University of Virginia Health System

Research in the DeSimone laboratory centers on the problem of morphogenesis, which is the process biological systems use to generate form and develop increasingly complex structures needed to carry out the specialized functions of tissues, organs and whole organisms. We are interested in elucidating how the "linear" information encoded in genomes is played out over time to yield the fantastic variety of 3-dimensional biological form that we associate with all multi-celled organisms. Our specific research focus is the regulation of cell adhesion and adhesion-dependent cell signaling pathways important for directing cell motility and polarity in amphibian embryos. One central hypothesis is that the embryonic extracellular matrix (ECM) serves to define compartments within which cell movements are confined and restricted. We have established that integrin signaling is involved in the maintenance of planar cell polarity and the regulation of cadherin-based cell-cell adhesion. Thus, we have proposed that integrin-ECM interactions are a necessary component of the cellular machinery regulating the radial and mediolateral cell-intercalation behaviors that drive midline convergence and axial extension in the frog. These studies complement other ongoing work in the laboratory that focuses on mechanisms of cranial neural crest cell migration and the roles of ADAM family membrane metalloproteases. ADAM metalloprotease activity is required for cranial neural crest cell migration by modifying the extracellular matrix that lines the migratory routes of these cells. We anticipate that basic knowledge derived from such "simple" model systems of morphogenetic change will be critical to advancing the field of regenerative medicine and the practical applications of tissue engineering.

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Other Websites for this mentor:
http://www.faculty.virginia.edu/desimonelab/