Photo of Wayne Lencer,  MD

Wayne Lencer, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2573

Wayne Lencer, MD

Boston Children's Hospital


  • Longwood Professor of Pediatrics, Pediatrics, Harvard Medical School
  • Division Chief Gastroenterology, Medicine, Boston Children's Hospital


Research Abstract

My laboratory studies the cell and molecular biology of vesicular transport and a novel mechanism of innate immunity unique to the polarized epithelial cells that line mucosal surfaces.These projects relate to how barrier epithelial cells interact with the luminal 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 luminal cell surface into the endoplasmic reticulum (ER), where they hijack the mechanics of ER Associated Degradation to enter the cytosol,almost the total reverse of protein biosynthesis.

We also recently discovered how the cell senses such invasion via the most ancient sensor ER stress – IRE1. Signal transduction originates in the ER lumen (previously thought to be devoid of pattern recognition molecules) and is transduced to both NFκB and IFN via the viral sensor RIG-I. The pathway is amplified at mucosal surfaces.

In another project, the lab studies the cell and molecular biology of transcytosis by the MHC Class I-like IgG receptor FcRn and the glycosphingolipid GM1. FcRn transports IgG across mucosal surfaces where it may function in immune surveillance and host defense. A new translational project tests if lipid sorting for GM1 can be applied clinically as a platform for biologic-drug delivery.

My work in each of these areas has led to over 14 patent awards. The FcRn research program led to the founding of a Biotech company that was acquired by Biogen Idec and we now have two novel biologics FDA approved.

Publications from Harvard Catalyst Profiles

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  • Grey MJ, Cloots E, Simpson MS, LeDuc N, Serebrenik YV, De Luca H, De Sutter D, Luong P, Thiagarajah JR, Paton AW, Paton JC, Seeliger MA, Eyckerman S, Janssens S, Lencer WI. IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress. J Cell Biol 2020. PubMed
  • Chang D, Whiteley AT, Bugda Gwilt K, Lencer WI, Mekalanos JJ, Thiagarajah JR. Extracellular cyclic dinucleotides induce polarized responses in barrier epithelial cells by adenosine signaling. Proc Natl Acad Sci U S A 2020; 117:27502-27508. PubMed
  • Luong P, Li Q, Chen PF, Wrighton PJ, Chang D, Dwyer S, Bayer MT, Snapper SB, Hansen SH, Thiagarajah JT, Goessling W, Lencer WI. A quantitative single-cell assay for retrograde membrane traffic enables rapid detection of defects in cellular organization. Mol Biol Cell 2019. PubMed
  • Royal JM, Oh YJ, Grey MJ, Lencer WI, Ronquillo N, Galandiuk S, Matoba N. A modified cholera toxin B subunit containing an ER retention motif enhances colon epithelial repair an unfolded protein response. FASEB J. 2019. PubMed
  • Garcia-Castillo MD, Chinnapen DJ, Te Welscher YM, Gonzalez RJ, Softic S, Pacheco M, Mrsny RJ, Kahn CR, von Andrian UH, Lau J, Pentelute BL, Lencer WI. Mucosal absorption of therapeutic peptides by harnessing the endogenous sorting of glycosphingolipids. Elife 2018. PubMed
  • Luong P, Hedl M, Yan J, Zuo T, Fu TM, Jiang X, Thiagarajah JR, Hansen SH, Lesser CF, Wu H, Abraham C, Lencer WI. INAVA-ARNO complexes bridge mucosal barrier function with inflammatory signaling. Elife 2018. PubMed
  • Nelms B, Dalomba NF, Lencer W. A targeted RNAi screen identifies factors affecting diverse stages of receptor-mediated transcytosis. J Cell Biol 2017; 216:511-525. PubMed
  • Saslowsky DE, Thiagarajah JR, McCormick BA, Lee JC, Lencer WI. Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion. Mol Biol Cell 2016; 27:1120-30. PubMed
  • Day CA, Baetz NW, Copeland CA, Kraft LJ, Han B, Tiwari A, Drake KR, De Luca H, Chinnapen DJ, Davidson MW, Holmes RK, Jobling MG, Schroer TA, Lencer WI, Kenworthy AK. Microtubule motors power plasma membrane tubulation in clathrin-independent endocytosis. Traffic 2015. PubMed
  • te Welscher YM, Chinnapen DJ, Kaoutzani L, Mrsny RJ, Lencer WI. Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1. J Control Release 2014; 175:72-8. PubMed
  • Luo R, Jeong SJ, Yang A, Wen M, Saslowsky DE, Lencer WI, Araç D, Piao X. Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation. PLoS ONE 2014; 9:e100043. PubMed
  • Zhou X, Massol RH, Nakamura F, Chen X, Gewurz BE, Davis BM, Lencer WI, Waldor MK. Remodeling of the intestinal brush border underlies adhesion and virulence of an enteric pathogen. MBio 2014. PubMed
  • Saslowsky DE, te Welscher YM, Chinnapen DJ, Wagner JS, Wan J, Kern E, Lencer WI. Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain. J Biol Chem 2013; 288:25804-9. PubMed
  • Weflen AW, Baier N, Tang QJ, Van den Hof M, Blumberg RS, Lencer WI, Massol RH. Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules. Mol Biol Cell 2013; 24:2398-405. PubMed
  • Chinnapen, D.J., W.T. Hsieh, Y.M. Te Welscher, D.E. Saslowsky, L. Kaoutzani, E. Brandsma, L. D'Auria, H. Park, J.S. Wagner, K.R. Drake, M. Kang, T. Benjamin, M.D. Ullman, C.E. Costello, A.K. Kenworthy, T. Baumgart, R.H. Massol, and W.I. Lencer. Lipid Sorting by Ceramide Structure from Plasma Membrane to ER for the Cholera Toxin Receptor Ganglioside GM1 Dev Cell 2012; 23:573-86.
  • Jin A. Cho, Ann-Hwee Lee, Barbara Platzer, Benedict C.S. Cross, Brooke M. Gardner, Heidi DeLuca, Phi Luong, Heather P. Harding, Laurie H. Glimcher, Peter Walter, Edda Fiebiger, David Ron, Jonathan C. Kagan, Wayne I. Lencer. Innate immune sensing of a bacterial protein in the ER by IRE1α and RIG-I ; 13:558-69.
  • Nelms BD, Waldron L, Barrera LA, Weflen AW, Goettel JA, Guo G, Montgomery RK, Neutra MR, Breault DT, Snapper SB, Orkin SH, Bulyk ML, Huttenhower C, Lencer WI. CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types. Genome Biol ; 17:201. PubMed