Decoding danger signals from the extracellular matrix reveals new strategies to treat inflammatory disease and cancer

Please note change of series location to Sherrington Library

All tissues are made up of cells surrounded by an extracellular matrix. The matrix is a complex, 3D network of secreted molecules, which defines tissue architecture by organizing the spatial positioning of resident cells, and which provides environmental signals that dictate cell behavior. The Midwood lab investigates how matrix molecules that are not found in healthy tissues, but which are specifically induced during tissue damage and cellular stress, act as danger signals, creating pro-inflammatory niches that orchestrate immune cell mobilization and activation, triggering inflammatory programmes designed to drive repair and restore homeostasis. We discovered how matrix molecules activate distinct immune signalling pathways compared to those induced upon pathogen invasion, and how regulatory control over these endogenous triggers of inflammation goes awry driving chronic inflammation in autoimmune, fibrotic and metabolic diseases. We also identified how tumors exploit these mechanisms to evade immune surveillance, mediating immune cell exclusion and immune suppression. Current work focuses on translating these discoveries into novel diagnostic tools, and developing new drugs that target the microenvironment to selectively ameliorate aberrant inflammation in inflammatory diseases, leaving host defence against infection intact, and to restore immunity against hard-to-treat tumors that have evolved to evade immune elimination.