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Qun  Zhou
 

Qun Zhou M.D., Ph.D.

Academic Title: Associate Professor
Primary Appointment: Biochemistry and Molecular Biology
qzhou@som.umaryland.edu
Location: Biomedical Research Facility, 337
Phone: (410) 706-1615 (Office)
Fax: (410) 706-8297
Lab: (410) 706-4360

Personal History:

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's laboratory at Johns Hopkins University, he started his independent research at the University of Maryland School of Medicine.

Research Interests:

Currently, Dr.Zhou's laboratory is focusing on epigenetic regulation of tumor suppressor genes, long non coding RNA, microRNA and 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.


Publications:

1. 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. PMID:
    17172825

2. Vered,S., Zhou,Q. and Davidson, N.E. (2007) Epigenetic Regulation as a New Target for Breast Cancer Therapy. Cancer
    Invest. 25:659-65. PMID: 18058459

3. 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. PMID: 18505931

4. 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 Res Treat 117:443-51 PMID:
    18683042

5. 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 PMID: 19208734

6. Yao, Y and Zhou, Q (2010) A Novel Antiestrogen Agent Shikonin Inhibits Estrogen Dependent Gene Transcription in Human
    Breast Cancer Cells. Breast Cancer Res Treat 121:233-40 PMID: 19760501

7. 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 PMID: 19995796

8. 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 PMID: 20049865

9. 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 PMID: 20623181

10. 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

11. 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

12. 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

13. Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou Q (2013) Downregulation of miR-140 Promotes Cancer Stem Cell Formation in
      Basal-like Early Stage Breast Cancer. Oncogene. [Epub ahead of print] PMID:23752191

14. Li Q, Yao Y, Eades G, Gong DW, Zhou Q (2013) Sulforaphane Inhibits Mammary Adipogenesis by Targeting Adipose
      Mesenchymal Stem Cells. Breast Cancer Res Treat. 141:317-24 PMID:24002734

15. Li Q, Eades G, Yao Y, Zhang Y, Zhou Q (2014) Characterization of a Stem-like Subpopulation in Basal-like Ductal
      Carcinoma in Situ (DCIS) Lesions. J Biol Chem. 289:1303-122 PMID24297178