Associate Professor of Microbiology, Immunology & Cell Biology Ph.D., Mississippi State University, 1994 1820 MBRCC, Health Science Center (Office) (304) 293- 5949 (Office) MBRCC Health Science Center (Lab) (304) 293-0493 (Lab.) bhjiang@hsc.wvu.edu Curriculum Vitae

The research conducted in our lab aims to understand the molecular mechanisms of prostate, ovarian, and lung cancer growth; then develop new therapeutic approaches for treating the cancers. Our primary focus is the investigation of the PI 3-kinase signaling pathway and its role in the process of angiogenesis and tumorigenesis. PI 3-kinase and Akt are activated upon activation of protein tyrosine kinase receptors by growth factors. PI 3-kinase and Akt have been shown to promote cell growth and inhibit cellular apoptosis. PI 3-kinase signaling pathway has been strongly implicated in human cancer. A better understanding of PI 3-kinase signaling pathway is of great theoretic and therapeutic interests.

Our interest is to further investigate the mechanism of PI 3-kinase in angiogenesis and tumorigenesis as well as to explore potentially new functions of the pathway. Our study initially demonstrated that PI 3-kinase signaling plays an important role in angiogenesis. Angiogenesis is required for tumorigenesis and its inhibition represents one of the most promising approaches in cancer therapeutic treatment as well as in certain vascular diseases. We therefore plan to further study the mechanism of PI 3-kinase and PTEN in angiogenesis. It is known that PI 3-kinase is activated in vitro by a variety of growth factors. Several of these growth factors are known to induce angiogenesis. Accordingly, we will determine whether all or only some of the growth factors-mediated angiogenesis requires PI 3-kinase activation in vivo. We have also performed representational difference analysis to identify novel Akt targets involved in angiogenesis. We have obtained several new targets that have growth regulatory functions. We will characterize their expression profiles in human cancer, study their regulation patterns, and determine their role in angiogenesis and tumorigenesis. In addition, we have found that PI 3-kinase activates expression of VEGF, MDM2, and hypoxia-inducible factor 1 (HIF-1). We will study how PI 3-kinase signaling regulates these molecules, and study the molecular mechanisms of angiogenesis and tumorigenesis induced by PI 3-kinase signaling.

Reactive oxygen species (ROS) are generated by cellular aerobic metabolism and are induced by heavy metals, growth factors, and cytokine. Our recent results show that ROS are spontaneously produced by ovarian and prostate cancer cells, and can be induced by growth factors; and that ROS are involved in cell proliferation, HIF-1 and VEGF expression through PI 3-kinase signaling. We plan to study the molecular mechanism of ovarian tumorigenesis and angiogenesis in response to ROS signaling, and identify ROS-mediated signaling molecules for establishing therapeutic strategies for human ovarian cancer in the future. Our recent study found that dietary flavonoid, apigenin inhibited PI3K activation and VEGF and HIF-1 expression in different human cancer cells. Apigenin can specifically induce apoptosis of cancer cells, but not the normal cells. Apigenin also inhibits ROS production in cancer cells. We will further study the molecular mechanism of apigenin in inhibiting angiogenesis, and its application for cancer prevention and therapy.

Publications:

Jiang, B.H., J.Z. Zheng, M. Aoki, and P.K. Vogt. 2000. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of VEGF in endothelial cells. Proc Natl Acad Sci U S A 97: 1749-1753.

Skinner, H.D., J.Z. Zheng, J. Fang, F. Agani, and B.H. Jiang. 2004. VEGF transcriptional activation is mediated by HIF-1a, HDM2, and p70S6K1 in response to PI3K/AKT signaling. J Biol Chem. 279(44): 45643-45651.

Fang, J., C. Xia, Z. Cao, J. Z. Zheng, E. Reed, and B.H. Jiang. 2005. Apigenin Inhibits VEGF and HIF-1 Expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. FASEB J. 19(3): 342-353.

Xia, C., Q. Meng, X. Shi, and B.H Jiang. 2006. Regulation of angiogenesis and tumor growth by p110 Alpha and AKT1 via VEGF expression. J Cell Physiol. 209(1): 56-66.

Fang, J., Q. Meng, P.K.Vogt, R. Zhang, and B.H. Jiang. 2006. A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates human double minute 2 protein phosphorylation and stability. J Cell Physiol. 209(2): 261-265.

Liu, L.Z., X.W. Hu, C. Xia, J. He, Q. Zhou, X. Shi, J. Fang, and B.H. Jiang. 2006. Reactive oxygen species regulate EGF-induced VEGF and HIF-1 expression through activation of AKT and p70S6K1 in human ovarian cancer cells. Free Radic Biol Med. 41(10):1521-1533.

Fang, J, Q. Zhou, L.Z. Liu, C. Xia, X.W. Hu, X. Shi, and B.H. Jiang. 2007. Apigenin inhibits tumor angiogenesis through decreasing HIF-1 and VEGF expression. Carcinogenesis. 28(3): 713-723.

Cao, Z., L.Z. Liu, D.A. Dixon, J.Z. Zheng, B. Chandran, and B.H. Jiang. 2007. Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 19(7): 1542-1553.

Fang, J, M. Ding, L. Yang, LZ. Liu, and B.H. Jiang. 2007. PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis. Cell Signal. In press.

Xia, C, Q. Meng, L.Z. Liu, Y. Rojanasakul, X.R. Wang, and B.H. Jiang. 2007. Reactive oxygen species in cancer cells regulate angiogenesis and tumor growth through expression of vascular endothelial growth factor. Cancer Res. In press.