Our laboratory focuses on the role
of the transforming growth factor-beta
(TGF-beta) signal transduction pathway
in cancer biology. The TGF-beta signaling
pathway functions as both a tumor-suppressor
and as tumor promoter during carcinogenesis
. This dichotomy of TGF-beta function
remains a fundamental problem in the
field both in terms of understanding
the mechanism of action of the TGF-beta
pathway, and directly impacting our
ability to target this pathway for
the chemoprevention or treatment of
human cancers. Resistance to the tumor
suppressor effects of TGF-beta is also
a common feature of epithelial-derived
human cancers, however, mechanisms
for TGF-beta resistance remain undefined
in the majority of cases. The laboratory
is currently focused on elucidating
mechanisms for TGF-beta resistance
and for the dichotomous function of
TGF-beta in human breast, colon, pancreatic
and renal cell cancers using a multidisciplinary
approach. TGF-beta and the TGF-beta
signaling pathway also have an important
role in vascular biology. Indeed, mutations
in two endothelial specific TGF-beta
receptors, endoglin and ALK-1, are
responsible for the human vascular
disease, hereditary hemorrhagic telangiectasia
(HHT), and mice which lack expression
of these receptors are embryonic lethal
due to defects in angiogenesis. Studies
are currently underway to identify
the ligand for these receptors, to
further elucidate the signal transduction
pathway downstream from these receptors
and to establish their role in regulating
tumor-induced angiogenesis. The ultimate
goal of these studies is the ability
to target the TGF-beta pathway for
the chemoprevention or treatment of
human cancers.
