EBC Symposium 2011 - Keynote Speakers
Joan S. Brugge, Ph.D.
Joan S. Brugge, Ph.D., is Professor of Cell Biology and Chair of the Department of Cell Biology at Harvard Medical School. The Brugge laboratory is investigating the cellular processes and pathways that are involved in normal morphogenesis of epithelial tissues and the initiation and progression of epithelial tumors. One of the major approaches employed by this laboratory involves culturing breast epithelial cells in reconstituted basement membrane gels, which allows the cells to organize into 3-D structures that resemble the hollow, spherical glandular units of the breast. This culture system is being used to model events that control the proliferation, survival and migration of normal epithelial cells, to identify cellular genes that allow escape from these controls and induce phenotypic changes resembling those associated with tumor progression, and to elucidate the mechanisms responsible for these events. The laboratory has found that multiple processes contribute to the death or clearance of cells from the lumen, including apoptosis, metabolic impairment, and an unusual process involving invasion of one cell into another (entosis). Because the induction of apoptosis and autophagy appears to be a consequence of lack of matrix protein deposition by the inner cells of the acinar structures, the laboratory is investigating how matrix proteins regulate apoptosis and metabolic activity and how oncogenes suppress apoptosis and allow rescue from metabolic impairment. Recently, the laboratory has been using the 3-D cultures and in vivo mouse models to understand mechanisms of drug resistance.
W. James Nelson, Ph.D.
W. James Nelson, Ph.D., is Professor of Biology at Stanford University. His research efforts have sought to understand how cell-cell interactions specify the correct cellular organization of complex tissues, and how structurally and functionally different plasma membrane domains are assembled and tailored to specific tissue and organ functions. His laboratory is at the forefront of studies of molecular mechanisms linking cell-cell adhesion to the development of structural and functional polarity of epithelial cells that are critical in tissue development. They have uncovered protein-protein interactions between the cell adhesion protein E-cadherin, the membrane-cytoskeleton, membrane proteins such as Na/K-ATPase and complexes regulating vesicle trafficking to cell-cell contacts. These results provided both evidence of a direct role of cell-cell adhesion as an extracellular spatial cue in controlling the distribution of basolateral membrane proteins and a specific mechanism for the selective retention and accumulation of membrane proteins in different plasma membrane domains, including the primary cilium. Dr. Nelson’s work has broad implications for understanding the basis for cell-cell adhesion and cell polarity in different tissues, and how defects in those pathways lead to metabolic diseases and cancer.