R. Schulz

 

Dr Richard Schulz

(Professor)

Contact:

Office: 4-62 Heritage Medical Research Centre  (☎) 780.492.6581
Lab: 4-62 Heritage Medical Research Centre  (☎) 780.492.9652
richard.schulz@ualberta.ca

Education:
BSc (Chemistry), Univ. of Calgary, 1982
PhD (Pharmacology), Univ. of Alberta, 1989

Research: Cardiovascular pathobiology of matrix metalloproteinases and reactive nitrogen-oxygen species


Research Interests / Laboratory Techniques

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.
Schulz-Img 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.)


Selected Recent Publications / Recent Funding

 

Niño ME, Serrano SE, Niño DC, McCosham DM, Cardenas ME, Villareal VP, Lopez M, Pazin-Filho A, Jaimes FA, Cunha F, Schulz R and Torres-Dueñas D. (2017) TIMP1 and MMP9 are predictors of mortality in septic patients in the emergency department and intensive care unit unlike MMP9/TIMP1 ratio: Multivariate model. PLoS One 12(2):e0171191. PMID: 28192449.

de Paula Costa G, Lopes LR, da Silva MC, Horta AL, Pontes WM, Milanezi CM, Guedes PM, de Lima WG, Schulz R, da Silva JS and Talvani A. (2016) Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from Chronic Trypanosoma cruzi-Infected Dogs. Mediators Inflamm 2016:3694714. PMID: 27688600.

Fan X, Hughes BG, Ali MA, Chan BY, Launier K and Schulz R. (2016) Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes. Am J Physiol Heart Circ Physiol 311(1):H183-9. PMID: 27199120.

Baghirova S, Hughes BG, Poirier M, Kondo MY and Schulz R. (2016) Nuclear matrix metalloproteinase-2 in the cardiomyocyte and the ischemic-reperfused heart. J Mol Cell Cardiol 94:153-61. PMID: 27079252.

Baghirova S, Hughes BG, Hendzel MJ and Schulz R. (2015) Sequential fractionation and isolation of subcellular proteins from tissue or cultured cells. MethodsX 2:440-5. PMID: 26740924.

de Souza P, Schulz R and da Silva-Santos JE. (2015) Matrix metalloproteinase inhibitors prevent sepsis-induced refractoriness to vasoconstrictors in the cecal ligation and puncture model in rats. Eur J Pharmacol 765:164-70. PMID: 26297976.

Cerisano G, Buonamici P, Gori AM, Valenti R, Sciagra R, Giusti B, Sereni A, Raspanti S, Colonna P, Gensini GF, Abbate R, Schulz R and Antoniucci D. (2015) Matrix metalloproteinases and their tissue inhibitor after reperfused ST-elevation myocardial infarction treated with doxycycline. Insights from the TIPTOP trial. Int J Cardiol 197:147-153. PMID: 26134371.

Fan X, Hughes BG, Ali MA, Cho WJ, Lopez W and Schulz R. (2015) Dynamic Alterations to alpha-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis. PLoS One 10(6):e0129176. PMID: 26076379.

Bautista-Lopez NL and Schulz R. (2014) Matrix metalloproteinases 2 and 9 as diagnostic tools in Chagas cardiomyopathy. Int J Cardiol 177(1):46-7. PMID: 25499336.

DeCoux A, Lindsey ML, Villarreal F, Garcia RA and Schulz R. (2014) Myocardial matrix metalloproteinase-2: inside out and upside down. J Mol Cell Cardiol. pii: S0022-2828(14)00297-1. PMID: 25261607.

Labossiere JR, Pelletier JS, Thiesen A, Schulz R, Bigam DL and Cheung PY. (2015) Doxycycline attenuates renal injury in a swine model of neonatal hypoxia-reoxygenation. Shock 43(1):99-105. PMID: 25105465.

Crawford BD, Po MD, Saranyan PV, Forsberg D, Schulz R, and Pilgrim DB. (2014) Mmp25beta facilitates elongation of sensory neurons during zebrafish development. Genesis 52(10):833-48. PMID: 25074687.

Ezekowitz JA, Becher H, Belenkie I, Clark AM, Duff HJ, Friedrich MG, Haykowsky MJ, Howlett JG, Kassiri Z, Kaul P, Kim DH, Knudtson ML, Light PE, Lopaschuk GD, McAlister FA, Noga ML, Oudit GY, Paterson DI, Quan H, Schulz R, Thompson RB, Weeks SG, Anderson TJ and Dyck JR. (2014) The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study. BMC Cardiovasc Disord. 14:91. PMID: 25063541.

Hughes BG and Schulz R. (2014) Targeting MMP-2 to treat ischemic heart injury. Basic Res Cardiol. 109 (4):424. PMID: 24986221.

Huyard F, Yzydorczyk C, Castro MM, Cloutier A, Bertagnolli M, Sartelet H, Germain N, Comte B, Schulz R, Deblois D, Nuyt AM. (2014) Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk. PLoS One 9(4):e92287. PMID: 24743169.

Hughes BG, Fan X, Cho WJ, Schulz R. (2014) MMP-2 is localized to the mitochondria-associated membrane of the heart. Am J Physiol Heart Circ Physiol. 306(5):H764-70. PMID: 24375642.

Labossiere JR, Pelletier JS, Ali MA, Thiesen A, Schulz R, Bigam DL, Cheung PY. (2014) Postresuscitation administration of doxycycline preserves cardiac contractile function in hypoxia-reoxygenation injury of newborn piglets. Crit Care Med. 42(4):e260-9. PMID: 24335448.

Neto-Neves EM, Sousa-Santos O, Ferraz KC, Rizzi E, Ceron CS, Romano MM, Gali LG, Maciel BC, Schulz R, Gerlach RF, Tanus-Santos JE. (2013) Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism. J Cell Mol Med. 17(12):1588-97. PMID: 24199964.

Jacob-Ferreira AL, Schulz R (2013) Activation of intracellular matrix metalloproteinase-2 by reactive oxygen-nitrogen species: Consequences and therapeutic strategies in the heart. Arch Biochem Biophys. 540(1-2):82-93. PMID: 24103691.

Jacob-Ferreira AL, Kondo MY, Baral PK, James MNG, Holt A, Fan X, Schulz R. (2013) Phosphorylation status of 72 kDa MMP-2 determines its structure and activity in response to peroxynitrite.  PLOS ONE 8(8):e71794. PMID: 24013357.

Schulze CJ, Castro MM, Kandasamy AD, Cena J, Bryden C, Wang SH, Koshal A, Tsuyuki RT, Finegan BA, Schulz, R. (2013) Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass. Crit Care Med (Aug.). PMID: 23928836.

Castro MM, Fuah J, Ali M, Sung M, Schulz J, Kondo MY, Fan X, Holt A, Schulz R. (2013) Inhibitory effects of caspase inhibitors on the activity of matrix metalloproteinase-2.  Biochemical Pharmacology 86:469-475. PMID: 23774623.

Ali MAM, Kandasamy AD, Fan X, Schulz R. (2013) Hydrogen peroxide-induced necrotic cell death in cardiomyocytes is independent of matrix metalloproteinase-2. Toxicology In Vitro 27:1686-1692. PMID: 23665313.

Bautista-Lopez NL, Morillo CA, Lopez-Jaramillo P, Quuiroz R, Luengas C, Silva SY, Galipeau J, Lalu MM, Schulz R. (2013) Matrix metalloproteinase-2 and -9 as diagnostic markers in the progression to Chagas cardiomyopathy. Am Heart J 165:558-566. PMID: 23537973.

Ali MAM, Fan X, Shulz R. (2012) Cardiac sarcomeric proteins: novel intracellular targets of matrix metalloproteinase-2 in heart disease. Trends Cardiovasc. Med. 21, 112 - 118. PMID: 22681966.

Ali MAM, Stepanko A, Fan X, Holt A, Schulz R. (2012) Calpain inhibitors exhibit matrix metalloproteinase-2 inhibitory activity. Biochem. Biophys. Res. Commun. 423(1), 1-5. PMID: 22575511.

Sariahmetoglu M, Skrzypiec-Spring M, Youssef N, Jacob-Ferreira AL, Sawicka J, Holmes C, Sawicki G, Schulz R. (2012) Phosphorylation status of matrix metalloproteinase-2 in myocardial ischemia-reperfusion injury. Heart 98(8), 656-662. PMID: 22397940.

Ali MAM, Chow AK, Kandasamy AD, Fan X, West LJ, Crawford BD, Simmen T, Schulz R. (2012) Mechanisms of cytosolic targeting of matrix metalloproteinase-2. J. Cell. Physio. 227, 3397-3404. PMID: 22212960.

Castro MM, Cena J, Cho W-J, Walsh MP, 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. PMID: 22199370.