Education & Training
- Postdoctoral Fellow
- McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), 2015
- Postdoctoral Fellow
- Harvard University, 2012
- Chinese Academy of Science, 2009
Areas of Interests
- Research Interest
- Phospholipid metabolism in human disease
Phospholipid metabolism in human disease
Phosphatidic acid (PA) is one of the major components for cellular membranes. In addition, PA is an important signaling molecule involved in a wide spectrum of biological processes as cell proliferation, cell survival, cytoskeletal reorganization and so on. In mammalian cells, the major source of signaling PA is from phospholipase D (PLD) by the hydrolysis of phosphatidylcholine (PC).
Inappropriate vascular remodeling is a major cause of most vascular pathologies, such as atherosclerosis and restenosis. We investigated the role of phospholipase D2 (PLD2), which generates PA, in injury-induced neointima formation using the carotid artery ligation model. We have found that PLD2 knockout mice showed significantly decreased occlusive neointima formation as compared to wild-type mice. This protection against occlusion is not related to proliferation changes. Instead, the migration ability is significantly impaired in vascular smooth muscle cells (VSMCs) isolated from PLD2 knockout mice or treated with a PLD2 inhibitor. We hypothesize that PA is playing a critical role for VSMC migration and pathological vascular remodeling. Currently, we are trying to figure out the mechanism in which PA regulates VSMC migration, which will lead to the potential therapy for limiting occlusive hyperplasia in atherosclerosis and restenosis.
Metastasis is the major cause of breast cancer death. However, despite considerable progress, the signaling events specifically driving cancer cell invasion and metastasis remain largely unknown. In our lab, we have found that removal of the gene encoding PLD2 strongly reduced circulating tumor cells and lung metastases in the MMTV-Neu breast cancer mouse model, whereas it had no effect on tumor initiation and growth. Consistently, migration, invasion and invadopodia, were greatly reduced in primary mouse tumor cells and human breast cancer cell lines lacking PLD2, suggesting that PLD2 promotes tumor metastasis by regulating the local invasion of tumor cells. All these evidences indicated that PLD2-generated PA may regulate cancer cell invasion ability in both in vivo and in vitro. Therefore, our running project to characterize the role of PA in cancer metastasis will provide new insights for the treatment of metastatic breast cancer.
- Wang Z, Luo Y, Shao Q, Kinlock BL, Wang C, Hildreth JEK, Xie H, Liu B. (2014). Heat-Stable Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication. Plos One. Aug 28; 9(8): e106078.
- Zhang F, Wang Z, Yonekubo Y, Zhang Y, Wu P, Zhou Y, Grinstein S, Hancock JF, and Du G. (2014). Temporal production of the signaling lipid phosphatidic acid by phospholipase D2 determines the output of ERK signaling in cancer cells. Mol Cell Biol. Jan; 34(1):84-95.
- Roach AN, Wang Z, Wu P, Zhang F, Chan RB, Yonekubo Y, DiPaolo G, Gorfe AA, and Du G. (2012). Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization. J of Lipid Res.. Dec; 53(12):2598-609. (Co-First Author)
- Ding Y, Zhang L, Goodwin JS, Wang Z, Liu B, Zhang J, Fan GH. (2008). Plectin regulates the signaling and trafficking of the HIV-1 co-receptor CXCR4 and plays a role in HIV-1 infection. Exp Cell Res. Feb 1; 314(3):590-602.
- Ding Y, Qiao A, Wang Z, Goodwin JS, Lee ES, Block ML, Allsbrook M, McDonald MP, Fan GH. (2008). Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer’s disease transgenic mouse model. J Neurosci. Nov 5; 28(45):11622-34.
- Wang Z, Zhang L, Qiao A, Watson K, Zhang J, Fan GH. (2008). Activation of CXCR4 triggers ubiquitination and down-regulation of major histocompatibility complex class I (MHC-I) on epithelioid carcinoma HeLa cells. J Biol Chem. Feb 15; 283(7):3951-9.