UNIVERSITÄT ZU KÖLN

Kopp, A., Hagelueken, G., Jamitzky, I., Moecking, J., Schiffelers, L.D.J., Schmidt, F.I., and Geyer, M. (2023) Pyroptosis inhibiting nanobodies block Gasdermin D pore formation. Nat Commun.  14, 7923. doi: 10.1038/s41467-023-43707-z.

Jenster, L-M, Lange, K-E, Normann, S., vom Hemdt, A., Wuerth, J.D., Schiffelers,
L.D.J., Tesfamariam, Y.M., Gohr, F.N., Klein, L., Kaltheuner, I.H., Ebner, S., Lapp, D.J., Mayer, J., Moecking, J., Ploegh, H.D. Latz, E., Meissner, F., Geyer, M., Kümmerer, B.M. and Schmidt, F.I., P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection. J. Exp. Med. 2023 Vol. 220 No. 1 e20220837 https://doi.org/10.1084/jem.20220837

Akbal, A., Dernst, A., Lovotti, M., Mangan, M.S.J., McManus, R.M., & Latz, E. How location and cellular signaling combine to activate the NLRP3 inflammasome. Cell Mol Immunol (2022). https://doi.org/10.1038/s41423-022-00922-w (review)

Christ, A., Latz, E. (2021) Deciphering How NLRP3 Incites the Stromal Response in Kawasaki Vasculitis. Circulation Research 2021;129:840–842 https://doi.org/10.1161/CIRCRESAHA.121.320131

Budden, C.F., Gearing, L.J., Kaiser, R., Standke, L., Hertzog, P J., & Latz, E. (2021). Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses. Journal of Extracellular Vesicles 10, e12127. https://doi.org/10.1002/jev2.1212

Hepowit, N.L., Kolbe, C.-C., Zelle, S.R., Latz, E., MacGurn, J.A. (2021) Regulation of Ubiquitin and Ubiquitin-like Modifiers by Phosphorylation. The FEBS Journal 02 July 2021https://doi.org/10.1111/febs.16101

Alvarez, C.R., Kee, C., Sharma, A.,K., Thomas, L., Schmidt, F.I., Stanifer, M.L., Boulant, S., Herrmann, C. (2021) The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity. PLOS Pathogens June 28, 2021 https://doi.org/10.1371/journal.ppat.1009687

Koenig,P.-A., Das, H., Liu, H., Kümmerer, B. M., Gohr, F. N., Jenster, L.-N., Schiffelers, L. D. J., Tesfamariam, Y. M., Uchima, M., Wuerth, J. D., Gatterdam, K., Ruetalo, N., Christensen, M., H., Fandrey, C. I., Normann, S., Tödtmann, J. M. P., Pritzl, S., Hanke, L., Boos, J., Yuan, M., Zhu, X., Schmid-Burgk, J.-L., Kato, H., Schindler, M., Wilson, I. A., Geyer, M., Ludwig, K. U., Hällberg, B. M., Wu, N. C., Schmidt, F. I. (2021) Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Science Jan 12:eabe6230. doi: 10.1126/

Christ, A., Günther, P., Lauterbach, M.A.R., Duewell, P., Biswas, D., Pelka, K., Scholz, C.J., Oosting, M., Haendler, K., Baßler, K., Klee, K., Schulte-Schrepping, J., Ulas, T., Moorlag, S.J.C.F.M., Kumar, V., Park, M.H., Joosten, L.A.B., Groh, L.A., Riksen, N.P., Espevik, T., Schlitzer, A., Li, Y., Fitzgerald, M.L., Netea, M.G., Schultze, J.L., and Latz, E. (2018). West-ern diet triggers NLRP3-dependent innate immune reprogramming. Cell 172, 162-175.

Venegas, C.M., Kumar, S., Franklin, B.S., Dierkes, T., Brinkschulte, R., Tejera, D., Vieira-Saecker, A., Schwartz, S., Santarelli, F., Kummer, M.P., Griep, A., Gelpi, E., Beilharz, M., Riedel, D., Golenbock, D.T., Geyer, M., Walter, J., Latz, E., and Heneka M.T. (2017). In-flammasome-triggered ASC specks cross-seed β-amyloid deposition in Alzheimer’s disease. Nature 552, 355–361.

Bertheloot, D., Naumovski, A.L., Langhoff, P., Horvath, G.L., Jin, T., Xiao, T.S., Garbi, N., Agrawal, S., Kolbeck, R., and Latz, E. (2016). RAGE Enhances TLR Responses through Binding and Internalization of RNA. J. Immunol. 197, 4118-4126.

Franklin, B.S., Bossaller, L., De Nardo, D., Ratter, J.M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S.R., Al-Amoudi, A., Mangan, M.S., Zimmer, S., Monks, B.G., Fricke, M., Schmidt, R.E., Espevik, T., Jones, B., Jarnicki, A.G., Hansbro, P.M., Busto, P., Marshak-Rothstein, A., Hornemann, S., Aguzzi, A., Kastenmüller, W., and Latz, E. (2014). The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation. Nat. Immunol.15, 727-737.

De Nardo, D., Labzin, L.I., Kono, H., Seki, R., Schmidt, S.V., Beyer, M., Xu, D., Zimmer, S., Lahrmann, C., Schilberg, F.A., Vogelhuber, J., Kraut, M., Ulas, T., Kerksiek, A., Krebs, W., Bode, N., Grebe, A., Fitzgerald, M.L., Hernandez, N.J., Williams, B., Knolle, P.A., Kneiling, M., Rocken, M., Lutjohann, D., Wright, S.D., Schultze, J.L., and Latz, E. (2014). HDL mediates anti-inflammatory transcriptional reprogramming of macrophages via ATF3. Nat. Immunol. 15, 152-160.

Heneka, M.T.*, Kummer, M.P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.C., Gelpi, E., Halle, A., Korte, M., Latz, E.*, and Golenbock, D.T.* (2013). NLRP3 is activated in Alzheimer's disease and contributes to pathol-ogy in APP/PS1 mice. Nature 493, 674-678. *equal contribution

Sirois, C.M., Jin, T., Miller, A.L., Bertheloot, D., Nakamura, H., Horvath, G.L., Mian, A., Jiang, J., Schrum, J., Bossaller, L., Pelka, K., Garbi, N., Brewah, Y., Tian, J., Chang, C., Chow-dhury, P.S., Sims, G.P., Kolbeck, R., Coyle, A.J., Humbles, A.A., Xiao, T.S., and Latz, E. (2013). RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA. J. Exp. Med. 210, 2447-2463.

Duewell, P., Kono, H., Rayner, K.J., Sirois, C.M., Vladimer, G., Bauernfeind, F.G., Abela, G.S., Franchi, L., Nunez, G., Schnurr, M., Espevik, T., Lien, E., Fitzgerald, K.A., Rock, K.L., Moore, K.J., Wright, S.D., Hornung, V., and Latz, E. (2010). NLRP3 inflammasomes are re-quired for atherogenesis and activated by cholesterol crystals. Nature 464, 1357-1361.

Schmidt, F.I., Hanke, L., Morin, B., Brewer, R., Brusic, V., Whelan, S.P., Ploegh, H.L. (2016). Phenotypic lentivirus screens to identify functional single domain antibodies. Nat. Microbiol. 1, 16080.

Schmidt, F.I.*, Lu, A.*, Chen, J.W., Ruan, J., Tang, C., Wu, H., Ploegh, H.L. (2016). A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly. J Exp Med. 213, 771-790. *equal contribution

Former participating Project Leader:

Eicke Latz

Institute of Innate Immunity, University Hospital Bonn, University of Bonn
Contact: eicke.latz(at)uni-bonn.de
For more information visit: Latz Lab

Former Abstract:

The identity of most pyroptosis-dependent proinflammatory and potentially regulatory factors and their effects on surrounding cells is poorly understood. The project will study the molecular details and functional consequences of pyroptosis-dependent secreted factors and the mechanisms and kinetics of pore formation by gasdermins. These studies aim to unravel novel pathways involved in chronic tissue damage and inflammatory diseases involving pyroptosis.