Dr. Mireille Ouimet

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Full name	Dr. Mireille Ouimet
Summary	Developing drugs to efficiently remove pre-existing plaques that have already established themselves in the arteries
Type of researcher	Principal Investigator
Introduce yourself, your experience and your credentials	Atherosclerosis, a form of heart disease caused by the build-up of cholesterol deposits in the artery wall, is responsible for one in five deaths in Canada. Meanwhile, existing cholesterol-lowering drugs are only partially effective at reducing the risk of heart attacks and strokes. New therapies are urgently needed to combat this deadly disease. Dr. Mireille Ouimet, Canada Research Chair in Cardiovascular Metabolism and Cell Biology, is looking for new ways to improve the removal of cholesterol from atherosclerotic plaques, stop the plaques from growing bigger, and possibly even reduce their size. Ouimet and her research team are testing whether increasing a process in cells called “autophagy”—which breaks down lipids and exports them—could achieve this. Autophagy plays a key role in recycling toxic elements from cells and promotes cell survival during periods of cell stress. Through autophagy, cellular components are delivered to organelles called lysosomes (the waste disposal system of the cell), which digest unwanted materials. Ouimet’s research has already shown that autophagy can also engulf and digest cholesterol that has accumulated in the artery wall. This process helps remove cholesterol, providing an entirely new therapeutic target to reverse atherosclerosis. By shedding light on the fundamental mechanisms of lipid autophagy, Ouimet and her research team hope to identify pathway components that can be targeted and manipulated to treat heart disease. They are also looking for new targets for developing drugs that can increase cholesterol breakdown and export by cells in the artery wall.
Describe your research	My project is to try to identify through which pathway fat gets degraded in cells. I isolate lipid droplets, which are highlighted here in green in order to see which proteins are involved in tagging them, so they can get degraded by the cells. My lab is focused on heart disease, particularly atherosclerosis: the build up of cholesterol inside the artery wall. Within these plaques, there are foam cells, and inside these foam cells there are organelles called lipid droplets. We are interested in the mechanism to break down these lipid droplets in order to remove the cholesterol that accumulates inside atherosclerotic plaques. One particular pathway that we are interested in is autophagy. Autophagy is an evolutionary conserved cell process by which cells degrade cytoplasmic components such as lipid droplets. If we can find ways to therapeutically enhance the autophagy breakdown of lipid droplets then we an promote the reverse transport of cholesterol out of the artery wall to the circulation for elimination out of the body through feces.
Explain its significance	Cholesterol is an essential part of the human body. We need cholesterol. We acquire cholesterol through our diets, and the cells of our body synthesis cholesterol. The problem is if there is too much cholesterol. There are a number of factors that can contribute to this such as poor diet, eating too much fatty foods and not exercising enough. Some people may also have a genetic predisposition to high cholesterol levels. But if you have high cholesterol levels in your circulation, overtime that leads to atherosclerosis and the buildup of cholesterol in plaques. And atherosclerosis can cause a heart attack or a stroke. We are looking at ways to clinically reduce cholesterol in patients. There are some drugs currently on the market to lower plasma cholesterol levels, such as statins. But the problem is that there really is no drug currently that efficiently removes pre-existing plaques that have already established in the arteries. Statins, cholesterol lowering and changing your diet can stop the plaques that are already formed from getting bigger but they won’t necessarily shrink them and eliminate them. That’s what my lab is interested in doing.