Dr. Qun Zhou received his M.D. training and a PhD in Pharmacology and Toxicology from West Virginia University School of Medicine. After completing postdoctoral training in Dr. Nancy Davidson' laboratory at Johns Hopkins University, he started as assistant professor at the University of Maryland School of Medicine.
Currently, his laboratory is focusing on epigenetic regulation of tumor suppressor genes, long non coding RNA, microRNA and cancer stem cells.
Project 1: microRNA and Breast Cancer Stem Cells
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene silencing that are known to regulate differentiation and cell fate and are dysregulated in nearly all human cancers. We have been investigating the roles of miRNAs in normal and transformed breast epithelium, seeking to understand the significance of miRNA dysregulation in breast cancer stem cells. Our studies have centered to a large extent on microRNAs and yielded considerable insights into molecular mechanisms that suppress transformation potential.
We began our work in early stage breast cancer. Ductal Carcinoma In Situ (DCIS), an early stage of human breast cancer, accounts for 20-45% of new cases of breast cancer each year. Patients with DCIS are at high risk for subsequent recurrences and development of invasive breast cancer even after they receive breast-conserving surgery and radiotherapy. Consequently, an important goal of breast cancer prevention is reducing the incidence of DCIS. However, as the molecular mechanisms that underlie DCIS development remain largely unclear, specific pathways that could be targeted for cancer prevention have yet to be identified. Moreover, a lack of information at a mechanistic level often leads to unnecessary treatment (radiotherapy and/or anti-hormone therapy) in cases of benign DCIS that is often associated with adverse toxic effects. For these reasons, our research project seeks to identify the molecular mechanisms that drive DCIS formation. By screening breast cancer tissues and performing array-based miRNA profiling in primary DCIS tissues, we identified that loss of miR-140 expression commonly occurs in DCIS. Our studies strongly support that miR-140 loss predisposes to DCIS development, which is associated with accumulation of breast cancer stem cells. We have developed novel cell culture-based models and animal models of DCIS, including miR-140 knockout cell lines and knockout mice that are being used in novel ways to gain a complete understating of the mechanisms involved in miR-140 promotion of DCIS. We initiated studies to understand the functional properties of miR-140 important to the development of breast cancer: obtaining a detailed understanding of how epigenetic mechanisms contribute to loss of miR-140 expression, understanding how loss of miR-140 expression alters stem cell self-renewal leading to transformation of normal mammary stem cells into breast cancer stem cells, and understanding how epigenetic therapy restores miR-140 expression and ultimately prevents breast cancer development.
Project 2: Identification of novel compounds that inhibit the estrogen genotoxic pathways
Long-term exposure to high levels of estrogens is considered a major risk factor for breast cancer. Estrogen exposure contributes to breast tumorigenesis through estrogen receptor alpha (ERÎ±) signaling and through genotoxic (DNA damaging) estrogen metabolites. Induction of detoxifying enzymes is considered an important mechanism of protection against estrogen-associated carcinogenesis because these enzymes facilitate removal of toxic estrogens. We have initiated studies screening natural compounds and identified novel compounds in breast cancer prevention. The goal of this project is to examine the role of estrogens in regulating detoxifying enzyme production and the role of novel compounds in protection against estrogen genotoxic effect.
Zhou, Q., Zaroui, M., Lucktong, A., Moniwa, M, Davie, J.R and Strobl, J.S. (2000) Rapid Induction of Histone Hyperacetylation and Cellular Differentiation in Human Breast Tumor Cells Lines Following Degradation of Histone Deacetylase. J Biol Chem 275: 35256-35263. PMCID: 10938272
Zhou, Q., McCraken, M.A and Strobl, J.S. (2002) Control of Mammary Tumor Cells Growth in vitro by Novel Cell Differentiation and Apoptosis. Breast Cancer Research and Treatment 75:107-17. PMCID: 12243503
Yao,Y., Zhou, Q., and Ericson, S.G. (2004) Vanadate Stimulates Monocytic Differentiation Activity of IL-6 by Enhancing Actin Filament Polymerization in HL-60 Cells. Journal of Biomedical Science 11:940-9. PMCID: 15591791
Zhou, Q., Yao,Y., and Ericson, S.G. (2004). The Protein Tyrosine Phosphatase CD45 is Required for IL-6 Signaling in U266 Myeloma Cells. International Journal of Hematology 79:63-73. PMCID: 14979481
Keen,J.C., Zhou, Q., Park, B.H., Pettit,C., Mack,K.M., Blair,B., Brenner,K. and Davidson, N.E. (2005) Protein phosphatase 2A (PP2A) Regulates Estrogen Receptor alpha (ER) Expression through Modulation of ER mRNA Stability. J Biol Chem 280:29519-24. PMCID: 15965230
Zhou, Q. and Davidson, N.E. (2006) Silencing Estrogen Receptor Î± in Breast Cancer Cells. Cancer Biology and Therapy 5:848-849. PMCID: 16921265
Zhou, Q., Atadja, P. and Davidson, N.E. (2007) Histone Deacetylase Inhibitor LBH589 Reactivates Silenced Estrogen Receptor Alpha (ER) Gene Expression without Loss of DNA Hypermethylation. Cancer Biology and Therapy 6: 64-9. PMCID: 17172825
Vered,S., Zhou, Q. and Davidson, N.E. (2007) Epigenetic regulation as a new target for breast cancer therapy. Cancer Invest. 25:659-65. PMCID: 18058459
Zhou, Q., Agoston,A.T., Atadja,P., Nelson,W.G., and Davidson, N.E. (2008) Inhibition of Histone Deacetylases Promotes Ubiquitin-dependent Proteasomal Degradation of DNMT1 in Human Breast Cancer Cells. Molecular Cancer Research 6: 873-83. PMCID: 18505931
Zhou, Q., Shaw, P.G. and Davidson, N.E., (2009). Inhibition of Histone Deacetylase Suppresses EGF Signaling Pathways by Destabilizing EGFR mRNA in ER-negative Human Breast Cancer Cells. Breast Cancer Research and Treatment 117:443-51 PMCID: 18683042
Zhou, Q., Shaw, P.G. and Davidson, N.E. (2009) Epigenetics meets estrogen receptor: regulation of estrogen receptor by direct lysine methylation. Endocrine-Related Cancer 16:319-23 PMCID: 19208734
Yao, Y and Zhou, Q* (2010) A Novel Antiestrogen Agent Shikonin Inhibits Estrogen Dependent Gene Transcription in Human Breast Cancer Cells. Breast Cancer Research and Treatment 121:233-40 PMCID: 19760501
Yao Y, Li H, Gu Y, Davidson NE, Zhou Q* (2010) Inhibition of Class III HDAC Activity Suppresses Estrogen-dependent Gene Transcription Carcinogenesis 31:382-7 PMCID: 19995796
Zhou Q, Chaerkady R, Shaw PG, Kensler TW, Pandey A, Davidson NE (2010) Screening for Therapeutic Targets of Vorinostat by SILAC-based Proteomic Analysis in Human Breast Cancer Cells Proteomics 10:1029-39 PMCID: 20049865
Yao Y, Brodie AM, Davidson NE, Kensler TW, Zhou, Q* (2010). Inhibition of estrogen signaling activates the NRF2 pathway in breast cancer. Breast Cancer Res Treat. 124:585-91 PMCID: 20623181
Eades G, Yao Y, Yang M, Zhang Y, Chumsri S, Zhou, Q.* (2011) MiR-200a regulates SIRT1 and EMT-like transformation in mammary epithelial cells. J Biol Chem. 286:25992-6002. PMID:21596753
Yang M, Yao Y, Eades G, Zhang Y, Zhou, Q.* (2011) MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism. Breast Cancer Res Treat. 129:983-91 PMID:21638050
Eades G, Yang M, Yao Y, Zhang Y, Chumsri S, Zhou, Q.* (2011) miR-200a Regulates Nrf2 Activation by Targeting Keap1 mRNA in Breast Cancer Cells. J Biol Chem. 286:40725-33. PMID:21926171
Zhang Y, Eades G, Yao Y, Li Q, Zhou, Q.* (2012) Estrogen Receptor α Signaling Regulates Breast Tumor-initiating Cells by Downregulating miR-140 which Targets the Transcription Factor SOX2. J Biol Chem. 287: 41514-22. PMID:23060440
Zhou, Q.*, Eades G (2012). MicroRNA Regulatory Networks Provide Feedback Mechanisms for Steroid Receptor Signaling (Review). J Steroids Hormon Sci 3:e103.
Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou, Q.* (2013) Downregulation of miR-140 Promotes DCIS Stem Cell Formation by Hijacking Mammary Stem Cell Circuitry. Oncogene (in press)
Stearns,V., Zhou, Q. and Davidson, N.E (2007) Chapter 26: Epigenetic Regulation as a New Target for Breast Cancer Therapy. In: Gary H. Lyman, Harold J. Burstein, editors. Breast Cancer Translational Therapeutic Strategies. New York: JOHN WILEY& SONS; p.285-295.
Eades G, Yao Y, Zhou, Q. (2013) Chapter 1: Breast Cancer MicroRNAs: Signaling Networks and Clinical Applications. MicroRNAs in Cancer, ISBN 1466576766, Science Publishers, Enfeld, NH.
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