University of Virginia Health System

The three main areas of research in this laboratory include growth factor signaling during morphogenesis of the vertebrate head, interactions of metastatic tumor cells with extracellular matrix, and regeneration of skeletal tissues. The first project focuses on the inductive interactions responsible for formation of the tissues overlying the developing brain -- particularly the sutural growth sites, which are responsible for appositional bone growth, and consequently, the global form of the face and skull. Currently we are determining the expression patterns of the elements of the FGF system -- fibroblast growth factors (FGF) 2 and 4 and FGF receptors 1, 2 and 3 and the specific functions of this signalling system in proliferation, differentiation and apoptosis of individual cells. We are also beginning the construction of transgenic mice expressing the human genes for FGFRs with the point mutations responsible for human craniofacial abnormalities to better understand when and where these mutations exert their harmful influence during skeletal development. A second area of research concerns the influence of extracellular matrix components such as laminin and vitronectin on gene expression, adhesion and movement of tumor cells. Integrin receptors for extracellular matrix are differentially expressed or show selective activity that enables certain tumor cells to metastasize. Long range goals include using the integrin-ligand interface to design drugs to block metastasis and determining why certain tumors (prostate and breast) primarily target bone. In the final project, combinations of native extracellular matrixes, stem cells and growth factors are being tested for capacity to regenerate bone, cartilage and associated tissues. Initial animal trials have proved successful, thus future goals include adaptation of current methodology to human tissue regeneration and surgical applications such as spinal fusion and bone grafting.

Other Websites for this mentor:
http://www.med.virginia.edu/medicine/basic-sci/cellbio/rco.htm