Education

Postdoctoral Fellow
Stony Brook University, 2002
Ph.D.
Peking Union Medical College & Chinese Academy of Medical Sciences, China, 1998
M.S.
Wuhan University, 1995

Areas of Interests

Research Interests

Phospholipid Signaling and Metabolism in Human Disease

Research Information

Phospholipid Signaling and Metabolism in Human Disease

Extracellular signals from cytokines, growth factors and nutrients regulate the activity of a key set of lipid-modifying enzymes that control phospholipid homeostasis: phospholipases, fatty acid synthase, lipid kinases and phosphatases. These enzymes and their downstream targets constitute a complex lipid signaling network with multiple nodes of interaction and cross-regulation, and control important cellular processes, including cell proliferation, apoptosis, metabolism and migration. Not surprisingly, aberrant lipid metabolism often contributes to the pathogenesis of human diseases.

Our previous studies have focused on the regulation and function of Phospholipase D (PLD), which generates the signaling phospholipid phosphatidic acid (PA) by hydrolyzing the most abundant membrane lipid, phosphatidylcholine. In past work we have demonstrated that PLD is involved in important cellular processes including membrane trafficking, cytoskeletal reorganization and cell transformation. Our current research focuses on understanding the signaling properties and the physiological and pathological functions of several phospholipid modifying enzymes, using in vitro biochemical approaches and in vivo mouse models. The proposed studies will further our understanding of lipid signaling in normal cells and in human disease, and will provide targets for novel therapeutic strategies.

A major emphasis in the laboratory is to understand the basic biology of phospholipid signaling pathways. In addition to more investigating the contributions of the known cohort of enzymes that control phospholipid signaling, we will also identify novel PA- and other phospholipid-binding proteins using a unique liposome pulldown system developed in our laboratory. By combining biochemical approaches with live cell imaging, we will then elucidate how phospholipids regulate these signaling proteins in different membrane compartments, and investigate the mechanisms by which these proteins regulate cellular functions, including membrane trafficking and cell proliferation. Another important direction in the lab is to discern how alterations in phospholipid signaling and metabolism contribute to human diseases, in particular to the initiation and progression of human breast cancer. Two phospholipid signaling nodes, PLD2 and Lipin 1, will be manipulated to address these questions.

A tutorial in my laboratory would provide experience with molecular and cell biology including cloning, DNA and RNA analysis, cell culture, protein and lipid techniques, modern microscopy and animal models. Also provided is a training for independent thinking on designing experiments for tackling scientific problems.

Publications

Publication Information

REFERENCES

  • He J, Zhang F, Tay LW, Boroda S, Nian W, Levental KR, Levental I, Harris TE, Chang JT, Du G. (2017). Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival. FASEB J. Jul;31(7):2893-2904. doi: 10.1096/fj.201601353R. Epub 2017 Mar 27.
  • Yin S*, Luo J*, Qian A, Du J, Yang Q, Zhou S, Yu W, Du G, Clark RB, Walters ET, Carlton SM, Hu H. (2013). Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity. J Clin Invest, 123(9):3941-51.
  • Roach AN, Wang Z, Wu P, Zhang F, Chan R, Yonekubo Y, Paolo GD, Gorfe AA, and Du G. (2012). Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization. J Lipid Res 53, 2598-2609. PMCID: PMC3494241
  • Wu P, Wilmarth MA, Zhang F, and Du G. (2012). miRNA and shRNA Expression Vectors Based on mRNA and miRNA Processing. Methods Mol Biol, 936:195-207. PMID: 23007510.
  • Zhang F and Du G. (2012). Dysregulated lipid metabolism in cancer. World J Biol Chem, 3(8):167-74. PMCID: PMC3430731.
  • Cho KJ, Hill MM, Chigurupati S, Du G, Parton RG, Hancock JF. (2011). Therapeutic Levels of the Hydroxmethylglutaryl-Coenzyme A Reductase Inhibitor Lovastatin Activate Ras Signaling via Phospholipase D2. Mol Cell Biol. 31(6):1110-20.
  • Yoon MS, Du G, Backer JM, Frohman MA, and Chen J. (2011). Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway. J Cell Biol, 195(3):435-47. PMCID: PMC3206351.
  • Ariotti N, Liang H, Xu Y, ZhangY, Yonekubo Y, Inder K, Du G, Parton RG, Hancock JF, and Plowman SJ. (2010). EGFR activation remodels the plasma membrane lipid environment to induce nanocluster formation. Mol Cell Biol 30, 3795-3804.
  • Scotto-Lavino E, Garcia-Diaz M, Du G, Frohman MA. (2010). The basis for the isoform-specific interaction of myosin phosphatase subunits protein phosphatase 1C beta and myosin phosphatase targeting subunit 1. J Biol Chem 285, 6419-24.
  • Tsukahara T, Tsukahara R, Fujiwara Y, Yue J, Cheng Y, Guo H, Zhang C, Balazs L, Du G, Frohman MA, Baker DL, Parrill AL, Uchiyama A, Kobayashi T, Murakami-Murofushi K, Tigyi G. (2010). Phospholipase D2-dependent Inhibition of the Nuclear Hormone Receptor PPARγ by Endogenous Cyclic Phosphatidic Acids. Mol Cell. 39(3):421-32.
  • Yin H, Gui Y, Du G, Frohman MA, Zheng XL. (2010). Dependence of phospholipase D1 multi-monoubiquitination on its enzymatic activity and palmitoylation. J Biol Chem 285,13580-8.
  • Yonekubo Y, Wu P, Esechie A, Zhang Y, Du G. (2010). Characterization of new serum biomarkers in breast cancer using lipid microarrays. Tumor Biol 31(3):181-7.
  • Su W, Yeku O, Olepu S, Genna A, Park JS, Ren H, Du G, Gelb M, Morris A, Frohman MA. (2009). FIPI, a Phospholipase D pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol Pharmacol  75, 437-46.
  • Esechie A and Du G. (2009). Increased lipogenesis in cancer. Commun Integr Biol 2, 86-90.
  • Mor A, Wynne J, Ahearn IM, Dustin M, Du G, and Philips MR. (2009). Phospholipase D1 Regulates Lymphocyte Adhesion via Upregulation of Rap1 at the Plasma Membrane. Mol Cell Biol 29, 3297-306.
  • Du G and Frohman MA. (2009). A lipid-signaled myosin phosphatase surge disperses cortical contractile force early in cell spreading. Mol Biol Cell, 20 200-8.
  • Zhang Y and Du G. (2009). Phosphatidic acid regulation of small GTPases and actin cytoskeletal reorganization. Biochem Biophys Acta, 1791, 850-5.
  • Wu J, Bonsra AN, and Du G. (2009). pSM155 and pSM30 vectors for miRNA and shRNA expression. Methods Mol Biol 487, 205-219.
  • Zhao C, Du G, Skowronek K, Frohman MA, and Bar-Sagi D. (2007). Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol 9(6):707-712.
  • Mor A, Campi G, Du G, Zheng Y, Foster DA, Dustin ML, and Philips MR. (2007). The lymphocyte function-associated antigen-1 receptor co-stimulates plasma membrane Ras via phospholipase D2.  Nat Cell Biol  9(6):713-9.
  • Scotto-Lavino E, Du G, and Frohman MA. (2006). Amplification of 5′ end cDNA with ‘new RACE’.  Nat. Protoc. 1(6):3056-61.
  • Su W, Chardin P, Yamazaki M, Kanaho Y, and Du G. (2006). RhoA-mediated Phospholipase D1 signaling is not required for the formation of stress fibers and focal adhesions. Cell Signal 18(4): 469-478.
  • Du G, Huang P, Liang BT, and Frohman MA. (2004). Phospholipase D2 localizes to the plasma membrane and regulates Angiotensin II receptor endocytosis. Mol Biol Cell, 15(3): 1024-1030.
  • Du G, Altshuller YM, Vitale N, Huang P, Chasserot-Golaz S, Morris AJ, Bader MF, and Frohman MA. (2003). Regulation of Phospholipase D1 subcellular cycling through coordination of multiple membrane association motifs. J Cell Biol 162(2): 305-315.