Stem cells and Neurodegenerative diseases
Our research interests lie primarily in the area of stem cells and regenerative medicine. Since 2011, we have focused on elucidating the molecular and cellular mechanisms that cause neurodegenerative diseases, in particular Parkinson’s disease (PD), with the ultimate goal of developing effective therapies. By reprogramming human skin cells from monogenic cases of PD associated to LRRK2 mutations, as well as idiopathic PD, and applying in house developed direct differentiation methods to generate disease region-specific CNS cell types, we have shown that iPSC technology can be used to recapitulate PD-relevant disease-associated phenotypes and provided the first evidences that neurons with the genome of sporadic PD patients exhibited similar phenotypes than those from familial PD . Co-cultures with human iPSC-derived dopamine neurons and PD-specific astrocytes have revealed a non-cell autonomous contribution of glial cells to PD-related neurodegeneration. We also adopt gene editing approaches in our iPSC models to determine how specific targets influence protein aggregation and neuronal pathophysiology and to reveal mechanisms by which new protective genetic variants impact disease onset and progression. Recently, we are also developing advanced experimental in vitro models, such as brain-like organoids, that truly recapitulate the complexity of the human brain.