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Cambridge Immunology Network

 

Research

Arthur chairs the Cambridge Immunology Strategic Network steering group and leads the Gastrointestinal Diseases theme of the NIHR Cambridge Biomedical Research Centre. This is a partnership, funded and supported by the NIHR, between Cambridge University Hospitals and the University of Cambridge to deliver ground-breaking research that benefits patients.

Arthur's laboratory investigates the biology of Crohn’s disease and ulcerative colitis. These are two inflammatory bowel diseases that can affect individuals at any age, most often in early adulthood. They emerge from a complex gene - environment interaction. The actual triggers remain still unknown.

Employing and developing a wide range of technologies, from complex genetic models to sophisticated liquid chromatography mass spectrometry, the team explores the major biological mechanisms that are affected by risk genes of inflammatory bowel disease. This has generated important insights into how autophagy and endoplasmic reticulum stress collude to drive a pathological unfolded protein response. And most recently led to the discovery of a very fundamental purine enzyme that enables a metabolic cycle balancing electron transfer into mitochondria and controlling immunometabolism of macrophages.

 

Group members:

James A West

Katharina Ramshorn

Lorraine M Holland

Lukas Unger

Sukritee Bhaskar

 

 

Alumni:

Ana Bélen Iglesias Romero

Svetlana Saveljeva

Timon E Adolph

Lukas Niederreiter

Jun Inoue

Sarah L Kempster

James O Jones

Jonathan W Ashcroft

Markus Tschurtschenthaler

Janice Y J Lee

Muhammad N B Md-Ibrahim

O Stephen Ojo

Ester Pagano

Tim Raine

Georg Thomas Schneditz

Giuseppe Sirago

Thomas Flint

Rodrigo Pereira de Almeida Rodrigues

Publications

Key publications: 

 

Kaser A. Genetic Risk of Severe Covid-19. N Engl J Med. 2020 Oct 15;383(16):1590-1591.

Cader MZ†, Rodrigues RPDA†, West JA†, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A. FAMIN is a multifunctional purine enzyme enabling the purine nucleotide cycle. Cell 2020 Jan 23; 180:278-295 † shared first authors

Grootjans J, Krupka N, Hosomi S, Matute JD, Hanley T, Saveljeva S, Gensollen T, Heijmans J, Li H, Limenitakis JP, Ganal-Vonarburg SC, Suo S, Luoma AM, Shimodaira Y, Duan J, Shi DQ, Conner ME, Glickman JN, Fuhler GM, Palm NW, de Zoete MR, van der Woude CJ, Yuan GC, Wucherpfennig KW, Targan SR, Rosenstiel P, Flavell RA, McCoy KD, Macpherson AJ, Kaser A, Blumberg RS. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response. Science. 2019 Mar 1;363(6430):993-998. doi: 10.1126/science.aat7186.

Schneditz G, Elias JE, Pagano E, Zaeem Cader M, Saveljeva S, Long K, Mukhopadhyay S, Arasteh M, Lawley TD, Dougan G, Bassett A, Karlsen TH, Kaser A, Kaneider NC. GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump. Sci Signal. 2019 Jan 1;12(562). pii: eaau9048. doi: 10.1126/scisignal.aau9048.

Aden K, Tran F, Ito G, Sheibani-Tezerji R, Lipinski S, Kuiper J, Tschurtschenthaler M, Saveljeva S, Bhattacharyya J, Häsler R, Bartsch K, Luzius A, Jentzsch M, Falk-Paulsen M, Stengel S, Welz L, Schwarzer R, Rabe B, Barchet W, Krautwald S, Hartmann G, Pasparakis M, Blumberg RS, Schreiber S, Kaser A, Rosenstiel P. ATG16L1 orchestrates interleukin-22-signaling in the intestinal epithelium via cGAS/STING. J Exp Med 2018 Sep 25. pii: jem.20171029. doi: 10.1084/jem.20171029.

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.

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.