The brain is a wonderful and mysterious machine, which makes us who we are. The activity of billions of neurons and glia orchestrate our thoughts and daily life. However, alterations in the number of neurons, their misplacement, or changes in the way they receive, handle, or send information can negatively impact our brain function and our lives. A mutation in a single gene can lead to such alterations resulting in a specific pathology and disorder. Our Mission is to understand how a mutated, dysfunctional protein will lead to abnormal brain formation and function.
Our attention has been focused on the mammalian Target of Rapamycin, mTOR. mTOR is a converging point in cell signaling, or in other terms an intracellular hub, that receives signals from diverse intracellular routes and extracellular ligands. Importantly, mTOR is dysregulated in many neurological disorders. These disorders referred to as mTORopathies include (but are not limited to) Tuberous Sclerosis Complex (TSC), autism, Alzheimer's disease, and Schizophrenia. We have focused on TSC.
TSC is the prototypical mTORopathy in which Tsc1 or Tsc2 mutations lead to mTOR hyperactivity. In TSC, epilepsy due to the presence of cortical malformations is observed in 75-85% of the patients where seizures often begin during the first year of life as infantile spasms. More than 50% of affected children exhibit mental retardation and cognitive delay, with many exhibiting autistic traits and more than 60% have neuropsychiatric problems. These neurological symptoms are thought to be independent of the lesions but rather result from subtle developmental abnormalities and synaptic dysfunction.
Our work has the following three lines of research related to the following keywords: mTOR, Neural stem cell, Neurogenesis, Cognitive functions, mTORopathies