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Xianjun Fang, Ph.D.
My research aims to identify and characterize small molecules that regulate the development and progression of ovarian cancer. We previously found a novel growth-stimulating activity in ascites of ovarian cancer patients that is not present in ascites of patients suffering from other, nonmalignant diseases. Later work showed that the activity stems from natural phospholipids: lysophosphatidic acid (LPA) and lysophosphatidylcholine.

My research concerns the role of these phospholipids in the regulation of ovarian cancer cell growth and the potential application of these lipids as targets in therapy. In collaboration with Dr. Yan Xu (The Cleveland Clinic Foundation), we demonstrated, in both anchorage-dependent and anchorage-independent assays, that LPA is capable of stimulating growth of ovarian and breast cancer cells. I recently examined the effect of LPA on cell survival. Experiments with fibroblasts and epithelial cells established that LPA is also capable of protecting cells from serum withdrawal-induced apoptosis. The antiapoptotic activity of LPA is separable from and independent of LPA's mitogenic action. In contrast to current dogma regarding the importance of phosphatidylinositol 3' kinase (PI-3K) in resistance to apoptosis, we demonstrated that the PI-3K pathway is not instrumental in LPA-mediated inhibition of apoptosis despite its essential role in the mitogenic response to LPA. The finding reveals a novel aspect of LPA and further highlights the importance of targeting this lipid mediator in cancer treatment.

Another line of my research is to study the role of oncogenes and tumor suppressor genes, including Ras, p16, retinoblastoma (RB), and the newly cloned candidate tumor suppressor gene NOEY2, in the pathogenesis of ovarian and breast cancer.

Selected Publications:
  1. Fang XJ, Gibson S, Flowers M, Furui T, Bast RC Jr, Mills GB. Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity. J Biol Chem 272:13683-13689, 1997
  2. Fang XJ, Jin X, Xu HJ, Liu L, Peng HQ, Hogg D, Roth JA, Yu YH, Xu F, Bast RC, Mills GB. Expression of p16 induces transcriptional downregulation of the RB gene. Oncogene 16:1-8, 1998
  3. Patton SE, Martin ML, Nelsen LL, Fang XJ, Mills GB, Bast RC Jr, Ostrowski MC. Activation of the Ras-MAP kinase pathway and phosphorylation of Ets-2 at position threonine 72 in human ovarian cancer cell lines. Cancer Res 58:2253-2259, 1998
  4. Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochem J 309:933-940, 1995