The extracellular matrix plays critical roles in regulating diverse biological and pathological processes, including developmental morphogenesis, tissue repair and remodeling, inflammation and host defense, and progression of diseases such as cancer. Our laboratory is interested in the biological functions of CCNs, a family of cysteine-rich, dynamically expressed matricellular proteins that regulates a broad range of cellular activities through direct binding to integrin receptors and heparan sulfate proteoglycans. Ccn1- and Ccn2-null mice are embryonic and perinatal lethal due to cardiovascular and skeletal defects, respectively, underscoring the importance of these matrix proteins. In addition, aberrant expression of Ccn1 and Ccn2 is associated with pathological conditions including wound healing, atherosclerosis, restenosis, rheumatoid arthritis, and cancer.
Our current studies aim to understand how CCN proteins function through integrin-mediated signaling to regulate diverse processes, including cell differentiation, migration and invasion, and survival and apoptosis. To investigate the biological significance of these cellular activities in an organismal context, we have established a variety of mouse models that include targeted knockout, conditional knockout, allelic replacement, and transgenic expression of Ccn1. Studies on these mouse models are being conducted to complement biochemical and cell biological approaches to elucidate the roles of CCN1 in inflammation, cancer, and cardiovascular development.