Imperial College London

Professor Richard Reynolds, BSc AKC PhD

Faculty of MedicineDepartment of Brain Sciences

Professor of Cellular Neurobiology
 
 
 
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Contact

 

+44 (0)20 7594 6668r.reynolds

 
 
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Location

 

E414Burlington DanesHammersmith Campus

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Summary

 

Summary

 

Graduated from King’s College, London University , with a BSc in Pharmacology (1978) and PhD in Neuropharmacology (1981). Joined Imperial College in 1986 and was awarded a Wellcome Trust Senior Research Fellowship in 1988. Professor of Cellular Neurobiology since 2000 in the Wolfson Neuroscience Laboratories, Division of Brain Sciences, on the Hammersmith Hospital Campus of Imperial College. Appointed Adjunct Professor of Neuroscience in the National Centre for Biomedical Engineering Sciences of the National University of Ireland Galway in 2009 and Visiting Professor at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore in 2015. Director of the UK Multiple Sclerosis Society Tissue Bank since 1998.

Professor Reynolds’ research focuses on understanding the pathogenetic mechanisms involved in demyelination and neurodegeneration in multiple sclerosis and the development of novel therapeutic pathways. This has involved extensive research on human brain tissue from the UK MS Society Tissue Bank, which he set up in 1998, and the development of novel models to investigate molecular pathways of disease. Through collaborations with the biopharmaceutical industry this work has led to a number of important translational approaches to treating clinical progression in MS.

Mechanisms of demyelination and neuronal loss in MS

Axonal damage and neuronal loss is now thought to be an early feature of MS pathology (Anderson et al, 2009; Kim et al, 2010) and evidence suggests that its accumulation may be the pathological correlate for the progression of disability. Recent evidence suggests a major role for neuronal loss in the cortical grey matter in MS (Magliozzi et al, 2007; Papadopoulos et al, 2009; Magliozzi et al, 2010). Therefore, we are using human tissues and experimental models of MS to investigate the mechanisms responsible for this neuronal loss. In collaboration with the group of Francesca Aloisi in Rome, we have demonstrated the involvement of ectopic meningeal lymphoid structures in cortical pathology in MS, in particular in sub-pial demyelination and neurodegeneration. The presence of these structures and associated pathology is associated with a more rapid and aggressive disease course (Magliozzi et al, 2007; Magliozzi et al, 2010; Howell et al, 2011, Choi et al, 2012). Our current studies are investigating the molecular nature of the mediators responsible for this pathology (Gardner et al, 2013).

Mechanisms of remyelination

Myelin repair in the adult CNS is thought to be brought about via the generation of new oligodendrocytes from quiescent progenitors, but very little is known about the signals that cause them to become reactivated in order to differentiate into oligodendrocytes for remyelination and to support their survival. We are investigating the characteristics of these cells in vitro using a combination of cellular and molecular techniques and are particularly interested in contact dependent signals from the axon that stimulate survival and process outgrowth. Recent studies in this laboratory (Palser et al, 2009) have demonstrated a role for the neural cell adhesion molecule (NCAM) in this process. 

Remyelination in the MS brain is suggested to fail at an early stage, although very little is known about the natural history of this repair process in the human brain. Our recent studies have indicated that remyelination can be extensive in MS despite a long disease course (Patani et al, 2007).

 


 

UK MS Tissue Bank

The UK MS Tissue Bank was set up at the beginning of 1998, funded by a 5-year grant from the UK MS Society, to provide a reliable source of post-mortem MS CNS material for researchers around the UK. We have developed extensive protocols for collection, dissection and storage of brain, spinal cord and CSF, to ensure that the tissue is of maximum use for a wide variety of experimental techniques (Durrenberger et al, 2010; 2012). This has proven to be extremely successful and we are now supplying tissue for research projects throughout the world. All tissue collected by the bank is obtained via a prospective donor scheme. In addition to research into optimizing the efficiency of our tissue banking, we are carrying out a number of studies looking at the best ways to characterise the variety of pathologies within MS tissue using combinations of histology, immunohistochemistry and molecular studies. The MS Tissue Bank is currently funded by a programme grant from the UK MS Society until 2014 and operates alongside the Parkinson’s Disease Society Tissue Bank.

Professor Richard Reynolds is the Scientific Director and principal grant holder for the UK Multiple Sclerosis Tissue Bank (www.ukmstissuebank.imperial.ac.uk) and grant holder for the UK Parkinson's Disease Society Tissue Bank (http://www.parkinsonstissuebank.org.uk/). Further information about tissue donation and requesting tissue samples for research can be found on the above web sites.

Selected Publications

Journal Articles

Magliozzi R, Fadda G, Brown RA, et al., 2022, "Ependymal-in" gradient of thalamic damage in progressive multiple sclerosis, Annals of Neurology, Vol:92, ISSN:0364-5134, Pages:670-685

Bates REJ, Browne E, Schalks R, et al., 2022, Lymphotoxin-alpha expression in the meninges causes lymphoid tissue formation and neurodegeneration, Brain, Vol:145, ISSN:0006-8950, Pages:4287-4307

Jayaraman A, Reynolds R, 2022, Diverse pathways to neuronal necroptosis in Alzheimer's disease, European Journal of Neuroscience, Vol:56, ISSN:0953-816X, Pages:5428-5441

Jayaraman A, Htike TT, James R, et al., 2021, TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus., Acta Neuropathologica Communications, Vol:9, ISSN:2051-5960, Pages:159-159

Magliozzi R, Pezzini F, Pucci M, et al., 2021, Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naive Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation, Cells, Vol:10

van Olst Y, Rodriguez-Mogeda C, Picon C, et al., 2021, Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration, Acta Neuropathologica, Vol:141, ISSN:0001-6322, Pages:881-899

Pardini M, Brown JWL, Magliozzi R, et al., 2021, Surface-in pathology in multiple sclerosis: a new view on pathogenesis?, Brain, Vol:144, ISSN:0006-8950, Pages:1646-1654

Picon C, Jayaraman A, James R, et al., 2021, Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter, Acta Neuropathologica, Vol:141, ISSN:0001-6322, Pages:585-604

Gallego-Delgado P, James R, Browne E, et al., 2020, Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier., PLOS Biology, Vol:18, ISSN:1544-9173, Pages:1-36

Wang J, Jelcic I, Muhlenbruch L, et al., 2020, HLA-DR15 molecules jointly shape an autoreactive T cell repertoire in multiple sclerosis, Cell, Vol:183, ISSN:0092-8674, Pages:1264-1281.e20

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