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Research Summary
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:
1. 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
2. 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
107:333-8
3. 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
4. Foronjy, B. and D’Armiento, J. (2001) The role of collagenase in emphysema. Respiratory Review.
2:348-52
5. 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.
107:1227-34
6. 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.
163:786-91
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