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Cambridge Immunology Network

 
Role of the microbial and inflammatory microenvironment in sporadic intestinal cancers

Technical University of Munich, Center for Translational Cancer Research (TranslaTUM)

Research

My principal research interests lie in the field of mucosal immunology, especially in the context of intestinal inflammation and colorectal cancer (CRC). Working with different disease models in my scientific career has sparked my interest in disease-relevant genes and their immunological functions. In my previous research in the lab of Prof. Arthur Kaser (University of Cambridge) I was investigating how genetic and environmental risk factors associated with inflammatory bowel disease (IBD) may contribute to the development of intestinal inflammation. 

In my current research at the Technical University of Munich I am elucidating the causes and consequences of inflammation in oncogene-induced intestinal tumourigenesis. Inflammation and carcinogenesis are well known to be associated, however, it remains obscure how oncogenes (Kras(G12D), Braf(V600E) and Pik3ca(H1047R)) determine the inflammatory milieu in subtypes of sporadic intestinal tumours and how this affects tumour development and survival. I therefore aim to decipher and to target relevant immune cell subsets as well as pro- and anti- inflammatory signalling pathways that are associated with specific oncogenes and are involved in the formation of subtypes of sporadic CRC.

 

Publications

Key publications: 

Tschurtschenthaler M & Adolph TE. The selective autophagy receptor Optineurin in Crohn’s disease. Front. Immunol., 2018 Apr 10;9:766. doi: 10.3389/fimmu.2018.00766. PMID: 29692785

 

Aden K, Tran F, Ito G, Sheibani-Tezerji R, Lipinski S, Kuiper JW, Tschurtschenthaler M, Saveljeva S, Bhattacharyya J, Häsler R, Bartsch K, Luzius A, Jentzsch M, Falk-Paulsen M, Stengel ST, 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-signalling in the intestinal epithelium via cGAS-STING. J. Exp. Med., 2018 Nov 5;215(11):2868-2886. doi: 10.1084/jem.20171029. PMID: 30254094

Hosomi S, Grootjans J, Tschurtschenthaler M, Krupka, N, Matute JD, Flak MB, Martinez-Naves E, Gomez Del Moral M, Glickman JN, Ohira M, Lanier LL, Kaser A & Blumberg RS. Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation. J. Exp. Med., 2017 Oct 2;214(10):2985-2997. doi: 10.1084/jem.20162041. PMID: 28747426

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, Janneke van der Woude C, 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 6;214(2):401-422. doi: 10.1084/jem.20160791. PMID: 28082357

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. PMID: 27538787

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 MJ, 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. PMID: 27478939

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 Dec;63(12):1921-31. doi: 10.1136/gutjnl-2013-305863. PMID: 24555997

Afrazi A, Branca MF, Sodhi CP, Good M, Yamaguchi Y, Egan CE, Lu P, Jia H, Shaffiey S, Lin J, Ma C, Vincent G, Prindle T Jr, Weyandt S, Neal MD, Ozolek JA, Wiersch J, Tschurtschenthaler M, Shiota C, Gittes GK, Billiar TR, Mollen K, Kaser A, Blumberg RS & Hackam DJ. Toll Like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis. J. Biol. Chem., 2014 Apr 4;289(14):9584-99. doi: 10.1074/jbc.M113.526517. PMID: 24519940

Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, 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 MN, 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. doi: 10.1038/nature12599. PMID: 24089213

Niederreiter L, Fritz TM, Adolph TE, Krismer AM, 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 Sep 23;210(10):2041-56. doi: 10.1084/jem.20122341. PMID: 24043762

 Markus   Tschurtschenthaler
Not available for consultancy

Affiliations

Classifications: 
Person keywords: 
mucosal immunology
microbiota
inflammation
Organoids