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Pelaseyed LaB

EXPLORING Cell-autonomous defenseS
AGAINST GUT MICROBES

Our intestines are home to trillions of bacteria. The interaction between bacteria and our immune system has received much attention. Yet, we know little about intestinal epithelial cells that physically separate bacteria from our immune cells. Long, extended glycoproteins called membrane mucins build up the glycocalyx on luminal surfaces of epithelial cells that line our intestines. Here, at the interface between 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 participate in host-microbe interactions.

Our aim is to elucidate the function of membrane mucins in intestinal barriers and to determine the role of membrane mucins in cell-autonomous defenses against pathogens.

OUr research

Membrane mucin MUC17 (green) is anchored to the outer tip of apical microvilli (magenta) on enterocytes in the human intestines.

The intestinal barrier encompasses the mucus barrier that consists of goblet cell-secreted mucins, membrane mucins in the glycocalyx of enterocytes, intercellular tight junctions and antimicrobial peptides (AMPs). Despite significant advances in understanding the function of the Muc2-based mucus barrier and the role of AMPs in health and disease, there is a critical knowledge gap regarding the function of membrane mucins and their role in the human intestines.

The aim of our research is to determine how membrane mucins in the apical glycocalyx of epithelial cells protect the intestine against gut pathogens in the context of diseases such as Inflammatory Bowel Disease (IBD). 

MAJOr Funding:

Swedish Society for Medical Research
Mucosal Immunology Studies Team/NIH
Wenner-Gren Foundations
Sahlgrenska Academy

PUBLICATions

1: 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. [Epub ahead of print] PubMed PMID: 31387973.

2: 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. Review. PubMed PMID: 30333133; PubMed Central PMCID:
PMC6215389.

3: 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. PubMed PMID: 29636525; PubMed Central PMCID:
PMC5893601.

4: 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. PubMed
PMID: 28430576; PubMed Central PMCID: PMC5400502.

5: 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. eCollection 2016. PubMed PMID:
26834743; PubMed Central PMCID: PMC4717187.

6: 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.
Review. PubMed PMID: 26566117.

7: 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. Review. PubMed
PMID: 24942678; PubMed Central PMCID: PMC4281373.

8: 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. Epub 2013 Jun 19. PubMed
PMID: 23784542; PubMed Central PMCID: PMC3891215.

9: 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. Epub 2013 Feb 21. PubMed PMID: 23331320; PubMed Central
PMCID: PMC3746175.

10: 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. Epub 2011 Sep 25. Review.
PubMed PMID: 21947475.

11: 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. Epub 2011 Aug 18. PubMed PMID:
21852426.

12: 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. PubMed PMID: 17990980.

See complete list of publications on Pubmed.

Grants & Awards


Active research grants as Principal Investigator

Swedish Society for Medical Research, Start grant #S17-0005 (2018-2023) (success rate 6%)
Sahlgrenska Academy PhD Training Grant #U2018/162 (2019-2023)
NIH/NIAID/MIST Scholar Award in Mucosal Immunity (2018-2020)
The Wenner-Gren Foundations, Starting grant #FT2017-0002 (2017-2019)
The Wenner-Gren Foundations, International Postdoc Training grant, #UPD2018-0065 (2019-2020)
The Wenner-Gren Foundations, International Postdoc Training grant, #WUP2017-0005 (2018-2019)
Åke Wiberg's Foundation, Research grant, #M17-0062 (2018-2019)
The Jeansson Foundations, Startup grant #JS2017-0003 (2018-2019)

Institutional support

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

Completed research grants

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)

Awards

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)

 

Our Team

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

 
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Thaher Pelaseyed, PhD
PI

Thaher Pelaseyed is a Assistant Professor in Department of Medical Biochemistry and Cell Biology at University of Gothenburg. 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 then did his postdoctoral work as a Wenner-Gren Postdoctoral Fellow at Cornell University where he studied the morphological regulation of apical membrane domains in epithelial cells. He returned to University of Gothenburg and Institute of Biomedicine in 2016.

Read his full CV here.

 
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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.

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ELENA Layunta HerNÁNdez, POstdoc

Elena has a PhD in Biomedical and Biotechnological Sciences from University of Zaragoza, Spain. Elena works on the crosstalk between gut microbiota and host epithelial cells in regulation of membrane mucins.

 
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Anandi Rajan
Postdoc

Anandi has a PhD in Virology from Umeå University, Sweden. Anandi is focusing on identifying microbial proteins that interact with and process intestinal membrane mucins.

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Gustaf Hellsén
STUDENT

Gustaf is an undergraduate medical student at University of Gothenburg. Gustaf is working on conformational changes that occur in membrane mucins upon bacterial interactions.

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 9A, 413 90 Gothenburg, Sweden
Mail: Box 440, 405 30 Gothenburg, Sweden