Assistant Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: xfang@vcu.edu
Telephone: 804-828-0787
Education
- B.S., 1983, Anhui Normal University, P.R. China
- M.S., 1986, Shanghai Medical University, P.R. China
- Ph.D., 1994, University of Toronto, Canada
Post-Doc
University of Texas MD Anderson Cancer Center 1995-1997
Research
The research in my lab focuses on identifying and
targeting small phospholipid molecules that regulate
the development and progression of human ovarian, breast
and prostate cancers. We previously identified a novel
growth-promoting activity present in ascites of ovarian
cancer patients mediated by lysophosphatidic acid (LPA).
Like many other biomediators, LPA interacts with cells
through specific cell surface receptors (G protein-coupled
receptors). Recent studies indicate that in many types
of human malignancies, LPA production is increased through
overexpression of an LPA-synthesizing enzyme called
autotaxin/Lyso-PLD, suggesting that amplification of
LPA signaling represents a common step of human carcinogenesis.
LPA has multiple biological effects on human cancer
cells including stimulation of cell proliferation, survival,
drug resistance, and motility. We have recently demonstrated
that LPA dramatically induces expression of multiple
pro-angiogenic factors such as vascular endothelial
growth factor (VEGF), interleukin 8 (IL-8), interleukin
(IL-6), and growth related oncogene 1 (Gro-1). These
factors are important mediators of cancer progression.
For example, VEGF increases vascular permeability, a
critical step in ascites formation in ovarian cancer.
IL-6 and IL-8 levels are elevated in ovarian, breast
and prostate cancer patients. The increased concentrations
of IL-6 and IL-8 correlate with poor response to chemotherapy
or poor prognosis. Thus LPA may exert its detrimental
effect through promoting tumor angiogenesis. The hypothesis
is also consistent with the migration-stimulating activity
of LPA. We are developing various approaches to modulate
LPA production or its receptor expression in vitro
and in vivo. An ability to manipulate the functionality
of LPA could potentially lead to novel and effective
therapies for cancer intervention.
Selected Publications
- Fang, X.J., Yu, S., Lu, Y., Bast, R.C., Woodgett, J.R., and Mills, G.B.
Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A.
Proc. Natl. Acad. Sci. USA 97:11960-11965, 2000
- Fang, X.J., Yu, S., Tanyi, J.L., Lu, Y., Woodgett, J.R., and Mills, G.B.
Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg
receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through
a protein kinase C-dependent intracellular pathway. Mol. Cell. Biol. 22:
2099-2110, 2002
- Hasegawa, Y., Erickson, J.R., Goddard, G.J., Yu, S., Cheng, K.W., Tabassam, F.H.,
Eder, A., Bandoh, K., Aoki, J., Lynch, K., Mills, G.B., and Fang, X.J.
Identification of a phosphothionate analogue of lysophosphatidic acid as a selective
agonist of the Edg7/LPA3 receptor. J. Biol. Chem. 278: 11962-11969, 2003
- Fang, X.J., Yu, S., Bast, R.C., Liu, S., Xu, H.J., Hu, S.X., LaPushin, R.,
Claret, F.X., Aggarwal, B.B., Lu, Y., Mills, G.B. Mechanisms for lysophosphatidic
acid-induced cytokine production in ovarian cancer cells. J. Biol. Chem. 279:
9653-9661, 2004
- Liu, S., Yu, S., Hasegawa, Y., LaPushin, R., Woodgett, J., Mills, G.B., and Fang,
X.J. Glycogen Synthase kinase 3b is a negative regulator of growth factor-induced
JNK activation. J. Biol. Chem. 2004 (In press)
|
