Our research focuses on the role of TGF-a and -b, two structurally related growth and differentiation factors, in epithelial and mesenchymal cell proliferation and differentiation. We use various cell biological, molecular and biochemical approaches to address cell physiological and developmental questions.

TGF-a is a growth factor for various cell types from ectodermal origin, including most epithelial cells, and exerts its functions in an autocrine and paracrine fashion. TGF-a is normally made as a transmembrane protein at the cell surface and functions in cell communication through its ability to interact with a tyrosine kinase receptor. The ectodomain can be proteolytically released in a highly regulated manner and is then released. Our TGF-a research focuses on the identification and functional characterization of proteins that form a complex in association with transmembrane TGF-a. We study their functions in the presentation of transmembrane TGF-a, signaling and regulation of TGF-a ectodomain cleavage in normal and transformed epithelial cells.

TGF-b is a prototype for a large family of growth and differentiation factors which regulate development. TGF-b is also a potent inducer of growth arrest in many cell types. Our research focus is on the mechanism of signaling by TGF-b receptors and its role in mesenchymal differentiation and apoptosis. We study how the Smads, a novel class of intracellular signaling effectors, act as signal transducers following receptor activation, are translocated into the nucleus and regulate gene expression. We also study how this signaling regulates mesenchymal cell differentiation into muscle, bone and fat cells, and cell death.