Professor Richard Mead
BSc, MSc, PhD
School of Medicine and Population Health
Professor of Translational Neuroscience
+44 114 222 2256
Full contact details
School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Profile
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2026 – present: Professor of Translational Neuroscience, Sheffield Institute for Translational Neuroscience
2018 – 2025: Senior Lecturer in Translational Neuroscience, Sheffield Institute for Translational Neuroscience
2017- 2025: Co-founder and Chief Scientific Officer, Keapstone Therapeutics (UoS spin-out)
2019 – 2023: Knowledge Exchange and Innovation Lead, Faculty of 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
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My research is dedicated to Translational Neuroscience, with a primary focus on identifying and validating novel therapeutic targets for Amyotrophic Lateral Sclerosis (ALS/MND) and other neurodegenerative disorders. My work bridges the gap between fundamental biology and clinical application, combining advanced preclinical modelling with innovative drug discovery strategies to develop new interventions.
My key areas of interest are in:
Drug Discovery and Development
The NRF2-ARE Pathway
A major focus of my lab is harnessing the NRF2 antioxidant pathway for neuroprotection. This includes the development of M102 (a dual NRF2/HSF-1 activator) which has obtained orphan drug designation and is now ready for Phase 1 clinical trials, and the co-founding of Keapstone Therapeutics to develop KEAP1 inhibitors.
AI-Augmented Discovery
I have collaborated extensively with industry partners like BenevolentAI to utilize artificial intelligence for identifying novel targets. This partnership has successfully nominated clinical candidates and identified repurposed drugs such as gefitinib and JAK inhibitors as potential ALS therapeutics. We are now working to incorporate AI driven drug discovery approaches (via collaboration with OpenFold) into our drug discovery
Gene and Stem Cell Therapies
Beyond small molecules, I am interested in cell and gene therapies, with recent projects evaluating ATXN2 gene therapy in vivo and the use of adipose-derived stem cells to protect motor neurons and reduce glial activation.
Innovative Biomarker Technology
In collaboration with Dr. James Alix, I have identified translational biomarkers such as CMAP which can be applied in both mouse models and humans and the use of Raman spectroscopy combined with electromyography (Optical EMG) as a sensitive, non-invasive tool for detecting muscle pathology and monitoring disease progression.
We have also developed mass spectrometry biomarkers of oxidative stress
Native Mass Spectrometry Imaging
Working with the University of Birmingham, we are applying cutting-edge mass spectrometry imaging to visualize protein-metal complexes (such as SOD1) directly in tissue, revealing new insights into proteinopathies in ALS.
Disease Mechanisms
My lab employs a diverse range of in vitro and in vivo models (SOD1, C9orf72, TDP-43) to dissect critical disease mechanisms. Recent work in collaboration with Dr Matt Livesey has identified a promising strategy to rebalance neuronal network properties in ALS.
- Publications
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Journal articles
- M102 activates both NRF2 and HSF1 transcription factor pathways and is neuroprotective in cell and animal models of amyotrophic lateral sclerosis. Molecular Neurodegeneration, 20. View this article in WRRO
- Glutathione oxidation in cerebrospinal fluid as a biomarker of oxidative stress in amyotrophic lateral sclerosis. Translational Neurodegeneration, 14(1). View this article in WRRO
- A bacterial artificial chromosome mouse model of amyotrophic lateral sclerosis manifests ‘space cadet syndrome’ on two FVB backgrounds. Disease Models & Mechanisms, 18(2). View this article in WRRO
- Maximizing the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 26(3-4), 322-330. View this article in WRRO
- In vivo raman spectroscopy of muscle is highly sensitive for detection of healthy muscle and highly specific for detection of disease. Analytical Chemistry, 96(40), 15991-15997. View this article in WRRO
- Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology. Nature Communications, 15. View this article in WRRO
- Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology. The Analyst, 149(9), 2738-2746. View this article in WRRO
- Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis. Translational Neurodegeneration, 12(1). View this article in WRRO
- Combining electromyography and Raman spectroscopy: optical EMG. Muscle & Nerve, 68(4), 464-470. View this article in WRRO
- 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. View this article in WRRO
- A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine, 15(685). View this article in WRRO
- 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, 54(3), 258-268. View this article in WRRO
- Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nature Reviews Drug Discovery, 22(3), 185-212. View this article in WRRO
- Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP. Brain Pathology, 33(1). 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, 66(3), 362-369. View this article in WRRO
- Caudal–rostral progression of alpha motoneuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Antioxidants, 11(5).
- 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, 55(2), 435-442. View this article in WRRO
- Confocal endomicroscopy of neuromuscular junctions stained with physiologically inert protein fragments of tetanus toxin. Biomolecules, 11(10).
- NRF2 as a therapeutic opportunity to impact in the molecular roadmap of ALS. Free Radical Biology and Medicine, 173, 125-141. View this article in WRRO
- 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
- Extensive phenotypic characterisation of a human TDP-43^Q331K transgenic mouse model of amyotrophic lateral sclerosis (ALS). Scientific Reports, 11(1). View this article in WRRO
- 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.
- Proteomic approaches to study cysteine oxidation: applications in neurodegenerative diseases. Frontiers in Molecular Neuroscience, 14. View this article in WRRO
- Author Correction: Female sex mitigates motor and behavioural phenotypes in TDP-43Q331K knock-in mice.. Sci Rep, 11(1), 11058.
- In vivo fiber optic raman spectroscopy of muscle in preclinical models of amyotrophic lateral sclerosis and Duchenne muscular dystrophy. ACS Chemical Neuroscience, 12(10), 1768-1776. View this article in WRRO
- 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(-), ---.
- 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.
- Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis.. Molecular neurodegeneration, 12(1), 85.
- 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.
- 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).
- 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.
- Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen.. Brain, 129(Pt 7), 1693-1709.
- Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target.. Biochim Biophys Acta, 1762(11-12), 1051-1067.
- 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.
- Examining iPSC derived motor neuron variability and genome stability monitoring as a solution. Scientific Reports, 15(1).
- TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD. Nature Neuroscience, 21, 552-563.
Conference proceedings
- Adipose derived stem cells for cell therapy of motor neuron disease (MND). HUMAN GENE THERAPY, Vol. 30(8) (pp A16-A16)
Preprints
- M102 activates both NRF2 and HSF1 transcription factor pathways and is neuroprotective in cell and animal models of amyotrophic lateral sclerosis, Springer Science and Business Media LLC.
- Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice, Cold Spring Harbor Laboratory.
- Artificial intelligence-augmented drug discovery identifies gefitinib as a potential treatment for ALS, Cold Spring Harbor Laboratory.
- M102, a combined NRF2 and HSF-1 activator for neuroprotection in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
- Maximising the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials, Cold Spring Harbor Laboratory.
- M102 activates both NRF2 and HSF1 transcription factor pathways and is neuroprotective in cell and animal models of amyotrophic lateral sclerosis. Molecular Neurodegeneration, 20. View this article in WRRO
- Research group
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Post-Doctoral Research Associates
- Dr Amelia Byers
- Dr Doaa Taha
Research Technicians
- Amandeep Kaur
- Chiara Sander
Current PhD Students
- Finbar Gaffey (Royal Commission of 1851 Scholarship)
- Viktoria Brachmaier (Royal Commission of 1851 Scholarship)
Former Staff and PhD students
- Dr Alannah Mole (Pre-Fellow, MNDA)
- Dr Marilina Douloudi (Field Application Scientist, MaxWell Biosystems)
- Dr Scott McKinnon (Post Doctoral Research Associate, University of Sheffield)
- Dr Sophie Badger (Post Doctoral Research Associate, University of Sheffield)
- Dr Amy Keerie (Post Doctoral Research Associate, University of Sheffield)
- Dr Martyna Matuszyk (Programme Manager, NIHR)
- Dr Ruth Thomas (Post Doctoral Research Associate, University of Sheffield)
- Dr Nazia Maroof (Biomarker Experimental Medicine Scientist, Roche)
- Dr Matthew Stopford (Senior Medical Writer, Helios Medical Communications)
- Dr Nora Markus (Lead Scientist, Nxera Pharma)
- Dr Nicole Stone (Lead Scientist External Drug Discovery, Medicines Discovery Catapult)
- Dr Trong Khoa Pham (Senior Technical Specialist, University of Sheffield)
- Dr Matthew Sellwood (Director at IQVIA)
- Dr Jodie Watkins (Senior Scientist, MSD)
- Dr Heledd Brown-Wright (Clinical Research Coordinator, 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 )
- Grants
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- 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
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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
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- Alzheimer’s Research UK: Chair, Drug Discovery Alliance Advisory Group (2025–present); Member (2020–2025).
- My Name’5 Doddie Foundation: Inaugural Chair, Research Review Committee (March 2023–December 2025).
- MND Drug Discovery & Development Roadmap: Expert Steering Group Member (2023). Co-authored international guidelines in partnership with the MND Association, My Name’5 Doddie Foundation, and Medicines Discovery Catapult.
- Medical Research Council (MRC): Panel Chair, Impact Acceleration Account (IAA) / Confidence in Concept Scheme (July 2019–2023).
- MND Association: Member, Biomedical Research Advisory Panel (BRAP) (April 2015–October 2019).
- Member of the British Pharmacological Society (2014–present) and British Neuroscience Association (2024–present).
- Peer Review: Grant reviewer for the MRC, BBSRC, Wellcome Trust, UKRI, LifeArc, MND Association, Parkinson’s UK, Fight MND, AriSLA, and the European Science Foundation.
- Current projects and collaborators
- AI-Driven Target Discovery and drug discovery: Machine learning for identification of novel targets and preclinical development in ALS.
- Collaborators: John Cooper-Knock, OpenFold.
- M102 Clinical Development: Progression of M102 (NRF2/HSF1 activator) for ALS.
- Collaborators: Aclipse Therapeutics, Prof. Pamela Shaw
- Cortical Hyperexcitability & Presynaptic Dysfunction: Investigating synaptic failure and network properties in ALS/FTD.
- Collaborators: Dr. Matthew Livesey, Dr. Kurt De Vos
- On-target Repositioning Candidates: Jakinibs as potential repurposing candidates for MND.
- Collaborators: LifeArc, Prof. Pamela Shaw, Prof. Chris McDermott.
- iPSC Screening Platforms: Development of iPSC-derived motor neuron screening and iPSC derived MN-Astrocyte co-cultures.
- Collaborators: LifeArc, Dr. Will, Stebbeds, Dr Sarah Jolly.
- Novel Disease Readouts (Optical EMG): Development of Raman spectroscopy combined with electromyography for detecting muscle pathology.
- Collaborators: Dr. James Alix
- Native Mass Spectrometry Imaging: Visualizing protein-metal complexes (e.g., SOD1) directly in preclinical and post-mortem ALS tissue.
- Collaborators: Dr. Helen Cooper and Dr. Oliver Hale (University of Birmingham), Dr. Robin Highley.
- Metabolic Defects: Investigating NRF2 pathway signalling and metabolic dysregulation in ALS.
- Collaborators: Dr. Scott Allen.
- AI-Driven Target Discovery and drug discovery: Machine learning for identification of novel targets and preclinical development in ALS.