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.
See a picture of
Dr. Bejsovec's research in our Gallery.
