The Midwood lab will employ state of the art tissue imaging at single cell and subcellular resolution to validate at the proteomic level pathways that are transcriptionally altered in each of the musculoskeletal diseases of interest. With a focus on how genetic variation in patients impacts the tissue microenvironment, we will map pathogenic extracellular matrix networks and cell neighbourhoods to identify lead candidates for therapeutic development, and we will generate tissue- and disease-specific matrisomal atlases to inform the design of relevant 3D models for functional examination of target pathways.