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 primary 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.
