Richard Schulz
Dr Richard Schulz
Professor
Education:
BSc (Chemistry), Univ. of Calgary, 1982
PhD (Pharmacology), Univ. of Alberta, 1989
Contact Information:
Teaching: PMCOL415/515*
Research: Cardiovascular pathobiology of matrix metalloproteinases and reactive nitrogen-oxygen species
Research Group:
Cardiovascular Research Centre
Mazankowski Alberta Heart Institute
Cancer Research Institute of Northern Alberta
Women and Children's Health Research Institute
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.
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
1. ZAHRAN, S., FIGUEIREDO, V., GRAHAM, M.M., SCHULZ, R., and HWANG, P.M. (2018). Proteolytic digestion of serum cardiac troponin I as a marker of ischemic severity. J Appl Lab Med 3:450-455. Highlighted by the journal on issue website.
2. FIGUEIREDO, V.P., LOPES JUNIOR, E.S., LOPES, L.R., SIMOES, N.F., PENITENTE, A.R., BEARZOTI, E., VIEIRA, P.M., SCHULZ, R., and TALVANI, A. (2018). High fat diet modulates inflammatory parameters in the heart and liver during acute experimental Trypanosoma cruzi infection. International Immunopharmacology 64:192-200.
3. CHAN, B.Y.H., ROCZKOWSKY, A., MOSER, N., POIRIER, M., HUGHES, B.G., ILARRAZA, R., and SCHULZ, R. (2018). Doxorubicin induces de novo expression of N-terminal truncated MMP-2 in cardiac myocytes. Can J Physiol Pharmacol 96: 1238-1245.
4. MAHMUD, Z., ZAHRAN, S., LIU, P.B., REIZ, B., CHAN, B.Y.H., ROCZKOWSKY, A., McCARTNEY, C.E., DAVIES, P.L., LI, L., SCHULZ, R., and HWANG, P.M. (2019). Structure and proteolytic susceptibility of the inhibitory C-terminal tail of cardiac troponin I. Biochim Biophys Acta-General Subjects 1863:661-671.
5. deMELLO, M.M.B., PARENTE, J.M., SCHULZ, R., and CASTRO, M.M. (2019). Matrix metalloproteinase (MMP)-2 activation by oxidative stress decreases aortic calponin-1 levels during hypertrophic remodeling in early hypertension. Vascular Pharmacol 116:36-44.
6. CHAN, B.Y.H., ROCZKOWSKY, A., CHO, W-J., POIRIER, M., LEE, T.Y.T., MAHMUD, Z., and SCHULZ, R. (2019). Junctophilin-2 is a target of matrix metallo-proteinase-2 in myocardial ischemia-reperfusion injury. Basic Res Cardiol 114:42. DOI: 10.1007/s00395-019-0749-7
7. ROCZKOWSKY, A., CHAN, B.Y.H., LEE, T.Y.T., MAHMUD, Z., HARTLEY, B., JULIEN, O., ARMANIOUS, G., YOUNG, H.S., and SCHULZ, R. (2020). Myocardial MMP-2 contributes to SERCA2a proteolysis during cardiac ischemia-reperfusion injury. Cardiovasc Res 116:1021-1031. DOI: 10.1093/cvr/cvz207. Highlighted by the journal with an editorial 116:876-878. DOI: 10.1093/cvr/cvz271
8. SERRANO-GOMEZ, S., BURGOS-ANGULO, G., NINO-VARGAS, D., NINO, M., CARDENAS, M., CHACON-VALENZUELA, E., McCOSHAM, D., PEINADO-ACEVEDO, J., LOPEZ M.M., CUNHA, F., PAZIN-FILHO, A., ILARRAZA, R., SCHULZ, R., and TORRES-DUENAS, D. (2020). Predictive value of matrix metalloproteinases and their inhibitors for mortality in septic patients: a cohort study. J Intensive Care Med 35:95-103.
9. CHAN, B.Y.H., ROCZKOWSKY, A., CHO, W-J., POIRIER, M., SERGI, C., KESCHRUMRUS, V., CHURKO, J.M., GRANZIER, H., and SCHULZ, R. MMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodelling. (2021). Cardiovasc Res 117:188-200. DOI:10.1093/cvr/cvaa017. Highlighted by the journal with an editorial--see Cardiovasc Res, cvaa198, https://doi.org/10.1093/cvr/cvaa198.
10. BASSIOUNI, W., ALI, M.A.M., and SCHULZ, R. Multifunctional intracellular matrix metalloproteinases: implications in disease. (2021). FEBS J 288:7162-7182. dx.doi.org/10.1111/febs.15701
11. ALI, M.A.M, GARCIA-VILAS J.G., CROMWELL, C.R., HUBBARD, B.P., HENDZEL, M.J., and SCHULZ, R. (2021). Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones. FEBS J 288:6736-6751. Highlighted by journal with issue cover photo. DOI: 10.1111/febs.16061.
12. PARENTE, J.M., BLASCKE de MELLO, M.M., LEITE da SILVA, P.H., OMOTO, M. A-C., PERNOMIAN, L., SOUSA de OLIVEIRA, I., MAHMUD, Z., FAZAN Jr, R., ARANTES, E.C., SCHULZ, R., and CASTRO, M.M. (2021). MMP inhibition attenuates hypertensive eccentric cardiac hypertrophy and dysfunction by preserving troponin I and dystrophin. Biochem Pharmacol 193:114744. DOI: 10.1016/j.bcp.2021.114744
13. BASSIOUNI, W., SEUBERT, J.M., and SCHULZ, R. (2022). Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2. Can J Physiol Pharmacol 100:184-191. DOI: 10.1139/cjpp-2021-0199
14. BAUTISTA-LÓPEZ, N.L., and SCHULZ, R. (2022). Call for consensus in the evaluation of circulating matrix metalloproteinases in Chagas disease. Am J Trop Med Hygiene 107:495-499. DOI:10.4269/ajtmh.21-0860
Graduate Students
Wesam Ferag Bassiouni (PhD programme)
Postdoctoral Fellow
Dr. Zabed Mahmud (PhD Biochemistry, University of Alberta)