Funk, Colin D - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

B.Sc. (Queen’s), Ph.D. (McGill) Research Interests: Gene editing in urea cycle disorders; Eicosanoid signaling pathways; Free fatty acid receptor 4 (FFAR4) signaling and relationship with omega3 polyunsaturated fatty acids In general, we study the molecular, cellular, and (patho)physiological contexts of health and disease. We are carrying out new genome editing strategies (TALENs, CRISPRs) using induced pluripotent stem cells derived from patients with urea cycle defects (arginase-1 deficiency) and an inducible knockout strain of mice with the corresponding genetic defect. We also study a group of lipid mediator molecules known as eicosanoids, the enzymes that biosynthesize these products, and the receptors that transduce their effects. We are exploring the roles of cyclo-oxygenase (COX) enzymes in various aspects of the cardiovascular system using unique mouse models achieved through gene-targeting methodology. Research in the Funk Lab also includes the study of omega 3 fatty acids and how they signal through the fatty acid receptor FFAR4 to modulate inflammation, especially within the context of the cardiovascular system.

研究领域

Gene-editing in urea cycle disorders (Arginase-1 deficiency) using induced pluripotent stem cells and mouse models Omega-3 polyunsaturated fatty acid signaling via GPR120/FFAR4 in health and disease Biology of the cyclooxygenase-2 (COX-2) pathway in the context of inflammation and the cardiovascular system

近期论文

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1.Funk, C.D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science, 294, 1871-1875 (2001). 2.Zhao, L., Moos, M.P.W., Gräbner, R., Pédrono, F., Fan, J., Kaiser, B., John, N., Schmidt, S., Spanbroek, R., Huang, L., Cui, J., Rader, D.J., Evans, J.F., Habenicht, A.J.R., and Funk, C.D. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nature Medicine, 10, 966-973 (2004). 3.Yu, Y., Fan, J., Chen, X.S., Klein-Szanto, A., FitzGerald, G.A., and Funk, C.D. Differential impact of prostaglandin H synthase 1 knock down on platelets and parturition. J. Clin. Invest., 115, 986-995 (2005) 4.Cheng, Y., Wang, M., Yu, Y., Lawson, J., Funk, C.D. and FitzGerald, G.A. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J. Clin. Invest., 116, 1391-1396 (2006). 5.Yu, Y., Fan, J., Chen, X.S., Wang, D., Klein-Szanto, A., Campbell, R.L., FitzGerald, G.A. and Funk, C.D. Genetic model of selective COX2 inhibition reveals novel heterodimer signaling. Nature Medicine, 12, 699-704 (2006). 6. Yu, Y., Fan, J., Hui, Y., Rouzer, C.A., Marnett, L.J., Klein-Szanto, A.J., FitzGerald, G.A. and Funk, C.D. Targeted cyclooxygenase gene (Ptgs) exchange reveals discriminant isoform functionality, J.Biol. Chem., 282, 1498-1506 (2007). 7. Jiang, W., Hall, S.R., Moos, M.P.W., Cao, R.Y., Ishii, S., Ogunyankun, K., Melo, L.G., and Funk, C.D. Endothelial cysteinyl leukotriene 2 receptor (CysLT2R) expression mediates myocardial ischemia-reperfusion injury. Am. J. Pathol., 172, 592-602 (2008). 8. Seta, F., Chung, A.D., Turner, P.V., Mewburn, J.D., Yu, Y., and Funk, C.D. Renal and cardiovascular characterization of COX-2 knockdown mice. Am. J. Physiol., 296, R1751-R1760 (2009). 9. Yu, Y., Stubbe, J., Ibrahim, S., Song, W.L., Smyth, E.M., Funk, C.D. and FitzGerald, G.A. COX-2 dependent prostacyclin formation and blood pressure homeostasis: targeted exchange of COX isoforms in mice. Circ. Res. 106,337-345 (2010). 10. Yan, D., Stocco, R., Sawyer, N., Nesheim, M.E., Abramovitz, M. and Funk, C.D. Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT2) agonist, N-methyl-leukotriene C4, in calcium reporter and beta arrestin assays. Mol. Pharmacol., 79, 270-278 (2011). 11. Funk, C.D. Leukotriene inflammatory mediators meet their match. (Perspective) Science Translational Med., 3(66), 66ps3(2011). 12.Cao, R.Y., St. Amand, T., Li, X., Yoon, S.-H., Wang, C.P., Brown, P.M., Zelt, D.T., Funk, C.D. Prostaglandin receptor EP4 involvement in abdominal aortic aneurysms, Am. J. Pathol. 181, 313-321 (2012). 13. Li, X., Yu, Y., and Funk, C.D. Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4). FASEB J., 27, 4987-4997 (2013). 14. Sin, Y.Y., Ballantyne, L.L., Mukherjee, K., St. Amand, T., Kyriakopoulou, L., Schulze, A., and Funk, C.D. Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism. PLoS ONE ;8(11):e80001 (2013). 15. Ni, N.C., Ballantyne, L.L., Mewburn, J.D., and Funk, C.D. Multiple-site activation of the cysteinyl leukotriene receptor 2 is required for exacerbation of ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol. 34:321-330 (2014). 16. Mukherjee, K., Edgett, B.A., Burrows, H., Giaid, A., Castro, C., Griffin, J.L, Gurd, B.J., and Funk, C.D. Whole blood transcriptomics and urinary metabolomics to define adaptive biochemical pathways of high intensity exercise in 50-60 year old Master’s athletes. PLoS ONE.,2014 Mar 18;9(3):e92031. 17.Li, X., Ballantyne, L., Che, X., Mewburn, J., Kang, J.X., Barkley, R., Murphy, R.C. Yu, Y., Funk, C.D. Endogenously generated omega 3 fatty acids attenuate vascular inflammation and neointimal hyperplasia by interaction with FFAR4 in mice. J Am Heart Assoc. 4:e001856 doi: 10.1161/ JAHA.115.001856 (2015). 18. Ballantyne, L., Sin, Y.Y., St. Amand, T., Si, J., Goossens, S., Haenebalke, L., Haigh, J.J., Schulze, A., Funk, C.D. Strategies to rescue the consequences of inducible arginase-1 deficiency in mice. PLoS ONE, 2015 May 4;10(5):e0125967. doi: 10.1371/journal.pone.0125967 (2015). 19. Sin, Y.Y., Baron, G., Schulze, A. and Funk, C.D. Arginase-1 deficiency. J. Mol. Med. 93, 1287-1296 (2015). http://www.ncbi.nlm.nih.gov/pubmed?term=funk cd