MD, Boston University School of Medicine, Scientific Advisory Board
Wayne I. Lencer obtained his MD degree from Boston University School of Medicine, USA in 1987. The title of his present position is Longwood Chair in Pediatrics at Harvard Medical School. He is also Director of Harvard Digestive Disease Center. His laboratory studies the cell and molecular biology of polarized epithelial cells lining mucosal surfaces. The projects focus on how barrier epithelial cells interact with the lumenal and sub-epithelial microenvironment, and on the biology of bacterial toxin pathogenesis and mucosal host defense. In a longstanding and broadly enabling research program, he has discovered how some enteric bacterial toxins breech the intestinal epithelial barrier to enter host epithelial cells and induce toxicity. These toxins hijack the cellular and molecular mechanisms of retrograde membrane transport to move from the lumenal cell surface into the endoplasmic reticulum (ER), where they co-opt the mechanics of ER Associated Degradation (ERAD) to enter the cytosol; and where they activate the ER stress sensor IRE1 to amplify their toxicity by inducing the unfolded protein response. We found the structure of the ceramide domain of the toxin’s GM1 glycosphingolipid receptor plays a decisive role in the trafficking of the toxin; and defined the structural motif in the ceramide domain that explains this biology. The discovery may have clinical applications enabling intracellular delivery of peptide and protein biologics and their amplified biodistribution. In another project, his lab studies the cell and molecular biology of transcytosis by the MHC Class I-like IgG receptor FcRn. FcRn transports IgG across mucosal surfaces where it may function in immune surveillance and host defense. The transcytotic pathway across barrier epithelial cells provides a critical link between the outside and inside worlds of the gut. His work has elucidated the itinerary and many genes operating in this pathway. The work of Wayne Lencer in each of these areas has led to >18 patent awards. The FcRn research program led to the founding of a Biotech company that was acquired by Biogen Idec and produced two novel biologics now FDA approved: Alprolix and Eloctate for treatment of hemophilia A and B. The glycosphingolipid trafficking project has led to new patents, a 2018 award from the Harrington Discovery institute for translation of this work to clinical practice, and a new biotechnology company was founded.
