Wayne I. Lencer, M.D.
Department of Cell Biology
Cell Biology, Enders Bldg., Rm. 609
300 Longwood Avenue
Boston, MA 02115
Visit my lab page here.
My laboratory studies the cell and molecular biology of vesicular transport in polarized epithelial cells and regulation of ion transport in the intestine. These projects relate to how intestinal epithelial cells interact with the luminal and sub-epithelial microenvironment, and to the biology of bacterial pathogenesis and mucosal host defense. A new project examines the mechanisms of protein retro-translocation from ER to cytosol.
In one project, we have discovered how the enteric bacterial toxin, cholera toxin (CT), breeches the intestinal epithelial barrier and enters host epithelial cells to cause disease. CT and the other AB5-subunit toxins hijack membrane lipids and the cellular and molecular mechanisms of retrograde membrane transport to move from the plasma membrane into the endoplasmic reticulum (ER) of affected cells. Once in the ER, a portion of the toxin, the A1-chain, co-opts components of ERAD (ER-associated degradation) to retro-translocate to the cytosol where it acts enzymatically to cause disease. The pathway from PM to ER and cytosol can be viewed in some ways as almost the total reverse of protein biosynthesis. In addition to robust cell-culture and biochemical model systems, we have recently defined the zebrafish as a genetic model for studies on toxin transport into the ER and retro-translocation to the cytosol. A forward genetic screen is in progress.
In another project, we study how IgG is transported by the Fcg-receptor FcRn across epithelial barriers to affect mucosal immunity and host defense. Here, the pathway taken by FcRn across the cell is bidirectional and strictly avoids the late-endosome and lysosome. These studies are cell-culture based using gene-silencing driven by conditional promoters to examine the membrane biology that explains sorting of the receptor in this pathway.
For a complete listing of publications click here.
Last Update: 1/7/2013