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Xiaoting Zhang, PhD
Vontz Center for Molecular Studies
3125 Eden Avenue
Cincinnati, OH 45267
Mechanisms of transcriptional and epigenetic regulation of gene expression in breast cancer and development of RNA-based nanotherapuetics.
Bachelor's Degree: Zhejiang University, 1993
Master's Degree: Fudan University, 1996
Doctoral Degree: The University of Iowa, 2001
Fellowship: Rockefeller University, 2007
Peer Reviewed Publications (in chronological order):
Leonard M, Zhang Y and Zhang X. (2015). Small non-coding RNAs and aptamers in diagnostics and therapeutics . Methods in Molecular Biology. Springer Protocols..
M Czyzyk-krzeska and Zhang X (2014). MiR-155 at the Heart of Oncogenic Pathways . Oncogene , 33 , 677–678.
Czyzyk-Krzeska, M. F., & Zhang, X. (2014). MiR-155 at the heart of oncogenic pathways. . Oncogene , 33 (6) , 677-8.
Germer K, Pi M, Guo P and Zhang X (2013). Conjugation of RNA aptamer to pRNA nanoparticles for RNA-based therapy . RNA Nanotechnology and Therapeutics , CRC Press (2013 July) , 399-408 .
Germer K and Zhang X (2013). RNA aptamer and its diagnostic and therapeutic applications. . Int J Biochem Mol Biol , 4(1):27-40.
Zhang L, Cui J, Leonard M, Nephew K, Li Y, and Zhang X (2013). Silencing MED1 Sensitizes Breast Cancer Cells to Anti-estrogen Fulvestrant Therapy in vitro and in vivo . PLoS ONE , 8(7): e70641. doi:10.1371/journal.pone.0070641.
Zhang, L., Cui, J., Leonard, M., Nephew, K., Li, Y., & Zhang, X. (2013). Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo. . PloS One , 8 (7) , e70641.
Germer, K., Leonard, M., & Zhang, X. (2013). RNA aptamers and their therapeutic and diagnostic applications. . International Journal of Biochemistry and Molecular Biology , 4 (1) , 27-40.
Cui J, Germer K, Wu T, Wang J, Luo J, Wang SC, Wang Q, and Zhang X (2012). Crosstalk Between HER2 and MED1 Regulates Tamoxifen Resistance of Human Breast Cancer Cells . Cancer Research , Epub online doi: 10.1158/0008-5472 .
Cui, J., Germer, K., Wu, T., Wang, J., Luo, J., Wang, S., Wang, Q., & Zhang, X. (2012). Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast cancer cells. . Cancer Research , 72 (21) , 5625-34.
Pfaff D, Waters J, Kahn I, Zhang X and Numan M. (2011). Estrogen receptor-initiated mechanisms causal to mammalian reproductive behaviors. . Endocrinology , 152 (4) , 1209-17.
Zhang D, Jiang P, Xu Q, and Zhang X (2011). ARGLU1 interacts with MED1 and is required for estrogen receptor-mediated transcription and breast cancer cell growth. . Journal of Biological Chemistry , 286(20):17746-54.
Chen Z, Zhang C, Wu D, Rorick A, Zhang X, and Wang Q (2011). Specific phosphorylation of coactivator Mediator 1coding for UBE2C locus looping leads to androgen receptor negative prostate cancer growth . EMBO J. , 30(12):2405-19.
Zhang, D., Jiang, P., Xu, Q., & Zhang, X. (2011). Arginine and glutamate-rich 1 (ARGLU1) interacts with mediator subunit 1 (MED1) and is required for estrogen receptor-mediated gene transcription and breast cancer cell growth. . The Journal of Biological Chemistry , 286 (20) , 17746-54.
Jiang, P., Hu, Q., Ito, M., Meyer, S., Waltz, S., Khan, S., Roeder, R. G., & Zhang, X. (2010). Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation . Proc Natl Acad Sci U S A , 107 (15 ) , 6765-70.
Chen, W., Zhang, X., Birsoy, K., & Roeder, R. G. (2010). A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism . Proc Natl Acad Sci U S A , 107 (22 ) , 10196-201.
Jiang, P., Hu, Q., Ito, M., Meyer, S., Waltz, S., Khan, S., Roeder, R. G., & Zhang, X. (2010). Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation. . Proceedings of the National Academy of Sciences of the United States of America , 107 (15) , 6765-70.
Zhang, X., Leung, Y., & Ho, S. (2007). AP-2 regulates the transcription of estrogen receptor (ER)-beta by acting through a methylation hotspot of the 0N promoter in prostate cancer cells. . Oncogene , 26 (52) , 7346-54.
Stumpf M, Waskow C, Krötschel M, Essen D, Rodriguez P, Zhang X, Guyot B, Roeder RG and Borggrefe T. (2006). The Mediator Complex Functions as a Coactivator for GATA1 in Erythropoiesis via Subunit Med1/TRAP220 . Proc. Natl. Acad. Sci. , 103:18504-9.
Zhang, X., Krutchinsky, A., Fukuda, A., Chen, W., Yamamura, S., Chait, B. T., & Roeder, R. G. (2005). MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription . Mol Cell , 19 (1 ) , 89-100.
Zhang, X., Kolaczkowska, A., Devaux, F., Panwar, S. L., Hallstrom, T. C., Jacq, C., & Moye-Rowley, W. S. (2005). Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination . J Biol Chem , 280 (4 ) , 2759-70.
Le Crom, S., Devaux, F., Marc, P., Zhang, X., Moye-Rowley, W. S., & Jacq, C. (2002). New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system . Mol Cell Biol , 22 (8 ) , 2642-9.
Zhang, X., & Moye-Rowley, W. S. (2001). Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the F(0) component of the mitochondrial ATPase . J Biol Chem , 276 (51 ) , 47844-52.
Zhang, X., Cui, Z., Miyakawa, T., & Moye-Rowley, W. S. (2001). Cross-talk between transcriptional regulators of multidrug resistance in Saccharomyces cerevisiae . J Biol Chem , 276 (12 ) , 8812-9.
Zhang, X., De Micheli, M., Coleman, S. T., Sanglard, D., & Moye-Rowley, W. S. (2000). Analysis of the oxidative stress regulation of the Candida albicans transcription factor, Cap1p . Mol Microbiol , 36 (3 ) , 618-29.
Zhang, X., Ma, B., Shu, N., Chen, SZ, and Zhao, SY. (1997). Cloning the Gene Coding for Human Glial Cell Line-derived Neurotrophic Factor and its Expression in Escherichia Coli . Chinese Journal of Biotechnology , 13(4): 426-9.
Zhang, X., Chen, SZ, and Zhao, SY. (1996). The Gene Structure of Ciliary Neurotrophic Factor and its Receptor . Foreign Med. Sci. (Molecular Biology) , 18(5):225-9.
Breast Cancer Alliance . Masin Young Investigator Award, Completed.
Hormone Research Foundation. C.H. Li Memorial Scholar Award, Completed.
Susan G. Komen Breast Cancer Foundation . Postdoctoral Fellowship, Completed.
University of Cincinnati Cancer Center and the Department of Cancer and Cell Biology. Start-up, Active.
University of Cincinnati Cancer Center. Cancer Center Pilot Grant, PI, Completed.
American Heart Association. Beginning Grant-in-Aid, Completed.
Ride Cincinnati Foundation. Ride Cincinnati Award, Completed.
University of Cincinnati. CCTST Junior Investigator Award, Completed.
Ohio Cancer Research Associate. Seed Money, PI, Completed.
Department of Defense. BRCP Idea Award, PI, Completed.
Susan G. Komen For the Cure Foundation. Career Catalyst Award, PI, Active.
American Cancer Society. Research Scholar Grant, PI, Active.
09BGIA2010011 American Heart Association - Great Rivers Affiliate. Novel Role of Transcriptional Coregulator MED1 in Muscle Metabolic Functions, PI, Closed.
SRS 007568 Ohio Cancer Research Associates. The ER/MED1 Axis and Mammary Stem/Progenitor Cells, PI, Closed.
KG110028 Susan G. Komen Breast Cancer Foundation. Crosstalk among MED1, ER and HER2: New Strategy to Overcome Endocrine Resistance in Breast Cancer, PI, Active.
RSG-12-268-01-CCG American Cancer Society - National Chapter. MED1: Molecular Mechanisms Regulating Cellular Senescence in Breast Cancer, PI, Active.
R01CA197865 National Institutes of Health. Role of MED1 in HER2-driven Breast Tumorigenesis, PI, Awarded.
Graduate Senator Travel Award. The University of Iowa, 2000
Masin Young Investigator Award. Breast Cancer Alliance, 2002
C.H. Li Memorial Scholar Award. Hormone Research Foundation, 2004
Postdoctoral Fellowship Award. Susan G. Komen Breast Cancer Foundation, 2005
Komen Mentorship Award. Susan G. Komen Breast Cancer Foundation, 2005
Ride Cincinnati Award. Ride Cincinnati Breast Cancer Foundation, 2010
IDEA award. Department of Defense BCRP, 2011
Career Catalyst Award . Susan G. Komen for the Cure Foundation, 2011
Research Scholar. American Cancer Society, 2012
Scientific Reviewer Panel, DOD Breast Cancer Research Program, 2014
Ad Hoc Reviewer, NIH Tumor Progression and Metastasis (TPM) Study Section, 2014
Grant Reviewer, Susan G. Komen for the Cure Foundation, 2014
Ad Hoc Reviewer. NIH Tumor Progression and Metastasis (TPM) Study Section, 2015
Our laboratory aims to elucidate the molecular mechanism of gene transcriptional regulation and its dysregulation in breast cancer. Breast cancer is the most common type of cancer and one of the leading causes of death among Western women. A vast majority (75%) of breast cancer has been found to express estrogen receptor (ER), which is the key mediator of estrogen functions and plays prominent roles in breast tumorigenesis and drug resistance. Anti-estrogens, such as tamoxifen, have been widely used in the treatment of ER-positive breast cancer, but acquired resistance and severe side effect on other estrogen-responsive tissues has greatly limited their usefulness. Hence, further development of novel strategies to selectively block estrogen signaling pathways is urgently needed. Our recent work has established MED1 (Mediator Subunit 1) as a key tissue-specific transcriptional coactivator in mediating estrogen receptor functions in both normal mammary gland development and breast cancer. Significantly, MED1 has been reported to be overexpressed or amplified in a high percentage (40% to 50%) of human breast cancers. Intriguingly, recent studies also discovered an increased frequency of MED1 mutations in metastasis “seeding” circulating tumor cells following endocrine therapies [Nature (2013) 497:108]. We are currently continuing to determine the role of MED1 and its associated proteins in breast cancer by using a combination of state-of-art biochemical, molecular and cellular techniques, as well as mouse genetic approaches with our newly generated MED1 mutant knockin, conditional knockout and overexpression models. Most recently, we have also started developing RNA nanotechnology-based strategies to target MED1 to explore its therapeutic potentials. Through these investigations, our ultimate goal is to provide novel insights and potential therapeutic targets for better diagnosis, prognosis and individualized treatment of human breast cancer.
Positions and Work Experience
1994-1996, Graduate Research Assistant, Institute of Genetics,Fudan University, Shanghai, P.R.China
1994-1995, Graduate Teaching Assistant, Institute of Genetics,Fudan University, Shanghai, P.R.China
1996-2001, Graduate Research Assistant, University of Iowa, Iowa City, IA
2002-2007, Postdoctoral Research Fellow, Rockefeller University, New York, NY
2007-2013, Assistant Professor, University of Cincinnati, Cincinnati, OH
2007, Faculty Member, Graduate Program in Cell and Cancer Biology, University of Cincinnati, Cincinnati, OH
2013, Associate Professor (with Tenure) University of Cincinnati Cincinnati, OH
Community Tumor Registries
University of Cincinnati
234 Goodman St., Cincinnati, OH 45219