NAME
Wang, Xiao-Fan eRA COMMONS USER NAME xiaofanwang
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
POSITION TITLE
Professor of Pharmacology and Cancer Biology
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Wuhan University, China
University of California, Los Angeles
Whitehead Inst. & MIT, Cambridge, MA
DEGREE
(if applicable)
B.S.
Ph.D.
Postdoctora l
MM/YY
02/82 Biochemistry
12/86 Biological Chemistry
02/92 Mol. Cancer Biology
FIELD OF STUDY
A. Personal Statement
One of the major research objectives of our laboratory is to determine the mechanisms by which changes in the tumor microenvironment promote tumorigenesis, particularly tumor invasion, angiogenesis and metastasis. We have extensive experiences in studying cellular activities and signaling mechanisms, including the roles of microRNAs, using both cultured cells and mouse models that are relevant to this project, so that we don’t anticipate in encountering major obstacles to achieve the stated goals. In the area of glioma/glioblastoma, we started our research more than a decade ago when Dr. Jeremy Rich joined my laboratory as a Research Faculty and we have continued our collaborations ever since he established his own laboratory. Together we have studied the roles of SPARC and interleukin-6 in the enhancement of glioma invasiveness and the survival of CD133+ tumor-initiating cells under stress conditions, so that we are familiar with the experimental approaches for this type of research. For this particular study to investigate the roles of microRNAs in the development of glioma/GBM, we have established collaboration with Dr.
Roger McLendon, Chief of Neuropathology and Surgical Pathology at Duke University so that we will have access to tumor samples from patients when they are needed. Dr. Qi-Jing Li in the
Immunology Dept. of Duke has collaborated with us on multiple projects related to microRNAs and two manuscripts describing some of the recent findings are undergoing review in journals. In addition, Dr. Jen-Tsan Chi in the Institute of Genome Science and Policy at Duke will continue to provide us with advice on bioinformatics analysis of expression profiles of microRNAs and their association with prognosis of patients, as well as studies on hypoxia. Their supporting letters are attached to this proposal.
B. Positions and Honors.
Positions and Employment
1982-1986
1987-1992
1992-1998
Graduate Student, Dept. of Biol. Chem., Sch. of Med., UCLA
Postdoctoral Fellow, Whitehead Inst. & Massachusetts Inst. Technology
Assistant Prof., Dept. of Pharm. and Cancer Biol, Duke Univ. Med Center
1998-2003
2003-
2006-
Associate Prof., Dept. of Pharm. and Cancer Biol., Duke Univ. Medical Center.
Professor, Dept. of Pharm. and Cancer Biology, Duke Univ. Medical Center.
Director, University Program in Molecular Cancer Biology, Duke University
2009- Donald and Elizabeth Cooke Professor of Experimental Oncology, Duke
University

Other Experience and Professional Memberships
1998-2010 Ad Hoc Member, Site-visit teams, NCI/NIH
1999-2010 Ad Hoc Member, various Study Sections, NIH
2002-2006 Member, Cell Signaling & Dynamics (formally CDF3) Study Section, NIH
1998-2001 Editorial Board, Molecular Endocrinology
1998-2002 Editorial Board, Cell Growth & Differentiation
2001-2006 Editorial Board, Journal of Biological Chemistry
2005-2013 Editorial Board, Molecular and Cellular Biology
2006- Editor and Editorial Board, Cell Research
2006.2- Associate Editor, Journal of Biological Chemistry
Honors
1982-1983
1987-1990
1993-1998
U.C. Regents University Fellowship
Damon Runyon-Walter Winchell Cancer Research Fund Fellow
Leukemia Society of America, Inc. Scholar
1998
2009
Stohlman Scholar Award
American Association for the Advancement of Science Fellow
C. Selected Peer-reviewed Publications (Selected from 107 peer-reviewed publications)
Five most relevant to the current application
1. Schilling, S., Hjelmeland, A. B., Radiloff, D. R., Liu, I., Wakeman, T., Fielhauer, J., Foster, E.,
Lathia, J. D., Rich, J., Wang, X.-F ., Datto, M. B. (2009) Ndrg4 is required for cell cycle progression and survival in glioblastoma cells. J Biol Chem, 284, 25160-25169. PMCID: PMC2757219
2. Wang, H., Lathia, J. D., Elderbroom, J., Wang, J., Heddlestion, J., Wu, Q., Cao, Y., McLendon,
R., Counter, C., Wang, X.-F ., Hjelmeland, A. B., Rich, J. N. (2009) Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells, 27, 2393-2404. PMCID:
PMC2825688
3. Wang, J., Wakeman, T., Lathia, J. D., Hjelmeland, A. B., Wang, X.-F ., White, R. R., Rich, J.,
Sullenger, B. A. (2010) Notch promotes radioresistance of glioblastoma stem cells. Stem Cells, 28,
17-28. PMCID: PMC2825687
4. Yang, P., Feng, Y.-X., Zhang, Y., Cheng, S.-Q., Jiang, S., Li, Q.-J., Xie, D., Wang, X.-F.
(2011)
TGF-
ß promotes hepatocellular carcinoma intrahepatic metastases by enhancing Treg cell recruitment via miR-34a-CCL22 pathway. Submitted.
5. Zhang, Y., Yang, P., Sun, T., Li, D., Xu, X., Rui, Y., Xie, D., Li, Q.-J., Wang, X.-F . (2011) MiR-126 and miR-126* inhibit breast cancer metastasis through mesenchymal stem cell recruitment.
Submitted.
Additional recent publications of importance to the field (in chronological order)
1. Rich, J. N., Shi, Q., Hjelmeland, M., Cummings, T. J., Kuan, C. T., Bigner, D., Counter, C. M.,
Wang, X.-F . (2003) Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. J. Biol. Chem. 278, 15951-15957.
2. Bao, S., Ouyang, G., Huang, Z., Bai, X., Liu, M., Ma, C., Shao, R. Anderson, R. M., Wang, X.-F .
(2004) Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell, 5, 329-339.
3. 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.
PMCID: PMC387763

4. Shi, Q., Bao, S., Maxwell, J. A., Reese, E. D., Friedman, H. S., Bigner, D. D., Wang, X.-F ., Rich,
J. N. (2004) Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation. J. Biol. Chem., 279, 52200-52209.
5. Frederick, J., Liberati, N., Waddell, D., Shi, Y., Wang, X.-F . (2004) TGFß 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. PMCID: PMC355825
6. 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.
PMCID: PMC338278
7. 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.
PMCID: PMC514932
8. Hjelmeland, A. B., Schilling, S., Guo, X., Quarles, D., Wang, X.-F . (2005) Loss of Smad3mediated negative regulation of Cbfa1 activity leads to an alteration in cell fate determination. Mol.
Cell Biol, 25, 9460-9468.
PMCID: PMC1265845
9. 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. PMCID:
PMC1280286
10. 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.
PMCID: PMC1413283
11. Guo, X., Ramirez, A., Waddell, D., Li, Z., X. Liu, Wang, X.-F . (2008) Axin-
GSK3ß control
Smad3 protein stability and modulate TGF-
ß signaling. Genes & Dev., 22, 106-120. PMCID:
PMC2151009
12. Guo, X., Waddell, D., Wang, W., Wang, Z., Liberati, N. T., Yong, S., X. Liu, Wang, X.-F . (2008)
Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2 (CKIg), an inhibitor of TGFß signaling. Oncogene, 27, 7235-7247.
PMCID: PMC2643063
13. 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., 22, 308-321. PMCID: PMC2216691
14. Jardim, M., Q. Wang, 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.
PMCID: PMC2735479
15. 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.
PMCID: PMC2772729
16. Liu, I., Schilling, S., Knouse, K., Choy, L., Derynck, R., Wang, X.-F . (2009) TGFß-stimulated
Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFß switch.
EMBO J., 28, 88-98.
PMCID: PMC2634733
17. Feng, Y.-X., Zhao, J.-S., Li, J.-J., Wang, T., Cheng, S.-Q., Yuan, Y., Wang, F., Wang, X.-F ., Xie,
D. (2010) Liver cancer: EphrinA2 promotes tumorigenicity through rack1/Akt/NF-kappa B signaling pathway. Hepatology, 51, 535-544.
18. Zhang, L., Park, C.-H., Wu, J., Kim, H., Liu, W., Fujita, T., Balasubramani, M., Schreiber, E.,
Wang, X.-F ., Wan, Y. (2010) Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress. EMBO J., 29, 1726-1737.
PMCID: PMC2876963
19. Dobaczewski, M., Bujak, M., Li, N., Gonzalez-Quesada, C., Mendoza, L. H., Wang, X.-F.
,
Fangogiannis, N. G. (2010) Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circulation Res., 107, 418-428.
PMCID: PMC2917472
20. Feng, Y.-X., Wang, T., Yang, P., Li, J.-J., Deng, Y.-Z., Yao, F., Wang, H., Li, N., Wu, M.-C.,

Wang, H.-Y., Wang, X.-F ., Cheng, S.-Q., Xie, D. (2011) Sorafenib suppresses postsurgical recurrence and metastasis of HCC through negative regulation of cell growth signaling related to liver regeneration. Hepatology, in press.
21. 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, in revision.
D. Research Support
Ongoing Research Support
R01-CA122998 Wang (PI) NIH/NCI 7/1/06-6/30/11
TGFBI and tumorigenesis
The main goal of this project is to determine the mechanism by which TGFBI/ßigh3 overexpression by colon cancer promotes metastasis
Role: PI
R01-CA123250 Wang (PI) NIH/NCI 7/1/06-6/30/11
Rad17- & p53-mediated apoptosis pathways in response to DNA damage
The main goal of this project is to determine the mechanism and relative contributions of the newly discovered pro-apoptosis activity of Rad17 verses p53 to DNA damage-induced apoptosis.
Role: PI
R01-GM083000 Wang (PI) NIH/NIGMS 3/1/08-2/28/12
TGF-
ß/Smad signaling
The main goal of this project is to determine the mechanisms of non-canonical pathways by which TGFß and Smads regulate specific biological processes.
Role: PI
R01-CA151541 Wang (PI) NIH/NCI 4/1/10-3/31/15
The role of TGF-
ß in tumorigenesis
The main goal of this project is to determine the function and mechanism of two new TGF-
ß pathways mediated by specific miRNAs to enhance metastasis by changing tumor microenvironment.
Role: PI
T32-CA059365 Wang (PI) NIH/NCI 7/1/10-6/30/15
Cancer Biology Training Grant
This is a training grant that supports both predoctoral and postdoctoral trainees in the
University Program in Molecular Cancer Biology.
Role: PI
Completed Research Support in the last three years
None