Xiao-Fan Wang, Ph.D.

Xiao-Fan Wang, Ph.D. Donald and Elizabeth Cooke Professor of Experimental Oncology
Professor of Pharmacology and Cancer Biology

Duke University School of Medicine
Box 3813
Durham, NC 27710

Phone: 919-681-4861

Research Interests

The current research in the Wang laboratory mainly focuses on the elucidation of molecular nature and signaling mechanisms associated with tumor microenvironment that promotes tumor progression and metastasis. Particularly, we are interested in the roles of specific microRNAs as mediators of TGF-β or hypoxia to affect the biological nature of tumor microenvironment, via the interactions with the immune system and the recruitment of various types of stromal cells, to enhance tumor metastasis. We are also studying the mechanisms underlying the phenomenon of cellular senescence. Ultimately, we hope that our studies in these areas to lead to the development of novel therapeutics for the treatment of various types of human cancer.

Representative Publications

Jian, H., Shen, X., Liu, I., Semenov, M., He, X., Wang, X.-F. (2006) TGF-β induces β-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-β 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 βig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes & Dev., 22, 308-321.

Liu, I., Schilling, S., Knouse, K., Choy, L., Derynk, R., Wang, X.-F. (2009) TGF-β- stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro- migratory TGF-β switch. EMBO J., 28, 88-98.

Jardim, M., Wang, Q., Furumai, R., Goodman, B., Wang, X.-F. (2009) Reduced ATR or Chk1 expression leads to chromosome instability and chemo-sensitization of mismatch repair deficient colorectal cancer cells. Mol Biol Cell, 20, 3801-3809.

Feng, J., Wakeman, T., Yong, S., Wu, X., Kornbluth, S., Wang, X.-F. (2009) PP2A-dependent dephosphorylation of replication protein A (RPA) is required for the repair of DNA breaks induced by replication stress. Mol. Cell Biol., 29, 5696-5709.

Radiloff, D., Wakeman, T., Feng, J., Schilling, S., Seto, E., Wang, X.-F. (2011) Trefoil factor-1 acts as a suppressor of senescence induced by oncogene-activation during the cellular transformation process. Proc. Natl. Acad. Sci. USA, 108, 6591-6596.

Wakeman, T., Wang, Q., Feng, J., Wang, X.-F. (2012) Bat3 facilitates histone H3 lysine 79 dimethylation by DOT1L and is required for DNA repair and cell survival following exposure to ionizing radiation. EMBO J, 31, 2169-2181.

Yang, P., Li, Q.-J., Feng, Y.-X., Zhang, Y., Markowitz, G., Ning, S., Deng, Y., Zhao, J., Jiang, S., Yuan, Y., Wang, H., Cheng, S.-Q., Xie, D., Wang, X.-F. (2012) TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastasis of HBV-positive hepatocellular carcinoma. Cancer Cell, 22, 291-303.

Zhang, Y., Yang, P., Sun, T., Li, D., Xu, X., Rui, Y., Li, C., Chong, M., Ibrahim, T., Mercatali, L., Amadori, D., Lu, X., Xie, D., Li, Q.-J., Wang, X.-F. (2013) Mir-126 and Mir-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nature Cell Biology, 15, 284-294.

Wang, Q., Goldstein, M., Alexander, P., Wakeman, T. P., Sun, T., Feng, J., Lou, Z., Kastan, M. B., Wang, X.-F. (2014) Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the cellular response to DNA double-strand breaks. EMBO J., 33, 862-877. PMID: 24534091

Wang, H., Sun, T., Hu, J., Zhang, R., Rao, Y., Wang, S., Chen, R., McLendon, R. E., Friedman, A. H., Kerr, S., Bigner, D. D., Li, Q.-J., Wang, H., Wang, X.-F. (2014) MiR-33a promotes glioma initiating cell self-renewal via modulation of the PKA/Notch pathways. J Clin Invest, 124, 4489-4502. PMID: 25202981.

Alexander, P., Yuan, L., Yang, P., Sun, T., Chen, R., Xiang, H., Chen, J., Wu, H., Radiloff, D., Wang, X.-F. (2015) EGF promotes mammalian cell growth by suppressing cellular senescence. Cell Res. 25, 135-138. PMID: 25367123.

Hu, J., Sun, T., Wang, H., Chen, Z., Wang, S., Liu, T., Yuan, L., Li, H.-R., Wang, P., Feng, Y., Wang, Q., McLendon, R. E., Friedman, A. H., Keir, S. T., Bigner, D. D., Rathmell, J., Fu, X.-D., Li, Q.-J., Wang, H., Wang, X.-F. (2016) MiR-215 is induced post-transcriptionally via HIF-Drosha complex and mediates glioma-initiating cell adaptation to hypoxia by targeting KDM1B. Cancer Cell, 29, 49-60. PMID: 26766590.

Markowitz, G., Yang, P., Fu, J., Michelotti, G., Chen, R., Sui, J., Yang, B., Qin, W.-H., Zhang, Z., Wang, F.-S., Diehl, A. M., Li, Q.-J., Wang, H., Wang, X.-F. (2016) Inflammation-dependent IL-18 signaling restricts hepatocellular carcinoma growth by enhancing the accumulation and activity of tumor-infiltrated lymphocytes. Cancer Res., Published Online First February 18, 2016; doi: 10.1158/0008-5472.CAN-15-1548.