About our research group/lab
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.
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.
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.
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.
A complete overview of publications can be found here:
Collaborations outside Erasmus MC
Funding & Grants
2014 JPNDSearching 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 NederlandRole of dipeptide repeat proteins in C9orf72-linked FTD using a zebrafish model.