Xiaoting Zhang

Xiaoting Zhang

Professor

Vontz Center

2316

COM Can Bio Zhang Lab - 0521

Vontz Center for Molecular Studies
3125 Eden Avenue
Cincinnati, Ohio 45267

Professional Summary

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

Bachelor's Degree, Zhejiang University 1993 (Biochemistry & Microbiology )

Master's Degree, Fudan University 1996 (Genetics )

Doctoral Degree, The University of Iowa 2001 (Molecular Biology )

Fellowship, Rockefeller University 2007 (Biochemistry, Molecular Biology and Genetics)

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,

Research and Practice Interests

Mechanisms of transcriptional and epigenetic regulation of gene expression in breast cancer and development of RNA-based nanotherapuetics.

Research Support

04-01-2002 -03-31-2004 Breast Cancer Alliance Masin Young Investigator Award Completed

04-01-2004 -03-31-2005 Hormone Research Foundation C.H. Li Memorial Scholar Award Completed

04-01-2005 -03-31-2008 Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship Completed

04-01-2007 -08-31-2011 University of Cincinnati Cancer Center and the Department of Cancer and Cell Biology Start-up Active

01-01-2008 -12-31-2008 University of Cincinnati Cancer Center Cancer Center Pilot Grant Role:PI Completed Level:University

07-01-2009 -06-30-2011 American Heart Association Beginning Grant-in-Aid Completed

03-01-2010 -02-28-2011 Ride Cincinnati Foundation Ride Cincinnati Award Completed

07-01-2011 -06-30-2012 University of Cincinnati CCTST Junior Investigator Award Completed

07-01-2011 -06-30-2013 Ohio Cancer Research Associate Seed Money Role:PI Completed

09-01-2011 -08-31-2014 Department of Defense BRCP Idea Award Role:PI Completed

09-21-2011 -09-20-2015 Susan G. Komen For the Cure Foundation Career Catalyst Award Role:PI Active

07-01-2012 -06-30-2016 American Cancer Society Research Scholar Grant Role:PI Active

Grant: #09BGIA2010011 Investigators:Zhang, Xiaoting 07-01-2009 -06-30-2011 American Heart Association - Great Rivers Affiliate Novel Role of Transcriptional Coregulator MED1 in Muscle Metabolic Functions Role:PI $132,000.00 Closed Level:Private Non-Profit

Grant: #SRS 007568 Investigators:Zhang, Xiaoting 07-01-2011 -06-30-2013 Ohio Cancer Research Associates The ER/MED1 Axis and Mammary Stem/Progenitor Cells Role:PI $60,000.00 Closed Level:Private Non-Profit

Grant: #KG110028 Investigators:Zhang, Xiaoting 09-21-2011 -09-20-2015 Susan G. Komen Breast Cancer Foundation Crosstalk among MED1, ER and HER2: New Strategy to Overcome Endocrine Resistance in Breast Cancer Role:PI $450,000.00 Active Level:Private Non-Profit

Grant: #RSG-12-268-01-CCG Investigators:Zhang, Xiaoting 07-01-2012 -06-30-2016 American Cancer Society - National Chapter MED1: Molecular Mechanisms Regulating Cellular Senescence in Breast Cancer Role:PI $705,000.00 Active Level:Private Non-Profit

Grant: #R01CA197865 Investigators:Zhang, Xiaoting 07-01-2015 -06-30-2020 National Institutes of Health Role of MED1 in HER2-driven Breast Tumorigenesis Role:PI $361,425.00 Awarded Level:Federal

Grant: #1R01CA229869-01A1 Investigators:Zhang, Xiaoting 09-20-2019 -07-31-2024 National Cancer Institute Small RNAs in Breast Cancer Metastasis Role:PI $367,144.00 Awarded Level:Federal

Publications

Peer Reviewed Publications

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 ,

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.; 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.; 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

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.; 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

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 ,

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

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 ,

Cui J, Germer K, Wu T, Wang J, Luo J, Wang SC, Wang Q, and Zhang X (2012. )Cross-talk Between HER2 and MED1 Regulates Tamoxifen Resistance of Human Breast Cancer Cells.Cancer Research, ,72 (21 ),5625-34

Zhang L; Cui J; Leonard M; Nephew K; Li Y and Zhang X (2013. )Silencing MED1 Sensitizes Breast Cancer Cells to pure Anti-estrogen Fulvestrant Therapy in vitro and in vivo.PLoS ONE , ,8(7): e70641 ,

Leonard M, Zhang Y and Zhang X. (2015. )Small non-coding RNAs and aptamers in diagnostics and therapeutics .Methods in Molecular Biology, ,1296 ,225-33

Germer, Katherine; Leonard, Marissa; Zhang, Xiaoting (2013. )RNA aptamers and their therapeutic and diagnostic applications. International Journal of Biochemistry and Molecular Biology, ,4 (1 ),27-40

Jiang, Pingping; Hu, Qiuping; Ito, Mitsuhiro; Meyer, Sara; Waltz, Susan; Khan, Sohaib; Roeder, Robert G; Zhang, Xiaoting (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

Leonard, Marissa; Zhang, Yijuan; Zhang, Xiaoting (2015. )Small non-coding RNAs and aptamers in diagnostics and therapeutics.Methods in molecular biology (Clifton, N.J.), ,1296 ,225-33

Yang, Yongguang; Leonard, Marissa; Zhang, Yijuan; Zhao, Dan; Mahmoud, Charif; Khan, Shugufta; Wang, Jiang; Lower, Elyse E; Zhang, Xiaoting (2018. )HER2-Driven Breast Tumorigenesis Relies upon Interactions of the Estrogen Receptor with Coactivator MED1.Cancer research, ,78 (2 ),422-435

Leonard, Marissa; Zhang, Xiaoting (2019. )Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer.Journal of Zhejiang University. Science. B, ,20 (5 ),381-390

Czyzyk-Krzeska, M F; Zhang, X (2014. )MiR-155 at the heart of oncogenic pathways.Oncogene, ,33 (6 ),677-8

Zhang, Lijiang; Cui, Jiajun; Leonard, Marissa; Nephew, Kenneth; Li, Yongquan; Zhang, Xiaoting (2013. )Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.PloS one, ,8 (7 ),e70641

Cui, Jiajun; Germer, Katherine; Wu, Tianying; Wang, Jiang; Luo, Jia; Wang, Shao-chun; Wang, Qianben; Zhang, Xiaoting (2012. )Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast cancer cells.Cancer research, ,72 (21 ),5625-34

Zhang, Dingxiao; Jiang, Pingping; Xu, Qinqin; Zhang, Xiaoting (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

Leonard M and Zhang X (2016. )First Therapeutic Aptamer: VEGF-Targeting Macugen .Aptamers: Tools for Targeted Nanotherapy and Molecular Imaging, ,Pan Stanford Publishing ,Page 319-335.

Zhang, X; Leung, Y-K; Ho, S-M (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

Zhang Y, Leonard M, Shu Y, Yang Y, Shu D, Guo P, and Zhang X. (2016. )Overcoming Tamoxifen Resistance of Human Breast Cancer by Targeted Gene Silencing Using Multifunctional pRNA Nanoparticles.ACS Nano , ,11 (1 ),335-346

Honors and Awards

2000 Graduate Senator Travel Award The University of Iowa

2002 Masin Young Investigator Award Breast Cancer Alliance

2004 C.H. Li Memorial Scholar Award Hormone Research Foundation

2005 Postdoctoral Fellowship Award Susan G. Komen Breast Cancer Foundation

2005 Komen Mentorship Award Susan G. Komen Breast Cancer Foundation

2010 Ride Cincinnati Award Ride Cincinnati Breast Cancer Foundation

2011 IDEA award Department of Defense BCRP

2011 Career Catalyst Award Susan G. Komen for the Cure Foundation

2012 Research Scholar American Cancer Society

2014 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

2015 Ad Hoc Reviewer NIH Tumor Progression and Metastasis (TPM) Study Section

2016 Ad Hoc Reviewer NIH Tumor Progression and Metastasis (TPM) Study Section

2016 Ad Hoc Reviewer, NIH Cancer Molecular Pathobiology (CAMP) Study Section

2016 Ad Hoc Reviewer, NIH Tumor Progression and Metastasis (TPM) Study Section

2016 Scientific Reviewer Panel, DOD Breast Cancer Research Program

2017 Ad Hoc Reviewer, American Cancer Society

2017 Grant Reviewer, Susan G. Komen for the Cure Foundation

2017 Grant Report Assessment, Research Grants Council, Hongkong

2017 Scientific Reviewer Panel, DOD Breast Cancer Research Program

2017 Member, AACR Breast Cancer Research Grants Scientific Review Committee

2017 Founding Council Member, International Society of RNA Nanotechnology and Nanomedicine

2017 Editor, Estrogen Receptor and Breast Cancer, Springer

2018 Ad Hoc Reviewer, NIH Nanotechnology (NANO) Study Section

Post Graduate Training and Education

2002-2007 Postdoctoral Fellow,, Laboratory of Biochemistry and Molecular biology, Rockefeller University, ,New York, NY

Keywords

Breast Cancer, Gene Expression and Regulation, Endocrine Resistance, RNA nanotherapeutics.

Professional Affiliation

2003: New York Academy of Science, New York, NY

2007: American Association for Cancer Research,

2007: American Society for Biochemistry and Molecular Biology,

2007: University of Cincinnati Cancer Center,

2007: The Endocrine Society,

Contact Information

Academic - Vontz Center for Molecular Studies
3125 Eden Avenue
Cincinnati  Ohio, 45267
Phone: 513-558-3017
xiaoting.zhang@uc.edu