Human brain organoid models of PCDH19-clustering epilepsy (PCE)PCDH19-clustering epilepsy (PCE) is a severe childhood epilepsy that manifests with medically refractory seizures, intellectual disability and frequent features of autism spectrum disorder (ASD). The disorder affects females and mosaic males while male carriers are spared.
In collaboration with Dr. Jack Parent, we have recently developed female "PCE patient” cortical organoids (COs) that robustly recapitulate PCE-related phenotypes. Assays such as examining synapse function, and MEA recordings of network activity in late-stage human COs and/or fused cortical-ventral organoids will be exploited to determine epilepsy-like phenotypes. |
POGZ-related neurodevelopmental disordersPOGZ is one of the genes which are most commonly associated with recurrent de novo variants in individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy.
We employ a multi-disciplinary approach including cell biology, molecular biology, and neuroscience, such as stem cells, brain organoid, CRISPR/CAS9 gene editing, imaging, and transcriptome analysis to understand how the loss of POGZ leads to developmental defects and altered inhibitory circuitry in the brain. |