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Research group/lab  |  PI Prof. R. (Rob) Willemsen

Diseases of Unstable Repeat Expansion

More than 20 genetic diseases have been associated with unstable repeat expansion; the pathogenic mechanisms involve either loss of protein function or gain of function at the protein or RNA level.

About our research group/lab

Our research

Background information

Initially, the group focused on trinucleotide repeat disorders, in particular fragile X syndrome. Fragile X syndrome is among the commonest human single gene disorders, and is the leading cause of inherited cognitive disability. In 1991, this led to the discovery of an CGG expansion in the non-coding region of the fragile X mental retardation 1 (FMR1) gene in fragile X syndrome.

Overall aim

Fragile X syndrome and FXTAS.
Using both in vitro studies (primary neurons) and animal models (mouse and zebrafish), the research is aimed to investigate the cellular function of FMRP and the pathogenesis of the fragile X syndrome as well as the molecular mechanisms. Translational endpoints are being identified that can facilitate novel therapies for fragile X syndrome. In 2001, a late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), has been described resulting in tremor, ataxia, brain atrophy, cognitive loss, dementia, and early death in individuals carrying a premutation. The overall aim of our research is to further understand the molecular processes involved in FXTAS pathology and to use this knowledge to develop strategies to intervene in these processes.

fragile x syndrome

Frontaltemporal lobar degeneration / amyotrophic lateral sclerosis
The repeat expansion in the C9orf72 gene induces gain-of-function by either RNA or protein toxicity. The aim of this research line is (1) to study protein toxicity in neurodegeneration using zebrafish; (2) to identify pharmacological compounds to alleviate protein induced neuronal toxicity.

Frontotemporal lobar degeneration

Research focus areas

The identification of a gene involved in human disease is a first step on the long road to the understanding of the biological basis of the disease. The laboratory mouse is, for both practical and technical reasons, the mammal of choice in functional studies.

In the last decade, the zebrafish (Danio rerio) has been successfully applied as well to elucidate the etiology of human genetic diseases.

Our projects

Key Publications

A complete overview of publications can be found here:


Funding & Grants

  • 2014 JPND 

    Searching for therapeutic interventions in frontotemporal dementia with C9ORF72 repeat expansions in the presymptomatic stage.
  • 2014 ERA-Net project E-Rare (project coordinator)

    Preclinical approaches towards therapeutic intervention for FXTAS.
  • 2018 Alzheimer Nederland  

    Role of dipeptide repeat proteins in C9orf72-linked FTD using a zebrafish model.

Our team

Prof. Rob Willemsen and his team

Prof.dr. Rob Willemsen, group leader

Saif Haify MSc, Phd-student

Ruchira Mankoe BSc, research technician

Rob Verhagen BSc, research technician

Esmay van der Toorn BSc, research technician

Any questions?

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