In the second funding period, Project B04 will investigate mechanisms underlying heterocellular crosstalk in cardiac repair and regeneration. Using complementary zebrafish and mouse model systems, genetic approaches to label and track interacting cell populations, as well as live-imaging and -omics approaches, we will define the molecular and cellular mechanisms that mediate intercellular communication and determine its functional importance for cardiac repair and regeneration.
In the first funding period, Project B04 investigated the importance of the AP-1-regulated stress response in cardiac repair and regeneration. We found that cardiomyocyte autophagy plays an important role in cardiac regeneration, in part by regulating gene expression programs in macrophages. These findings reveal an unexpected crosstalk between processes originating in cardiomyocytes and innate immune cells in the regenerating heart.
Wu B*, Constanty F*, Beisaw A.
Seminars in Cell and Developmental Biology. 2025; 171: 103619.
Constanty F, Wu B, Wei KH, Lin IT, Dallmann J, Guenther S, Lautenschlaeger T, Priya R, Lai SL, Stainier DYR & Beisaw A.
Nature Communications. 16:3823, 2025.
Miyara S, Adler M, Umansky KB, Haussler D, Bassat E, Divinsky Y, Elkahal J, Kain D, Lendengolts D, Ramirez Flores RO, Bueno-Levy H, Golani O, Shalit T, Gershovits M, Weizman E, Genzelinakh A, Kimchi DM, Shakked A, Zhang L, Wang J, Baehr A, Petrover Z, Sarig R, Dorn T, Moretti A, Saez-Rodriguez J, Kupatt C, Tanaka EM, Medzhitov R, Kruger A, Mayo A, Alon U & Tzahor E.
Cell Syst. 16:101198, 2025.
Hofmann C, Serafin A, Schwerdt OM, Fischer J, Sicklinger F, Younesi FS, Byrne NJ, Meyer IS, Malovrh E, Sandmann C, Jürgensen L, Kampf-Schenk V, Stroh C, Löwenthal Z, Finke D, Boileau E, Beisaw A, Bugger H, Bettel M, Stein F, Katus HA, Jakobi T, Frey N, Leuschner F, Völkers M.
Circulation. 150:1248-67, 2024.
Cordero J, Elsherbiny A, Wang Y, Jürgensen L, Constanty F, Guenther S, Boerries M, Heineke J, Beisaw A, Leuschner F, Hassel D, Dobreva G.
Nucleic Acids Res. 52:4215-33, 2024.
Aviel G, Elkahal J, Umansky KB, Bueno-Levy H, Petrover Z, Kotlovski Y, Lendengolts D, Kain D, Shalit T, Zhang L, Miyara S, Kramer MP, Merbl Y, Kozlovski S, Alon R, Aharoni R, Arnon R, Mishali D, Katz U, Nachman D, Asleh R, Amir O, Tzahor E & Sarig R.
Nat Cardiovasc Res. 3:1049-66, 2024.
Tzahor E & Dimmeler S.
Science. 377:eabm4443, 2022.
Srishti Shekhar
