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Pelaseyed LaB

membrane mucins in mucosal innate immunity



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.

OUr research

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.

MAJOr Funding:

Marie Skłodowska-Curie Actions
Swedish Society for Medical Research
ALF Västra Götalandsregionen
Mucosal Immunology Studies Team/NIH
Wenner-Gren Foundations
Sahlgrenska Academy

PUBLICATIONS

  1. 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

  2. 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. bioRxiv [Preprint]. 2023 Mar 7:2023.03.06.530313. doi: 10.1101/2023.03.06.530313. PMID: 36945389.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

Grants & Awards


Active research grants

Institutional support

  • Sahlgrenska Academy co-funding of SSMF Large Grant, #E2018/611 (2018-2022)

Completed research grants

Awards

Our Team

The Pelaseyed Lab consists of a team of devoted researchers. We are undergraduates, graduates, and postdocs.

Thaher Pelaseyed, PhD, PI

Thaher Pelaseyed is a Assistant Professor 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

 

Undergraduate Students

Fleur van de Koolwijk, Master’s student in Biomedical Sciences

Nirary Nissan, Master’s student in Pharmaceutical Sciences

Molly Sivertsson, undergraduate student in Pharmaceutical Sciences

Former members

Elena Layunta, postdoc (2018-2023)
Currently: Assistant Professor
Facultad de Veterinaria. Universidad de Zaragoza

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

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Anandi Rajan
Postdoc

Anandi has a PhD in Virology from Umeå University, Sweden. Anandi is focusing on identifying microbial virulence factors that interact with intestinal membrane mucins during enteric infections.

 
 

Sofia Jäverfelt
PhD Student

Sofia is a MSc in Pharmacy from University of Gothenburg, Sweden. Sofia is using mass spectrometry to study the dynamic interactome of intestinal membrane mucins.

careers

Open positions:

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.

 

Contact Us

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