Grant: Operating Grant: ECRs in Human Development, Child and Youth Health

The human brain is vulnerable to too much of mTOR signaling, an important neuronal pathway regulating neuronal development and activity. We study TSC, a neurodevelopmental disorder in which patients inherit a germline heterozygous mutation in genes regulating the mTOR pathway and commonly, a second somatic mutation causing mTOR hyperactivation in a small number of brain cells in the neocortex, an important brain region implicated in cognitive dysfunction and epilepsy. How mTOR hyperactivation in a small number of brain cells drives systemic dysfunction is not fully understood. This project will perform a single cell transcriptomic method using a novel mouse model to recapitulate the symptoms and identify druggable candidates that can be used to specifically target cells with mTOR hyperactivation and reduce disease manifestation.