When I started my PhD in the department of clinical genetics in the Erasmus MC, my ambition was to understand the molecular mechanisms underlying toxicity in neurodegenerative disorders and use this knowledge to develop RNA targeting strategies. Using neuronal cell models and mouse models I showed that a protein gain-of-function mechanism drives pathogenesis in the neurodegenerative CGG repeat expansion disorder FXTAS. Additionally, I demonstrated that RNA-targeting compounds have great potential to ameliorate FXTAS.
At the end of 2016, I moved to the LUMC to work on a different neurodegenerative disorder, Spinocerebellar ataxia type1 (SCA1). I showed that patient-derived cells recapitulate key pathological features of SCA1 pathogenesis providing a valuable tool for the identification of novel disease-specific processes. This model can be used for high throughput screenings to identify compounds which may prevent or rescue neurodegeneration in this devastating disease. My current research focuses on developing an AON-based therapy targeting the ataxin-1 transcript. I designed various antisense oligonucleotide-based intervention strategies and I am currently testing and optimizing their efficiency in newly developed patient-specific cell models.
Within the CureQ consortium, I will be working on WP1, determining the disease landscape for SCA1, and WP3, validating polyQ isogenic iPSC disease landscape with heterogenic iPSCs from phenotyped patients.