Assistant Research Fellow
Lab phone: +886-2-27898804
EDUCATION AND POSITIONS HELD:
- Ph.D., Environmental Toxicology, University of California-Riverside, 2007
- Master of Environmental Management, Environmental Toxicology, Chemistry and Risk Assessment, Duke University, 2002
- Postdoctoral Fellow, Genomics Research Center, Academia Sinica, 2008-2014
- Research Scientist, Department of Biology, Washington University in St. Louis, 2014-2015
- Assistant Research Fellow, Genomics Research Center, Academia Sinica, 2015-present
- Taiwan National Science Council 2013 Postdoctoral Fellow Academic Publication Award
- The 72nd Annual Meeting of the Japanese Cancer Association Travel Grant Award Oct 2013
- The 1st GRC Best Performance-and-Service Award, Genomics Research Center, Academia Sinica, Feb 2012
- The 70th Annual Meeting of the Japanese Cancer Association Travel Grant Award Oct 2011
- Academia Sinica Postdoctoral Research Fellowship Jan 2010- Dec 2011
- Academia Sinica Distinguished Postdoctoral Scholar Fellowship Jan 2008- Dec 2009
- Sigma Xi Grants-in-Aid of Research Award, Jan 2007
- Fukuto Award, University of California-Riverside June 2006
Rooted in our modern lifestyle, the flexibility to sleep, eat, exercise at any time and travel between different time zones makes the disruption of circadian rhythms both easy and common. Accumulating epidemiological and animal studies have shown that such disruption is strongly associated with many diseases, including cancer. Although the World Health Organization has listed disrupted circadian rhythm as a potential carcinogen, how circadian rhythm underlies oncogenic mechanisms or impacts prevention and cure continues to be elusive. Long term goals of the Hwang-Verslues laboratory is to investigate: 1, whether the core circadian proteins exhibit oncogenic or tumor suppressive functions which can directly contribute to tumorigenesis and malignancy, particularly via regulating cancer stem cell phenotypes; 2, whether and how environmental factors/drugs alter the circadian rhythm or circadian gene functions to facilitate tumorigenesis and malignancy.
Two concurrent research aims are:
1. Identify PER2 downstream targets associated with CSC properties and cancer progression and elucidate the underlying regulatory mechanisms
The core circadian clock gene Period 2 (PER2) exhibited critical tumor suppressor function in breast cancer (Hwang-Verslues et al., 2013). Loss of PER2 not only increased the prevalence of breast cancer stem cells (CSCs) and facilitated tumor growth, it also allowed hypoxia to activate Octameric Transcription Factor1 (OCT1)-mediated EMT gene expression (Figure 1). A strong negative correlation between PER2 expression and breast cancer malignancy indicated that PER2 may have additional targets critical for breast cancer progression yet to be identified. In this research aim, we intend to find novel PER2 target genes, particularly those that facilitate breast cancer metastasis and stemness phenotypes.
2. Determine how hypoxia regulates PER2 to promote EMT and cancer progression
Our previous research indicated that PER2 protein was phosphorylated, ubiquitinated and rapidly degraded through proteasome degradation pathway under hypoxia (Figure 2 is from (Hwang-Verslues et al., 2013)). We are currently seeking to understand how hypoxia regulates PER2 protein post-translationally to facilitate EMT and cancer progression by identifying the responsible kinase and ubiquitination machinery (Figure 2).
- Cheung, S.K.C., Chuang, P.-K., Huang, H.-W., Hwang-Verslues, W.W., Cho C.H.-H., Yang, W.-B., Shen, C.-N., Hsiao, M., Hsu, T.-L., Chang, C.-F., Wong, C.-H., 2016, “Stage-Specific Embryonic Antigen-3 (SSEA-3) and β3GalT5 are Cancer Specific and Significant Markers for Breast Cancer Stem Cells”, Proceedings of the National Academy of Sciences of the United States of America, 113(4), 960-965. (SCI)
- Wu, H.-H*, Hwang-Verslues, W.W.*, Lee, W.-H., Huang, C.-K., Wei, P.-C., Chen, C.-L. , Shew, J.-Y., Lee, E. Y.-H. P., Jeng, Y.-M., Tien, Y.-W., Ma, C., Lee, W.-H., 2015, “Targeting IL-17B/RB signaling with an anti-IL17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines”, JOURNAL OF EXPERIMENTAL MEDICINE, 212(3), 333-349. (SCI)
- Hwang-Verslues, W.W., Chang, P.-H., Jeng, Y.-M., Kou, W.-H., Chang, Y.-C., Chiang, P.-H., Hsieh, T.-H., Su, F.-Y., Lin, L.-C., Abbondante, S., Yang, C.-Y., Hsu, H.-M., Yu, J.-C., Chang, K.-J., Shew, J.-Y., Lee, E. Y.-H. P., Lee, W.-H., 2013, “Loss of corepressor PER2 under hypoxia upregulates OCT1-mediated EMT gene expression and enhances tumor malignancy”, Proceedings of the National Academy of Sciences of the United States of America, 110(30), 12331-12336. (SCI)
- Chang, P.-H., Hwang-Verslues, W.W., Chang, Y.-C., Chen, C.-C., Hsiao, M., Jeng, Y.-M., Chang, K.-J., Lee, E. Y.-H. P., Shew, J.-Y., Lee, W.-H., 2012, “Activation of Robo1 signaling of breast cancer cells by Slit2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/β-catenin pathway”, CANCER RESEARCH, 72(18), 4652-4661. (SCI)
- Hwang-Verslues, W.W.*, Lee, W.-H., Lee, E.Y.-H.P., 2012, “Biomarkers to target heterogeneous breast cancer stem cells (invited review)”, Journal of Molecular Biomarkers & Diagnosis, S8, 006.
- Hwang-Verslues, W.W., Chang P.-H., Wei P.-C., Yang C.-Y., Huang C.-K., Kuo W.-H., Shew J.-Y., Chang K.-J., Lee E.-Y., Lee W.-H., 2011, “miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1”, ONCOGENE, 30(21), 2463-2474. (SCI)
- Hwang-Verslues, W.W., Sladek, F.M., 2010, “HNF4a-role in drug metabolism and potential drug target? (review)”, CURRENT OPINION IN PHARMACOLOGY, 10(6), 698-705. (SCI)
- Bolotin E., Liao H., Ta T.C., Yang C., Hwang-Verslues W.W., Evans J.R., Jiang T., Sladek F.M., 2010, “Integrated approach for identification of HNF4α target genes using protein binding microarrays”, HEPATOLOGY, 51(2), 642-653. (SCI)
- Hwang-Verslues, W.W., Kuo W.-H., Chang P.-H. Pan C.-C., Wang H.-H., Tsai S.-T., Jeng Y.-M., Shew J.-Y., Kung J.T, Chen C.-H., Lee E. Y.-H. P., Chang K.-J., Lee W.-H., 2009, “Multiple lineages of human breast cancer stem/progenitor cells identified by profiling with stem cell markers”, PLoS One, 4(12), e8377. (SCI)
- Hwang-Verslues, W.W., Chang, K.J., Lee, E.Y-H.P., Lee, W.-H., 2008, “Breast cancer stem cells and tumor suppressor genes”, Journal of Formosan Medical Association, 107(10), 751-766.
- Hwang-Verslues, W.W., Sladek, F.M., 2008, “Nuclear receptor HNF4alpha1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter”, MOLECULAR ENDOCRINOLOGY, 22(1), 78-90. (SCI)
- Maeda, Y.*, Hwang-Verslues, W.W.*, Wei, G., Fukazawa, T., Durbin, M.L., Owen, L. B., Liu, X. and Sladek, F.M., 2006, “Tumor suppressor p53 down regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4a) gene”, BIOCHEMICAL JOURNAL, 400(2), 303-313. (SCI)