Zhen Y. Jiang, M.D., Ph.D.
Ph.D. (Biochemistry): University College, University of London, London, U.K. M.D.: Jiangxi Medical College, Nanchang, Jiangxi, China. M.Sc. (Pharmacology): Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Metabolic Syndrome, Obesity, Diabetes and Innate Immunity
Currently, my lab mainly focuses on understanding how insulin signaling networks and innate immunity regulate metabolic functions.
1. CDP138 and its signal networks related to glucose and lipid metabolisms. In collaboration with Dr. Marcus Krueger and Dr. Matthias Mann’s laboratory at the Planck Institute of Biochemistry in Munich, Germany, we applied a SILAC-based quantitative proteomics approach and identified multiple phosphoproteins from insulin-stimulated adipocytes. As a result, we found that CDP138, a novel phosphoprotein containing C2 domain, is involved in the regulation of GLUT4 translocation. We also produced CDP138 knockout mouse model. Currently, we are using TIRF microscopy-based live cell imaging, protein-protein interactions, gene expression profiling and the knockout mouse model to study the signal network of CDP138 and its role in the regulation of glucose and lipid metabolisms and neuronal functions.
2. Exploring the role of neutrophils and neutrophil elastase (NE) in the development of obesity-related adipose inflammation, insulin resistance and cardiovascular dysfunction. Using quantitative serum proteomic approach, we recently identified that there is an imbalance between NE and its inhibitor alpha-1-antitrypsin in both obese human subjects and mouse models. Interestingly, both NE knockout mice and human A1AT transgenic mice are resistant to high-fat diet-induced body weight gain, adipose inflammation, fatty liver and insulin resistance. We also observed that NE knockout mice have higher AMP kinase activity and fatty acid oxidation rate. Currently, we are exploring molecular and cellular mechanisms whereby obesity regulates neutrophils activity and subsequent adipose inflammation, fatty liver, insulin resistance and cardiovascular dysfunctions using approaches such as live animal imaging, bone marrow transplantation, transcriptional regulation and lipidomics with different mouse models.
Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang JY, Khan AR, Aubert G, Candelaria K, Thomas S, Shin DJ, Booth S, Baig SM, Bilal A, Hwang D, Zhang K, Lovell-Badge R, Smith SR, Awan FR, Jiang ZY. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 2013 Apr 2; 17(4):534-48. PMID:23562077. Full article.
Xie X, Gong Z, Mansuy-Aubert V, Zhou QL, Tatulian SA, Sehrt D, Gnad F, Brill LM, Motamedchaboki K, Chen Y, Czech MP, Mann M, Krüger M, Jiang ZY. C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane. Cell Metab. 2011 Sep 7;14(3):378-89. PMID:21907143. .
Zhou QL, Jiang ZY, Mabardy AS, Del Campo CM, Lambright DG, Holik J, Fogarty KE, Straubhaar J, Nicoloro S, Chawla A, Czech MP. A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. J Biol Chem. 2010 Sep 3;285(36):27581-9. PMID: 20587420. .
Zhou QL, Jiang ZY, Holik J, Chawla A, Hagan GN, Leszyk J, Czech MP. Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytes. Biochem J. 2008 May 1;411(3):647-55. PMID: 18215134. .
Jiang ZY, Zhou QL, Holik J, Patel S, Leszyk J, Coleman K, Chouinard M, Czech MP. Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells. J Biol Chem. 2005 Jun 3;280(22):21622-8. PMID: 15799971. .
Zhou QL, Park JG, Jiang ZY, Holik JJ, Mitra P, Semiz S, Guilherme A, Powelka AM, Tang X, Virbasius J, Czech MP. Analysis of insulin signalling by RNAi-based gene silencing. Biochem Soc Trans.2004 Nov;32(Pt 5):817-21. Review. PMID: 15494023. .
Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, Czech MP. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7569-74. PMID: 12808134. .
Bose A, Guilherme A, Robida SI, Nicoloro SM, Zhou QL, Jiang ZY, Pomerleau DP, Czech MP. Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c. Nature. 2002 Dec 19-26;420(6917):821-4. PMID: 12490950. .
Jiang ZY, Chawla A, Bose A, Way M, Czech MP. A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recycling. J Biol Chem. 2002 Jan 4;277(1):509-15. PMID: 11694514. .
Jiang ZY, Zhou QL, Chatterjee A, Feener EP, Myers MG Jr, White MF, King GL. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. Diabetes. 1999 May;48(5):1120-30. PMID: 10331419. .
Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF, King GL. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.J Clin Invest. 1999 Aug;104(4):447-57. PMID: 10449437. .
Jiang ZY, Zhou QL, Eaton JW, Koppenol WH, Hunt JV, Wolff SP. Spirohydantoin inhibitors of aldose reductase inhibit iron- and copper-catalysed ascorbate oxidation in vitro. Biochem Pharmacol. 1991 Aug 22;42(6):1273-8. PMID: 1909528. Abstract: .
Both postdoctoral and graduate student positions are available. Please contact Dr. Jiang: email@example.com
Office: Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany Street, Room: To be Announced, Boston, MA 02118
Fax: To Be Announced
Lab Phone: To Be Announced