DeSimone, Douglas W.
Professor and Chair, Cell Biology
- BS, Life Sciences, Worcester Polytechnic Institute
- PhD, Biology, Dartmouth College
- Postdoc, Cell and Molecular Biology, Massachusetts Institute of Technology
Biotechnology, Cell and Developmental Biology, Development, Stem Cells & Regeneration
Cell Adhesion and Adhesion-Dependent Cell Signaling in Vertebrate Morphogenesis
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 cell 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 regulated. We have established that integrin-ECM interactions are a necessary component of the cellular machinery regulating collective cell migration and the radial and mediolateral cell-intercalation behaviors that drive midline convergence and axial extension at gastrulation. In recent years our studies have focused increasingly on the signaling crosstalk between cadherin adhesions at cell-cell interfaces and integrin adhesions to the ECM. We have determined that tugging forces on cadherin adhesions are required to establish the polarized protrusions of collectively migrating cells. Current research seeks to elucidate the instructive importance of mechanical signals in directing morphogenetic behaviors of cells and tissues and related mechanisms of adhesion-dependent mechanotransduction. 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.