MCGUIRE LAB.ca
Research for Cardiovascular and Experimental Therapeutics
We conduct research to discover novel pharmacological compounds targeting the endothelium, and vascular smooth muscle for treatment of cardiovascular diseases.
We investigate the effects and mechanisms of potential therapeutics in the contexts of cardiovascular health, and disease.
We provide hands-on training experiences to students, scientists and health professionals who will drive cardiovascular and pharmacology scientific advancements and translate research to better health outcomes. We support experiential learning and career training opportunities in basic medical sciences disciplines, such as medical biophysics, physiology, and pharmacology, for all levels of trainee education and staff expertise.
Looking for ways to join us?
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Dr McGuire supervises undergraduate and graduate students, Post-Doctoral Fellows, and research support staff at Western University.
Check out opportunities available through:
10-week project in General biophysics laboratory course (MEDBIO 3980). Requires co-/pre-requisites and registration in Medical Biophysics Honours Specialization Medical Sciences concentration or Medical Biophysics Major.
Honours thesis projects in Medical Biophysics (MEDBIO 4980), and Physiology & Pharmacology (PhysPharm 4980). Requires admission to Fourth year of the Honours Specialization. Some Departments allow their Honours thesis students to be supervised by faculty from outside of their home Department. Contact your undergraduate program for information.
Work study program at Western. Dr McGuire posts student research assistant employment opportunities in the Work Study portal. Students must be eligible and approved for hours (normally 100-200 h per semester). Undergraduate students from basic medical science and natural sciences undergraduate programs are encouraged to apply.
Summer student research assistants. Undergraduate students from natural science as well as basic medical science disciplines with prior laboratory or applicable academic experience are encouraged to apply.
Master’s (MSc), and Doctoral (PhD) graduate programs in Medical Biophysics (Microcirculation and Cellular Biophysics), and Physiology and Pharmacology (Heart, Blood Vessels, and Lungs). Applicants with strong backgrounds in the basic medical sciences or natural sciences disciplines (e.g., biology, chemistry, physics) with prior laboratory or other training are encouraged to apply.
Recruitment is always open to Post-doctoral fellows. Candidates with research expertise in areas of the microcirculation, cellular biophysics, heart, blood vessels, molecular pharmacology, fluorescence microscopy, primary cell culture, transgenic mice, or in vivo cardiovascular physiology assessment are invited.
Interested? Contact us here.
PROJECTS
Current Focus
We study the protease-activated receptor (PAR2) found on endothelial cells. Our goals are to determine the effects novel PAR2-modulating compounds have on healthy and diseased cells. Our interests focus on PAR2 activation resulting in endothelium-dependent vasodilation of small and large caliber arteries, and thus, the potential role for PAR2 in cardiovascular functions, such as blood pressure and blood flow. These interests are combined with understanding the role of PAR2 in other endothelium functions and pathophysiology. We investigate PAR2 and endothelium functions by conducting experiments with model systems ranging from molecules, cells, and tissues to whole organism.
One strategy for our work involves study of a unique mouse strain where the PAR2 is absent or "knocked out" so that the effects of this receptor can be compared to the intact model. Another facet of our work is the creation of a chemical library for PAR2 where we analyze and identify promising PAR2 agents. The significance of this research is underscored by the need for pharmacological treatments that are more selective for desired actions and thus, produce less adverse effects.
Other Projects
Wang AN, Carlos J, Singh KK, Fraser GM, McGuire JJ.
Biochemical Pharmacology. 206:115319. 2022.
doi: 10.1016/j.bcp.2022.115319 PMID: 36279920
Type 2 diabetes (T2D) is a global health problem. The risk of worsened outcomes and serious events increases with T2D due in part to adverse effects of hyperglycemia on vascular endothelial cells. In this study, we looked at PAR2 and endothelium function using a rat model of Type 2 diabetes. We assessed the effects of a PAR2 activator, and an inhibitor of thromboxane A2 synthase (ozagrel) on endothelium function in Zucker Diabetic-Sprague Dawley (ZDSD) rats. We found several different artery types in the hindlimbs of ZDSD exhibited endothelium dysfunction with higher sensitivities to PAR2 activator, and a nitric oxide releasing drug. Ozagrel treatment reduced sensitivities to the PAR2 activator in the ZDSD. These findings advance knowledge about the microvascular endothelium responses to PAR2 activation in diabetes and were part of a collaboration with Dr. G. Fraser (Memorial University of Newfoundland; please see other examples below.
Wang AN, Fraser GM, McGuire JJ.
Biomolecules. 25;12(7):889. 2022.
doi: 10.3390/biom12070889 PMID: 35883445
Longevity and a healthy circulation are believed to be linked. In this study, we assessed ageing on endothelium and PAR2 function of arteries that supply blood to the hindlimbs in rodent models, commonly used in cardiovascular research. Specifically, we looked at the saphenous artery and the caudal branches in young and old Sprague Dawley rats. We compared a PAR2-specific activator to a commonly used pharmacological agent, acetylcholine, to assess endothelium-mediated relaxation (EDR) of arterial smooth muscle. We found that regional segments of the saphenous artery and caudal branches have varying responses to EDR agonists, endothelial NO synthase inhibitors, and changes in endothelium function with increased age. This project set up the methodology for selecting the particular types of blood vessels that we subsequently used for investigating PAR2 in a diabetic rat model. It was part of a larger study with collaborators that aimed to look broadly at the effects of diabetes on microvascular function.
Wang AN, Carlos J, Fraser GM, McGuire JJ.
Experimental Physiology. 107(4):265-282. 2022.
doi:10.1113/EP089947 PMID: 35178802
Our long-held interests in finding novel treatments for diseases by targeting blood vessels have led us to explore different experimental models of human disease. This paper is our review of the Zucker Diabetic-Sprague Dawley (ZDSD) rat, a model developed by other researchers for experimental studies of Type 2 diabetes (T2D). The published literature shows that diabetes in ZDSD rats leads to endothelial dysfunction, impaired wound healing, changed bone composition, and other pathologies, and consequences for cardiovascular health. In this review, we highlighted sex-related differences in the ZDSD models. We concluded that the literature supports the use of ZDSD to effectively model the disease progression of diabetes in humans. This work was conducted as part of a larger project with collaborators to study microvascular function and diabetes.
Kagota S, Futokoro R, McGuire JJ, Maruyama-Fumoto K, Shinozuka K.
Biomolecules. 12(7):870. 2022.
doi: 10.3390/biom12070870 PMID: 35883426
Perivascular adipose tissue (PVAT) is fat tissue that surrounds blood vessels. For this study, the effects of PVAT on the vascular reactivity of renal arteries (supply the kidneys) was studied in two different rat models: a model of human hypertension with metabolic syndrome (SPZF) and a model of genetic leptin receptor deficiency (CP). The impact of PVAT on artery relaxation varied between the two groups and was influenced by differences in Angiotensin-II receptor activity, and the responses of blood vessels to the endothelium-derived dilator compound nitric oxide. This project is part of a larger program of research led by Dr. Satomi Kagota (Mukogawa Women's University in Japan) that is evaluating the role of PVAT in the modulation of vascular function. Please see other examples of our long term collaborations with Dr Kagota below.
Kagota S, Futokoro R, Maruyama-Fumoto K, McGuire JJ, Shinozuka K.J.
Vascular Research. 59(4):209-220. 2022.
doi: 10.1159/000524187 PMID: 35490668
Cardiovascular risk differs with age as well as between biological sexes in humans. Metabolic syndrome, a condition associated with increased fat (adipose) surrounding organs and blood vessels (i.e., perivascular), increases CVD risk in men and women. We found that the influence of perivascular adipose tissue (PVAT) on endothelium-mediated relaxations (EDR) of arterial smooth muscle differs between male and female rats during early-stage metabolic syndrome. While PVAT enhanced smooth muscle relaxation mechanisms in 23-week-old females, it did not have the same effect in males. Also, the presence of specific molecules in PVAT correlated with sex differences and suggests PVAT compensatory mechanisms for reduced EDR last longer in ageing female rats.
Kagota S, Maruyama-Fumoto K, McGuire JJ, Shinozuka K.
Journal of Cardiovascular Pharmacology and Therapeutics. 26(5):480-489. 2021.
doi: 10.1177/10742484211001853 PMID: 33764804
Ageing and co-morbidities affect cardiovascular disease risk. Similarly, the efficacies of therapeutic treatments may differ based on these factors as well as by biological sex. We tested the hypothesis that the glucose cotransporter 2 inhibitor, tofogliflozin, enhances the beneficial effects of perivascular adipose tissue (PVAT) and thus, prevent heart function deterioration in ageing rats with metabolic syndrome. However, we found that the treatment with tofogliflozin did not have a significant impact on PVAT effects or cardiac function in this model.
LAB MEMBERS
John J. McGuire, PhD, MBA.
Associate Professor
Medical Biophysics (primary appointment)
Physiology & Pharmacology (cross-appointment)
Schulich School of Medicine & Dentistry
London, Ontario, Canada
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Education
PhD, Pharmacology and Toxicology, Queen’s University at Kingston
Post-Doctoral Fellow, University of Calgary
MBA, Memorial University of Newfoundland
BSc Honours Life Sciences Subject Specialization, Queen's University at Kingston
Dr John McGuire is Associate Professor in the Departments of Medical Biophysics, and Physiology & Pharmacology at Western University in London, Ontario, Canada. Dr. McGuire is a cardiovascular pharmacologist and experimental therapeutics researcher. The McGuire Lab utilizes crosscutting-disciplinary technologies and model systems from molecules, cells to tissues and whole animals to study the effects of pharmacological compounds on endothelium, vascular smooth muscle and the cardiovascular system.
Dr McGuire’s research program is supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. The McGuire Lab is located physically on the main campus at Western.
Testimonials
Jesutofunmi Ayomidipupo Adesuyi
Position: Master's student (Physiology and Pharmacology)
I must say it has been an amazing experience working with Dr. McGuire over the past few months. He is incredibly helpful in teaching and guiding me through, and I am able to merge my current interests with my laboratory research experience. The team is also an awesome and collaborative one that is always willing to assist each other. Overall, McGuire's Lab is an extremely supportive environment where I am able to develop the skills I need to be successful in my Master's research and career.
Video Testimonial
Current Members
Lida Benam
Trinity Park
Isabelle Kapteyn
Andrea Kim
Olivia MacPhee
Jesutofunmi Adesuyi
Stephanie Viola
Veronika Glova
Cristian Ciciretto
Cassandra Curran
Western Alumni
Christy Wong, Honour thesis Medical Biophysics
Ada Chan, BMSc
Caroline Marszal, Honours thesis Medical Biophysics
Jasjeet Singh, Honours thesis Physiology & Pharmacology
Armeen Nabavi, Honours thesis Physiology & Pharmacology
Haleh Zabihi, Honours thesis Physiology
Anvita Dias, Honour thesis Medical Biophysics
Cheryl Tong, Honour thesis Physiology
Noah Kim, Honours thesis Physiology
Mariam Alabi, BSc
Ryan Singer, Honour thesis Medical Biophysics
Max Body, third-year project Medical Biophysics
Joselia Carlos, MSc thesis Medical Biophysics
Andrea Wang, MSc thesis Medical Biophysics
Cheng Yen-Lim, Honour thesis Medical Biophysics
Qing Zhong, Honour thesis Medical Biophysics
Hassan Abdallah, Honour thesis Medical Biophysics
Anum Anjum, MSc IMS Basic Science Internship
Rebecca Kim, MSc IMS Basic Science Internship
Srinidhi Srinivasan, MSc IMS Basic Science Internship
Cheaten Parhar, MSc IMS Basic Science Internship
RECENT PUBLICATIONS
Huang Y, Cui D, Chen L, Tong H, Wu H, Muller GK, Qi Y, Wang S, Xu J, Gao X, Fifield KE, Wang L, Xia Z, Vanderluit JL, Liu S, Leng L, Sun G, McGuire J, Young LH, Bucala R, Qi D. iScience. 26(6):106923. 2023.
doi: 10.1016/j.isci.2023.106923 PMID: 37283810
Nguyen, H. C., Bu, S., Nikfarjam, S., Rasheed, B., Michels, D. C. R., Singh, A., Singh, S., Marszal, C., McGuire, J. J., Feng, Q., Frisbee, J. C., Qadura, M., & Singh, K. K. Loss of fatty acid binding protein 3 ameliorates lipopolysaccharide-induced inflammation and endothelial dysfunction. Journal of Biological Chemistry, 299(3), 102921. 2023.
Halvorson, B. D., McGuire, J. J., Singh, K. K., Butcher, J. T., Lombard, J. H., Chantler, P. D., & Frisbee, J. C. Can Myogenic Tone Protect Endothelial Function? Integrating Myogenic Activation and Dilator Reactivity for Cerebral Resistance Arteries in Metabolic Disease. Journal of Vascular Research, 58(5), 286–300. 2021.
Hennessey, J. C., Stuyvers, B. D., & McGuire, J. J. Small caliber arterial endothelial cells calcium signals elicited by PAR2 are preserved from endothelial dysfunction. Pharmacology Research & Perspectives, 3(2), e00112. 2015.
