Anna Williams (BSc, MB ChB, MRCP, PhD, FRCP)

Group Leader, Professor of Regenerative Neurology and Honorary Consultant Neurologist

Background

I first studied medicine at Edinburgh University with an intercalated degree in pathology. After a few years as a junior doctor I did a PhD with Prof. Peter Brophy studying Periaxin in human peripheral neuropathy, leading to the genetic description of CMT4F. After a few more years as a Neurology trainee, I went to Paris to the laboratory of Prof Catherine Lubetzki, where I moved my itnerest in myelin into the central nervous system and into brain neuropathology and multiple sclerosis. Returning from France, I completed my training as a neurologist, and gained a Wellcome Trust Intermediate Fellowship to start my own group in Edinburgh, with a honorary consultant neurologist position on the side. A Scottish Senior Clinical Fellowship followed this after 5 years, with a personal chair in Regenerative Neurology in 2016.

Qualifications

B.Sc. (Med. Sci.) Pathology (1st Class)

MB ChB (Honours) University of Edinburgh

M.R.C.P. (U.K.)

Ph.D. University of Edinburgh

F.R.C.P. (UK)

Responsibilities & affiliations

Research group: with 14 members researching white matter pathology

Clinical work:  honorary consultant neurologist, with a busy MS clinic in the Anne Rowling Regenerative Neurology clinic at the Royal Infirmary of Edinburgh

Director of the Wellcome Trust Translational Neuroscience PhD programme

Member of the CRM Postgraduate committee

Member of the MRC  Neurosciences and Mental Health Board from April 2020

Scientific Advisory Committee of the French MS Society ARSEP

Grant Panel member for MS Society UK

Co-chair of the scientific advisory committee to the Clinical trials Platform for the MS Society UK

Scientific Ambassador for the MS Society, UK

Founder of WREN -work shadowing scheme for senior academic women

 

Undergraduate teaching

I teach medical students in their clinical years, and honours students on two final year courses.

Open to PhD supervision enquiries?

Yes

Current PhD students supervised

Ana-Maria Rondelli (PhD student)

Sophie Quick (PhD Student)

Foteini Tsouki (PhD Student)

Nina Lydia Kazakou (PhD Student)

Sunniva Boestrand (PhD student)

 

Past PhD students supervised

Hui Zhang

Jolanda Muenzel

Rikesh Rajani

Elitsa Peeva

Catriona Ford

Sally Vanden Hehir

Research summary

The Williams group is interested in how myelin in the brain works in health and in disease, with a focus on human neuropathology, particularly multiple sclerosis and cerebral small vessel disease.

In the brain and spinal cord, nerves are covered by an insulating sheath of membrane called a myelin sheath. This allows fast transmission of electrical impulses and protects and maintains the nerve. In multiple sclerosis (MS), patches of demyelination occur, where these myelin sheaths are damaged and stripped off the nerve. This causes neurological symptoms such as paralysis, sensory changes and blindness. Replacement of these myelin sheaths (remyelination) can happen in MS, which can restore nerve function. This is generally inefficient, and often a scar forms instead, causing a long-term problem for the patient. Remyelination is carried out in part by by oligodendrocyte precursor cells which are attracted to the damaged area, make contact with nerves, mature and form myelin sheaths to replace those that are damaged. A failure of remyelination can occur with a problem at any one of these steps. If we can understand the mechanisms of each step, we may be able to manipulate them to improve the efficiency of remyelination. 

We also know that oligodendrocytes in the brain are heterogeneous, suggesting that different types have different functions and that the proportion of these types is skewed in MS compared to control human brains. This may suggest that the efficiency of remyelination in the context of such diseases may be different due to this skew and that righting this difference may help remyelination.

We want to understand why remyelination fails in Multiple Sclerosis, why neurodegeneration occurs and to improve the efficiency of remyelination.

To study this we use in vitro and ex vivo cultures from rodents and use human ES derived cells, human post mortem tissue and in vivo rodent and zebrafish models. We seek to understand better the remyelination process (often using imaging), and find targets to be able to manipulate it, using both candidate and screening approaches. We manipulate levels of molecules of interest with recombinant proteins, lentiviral transduction and using transgenic animals. 

Oligodendrocytes are important in other diseases besides MS, and we also study cerebral small vessel disease (SVD) which is common, important as a cause of dementia and stroke, yet relatively understudied. Here, we have recently discovered that dysfunctional endothelial cells are the key problem, secreting molecules preventing maturation of oligodendrocyte precursor cells into mature myelinating oligodendrocytes, causing white matter vulnerability. We have uncovered genetic changes which provoke endothelial cell dysfunction and cause SVD in a rodent model and are associated with the disease in humans. Reversing this endothelial dysfunction can reverse the pathology in a rat model. 

We want to better understand how dysfunctional endothelial cells affect oligodendroglia and myelin, causing the symptoms of the disease and how to reverse it.

To do this we use in vitro and ex vivo cultures from humans and rodents, human and rodent post mortem tissue and in vivo rat models, manipulating pathology using drugs, viruses and molecular biology techniques, imaging at light and electron microscopy level.  

Current research interests

1) Understanding mechanisms of remyelination in Central Nervous System (CNS) repair. We investigate a) which signals in the oligodendrocyte precursor cell (OPC) microenvironment direct their activation, migration and maturation for repair, b) how OPCs themselves can be manipulated to ensure more efficient repair c) how OPCs interact with other cells, including axons via synapses in the context of demyelination and remyelination, using a hierarchy of in vitro and in vivo models and d) how oligodendroglia are functionally heterogeneous, how this alters in disease and how we can model this in the lab. 2) Understanding mechanisms of cerebral small vessel disease (SVD). We investigate a) the crosstalk between endothelial cells and oligodendroglia in health and in the context of small vessel disease in humans and animal models, b) how dysfunctional endothelial cells which are dysfunctional change at the ultrastructural and functional level and c) whether we can better model this in a rat model of SVD.

Past research interests

Recent publication Our group recently published on the therapeutic potential of drugs to reverse endothelial dysfunction in the treatment of Small Vessel Disease, a major cause of dementia and stroke. To obtain free access to this publication, follow the links below.  Rajani et al (2018). Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats. Science Translational Medicine  04 Jul 2018: Vol. 10, Issue 448, eaam9507. DOI: 10.1126/scitranslmed.aam9507 

Knowledge exchange

We are involved in MS Society UK events, Science Festivals, teaching in schools and to teachers, art workshops and much more!

Affiliated research centres

  • MRC Centre for Regenerative Medicine
  • Institute for Regeneration and Repair
  • Centre for Discovery Brain Sciences

Current project grants

2016-2019: MS Society project grant, “Is Fractalkine (CX3CL1) a master regulator of remyelination in MS? £254k
2017-2019: MRC Research Grant, “Transplantation of "super-OPCs" to improve central nervous system remyelination” £300k
2018-2020: Roche Transcriptomics in MS brain ~£600k
2018-2022: Dementia Research Initiative funding (co-applicant)
2018-2020 MRC funding for Human Cell Atlas project – Human oligodendrocyte heterogeneity £450k
2019-2022 MRC/MS Society UK - Do adult human oligodendrocytes remyelinate poorly and can we change this to better treat progressive multiple sclerosis? £600k
2020-2022 Roche Postdoctoral fellowship £300k

Past project grants

MRC UK Regenerative Medicine Platform - Exploring the Stem Cell Niche Hub - Co-applicant, with Hub receiving £5.6 million. Starts Nov 2013 for 5 years.
Scottish Senior Fellowship – May 2013-2017 £330k CSO - Targeting OPC migration towards remyelination therapies in multiple sclerosis May 2013. 12 months. £95k.
Wellcome Trust Intermediate Fellowship - Semaphorins in the control of remyelination in multiple sclerosis– May 2008- May 2013 - £824,795.
Co-applicant for CSO grant with Prof. Steve Anderton - Probing regulatory T cells in multiple sclerosis brain Jan 2011-July 2012 - £165k.
Wellcome Trust Institutional Strategic Support Fund (WT-ISSF)- Highly multiplexed single-cell RNA sequencing with Dr Keisuke Kaji and Dr Sally Lowell – June-Sept 2012 - £20k
Wellcome Trust Institutional Strategic Support Fund (WT-ISSF) - Label-free imaging of compact myelin; enabling high-throughput screens for novel remyelination therapies – with Prof. Alistair Elfick, Dr Rabah Mouras, School of Engineering, and Prof. Charles ffrench-Constant July -Nov 2012 - £50k
Alzheimer’s Research UK Pilot Grant, Three-dimensional modelling of endothelial cell dysfunction in cerebral small vessel disease. 2016-2017 £50k
GSK - CNS slice cultures as a tool for remyelination research – starts April 2015 for 2 years. £350k
Sanofi-Genzyme - Identification of selective and potent inhibitors of the Semaphorin 3A Receptor Neuropilin-1 interaction on oligodendrocyte precursor cells to promote remyelination in Multiple Sclerosis – March 2015 for 2 years.
MS society innovative grant - Optogenetic cell ablation in a focal CNS demyelination model in slice cultures – starts January 2015 for 1 year. £40k

View all 48 publications on Research Explorer

2016-2019: MS Society project grant, “Is Fractalkine (CX3CL1) a master regulator of remyelination in MS? £254k

2017-2019: MRC Research Grant, “Transplantation of "super-OPCs" to improve central nervous system remyelination” £300k

2018-2020: Roche Transcriptomics in MS brain ~£600k

2018-2022: Dementia Research Initiative funding (co-applicant)

2018-2020  MRC funding for Human Cell Atlas project – Human oligodendrocyte heterogeneity £450k

2019-2022 MRC/MS Society UK  -  Do adult human oligodendrocytes remyelinate poorly and can we change this to better treat progressive multiple sclerosis? £600k

2020-2022 Roche Postdoctoral fellowship £300k

MRC UK Regenerative Medicine Platform - Exploring the Stem Cell Niche Hub - Co-applicant, with Hub receiving £5.6 million. 2013-2018. 

Scottish Senior Fellowship – May 2013-2017 £330k CSO - Targeting OPC migration towards remyelination therapies in multiple sclerosis 2013-14  £95k. 

Wellcome Trust Intermediate Fellowship - Semaphorins in the control of remyelination in multiple sclerosis– 2008-2013 - £824,795. 

Co-applicant for CSO grant with Prof. Steve Anderton - Probing regulatory T cells in multiple sclerosis brain Jan 2011-July 2012 - £165k.

Alzheimer’s Research UK Pilot Grant, Three-dimensional modelling of endothelial cell dysfunction in cerebral small vessel disease. 2016-2017 £50k

GSK - CNS slice cultures as a tool for remyelination research – starts April 2015 for 2 years. £350k

Sanofi-Genzyme - Identification of selective and potent inhibitors of the Semaphorin 3A Receptor Neuropilin-1 interaction on oligodendrocyte precursor cells to promote remyelination in Multiple Sclerosis – march 2015 for 2 years.

MS society innovative grant - Optogenetic cell ablation in a focal CNS demyelination model in slice cultures –  2015 for 1 year. £40k

  • Dr Pascale Durbec, University of Marseille
  • Prof Goncalo Castelo-Branco, Karolinska Institute
  • Dr Gioele La Manno, Lausanne
  • Prof Robin Franklin, University of Cambridge
  • Prof Charles ffrench-Constant, University of Edinburgh
  • Dr Veronique Miron, University of Edinburgh
  • Dr Catalina Vallejos, University of Edinburgh
  • Dr Alison Hulme, University of Edinburgh
  • Dr Scott Webster, University of Edinburgh
  • Dr Tara Spires-Jones, University of Edinburgh
  • Prof Joanna Wardlaw, University of Edinburgh
  • Prof Colin Smith, University of Edinburgh
  • Prof Siddarthan Chandran, University of Edinburgh
  • Prof David Lyons, University of Edinburgh
  • Prof Steve Pollard, University of Edinburgh