- NMR Facility
- About Us
PI: Rong Tian, MD, PhD
Research in the Tian Laboratory focuses on the role of cell metabolism and mitochondrial function in the pathogenesis of human diseases. The laboratory uses multi-disciplinary approaches to identify novel regulatory mechanisms, perturb the metabolic networks, and interrogate metabolic fluxes and bioenergetics in a variety of model systems. Current studies concentrate on cardiac substrate metabolism, mitochondrial function and metabolic signaling by combining the powerful NMR techniques and metabolomics with ability to target the molecular regulatory mechanisms via genetic manipulation in animal models. Dr. Tian is also interested in bi-directional translational research between the bench and the bedside to elucidate the functional significance of altered cellular metabolism in ischemic heart disease, obesity, diabetes and heart failure.
An adult human heart has the highest oxygen uptake rate in the body (~0.1ml O2/g/min at basal conditions); it generates and consumes about 6 Kg of ATP daily, 15-20 times its own weight. Even though the heart has developed extensive metabolic machinery and sophisticated regulatory networks to ensure energy homeostasis, impairment of cardiac metabolism has been found in a variety of disease conditions. Importantly, the consequence of abnormal cardiac metabolism is no longer limited to deficient energy production, as the biological roles of mitochondria and reactive oxygen species have been increasingly recognized.
Part of our current research examines the fundamental mechanisms linking altered cardiac metabolism and mitochondrial dysfunction to the pathogenesis of heart diseases. This line of work seeks to generate a basis for metabolic therapy for heart failure and cardiac lipotoxicity in obesity and diabetes. Studies in this direction extend to nutrient-mediated gene expression and programming of the cell during development, aging and disease conditions.
Another focus of our lab is to understand metabolic signaling in cardiovascular biology. We are interested in signaling mechanisms regulating cell metabolism under disease conditions as well as novel signaling functions of metabolites. For example, we were first to report that bioenergetic stress in pathological cardiac hypertrophy activates the AMP-activated protein kinase (AMPK), an energy sensor and master switch of metabolism. We subsequently generated mouse models with "gain-of-function" and "loss-of-function" of AMPK. Ongoing investigations in the lab address novel roles of AMPK in mitochondria biogenesis/function, cell growth and survival.
Stephen Kolwicz, PhD Acting Instructor
Research Focus: Cardiac metabolism in hypertrophy and failure
Maengjo Kim, PhD Senior Fellow
Naveen Bojjireddy, PhD Senior Fellow
Chi Fung Lee, PhD Senior Fellow
Zhen Zhang, MS PhD Visiting PhD Student, China
Nathan Roe, PhD Senior Fellow
Maria Elena Danoviz, PhD Senior Fellow
Fan Fan, Visiting PhD Student, China
Yongseon Choi, Volunteer
Tian Lab Publications
- KaramanlidisG, Lee CF, Garcia-MenendezL, Kolwicz Jr. SC, Suthammarak W, Gong G, Sedensky MM, Morgan PG, WangW, Tian R. Mitochondrial Complex I Deficiency Increases Protein Acetylation and Accelerates Heart Failure. Cell Metabolism. 2013, in press
- Garcia-Menendez L, Karamanlidis G, Kolwicz SC, Tian R. Substrain specific response to cardiac pressure overload in C57BL/6 mice. Am J Physiol.2013 May 24.
Nowakowski SG, Kolwicz SC, Korte FS, Luo Z, Robinson-Hamm JN, Page JL, Brozovich F, Weiss RS, Tian R, Murry CE, Regnier M. Transgenic overexpression of ribonucleotide reductase improves cardiac performance.Proc Natl Acad Sci USA. 2013 Mar 25.
- Matsushima S, Kuroda J, Ago T, Zhai P, Ikeda Y, Oka S, Fong GH, Tian R, Sadoshima J. Broad Suppression of NADPH Oxidase Activity Exacerbates Ischemia/Reperfusion Injury Through Inadvertent Downregulation of HIF-1 and Upregulation of PPARα. Circ Res. 2013 Mar 8. [Epub ahead of print]
- Marney LC, Kolwicz, Jr. SC, Tian R, Synovec RE. Sample preparation methodology for mouse heart metabolomics using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry. Talanta 2013,108:123–130
- Kim M, Tian R. Transcript Variants dictate PRKAG2 cardiomyopathy? J Mol Cell Cardiol. 2012, Oct; 51(4):548-53. PMID: 21147121
- Kolwicz, Jr. SC, Olson DP, Marney LC, Garcia-Menendez L, Synovec RE, Tian R. Cardiac-specific deletion of acetyl CoA carboxylase 2 (ACC2) prevents metabolic remodeling during pressure-overload hypertrophy. Circ Res 2012,Aug 31; 111(6): 728-38. PMID: 22730442
- Kim M, Shen M, Ngoy S, Karamanlidis G, Liao R, Tian R.AMPK Isoform expression in the normal and failing hearts. J Mol Cell Cardiol. 2012 May;52(5):1066-73. Epub 2012 Jan 31. PMID: 22314372
- Yoshioka J, Chutkow WA, Lee S, Kim JB, Yan J, Tian R, Lindsey ML, Feener EP, Seidman CE, Seidman JG, Lee RT. Deletion of Thioredoxin-Interacting Protein Impairs Mitochondrial Function but Protects the Myocardium from Ischemia-Reperfusion Injury. J Clin Invest 2012 Jan 3;122(1):267-79. Epub 2011 Dec 27. PMID: 22201682
- Karamanlidis G, Bautista-Hernandez V, Fynn-Thompson F, Del Nido P, Tian R. Impaired Mitochondrial Biogenesis Precedes Heart Failure in Right Ventricular Hypertrophy in Congenital Heart Disease. Circ Heart Fail.2011 Nov 1; 4 (6): 707-13. Epub 2011 Aug 12 PMID: 21840936
- Dzeja PP, Hoyer K, Tian R, Zhang S, Nemutlu E, Spindler M, Ingwall JS. Rearrangement of energetic and substrate utilization networks compensate for chronic myocardial creatine kinase deficiency. J Physiol. 2011 Nov1; 589 (Pt 21): 5193-211 Epub 2011 Aug 30. PMID: 21878522
- Pinz I, Tian R, Belke D, Swanson E, Dillmann W, Ingwall JS. Compromised myocardial energetics in hypertrophied mouse hearts diminish the beneficial effect of overexpressing SERCA2a. J Biol Chem. 2011 Mar 25; 286(12):10163-8. Epub 2011 Jan 29. PMID: 21278384 PMCID: PMC3060468
- Xie Z, LauK Eby B, Lozano P, He C, Pennington B, Li H, Rathi S, Dong Y, Tian R, Kem D, Zou MH. Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice. Diabetes. 2011 Jun; 60(6):1770-8. Epub 2011 May 11. PMID: 21562078 PMCID: PMC3114402
- Kolwicz SC Jr, Tian R. Glucose metabolism and cardiac hypertrophy. Cardiovasc Res 2011 May 1; 90(2):194-201. PMID:21502371 [PubMed- in process]
- Kim M, Tian R. Targeting AMPK for cardiac protection: Opportunities and Challenges. J Mol Cell Cardiol 2011 Oct; 5 (4): 548-53. Epub 2010 Dec 13 PMID:21147121
- Kolwicz SC Jr, Tian R. Assessment of cardiac function and energetics in isolated mouse hearts using 31P NMR spectroscopy. . J Vis Exp. 2010 Aug 31;(42). pii: 2069. doi: 10.3791/2069. PMID: 20834220
Mitochondria and Metabolism Center
850 Republican St, Room N130
University of Washington, Box 358057
Seattle, WA 98109-8057
Email: Rong Tian