Molecular mechanisms and therapeutic implications of vascular permeability defects in inflammatory bowel diseases
Project Summary
The intestinal vascular system plays a critical barrier role in inflammatory bowel diseases. Interferon-gamma (IFN-γ) is a key pathogenic factor in IBD with strong effects on the vasculature. The main goal of this project is to uncover the molecular mechanisms by which IFN-γ activation of vascular endothelial cells impairs vascular barrier functions and disrupts immune–epithelial crosstalk during the course of IBD pathogenesis. In the long term, we aim to identify novel molecular pathways involved in IFN-γ–induced dysfunction of the intestinal vascular barrier, which could serve as potential targets for future IBD therapies.
Selected project-relevant publications
Passen CV, Krug J, Weiß L, Abdou MM, Tripal P, Schmid B, Krüger R, Lyu Y, Zohud BA, Petter K, Geppert C, Merkel S, Bärthlein B, Busenhart P, Scharl M, Naschberger E, Stürzl M.
Integrin β6 expression in colorectal cancer cells promotes liver metastasis through enhanced adhesion to endothelial fibronectin.
Int J Cancer. 2025 Oct 1;157(7):1481-1495. doi: 10.1002/ijc.35504. Epub 2025 Jun 9. PMID: 40488391; PMCID: PMC12334909.
Yong Y, Demmler R, Zohud BA, Fang Q, Zhang T, Zhou Y, Petter K, Flierl C, Gass T, Geppert CI, Merkel S, Schellerer VS, Naschberger E, Stürzl M.
AMIGO2 characterizes cancer-associated fibroblasts in metastatic colon cancer and induces the release of paracrine active tumorigenic secretomes.
J Pathol. 2025 Jan;265(1):14-25. doi: 10.1002/path.6363. Epub 2024 Nov 11. PMID: 39523830; PMCID: PMC11638658.
Bao LL, Yu YQ, González-Acera M, Patankar JV, Giessl A, Sturm G, Kühl AA, Atreya R, Erkert L, Gámez-Belmonte R, Krug SM, Schmid B, Tripal P, Chiriac MT, Hildner K, Siegmund B, Wirtz S, Stürzl M, Mohamed Abdou M, Trajanoski Z; TRR241 IBDome Consortium; Neurath MF, Zorzano A, Becker C.
Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.
Sci Transl Med. 2025 Jan 15;17(781):eadn8699. doi: 10.1126/scitranslmed.adn8699.
Gonzalez-Acera M, Patankar JV, Erkert L, Cineus R, Gamez-Belmonte R, Leupold T, Bubeck M, Bao LL, Dinkel M, Wang R, Schickedanz L, Limberger H, Stolzer I, Gerlach K, Diemand L, Mascia F, Gupta P, Naschberger E, Koop K, Plattner C, Sturm G, Weigmann B, Günther C, Wirtz S, Stürzl M, Hildner K, Kühl AA, Siegmund B, Gießl A, Atreya R; TRR241 IBDome Consortium; Hegazy AN, Trajanoski Z, Neurath MF, Becker C.
Integrated multimodel analysis of intestinal inflammation exposes key molecular features of preclinical and clinical IBD.
Gut. 2025 Apr 29:gutjnl-2024-333729. doi: 10.1136/gutjnl-2024-333729.
Thoma OM, Naschberger E, Kubánková M, Larafa I, Kramer V, Menchicchi B, Merkel S, Britzen-Laurent N, Jefremow A, Grützmann R, Koop K, Neufert C, Atreya R, Guck J, Stürzl M, Neurath MF, Waldner MJ.
p21 Prevents the Exhaustion of CD4+ T Cells Within the Antitumor Immune Response Against Colorectal Cancer.
Gastroenterology. 2024 Feb;166(2):284-297.e11. doi: 10.1053/j.gastro.2023.09.017. Epub 2023 Sep 19. PMID: 37734420.
Naschberger E, Fuchs M, Dickel N, Kunz M, Popp B, Anchang CG, Demmler R, Lyu Y, Uebe S, Ekici AB, Geppert CI, Hartmann A, Flierl C, Petter K, Gass T, Völkl S, Scharl M, Ramming A, Günther C, Merkel S, Schellerer VS, Stürzl M.
Tumor microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome.
Cancer Commun (Lond). 2023 Nov;43(11):1280-1285. doi: 10.1002/cac2.12489. Epub 2023 Oct 19. PMID: 37859581; PMCID: PMC10631479.
Gamez-Belmonte R, Mahapatro M, Erkert L, Gonzalez-Acera M, Naschberger E, Yu Y, Tena-Garitaonaindia M, Patankar JV, Wagner Y, Podstawa E, Schödel L, Bubeck M, Neurath MF, Stürzl M, Becker C.
Epithelial presenilin-1 drives colorectal tumour growth by controlling EGFR-COX2 signalling.
Gut. 2023 Jun;72(6):1155-1166. doi: 10.1136/gutjnl-2022-327323. Epub 2022 Oct 19. PMID: 36261293.
Krug J, Rodrian G, Petter K, Yang H, Khoziainova S, Guo W, Bénard A, Merkel S, Gellert S, Maschauer S, Spermann M, Waldner M, Bailey P, Pilarsky C, Liebl A, Tripal P, Christoph J, Naschberger E, Croner R, Schellerer VS, Becker C, Hartmann A, Tüting T, Prante O, Grützmann R, Grivennikov SI, Stürzl M, Britzen-Laurent N.
N-glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy.
Gastroenterology. 2023 Mar;164(3):392-406.e5. doi: 10.1053/j.gastro.2022.11.018. Epub 2022 Nov 17. PMID: 36402190; PMCID: PMC10009756.
Wang H, Stehr AM, Singh J, Zlatar L, Hartmann A, Evert K, Naschberger E, von Stillfried S, Boor P, Muñoz LE, Knopf J, Stürzl M, Herrmann M.
Anti-DNA-IgM Favors the Detection of NET-Associated Extracellular DNA.
Int J Mol Sci. 2023 Feb 17;24(4):4101. doi: 10.3390/ijms24044101. PMID: 36835515; PMCID: PMC9958910.
Yu YQ, Thonn V, Patankar JV, Thoma OM, Waldner M, Zielinska M, Bao LL, Gonzalez-Acera M, Wallmüller S, Engel FB, Stürzl M, Neurath MF, Liebing E, Becker C.
SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth.
Cell Death Dis. 2022 Jan 12;13(1):52. doi: 10.1038/s41419-021-04483-0. PMID: 35022391; PMCID: PMC8755774.