Dr Laura Ferraiuolo PhDlaura_ferraiuolo

Lecturer in Translational Neurobiology

Department of Neuroscience
Sheffield Institute of Translational Neuroscience
University of Sheffield
Room B36
385a Glossop Road
Sheffield
S10 2HQ

Tel: +44 (0) 114 222 2257
Fax: +44 (0) 114 273 0547

Email: l.ferraiuolo@sheffield.ac.uk

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

Profile

Biography

I studied Biotechnology at the University of Milan, Italy. During my degree I completed a 2-year internship at the Mario Negri Institute under the supervision of Dr Caterina Bendotti, where I developed a deep interest in motor neuron disease (MND).

In 2005 I joined the Department of Neuroscience at the University of Sheffield, UK, and won the MND Association Prize studentship that funded my PhD under the supervision of Professor Dame Pamela Shaw and Dr Janine Kirby. During my PhD I used laser capture microdissection and microarray analysis to interrogate the pathways involved in the response of motor neuron to stress, from expression of mutant SOD1 to intense exercise (Journal of Neuroscience 2007 and Journal of Neurochemistry 2009).

I was then awarded the Peake Fellowship to investigate the crosstalk between motor neurons and astrocytes in MND using microarray analysis and cellular models (Brain 2011) in Sheffield at the Institute for Translational Neuroscience. I had the great opportunity to deepen my knowledge on glia and gene therapy in Prof Kaspar’s lab in Columbus, Ohio, USA from 2012 to 2014 when I was awarded the prestigious International Outgoing Marie Curie Fellowship funded by the European Union. In Professor Kaspar’s lab I had the opportunity to contribute to the development of new cell models to study ALS in vitro (Neuron 2014 and PNAS 2014) and explore different routes of delivery for gene therapy clinical trials in MND (Molecular Therapy 2013) and spinal muscular atrophy (SMA) (Molecular Therapy 2014).

At the end of 2014 I came back to Sheffield to complete my Marie Curie Fellowship and the study investigating the role of oligodendrocytes in MND (PNAS 2016).

Since the end of my Fellowship I have established my research team at SITraN, focussing on modelling the role of human glial cells in neurodegenerative diseases (EBioMedicine 2019). I am now Reader in Translational Neurobiology

Research Interests The main research focus of my research group is identifying the role of glia in neurodegenerative conditions, with particular interest in Motor Neurone Disease (MND). Our primary aim is to develop therapeutic strategies using gene therapy approaches.

In MND, like in many other neurodegenerative disorders, neuronal damage and death are the most striking signs of disease, however, our research, along with the work of others, has demonstrated that glia play an active role in neuronal degeneration.

We use various in vitro cell models, including primary cells and genetically reprogrammed human progenitor cells, to investigate the interaction between astrocytes and oligodendrocytes from patients affected by MND with neurons.

The main research tools and techniques used in my laboratory:

  1. Human astrocytes, oligodendrocytes and neurons derived from fibroblasts through genetic reprogramming
  2. Mouse stem cells expressing the green fluorescent protein under the Hb9 promoter, resulting in GFP+ motor neurons
  3. 2D and 3D Co-culture system to study the interaction between glia, neurones and other cell types
  4. Viral constructs to target specific therapeutic candidates for gene therapy approaches
  5. Gene expression profiling
  6. High-throughput drug screening for precision medicine approaches
Teaching Interests

I teach on the MSc courses in Translational Neuroscience, Translational Pathology and Molecular Medicine focussing on disease cell modelling and disease mechanisms. I also supervise MSc and BMedSci students during their research projects.

Research Team

Matthew Stopford, PhD

My desire to study molecular biology in a medical context was sparked whilst I was an undergraduate student studying Genetics at the University of Manchester. I completed my PhD in 2016 in the Sheffield Institute for Translational Neuroscience (SITraN), where I studied how a repeat expansion in the DNA may cause C9ORF72-related Amyotrophic Lateral Sclerosis (ALS). I am currently a post-doctoral research associate working with Dr Laura Ferraiuolo and Dr Richard Mead in collaboration with BenevolentAI, a biotechnology company based in London. BenevolentAI have created an artificial intelligence system to identify novel therapeutics for ALS, and I am validating any drug candidates for efficacy in both ALS patient-derived in vitro models, as well as in vivo models of ALS.

Nora Markus, PhD

I completed my BSc in Biological Sciences (Hons Neuroscience) at the University of Edinburgh, where I became interested in neuroprotection and neurodegeneration. Thus, I went on to do a PhD studying neuroprotective and neurodestructive Ca2+ signalling pathways in cortical neurons at the University of Edinburgh under the supervision of Prof. Giles Hardingham, which I completed in 2017. I am currently a postdoctoral research associate in the laboratories of Dr Laura Ferraiuolo and Dr Richard Mead. I am working in collaboration with the biotechnology company BenevolentAI, to test compounds they identify for treating glial toxicity in amyotrophic lateral sclerosis (ALS) in human ALS patient-derived neural cells in vitro and mouse ALS models in vitro and in vivo.

Monika Myszczynska, MSc

​I graduated from Keele University in 2013 with a BSc (dual hons) in English and Neuroscience and MSc in Neuroscience Research in 2014. ​As a part of my MSc project, I completed a placement at Albert-Ludwigs-Universität Freiburg, Germany, where I worked​ on a project investigating the role of neuropoietic cytokines on adult murine neural stem cells, with a focus on JAK-STAT pathway inhibition.​ After two years of working as a research technician in the Ferraiuolo lab, I am now studying towards a PhD in collaboration with BenevolentAI. My project aim is to unveil the modes of action of novel ALS drug candidates by combining translatome profiling and next-generation sequencing. Outside the lab, I am an active volunteer in fundraising, outreach and public engagement activities.

Noemi Gatto, MSc

I obtained my MSc in Biology Applied to Biomedical Research at the University of Milan. In 2014, I joined the Molecular Neurobiology group, led by Dr Caterina Bendotti at the Mario Negri Institute, where I evaluated the effects of an anti-inflammatory drug in in vitro and in vivo models of ALS. Since my strong interest in this neurodegenerative disorder, I decided to pursue a PhD in Sheffield, where I am investigating the role of wild-type SOD1 in sporadic ALS cases, under the supervision of Dr Laura Ferraiuolo.

Chloe Allen, BSc

In 2014, I graduated from the University of East Anglia with a BSc in Biological Sciences. During my Developmental Biology module in my final year, I learnt about how adult cells were being reprogrammed into induced pluripotent stem cells which I found fascinating. This led me into my position as a Research Assistant at the Wellcome Trust Sanger Institute from September 2014, contributing to the derivation of a large bank of iPSCs for the HIPSCI project.

In 2016, I was awarded the DiMeN DTP scholarship under the supervision of Dr Laura Ferraiuolo. My research project will investigate to possibility of moving towards a personalised medicine approach in Amyotrophic Lateral Sclerosis through the identification of drugs suited to patient genotype. I will investigate this using an in vitro model of astrocytes derived from the reprogramming of patient fibroblasts.

Andre Varcianna, MSc

​In 2014 I graduated from Coventry University with a BSc(Hons) in Medical and Pharmacological Sciences. During my final year I undertook a research project investigating the mechanism by which the bronchodilator ipratopium bromide induces cardiotoxicity. I continued to develop my passion for research by studying a Masters in Biomedical and Translational Medicine at the University of Liverpool, where I gained a particular interest in neurodegenerative diseases and stem cells. Most recently I have joined Dr Laura Ferraiuolo's lab as a research technician and am very keen to further investigate the causes of motor neuron disease.

Allan Shaw MSc

In 2014, I graduated from the University of Salford with a BSc (Hons) in Biology with Studies in the USA, during this degree I undertook an exchange programme to the University of Toledo, Ohio, USA. I then moved to Sheffield to undertake an MSc in Stem Cell and Regenerative Medicine. During the MSc I completed an extended research project under the supervision of Professor John Haycock, where I refined a 3D co-culture model of the epidermis, developed for toxicology testing.

After graduating in 2015, I joined the Centre for Stem Cell Biology within The University of Sheffield as a Research Technician under the joint supervision of Professor Peter Andrews, Professor Marcelo Rivolta and Dr Zoe Hewitt. Funded by the UK Regenerative Medicine Platform, I generated fully characterised banks of human pluripotent stem cells (hESC/iPSC) with a focus on developing clonal lines from mosaic populations with common genetic variance. I also developed a xeno-free version of Prof. Rivota’s established protocol for the generation of Otic Neural Progenitors, which aims to be fully-GMP compliant moving towards the clinic.

I have joined the lab group of Dr Laura Ferraiuolo as a Research Assistant to work on a collaboration with Pfizer Inc. and Prof Dame Pamela Shaw aiming to correlate in vitro astrocyte toxicity with disease pathology and clinical progression in C9ORF72-related Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).

Jannigje R Kok, MSc

I graduated from the University of Edinburgh in 2018 with an MScR in Neuroscience, following a BSc (hons) in Biomedical Sciences (Neuroscience) at the same university. My research interests are primarily focused on studying mechanisms of neurodegeneration in motor neuron diseases. For my master’s research project, I used array tomography to investigate synapse loss in the prefrontal cortex of mouse models of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) carrying mutations in the TARDBP gene. In 2018, I started my PhD in the Ferraiuolo lab group in collaboration with Prof El-Khamisy, funded by the MRC DiMeN DTP PhD programme, where I am currently studying whether astrocyte-induced DNA damage contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

Lai Mei Wan, Msc

In 2017, I graduated from The University of Manchester with a BSc (Hons) in Biochemistry. During my final year I conducted a research project on focal adhesion dynamics in cells grown on 2D and 3D culture. Following my degree, I decided to pursue a Masters in Cell and Gene Therapy at University College London (UCL), where I learnt about the potential uses of stem cells and gene editing for treating disease. During my time there, I became particularly interested in translational research and undertook a project on the use of combinatorial treatments for MYCN-amplified neuroblastoma at the UCL Great Ormond Street Institute of Child Health.

I am now working as a research technician in the Department of Neuroscience under the supervision of Dr Laura Ferraiuolo, where I am keen to further my research skills and contribute towards advancing the field of neurodegenerative diseases.

Cleide Souza, PhD

In 2008, I graduated from the Federal University of Bahia (UFBA), with a BSc in veterinary medicine. During my Master in Tropical Animal Science I had the opportunity to work with mouse and human neural cells derived from pluripotent stem cells as well as primary culture of neurons and glial cells. This led me into my PhD in “Morphological Sciences” at Federal University of Rio de Janeiro under the supervision of Professor Stevens Rehen, with a collaborative period at The Institute of Psychiatry, Psychology and Neuroscience at King’s College London in Professor Jack Price Lab. Here I used Human iPS Cells as Model of study for Neurodevelopment disorders such as Autism Spectrum Disorders and Schizophrenia.

After my PhD I undertook a post-doc in neuroimmunology at Laboratory of Neurochemistry where we investigated the inflammatory response and mechanisms of neurotoxicity in neurodegenerative disorders such as Parkinson and Alzheimer diseases. As part of the project I investigated the effect of compounds derived from plants as new alternative agents for treatment of these disorders to promote neurogenesis and synaptogenesis.

In 2016, I was awarded a Marie Curie Fellowship at the University of Sheffield, researching “The Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease, Marie Curie Industry-Academia Partnerships and Pathways (IAPP)”, where I used iPS as a disease modelling and drug screening platform for Alzheimer disease. Most recently I have joined Dr Laura Ferraiuolo’s lab as a Research Associate to work on a collaboration with AstraZeneca and Prof El-Khamisy’s team at the University of Sheffield. This project focuses on the neurotoxic properties of ALS patient astrocyte on human neurons derived from direct reprogramming of patient fibroblasts.

Sophie Nyberg, PhD

I became interested in drug delivery to the central nervous system (CNS) while studying for my BSc in Biomedical Science at the University of Sheffield. I enjoy interdisciplinary approaches to biological questions, and obtained my PhD in Nanomedicine from the University College London under the supervision of Prof. Giuseppe Battaglia. My PhD entailed using biocompatible polymer nanoparticles

(polymersomes) targeted across the blood-brain barrier as CNS drug delivery vehicles. I completed my first post-doc at the University of Toronto under the supervision of Dr. Alain Dabdoub, working on drug delivery across the blood-inner ear barrier.

I am now a post-doc in Dr Ferraiuolo’s and Mead’s teams collaborating with BenevolentAI on a project developing biomarkers for ALS and validating the mechanism of action of novel ALS drugs.

Marco Destro, MSc

In 2016, I graduated from the University of Trento with a BSc in Biomolecular Sciences and Technologies. This course provided for a 4 month experimental internship where I had the opportunity to join the Dulbecco Telethon Laboratory of Neurodegenerative Diseases (Prof. Maria Pennuto PhD) at CIBIO (Centre for Integrative Biology, Trento). During this internship, I studied the interaction between Cyclin-Dipendent Kinase 1 and Androgen Receptor in the context of Spinal and Bulbar Muscular Atrophy, and developed C. elegans lines stably expressing elongated PolyQ Androgen Receptor.

In 2018, I completed my MSc in Molecular Biology and Genetics at the University of Pavia. During the MSc, I carried out a 2-year experimental internship in the Laboratory for Research on Neurodegenerative Disorders (Dr. Daniela Rossi PhD) at the Clinical Scientific Institutes Maugeri (ICS Maugeri, Pavia), where I started working on the role of glia in MND.

In September 2018 I was awarded with the prestigious Marie Skłodowska-Curie fellowship (funded from the European Union's Horizon 2020 under grant agreement No 765704), and I joined the Euroneurotrophin ITN as a PhD student at the University of Sheffield; supervised by Dr. Laura Ferraiuolo and Prof. Dame Pamela Shaw. My PhD project is aimed at evaluating the neuroprotective effects of neurotrophins in novel patient models of Motor Neuron Disease (MND/ALS).

Professional Activities Membership of societies and scientific communities
  • 2019 – Local Organising Committee of the British Society for Gene and Cell Therapy meeting
  • 2017 – Editorial Board Member, Frontiers in Neurodegeneration
  • 2012 - Society for Neuroscience, USA
  • 2008 - Biochemical Society, UK
  • 2008 - British Society for Cell Biology, UK
Reviewer for several journals, including Cell Stem Cells, PNAS, Brain and Glia
Reviewer for several funding bodies, including the MRC, Motor Neurone Disease Association (MNDA) and The ALS Association
Enthusiastic participant to fundraising activities and public events.
For some of our past and future activities:
http://festivalofthemind.group.shef.ac.uk/stars-brain/
https://www.eventbrite.co.uk/e/cinescience-sheffield-tickets-38413545950
Current Projects
  1. The role of oxidative stress in astrocyte toxicity against motor neurones in MND: a drug screening for Nrf2 activators
  2. A high-throughput drug screening to identify novel therapeutic targets to silence astrocyte toxicity in MND via small chemical compounds
  3. Identifying the mechanisms underlying personalised drug-treatment and patient stratification in MND
  4. Metabolic dysregulation in astrocytes derived from Parkin-mutant patients (collaboration with Dr Mortiboys)
  5. The role of exosomal RNA in astrocyte toxicity

My research group is involved in several internal collaborations with other PIs within SITraN as well as international collaborations in the USA, Australia, Italy and Israel.

Our Funders
  • Thierry Latran Fondation
  • The Motor Neurone Disease Association (MNDA)
  • Parkinson’s UK
  • Medical Research Council (MRC)
Recent Publications

Varcianna A*, Myszczynska MA *, Castelli LM, O’Neill B, Kim Y, Talbot J, Nyberg S, Nyamali I, Heath PR, Stopford MJ, Hautbergue GM, Ferraiuolo L. Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS. EBioMedicine 2019 available online (https://doi.org/10.1016/j.ebiom.2018.11.067)

Allen SP, Hall B, Castelli L, Francis L, Woof R, Siskos AP, Kouloura E, Gray E, Thompson AG, Talbot K, Higginbottom A, Myszczynska M, Allen CF, Stopford MJ, Bauer CS, Webster CP, De Vos K, Turner MR, Keun HC, Hautbergue GM, Ferraiuolo L and Shaw PJ. Brain. 2019 Jan 28. doi: 10.1093/brain/awy353

Iannitti T, Scarrott JM, Likhite S, Coldicott IRP, Lewis KE, Heath PR, Higginbottom A, Myszczynska MA, Milo M, Hautbergue GM, Meyer K, Kaspar BK, Ferraiuolo L, Shaw PJ*#, Azzouz M*#. Translating SOD1 gene silencing towards the clinic: A highly efficacious, off-target free and biomarker-supported strategy for familial ALS. Mol Ther Nucleic Acids. 2018 Sep 7;12:75-88. doi:10.1016/j.omtn.2018.04.015

CF Allen, PJ Shaw, L Ferraiuolo. Can Astrocytes Be a Target for Precision Medicine?Adv Exp Med Biol. 2017;1007:111-128. doi: 10.1007/978-3-319-60733-7_7.

Hautbergue GM*, Castelli LM*, Ferraiuolo L*, Sanchez-Martinez A, Cooper-Knock J, Higginbottom A, Lin YH, Bauer CS, Dodd JE, Myszczynska MA, Alam SM, Garneret P, Chandran JS, Karyka E, Stopford MJ, Smith EF, Kirby J, Meyer K, Kaspar BK, Isaacs AM, El-Khamisy SF, De Vos KJ, Ning K, Azzouz M, Whitworth AJ, Shaw PJ. SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nat Commun. 2017 Jul 5;8:16063. doi: 10.1038/ncomms16063. *Equal contribution

Ferraiuolo L, Meyer K, Sherwood TW, Vick J, Likhite S, Frakes A, Miranda CJ, Braun L, Heath PR, Pineda R, Beattie CE, Shaw PJ, Askwith CC, McTigue D, Kaspar BK. Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):E6496-E6505. Epub 2016 Sep 29.

SW Song, CJ Miranda, L Braun, K Meyer,AE Frakes, L Ferraiuolo, S Likhite, AK Bevan, KD Foust, Michael J. McConnell, Christopher M. Walker, Brian K. Kaspar. Sustained expression of MHC class I protects motor neurons from ALS astrocyte-induced toxicity.In press Nature Medicine, 2015.

K Meyer*, L Ferraiuolo*, L Schmelzer, O Michels, V McGovern, L Braun, S Likhite, P Morales, J Ebel, K Foust, A Burghes, BK. Kaspar. Improving CSF delivery of AAV9-mediated gene therapy for SMA – a dose response study in mice and nonhuman primates. Mol Ther. 2014 Oct 31. *Equal contribution.

AE Frakes, L Ferraiuolo, AM Haidet-Phillips, L Schmelzer , L Braun, CJ Miranda, A Bevan, KD Foust, JP Godbout, PG Popovich, DC Guttridge, BK Kaspar. Microglia induce motor neuron death via the classical NF-κB pathway in inherited Amyotrophic Lateral Sclerosis. Neuron 2014 Mar 5;81(5):1009-23.

K Meyer, L Ferraiuolo, CJ Miranda, S Likhite, S McElroy, S Renusch, D Ditsworth, C Lagier-Tourenne, RA Smith, J Ravits, AH Burghes, PJ Shaw, DW Cleveland, SJ Kolb, BK Kaspar. Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. PNAS 2014 Jan 14;111(2):829-32.

KD Foust *, DL Salazar *, S Likhite *, L Ferraiuolo*, D Ditsworth *, H Ilieva, K Meyer, L Schmelzer, L Braun, DW Cleveland, BK Kaspar.Therapeutic AAV9-mediated suppression of mutant SOD1 slows disease progression and extends survival in models of inherited ALS. Mol Ther. 2013 Dec;21(12):2148-59 *The first five authors contributed equally to this work.

L Ferraiuolo, A Higginbottom, PR Heath, S Barber, D Greenald, J Kirby, PJ Shaw. Dysregulation of astrocyte-motor neuron cross-talk in mSOD1 related amyotrophic lateral sclerosis. Brain 2011 Sep;134(Pt 9):2627-41.

L Ferraiuolo, J Kirby, AJ Grierson, M Sendtner, PJ Shaw. Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nature Rev Neurol 2011 Nov;7(11):616-30. Review.

Also see

https://www.researchgate.net/profile/Laura_Ferraiuolo
https://publons.com/researcher/1663671/laura-ferraiuolo/