Ph.D, National University of Singapore
MD, Tongji Medical University
My laboratory currently has three research areas: (1) Epigenetic mechanisms of metal carcinogenesis; (2) Mechanisms of breast cancer metastasis; and (3) Drug repurposing and nanoparticle-mediated anti-cancer drug delivery for cancer therapy and prevention. Our mechanistic studies foucs on the role of non-coding RNAs and functional RNA modifications. The goals of my research are to understand the mechanism of cancer initiation and metastasis; and to develop mechanism-based cancer prevention and therapeutic strategies. Epigenetics refers to heritable alterations in the pattern of gene expression that are not caused by changes in DNA sequence, but are mediated by DNA methylation, histone posttranslational modifications, and non-coding RNAs such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). It is now well recognized that epigenetics is often deregulated in cancer and that epigenetics deregulation plays important roles in cancer development and progression. Cancer stem cells (CSCs) are cancer cells possessing characteristics of normal stem cells and CSCs or CSC-like cells are considered as cancer initiating and maintaining cells. While the mechanisms of generating CSCs or CSC-like cells are not elucidated, studies showed that deregulation of epigenetics play important roles in producing CSCs or CSC-like cells. Metal carcinogens such as arsenic, cadmium and hexavalent chromium [Cr(VI)], are common environmental contaminants causing lung and other cancer. However, the mechanism of metal carcinogenesis has not been clearly defined. The research work in my laboratory investigates how metal carcinogen exposures cause epigenetic deregulation and how deregulated epigenetics and functional RNA modifications contributes to metal carcinogenesis. Cancer is now considered as a stem cell disease, our research studies the mechanism by which metal carcinogen exposures produce cancer stem cell-like cells. Our cancer metastasis studies focus on triple negative breast cancer (TNBC), which usually has more aggressive metastasis and worse prognosis with no effective targeted therapies being available. Our research work investigates the role of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and functional RNA modifications in TNBC metastasis. Based on the molecular targets identified from our non-coding RNA studies, we are exploring the therapeutic effects of nanoparticle-mediated active-targeting anticancer drug/gene delivery approaches.
1. Yang C. ToxPoint: Dissecting Functional RNA Modifications in Responses to Environmental Exposure—Mechanistic Toxicology Research Enters a New Era. Toxicological Sciences 174: 1-2. 2020.
doi: 10.1093/toxsci/kfz252. (ToxPoint Article)
2. Uddin, M.B., Wang, Z., Yang, C. Dysregulations of functional RNA modifications in cancer, cancer stemness and cancer therapeutics Theranostics 10: 3164-3189. 2020.
3. Wang, Z., Yang, P., Xie, J., Lin, H.P., Kumagai, K., Harkema, J., Yang, C. Arsenic and benzo[a]pyrene co-exposure acts synergistically in inducing cancer stem cell-like property and tumorigenesis by epigenetically down-regulating SOCS3 expression. Environment International 137:105560. doi: 10.1016/j.envint.2020.105560. 2020.
4. Wang, Z., Lin, H.P., Li, Y., Tao, H., Yang, P., Xie, J., Maddy, D., Kondo, K., Yang, C. Chronic hexavalent chromium exposure induces cancer stem cell-like property and tumorigenesis by increasing c-Myc expression. Toxicological Sciences 172: 252-264. 2019. (Tox Spotlight Featured article)
5. Wang, Z., Yang C. Metal carcinogen exposure induces cancer stem cell-like property through epigenetic reprograming: A novel mechanism of metal carcinogenesis. Seminars in Cancer Biology doi: 10.1016/j.semcancer.2019.01.002. 2019.
6. Li, Y., Xiao, Y., Reichel, D., Bae, Y., Lee, E., Jiang, Y., Huang, X., Yang, C., and Wang, Z. In vivo β-Catenin attenuation by the integrin α5-targeting nano-delivery strategy suppresses triple negative breast cancer stemness and metastasis. Biomaterials 188:160-172. 2019.
7. Wang, Z., Li, Y., Xiao, Y., Lin, H.P., Yang, P., Humphries, B., Gao, T., Yang, C. Integrin α9 depletion promotes β-catenin degradation to suppress triple negative breast cancer tumor growth and metastasis. Int J Cancer. 145: 2767-2780. 2019.
8. Xiao, Y., Li, Y., Tao, H., Humphries, B., Li, A., Jiang, Y., Yang, C., Luo, R., and Wang, Z. Integrin α5 downregulation by miR-205 suppresses triple negative breast cancer stemness and metastasis by inhibiting Src/Vav2/Rac1 pathway. Cancer Letters 433:199-209. 2018.
9. Humphries, B., Wang, Z., Li, Y., Jhan, J.R., Jiang, Y., Yang, C. ARHGAP18 downregulation by miR-200b suppresses metastasis of triple negative breast cancer by enhancing activation of RhoA. Cancer Research 77: 4051-4064. 2017
10. Li, Y., Humphries, B., Wang, Z., Lang, S., Huang, X., Xiao, H., Jiang, Y. Yang, C. Complex coacervation-integrated hybrid nanoparticles increase plasmid DNA delivery efficiency in vivo. ACS Applied Materials & Interfaces 8: 30735-30746. 2016
11. Wang, Z., Humphries, B., Xiao, H., Jiang, Y., and Yang, C. MicroRNA-200b Suppresses Arsenic-transformed Cell Migration by Targeting Protein Kinase Cα and Wnt5b-Protein Kinase Cα Positive Feedback Loop and Inhibiting Rac1 Activation. Journal Biological Chemistry 289: 18373-86. 2014.
12. Humphries, B., Wang, Z., Oom, A.L., Fisher, T., Tan, D., Cui, Y., Jiang, Y., and Yang, C. MicroRNA-200b targets protein kinase Cα and suppresses triple negative breast cancer tumor metastasis. Carcinogenesis 35: 2254-63. 2014.
13. Wang, Z., Yang, J., Fisher, T., Xiao, H., Jiang, Y., and Yang, C. Akt Activation is Responsible for Enhanced Migratory and Invasive Behavior of Arsenic-Transformed Human Bronchial Epithelial Cells. Environmental Health Perspectives 120: 92-97. 2012.
14. Wang, Z., Zhao, Y., Smith, E., Goodall, G.J., Drew, P.A., Babletz, T., and Yang, C. Reversal and prevention of arsenic-induced human bronchial epithelial cell malignant transformation by microRNA-200b. Toxicological Sciences 121: 110-122. 2011.