Cell Survival; Diabetes Mellitus; Insulin Resistance; Myocardial Ischemia; Apoptosis; Glucose Transporter Type 4; AMP-Activated Protein Kinases
Our laboratory is studying the cellular and molecular mechanisms responsible for the metabolic adaptation to the hypoxic stress associated with myocardial ischemia.
Specialized Terms: Myocardial ischemia; Metabolic adaptation to hypoxic stress; Cardio-protection; Cardiomyopathy; LKB1-AMPK pathway; Diabetes
Extensive Research Description
Our laboratory is studying the cellular and molecular mechanisms responsible for the metabolic adaptation to the hypoxic stress associated with myocardial ischemia, recently focusing on the AMP-activated protein kinase (AMPK) signaling pathway. AMPK has emerged as a key regulator of glucose transporter (GLUT4) translocation, cellular metabolism, ion channel activity, and cell survival and apoptosis in the heart.
Combining physiologic models of ischemia with cellular and molecular techniques, we are interested in the cardio-protective action of AMPK in the heart, the upstream mechanisms of AMPK activation and its downstream interaction with other signaling pathways, as well as the discovery of novel AMPK targets. The use of transgenic mouse models allows us to dissect the role of AMPK and other signaling pathways in the intact perfused heart and in vivo. The goal of this research is to develop novel strategies to protect the heart against injury during myocardial ischemia.
- Stress signaling pathways is the heart.
- Alterations in metabolism in cardiac disease.
- AMPK as a target for protecting the heart against ischemic injury.
- LKB1 regulation of metabolic signaling and cardic growth.
- Cardiac-derived autocrine-paracrine secreted proteins in the regulation of cardiac signaling pathways.
- Insulin resistance and diabetes in cardiovascular disease.
- Qi D, Atsina K, Hu X, Wu X, Xu B, Piecychna M, Leng L, Fingerle-Rowson G, Zhang J, Bucala R, Young LH. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. J Clin Invest 2014; 124;3540-50.
- Li J, Qi D, Cheng H, Miller EJ, Wu X, Russell, KS, Mikush N, Zhang J, Xiao L, Sherwin RS, Young LH. Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart. PNAS 2013; 110:16133-8.
- Zaha VG, Young LH. AMP-activated protein kinase regulation and biological actions in the heart. Circ Res. 2012; 111:800-814.
- Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol, 2011;51:24-32.
- Qi D, Hu X, Wu X, Merk M, Leng L, Bucala R, Young LH. Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia-reperfusion. J Clin Invest 119:3807-3816, 2009.
- Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature, 451:578-82, 2008.