Steven Wiley

Bio: Dr. Wiley's research over the last 25 years has focused on understanding mechanisms of cell communication using the EGFR system as a model. He pioneered methods for the quantitative analysis of receptor dynamics in mammalian cells and published some of the first computer models of receptor regulation. He has been a major contributor to the field of receptor research, particularly with regard to the control of receptor distribution within cells. More recently, his work has focused on understanding regulation of growth factor shedding and autocrine signaling as a mechanism by which cells interpret their microenvironment. This work also involves mapping cellular networks connected to ligand shedding and receptor heterodimerization to determine how information is decoded from multiple inputs. Dr. Wiley's work is notable for combining the techniques of molecular and cellular biology with both biochemical and optical assays. The results are then used to build computer models of the underlying cellular processes. He is the author or co-author of more than 100 scientific journal articles, review articles and book chapters.

Talk Title: Autocrine Circuits and EGF Receptor Signaling

Abstract: All living cells sense and respond to their environment through a complex set of signal transduction cascades. The epidermal growth factor receptor (EGFR) is a central player in the signaling system of epithelial cells and regulates diverse biological responses such as proliferation, migration and differentiation. Human epithelial cells express multiple members of the EGFR family as well as various cognate ligands, such as TGF-alpha, amphiregulin and HB-EGF. To activate the EGFR, these ligands must undergo regulated proteolysis through a process that is dependent on multiple signal transduction pathways. We have recently found that a variety of different growth factors and hormones can stimulate autocrine signaling through the EGFR. This autocrine loop, in turn, stimulates the expression of EGFR ligand genes themselves as well as genes for a variety of other growth factors and cytokines. We have analyzed the response of cells to EGFR activation, using whole-genome microarrays and quantitative proteomics of total cellular and extracellular proteins. Our data suggest that EGFR signaling is a primary mechanism by which epithelial cells detect their context. A primary stimulus, such as a cytokine or hormone, is shunted through the EGFR by an autocrine loop. This autocrine loop regulates both the decision of a given cell to enter the cell cycle and/or to remodel the extracellular matrix. The action taken by the cells is also broadcast to neighboring cells in the form of secondary growth factors and cytokines, suggesting that regulated ligand production and shedding is part of an extracellular signaling network that coordinates the response of cell communities to a given stimulus.