland A, Folco EG, Reed R & Wilson SA (2013) Erratum: TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 4, 2377.
Viphakone N, Hautbergue GM, Walsh M, Chang C-T, Holland A, Folco EG, Reed R & Wilson SA (2012) TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export.. Nat Commun, 3, 1006. View this article in WRRO
Hautbergue GM & Wilson SA (2012) BLF1, the first Burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.. Biochem Soc Trans, 40(4), 842-845.
Knuckles P, Vogt MA, Lugert S, Milo M, Chong MMW, Hautbergue GM, Wilson SA, Littman DR & Taylor V (2012) Drosha regulates neurogenesis by controlling neurogenin 2 expression independent of microRNAs.. Nat Neurosci, 15(7), 962-969.
Phelan MM, Goult BT, Clayton JC, Hautbergue GM, Wilson SA & Lian L-Y (2012) The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.. Nucleic Acids Res, 40(7), 3232-3244. View this article in WRRO
Hautbergue G (2012) [Characterisation of Burkholderia pseudomallei Lethal Factor 1 (BLF1). A breakthrough against melioidosis].. Med Sci (Paris), 28(3), 262-264.
Cruz-Migoni A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang C-T, Dickman MJ, Essex-Lopresti A, Harding SV, Mahadi NM , Marshall LE et al (2011) A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824. View this article in WRRO
Jackson BR, Boyne JR, Noerenberg M, Taylor A, Hautbergue GM, Walsh MJ, Wheat R, Blackbourn DJ, Wilson SA & Whitehouse A (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.. PLoS Pathog, 7(7), e1002138. View this article in WRRO
Van Hateren NJ, Das RM, Hautbergue GM, Borycki A-G, Placzek M & Wilson SA (2011) FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools.. Development, 138(10), 1893-1902.
Tunnicliffe RB, Hautbergue GM, Kalra P, Jackson BR, Whitehouse A, Wilson SA & Golovanov AP (2011) Structural basis for the recognition of cellular mRNA export factor REF by herpes viral proteins HSV-1 ICP27 and HVS ORF57.. PLoS Pathog, 7(1), e1001244. View this article in WRRO
Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & Lian L-Y (2011) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing.. Biomol NMR Assign, 5(1), 7-10.
Hung ML, Hautbergue GM, Snijders AP, Dickman MJ & Wilson SA (2010) Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.. Nucleic Acids Res, 38(10), 3351-3361. View this article in WRRO
Walsh MJ, Hautbergue GM & Wilson SA (2010) Structure and function of mRNA export adaptors.. Biochem Soc Trans, 38(Pt 1), 232-236.
Clayton JC, Phelan M, Goult BT, Hautbergue GM, Wilson SA & Lian L-Y (2010) The 1H, 13C and 15N backbone and side-chain assignment of the RRM domain of SC35, a regulator of pre-mRNA splicing. Biomolecular NMR Assignments, 1-4.
Hautbergue GM, Hung M-L, Walsh MJ, Snijders APL, Chang C-T, Jones R, Ponting CP, Dickman MJ & Wilson SA (2009) UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.. Curr Biol, 19(22), 1918-1924.
Hautbergue GM & Golovanov AP (2008) Increasing the sensitivity of cryoprobe protein NMR experiments by using the sole low-conductivity arginine glutamate salt.. J Magn Reson, 191(2), 335-339.
Hautbergue GM, Hung M-L, Golovanov AP, Lian L-Y & Wilson SA (2008) Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP.. Proc Natl Acad Sci U S A, 105(13), 5154-5159.
Tintaru AM, Hautbergue GM, Hounslow AM, Hung M-L, Lian L-Y, Craven CJ & Wilson SA (2007) Structural and functional analysis of RNA and TAP binding to SF2/ASF.. EMBO Rep, 8(8), 756-762.
Tintaru AM, Hautbergue GM, Hounslow AM, Lian L-Y, Wilson SA & Craven CJ (2007) Assignment of 1H, 13C, and 15N resonances for SF2 RNA recognition motif 2.. J Biomol NMR, 38(2), 193.
Hargous Y, Hautbergue GM, Tintaru AM, Skrisovska L, Golovanov AP, Stevenin J, Lian L-Y, Wilson SA & Allain FH-T (2006) Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.. EMBO J, 25(21), 5126-5137.
Golovanov AP, Hautbergue GM, Tintaru AM, Lian L-Y & Wilson SA (2006) The solution structure of REF2-I reveals interdomain interactions and regions involved in binding mRNA export factors and RNA.. RNA, 12(11), 1933-1948.
Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2006) Assignment of 1H, 13C, and 15N resonances for the REF2-I mRNA export factor.. J Biomol NMR, 36 Suppl 1, 41.
Williams BJL, Boyne JR, Goodwin DJ, Roaden L, Hautbergue GM, Wilson SA & Whitehouse A (2005) The prototype gamma-2 herpesvirus nucleocytoplasmic shuttling protein, ORF 57, transports viral RNA through the cellular mRNA export pathway.. Biochem J, 387(Pt 2), 295-308.
Golovanov AP, Hautbergue GM, Wilson SA & Lian L-Y (2004) A simple method for improving protein solubility and long-term stability.. J Am Chem Soc, 126(29), 8933-8939.
Bouchoux C, Hautbergue G, Grenetier S, Carles C, Riva M & Goguel V (2004) CTD kinase I is involved in RNA polymerase I transcription.. Nucleic Acids Res, 32(19), 5851-5860.
Hautbergue G & Goguel V (2001) Activation of the cyclin-dependent kinase CTDK-I requires the heterodimerization of two unstable subunits.. J Biol Chem, 276(11), 8005-8013.
Hautbergue G & Goguel V (1999) The yeast C-type cyclin Ctk2p is phosphorylated and rapidly degraded by the ubiquitin-proteasome pathway.. Mol Cell Biol, 19(4), 2527-2534.
Mihaylov SR, Castelli LM, Lin Y-H, Gül A, Soni N, Hastings C, Flynn HR, Păun O, Dickman MJ, Snijders AP , Goldstone R et al () The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function. Nature Communications, 14(1).
Hautbergue G () A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine.
Cooper‐Knock J, Julian TH, Feneberg E, Highley JR, Sidra M, Turner MR, Talbot K, Ansorge O, Allen SP, Moll T , Shelkovnikova T et al () Atypical TDP ‐43 protein expression in an ALS pedigree carrying a p. Y374X truncation mutation in TARDBP. Brain Pathology.
Rust A, Partridge L, Davletov B & Hautbergue G () The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations. Toxins, 9(11), 344-344. View this article in WRRO
Patera F, Hautbergue GM, Wilson P, Evans PC, Ong ACM & Fragiadaki M () Ankhd1 enhances polycystic kidney disease development via promoting proliferation and fibrosis.

Chapters

Shelkovnikova TA & Hautbergue GM (2024) RNP granules in ALS and neurodegeneration: From multifunctional membraneless organelles to therapeutic opportunities, International Review of Neurobiology Elsevier

Conference proceedings papers

Cooper-Knock J, Moll T, Ramesh T, Castelli L, Shaw C, Al-Chalabi A, McDermott C, Hautbergue G & Shaw P (2019) 11.30 Mutations in the glycosyltransferase domain of GLT8D1 cause ALS. Journal of Neurology Neurosurgery & Psychiatry, Vol. 90(12) (pp e10)
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Shaw C, Al-Chalabi A, McDermott C, Hautbergue G & Shaw P (2019) MUTATIONS IN THE GLYCOSYLTRANSFERASE DOMAIN OF GLT8D1 CAUSE ALS. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 90(12) (pp E20-E21)
Alves-Cruzeiro JM, Karyka E, Bauer C, Coldicott I, Simon S, Hautbergue GM, Webster C, Myszczynska M, Higginbottom A, Ferraiuolo L & Azzouz M (2019) Gene editing as a potential therapeutic approach for ALS/FTD-associated with expanded C9ORF72. HUMAN GENE THERAPY, Vol. 30(8) (pp A22-A22)
Alves-Cruzeiro J, Karyka E, Bauer C, Coldicott I, Hautbergue G, Webster C, Castelli L, Simon S, Myszczynska M, Ferraiuolo L & Azzouz M (2019) AAV-mediated gene editing as a potential therapeutic approach for C9ORF72-linked ALS/FTD. HUMAN GENE THERAPY, Vol. 30(11) (pp A96-A96)
Allen SP, Hall B, Castelli L, Francis L, Woof R, Higginbottom A, Myszczynska M, Allen CF, Stopford MJ, Webster CP , De Vos K et al (2018) Inosine reverses motor neuron toxicity observed in amyotrophic lateral sclerosis patient astrocytes with an adenosine deaminase deficiency. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1859 (pp e23-e23)
Tazzyman S, Hautbergue G, Khurram A, Bryan M, Chantry A & Fragiadaki M (2015) The application of antibotoxsome, a novel cytotoxic conjugate, in cell death in in vitro models of pancreatic, liver, breast, cervical cancer, and myeloma.. Journal of Clinical Oncology, Vol. 33(15)

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..

Preprints

Lin Y-H, Dodd JE, Cutillo L, Castelli LM, Mihaylov SR, Norris K, Higginbottom A, Walsh MJ, Cooper-Knock J, Highley JR , Granata I et al (2024) GRASPS: a simple-to-operate translatome technology reveals omics-hidden disease-associated pathways in TDP-43-related amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
Burrows DJ, McGown A, Abduljabbar O, Castelli LM, Shaw PJ, Hautbergue GM & Ramesh TM (2024) RAN translation of C9ORF72-related dipeptide repeat proteins recapitulates hallmarks of motor neurone disease and identifies hypothermia as a therapeutic strategy in zebrafish, Cold Spring Harbor Laboratory.
Marchi PM, Marrone L, Brasseur L, Bousset L, Webster CP, Destro M, Smith EF, Walther CG, Alfred V, Marroccella R , Robinson D et al () C9orf72-derived poly-GA DPRs undergo endocytic uptake in iNPC-derived astrocytes and spread to motor neurons, Cold Spring Harbor Laboratory.
Mihaylov SR, Castelli LM, Lin Y-H, Gül A, Soni N, Hastings C, Flynn HR, Dickman MJ, Snijders AP, Bandmann O , Mortiboys H et al () The master energy homeostasis regulator PGC-1α couples transcriptional co-activation and mRNA nuclear export, Cold Spring Harbor Laboratory.
Castelli LM, Sanchez-Martinez A, Lin Y-H, Upadhyay SK, Higginbottom A, Cooper-Knock J, Gül A, Walton A, Montmasson C, Cohen R , Bauer CS et al () A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration, Cold Spring Harbor Laboratory.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Myszczynska MA, Heath PR, Livesey MR, Ning K, Azzouz M , Shaw PJ et al () Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
Cooper-Knock J, Moll T, Ramesh T, Castelli L, Beer A, Robins H, Fox I, Niedermoser I, Van Damme P, Robberecht W , Hardiman O et al () Mutations in the Glycosyltransferase Domain of GLT8D1 Cause Amyotrophic Lateral Sclerosis.

Research group

Dr Ya-Hui Lin (Post-doctoral Research Associate)
Dr Kamallia Mohd Imran (Post-doctoral Research Associate)
Dr Dave Burrows (Post-doctoral Research Associate)
Dr Monika Myszczynska (Post-doctoral Research Associate)
Dr Cleide Dos Santos Souza (Post-doctoral Research Associate)
Chloé Moutin (Research Technician)
Aytaç Gül (PhD student, primary supervisor)
Nikita Soni (PhD student, primary supervisor)
Sajid Shah (PhD student, primary supervisor)
Emma Bray (PhD student, primary supervisor)
Emily Tilley (PhD student, secondary supervisor)
Andreas Kosteletos (PhD student, secondary supervisor)
Duncan Garner (PhD student, secondary supervisor)
André Varcianna (PhD student, secondary supervisor)
Allan Shaw (PhD student, secondary supervisor)
Farah Mahiddine (PhD student, secondary supervisor)
Ouidad Khechaoui (PhD student, secondary supervisor)

Grants

Many thanks to the following funding bodies supporting our research:

Medical Research Council (MRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Engineering and Physical Sciences Research Council (EPSRC)
LifeArc
Motor Neurone Disease Association
The Royal Society
Alzheimer's Research UK
Industry: Takeda

Teaching activities

MBChB Research SSC Academic Lead for the Medical School (MED211)

MSc Advanced Cell and Gene Therapies course

- Module Lead Principles of Gene and Cell therapies (NEU61008)

- Module Lead Lab Research projects (MED625)

- Academic Drug Discovery case study (NEU61009)

- Journal club (NEU61011)

MSc in Translational Neuroscience and MSc in Translational Neuropathology courses:

- Introduction to RNA biology (MED620)
- RNA dysregulation in Amyotrophic Lateral Sclerosis (MED623)

- Introduction to translatomes (MED671)
- Laboratory research projects

Laboratory projects concerning the molecular mechanisms of neurodegeneration in MND/ALS are available during the Student Selected Component of Phase 2A medical students.

Outreach engagement with local primary and secondary schools and the public during Science week and Festival of the Mind and SITraN open days/symposium.

Professional activities and memberships

Invited and elected Fellow of the Royal Society of Biology (FRSB) in recognition of a prominent contribution to the advancement of the biological sciences (since 2019)
Member of the Biochemical Society (since 2013)
Editorial board member of the journal “RNA and Disease” (since 2014)
My Name’5 Doddie Foundation Grant Panel member (since 2023)
Member of the Department of Neuroscience Health and Safety Committee (since 2015)
Responsible and Holder of the Departmental licenses for radioactive work (since 2013)
PhD examination: (i) External examiner on 7 occasions (University College London, University of Oxford, King’s College London, Rhodes University in South Africa); (ii) Internal examiner on 6 occasions
Reviewing activities (since 2013): Grants: Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC), MND Association, Academy of Medical Sciences, MRC Foundation (MRF), European Research Council (ERC), French National Research Agency (ANR), French AFM Telethon, US National Science Foundation, Dutch ZonMw Vidi programs, Fondation Suisse de Recherche sur les Maladies Musculaires, Belgian Foundation against Cancer, etc.
Research articles and reviews: Nature, Nature Communications, Gene Therapy, Science Translational Medicine, Nucleic Acids Research, Neuron, EMBO J, Brain, Nature Methods, Nature Chemical Biology, Science Advances, Scientific Reports, etc.
Outreach activities in local schools and for public events in Sheffield (since 2013)

Research group collaborators

ALS and neurodegeneration: Prof Dame Pamela Shaw, Prof Mimoun Azzouz, Dr Richard Mead, Dr Tatyana Shelkovnikova, Dr Ryan West, Dr Suman De, Dr Johnathan Cooper-Knock, Prof Kurt De Vos and other colleagues (SITraN, University of Sheffield, UK); Dr Alexander Withworth (MRC Mitochondrial Biology Unit, University of Cambridge, UK); Prof Kung-Yao Chang (National Chung-Hsing University, Taiwan); Dr Adrian Isaacs (University College London Institute of Neurology, UK)
Structure determination of ribonucleoprotein complexes: Prof Frédéric HT Allain (Institute of Molecular Biology and Biophysics, ETH Zürich, Switzerland) and Dr Cyril Dominguez (Department of Molecular and Cell Biology, University of Leicester, UK)
Protein methylation and citrullination, mass spectrometry, quantitative proteomics: Prof Mark Dickman (Chemical and Biological Engineering, University of Sheffield, UK)
Neuropathology, ageing and senescence: Prof Steve Wharton and Dr Robin Highley (SITraN, University of Sheffield); Prof Ilaria Bellantuono (Clinical Medicine, University of Sheffield, UK).
Parkinson’s disease: Prof Oliver Bandmann and Prof Heather Mortiboys (SITraN, University of Sheffield, UK)

School of Medicine and Population Health