1998 Ph.D., Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R.China
1998-1999 Postdoctoral Fellow, Cell Biology and Pharmacology, The Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, MN
1999-2003 Postdoctoral Fellow, Molecular Biology and Signal Transduction, Diabetes and Metabolism Unit, Boston University School of Medicine, MA
General field of research:
Cell metabolism and Diabetes
Affiliations other than medicine:
Evans Center for Interdisciplinary Biomedical Research
Vascular Biology Unit, Department of Medicine
650 Albany Street, X726
Phone: (617)-638 2799
Phone: (617)-638 2796
Fax: (617)-638 7113
Other research websites:
Diabetes; Atherosclerosis; Protein kinase; NAD-dependent deacetylase; Cell Metabolism; Hepatocyte
Summary of research interest:
The main goal of Dr. Zang’s laboratory is to investigate the physiological and pathological regulation of novel nutrient signaling in energy homeostasis and in diabetes and its cardiovascular complications. A major focus is to determine how protein kinases or their signaling networks modulate hepatic glucose and lipid metabolism through regulation of kinase phosphorylation, protein-protein interactions and gene expression, and their implication in the pathogenesis of diabetes. Recent studies have focused on the role of key nutrient sensors, such as AMP-activated protein kinase (AMPK) and the NAD-dependent deacetylase (SIRT1), in the control of cell metabolism and diabetes, and found that AMPK is required for metformin, an anti-diabetic drug, to prevent hepatocyte lipid accumulation. Importantly, she has identified AMPK activation as a novel molecular mechanism for the beneficial effects of nature products, such as polyphenols including resveratrol, on hepatic lipid accumulation, hyperlipidemia and atherogenesis in diabetic mice. She and her colleagues have also defined SIRT1 as a critical regulator responsible for activation of LKB1/AMPK signaling by polyphenols, which explains their therapeutic effects on hepatocyte lipid accumulation, obesity and insulin resistance. The ultimate goal is to provide new insight into the mechanism of dyslipidemia and diabetes and identification of potential therapeutic interventions.
1. Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice. Cell Metabolism (Impact Factor, 17.350), 2011, 13(4):376-88. PMID: 21459323
2. Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, Donmez G, Li J, Luo Z, Walsh K, Guarente L, Zang M. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB Journal, 2011, 25(5):1664-79. PMID: 21321189.
3. Xu S, Jiang B, Hou X, Shi C, Bachschmid M, Zang M, Verbeuren TJ, Cohen RA. High fat diet increases and the polyphenol, S17834, decreases acetylation of the SIRT1-dependent lysine-382 on p53 and apoptotic signaling in atherosclerotic lesion-prone aortic endothelium of normal mice. J Cardiovasc Pharmacol. 2011 Jun 3, 58(3):263-71. PMID: 21654327.
4. Ponugoti B, Xiao Z, Wu S, Chiang C, Zang M, Veenstra TD, Kemper J Kim. SIRT1 deacetylates and inhibits SREBP-1c activity in hepatic lipid metabolic regulation. Journal of Biological Chemistry, 2010; 285: 33959–33970. PMCID: PMC2962496.
5. Luo Z, Zang M, Wen G. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncology, 2010, 6: 457-470. PMCID: PMC2854547
6. Wang J, Ma H, Tong C, Zhang H, Lawlis GB, Li Y, Zang M, Ren J, Nijland MJ, Ford SP, Nathanielsz PW, Li J. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. FASEB Journal, 2010, 24:2066-2076. PMCID: PMC2874473
7. Tao R, Gong J, Luo X, Zang M, Guo W, Wen R, Luo Z. AMPK exerts dual regulatory effects on the PI3K pathway. Journal of Molecular Signaling, 2010, 5:1-9. PMCID: PMC2848036
8. Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, Lan F, K. Walsh, Wierzbicki M, Verbeuren TJ, Cohen RA, Zang M. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-Activated protein kinase. Journal of Biological Chemistry, 2008, 283: 20015-26. PMCID: PMC2459285
9. Zang M, Gong J, Luo L, Zhou J, Xiang X, Huang W, Huang Q, Luo X, Olbrot M, Peng Y, Chen C, Luo Z. Characterization of S338 phosphorylation for Raf-1 activation. Journal of Biological Chemistry, 2008, 283: 31429-37. PMCID: PMC2581588
10. Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren TJ, Cohen RA. Polyphenols stimulate AMP-activated protein Kinase, lower lipids, and inhibit accelerated atherogenesis in diabetic LDL receptor-deficient mice. Diabetes, 2006, 55: 2180-2191. PMID: 16873680.
11. Zuccollo A, Shi C, Mastroianni R, Maitland KA, Weisbrod RM, Zang M, Xu S, Cayatte A, Corda S, Lavielle G, Verbeuren TJ, Cohen RA. The thromboxane A2 receptor antagonist, S18886, prevents enhanced atherogenesis caused by diabetes mellitus. Circulation, 2005, 112: 3001-3008. PMID: 16260636
12. Zang M, Zuccollo A, Hou X, Nagata D, Walsh K, Herscovitz H, Brecher P, Ruderman NB, Cohen RA. AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. Journal of Biological Chemistry, 2004, 279:47898-47905. PMID: 15371448.
13. Zang M, Dong M, Pinon DI, Ding X, Hadac EM, Miller LJ. Spatial approximation between a photolabile residue in position 13 of secretin and the amino-terminal tail of the secretin receptor. Molecular Pharmacology, 2003, 63: 993-1001. PMID: 12695527
14. Dong M, Li Z, Zang M, Pinon DL, Lybrand TP, Miller LJ. Spatial approximation between two residues in the mid-region of secretin and the amino terminus of its receptor. Journal of Biological Chemistry, 2003, 278:48300-48312. PMID:14500709
15. Xiang X, Zang M, Waelde CA, Wen R, Luo Z. Phosphorylation of S338SYY341 regulates specific interaction between Raf-1 and MEK1. Journal of Biological Chemistry, 2002, 277: 44996-45003. PMID: 12244094
16. Zang M, Hayne C, Luo Z. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. Journal of Biological Chemistry, 2002, 277: 4395-4405. PMID: 11733498
17. Huang YZ, Zang M, Xiong WC, Luo Z, Mei L. Erbin suppresses the MAP kinase pathway: Down-regulation of AChR epsilon-subunit gene transcription. Journal of Biological Chemistry, 2002, 278, 1108-1114. PMID: 12379659
18. Dong M, Zang M, Pinon DI, Li Z, Lybrand TP, Miller LJ. Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus. Molecular Endocrinology, 2002, 16: 2490-2501. PMID: 12403838
19. Zang M, Waelde CA, Xiang X, Rana A, Wen R, Luo Z. Microtubule integrity regulates Pak leading to Ras-independent activation of Raf-1. Journal of Biological Chemistry, 2001, 276: 25157-25165. PMID: 11274179
20. Dong M, Asmann YW, Zang M, Pinon DI, Miller LJ. Identification of two pairs of spatially approximated residues within the carboxyl-terminus of secretin and its receptor. Journal of Biological Chemistry, 2000; 275: 26032-26039. PMID: 10859300
Technologies available for sharing upon request:
Molecular Biology; Protein Biochemistry; Protein kinase Assay; Protein-protein interaction; Diabetes mouse model; Atherosclerotic mouse model.