Pharmacology & Cancer Biology | Duke University Medical Center

Dr. Xiao-Fan Wang

Xiao-Fan Wang, Ph.D.
Professor of Pharmacology and Cancer Biology

Duke University Medical Center
C218 LSRC
Box 3813
Durham, NC 27710

Phone: 919-681-4861
E-mail: wang0011@mc.duke.edu

Research Interests

The main research interest of our laboratory is to reveal and elucidate the molecular mechanisms of human diseases, such as cancer and immune disorders. The first area of research involves study of TGF-ß signal mechanisms in the context of both cultured cells and animal model systems. We intend to determine the role of Smad proteins, two of which are tumor suppressors mutated in human cancers, in regulating cell proliferation and differentiation. Using Smad3 deficient mouse as a model system, we are currently investigating the involvement of TGF-ß signaling and Smad3 function, as well as crosstalk with the Wnt signaling pathway, in the regulation of mesenchymal stem cell proliferation and differentiation. The second area of research aims to determine the signaling mechanism of cell cycle checkpoint in response to DNA damage and DNA replication block. The main focus is the study of functions of ATM, ATR and Rad17 as key components of the checkpoint pathways in mammalian cells. We intend to determine the mechanism through which the activities of ATM and ATR are activated in response to genotoxic stress and the molecular link between checkpoint and activation of apoptosis. The third area of research aims to determine the mechanisms of tumor progression and metastasis promoted by the activity of a novel protein, termed periostin that is secreted by many types of human tumors, using both cultured cells and animal model systems.

Publications

Bao, S., Tibbetts, R. S., Brumbaugh, K. M., Fang, Y., Richardson, D., Ali, A., Chen, S., Abraham, R. T., Wang, X.-F. (2001) Requirement for ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature, 411, 969-974

Frederick, J., Liberati, N., Waddell, D., Shi, Y., Wang, X.-F. (2004) TGF-ß mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel Repressive Smad Binding Element. Mol Cell Biol., 24, 2546-2559.

Ali, A., Zhang, J., Bao, S., Liu, Y., Otterness, D., Abraham, R. T., Wang, X.-F. (2004) Protein phosphatase 5 regulates ATM kinase activity during cellular responses to genotoxic stress. Genes & Dev., 18, 249-254.

Shao, R., Bao, S., Bai, X., Blanchette, C., Anderson, R. M., Marks, J. R., Wang, X.-F. (2004) Acquired expression of a mesenchyme-specific gene periostin by epithelial cancers promotes tumor angiogenesis. Mol. Cell Biol., 24, 3992-4003.

Bao, S., Ouyang, G., Huang, Z., Bai, X., Liu, M., Ma, C., Shao, R. Anderson, R. M., Wang, X.-F. (2004) Differential expression of periostin in colon cancers promotes tumor metastasis by activating AKT/PKB to enhance endothelial and cancer cells survival. Cancer Cell, 5, 329-339.

Waddell, D., Liberati, N., Frederick, J., Wang, X.-F. (2004) Casein kinase Ie plays a functional role in the transforming growth factor ß signaling pathway. J. Biol. Chem., 279, 29236-29246.

Fang, Y., Tsao, C., Goodman, B., Furumei, R., Tirado, C., Abraham, R., Wang, X.-F. (2004) ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair deficient background. EMBO J., 23, 3164-3174.

Hjelmeland, A. B., Schilling, S., Guo, X., Quarles, D., Wang, X.-F . (2005) Loss of Smad3-mediated negative regulation of Cbfa1 activity leads to an alteration in cell fate determination. Mol. Cell Biol., 25, 9460-9468.

Zhang, J., Bao, S., Kucera, K., Dean, N., Wang, X.-F. (2005) DNA damage-induced ATR activation is mediated by protein phosphatase 5. Mol. Cell Biol., 25, 9910-9919.

Jian, H., Shen, X., Liu, I. , Semenov, M., He, X., Wang, X.-F. (2006) TGF-ß induces ß-catenin nuclear translocation in a Smad3-dependent manner in human mesenchymal stem cells. Genes & Dev., 20, 666-674.

Guo, X., Ramirez, A.,Waddell, D., Li, Z., X. Liu, Wang, X.-F. (2008) Axin and GSK3ß control Smad3 protein stability and modulate TGF-ß signaling. Genes & Dev., 22, 106-120.

Ma, C., Rong, Y., Radiloff, D., Datto, M., Centeno, B., Bao, S., Chen, A., Lin, F., Jiang, S., Yeatman, T., Wang, X.-F. (2008) Extracellular matrix protein ßig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes & Dev., in press.

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