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Atoh1 is a basic helix-loop-helix transcription factor that is essential for the formation of intestinal secretory cells (goblet, Paneth, and enteroendocrine cells).
We have studied the role of Atoh1 in regulating normal intestinal function and response to pathological states by generating mice with an intestine-specific ablation of Atoh1.
Our recent studies demonstrate that Atoh1 functions as a tumor suppressor in the colon, where its expression is silenced in ~80% of sporadic colon cancers. We modeled this in using the intestine-specific Atoh1 mutant mice and discovered that they develop 10-14 times more colon tumors than control mice that retain Atoh1 expression.
Current projects will determine the mechanism by which Atoh1 functions as a tumor suppressor, and how this gene can be targeted to develop new cancer therapies.
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