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Rik M. Derynck Ph.D.

Smad-mediated and non-Smad mechanisms of TGF-β signaling

Rik M. Derynck Ph.D.

Research in the Derynck lab focuses on the role of transforming growth factors- and , two structurally unrelated growth and differentiation factors, in mesenchymal and epithelial cells. We use molecular, genetic cell biological and biochemical approaches to address several cell physiological and developmental questions. The work has direct relevance to many questions in orofacial development and healing and is therefore of value to the proposed NRSA.

TGF- is a growth factor for many cell types of non-hematopoietic origin and exerts its functions in an autocrine/paracrine fashion mainly in normal epithelia and in solid tumor development. It is present as a transmembrane protein at the cell surface, from which the ecodomain can be proteolytically released as a secreted polypeptide. The transmembrane form of TGF- functions as a growth factor involved in cell-cell communication. Our major projects focus on the role of the cytoplasmic domain. We specifically study its ability to interact with cytoplasmic proteins that constitute an associated protein kinase complex and its potential role as a signaling entity, as well as its function in cell physiology and development.

TGF- is a growth and differentiation factor which induces growth arrest in epithelial cells, yet stimulates proliferation in mesenchymal cells, and furthermore, is a potent inducer of extracellular matrix deposition and integrin expression. TGF- is a prototype factor for the many related differentiation factors in the TGF- superfamily. Two major lines of research are followed. In one large project, we address the mechanism of signaling of the TGF- receptors, which are transmembrane serine/threonine kinases. In the other major project, we study the role of TGF- and vgr-1, a related factor, in mesenchymal differentiation, specifically in differentiation into the muscle, bone and cartilage lineages. These developmental questions are approached in cell culture andin vivo, including transgenic models.