Alessandro Annibaldi | Mechanisms of cross-talk between different cell death pathways
Dr. Alessandro Annibaldi
Center for Molecular Medicine Cologne, University of Cologne
Contact: a.annibaldi(at)uni-koeln(dot)de
For more information visit: Annibaldi Lab
Abstract
The plasticity between different forms of programmed cell death, in particular apoptosis, necroptosis and pyroptosis, is crucially important for tissue homeostasis and repair following different types of insults, such as pathogenic infection or injury. However, the mechanisms controlling such plasticity are only starting to be understood. Here, we want to investigate the cross-talk between apoptosis, necroptosis and pyroptosis, its regulatory mechanisms and relevance to tissue homeostasis and repair. One of the signalling nodes that plays a key role in the regulation of these three forms of cell death is represented by the heterodimer composed of Caspase-8 and cFLIP long (here referred to as cFLIP). Although cFLIP has long been known as regulator of Caspase-8 activity, the mechanisms by which cFLIP does so are still poorly understood. In this project, we will use a newly generated, as well as already existing models of genetically altered mice to understand the function of cFLIP in the regulation of Caspase-8 activity and the role of cFLIP for the ability of Caspase-8 to orchestrate different types of cell death. The findings coming from this research proposal will help understand how cells coordinate different cell death programs and their pathophysiological role.
Recent Publications
2026
Kashkar H, Pasparakis M. Cell-death networks. Mol Cell. 2025 Oct 16;85(20):3890-3890.e1. doi: 10.1016/j.molcel.2025.09.028. PMID: 41106376.
Project Annibaldi Publications 2nd Funding Period 2024 - 2027
2025
Hildebrandt X, Veli Ö, Hyoubi A, Zinngrebe J, Abdallah AT, Rodefeld J, Hoffmann A, Gardeweg L, Kaya Ö, Wagner E, Lindhorst A, Poggenberg M, Wang Y, Dimmler J, Schillings J, Koci P, Bonechi F, Capuccino LV, Kiefer C, Kelepouras K, Ghosh A, Noé F, Wolfrum C, Singer M, Liccardi G, Luedde T, Yavas A, Ghallab A, Hengstler JG, Antczak P, Gericke M, Winkels H, Blüher M, Walczak H, Annibaldi A, Fischer-Posovszky P, Peltzer N. Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome. Sci Adv. 2025 Sep 19;11(38):eadw2539. doi: 10.1126/sciadv.adw2539. Epub 2025 Sep 17. PMID: 40961178; PMCID: PMC12442851.
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.
Project Annibaldi Publications 1st Funding Period 2020 - 2023
2023
Martinez Lagunas, K., Savcigil, D.P., Zrilic, M., Carvajal Fraile, C., Craxton, A., Self, E., Uranga-Murillo, I., de Miguel, D., Arias, M., Willenborg, S., Piekarek, M., Albert, MC., Nugraha, K., Lisewski, I., Janakova, E., Igual, N., Tonnus, W., Hildebrandt, X., Ibrahim, M., Ballegeer, M., Saelens, X., Kueh, A., Meier, P., Linkermann, A., Pardo, J., Eming, S., Walczak, H., MacFarlane, M., Peltzer, N., Annibaldi, A. (2023) Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair. Sci Adv. doi: 10.1126/sciadv.adg2829
2020
Annibaldi A, Walczak H. Death Receptors and Their Ligands in Inflammatory Disease and Cancer.Cold Spring Harb Perspect Biol. 2020 Jan 27. doi: 10.1101/cshperspect.a036384.
Project related Publications
2017 - 2019
Liccardi G, Ramos Garcia L, Tenev T, Annibaldi A, Legrand AJ, Robertson D, Feltham R, Anderton H, Darding M, Peltzer N, Dannappel M, Schünke H, Fava LL, Haschka MD, Glatter T, Nesvizhskii A, Schmidt A, Harris PA, Bertin J, Gough PJ, Villunger A, Silke J, Pasparakis M, Bianchi K, Meier P. RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation. Mol Cell. 2019 Feb 7;73(3):413-428.e7. doi: 10.1016/j.molcel.2018.11.010. Epub 2018 Dec 28. PubMed PMID: 30598363; PubMed Central PMCID: PMC6375735.
Feltham R, Jamal K, Tenev T, Liccardi G, Jaco I, Monteiro Domingues C, Morris O, Wicky John S, Annibaldi A, Widya M, et al. (2018) Mind bomb regulates cell death during TNF signalling by suppressing RIPK1’s cytotoxic potential.Cell Reports, Apr 10;23(2):470-484.
Annibaldi A, Wicky John S, Vanden Berghe T, Ruan J, Wu H, Bianchi K, Elliot P, Komander D, Choi S. M, Van Coillie S, et al. (2018). Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2. Molecular Cell, Feb 15;69(4):566-580
Annibaldi A. and Pascal Meier. (2017)Checkpoints in TNF-induced cell death: implications in inflammation and cancer.Trends Mol Med, Dec 4, S1471-4914(17)30202-2
*Jaco I, *Annibaldi A, Lalaoui N, Wilson, R, Tenev, T, Laurien, L, Kim, C, Jamal K, Wicky John S, Liccardi G, et al. (2017). MK2 phosphorylates RIPK1 to prevent TNF induced cell death.Molecular Cell,Jun1;66(5), 698-710. *: Joint authorship