Lucille P. Markey Charitable Trust

sponsor of

Basic and Clinical Research Career Tracks in Internal Medicine at

Columbia-Presbyterian Medical Center

Research Interests

We are interested in the role of matrix metalloproteases in disease and the inhibition of these enzymes as potential therapy in destructive lung diseases.

Research Activities

The research in our laboratory centers on several projects directed at understanding the role of matrix metalloproteinases in tissue destruction during particular disease processes. Our laboratory has made use of transgenic mice in which to express these enzymes at pathophysiological levels in specific tissues so as to recreate the natural proteolytic imbalance that occurs during disease. Through the generation of these transgenic animals we have been able to develop several mouse models of emphysema, atherosclerosis and heart failure and also gain insight into the role these enzymes may be playing in the pathogenesis of these diseases.

Selected Publications

D’Armiento, J., Dalal, S., Okada, Y., Berg, R. A., and Chada, K. (1992). Collagenase Expression in the Lungs of Transgenic Mice Causes Pulmonary Emphysema. Cell, 71:955-961.

Kim, H., Dalal., S.S., Young, E., Legado,M., Weisfeldt, M.L., and D’Armiento, J. (2000) Disruption of the cardiac matrix leads to altered myocardial function in transgenic mice expressing collagenase (MMP-1) in the heart. J. Clin. Invest. 106:857-866.

Imai, K., Dalal, S., Chen, E.S., Downey, R., Shulman, L., Ginsburg, M., and D’Armiento, J. (2001) Presence of Human Collagenase (MMP-1) in the lung of Patients with Emphysema. Am. J. Resp, Crit. Care Med. 163:786-791.

Lemaitre, V., O’Byrne, T.K., Okada, Y., Borczuk, A. C., Tall, A.R. and D’Armiento, J. (2001) Apo E knock-out mice expressing human interstitial collagenase (MMP-1) in macrophages have less advanced atherosclerosis. J. Clin. Invest. 107:1227-1234.

Foronjy, B. and D’Armiento, J. (2001) The role of collagenase in emphysema. Respiratory Review. 2:348-352.

Shiomi, T., Okada, Y., Foronjy, B., Schiltz, J., Jaenish, R., and D'Armiento, J. (2003). Emphysematous changes are caused by degradation of type III collagen in transgenic mice overexpressing tissue collagenase. Exp. Lung Res. 29:1-15.

Lemaitre, V., Soloway, P.D., and D’Amiento, J. (2003) Increased medial Degradation with Pseudo-aneurysm Formation in ApoE Knockout Mice deficient in Tissue Inhibitor of Metalloproteinases-1. Circulation.107:333-338.

Foronjy, R. F., Okada, Y., Cole, R., and D’Armiento, J. (2003) Progressive Adult-Onset Emphysema in Transgenic Mice Expressing Human MMP-1 in the Lung. Am. J. Physiol. Lung Cell Mol. Physiol. 284:L727-37.