Our mission is to identify the pathomechanisms of human genetic disease and develop new therapeutic strategies based on this knowledge.

The AMC laboratory of Genome analysis has a longstanding reputation in identification of disease genes. We use expression profiling and pathway analysis to dissect disease mechanisms. Genomics based drugs, like RNA antagonists are developed. To expedite this process, we also host the genetics core facility of the AMC.

Our research is focussed on neurodegenerative diseases, like peripheral neuropathies (Charcot-Marie-Tooth disease, CMT) and ponto-cerebellar hypoplasia (PCH), a fatal early onset neurodegenerative disease.

In this research we have identified many genes for neurogenetic diseases (CMT, ALS and PCH). Our strong link with the clinic allowed us to perform genotype-phenotype correlation. Genetic studies also showed that patients with severe neuropathies can have multiple mutations in different genes related to neuropathy. However, the contribution of additional mutations in monogenic disease causing genes is low, only a few cases show digenic inheritance. In our search for modifiers of peripheral neuropathies we identified the complement system as a major determinant for nerve regeneration. Both genetic defects of and pharmacological intervention in activation of the complement system has a major impact of regeneration of the injured brain and nerve. Our current research is aimed at dissecting the riole of the innate immune system in neuroinflammation and its relation to disease progression. In this way we we made substantial progress in understanding the factors that influence recovery of the nervous system after trauma.

The PCH research line led to the identification of tRNA processing in brain development and degeneration. In 2008 we identified the TSEN genes as cause for PCH, this was followed by the identification of other RNA processing genes like CLP1 and EXOSC3. Our research is now directed to identify the mechanisms by which defects in (t)RNA processing lead to neurodegeneretion. To this end iPS and zebrafish models are developed.
Effective start/end date01/02/2007 → …

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