Abstract
Our work has focused on understand the signaling pathways that regulate the choice between stem cell renewal and commitment, and define how the same signals are subverted in cancer. We have specifically studied developmental signals such as Wnt, Notch and Hedgehog which are critical regulators of normal development in a variety of systems, and a major target of mutation in human cancer. Our research using knockout and transgenic approaches suggests that these signals are activated in hematopoietic stem cells, and that they functionally contribute to stem cell self-renewal in vivo. In addition our data also shows that inhibition of these signals can block leukemia development and propagation in mouse models of the disease as well as in human leukemia cells.
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