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.
