Fearful Symmetry: Developmental Signaling in Stem Cells and Cancer

Our work focuses on the signals that control hematopoietic stem cell self-renewal and differentiation, how these signals are utilized during regeneration and how their dysregulation may lead to cancer. Using a multitude of genetic models, we have shown that classic developmental signaling pathways such as Wnt, Hedgehog and Notch play key roles in stem cell maintenance and regeneration and are dysregulated during leukemia development. In addition, we have used real-time imaging strategies to show that hematopoietic stem cells have the capacity to undergo both symmetric and asymmetric division, and that shifts in the balance between these modes of division is controlled by the microenvironment and subverted by oncogenes. 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 hematopoietic stem cells with the microenvironment within living animals, and define how these change during regeneration and cancer formation.