All the cells in the blood are derived from a single progenitor, the hematopoietic stem cell. This cell has the remarkable ability to self-renew as well as to differentiate into mature blood cells of all lineages. A fundamental question that remains largely unanswered is how stem cells make the choice between self-renewal and differentiation.
The overall goal of our lab is to elucidate the signaling pathways that regulate stem cell fate. We have focused specifically on the Wnt signaling pathway, which is a critical regulator of normal growth and development, and a major target of mutation in human cancer. Our recent work shows that activation of Wnt signaling can promote stem cell self-renewal in vitro. Currently, we are using a combination of cellular, molecular and transgenic approaches to determine the role of Wnt signaling in stem cell self-renewal in vivo and to characterize the molecular mechanisms through which Wnt exerts its effect on stem cells. Moreover, since uncontrolled self-renewal is a hallmark of oncogenesis, we are also developing transgenic mouse models to test whether dysregulation of the Wnt pathway can contribute to hematopoietic tumors. Finally, we are interested in identifying the signals that modulate the differentiation of stem cells, to both hematopoietic and non-hematopoietic lineages.
These studies will not only shed light on the basic mechanisms that regulate stem cell development and oncogenesis, but also contribute to stem cell based therapies for treatment of human disease.
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