Identification of novel bioactive mediators of tissue scarring, inflammation and extracellular matrix remodeling after spinal cord injury
Project aim: Dysregulated inflammation, scarring and extracellular matrix remodelling underlie the chronic pathology that leads to the failure of tissue repair and recovery after traumatic spinal cord injury (SCI). Our multidisciplinary translational project combines basic science and clinical approaches with innovative technology to: a) characterize how intrinsic pattern-recognition inflammatory mechanisms affect matrix synthesis and proteolysis after SCI, b) identify novel cellular and extracellular bioactive proteins in SCI tissue and c) identify proteins with therapeutic potential in human SCI. Work plan: We will examine the role of inflammatory activation on tissue remodeling and scarring in clinically relevant rat (Bradbury group) and mouse (David group) models of SCI, while the presence of endogenous alarmins will be assessed for the first time in human SCI plasma (Schwab group). Advanced proteomics analysis (Schlapbach group) will characterize changes in the extracellular proteome related to alarmin signaling in rodent SCI tissues and human SCI cerebrospinal fluid. Exploitation of results: The high-throughput discovery approach utilised in this study will provide a valuable dataset resource for the field, leading to new mechanistic insight and the identification of novel bioactive mediators of inflammatory tissue remodelling after SCI. This work should lead to the development of novel therapeutics to target post-injury remodelling and improve outcome for SCI patients.
Computational neurosciences, Molecular modelling techniques, Pharmacology, Biomarkers, proteomics, Clinical trial, "omics" approaches, extracellular matrix, cerebrospinal fluid, tissue remodelling, inflammation, glial scar
2017 - 2021
Elizabeth Bradbury (Coordinator)
United Kingdom (MRC)