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.
Laboratory: Laboratory of Diabetes and Obesity Research
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.
Dr. Zhen Jiang’s New C2 Domain Discovery featured in April 2018 Molecular and Cell Biology “Selected as Article of Significant Interest by the Editors.”
1. Ushakumari CJ, Zhou QL, Wang Y-H, Na S, Rigor MC, Zhou CY, Kroll MK, Lin BD, Jiang ZY*. Neutrophil Elastase Increases Vascular Permeability and Leukocyte Transmigration in Cultured Endothelial Cells and Obese Mice. Cells. 11(15):2288, 2022.
2. Zhou QL, Song Y, Huang CH, Huang J-Y, Gong Z, Liao ZP, Sharma AG, Greene L, Deng JZ, Rigor MC,
Xie X, Qi S, Ayala JE, and Jiang ZY. Membrane Trafficking Protein CDP138 Regulates Fat Browning and
Insulin Sensitivity through Controlling Catecholamine Release. Molecular and Cellular Biology, April 2018 Volume 38 Issue 8 e00153-17. [Epub ahead of print] Jan 29, 2018. PMID: 29378832, PMCID: PMC5879461, DOI: 10.1128/MCB.00153-17.
3. Huang JY, Zhou QL, Huang CH, Song Y, Sharma AG, Liao Z, Zhu K, Massidda MW, Jamieson RR, Zhang JY, Tenen DG, Jiang ZY. Neutrophil elastase regulates emergency myelopoiesis preceding systemic inflammation in diet-induced obesity. J. Biol. Chem. 292: 4770-4776, 2017 doi:10.1074/jbc.C116.758748. [Epub ahead of print] PMID: 28202548; PMCID: PMC28202548.
4. Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang J-Y, Khan AR, Aubert G, Candelaria K, Thomas S,
Shin D-J, Booth B, Baig SM, Bilal A, Hwang D, Zhang H, Lovell-Badge R, Smith S, Awan FR and Jiang
ZY. Imbalance between neutrophil elastase and its inhibitor a1-antitrypsin in obesity alters insulin
sensitivity, inflammation and energy expenditure. Cell Metabolism 17: 534-548, 2013. PMID: 23562077;
5. Xie X, Gong Z, Mansuy-Aubert V, Zhou QL, Tutalian SA, Sehrt D, Gnad F, Brill L, Motamedchaboki K,
Czech MP, Mann M, Kruger M, Jiang ZY. C2 domain containing phosphoprotein CDP138 regulates
GLUT4 insertion into the plasma membrane. Cell Metabolism 14:378-89, 2011. PMID: 21907143;
6. Jiang ZY, Chawla A, Bose A, Way M, and Czech MP. A PI 3-kinase-independent Insulin Signaling
Pathway through N-WASP-Arp2-3/F-Actinin Required for GLUT4 Glucose Transporter Recycling J. Biol. Chem. 277:509-515, 2002.
7. Jiang ZY, Zhou QL, Holik J, Patel S, Leszyk J, Coleman K, Chouinard M and Czech MP. Identification of protein kinase WNK1 as a substrate of protein kinase B/Akt and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells. J. Biol. Chem. 280:21622-8, 2005.
8. 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. 280(22):21622-8, 2005
9. Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, and Czech MP. Insulin Signaling Through
Akt/PKB Analyzed by siRNA-mediated Gene Silencing. Proc. Natl. Acad. Sci. USA 100:7569-7574, 2003.
PMID: 12808134 PMCID: PMC164627.
10. Jiang ZY, He Z, King BL, Kuroki T, Opland DM, Suzuma K, Suzuma I, Ueki K, Kulkarni RN, Kahn CR, King GL. Characterization of multiple signaling pathways of insulin in the regulation of vascular
endothelial growth factor expression in vascular cells and angiogenesis. J. Biol. Chem. 278(34):31964-
11. Jiang ZY, He Z, King BL, Kuroki T, Opland DM, Suzuma K, Suzuma I, Ueki K, Kulkarni RN, Kahn CR, King GL. Characterization of multiple signaling pathways of insulin in the regulation of vascular
endothelial growth factor expression in vascular cells and angiogenesis. J. Biol. Chem. 278: 31964-
12. 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 420(6917):821-4,
13. Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, Feener EP, Herbert TP, Rhodes CJ, King GL. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 101:676-81, 2000. PMID: 10673261.
14. Jiang ZY, Lin YW, Clermont AC, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF and King GL. Selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J. Clin. Invest. 104:447-457, 1999. PMID: 10449437 PMCID: PMC408521.
15. Jiang ZY, Zhou QL, Chatterjee A, Feener EP, Myers Jr. MG, White MF, and King GL. Endothelin-1
modulates insulin signaling through PI 3-kinase pathway in vascular smooth muscle cells. Diabetes
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, W-607B, Boston, MA 02118