A01 - Mechanisms of cell death-induced inflammation
Manolis Pasparakis
Institute for genetics, CECAD, University of Cologne
Contact: pasparakis(at)uni-koeln.de
For more information visit: Pasparakis lab
Abstract
Studies in mouse models provided evidence that cell death triggers inflammation, however the underlying mechanisms remain elusive. Using relevant genetic mouse models, this project will study the mechanisms by which different types of cell death trigger inflammation in vivo, focusing primarily on apoptosis and necroptosis. Major focus areas will be the in vivo role of specific DAMPs and their receptors as well as the mechanisms determining DAMP release via plasma membrane permeabilisation and their functional consequences in triggering cell death-induced inflammation.
Recent Publications
Schorn, F., Werthenbach, J.P., Hoffmann, M., Daoud, M., Stachelscheid, J., Schiffmann, L.M., Hildebrandt, X., Lyu, S.I., Peltzer, N., Quaas, A., Vucic, D., Silke, J., Pasparakis, M. and Kashkar, H. (2023) cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation. EMBO J. doi: 10.15252/embj.2023113614
Injarabian, L., Willenborg, S., Welcker, D., Sanin, D.E., Pasparakis, M., Kashkar, H. and Eming, S.A. (2023) FADD- and RIPK3-mediated cell death ensures clearance of Ly6Chigh wound macrophages from damaged tissue. J Invest Dermatol. doi: 10.1016/j.jid.2023.06.203.
Imai, T., Van, TM., Pasparakis, M., Polykratis, A. (2022). Smooth muscle cell specific NEMO deficiency inhibits atherosclerosis in ApoE−/− mice. Sci Rep 12, 12538 (2022). https://doi.org/10.1038/s41598-022-16737-8
Jiao, H., Wachsmuth, L., Wolf, S., Lohmann, J., Nagata, M., Kaya, G. G., Oikonomou, N., Kondylis, V., Rogg, M., Diebold, M., Tröder, S.E., Zevnik, B., Prinz, M., Schell, C., Young, G.R., Kassiotis, G: & Pasparakis, M. (2022) ADAR1 averts fatal type I interferon induction by ZBP1. Nature (2022). https://doi.org/10.1038/s41586-022-04878-9
Theobald, S.J., Gräb, J., Fritsch, M., Suárez, I., Eisfeld, H.S., Winter, S., Koch, M., Hölscher, C., Pasparakis, M., Kashkar, H., and Rybniker, J. (2021) Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis-infected macrophages. Cell Death Discov. 7, 327 (2021). https://doi.org/10.1038/s41420-021-00716-5
Wenzel, J., Lampe, J., Müller-Fielitz, H., Schuster, R., Zille, M., Müller, K., Krohn, M., Körbelin, J., Zhang, L., Özorhan, Ü., Neve, V., Wagner, J.U.G., Bojkova, D., Shumliakivska, M., [...] Altmeppen, H.C., Pasparakis, M., Dimmeler, S., Cinatl, J., Püschel, K., Zelic, M., Ofengeim, D., Stadelmann, C., Trottein, F., Nogueiras, R., Hilgenfeld, R., Glatzel, M., Prevot, V., & Schwaninger, M. (2021) The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nat Neurosci. https://doi.org/10.1038/s41593-021-00926-1
Schünke, H., Göbel, U., Dikic, I., Pasparakis, M. (2021). OTULIN inhibits RIPK1-mediated keratinocyte necroptosis to prevent skin inflammation in mice. Nature Communications 12, Article Number: 5912 https://doi.org/10.1038/s41467-021-25945-1
Oikonomou, N., Schuijs, M.J., Chatzigiagkos, A., Androulidaki, A., Aidinis, V., Hammad, H., Lambrecht, B.N., and Pasparakis, M. (2021) Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation. Mucosal Immunology https://doi.org/10.1038/s41385-021-00415-5
Kumari, S., Van, T.-M., Preukschat, D., Schuenke, H., Basic, M., Bleich, A., Klein, U., Pasparakis, M. (2021) NF-κB inhibition in keratinocytes causes RIPK1-mediated necroptosis and skin inflammation. Life Science Alliance 15 April 2021. DOI: 10.26508/lsa.202000956
Laurien, L., Nagata, M., Schünke, H., Delanghe, T., Wiederstein, J., L., Kumari, S., Schwarzer, R., Corona, T., Krüger, M., Bertrand, M., J., M., Kondylis, V. & Pasparakis, M. (2020). Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation. Nat. Comm. Volume 11, Article number: 1747. https://doi.org/10.1038/s41467-020-15466-8
Schwarzer, R., Jiao, H., Wachsmuth, L., Tresch, A., Pasparakis, M. (2020). FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. Immunity Volume 52, Pages 1-16. https://doi.org/10.1016/j.immuni.2020.04.002 For free acces please go here
Schwarzer, R., Laurien, L., Pasparakis, M. (2020). New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8. Curr. Opin. Cell Biol. Volume 63, Pages 186-193. https://doi.org/10.1016/j.ceb.2020.02.004
Jiao, H., Wachsmuth, L., Kumari, S., Schwarzer, R., Lin, J., Eren, R., O., Fisher, A., Lane, R., Young, G., R., Kassiotis, G., Kaiser W., J., Pasparakis, M. (2020). Z-nucleic-acid sensing triggers ZBP1dependent necroptosis and inflammation. Nature, https://doi.org/10.1038/s41586-020-2129-8