Wayne Lencer, MD
Professor, Department of Pediatrics, Harvard Medical School
Division Chief Gastroenterology, Medicine, Boston Children's Hospital
DF/HCC Program AffiliationGastrointestinal Malignancies
Research AbstractMy 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 lumenal and sub-epithelial microenvironment, and to the biology of bacterial pathogenesis and mucosal host defense. We have discovered how some enteric bacterial toxins breech the intestinal epithelial barrier and enter host epithelial cells to cause disease. These toxins hijack the cellular and molecular mechanisms of retrograde membrane transport to move from the lumenal cell surface into the endoplasmic reticulum (ER) and then into the cytosol of affected cells, the total reverse of protein biosynthesis. In another project, the lab studies the cell and molecular biology of the MHC Class I-like IgG receptor FcRn. FcRn transports IgG across mucosal surfaces where it may function in immune surveillance and host defense. In a third area of interest, the lab aims to understand the mechanisms and regulation of intestinal Cl- secretion, the initial ion transport event in secretory diarrhea.
We study basic cell biology of the intestinal epithelial cell, which ultimately deals with processes relevant to the biology of cancer. Additionally, we recently identified a novel innate immune mechanism of host defense originating from within the ER lumen by activation of IRE1α, an ER protein essential for the unfolded protein response. Newly emerging evidence indicates that ER stress contributes to the development of cancer in the GI tract.