Modeling neurodevelopmental disorders with genetically defined human neurons
Model experimental systems, such as mice, are often used to investigate the mechanisms of neurological disease. However, it would be ideal to examine the causes of disease and test potential therapeutics in a human cellular context. To achieve this we are utilizing a “disease-in-a-dish” approach based on state-of-the-art technology to transform skin cells obtained from patients into human brain cells, called neurons. These neurons retain the genetic information of the patient from which they were derived allowing us to investigate disease mechanisms in a clinically relevant context. We propose to use this system to investigate how mutations in genes that cause the autism and epilepsy-related disorder Tuberous Sclerosis Complex (TSC) affect the ability of neurons to communicate with each other, and how altered neuronal communication leads to imbalanced neural network activity. In addition to revealing the causes of brain dysfunction in neurodevelopmental disorders, our future studies will test the ability of potential therapeutics to restore normal patterns of activity directly in patient-derived neurons.