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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 and collaboration

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).

Central collaborators in our projects are: Richard Blumberg (Brigham and Women’s Hospital / Harvard), Mark Exley (Brigham and Women’s Hospital / Harvard) and Arthur Kaser (Cambridge University). The surgically induced cholangitis models are performed together with the Department of Transplantation Surgery (Bjarte Fosby).

Selected Publications

  • Berntsen NL, Fosby B, Valestrand L, Tan C, Reims HM, Schrumpf E, Karlsen TH, Line PD, Espen Melum E. Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree. American Journal of Physiology - GI (in press)
  • Alberts R, de Vries EMG, Goode EC, Jiang X, …, Melum E, …, Franke A, Anderson CA, Karlsen TH, Ponsioen CY, Weersma RK. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. Gut. 2017 Aug 4. pii: gutjnl-2016-313598. doi: 10.1136/gutjnl-2016-313598. [Epub ahead of print]
  • Meijerink H, White RA, Løvlie A, de Blasio BF, Dalgard O, Amundsen EJ, Melum E, Kløvstad H. Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973-2030. BMC Infect Dis. 2017 Aug 3;17(1):541. doi: 10.1186/s12879-017-2631-2.
  • Landskron J, Kraggerud SM, Wik E, Dørum A, Bjørnslett M, Melum E, Helland Ø, Bjørge L, Lothe RA, Salvesen HB, Taskén K. C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease. PLoS One. 2017 Jul 31;12(7):e0182030. doi: 10.1371/journal.pone.0182030. eCollection 2017.
  • Jiang X, Björkström NK, Melum E. Intact CD100-CD72 Interaction Necessary for TCR-Induced T Cell Proliferation. Front Immunol. 2017 Jun 30;8:765. doi: 10.3389/fimmu.2017.00765. eCollection 2017.
  • Henriksen EKK, Viken MK, Wittig M, Holm K, Folseraas T, Mucha S, Melum E, Hov JR, Lazaridis KN, Juran BD, Chazouillères O, Färkkilä M, Gotthardt DN, Invernizzi P, Carbone M, Hirschfield GM, Rushbrook SM, Goode E; UK-PSC Consortium, Ponsioen CY, Weersma RK, Eksteen B, Yimam KK, Gordon SC, Goldberg D, Yu L, Bowlus CL, Franke A, Lie BA, Karlsen TH. HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry. HLA. 2017 Jul 11. doi: 10.1111/tan.13076. [Epub ahead of print]
  • Sampaziotis F, Justin AW, Tysoe OC, Sawiak S, Godfrey EM, Upponi SS, Gieseck RL 3rd, de Brito MC, Berntsen NL, Gómez-Vázquez MJ, Ortmann D, Yiangou L, Ross A, Bargehr J, Bertero A, Zonneveld MCF, Pedersen MT, Pawlowski M, Valestrand L, Madrigal P, Georgakopoulos N, Pirmadjid N, Skeldon GM, Casey J, Shu W, Materek PM, Snijders KE, Brown SE, Rimland CA, Simonic I, Davies SE, Jensen KB, Zilbauer M, Gelson WTH, Alexander GJ, Sinha S, Hannan NRF, Wynn TA, Karlsen TH, Melum E, Markaki AE, Saeb-Parsy K, Vallier L. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nat Med. 2017 Aug;23(8):954-963. doi: 10.1038/nm.4360. Epub 2017 Jul 3.
  • Schrumpf E, Jiang X, Zeissig S, Pollheimer MJ, Anmarkrud JA, Tan C, Exley MA, Karlsen TH, Blumberg RS, Melum E. The role of natural killer T cells in a mouse model with spontaneous bile duct inflammation. Physiol Rep. 2017 Feb;5(4). pii: e13117. doi: 10.14814/phy2.13117.
  • Vesterhus M, Holm A, Hov JR, Nygård S, Schrumpf E, Melum E, Thorbjørnsen LW, Paulsen V, Lundin K, Dale I, Gilja OH, Zweers SJLB, Vatn M, Schaap FG, Jansen PLM, Ueland T, Røsjø H, Moum B, Ponsioen CY, Boberg KM, Färkkilä M, Karlsen TH, Lund-Johansen F. Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis. J Hepatol. 2017 Jun;66(6):1214-1222. doi: 10.1016/j.jhep.2017.01.019. Epub 2017 Feb 2.
  • Chellappa S, Hugenschmidt H, Hagness M, Subramani S, Melum E, Line PD, Labori KJ, Wiedswang G, Taskén K, Aandahl EM. CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer. J Immunol. 2017 Feb 15;198(4):1729-1739. doi: 10.4049/jimmunol.1600061. Epub 2017
  • Maroni L, Agostinelli L, Saccomanno S, Pinto C, Giordano DM, Rychlicki C, De Minicis S, Trozzi L, Banales JM, Melum E, Karlsen TH, Benedetti A, Baroni GS, Marzioni M. Nlrp3 Activation Induces Il-18 Synthesis and Affects the Epithelial Barrier Function in Reactive Cholangiocytes. Am J Pathol. 2017 Feb;187(2):366-376. doi: 10.1016/j.ajpath.2016.10.010. Epub 2016 Nov 30.
  • Sun-Gou J, Juran BD, Mucha S, Folseraas T, Jostins L, Melum E, Kumasaka N, Atkinson EJ, ... , ... , Lazaridis KN, Anderson CA. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. Nature Genetics Nat Genet. 2017 Feb;49(2):269-273. doi: 10.1038/ng.3745. Epub 2016 Dec
Published Feb. 4, 2014 2:45 PM - Last modified Apr. 29, 2020 10:33 AM

Contact

Group leader

Espen Melum

Participants

  • Espen Melum
  • Zheng Fei
  • Anne Pharo
  • Jonas Øgaard
  • Kathrine Sivertsen Åsrud
  • Laura Valestrand
  • Lisa Yuen Løvold
  • Natalie L. Berntsen
  • Tine Simensen Oldereid
  • Xiaojun Jiang
Detailed list of participants