Research Interests
In most animals, many vital organs such as the heart and lungs, the GI-tract and liver, as well as the female reproductive organs are surrounded by a serosal space and contained within the greater body cavity. Our lab investigates how injuries within this serosal space are detected and repaired and how implanted foreign materials are recognized and encapsulated by a foreign body reaction. These repair mechanisms are relevant in the context of cardiothoracic and visceral surgeries, where both incomplete healing as well as excessive scarring significantly impact health and disease.
Our group aims to better understand how GATA6+ cavity macrophages recognize a deviation from homeostasis, how they are activated, and whether we can influence their activation in response to injuries and implants and thus trigger an effective healing while avoiding detrimental scarring. We also study how mesothelial cells give rise to collagen-producing myofibroblasts, a process referred to as mesothelial to mesenchymal transition (MMT). We investigate the molecular principles that govern MMT and how transformed mesothelial cells migrate towards injuries and GATA6+ cavity macrophages. Our goal in collaboration with scientists at the EMPA and ETH Zurich is to design implantable biomaterials and biochemical strategies which reduce the foreign body reaction to increase the lifetime of implantable medical devices in the peritoneal space.
To address these questions, we use tissues from human cohort studies and dedicated mouse model systems. For our research, we use animals, and we do so compassionately and in strict adherence to the legal and 3R guidelines. With our Leica Stellaris DIVE multi-photon microscope, which is equipped with a resonant scanner, we visualize cell migratory dynamics in living organs or fresh tissues from the operation room. We correlate intravital microscopy and in vitro migration assays with spatially resolved transcriptomics to infer on the underlying mechanism of cell migration. Findings from the mouse are confirmed experimentally using in vitro model systems derived from primary patient material.
Zindel J, Peiseler M, Hossain M, Deppermann C, Lee WY, Haenni B, Zuber B, Deniset JF, Surewaard BGJ, Candinas D, Kubes P. Primordial GATA6 macrophages function as extravascular platelets in sterile injury. Science. 2021 Mar 5;371(6533). doi: 10.1126/science.abe0595. PubMed PMID: 33674464.
Zindel J, Mittner J, Bayer J, April-Monn SL, Kohler A, Nusse Y, Dosch M, Büchi I, Sanchez-Taltavull D, Dawson H, Gomez de Agüero M, Asahina K, Kubes P, Macpherson AJ, Stroka D, Candinas D. Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling. Nat Commun. 2021 Dec 16;12(1):7316. doi: 10.1038/s41467-021-27612-x. PubMed PMID: 34916513; PubMed Central PMCID: PMC8677808.
Bayer J, Stroka D, Kubes P, Candinas D, Zindel J. Combination of Sterile Injury and Microbial Contamination to Model Post-surgical Peritoneal Adhesions in Mice. Bio Protoc. 2022 Aug 20;12(16). doi: 10.21769/BioProtoc.4491. eCollection 2022 Aug 20. PubMed PMID: 36199704; PubMed Central PMCID: PMC9486694.
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