Invited Lecture – Irit Sagi

The dysregulation of signaling pathways in acute inflammation can lead to chronic disease and cancer, with poorly understood specific mechanisms. In the context of inflammation, tissue damage and repair processes often involve significant remodeling of the extracellular matrix (ECM), impacting interactions with local stem cells. We propose the concept of "ECM memory for damage," suggesting that accumulated changes from inflammation perpetuate chronic inflammatory conditions. Employing advanced imaging and proteomic techniques, our study investigated ECM remodeling in an inflammation model, revealing persistent alterations in structural proteins and matrix-associated factors post-repair. Using advanced organoid model, we observed that inflamed or regenerated ECM induces inflammatory responses in local stem cells, potentially contributing to sustained inflammation. Furthermore, this model predicted abnormal stem cell behavior. Our findings shed light on the intricate interplay between ECM dynamics, stem cells, and chronic inflammation, applicable beyond specific disease contexts while offering novel opportunities for drug discovery.