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

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 Prof. 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 Prof. 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 I am now Lecturer in Translational Neurobiology in SITraN, where I am setting up my research group.

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
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.

Professional Activities
  • 2012 - Society for Neuroscience, USA
  • 2011 - Delegate for the ALS/MND Research and Care Community Blog
  • 2008 - Biochemical Society, UK
  • 2008 - British Society for Cell Biology, UK
  • Reviewer for several journals, including Brain and Glia
  • Reviewer for several funding bodies, including the Motor Neurone Disease Association (MNDA) and Action Medical Research
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

L Ferraiuolo, K Meyer, T Sherwood, J Vick, S Likhite, AE. Frakes, C Miranda, L Braun, R Pineda, CE Beattie, C Askwith, DM McTigue, BK Kaspar. Oligodendrocytes contribute to motor neuron death in ALS via SOD1 dependent mechanism. In press PNAS.


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. Nature Medicine 22, 397–403 (2016) doi:10.1038/nm.4052


S Sun, Y Sun, S Ling, L Ferraiuolo, M McAlonis-Downes, Y Zou, K Drenner, Y Wang, D Ditsworth, S Tokunaga, A Kopelevich, BK Kaspar, C Lagier-Tourenne, and DW Cleveland. Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS. PNAS, 2015 Nov 30. pii: 201520639


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


L Ferraiuolo. The non-cell-autonomous component of ALS: new in vitro models and future challenges. Biochemical Society Transactions, September 2014, Vol. 42, No. 5, Pages 1270-1274


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 Frakes, BK Kaspar. Neural stem cells as a therapeutic approach for amyotrophic lateral sclerosis. Mol Ther 2013 Mar;21(3):503-5. Commentary.


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.