Research

  • Xiaoting Zhang, PhD
  • Associate Professor
  • Academic Office:
    Vontz Center for Molecular Studies
    3125 Eden Avenue
    ML 0521
    Cincinnati, OH 45267
  • Phone: 513-558-3017
  • Email: xiaoting.zhang@uc.edu

    Research/Clinical Interests:

  • 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.

    Education/Credentials:

  • 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):

  • M Czyzyk-krzeska and Zhang X (2013). MiR-155 at the Heart of Oncogenic Pathways . Oncogene , Advance online publication, 18 February 2013; doi:10.1038/onc.2013.26.
  • 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.
  • 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 .
  • 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.
  • 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.
  • 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.

    Research Grants:

  • 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, Active.
  • Department of Defense. BRCP Idea Award, PI, Active.
  • 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.
  • W81XWH-11-1-0118 Department of the Army. Targeting MED1 LxxLL Motifs for Tissue Selective Treatment of Human Breast Cancer, PI, Active.
  • SRS 007568 Ohio Cancer Research Associates. The ER/MED1 Axis and Mammary Stem/Progenitor Cells, PI, Active.
  • 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.

Recent Awards/Honors:

  • 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