Lab phone: +886-2-27898804
EDUCATION AND POSITIONS HELD:
- Ph.D., Environmental Toxicology, University of California-Riverside, June 2007
- Master of Environmental Management, Environmental Toxicology, Chemistry and Risk Assessment, Duke University, May 2002
- Postdoctoral Fellow, Genomics Research Center, Academia Sinica, Jan 2008- Dec 2014
- Research Scientist, Department of Biology, Washington University in St. Louis, Sep 2014- May 2015
- Assistant Professor, Genomics Research Center, Academia Sinica, Dec 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 are to decipher the links among circadian rhythm, core clock gene functions and stem cell (SC) fate/characteristics in tissue development and disease progression.
There are two research programs currently conducted in our lab:
The main program is to use mice and cell cultures as models to investigate whether circadian rhythms or core clock genes contribute to intestinal SC (ISC) fate determination, and how the circadian clocks in the brain and the intestine coordinate with each other to regulate ISC fate. We also aim to understand how heterogeneous cell types in the intestine synchronize their circadian rhythms to generate a SC niche and how the circadian-SC relationship influences disease development, such as chronic inflammation and cancer. By mechanistically linking circadian regulation to SC fate and function, we will not only gain fundamental knowledge in chronobiology but also provide new strategies or targets for disease prevention and treatment.
|Diagram depicts our main research program to investigate the
relationship among the master clock, intestinal peripheral clock,
the intestinal (cancer) stem cell self- renewal and differentiation.
The second program stems from our previous findings of PER2 tumor suppressive function and its regulation by hypoxia (Hwang-Verslues et al., PNAS, 2013). We are exploring how cellular stress such as oxidative stress regulates PER2 to repress its function to promote breast cancer progression. We are also studying how inflammatory microenvironment affects the circadian regulation in breast epithelial cells to promote tumorigenesis. At the molecular level, we are examining how PER2 protein is post-translationally regulated and investigating the subsequent effects on PER2 function. We are confident that these findings will provide the basis for the association between disrupted circadian rhythm and breast cancer development that has been observed in epidemiological studies.
Diagram of the proposed mechanism by which pro-inflammatory cytokines
|Hwang-Verslues Lab Party, Feb 2018|
- Fararjeh, A., Tu, S.H., Chen, L.C., Cheng, T.C., Liu, Y.R., Chang, H.L., Chang, H.W., Huang, C.C., Wang, H.C.R., Hwang-Verslues, W.W., Wu, C.H., Ho, Y.S.*, 2019, “Long-term exposure to extremely low-dose of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induce non-malignant breast epithelial cell transformation through activation of the a9-nicotinic acetylcholine receptor-mediated signaling pathway”, ENVIRONMENTAL TOXICOLOGY, 34(1), 73-82. (SCI)
- Yu, C.-W., Cheng, K.-C., Chen, L.-C., Lin, M.-X., Chang, Y.-C., Hwang-Verslues, W.W.*, 2018, “Pro-inflammatory cytokines IL-6 and CCL2 suppress expression of circadian gene Period2 in mammary epithelial cells”, BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 1861(11), 1007-1017. (SCI, SSCI)
- Fattah Fararjeh-Salah Abdul, Tu Shih-Hsin, Chen Li-Ching, Liu Yun-Ru, Lin Yen-Kuang, Chang Hang-Lung, Chang Hui-Wen, Wu Chih-Hsiung, Verslues Wendy-Hwang, Ho Yuan-Soon, 2018, “The Impact of the effectiveness of GATA3 as a prognostic factor in breast cancer”, Human Pathology, 80, 219-230. (SCI)
- Wu YW, Hsu KC, Lee HY, Huang TC, Lin TE, Chen YL, Sung TY, Liou JP, Hwang-Verslues WW, Pan SL, Huang-Fu WC,, 2018, “A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo”, FRONTIERS IN PHARMACOLOGY, 9, 205. (SCI) (IF: 4.4; SCI ranking: 12.8%)
- Huang S.-C., Wei P.-C., Hwang-Verslues W.W., Kuo W.-H., Jeng Y.-M., Hu C.-H., Shew J.-Y., Huang C.-S., Chang K.-J., Lee E. Y.-H. P., Lee W.-H.*, 2017, “TGF-β1 secreted by Tregs in lymph nodes promotes breast cancer malignancy via up-regulation of IL-17RB”, EMBO MOLECULAR MEDICINE, 9(12), 1660-1680. (SCI)
- 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)
- Ling-Chih Chen, Yung-Lin Hsieh, Tai-Yun Kuo, Yu-Chi Chou, Pang-Hung Hsu, Wendy W Hwang-Verslues*, Unpublished, “Differential Effects of SUMO1/2 on Circadian Protein PER2 Stability and Function”, BioRxiv. (Cold Spring Harbor Laboratory)
- Po-Hao Chang, Min-Che Chen, Ya-Ping Tsai, Pang-Hung Hsu, Yung-Ming Jeng, Wendy W Hwang-Verslues*, Unpublished, “Interplay between Desmoglein2 and hypoxia controls intravasation and circulating tumor cell clustering in breast cancer metastasis”, Cold Spring Harbor Laboratory bioRxiv the preprint server for biology. (bioRxiv)