A03 - Identification of molecules and key pathways that drive necroptosis-dependent inflammation
Veit Hornung
Gene Center Munich, Department for Biochemistry, Ludwig-Maximilians-University Munich
Contact: hornung(at)genzentrum.lmu.de
For more information visit: Hornung lab
Abstract
Unlike apoptosis, necroptosis results in the release of cytosolic contents that are believed to induce inflammation. Using a well-established in vitro model of human cells, this project aims to characterise necroptosis-driven inflammation in vitro and to identify necroptosis-dependent DAMP or alarmin molecules. By systematically perturbing all known PRR- and cytokine receptor-dependent signalling cascades within bystander cells this project will additionally characterise the dominant sensing modalities in this setting. These efforts will provide novel mechanistic insights into how necroptosis triggers inflammation.
Recent Publications
Sun, Z., Cernilogar, F.M., Horvatic, H., Yeroslaviz, A., Abdullah, Z., Schotta, G. and Hornung. V. (2023) β1 integrin signaling governs necroptosis via the chromatin-remodeling factor CHD4. Cell Rep. 42, 113322. doi: 10.1016/j.celrep.2023.113322. Epub ahead of print. PMID: 37883227.
Pinci, F., Gaidt, M.M., Jung, C., Nagl, D., Kuut, G., Hornung, V. (2022) Tumor necrosis factor is a necroptosis-associated alarmin. Front. Immunol. 13:1074440. doi: 10.3389/fimmu.2022.1074440
Schmacke, N.A., O'Duill, F., Gaidt, M.M., Szymanska, I., Kamper, J.M., Schmid-Burgk, J.L., Mädler, S.C., Mackens-Kiani, T., Kozaki, T., Chauhan, D., Nagl, D., Stafford, C.A., Harz, H., Fröhlich, A.L.. Pinci, F., Ginhoux, F.L., Beckmann, R., Mann, M., Leonhardt, H., Hornung, V. (2022) IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. Immunity 2022 Nov 9;S1074-7613(22)00562-3. doi: 10.1016/j.immuni.2022.10.021.
Stafford, C.A., Gassauer, A.-M., de Oliveira Mann, C.C., Tanzer, M.C., Fessler, E., Wefers, B., Nagl, D., Kuut, G., Sulek, K., Vasilopoulou, C., Schwojer, S.J., Wiest, A., Pfautsch, M.K., Wurst, W., Yabal, M., Fröhlich, T., Mann, M., Gisch, N., Jae, L.T., & Hornung, V. Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation. Nature 609, 590–596 (2022). https://doi.org/10.1038/s41586-022-05125-x
Bauernfried. S., & Hornung, V. (2021) DPP9 restrains NLRP1 activation. Nat Struct Mol Biol. https://doi.org/10.1038/s41594-021-00580-y
Pinci, F., Gaidt, M. M., Jung,C., Kuut, G., Jackson, M. A., Bauernfried, S., and Hornung, V. (2020) C-tag TNF: a reporter system to study TNF shedding. Journal of Biological Chemistry Vol 295, Issue 52. DOI 10.1074/jbc.RA120.015248