Dake Qi

Assistant Professor in Cardiovascular Sciences M.B. China, M.Sc. and Ph.D. UBC




Academic Education:
M.Sc. (Pharmacology and Therapeutics), University of British Columbia
Ph.D. (Pharmaceutical Sciences), University of British Columbia


Postdoctoral Fellow, Yale Cardiovascular Research Center, Yale University School of Medicine, USA

Research interests: Pro-inflammatory factors, metabolism and heart disease


RESEARCH PROGRAM

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is widely expressed in multiple organ systems including immune cells (macrophage/monocyte), smooth muscles and the heart. MIF is released from pre-formed storage pools in response to stimulation and is classically involved in rheumatoid arthritis, atherosclerosis and sepsis. MIF also functions as a regulator of metabolism by increasing skeletal muscle glycolysis and glucose utilization. In the heart, MIF acutely activates the “energy gauge” AMP-activated protein kinase (AMPK) during ischemia, implicating that MIF may also regulate cardiac metabolism. Thus, our major research interests focus on studying the role of MIF in regulating metabolism (whole body and tissue specific) during stress.

MIF, cardiac metabolism and ischemia-reperfusion injury: Ischemic heart disease caused by partial or complete occlusion of coronary arteries is a leading cause for death around the world. In clinical practice, early and successful restoration of coronary blood flow by using thrombolytic therapy or primary percutaneous coronary intervention (PCI) is the most effective strategy to prevent ischemic injury and improve the clinical outcome. However, the recovery of blood flow simultaneously results in additional cardiac damage and complications, referred to as “reperfusion injury”. Ischemia-reperfusion attenuates aerobic myocardial metabolism, which could contribute to inadequate ventricular function recovery and cardiac injury. Thus, any mechanism that facilitates a rapid recovery of aerobic metabolism has the potential to limit ischemia-reperfusion injury in the heart. Our current research is to investigate how MIF and its homolog D-dopachrome tautomerase (DDT) acutely regulate cardiac metabolism during ischemia-reperfusion.

MIF and insulin resistance: MIF expression is chronically augmented in monocytes and adipose tissue in obese individuals, and may contribute to the pathogenesis of insulin resistance by attenuating insulin signaling. Our second research direction is to explore the molecular mechanisms of MIF in mediating insulin resistance and metabolic syndrome.


Publications:

1. Qi D, Young LH. (2015) AMPK: energy sensor and survival mechanism in the ischemic heart. Trends in Endocrinology and Metabolism 26(8): 422-9.

2. Song K, Wang S, Qi D. (2015) Effects of Cyclosporine on Reperfusion Injury in Patients: A Meta-Analysis of Randomized Controlled Trials. Oxidative Medicine and Cellular Longevity 2015:287058.

3. Qi D, Atsina K, Qu L, Hu X, Wu X, Xu B, Piecychna M, Leng L, Fingerle-Rowson G, Zhang J, Bucala R, Young LH. (2014) The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. Journal of Clinical Investigation 124 (8): 3540-50.

4. Li J, Qi D, Cheng H, Hu X, Miller EJ, Wu X, Russell KS, Mikush N, Zhang J, Xiao L, Sherwin RS, Young LH. (2013) Activation of AMP activated protein kinase by Urocortin 2 treatment and autocrine-paracrine actions in the heart. Proc Natl Acad Sci USA 110 (40): 16133-8.

5. Li Z*, Qi D*, Chen J, Zhang C, Yi Z, Yuan C, Wang Z, Wu H, Y s, Cu D, Fang Y. (2013) Venlafaxine inhibits the upregulation of plasma tumor necrosis factor-alpha (TNF-α) in the Chinese patients with major depressive disorder: a prospective longitudinal study. Psychoneuroendocrinology 38 (1): 107-14. (*Authors with equal contributions).

6. Dong B*, Qi D*, Yang L, Huang Y, Xiao X, Tai N, Wen L, Wong FS. (2012) TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the Non Obese Diabetic mouse model of type 1 diabetes. American Journal of Physiology - Heart and Circulatory Physiology 303 (6): H732-42. (*Authors with equal contributions).

7. Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH . (2011) A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. Journal of Molecular and Cellular Cardiology 51(1): 24-32 .

8. Yu J, Qi D, Jiang K, Peng Y, Cui D. (2011) MK-801 induces schizophrenic behaviors through downregulating Wnt signaling pathways in male mice. Brain Research 1385:281-92 .

9. Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH. (2009) Cardiac Macrophage Migration Inhibitory Factor Inhibits the JNK Pathway and Prevents Injury during Ischemia Reperfusion. Journal of Clinical Investigation 119(12): 3807-16.

10. Xiao X, Zhao P, Rodriguez-Pinto D, Qi D, Henegariu O, Alexopoulou L, Flavell RA, F Wong S and Wen L. (2009) Inflammatory Regulation by Toll-like Receptor 3 in Acute Hepatitis. Journal of Immunology 15; 183(6): 3712-9.

11. Qi D, and Rodrigues B. (2007) Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism. ( Invited Review) American Journal of Physiology – Endocrinology and Metabolism 292 (3): E654-67.

12. Kewalramani G, An D, Kim MS, Ghosh S, Qi D, Abrahani A, Pulinilkunnil T, Sharma V, Wambolt RB, Allard MF, Innis SM, Rodrigues B. (2007) AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes. Journal of Molecular and Cellular Cardiology 42(2): 333-42.

13. An D, Kewalramani G, Chan JK, Qi D , Ghosh S, Pulinilkunnil T , Abrahani A, Wambolt RB, Allard MF, and Rodrigues B. (2006) Metformin influences cardiomyocyte cell death by both caspase-3 dependent and independent pathways. Diabetologia 49(9): 2174-84.

14. Qi D, Kuo K-H, Abrahani A, An D, Qi Y, Heung J, Kewalramani G, Pulinilkunnil T, Ghosh S, Innis MS, Rodrigues B. (2006) Acute intralipid infusion reduces cardiac luminal lipoprotein lipase but recruits additional enzyme from cardiomyocytes. Cardiovascular Research 72(1): 124-33.

15. Qi D, An D, Kewalramani G, Qi Y, Pulinilkunnil T, Abrahani A, Al-Atar U, Ghosh S, Wambolt RB, Allard MF, Innis SM, and Rodrigues B. (2006) Altered cardiac fatty acid composition and utilization following dexamethasone induced insulin resistance. American Journal of Physiology – Endocrinology and Metabolism 291: 420-427.

16. Ghosh S, Kewalramani G, Yuen G, Pulinilkunnil T, An D, Innis SM, Allard MF, Wambolt RB, Qi D, Abrahani A, Rodrigues B. (2006) Induction of mitochondrial nitrative damage and cardiac dysfunction by chronic provision of dietary omega-6 polyunsaturated fatty acids. Free Radical Biology & Medicine 41(9): 1413-24.

17. Ghosh S, Pulinilkunnil T, Yuen G, Kewalramani G, An D, Qi D, Abrahani A, Rodrigues B. (2005) Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion. American Journal of Physiology - Heart and Circulatory Physiology 289(2): H768-76.

18. An D, Kewalramani G, Qi D, Pulinilkunnil T, Ghosh S, Abrahani A, Wambolt R, Allard M, Innis SM, Rodrigues B. (2005) beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload. American Journal of Physiology – Endocrinology and Metabolism 288(6): E1120-7.

19. Pulinilkunnil T, An D, Ghosh S, Qi D, Kewalramani G, Yuen G, Virk N, Abrahani A, Rodrigeus B. (2005) Lysophosphatidic acid-mediated augmentation of cardiomyocyte lipoprotein lipase involves actin cytoskeleton reorganization. American Journal of Physiology – Heart and Circulatory Physiology 288(6): H2802-10.

20. An D, Pulinilkunnil T, Qi D, Ghosh S, Abrahani A, Rodrigues B. (2005) The metabolic "switch" AMPK regulates cardiac heparin-releasable lipoprotein lipase. American Journal of Physiology - Endocrinology and Metabolism 288(1): E246-53.

21. Ghosh S, Ting S, Lau H, Pulinilkunnil T, An D, Qi D, Abrahani MA, Rodrigues B. (2004) Increased efflux of glutathione conjugate in acutely diabetic cardiomyocytes. Canadian Journal of Physiology and Pharmacology 82(10): 879-87.

22. Pulinilkunnl T, An D, Yip P, Chan N, Qi D, Ghosh S, Abrahani A, Rodrigeus B. (2004) Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation. Journal of Molecular and Cellular Cardiology 37(5): 931-8.

23. Qi D, Pulinilkunnil T, Ghosh S, Abrahani A, Pospisilik JA, Brownsey R, Wambolt R, Allard M, Rodrigues B. (2004) Single-dose dexamethasone induces whole-body insulin resistance and alters both cardiac fatty acid and carbohydrate metabolism. Diabetes 53(7): 1790-7.

24. Ghosh S, An D, Pulinilkunnil T, Qi D, Lau HC, Abrahani A, Innis SM, Rodrigues B. (2004) Role of dietary fatty acids and acute hyperglycemia in modulating cardiac cell death. Nutrition 20(10): 916-23.

25. Ghosh S, Qi D, An D, Pulinilkunnil T, Abrahani A, Kuo K-H, Wambolt RM, Allard M, Innis SM, Rodrigues B. (2004) Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA.
American Journal of Physiology - Heart and Circulatory Physiology 287(6): H2518-27.

26. Pulinilkunnil T, Qi D, Ghosh S, Cheung C, Yip P, Varghese J, Abrahani A, Brownsey R, Rodrigues B. (2003) Circulating triglyceride lipolysis facilitates lipoprotein lipase translocation from cardiomyocyte to myocardial endothelial lining. Cardiovascular Research 59(3): 788-97.

27. Qi D, Mitchell RW, Burdyga T, Ford LE, Kuo K-H, and Seow CY. (2002) Myosin light chain phosphorylation facilitates in vivo myosin filament reassembly after mechanical perturbation. American Journal of Physiology - Cell Physiology 282: C1298-C1305.

Book Chapters

Miller EJ, Qi D, Li J, Young LH. (2012) Chapter 2, part 5: MIF in Cardiovascular Disease. The MIF Handbook edited by Richard Bucala. B1295-1304.