Membrane mucins cover the brush border membrane of enterocytes throughout the intestine, but their function remains undefined. Our aim is to elucidate the function of membrane mucins in intestinal barriers and to determine how we can harness the function of membrane mucins in order to combat diseases such as Inflammatory bowel disease (IBD) and endemic intestinal infections.
Membrane mucin MUC17 (green) is anchored to the outer tip of apical microvilli (magenta) on enterocytes in the human intestines.
The gastrointestinal tract is home to trillions of bacteria and the interaction between bacteria and our immune system has received much attention. Yet, we know little about the barrier function of absorptive epithelial cells, also called enterocytes, that line the intestine and physically separate bacteria from immune cells within the lamina propria
Long, extended glycoproteins called membrane mucins build up a dense glycocalyx on luminal surfaces of enterocytes. Here, at the interface between the host and the outer environment, membrane mucins reach 1 micrometer into the microbe-rich gut lumen, farther than any other known membrane protein or receptor. Consequently, membrane mucins are ideally positioned to function as epithelial barriers and to participate in host-microbe interactions.
Our research group is part of Mucin Biology Groups at the University of Gothenburg. We are one of few research labs in the world who study the function and regulation of membrane mucins in defending our gastrointestinal tract.
Our aim is to elucidate the function of membrane mucins in intestinal barriers and to determine how we can harness the function of membrane mucins in order to combat diseases such as Inflammatory bowel disease (IBD) and endemic intestinal infections.
Marie Skłodowska-Curie Actions
Swedish Society for Medical Research
ALF Västra Götalandsregionen
Mucosal Immunology Studies Team/NIH
Wenner-Gren Foundations
Sahlgrenska Academy
Jäverfelt S, Hellsén G, Kaji I, Goldenring JR, Pelaseyed T. The MYO1B and MYO5B motor proteins and the SNX27 sorting nexin regulate membrane mucin MUC17 trafficking in enterocytes. Biochem J 2024; BCJ20240204. doi: doi.org/10.1042/BCJ20240204. PMID: 36945389.
Rajan A, Gallego P, Dolan B, Patel P, Dwibedi C, Luis AS, Trillo-Muyo S, Arike L, van der Post S, Simrén M, Pelaseyed T. BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection. Gut Microbes. 2024 Jan-Dec;16(1):2409247. doi: 10.1080/19490976.2024.2409247. PMID: 39349383
Layunta E, Jäverfelt S, van de Koolwijk FC, Sivertsson M, Dolan B, Arike L, Thulin S, Vallance BA, Pelaseyed T. MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn's disease. bioRxiv [Preprint]. 2024 Feb 8:2024.02.08.578867. doi: 10.1101/2024.02.08.578867
Lang T, Pelaseyed T. Discovery of a MUC3B gene reconstructs the membrane mucin gene cluster on human chromosome 7. PLoS One. 2022;17(10):e0275671. doi: 10.1371/journal.pone.0275671. PMID: 36256656.
Layunta E, Jäverfelt S, Dolan B, Arike L, Pelaseyed T. IL-22 promotes the formation of a MUC17 glycocalyx barrier in the postnatal small intestine during weaning. Cell Rep. 2021 Feb 16;34(7):108757. doi: 10.1016/j.celrep.2021.108757. PMID: 33596425.
Pelaseyed T, Hansson GC. Membrane mucins of the intestine at a glance. J Cell Sci. 2020 Mar 13;133(5). doi: 10.1242/jcs.240929. PMID: 32169835
Schneider H, Berger E, Dolan B, Martinez-Abad B, Arike L, Pelaseyed T, Hansson GC. The human transmembrane mucin MUC17 responds to TNFα by increased presentation at the plasma membrane. Biochem J. 2019 Aug 6. pii: BCJ20190180. doi: 10.1042/BCJ20190180. PMID: 31387973.
Pelaseyed T, Bretscher A. Regulation of actin-based apical structures on epithelial cells. J Cell Sci. 2018 Oct 17;131(20). pii: jcs221853. doi: 10.1242/jcs.221853. PMID: 30333133
Schneider H, Pelaseyed T, Svensson F, Johansson MEV. Study of mucin turnover in the small intestine by in vivo labeling. Sci Rep. 2018 Apr 10;8(1):5760. doi:10.1038/s41598-018-24148-x. PMID: 29636525
Pelaseyed T, Viswanatha R, Sauvanet C, Filter JJ, Goldberg ML, Bretscher A. Ezrin activation by LOK phosphorylation involves a PIP(2)-dependent wedge mechanism. Elife. 2017 Apr 21;6. pii: e22759. doi: 10.7554/eLife.22759. PMID: 28430576
Lebrero-Fernández C, Bergström JH, Pelaseyed T, Bas-Forsberg A. Murine Butyrophilin-Like 1 and Btnl6 Form Heteromeric Complexes in Small Intestinal Epithelial Cells and Promote Proliferation of Local T Lymphocytes. Front Immunol. 2016 Jan 19;7:1. doi: 10.3389/fimmu.2016.00001. PMID: 26834743
Sauvanet C, Wayt J, Pelaseyed T, Bretscher A. Structure, regulation, and functional diversity of microvilli on the apical domain of epithelial cells. Annu Rev Cell Dev Biol. 2015;31:593-621. doi: 10.1146/annurev-cellbio-100814-125234. PPMID: 26566117.
Pelaseyed T, Bergström JH, Gustafsson JK, Ermund A, Birchenough GM, Schütte A, van der Post S, Svensson F, Rodríguez-Piñeiro AM, Nyström EE, Wising C, Johansson ME, Hansson GC. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014 Jul;260(1):8-20. doi: 10.1111/imr.12182. PubMed 24942678
Pelaseyed T, Gustafsson JK, Gustafsson IJ, Ermund A, Hansson GC. Carbachol-induced MUC17 endocytosis is concomitant with NHE3 internalization and CFTR membrane recruitment in enterocytes. Am J Physiol Cell Physiol. 2013 Aug 15;305(4):C457-67. doi: 10.1152/ajpcell.00141.2013. PMID: 23784542
Pelaseyed T, Zäch M, Petersson AC, Svensson F, Johansson DG, Hansson GC. Unfolding dynamics of the mucin SEA domain probed by force spectroscopy suggest that it acts as a cell-protective device. FEBS J. 2013 Mar;280(6):1491-501. doi: 10.1111/febs.12144. PMID: 23331320
Johansson ME, Ambort D, Pelaseyed T, Schütte A, Gustafsson JK, Ermund A, Subramani DB, Holmén-Larsson JM, Thomsson KA, Bergström JH, van der Post S, Rodriguez-Piñeiro AM, Sjövall H, Bäckström M, Hansson GC. Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci. 2011 Nov;68(22):3635-41. doi: 10.1007/s00018-011-0822-3. PubMed PMID: 21947475.
Pelaseyed T, Hansson GC. CFTR anion channel modulates expression of human transmembrane mucin MUC3 through the PDZ protein GOPC. J Cell Sci. 2011 Sep 15;124(Pt 18):3074-83. doi: 10.1242/jcs.076943. PMID: 21852426.
Malmberg EK, Pelaseyed T, Petersson AC, Seidler UE, De Jonge H, Riordan JR, Hansson GC. The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine. Biochem J. 2008 Mar 1;410(2):283-9. PMID: 17990980.
See complete list of publications on Pubmed.
Marcus Wallenberg Foundation, Grant for external symposium, MWS 2023.0006 (2024) (co-applicant)
Wenner-Gren Foundation, Grant for external symposium, ESh2023-0020 (2024) (co-applicant)
ALF Grant from Västra Götalandsregionen, Clinical research grant, ALFGBG-991311 (2024) (main applicant)
Marie Curie Actions Doctoral Network, PhD training grant, 101119504-SurfEx (2023-2027) (co-applicant)
Swedish Society for Medical Research, Extention grant #S17-0005 (2022-2023) (main applicant)
Biocodex Microbiota Foundation, National grant (2022-2024) (main applicant)
Stiftelsen Clas Groschinskys Minnesfond #M2254 (2022-2023) (main applicant)
The Wenner-Gren Foundations, Starting grant #FT2017-0002 (2017-2023) (main applicant)
Sahlgrenska Academy co-funding of SSMF Large Grant, #E2018/611 (2018-2022)
Sahlgrenska Academy PhD Training Grant #U2018/162 (2019-2023)
Åke Wiberg's Foundation, Research grant, #M21-0022 (2021-2022)
Swedish Society for Medical Research, Start grant #S17-0005 (2018-2023) (success rate 6%)NIH/NIAID/MIST Scholar Award in Mucosal Immunity (2018-2020)
The Wenner-Gren Foundations, International Postdoc Training grant, #UPD2018-0065 #WUP2017-0005 (2018-2020)
Åke Wiberg's Foundation, Research grant, #M17-0062 (2018-2019)
The Jeansson Foundations, Startup grant #JS2017-0003 (2018-2019)
Sahlgrenska Academy International Starting Grant, #E2015/521 (2015)
Wilhem and Martina Lundgren’s Foundation, #2017-1655 (2017-2018)
Wenner-Gren Postdoctoral Fellowship (2014-2017) (success rate 5%)
The Swedish Cystic Fibrosis Association’s Postdoctoral stipend (2014)
Birgit and Hellmuth Hertz Foundation’s Postdoctoral scholarship (2013)
Research Supervisor of the Year Award 2021 to Thaher Pelaseyed
Biocodex Microbiota Foundation, National grant
NIH/NIAID/MIST Scholar Award in Mucosal Immunity (2018-2020)
Wilhelm and Martina Lundgren’s Foundation (2006-2012)
European CF Young Investigators meeting, Lille, France (2008) * 1st prize for the best oral presentation
The Swedish Cystic Fibrosis Association’s scholarship (2006-2009)
The Pelaseyed Lab consists of a team of devoted researchers. We are undergraduates, graduates, and postdocs.
Thaher Pelaseyed is a group leader in Department of Medical Biochemistry and Cell Biology. After graduating with a Masters degree in Pharmaceutical Bioscience (2006), Thaher did his graduate study at University of Gothenburg, receiving a PhD in Medical Biochemistry (2012). He became a Wenner-Gren Postdoctoral Fellow at Cornell University, where he studied the morphological regulation of apical membrane domains in epithelial cells. He became an independent group leader in 2018.
thaher.pelaseyed@medkem.gu.se
+46(0)31-786 31 54
ORCID
LinkedIn
ResearchGate
Molly Sivertsson, undergraduate student in Pharmaceutical Sciences
Diana Jaghobi, undergraduate student in Pharmaceutical Sciences
Anandi Rajan, postdoc (2019-2024)
Currently: R&D Manager, Kromnigon
Sweden
Elena Layunta, postdoc (2018-2023)
Currently: Assistant Professor
Facultad de Veterinaria. Universidad de Zaragoza
Nirary Nissan, Master’s student in Pharmaceutical Sciences
Asmaa Ghanem, Master’s student in Pharmaceutical Sciences
Majd Tabbara, Master’s student in Pharmaceutical Sciences
Fadumo Mohamed Salad, Bachelor’s studeent in Medical Laboratory Sciences
Gustaf Hellsén, Master’s student in Medicine
Fleur has a MSc in Biomedical Sciences from Universiteit van Amsterdam, the Netherlands. Fleur studies the role of membrane mucin gene polymorphism in host-microbe interactions. Fleur’s project is part of the SurfEx, a Marie Skłodowska-Curie Actions Doctoral Network.
Sofia has PhD in Medical Biochemistry from University of Gothenburg, Sweden. Sofia is using mass spectrometry to study the dynamic interactome of intestinal membrane mucins.
We are always looking for motivated young researcher who want to investigate host epithelial defense system. We offer a number of exciting projects associated with clarifying the fundamental function of intestinal membrane mucins. Current projects include,
Project 1: To determine how membrane mucins participate in cell-autonomous defense against intestinal pathogens.
Project 2: To identify the interactome of intestinal membrane mucins.
Project 3: To define the extrinsic and intrinsic programs that regulate membrane mucins.
Project 4: To determine the function of the extracellular SEA domain of intestinal membrane mucins.
We welcome enthusiastic and independently-minded postdocs as well as graduate and undergraduate students.
Applicants should email Thaher Pelaseyed with a cover letter, CV + bibliography and three letters of recommendation.
Thaher Pelaseyed, PhD
Institute of Biomedicine
Department of Medical Biochemistry and Cell Biology
University of Gothenburg
SWEDEN
Office: +46 (0) 31-786 31 54
Cell: +46(0)733-79 43 47
thaher.pelaseyed@medkem.gu.se
Visit: Medicinaregatan 9C, 413 90 Gothenburg, Sweden
Mail: Box 440, 405 30 Gothenburg, Sweden
