The overarching goal of my research program is to study the various aspects of blood flow regulation, with a specific focus on how it is altered by pathological changes in cardiomyocyte and vascular smooth muscle cell structure and function. The aim is to further the understanding of these organ systems with respect to cell signaling, contractility and, in smooth muscle cells, dedifferentiation markers. My program of research is guided by three main pillars:
1. Modifications of blood vessels in health and disease (including both endothelial and smooth muscle cells)
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2. Modifications of cardiomyocytes in pathologies like diabetes and dyslipidemia.
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3. The effects these modifications, as well as other pathologies (like cancer) have on functional capacity.
Pillar 1: The blood vessels
My primary research interest lies in the area of vascular physiology and particularly in smooth muscle cell (SMC) proliferation and dedifferentiation from the contractile to the synthetic phenotype. Until now, these processes, active in the development of angiogenesis, atherosclerosis and hypertension continue to be inadequately understood. This research stream, dealing with the consequences of a progressive narrowing and blocking of blood vessels by plaque, is of huge importance as this is the leading cause of death in developed countries and accounts for about 20% of all deaths in Canada.
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Examples of projects under this pillar:
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Implications of bioenergetics and mitochondrial respiration on smooth muscle cell dedifferentiation and early atherogenesis
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Effects of the cholesterol lowering drug Simvastatin on smooth muscle cell oxidative phosphorylation
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Whether a low carbohydrate/high protein (Atkin's) diet potentiates atherogenesis as much, or more than a Western type diet.
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Clarification of the underpinnings related to accelerated atherosclerosis seen in hyperglycemia/diabetes
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Pillar 2: The heart
One important aspect of my research related to the heart is to define how cardiomyocytes respond to, and alter their function, in response to increased plasma lipid levels. This is of paramount interest as it is known that excess lipids will be shunted into pathways that ultimately disrupt normal cellular function leading to altered metabolic demands and damaging effects, in part due to a reprogramming of the bioenergetics. The heart is a highly oxidative muscle and any disruption in mitochondrial function can cause disturbed cardiac function and ultimately myocardial infarction. Heart failure is thought to be the end result following the combination of mitochondrial derived oxidative stress and decreased energy production. The purpose of this research pillar is to evaluate the heart’s ability to utilize fat. A greater understanding of the influence and mechanism of modified oxidative capacity of the cardiomyocytes is of importance, considering the heart consumes the most oxygen in the body.
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Examples of projects under this pillar:
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How various diet models affect the heart's ability to produce energy and evaluate the effects by focusing on the mitochondrial respiration
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Systemic implications of 'cardiolipin' , a phospholipid that gets released in large amounts from the heart following a myocardial infarction.
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How a lack of the lipid transporter 'ApoE' affects the cardiac metabolism and hypertrophy.
Pillar 3: Functional capacity
Furthermore, I am interested in the use of exercise (dose, intensity, and modality) in the treatment/management of pathological conditions that involve inflammation, such as diabetes, cancer and vascular disease. Another interest lies in the area of how we can use non-invasive cardiovascular measurements to improve training and injury prevention among athletes.
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Examples of projects under this pillar:
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Whether the acute:chronic workload ratio, measured through heart rate predicts injury in male varsity soccer players. Should athletes be training harder but smarter to avoid injury?
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The effects of concurrent aerobic/resistance training in male football players. Are there reasons for concern?
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Studies addressing the concept of exercise 'dose' to optimize pre-operative functional capacity and insulin sensitivity in elderly colorectal cancer patients. (in collaboration with the Peri-operative Programme (POP) at the Montreal General Hospital).
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