Department of Pharmacology

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The Schulz lab has expertise in cardiovascular pharmacology and pathophysiology, particularly in relation to understanding the impact of oxidative stress. Many cardiovascular diseases involve an increase in oxidative stress to the heart and blood vessels, including ischemic heart disease, reperfusion injury, heart failure and shock.
Our lab investigates the role of specific molecules and how they contribute to oxidative stress damage. Specifically we are interested in the roles of nitric oxide, superoxide and peroxynitrite in both cardiac and vascular injury relating to the activation of the immune system as well as in myocardial ischemia and reperfusion injury.
We have discovered that some of these reactive oxygen species mediate their damaging effects through activation of an enzyme called matrix metalloproteinase-2 (MMP-2) within the cardiac myocyte. Although MMP-2 was previously thought to act only on extracellular targets, our lab has discovered that MMP-2 also targets (and subsequently damages) intracellular proteins.
Our short-term objective is to understand the contribution of each of these molecules in the development of acute heart failure. Our long-term objective is to develop and test specific pharmacological treatments to protect the heart from oxidative stress injury (e.g. matrix metalloproteinase or nitric oxide synthase inhibitors, superoxide or peroxynitrite scavengers.)

Ali, M.A.M., Fan, X., & Shulz, R. (2012) Cardiac sarcomeric proteins: novel intracellular targets of matrix metalloproteinase-2 in heart disease. Trends Cardiovasc. Med. 21, 112 - 118.

Castro, M.M., Cena, J., Cho, W-J., Walsh, M.P., & Schulz, R. (2012) Matrix metalloproteinase (MMP)-2 proteolysis of calponin-1 contributes to vascular hyporeactivity in endotoxemic rats. Arterioscler Thromb. Vas. Biol. 32, 662-668.

Ali, M.A.M., Chow, A.K., Kandasamy, A.D., Fan, X., West, L.J., Crawford, B.D., Simmen, T., & Schulz, R. (2012) Mechanisms of cytosolic targeting of matrix metalloproteinase-2. J. Cell. Physio. 227, 3397-3404.

Sariahmetoglu, M., Skrzypiec-Spring, M., Youssef, N., Jacob-Ferreira, A.L., Sawicka, J., Holmes, C., Sawicki, G., & Schulz, R., (2012)  Phosphorylation status of matrix metalloproteinase-2 in myocardial ischemia-reperfusion injury. Heart 98, 656-662.

Ali, M.A.M., Stepanko, A., Fan, X., Holt, A., & Schulz, R. (2012) Calpain inhibitors exhibit matrix metalloproteinase-2 inhibitory activity. Biochem. Biophys. Res. Commun. 423, 1-5.

Ali, M.A., Cho, W.J., Hudson, B., Kassiri, Z., Granzier, H. & Schulz, R. (2010) Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury. Circulation 122, 2039-2047. PMID: 21041693.

Kandasamy, A.D., Chow, A.K., Ali, M.A. & Schulz, R. (2010) Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix. Cardiovasc. Res. 85, 413-423. PMID: 19656780.

Sariahmetoglu, M., Crawford, B.D., Leon, H., Sawicka, J., Li, L., Ballermann, B.J., Holmes, C, Schulz, R. (2007) Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches. Annu Rev Pharmacol Toxicol. 47, 211-242. PMID: 17129183.

Sawicki, G., Leon, H., Sawicka, J., Sariahmetoglu, M., Schulze, C.J., Scott, P.G., Szczesna-Cordary, D. & Schulz, R. (2005) Degradation of myosin light chain in isolated rat hearts subjected to ischemia-reperfusion injury: a new intracellular target for matrix metalloproteinase-2. Circulation 112, 544-552. PMID: 16027249.

Lalu, M.M., Pasini, E., Schulze, C.J., Ferrari-Vivaldi, M., Ferrari-Vivaldi, G., Bachetti, T. & Schulz, R. (2005) Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart. Eur Heart J. 26, 27-35. PMID: 15615796.

Wang, W., Schulze, C.J., Suarez-Pinzon, W.L., Dyck, J.R., Sawicki, G. & Schulz, R. (2002) Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury. Circulation. 106, 1543-1549. PMID: 12234962.

Ferdinandy, P., Danial, H., Ambrus, I., Rothery, R.A. & Schulz, R. (2000) Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. Circ Res. 87, 241-247. PMID: 10926876.