Dr. Guangwei Du
The University of Texas Health Science Center at Houston
Department of Integrative Biology and Pharmacology
- Phospholipid signaling
- Signal transduction
- Breast cancer
- Membrane trafficking
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.
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.
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.
Zhao C, Du G, Skowronek K, Frohman MA, 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, Philips MR. (2007). The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2. Nat Cell Biol. 9(6):713-9.
Yang JS, Gad H, Lee S, Zhang L, Turacchio, G, Bonsra AN, Du G, Bourgion S, Frohman MA, Luini A and Hsu VW. (2008). Fission of COPI vesicles from Golgi membrane requires both protein and lipid components. Nat Cell Biol. 10(10):1146-53.
Du G and Frohman MA. (2009). A lipid-signaled myosin phosphatase surge disperses cortical contractile force early in cell spreading. Mol Biol Cell. 20(1):200-8.
Yonekubo Y, Wu P, Esechie A, Zhang Y, Du G. (2010). Characterization of new serum biomarkers in breast cancer using lipid microarrays. Tumour Biol. 31(3): 181-7.
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.