A05 | Inflammatory signalling in ferroptotic cell death
Prof. Dr. Silvia von Karstedt
Department of Translational Genomics,
CECAD - Center for Molecular Medicine Cologne
Contact: s.vonkarstedt(at)uni-koeln(dot)de
For more information visit: von Karstedt Lab
Abstract
Ferroptosis is a newly described form of regulated necrosis independent of caspases and the necrosome, but dependent on ferrous iron that is accompanied by an inflammatory response. The identity of inflammatory mediators released from ferroptotic cells and how they might elicit an inflammatory response remain unknown. The project aims to achieve a first in-depth characterisation of ferroptotic DAMPs, characterise inflammatory signaling events relevant to bystander cells and to study the role of ferroptosis on immune cell activation in vivo.
Recent Publications
2026
Tishina S, Dahlhaus A, Manik M, Mulalic L, Murr J, Kotliar M, Rakhsh-Khorshid H, Kostopoulou M, Hocher F, Stroh J, Beck J, Williams RM, Balta GG, Liu F, Abdallah AT, Bebber CM, Reese M, Lim JKM, Quaas A, Brägelmann J, Pasparakis M, Beleggia F, Balachandran S, Trauzold A, Liccardi G, Astsaturov I, Reichert M, Androulidaki A, von Karstedt S. Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis. Nat Commun. 2026 Jun 15;17(1):5288. doi: 10.1038/s41467-026-73189-8. PMID: 42297776; PMCID: PMC13269921.
Jacobs LJ, Doll S, Trümbach D, Veronese M, Di Pietro G, Yapici FI, Hasberg L, Gentzsch P, Gerlich S, Hansen J, von Karstedt S, Rugarli EI, Conrad M, Salvador A, Riemer J. Cytosolic PRDX1 acts as an extramitochondrial sink to set mitochondrial H2O2 levels and enable resilience to chronic mitochondrial oxidative stress. Redox Biol. 2026 Apr 30;94:104195. doi: 10.1016/j.redox.2026.104195. Epub ahead of print. PMID: 42085864; PMCID: PMC13158620.
Seidel E, Itak EY, Müller F, Yapici FI, Brägelmann J, Berg J, von Karstedt S. A feedback loop between cell proliferation and ROS regulates ferroptosis sensitivity. Front Cell Dev Biol. 2026 Mar 25;14:1756238. doi: 10.3389/fcell.2026.1756238. PMID: 41960191; PMCID: PMC13059718.
Project A05 Publications 2nd Funding Period 2024 - 2027
2025
Androulidaki A, Liu F, Bebber CM, Kisis I, Sakthivelu V, Hunold P, Koerner L, Dahlhaus A, Yapici FI, Grimm C, Pacholewska A, Tishina S, Doskotz F, Torres Fernández LA, Stroh J, Abdallah AT, Beck J, Mulalic L, Schmitt A, Grüll H, Persigehl T, Quaas A, Peifer M, Brägelmann J, Reinhardt HC, Nieper P, Hänsel-Hertsch R, Thomas RK, George J, Schweiger MR, Pasparakis M, Beleggia F, von Karstedt S. Lack of caspase 8 directs neuronal progenitor-like reprogramming and small cell lung cancer progression. Nat Commun. 2025 Dec 18;16(1):11280. doi: 10.1038/s41467-025-67142-4. PMID: 41413044; PMCID: PMC12717127.
Langpape A, Bonasera D, Stroh J, Reese M, Cartolano M, Liccardi G, von Karstedt S. Redox destabilization by ibrutinib promotes ferroptosis in diffuse large B-cell lymphoma (DLBCL). Cell Death Discov. 2025 Oct 31;11(1):495. doi: 10.1038/s41420-025-02826-w. PMID: 41173858; PMCID: PMC12578790.
Sakthivelu V, Schmitt A, Odenthal F, Ndoci K, Touet M, Shaib AH, Chihab A, Wani GA, Nieper P, Hartmann GG, Pintelon I, Kisis I, Boecker M, Eckert NM, Iannicelli Caiaffa M, Ibruli O, Weber J, Maresch R, Bebber CM, Chitsaz A, Lütz A, Kim Alves Carpinteiro M, Morris KM, Franchino CA, Benz J, Pérez-Revuelta L, Soriano-Campos JA, Huetzen MA, Goergens J, Jevtic M, Jahn-Kelleter HM, Zempel H, Placzek A, Hennrich AA, Conzelmann KK, Tumbrink HL, Hunold P, Isensee J, Werr L, Gaedke F, Schauss A, Minère M, Müller M, Fenselau H, Liu Y, Heimsoeth A, Gülcüler Balta GS, Walczak H, Frezza C, Jachimowicz RD, George J, Schmiel M, Brägelmann J, Hucho T, von Karstedt S, Peifer M, Annibaldi A, Hänsel-Hertsch R, Persigehl T, Grüll H, Sos ML, Reifenberger G, Fischer M, Adriaensen D, Büttner R, Sage J, Brouns I, Rad R, Thomas RK, Anstötz M, Rizzoli SO, Bergami M, Motori E, Reinhardt HC, Beleggia F. Functional synapses between neurons and small cell lung cancer. Nature. 2025 Sep 10. doi: 10.1038/s41586-025-09434-9. Epub ahead of print. Erratum in: Nature. 2025 Sep 19. doi: 10.1038/s41586-025-09638-z. PMID: 40931078.
Stachura P, Lu Z, Kronberg RM, Xu HC, Liu W, Tu JW, Schaal K, Kameri E, Picard D, von Karstedt S, Fischer U, Bhatia S, Lang PA, Borkhardt A, Pandyra AA. Deep transfer learning approach for automated cell death classification reveals novel ferroptosis-inducing agents in subsets of B-ALL. Cell Death Dis. 2025 May 18;16(1):396. doi: 10.1038/s41419-025-07704-y. PMID: 40382332; PMCID: PMC12085637.
Yapici FI, Seidel E, Dahlhaus A, Weber J, Schmidt C, de Britto Chaves Filho A, Yang M, Nenchova M, Güngör E, Stroh J, Kotouza I, Beck J, Abdallah AT, Lackmann JW, Bebber CM, Androulidaki A, Kreuzaler P, Schulze A, Frezza C, von Karstedt S. An atlas of ferroptosis-induced secretomes. Cell Death Differ. 2025 Apr 25. doi: 10.1038/s41418-025-01517-4. Epub ahead of print. PMID: 40281125.
Roeck BF, Lotfipour Nasudivar S, Vorndran MRH, Schueller L, Yapici FI, Rübsam M, von Karstedt S, Niessen CM, Garcia-Saez AJ. Ferroptosis spreads to neighboring cells via plasma membrane contacts. Nat Commun. 2025 Mar 26;16(1):2951. doi: 10.1038/s41467-025-58175-w. PMID: 40140422; PMCID: PMC11947162.
Project A05 Publications 1st Funding Period 2020 - 2023
2023
Müller, F., Lim, J.K.M., Bebber, C.M., Seidel, E., Tishina, S., Dahlhaus, A., Stroh, J., Beck, J., Yapici, F.I., Nakayama, K., Torres Fernández, L., Brägelmann, J., Leprivier, G., and von Karstedt, S. (2023. Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation. Cell Death Differ30, 442-456. doi: 10.1038/s41418-022-01096-8.
2022
Seidel, E., & von Karstedt, S. (2022) Extrinsic cell death pathway plasticity: a driver of clonal evolution in cancer? Cell Death and Differentiation 8, Article number: 465 (review)
2021
Montinaro, A., Areso Zubiaur, I., Saggau, J., Kretz, A-L-, Ferreira, R.M.M., Hassan, O., Kitzig, E., Müller, I., El-Bahrawy, M.A., von Karstedt, S., Kulms, D., Liccardi, G., Lemke J. & Walczak, H. (2021) Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers. Cell Death Differentiation. https://doi.org/10.1038/s41418-021-00869-x
Bebber, C.M., Thomas, E.S., Stroh, J., Chen, Z., Androulidaki, A., Schmitt, A., Höhne, M.N., Stüker, L., de Pádua Alves,C., Khonsari, A., Dammert, M.A., Parmaksiz, F., Tumbrink, H.L., Beleggia, F., Sos, M.L., Riemer, J., George, J., Brodesser, S., Thomas, R.K., Reinhardt, H.C. & von Karstedt, S. (2021) Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes.Nature Communications volume 12, Article number: 2048. https://doi.org/10.1038/s41467-021-22336-4
2020
Clemente, L.P., Rabenau, M., Tang, S., Stanka, J., Cors, E., Stroh, J.,Culmsee, C., von Karstedt, S. (2020) Dynasore Blocks Ferroptosis through Combined Modulation of Iron Uptake and Inhibition of Mitochondrial Respiration. Cells Oct 9;9(10):E2259. doi: 10.3390/cells9102259
Bebber, C.M., Müller, F., Clemente, L.P., Weber, J., von Karstedt, S., (2020). Ferroptosis in Cancer Cell Biology. Cancers (Basel) 2020 Jan; 12(1):164.
Project related Publications
2015 - 2019
Lim, J.K.M., Delaidelli, A., Minaker, S.W., Zhang, H.-F., Colovic, M., Yang, H., Negri, G.L., Karstedt, von, S., Lockwood, W.W., Schaffer, P., et al. (2019). Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance. Proc. Natl. Acad. Sci. U.S.A. 1092, 201821323.
Hartwig, T.*, Montinaro, A.*, von Karstedt, S.*, Sevko, A., Surinova, S., Chakravarthy, A., Taraborrelli, L., Draber, P., Lafont, E., Arce Vargas, F., et al. (2017). The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2. Mol. Cell 65, 730–742.e5. * These authors contributed equally to this work.
von Karstedt, S., Conti, A., Nobis, M., Montinaro, A., Hartwig, T., Lemke, J., Legler, K., Annewanter, F., Campbell, A.D., Taraborrelli, L., et al. (2015). Cancer cell-autonomous TRAIL-R signaling promotes KRAS-driven cancer progression, invasion, and metastasis. Cancer Cell 27, 561–573.
von Karstedt, S.*, Montinaro, A.*, and Walczak, H. (2017). Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy. Nat. Rev. Cancer 17, 352–366. * These authors contributed equally to this work.
Patents: Named inventors: H. Walczak, S. von Karstedt; Methods for treating cancer (publication date 08.01.2015; WO2015001345)