Our research explores the Wingless(Wg)/Wnt signaling
pathway. The Wnt class of secreted growth factor promotes
a wide variety of cell fate decisions during the development
of both vertebrate and invertebrate embryos. In addition,
the Wnt pathway is associated with certain cancers,
particularly colon cancer, when it is inappropriately
activated in adult humans. Wnt molecules have proven
difficult to work with biochemically because they
associate tightly with cell membranes. Therefore,
we exploit the powerful genetic and molecular techniques
available in Drosophila to approach basic questions
about Wg/Wnt signal transduction. We have demonstrated
that the Drosophila transcription factor, TCF, can
act as either a repressor or an activator of Wg target
genes, depending on the signaling state of the responding
cell. We have also characterized a Drosophila homolog
of the human tumor suppressor, APC, which negatively
regulates the Wg/Wnt signaling pathway and is a prime
target during oncogenesis. In addition, we have discovered
that active cellular processes are responsible for
distributing Wg protein throughout the epidermal cells.
This novel ligand transport pathway discovered in
flies may be relevant to human Wnt function, since
mutations in Wg that disrupt the transport process
alter residues that are highly conserved in vertebrate
Wnts. Recently, we have isolated a set of Drosophila
mutations in a genetic screen for molecules that interact
with the Wg/Wnt pathway. We are currently working
to identify the genes disrupted, some of which appear
to be novel regulators of pathway activity.
