cardioprotection ischemia-reperfusion mitochondria pharmacology/toxicology fatty acids immune response cell death
“Imagination is more important than knowledge...’ ”
― Albert Einstein
BSc Biology (Emphasis Toxicology) and Minor in Psychology, 1992, Simon Fraser University, Burnaby, BC, Canada
MSc Biology - Aquatic Toxicology (Modulators of Toxicokinetics), 1997, Simon Fraser University, Burnaby, BC, Canada. Advisor: Dr. CJ Kennedy
PhD Pharmacology and Toxicology (Molecular Toxicology), 2002, University of Western Ontario, London, Ontario, Canada. Advisor: Dr. JR Bend
PDF Cardiovascular Pharmacology, 2002-2005, National Institute of Environmental Health Sciences, RTP, NC. Advisor: Dr. DC Zeldin
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in elderly individuals who have increased susceptibility to stress factors likely to cause lethal outcomes. As such, older individuals comprise greater than 75% of the patients presenting with coronary artery disease or congestive heart failure. While the etiology of age-related cardiovascular pathogenesis is poorly understood, it has been shown that deterioration of mitochondria over time plays a critical role in age-related cardiac dysfunction. Mitochondria are critical to cardiomyocyte survival and heart function, so maintenance of a healthy mitochondrial population is essential for the preservation of healthy cardiac muscle. Dietary sources of essential fatty acids have a significant effect on cardiovascular health, but many of the benefits are poorly understood.
My research focuses on investigating the role of cytochrome P450 (CYP)-derived eicosanoids in cardiovascular homeostasis and function. Specifically, we are interested in understanding the role of CYP epoxygenase metabolites of arachidonic acid (N-6 PUFA), called epoxyeicosatrieanoic acids (EETs), in maintaining tissue homeostasis and reducing injury. As well, we have recently begun exploring CYP-derived metabolites of docosahexaenoic acid (N-3 PUFA, ‘fish oil’), called epoxydocosapentaenoic acids (EDPs). Both of these 'epoxylipids', EETs and EDPs, are converted into less active diol compounds by a soluble epoxide hydrolase (sEH). We have shown that epoxylipids have significant cardioprotective properties, enabling them to limit damage to mitochondria during cardiac events. Our program is working to understand the fundamental mechanisms involved in how these epoxylipids can regulate mitochondrial quality in young and aged hearts. We are working closely with our collaborators to develop new compounds based on the structure and function of these compounds with the ultimate goal to identify therapeutic strategies that prevent and/or treat cardiac injury and improve overall cardiac health.
Major Research Questions:
1) What role do EETs and EDPs have in cardiac physiology and pathophysiology in both young and aged hearts?
2) What are the intracellular targets of EETs and EDPs?
3) How do EETs and EDPs limit mitochondrial damage from ischemic injury?
4) Can we design and develop novel compounds based on the chemical structure and function of EETs and EDPs?
Graduate Students – Current
Ahmed Darwesh Essa (PhD student – Jan 2017- present) Project: Improving Cardiac Mitochondria in with Novel Epoxy Lipids
Deanna Sosnowski (MSc, Sept 2019 – present) Project: Investigating Mitochondria in Cardiac Aging
Wesam Farag Bassiouni (PhD, Sept 2019 - present) Co-supervised Dr. Richard Schulz Project: Role of MMP-2 in IR Injury
Robert Valencia (MSc, Sept 2020 - Present) Project: Epoxylipids and the Innate Immune Response
Graduate Students – Past
Dharmendra Katragadda (MSc, 2009) Project: Effects of Epoxyeicosatrienoic Acid on Mitochondrial Membrane Potential
Mohamed Abukhashim (MSc, 2011) Project: Epoxyeicosatrienoic Acid Effects on GPCR Responsiveness
Sri Nagarjun Batchu (PhD, 2011) Project: Epoxyeicosatrienoic Acid Effects on Membrane Ion Channels.
Ketul Chaudhary (PhD, 2012) Project: The Role in B-Type Natriuretic Peptide in Epoxyeicosatrienoic Acid Mediated Cardioprotection
Rawabi Qadhi (MSc, 2012) Project: The Role of N-3 PUFA and Caveolin-1 in Ischemia-Reperfusion Injury
Nasser Alsaleh (MSc, 2014) Project: Epoxyeicosatrienoic Acid Affects on Autophagy
Igor Zlobine (MSc, 2014) Project: DHA Mediated Cell Death
Jelle Vriend (Visiting MSc, 2013 – 2014) Project: Eicosanoid Regulation of LPS Mediated Cell Death
Ahmed Abdelmoneim (PhD, co-supervisor with Dr. Scot Simpson 2015) Project: Cardiovascular Risk Difference Between Glyburide and Gliclazide
Maria Akhnokh (MSc student – Jan 2013-Sept2015) Project: Epoxyeicosatrienoic Acids and Cardioprotection
Haitham El-Sikhry (PhD, 2016) Project: Epoxyeicosatrienoic Acids and Mitochondrial Function
Tomoko Endo (visiting PhD, 2015-2018) Project: N-3 PUFA Induced Cytotoxicity
Kristi Lockhart Jamieson (PhD, 2020) Project: Cardioprotective Effects of Soluble Epoxide Hydrolase Inhibition in Aged Hearts
Hedieh Keshavarz-Bahaghighat (2018- ) Project: Protecting Cardiac Mitochondria with Epoxy Lipids in Aged Hearts
Dr. Victor Samokhvalov (Research Associate, 2012 – 2019) Project: Mechanisms of EET-Mediated Regulation of Cell Death
Dr. Chuying Wang (Visiting Scientist, 2017- 2018) Project: Cardioprotective Mechanisms of Tetramethylpyrazine and Astragaloside IV
Dr. YunFang Zhang (Post-Doctoral Fellow, 2007 – 2009) Project: Cardioprotective Effects of EETs Toward Doxorubicin Toxicity
Dr. Fenghua Yang (Post-Doctoral Fellow, 2012 – 2013) Project: In Vivo Analysis of Mechanisms of EET-mediated Cardioprotection
Pharmacy 203 – Introduction to Pharmacology
Pharmacy 401 – Toxicology, Drugs of Abuse and Advanced Pharmacology (new 2021)
Pharmacy 566 – Cellular Aspects of Drug Delivery and Targets
Pharmacy 564 – Toxicology
Pharmacy 573 – Analytical Techniques
Pharmacy 630 – Drug Metabolism
PMCOL 303 (Dept. Pharmacology) –Toxicology
Provides students with fundamental knowledge of toxicology of prescription and non-prescription medications and drugs of abuse, as well as select specialized topics in pharmacology. Clinical relevance of toxicology, including pharmacogenomic concepts, will be explored through the examination of drug toxicity to specific target organs and approaches to managing poisoning and adverse drug reactions. (Restricted to Pharmacy students.)Winter Term 2021