Neurotrophic factors such as neurotrophins play a critical role in regulating neuronal survival, differentiation, and function, primarily by activating the Trk family of receptor tyrosine kinases. Recently, the precursors of these factors, the proneurotrophins, have been shown to cause neuronal cell death via a distinct receptor, the p75 neurotrophin receptor. The balance between signaling neuronal survival or death depends on the expression of these factors and their receptors, and the regulation of cleavage of the proneurotrophins to yield a ligand for either the Trk or p75 receptor, leading to survival or death.

We use both in vitro and in vivo analysis to investigate mechanisms of neurotrophin signaling and the consequences for neuronal function. In vivo, we use seizures as a model of neuronal injury in which p75NTR is induced on neurons and regulates cell death. The regulation of neuronal survival or death has critical implications for normal brain function, as well as neuronal degeneration as a consequence of injury or disease. Our research seeks to understand the mechanisms that govern the balance between neuronal survival and death.