Genetica, spinocerebellaire ataxie


My research is focused on unraveling the genetics and biological pathways leading to various movement disorders with special attention to spinocerebellar ataxia (SCA) using the latest sequencing technologies and unique disease models. This line of research was initiated after my PhD, in which I used various gene mapping strategies to localize and identify novel disease genes for spinocerebellar ataxia in Dutch families. Upon the identification of a novel SCA disease gene, I was awarded a pre-doctoral fellowship to work in the laboratory of prof. dr. K. Fishbeck at NIH (Bethesda, USA) to unravel the functional consequence of mutations in the SCA14 disease gene, protein kinase C gamma. After my PhD graduation, I successfully continued this line of research as a postdoc in Dr Eric Reits' laboratory in the AMC (Amsterdam, the Netherlands).
In recent years, I have been at the forefront of the identification of novel SCA disease genes within Europe, and started to combine genetics with functional research. I have generated disease models for different SCA types including various cell models expressing mutant proteins as well as a transgenic fly model for SCA19 and transgenic mice mimicking SCA23 disease. These models are used to substantiate my genetic findings and to reveal the molecular mechanisms leading to cerebellar neurotoxicity and neurodegeneration.
My recent work identified an additional 7 novel SCA disease genes in a small subset of Dutch ataxia families. Bioinformatic analysis revealed that many of these disease proteins converge into only a few biological pathways. The identification of these pathways and its target are of major importance for future research will pave the way for the development of therapeutic interventions.