Integration of inflammation and pattern recognition receptor signaling into unfolded protein response-driven colonic tumorigenesis
Prof. Dr. rer. nat. Dirk Haller
Technical University of Munich
School of Life Sciences
Chair of Nutrition and Immunology(link is external)
Project Summary
Unfolded protein responses (UPR) of the endoplasmic reticulum is associated with intestinal inflammation and tumorigenesis. We created novel mouse models in which epithelial cell-specific activation of the UPR pathway is enforced using constitutively active forms of activating transcription factor 6 (ATF6). Using germ-free mice, we made the striking observation that the presence of microbiota in the context of aberrant UPR activation is necessary for spontaneous colon tumor formation. In the proposed project, they will study which innate immune receptors and pathways are engaged by the microbiota and synergize with epithelial cell-specific UPR to promote tumorigenesis.
Dirk Haller is awarded the distinguished UEG Research Prize 2021 for his outstanding project “Repurposing mitochondria-protective targets for adjuvant IBD therapy”.
Prof. Dr. Dirk Haller received the Heinz Maier-Leibnitz Medaille 2020 "in recognition of his outstanding, internationally recognized research on the role of nutrition and the microbiome in the pathogenesis of chronic diseases".
The composition and function of bacteria in the human intestine – the so-called gut microbiome – changes as the day progresses.
Crohn’s disease is a chronic inflammatory disorder of the intestine that, in most cases, relapses episodically. As of now, there is no cure for this disease.
The team of Professor Dirk Haller at the Technical University of Munich (TUM) made an unexpected discovery while investigating the triggering factors of colon cancer: Cell stress in combination with an altered microbiota in the colon drives tumour growth. Previously, it was assumed that this combination only contributes to inflammato
Coleman, O., Ecker, M., Haller, D. (2022). Curr Opin Gastroenterol 38, 162-167.
DOI:10.1097/MOG.0000000000000811
Coleman, O. I., Haller, D. (2021). Cancers (Basel) 13, 616.
DOI:10.3390/cancers13040616(link is external)
Papaioannou, N. E., Salei, N., Rambichler, S., Ravi, K., Popovic, J., Kuntzel, V., Lehmann, C. H. K., Fiancette, R., Salvermoser, J., Gajdasik, D. W., Mettler, R., Messerer, D., Carrelha, J., Ohnmacht, C., Haller, D., Stumm, R., Straub, T., Jacobsen, S. E. W., Schulz, C., Withers, D. R., Schotta, G., Dudziak, D., Schraml, B. U. (2021). Nat Commun 12, 464.
DOI:10.1038/s41467-020-20659-2(link is external)
Stengel, S. T., Fazio, A., Lipinski, S., Jahn, M. T., Aden, K., Ito, G., Wottawa, F., Kuiper, J. W. P., Coleman, O. I., Tran, F., Bordoni, D., Bernardes, J. P., Jentzsch, M., Luzius, A., Bierwirth, S., Messner, B., Henning, A., Welz, L., Kakavand, N., Falk-Paulsen, M., Imm, S., Hinrichsen, F., Zilbauer, M., Schreiber, S., Kaser, A., Blumberg, R., Haller, D., Rosenstiel, P. (2020). Gastroenterology 159, 1357-1374 e1310.
DOI:10.1053/j.gastro.2020.06.088 (link is external)
Coleman, O. I. and Haller, D. (2019). Front Immunol 10, 2825.
DOI:10.3389/fimmu.2019.02825(link is external)
Coleman, O.I., Lobner, E.M., Bierwirth, S., Sorbie, A., Waldschmitt, N., Rath, E., Berger, E., Lagkouvardos, I., Clavel, T., McCoy, K.D., Weber, A., Heikenwalder, M., Janssen, K.P., Haller, D. (2018). Gastroenterology 155, 1539-1552 e1512.
DOI: 10.1053/j.gastro.2018.07.028(link is external)