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.
