Joint Professor of Anesthesiology and Bioengineering
Office: South Lake Union Campus, N135
I seek to identify and target key players in cell metabolism and mitochondrial function to engineer cells more resistance to environmental stresses.
Energy metabolism in cardiovascular diseases
Mitochondrial function and metabolic signaling
NMR spectroscopy and Imaging-guided spectroscopy
Our laboratory is interested in identifying and targeting the key regulators of cell metabolism and mitochondrial function for the treatment of cardiovascular and metabolic diseases. 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 test the effects of metabolic intervention in a wide range of therapeutic strategies including preventive and regenerative medicine. One focus of our research is on the dual role of mitochondria as a power plant (ATP production) and a death engine (triggers of necrosis and apoptosis). We seek to identify nodal points for promoting mitochondria-based cardioprotection and stem cell differentiation. Our effort in this direction includes mitochondrial biogenesis, redox regulation and protein (de)acetylation. The second focus of our work is on substrate metabolism and metabolic signaling that involve lipids, sugar and amino acid metabolism. This line of research seeks to optimize cell metabolism in response to stresses via bioengineering approaches. We are particularly interested in the AMPK signaling cascade, a cellular energy sensor and a master regulator of cell metabolism and survival. We are searching for novel targets of AMPK in the heart utilizing gain-of-function and loss-of function approaches in both cellular and whole animal models.
MD, West China University of Medical Sciences, 1986
PhD (pharmacology), University of Aarhus, Denmark, 1992
Postdoc, Harvard Medical School, 1996
2010 Distinguished Achievement Award of the American Heart Association Basic Science Council
2008 Elected to American Society of Clinical Investigation
2003-07 Established Investigator of the American Heart Association
2004 Young Investigator Award of the American Physiological Society
1999 Scholars in Medicine at the Harvard Medical School
1998 Scientist Development Award of the American Heart Association
1995 Upjohn Award for Young Investigators (Finalist), International Society for Heart Research
1988-1991 Award from Chinese State Committee of Education for Ph.D. studies in Denmark
BIOEN 299: Introduction to Bioengineering
Kim M, Hunter RW, Garcia-Menendez L, Gong G, Yang YY, Kolwicz SC Jr, Xu J, Wang W, Sakamoto K, Tian R. Mutation in the γ2-subunit of AMPK Stimulates Cardiomyocyte Proliferation and Hypertrophy Independent of Glycogen Storage. Circ Res. 2014 Mar 14;114(6):966-75.
Karamanlidis G, Lee CF, Garcia-Menendez L, Kolwicz Jr. SC, Suthammarak W, Gong G, Sedensky MM, Morgan PG, Wang W, Tian R. Mitochondria Complex I Deficiency Increases Protein Acetylation and Accelerates Heart Failure. Cell Metab. 2013 Aug 6;18(2):239-50.
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. [Epub ahead of print]
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.
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, Nascimben L, Couper GS, Shekar PS, Tian R. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res. 2010, 109:1541-1549. PMID: 20339121 PMCID: PMC2880225
Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian R. Increased glucose uptake and oxidation in mouse hearts prevents high fatty acid oxidation but causes cardiac dysfunction in diet-induced obesity. Circulation. 2009; 119:2818-2828. Epub 2009 May 18. PMID:19451348 PMCID: PMC2765220
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 May;117(5):1432-9. Epub 2007 Apr 12. PMID:17431505 PMCID: PMC1847536