Translational Control in Brain Development

The cerebral cortex is a major brain structure responsible for higher level cognitive functions, such as memory, language, thought, and reasoning. The development of the cerebral cortex is governed by precisely timed and coordinated molecular signaling and sequential gene expression, and many neurodevelopmental disorders arise when these critical events are disrupted.  Our lab aims to understand how translational control of gene expression modulates healthy brain development and examine how perturbations in these regulatory processes lead to neurological defects at the cellular, network, and behavioral levels. We are particularly interested in studying the impacts of altered translational control on the development and integration of neurons into cortical circuits.

Mechanisms of Epileptogenesis in Developmental mTORopathies

Malformations of cortical development – such as focal cortical dysplasia, hemimegalencephaly, and tuberous sclerosis complex – are the leading causes of intractable epilepsy in children. These neurodevelopmental disorders (termed “mTORopathies”) are caused by mutations in the mTOR pathway, leading to hyperactive mTOR signaling. The mTOR pathway serves as a hub for signaling integration and is an essential regulator of numerous cellular processes, including cell growth, autophagy, and metabolism. How dysregulated mTOR signaling leads to epilepsy is not fully understood. We use a combination of animal models and molecular, histological, and electrophysiological approaches to investigate how aberrant mTOR signaling causes abnormal brain development and the formation of hyperexcitable brain networks leading to epilepsy. We hope that knowledge gained from this research will help guide new therapeutic strategies to treat, modify, or prevent intractable epilepsy in mTOR-associated neurodevelopmental disorders.

*Parts of this research is funded by the TSC Alliance

Research areas:
Development of the cerebral cortex
Neurodevelopmental disorders
Malformations of cortical development
Tuberous sclerosis complex
Focal cortical dysplasia
Epilepsy
mTOR signaling
Translational control