Dr. Mireille Ouimet

Biography

Research Interests

Cardiovascular disease is the leading global cause of death, accounting for more than 17 million deaths per year. Atherosclerosis is the major cause of cardiovascular diseases and, in Canada alone, one in five deaths is due to some form of atherosclerosis. Existing lipid-lowering therapies such as statins can prevent atherosclerosis, but they are not universally effective and do not reverse atherosclerosis. Therefore, there is an urgent need to develop new therapies to stop and reverse atherosclerosis.

In atherosclerosis, fatty plaques build up in the artery wall, and Dr. Ouimet recently identified lipophagy as a novel pathway that degrades fat which accumulates in cells of atherosclerotic plaques (foam cells). Increasing foam cell lipophagy thus represents a novel strategy to prevent and reverse atherosclerotic plaques. Dr. Ouimet’s laboratory seeks to i) understand the fundamental mechanisms of autophagy-mediated lipid droplet degradation (lipophagy), ii) investigate its specific role in atherosclerosis and immunometabolism, and iii) define the molecular components of this pathway that can be specifically therapeutically manipulated.

Select Publications

• Maus, M., Cuk, M., Patel, B., Lian, J., Ouimet, M., Kaufmann, U., Yang, J., Horvath, R., Hornig-Do, H., Chrzanowska-Lightowlers, Z., Moore, K.H., Cuervo, A.M., Feske, S. (2017). Store-Operated Ca2+ Entry Controls Induction of Lipolysis and the Transcriptional Reprogramming to Lipid Metabolism. Cell Metabolism. In press.
• Tang, J., Baxter, S., Menon, A., Alaarg, M., Sanchez-Gaytan, B.L., Fay, F., Zhao Y., Ouimet, M., Braza M.S., Longo, V., Abdel-Atti, D., Duivenvoorden, R., Calcagno, C., Sotrm, G., Tsimikas, S., Moore, K.J., Swirski, F., Nahrendorf, M., Fisher, E.A, Perez-Medina, C., Fayad, Z.A., Reiner, T., Mulder, W.J.M. (2016). Immune Cell Screening of a Nanoparticle Library Improves Atherosclerosis Therapy. Proceedings of the National Academy of Sciences of the USA. Nov 1;113(44):E6731-E6740.
• Ouimet, M., Koster, S., Sakowski, E., Ramkhelawon, B., van Solingen, C., Oldebeken, S., Karunakaran, D., Portal Celhay, C., Sheedy, F.J., Dutta Ray, T., Cecchini, K., Zamore, P.D., Rayner, K.J., Marcel, Y.L., Philips, J.A, Moore, K.J. (2016). Mycobacterium tuberculosis induces the miR-33 locus to inhibit autophagy and reprogram host lipid metabolism. Nature Immunology. doi: 10.1038/ni.3434.
• Ouimet, M.*, Hennessy, E.J.*, Koelwyn G.J., van Solingen, C., Hussein, M., Ramkhelawon, B., Rayner, K.J., Garabedian, M., Temel, R.E., Holdt, L.M., Teupser, D., Moore, K.J. miRNA targeting of oxysterol binding protein-like 6 (OSBPL6) regulates cholesterol trafficking and efflux. (2016). Arteriosclerosis, Thrombosis, and Vascular Biology. ATVBAHA.116.307282. *Authors contributed equally.
• Ouimet, M.*, Ediriweera, H.N.*, Gundra, U.M., Sheedy, F.J., Ramkhelawon, B., Hutchison, S.B., Rinehold, K., van Solingen, C., Fullerton, M.D., Cecchini, K., et al. (2015). MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. The Journal of Clinical Investigation. 125 (12), 4334-4348. *Authors contributed equally.
• Karunakaran, D., Thrush, A.B., Nguyen, M.A., Richards, L., Geoffrion, M., Singaravelu, R., Ramphos, E., Shangari, P., Ouimet, M., Pezacki, J.P., et al. (2015). Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis. Circulation research. 117, 266-278.
• Sanchez-Gaytan, B.L., Fay, F., Lobatto, M.E., Tang, J., Ouimet, M., Kim, Y., van der Staay, S.E., van Rijs, S.M., Priem, B., Zhang, L., et al. (2015). HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages. Bioconjugate chemistry. 26, 443-451.
• Vengrenyuk, Y., Nishi, H., Long, X., Ouimet, M., Savji, N., Martinez, F.O., Cassella, C.P., Moore, K.J., Ramsey, S.A., Miano, J.M., et al. (2015). Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arteriosclerosis, Thrombosis, and Vascular Biology. 35, 535-546.
• Ouimet, M. (2013). Autophagy in obesity and atherosclerosis: Interrelationships between cholesterol homeostasis, lipoprotein metabolism and autophagy in macrophages and other systems. Biochimica et Biophysica Acta. 1831, 1124-1133.
• Ouimet, M., and Moore, K.J. (2013). A big role for small RNAs in HDL homeostasis. Journal of Lipid Research. 54, 1161-1167.
• Ouimet, M., and Marcel, Y.L. (2012). Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 32, 575-581.
• Ouimet, M., Franklin, V., Mak, E., Liao, X., Tabas, I., and Marcel, Y.L. (2011). Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metabolism. 13, 655-667.