Malformations of the human neocortex are present in >1% of the general population and represent a major cause of developmental disabilities and severe epilepsies. My lab focuses on understanding the regulation of all processes of neurogenesis and neuronal migration in order to discover the biological mechanisms and therefore identify potential therapies for cortical malformations.
In order to achieve this, we will map the genome of patients that do not have mutations in the genes that are known to cause cortical malformations and investigate the molecular and cellular mechanisms underlying these diseases by loss- and gain-of-function in the mouse model and human cerebral organoids derived from induced pluripotent stem cells and fibroblasts from patients affected by malformations. In addition, we will characterize the functional aspects of these disorders by using our mouse/human models of cortical malformations.
In this way, we will be able to screen for several candidate genes identified from human patients as well as from known mouse models and assemble a network of genes and possible pathways responsible for cortical malformations.