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The Experimental Liver Research Group

The projects in the experimental group aim to understand the triggering and regulatory events taking place during cholangitis development. We do this by using different murine models of cholangitis and in vitro assays.

About the group

The main aim of our research is to understand mechanisms regulating cholangitis with a clear focus on immunology. In addition to the cholangitis focused studies, we are also doing basic research related to the function natural killer T-cells and mucosal associated invariant T (MAIT)-cells. NKT and MAIT cells are especially interesting in the context of liver diseases since they are abundantly present in the liver.

From the genome-wide association studies headed by NoPSC it is clear that the genetic risk factors for PSC are genes involved in the immune response. We have therefore chosen to study various immune driven models of cholangitis along with models based on specific genetic findings in the human studies.

To complement the in vivo studies the group is also using selected in vitro cellular models to study the role of various cell types in the liver and bile duct immune responses. A special emphasis in our studies is put on natural killer T-cells, an abundant population of lymphocytes in the liver with regulatory properties. Several ongoing studies aim to clarify the role of these cells in cholangitis development. In addition to the cholangitis-centered studies we perform basic studies related to activation and development of NKT-cells.

Financial support 

The experimental projects are funded by the Norwegian PSC research center, the South Eastern Norwegian Health trust as well as The Research Council of Norway (NFR).

Selected Publications

  • Jiang X, Bergquist A, Löscher BS, Venkatesh G, Mold JE, Holm K, Laerdahl JK, Skånland SS, Maleki KT, Cornillet M, Taskén K, Franke A, Karlsen TH, Björkström NK, Melum E. A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis. Sci Transl Med. 2021 Feb 24;13(582):eabb0036. doi: 10.1126/scitranslmed.abb0036. PMID: 33627483.
  • Sampaziotis F, Muraro D, Tysoe OC, Sawiak S, Beach TE, Godfrey EM, Upponi SS, Brevini T, Wesley BT, Garcia-Bernardo J, Mahbubani K, Canu G, Gieseck R 3rd, Berntsen NL, Mulcahy VL, Crick K, Fear C, Robinson S, Swift L, Gambardella L, Bargehr J, Ortmann D, Brown SE, Osnato A, Murphy MP, Corbett G, Gelson WTH, Mells GF, Humphreys P, Davies SE, Amin I, Gibbs P, Sinha S, Teichmann SA, Butler AJ, See TC, Melum E, Watson CJE, Saeb-Parsy K, Vallier L. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science. 2021 Feb 19;371(6531):839-846. doi: 10.1126/science.aaz6964. PMID: 33602855; PMCID: PMC7610478.
  • Valestrand L, Berntsen NL, Zheng F, Schrumpf E, Hansen SH, Karlsen TH, Blumberg RS, Hov JR, Jiang X, Melum E. Lipid antigens in bile from patients with chronic liver diseases activate natural killer T cells. Clin Exp Immunol. 2021 Feb;203(2):304-314. doi: 10.1111/cei.13541. Epub 2020 Nov 16. PMID: 33089489; PMCID: PMC7806449.
  • Melum E, Jiang X, Baker KD, Macedo MF, Fritsch J, Dowds CM, Wang J, Pharo A, Kaser A, Tan C, Pereira CS, Kelly SL, Duan J, Karlsen TH, Exley MA, Schütze S, Zajonc DM, Merrill AH, Schuchman EH, Zeissig S, Blumberg RS. Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin. Nat Immunol. 2019 Dec;20(12):1644-1655. doi: 10.1038/s41590-019-0504-0. Epub 2019 Oct 21. PMID: 31636468; PMCID: PMC7249499.
  • Berntsen NL, Fosby B, Tan C, Reims HM, Ogaard J, Jiang X, Schrumpf E, Valestrand L, Karlsen TH, Line PD, Blumberg RS, Melum E. Natural killer T cells mediate inflammation in the bile ducts. Mucosal Immunol. 2018 Nov;11(6):1582-1590. doi: 10.1038/s41385-018-0066-8. Epub 2018 Aug 16. PMID: 30115993; PMCID: PMC6402771.
  • Berntsen NL, Fosby B, Valestrand L, Tan C, Reims HM, Schrumpf E, Karlsen TH, Line PD, Melum E. Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree. Am J Physiol Gastrointest Liver Physiol. 2018 Mar 1;314(3):G349-G359. doi: 10.1152/ajpgi.00124.2017. Epub 2017 Dec 6. PMID: 29212771.
Published Feb. 4, 2014 2:45 PM - Last modified June 22, 2021 11:24 AM

Contact

Group leader

Espen Melum

Participants

Detailed list of participants