Thomas Kidd, Ph.D.

It is now widely accepted that classical neurotrophic factors can also act as axon guidance factors, but the role of axon guidance factors as neuronal survival factors has only recently emerged. We are investigating the role of novel secreted molecules with dual abilities to both guide axons and promote neuronal survival. Preliminary data suggests that the Drosophila embryonic nervous system may be more plastic then previously suspected.

These signals may also ensure that there is a sufficiently large pool of neurons and other cell types present prior to post-mitotic development. In vertebrates, neurotrophic factors frequently operate through so-called dependence receptors: in the absence of ligands, these receptors trigger apoptosis. As cells are dependent on the presence of ligands, these receptors are candidate tumor suppressor molecules. Their loss makes cells insensitive to the absence of survival factors.

We are examining whether dependence receptor mechanisms operate in the fly. Cell survival is frequently mediated by the PI3K and MAPK signaling pathways, and we are exploring the role of these and other potential downstream factors required for survival in the Drosophila nervous system. Identifying specific signaling pathways could permit the development of alternative therapeutics that would promote neuronal survival. This work has the potential to uncover novel signaling pathways and allow greater understanding of how different neurotrophic pathways collaborate to promote neuronal survival.

Project 1 Team

Thomas Kidd, Ph.D.
Project 1 Leader
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Grant Mastick, Ph.D.
Project 1 Mentor / CORE C Leader
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Sean M. Ward, Ph.D.
Project 1 Mentor
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