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Dr Ewout JN Groen

My research focuses on motor neuron diseases: I want to find out more about the mechanisms that cause these diseases and I want to contribute to finding new therapies.

Ewout JN Groen

Postdoctoral Researcher - Gillingwater Group

  • Hugh Robson Building
  • 15 George Square
  • Edinburgh, EH8 9XD

Contact details

Personal profile

  • 2015 – present Sir Henry Wellcome Postdoctoral Fellow, University of Edinburgh

  • 2014 – 2015 Postdoctoral researcher, Gillingwater lab, University of Edinburgh
  • 2008 – 2013 PhD in translational neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands
  • 2006 – 2008 MSc Neuroscience and Cognition, Utrecht University, Utrecht, the Netherlands
  • 2003 – 2006 BSc Biomedical Sciences, Utrecht University, Utrecht, the Netherlands

Research

Motor neuron diseases (MND) are neurological diseases caused by the death of specific nerve cells that control muscles (motor neurons). This causes progressive paralysis and leads to the early death of the patient. The most common childhood-onset MND is spinal muscular atrophy (SMA) and the most common adult-onset MND is ALS. As the death of motor neurons characterises both diseases, I think that similar changes in cellular pathways contribute to motor neuron death in both ALS and SMA.

SMA is caused by depletion of SMN protein because of homozygous deletion (or other deleterious variants) in SMN1. A second SMN gene -called SMN2- is almost identical to SMN1, however, due to aberrant splicing only produces a fraction of the full-length SMN protein that is normally derived from SMN1. This genetic defect has now long been known and has recently led to the development of nusinersen, an antisenseoligonucleotide that increases SMN protein levels by correcting SMN2 splicing. This treatment is particularly effective in young patients in which treatment was started as early as possible. Although the approval of nusinersen is a milestone for SMA patients and researchers, not all patients respond equally and many questions remain to be addressed to eventually be able to treat all patients effectively.

The questions I currently find most interesting and focus my research on are the following:

1) Motor neuron specificity. The cell-type that is mainly affected in SMA is the motor neuron, however, other tissues and cell-types are also affected. Why motor neurons are the most vulnurable to low levels of SMN remains to be determined.

2) Requirements for SMN expression in tissues and over time. Much research on SMA has focused on better understanding the molecular mechanisms that regulate splicing of the SMN2. However, how RNA levels are related to protein levels in different tissues and during development is still poorly understood. 

3) Cellular pathways affected by SMN depletion. Many cellular pathways have been shown to be affected by SMN depletion in SMA. However, it is unclear how these pathways are related and if processes can be identified that provide a mechanistic link between these pathways.

Recent publications

  • EJN Groen, K Talbot, TH Gillingwater, “Advances in therapy for spinal muscular atrophy: promises and challenges.” Nature Reviews Neurology 2018.
  • P Bernabò*, T Tebaldi*, EJN Groen*, FM Lane*, et al., “In vivo translatome profiling reveals early defects in ribosome biology underlying SMA pathogenesis.” Cell Reports 2017, 21(4);953-65.
  • AM Blokhuis*, M Koppers*, EJN Groen, et al., “Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways.” Acta Neuropathologica, 2016, 132(2);175-96
  • EJN Groen, TH Gillingwater, “UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration.” Trends in Molecular Medicine, 2015, 21(10);622-632.
  • EJN Groen, et al., “ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN.” Human Molecular Genetics, 2013, 22(18);3690-3704.
  • EJN Groen*, MA van Es*, et al., “FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands.” Archives of Neurology, 2010, 67(2);224-230.