Dr Richard Mead
BSc, MSc, PhD
Neuroscience, School of Medicine and Population Health
Senior Lecturer in Translational Neuroscience
r.j.mead@sheffield.ac.uk
+44 114 222 2256
+44 114 222 2256
+44 114 222 2278
(Administrator: Heather Cartledge)
Sheffield Institute for Translational Neuroscience (SITraN)
Full contact details
Dr Richard Mead
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Profile
-
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 - 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
-
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.
- Publications
-
Journal articles
- 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.
- Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology. The Analyst. View this article in WRRO
- Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis. Translational Neurodegeneration, 12(1). 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.
- 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.
- Mass spectrometry imaging of SOD1 protein-metal complexes in SOD1G93A transgenic mice implicates demetalation with pathology. Nature Communications, 15(1).
- Combining
electromyography and 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.
Conference proceedings papers
- Adipose derived stem cells for cell therapy of motor neuron disease (MND). HUMAN GENE THERAPY, Vol. 30(8) (pp A16-A16)
Preprints
- Glutathione Oxidation in Cerebrospinal Fluid as a Biomarker of Oxidative Stress 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.
- 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.
- 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
Research Technicians
- 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 )
- Grants
-
- 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
Patents
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