Matthew Layne

The primary goal of our laboratory is to identify novel pathways that control extracellular matrix (ECM) synthesis and assembly as they relate to fibroproliferative and connective tissue diseases. Our long term goal is to use this knowledge to develop therapeutic strategies for these conditions. Fibroproliferative responses are similar to wound healing processes involving accumulation of contractile myofibroblasts and ECM secretion and assembly. Because organ fibrosis, cardiovascular, metabolic/obesity, and cancer pathologies are now recognized to be impacted by fibroblast-myofibroblast differentiation and ECM remodeling our research is examining novel pathways and control mechanisms in these diseases. In collaborative work, we are investigating the mechanisms of adipose tissue fibrosis and remodeling. Central to our studies is determining the function of Aortic Carboxypeptidase-like Protein (ACLP), a secreted, collagen-binding protein that enhances fibrosis and myofibroblast differentiation through mechanisms that involve stimulating the transforming growth factor ß (TGFß) receptor signaling complex and controlling mechanical signaling and ECM remodeling. Recent work is uncovering the role of ACLP (and AEBP1 genetic mutations in the connective tissue disease Ehlers-Danlos syndrome. There are several active projects in the lab including:

• Investigating the mechanisms of how ACLP/AEBP1 mutations cause Ehlers-Danlos syndrome (EDS)
• Defining the role of ACLP in mechanotransduction pathways that control progenitor differentiation.
• Developing strategies to organ fibrosis through targeting ACLP
• Uncovering new mechanisms that control adipose tissue fibrosis.