Gavin E. Arteel, PhD

Our group is investigating the magnitude and impact of the changes to the hepatic matrisome in the context of the development and recovery from liver disease. As the main detoxifying organ in the body, the liver has tremendous ability to heal and regenerate from injury. The regenerative response in the liver can be perturbed and impacts recovery from injury or damage. The extracellular matrix (ECM) consists of a diverse range of components that work bi-directionally with surrounding cells to create a dynamic microenvironment that regulates cell signaling, recruitment, and tissue function. The basic definition of the ECM comprises fibrillar proteins (e.g., collagens, glycoproteins and proteoglycans). More recently, groups have extended the definition to include ECM affiliated proteins, regulator/modifier proteins and secreted factors (i.e., the ; 'matrisome'). Quantitative and qualitative changes to the ECM structure and superstructure can impact overall health of the organ and organism. Remodeling of the hepatic ECM/matrisome in response to injury is well understood in some contexts. For example, changes to the ECM associated with fibrosis are considered almost synonymous with hepatic ECM changes. Proteomic-based studies in other organs haves demonstrated that the matrisome responses dynamically in composition after insult well before fibrotic changes to the organ. These changes to the ECM may not alter overall ECM architecture and are therefore histologically undetectable. Nevertheless, these changes have potential to alter hepatic phenotype and function. These acute responses can be viewed as an arm of the wound healing response and facilitate recovery from damage, which resolves once the damage is repaired. However, under conditions of chronic injury, these changes likely contribute to activation of a significant remodeling response that leads to scar formation (i.e., fibrosis). It is our goal to better understand this process, as well as to develop minimally-invasive biomarkers to predict interindividual risk.