My research focuses on elucidating the mechanism(s) of cell death and survival of primary alveolar epithelial cells and lung fibroblasts in response to the extracellular matrix associated signaling molecule, CCN1/Cyr61. CCN1/Cyr61 is an extracellular matrix (ECM)-associated signaling molecule that functions to promote cell adhesion, migration, survival and differentiation in the context of vascular development. Most recently we have shown that CCN1/Cyr61 can also modulate cell death in certain cells and can promote cell death in response to TNFa. In the context of the lung, I have found that CCN1/Cyr61 together with TNFa causes apoptosis of alveolar epithelial cells and lung fibroblasts. Because CCN1/Cyr61 has been shown to be induced in the lungs of patients with COPD and ARDS, I hypothesize that CCN1/Cyr61, together with inflammatory mediators such as TNFa causes cell death of primary lung cells in vivo, thus contributing to lung injury. I have also found that CCN1/Cyr61 functional knock-out mice have greatly reduced pulmonary inflammation at early times (<24 hrs) after LPS treatment, suggesting that CCN1/Cyr61, in addition to playing a role in apoptosis and cell survival, is likely to be involved in the initial inflammatory response as well. My research goals include determining a role for CCN1/Cyr61 in lung injury and inflammation and defining the mechanism by which CCN1/Cyr61 and TNFa cause cell death of lung cells in vivo. The ultimate goal of these studies is to gain a better understanding of the complex pathology of lung diseases such as COPD and ARDS so that better treatments for these lung diseases can be developed.
