Our research focuses on the neurobiology of progenitor cells, specifically the mechanisms by which neural progenitors make cell fate decisions during development.
We have used the human genetic disease tuberous sclerosis complex (TSC) as a model system to investigate neural progenitor cell differentiation. TSC is due to inactivation of the TSC1 or TSC2 genes and is seen in approximately 1:6,000 people.
Multiple organs are affected in TSC though brain abnormalities generally cause the greatest suffering with many patients having seizure disorders (epilepsy), autism, developmental delay, psychiatric, and behavioral problems. These neurologic features are thought to be due to brain malformations called tubers.
Tubers have severe disruption of cortical layers and contain many abnormal large cells that express neuronal as well as glial markers. While multiple alterations have been discovered, dysregulation of the mTOR signaling appears to be a central abnormality. While these and other findings represent very exciting advances, much remains about the role of the TSC genes during normal development and how their mutation leads to the clinical manifestations of TSC.