Functional Human Brain Models of Disease
Our lab is primarily focused on the development new approaches for studying human brain development and uncovering the mechanisms of neuropsychiatric disorders. To achieve this, we derive induced pluripotent stem cells (hiPSC) from patients and we have pioneered approaches for deriving neural cell types in vitro.
We are pursuing questions in three major inter-related areas:
First, we are interested in understanding human brain development, and in particular deciphering what makes human corticogenesis unique. We have developed methods for generating from hiPSC a tridimensional (3-D) laminated human cortex, named cortical spheroids or hCSs (Nature Methods). These hCSs contain functional synapses, non-reactive astrocytes and can be sliced for electrophysiological recordings. More recently, we demonstrated how to obtain other human brain regions in 3-D, and introduced a novel modular approach for assembling them into forebrain circuits, for studying interneuron migration and integration (Nature). We are actively working on modeling in vitro other brain inter-regional interactions (see also our Cell Cinema gallery and an NIH video material explaining our work).
Second, we are using state-of-the-art stem cell biology, genome engineering and neurobiology approaches in combination with high-throughput in vitro assays to identify specific cellular and molecular features associated with developmental neuropsychiatric disorders, such as autism or schizophrenia. Our ultimate objective is to identify novel and reliable drug targets.