Rong Tian, Professor
Joint with Anesthesiology & Pain Management
Instrumentation, Imaging and Image-Guided Therapy
Molecular and Cellular Engineering
Systems, Synthetic and Quantitative Biology
EducationMD, West China University of Medical Sciences, (1986)
PhD (pharmacology), University of Aarhus (Denmark), 1992
- Energy metabolism in cardiovascular diseases
- Mitochondrial dysfunction and metabolic signaling
- NMR spectroscopy and Imaging-guided spectroscopy
Contact InformationDepartment of Bioengineering
University of Washington
815 Mercer St. N135
Research DescriptionOur laboratory is interested in the molecular mechanisms regulating cardiac metabolism. The heart has the highest oxygen uptake rate in the body (0.1ml O2/g/min at basal conditions), and an adult human heart generates and consumes 6 Kg of ATP daily, 15-20 times of its own weight. Thus, the heart is a most robust metabolic organ and energy metabolism is integral of cardiac function and pathogenesis of heart failure. Our studies seek novel mechanisms and targets for metabolic therapy of heart disease.
To achieve our goals we perturb the metabolic network by altering its key element using bioengineered mice and determine the metabolic and functional outcomes using multi-nuclear NMR spectroscopy, MRI-guided metabolic imaging and mass spectrometry. We also create disease models and test the role of a specific metabolic alteration in the pathogenesis and progression of heart disease such as cardiac hypertrophy or diabetic cardiomyopathy. These strategies allow us to investigate cell metabolism in human diseases using a system biology approach. To this end, we are particularly interested in the dual role of mitochondria as a power plant and a death engine, and hope to identify nodal points for mitochondria-based cardioprotection that sustains oxidative metabolism and prevents cell death.
A related effort is to understand the signaling mechanisms that regulate cellular metabolism in normal and disease conditions. For example, the LKB-1/AMPK pathway is highly sensitive to cellular energy status and activation of AMPK cascade regulates multiple aspects of cell metabolism and growth. We were the first to identify the hypertrophied heart as a chronic model in which AMPK was activated by impaired myocardial energetic. We are studying the biological role of AMPK in the heart utilizing gain-of-function and loss-of function approaches in both cellular and whole animal models.
- Xing Y, Musi N, Fujii N, Zou L, Luptak I, Hirshman MF, Goodyear LJ, Tian R. Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative a2 subunit of AMP-activated protein kinase. J Biol Chem 2003, 278:28372-28377.
- Luptak I, Balschi JA, Xing Y, Leone TC, Kelly DP, Tian R. Decreased contractile reserve in PPARa-null hearts can be rescued by increasing glucose transport and utilization. Circulation 2005, 112:2339-2346.
- Zou L, Shen M, Arad M, He H, Lofgren B, Ingwall JS, Seidman CE, Seidman JG, Tian R. N488I mutation of the g2-subunit results in bi-directional changes in AMPK activity. Circ Res 2005 97(4):323-8.
- Luptak I, Shen M, He H, Hirshman MF, Musi N, Goodyear LJ, Yan J, Wakimoto H, Morita H, Arad M, Seidman CE, Seidman JG, Ingwall JS ,Balschi JA, Tian R. Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage. J Clin Invest. 2007, 117(5):1432-9.
- Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian, R. Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian, R. Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity Circulation 2009; 119:2818-2828.