Douglas W. DeSimone, PhD
The role of extracellular matrix cell in the regulation of cell adhesion, migration and differentiation
The DeSimone laboratory studies how the extracellular matrix (ECM) influences a variety of cellular activities that include adhesion, migration and differentiation. The primary focus of this research is fibronectin (FN) and the integrin receptors that bind FN. Recent findings from the lab indicate that integrin adhesion can lead to modulation of cadherin-based cell-cell adhesive behaviors important for cell motility within embryonic tissues undergoing morphogenetic rearrangements and epithelial to mesenchymal transitions. This research has revealed that the regulation of polarized cell protrusive activities attributed to the non-canonical wnt signaling pathway also requires integrin signaling. Projects are also underway with Martin Schwartz to develop FRET-based biosensors that will enable real time monitoring of tension-based changes in tissues that may alter cell signaling, motility and cell polarity. In collaboration with Dr. Judy White's laboratory, the DeSimone group is studying the ADAM (A Disintegrin And Metalloprotease) family of transmembrane metalloproteases. This work led to the discovery of a novel ADAM expressed in migratory neural crest cells (CNCs) that is important in regulating CNC invasion and migration. Current efforts are directed at structure/function analyses of this and other ADAMs expressed in the neural crest in order to elucidate the roles of specific ADAM structural domains. These studies have led to the discovery of ADAM domains involved in directing protease specificty and interactions with other molecules. It has also been determined that ADAMs participate in cell migration events by proteolytically modifying the extracellular matrix upon which they migrate. New studies focus on the discovery of molecules released from neural crest cell surfaces by ADAM-dependent sheddase activity. Basic knowledge of cell-adhesive interactions in vertebrate embryos is likely to be of fundamental importance to their understanding of the mechanistically parallel processes that regulate the adhesive and migratory behaviors of cancerous cells.