Pharmacologic regulation of Wnt/β-Catenin Signaling in Stem and Progenitor Cells

Abstract

The Wnt/Ã -Catenin signaling pathway is a key regulator of proliferation, differentiation, and programmed cell death in stem and progenitor cells. Misregulated or aberrant signaling events in the pathway contributes to the pathology of diseases such as cancer and neurodegeneration. It stands to reason that if we can monitor and influence Wnt/Ã -Catenin signaling in stem and progenitor cells with sufficient resolution, it will be possible to design rationally targeted therapies. The body of work presented in this thesis contributes to the realization of this goal through discovery of molecular agents for controlling Wnt/Ã -catenin signaling, examination of the biological mechanisms linking this pathway to disease, and identification of cases where the pharmacological perturbation of Wnt/Ã -Catenin signaling may have therapeutic utility.