Research Interest:

Neuronal degeneration

The aim of our research is to determine the molecular pathways by which neurons undergo degeneration upon altered expression of certain genes. We use cultured PC12 cells as model neurons.

PC12 is a clonal line of dopamine-secreting cells that differentiate into neurons upon exposure to certain growth factors or expression of certain oncogenes. The Wnt1 oncogene, which functions by an unknown molecular mechanism in normal neuronal differentiation and is essential for normal brain development, surprisingly causes PC12 cells to cease expression of almost all neuron-specific genes and to upregulate a glial-specific gene. We have found that only transient expression of Wnt1 by PC12 is required to induce these changes. (The same transient Wnt1 expression occurs to induce brain differentiation in vivo.) This requirement for only transient Wnt1 expression makes it difficult to elucidate the Wnt1-induced signally pathway. Wnt1 also causes the C6 glial cells to upregulate their expression of certain glial-specific genes. We recently identified a gene that is upregulated by Wnt1 and whose upregulation only occurs when Wnt1 is expressed. We are using this gene as a reporter for Wnt1 expression in order to elucidate the intermediates in the Wnt1-induced signalling pathway.

We are also using PC12 cell mutants deficient in the fetal brain protein neuronatin to determine the mechanism by which neuronatin protects neuronal cells against certain forms of toxic insult.