Human genetics approaches in the past several years have led to the identification of a large number of genetic defects associated with familial and sporadic forms of ALS. In our research, we use these genetic defects as a starting point to dissect the disease mechanisms underlying ALS. Our studies concentrate on mouse, zebra fish and humanized cell models (iPSC) using an integrated approach involving molecular biology, cell biology, neuroanatomy, (in vivo) functional proteomics,
imaging, high-content screening, and mouse genetics. Major research lines in our pre-clinical work focus on the generation of new animal and cellular models for genetic defects identified in patients, determining the interactomes of aggregated proteins in ALS, unraveling how and why neuronal connectivity changes in AL, and the development of therapeutic approaches.