Dr Richard Mead
BSc, MSc, PhD
Neuroscience, School of Medicine and Population Health
Senior Lecturer in Translational Neuroscience
+44 114 222 2256
Full contact details
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
2018-present Senior Lecturer in Translational Neuroscience, Sheffield Institute for Translational Neuroscience
2017-present Co-Founder and Chief Scientific Officer - Keapstone Therapeutics (UoS spin-out)
2019- Feb 2023 present Knowledge Exchange and Innovation Lead- Faculty of Medicine, Dentistry and Health
2013 -2018: Kenneth Snowman-MND Association Lecturer in Translational Neuroscience
2010- 2013: SITraN Senior Research fellow in Translational Neuroscience, University of Sheffield, UK.
2005-2010: Postdoctoral Research Fellow, University of Sheffield, UK.
2002-2004: Pharmacology Team leader, Celltech/UCB, Cambridge, UK.
2001-2002: Postdoctoral research assistant, Department of Biochemistry, University of Wales College of Medicine, Cardiff, UK.
1998-2001: PhD (Neuroimmunology), University of Wales College of Medicine, Cardiff, UK.
- Research interests
Research focused on preclinical drug discovery in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS), frontotemporal dementia (FTD) and Parkinson’s disease. All stages from target identification to in vivo disease model testing and development of translational biomarkers for early clinical studies. Specific areas include:
- Pharmacological manipulation of in vitro and in vivo model systems to dissect mechanisms in MND and find new targets
- Small molecule drug development for inflammatory and oxidative stress targets including NRF2 pathway activators
- Improving screening methodologies, evolving new in vivo screening paradigms with improved welfare, reduced biological variation and faster throughput
- Identification of ‘translational’ biomarkers, applicable in both preclinical and clinical settings
- Investigating novel cell therapy paradigms in MND/ALS
A large proportion of the work in my group is conducted in collaboration with Pharma and Biotech.
I am also co-founder and CSO of Keapstone Therapeutics, a spin-out from the University of Sheffield investigating KEAP1 inhibitors for disease modification in ALS and PD.
- 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.
- A cell-penetrant peptide blocking C9ORF72 -repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine, 15(685).
- Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP. Brain Pathology. View this article in WRRO
- Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy: An assessment using the mdx model and human muscle. Muscle and Nerve. View this article in WRRO
- Caudal–rostral progression of alpha motoneuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Antioxidants, 11(5).
- Extensive phenotypic characterisation of a human TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis (ALS). Scientific Reports, 11(1).
- Confocal endomicroscopy of neuromuscular junctions stained with physiologically inert protein fragments of tetanus toxin. Biomolecules, 11(10).
- The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS. Scientific Reports, 11. View this article in WRRO
- NRF2 as a therapeutic opportunity to impact in the molecular roadmap of ALS. Free Radical Biology and Medicine, 173, 125-141.
- Adipose-derived stem cells protect motor neurons and reduce glial activation in both in vitro and in vivo models of ALS. Molecular Therapy — Methods & Clinical Development, 21, 413-433. View this article in WRRO
- Author Correction: Female sex mitigates motor and behavioural phenotypes in TDP-43Q331K knock-in mice (Scientific Reports, (2020), 10, 1, (19220), 10.1038/s41598-020-76070-w). Scientific Reports, 11(1).
- In Vivo Fiber Optic Raman Spectroscopy of Muscle in Preclinical Models of Amyotrophic Lateral Sclerosis and Duchenne Muscular Dystrophy.. ACS Chem Neurosci.
- Female sex mitigates motor and behavioural phenotypes in TDP-43Q331K knock-in mice. Scientific Reports, 10(1).
- Applications of machine learning to diagnosis and treatment of neurodegenerative diseases. Nature Reviews Neurology, 16, 440-456. View this article in WRRO
- Sarm1 deletion suppresses TDP-43-linked motor neuron degeneration and cortical spine loss. Acta Neuropathologica Communications, 7. View this article in WRRO
- Publisher Correction: TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD. Nature Neuroscience, 21(8), 1138-1138.
- TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD. Nature Neuroscience, 21, 552-563. View this article in WRRO
- Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis.. Molecular neurodegeneration, 12(1), 85. View this article in WRRO
- Early detection of motor dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis (ALS) using home cage running wheels.. PloS one, 9(9), e107918. View this article in WRRO
- S[+] Apomorphine is a CNS penetrating activator of the Nrf2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis.. Free Radic Biol Med, 61, 438-452.
- Optimised and Rapid Pre-clinical Screening in the SOD1(G93A) Transgenic Mouse Model of Amyotrophic Lateral Sclerosis (ALS). PLOS ONE, 6(8). View this article in WRRO
- Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy.. Sci Transl Med, 2(35), 35ra42.
- Guidelines for preclinical animal research in ALS/MND: A consensus meeting. AMYOTROPH LATERAL SC, 11(1-2), 38-45.
- An in vitro screening cascade to identify neuroprotective antioxidants in ALS.. Free Radic Biol Med, 46(8), 1127-1138.
- Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target.. Biochim Biophys Acta, 1762(11-12), 1051-1067.
- Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen.. Brain, 129(Pt 7), 1693-1709.
- Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis.. Lab Invest, 84(1), 21-28.
- Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis. Laboratory Investigation, 84(1), 21-28.
- Rat T cells express neither CD55 nor CD59 and are dependent on Crry for protection from homologous complement.. Eur J Immunol, 32(2), 502-509.
- The membrane attack complex of complement causes severe demyelination associated with acute axonal injury.. J Immunol, 168(1), 458-465.
- The membrane attack complex (MAC) of complement causes severe demyelination in vivo. Evidence from C6 deficient rats. Immunopharmacology, 49(1-2), 7-7.
- Molecular cloning, expression and characterization of the rat analogue of human membrane cofactor protein (MCP/CD46).. Immunology, 98(1), 137-143.
- Molecular cloning and characterisation of the rat homologue of human membrane cofactor protein. Molecular Immunology, 35(6-7), 377-377.
- Mannose-binding lectin alleles in a prospectively recruited UK population. LANCET, 349(9066), 1669-1670.
electromyographyand Raman spectroscopy: optical EMG. Muscle & Nerve.
- Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nature Reviews Drug Discovery.
- Non‐negative matrix factorisation of Raman spectra finds common patterns relating to neuromuscular disease across differing equipment configurations, preclinical models and human tissue. Journal of Raman Spectroscopy.
- Proteomic Approaches to Study Cysteine Oxidation: Applications in Neurodegenerative Diseases. Frontiers in Molecular Neuroscience, 14.
- Assessment of the Precision in Measuring Glutathione at 3 T With a MEGA‐PRESS Sequence in Primary Motor Cortex and Occipital Cortex. Journal of Magnetic Resonance Imaging.
- Research group
Post-Doctoral Research Associates
- Dr Amy Keerie
- Dr Ali Malik (With Dr James Alix)
- Dr Martyna Matuszyk
- Dr Alannah Mole
- Dr Ruth Thomas
- Tania Atienzar
- Chiara Sander
- Tyler Wells
- Ailsa Williams
Current PhD Students
- Marilina Douloudi (Neuroscience Institute Scholarship)
- Finbar Gaffey (Royal Commission of 1851 Scholarship)
- Scott McKinnon (UoS/Industry Funded Scholarship. Collaboration, with SoseiHeptares)
- Sophie Badger (Staff candidate MNDA funded, Secondary supervisor; PI: Dr James Alix)
Former Staff and PhD students
- Dr Nazia Maroof (Biomarker Experimental Medicine Scientist, Roche)
- Dr Matthew Stopford (Medical Writer, Helios Medical Communications)
- Dr Nora Markus (Senior Scientist, Mission Therapeutics)
- Dr Nicole Stone (Associate Scientist, Compass Pathways)
- Dr Trong Khoa Pham (Post Doctoral Research Associate, University of Sheffield)
- Dr Matthew Sellwood (Associate Director at IQVIA)
- Dr Jodie Watkins (Senior Scientist, MSD)
- Dr Heledd Brown-Wright (Postdoctoral Research Fellow, University of Queensland)
- Dr Yuri Ciervo (Senior Postdoctoral Fellow, Università degli Studi di Padova
- Dr Maria Plesia (Teacher Training, Sheffield Hallam University)
- Ms Amisha Parmar (PhD scholarship, University of Turin)
- Ms Shivani Suresh (DPhil scholarship, University of Oxford )
- Medical Research Council
- Parkinson’s UK
- Fight MND
- ALS Association (US)
- Motor Neuron Disease Association, UK
- University of Sheffield IP development and commercialisation fund
- Various Industry funded projects
- Teaching activities
I teach and co-lead a module on the MSc course in Translational Neuroscience and lead a module on the Masters course in Advanced Therapies running in SITraN. My teaching focusses on preclinical study design, analysis of motor function, statistics and drug discovery.
- Professional activities and memberships
- Panel Chair My Name’5 Doddie Foundation Research Review Committee Mrach 2023 to present
- Expert Steering Group member of the MND drug discovery and development (MND-DDD) roadmap with the MND Association, My Name’5 Doddie Foundation and Medicines Discovery Catapult
- Alzheimer’s Research UK Drug Discovery Alliance Advisory Group member Jan 2020- present
- Member of the EU COST action BenBedPhar- Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases
- PI and Panel Chair – MRC Impact Acceleration Account, University of Sheffield July 2019 –present
- MNDA Biomedical Research Advisory panel (BRAP) member April 2015 –October 2019
- Full Member, British Pharmacological Society
- Grant reviewer for MND association, MRC, BBSRC, Welcome Trust, UKRI
- Current projects and Collaborators
- CAR Treg cell therapy in ALS: Quell Therapeutics, Professor Pamela Shaw
- Machine learning for identification of novel targets and preclinical development in ALS: Benevolent AI, Prof Laura Ferraiuolo
- mGlu5 in ALS: SoseiHeptares Therapeutics
- Development of M102 for ALS, Aclipse Therpaeutics, Prof Pam Shaw, Prof Laura Ferraiuolo
- Standardisation of iPSC derived motor neuron screening platforms for ALS; LifeArc, Dr Zhi Yao
- miRNA-adapted shRNA technology for Gene targeted Therapy in ALS: Drishti Discoveries
- Cortical Hyperexcitability in ALS: Dr Matthew Livesey, University of Sheffield
- Development of novel readouts of disease progression in preclinical models: Dr James Alix, University of Sheffield
- Ambient native mass spectrometry imaging in ALS preclinical and post-mortem tissue: Dr Helen Cooper and Dr Oliver Hale, University of Birmingham. Dr Robin Highley, University of Sheffield
- Metabolic defects in ALS related to NRF2 pathway signalling: Dr Scott McKinnon, University of Sheffield
- Axonal Transport in ALS: Dr Kurt DeVos, Dr Andrew Grierson, University of Sheffield
Author on 38 published patents and patent applications in 5 patent families:
- Method for the treatment of Multiple Sclerosis by Inhibiting IL17 activity. Inventors Christie MI, Mead RJ, Robinson MK, Rapecki, SE. (2005) EP1687026 2006-08-09. WO2005051422. CA2544920. AU2004292393.
- Benzophenone Compounds. Inventors Shaw P, Mead R, Higginbottom A, Barber SC (2009). Publication number WO2009081141 . Describes compounds that inhibit oxidative stress in an in vitro model of MND
- Therapeutics for neurological disorders. Inventors Shaw P, Mead R, Higginbottom A, Barber SC (2010). Publication number WO2010046710 (A1) describing NRF2 activating compounds for treatment of neurodegenerative diseases.
- 'Treatment of Neurodegenerative Diseases' Richard Mead, Laura Ferraiuolo, Peter Richardson (30/03/2017). WO2017051188 University of Sheffield and BenevolentAI. Describes methods for the prevention and treatment of neurodegenerative diseases, in particular motor neuron diseases such as amyotrophic lateral sclerosis (ALS).
- ‘Treatment of Neurological Diseases’ Richard Mead, Pamela Shaw, Claude Ogoe, Ning Shan, Laura Ferraiuolo (23/4/2020) WO2020/081973 A1 Aclipse One Inc and University of Sheffield