Developmental signaling pathways govern the formation and function of stem
cells, thereby holding the key to unlocking the promise of adult tissue
regeneration, and to inhibiting cancer development. In our laboratory, we use
zebrafish as the primary model to study the liver and explore the regulation of
endodermal progenitor cell specification, organ differentiation and growth. We
then examine the conserved role of these signaling pathways in regulating tissue
growth in surgical and chemical models of liver regeneration and genetic liver
cancer models. We also use murine liver injury models to demonstrate
evolutionary conservation and relevance for human disease. Our prior work has
shown that we can translate our findings from the fish tank to the bedside, as
the first clinical trial originating from our findings in the fish has begun to
enroll patients.
We have found that the wnt pathway is an important regulator of liver
development and regeneration.

Recently, we showed that prostaglandin signaling interacts with wnt, offering a
chance to therapeutically modify wnt-mediated stem and progenitor cell growth.
In an effort to identify new pathways and genes important for liver development,
we performed a genetic screen and characterized several mutants with disturbed
liver formation. In addition, we are proceeding with a chemical genetic screen
to characterize regulators of liver growth. We aim to use these findings and
genomic analyses of clinical cohorts to better understand the interaction of
regulatory signals that affect liver function and regeneration. The work in our
laboratory is directly relevant for developing new treatment options for
patients with liver failure and liver cancer.