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Professor Arthur Kaser

Professor Arthur Kaser

Arthur Kaser is accepting applications for PhD students.

Arthur Kaser is available for consultancy.


Departments

Department of Medicine:
University Chair of Gastroenterology

Research Interests

We investigate the mechanisms that underlie inflammation at mucosal surfaces.

A single layer of intestinal epithelial cells – which may be considered the evolutionary most ancient innate immune cell type – separates the complex and densely populated habitat of the microbiota from the sterile host tissue of the gut, which itself harbours the majority of the host's bona fide immune cells. A loss of the mutualistic relationship between host and microbiota is thought to be at the basis of the inflammatory bowel diseases Crohn's disease and ulcerative colitis.

Using a variety of techniques, including complex genetic models, we explore the major biological mechanisms that are affected by risk genes of inflammatory bowel disease. This approach opens up a window to explore the environmental factors that may trigger disease in genetically susceptible individuals, and which are the cause for the steep increase in incidence and prevalence of these diseases around the world. Following this path, we have reported mechanisms of how hypomorphic autophagy and mediators of the unfolded protein response lead to inflammatory bowel disease, defining a key pathway of Crohn's disease pathogenesis. Further following this paradigm, we have more recently discovered an entirely novel immunometabolic pathway that determines risk for Crohn's disease, leprosy, and systemic juvenile idiopathic arthritis.

Group members:

Liz Andersen

Nicole C Kaneider

Tim Raine

Rodrigo Pereira de Almeida Rodrigues

Svetlana Saveljeva

Alumni:

Timon E Adolph

Lukas Niederreiter

Sarah L Kempster

Markus Tschurtschenthaler

Keywords

gastroenterology ; epithelial cells ; microbiota ; unfolded protein response ; mucosal immunology ; endoplasmic reticulum stress

Topics

  • inflammatory bowel disease
  • Crohn's disease

Key Publications

Feagan BG, Sandborn WJ, D'Haens G, Panés J, Kaser A, Ferrante M, Louis E, Franchimont D, Dewit O, Seidler U, Kim KJ, Neurath MF, Schreiber S, Scholl P, Pamulapati C, Lalovic B, Visvanathan S, Padula SJ, Herichova I, Soaita A, Hall DB, Böcher WO. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017 Apr 29;389(10080):1699-1709. doi: 10.1016/S0140-6736(17)30570-6. Epub 2017 Apr 12.

Tschurtschenthaler M, Adolph TE, Ashcroft JW, Niederreiter L, Bharti R, Saveljeva S, Bhattacharyya J, Flak MB, Shih DQ, Fuhler GM, Parkes M, Kohno K, Iwawaki T, van der Woude CJ, Harding HP, Smith AM, Peppelenbosch MP, Targan SR, Ron D, Rosenstiel P, Blumberg RS, Kaser A. Defective ATG16L1-mediated removal of IRE1α drives Crohn's disease-like ileitis. J Exp Med 2017 Feb;214(2):401-422. doi: 10.1084/jem.20160791. Epub 2017 Jan 12.

Cader MZ, Boroviak K, Zhang Q, Assadi G, Kempster SL, Sewell GW, Saveljeva S, Ashcroft JW, Clare S, Mukhopadhyay S, Brown KP, Tschurtschenthaler M, Raine T, Doe B, Chilvers ER, Griffin JL, Kaneider NC, Floto RA, D'Amato M, Bradley A, Wakelam MJO, Dougan G, Kaser A. C13orf31 (FAMIN) is a central regulator of immunometabolic function. Nat Immunol 2016 Sep;17(9):1046-56. doi: 10.1038/ni.3532. Epub 2016 Aug 1.

Aden K, Rehman A, Falk-Paulsen M, Secher T, Kuiper J, Tran F, Pfeuffer S, Sheibani-Tezerji R, Breuer A, Luzius A, Jentzsch M, Häsler R, Billmann-Born S, Will O, Lipinski S, Bharti R, Adolph T, Iovanna JL, Kempster SL, Blumberg RS, Schreiber S, Becher B, Chamaillard M, Kaser A, Rosenstiel P. Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation. Cell Rep. 2016 Aug 23;16(8):2208-18. doi: 10.1016/j.celrep.2016.07.054. Epub 2016 Aug 11.

Tschurtschenthaler M, Kachroo P, Heinsen FA, Adolph TE, Rühlemann MC, Klughammer J, Offner FA, Ammerpohl O, Krueger F, Smallwood S, Szymczak S, Kaser A*, Franke A*. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis. Sci Rep. 2016 Aug 19;6:31640. doi: 10.1038/srep31640. * shared senior and communicating authors

Adolph TE†, Tomczak MF†, Niederreiter L†, Ko H-J†, Böck J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon M-N, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A* & Blumberg RS*. Paneth cells as a site of origin for intestinal inflammation. Nature 2013 Nov 14; 503(7475):272-6. † shared first authors, * shared senior and communicating authors

Niederreiter L, Fritz TMJ, Adolph TE, Krismer A-M, Offner FA, Tschurtschenthaler M, Flak, MB, Hosomi, S, Tomczak MF, Kaneider NC, Sarcevic E, Kempster SL, Raine T, Esser, D, Rosenstiel P, Kohno K, Iwawaki T, Tilg H, Blumberg RS & Kaser A. ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells. J Exp Med 2013; 210 (10): 2041.

Tschurtschenthaler M, Wang J, Fricke C, Fritz TM, Niederreiter L, Adolph TE, Sarcevic E, Künzel S, Offner FA, Kalinke U, Baines JF, Tilg H, Kaser A. Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration. Gut 2014 Feb 20. doi: 10.1136/gutjnl-2013-305863.

Raine T, Liu JZ, Anderson CA, Parkes M, Kaser A. Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease. Gut 2014 May 5. doi: 10.1136/gutjnl-2013-306657.

Olszak T, Neves JF, Dowds CM, Baker K, Glickman J, Davidson NO, Lin CS, Jobin C, Brand S, Sotlar K, Wada K, Katayama K, Nakajima A, Mizuguchi H, Kawasaki K, Nagata K, Müller W, Snapper SB, Schreiber S, Kaser A, Zeissig S, Blumberg RS. Protective mucosal immunity mediated by epithelial CD1d and IL-10. Nature 2014 May 22;509(7501):497-502.

Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (2008), XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease, Cell 2008; 134(5):743–56.

Crypt abscess in the intestinal mucosa as a consequence of unresolved endoplasmic reticulum stress due to hypomorphic XBP1 function (H&E staining).