Asymmetry and Cell Fate in Stem Cells and Cancer

Our research focuses on the signals that control stem cell self-renewal and how these signals are hijacked in cancer. Using genetic models, we have shown that classic developmental signaling pathways such as Wnt and Hedgehog play key roles in stem cell growth and regeneration and are dysregulated during leukemia development. In addition, we have used real-time imaging strategies to show that stem cells have the capacity to undergo both symmetric and asymmetric division, and that shifts in the balance between these modes of division are controlled by the microenvironment and subverted by oncogenes. This work led to the discovery that regulators of asymmetric division, such as the cell fate determinant Musashi, can promote aggressive leukemias and may serve as critical targets for diagnostics and therapy in hematologic malignancies. Most recently, we have developed a high resolution in vivo imaging system that has allowed us to begin to map the behavior and interactions of stem cells with the microenvironment within living animals and to define how these change during cancer formation.