Programme

AFFILIATION:

Chang Gung Memorial Hospital at Linkou

POSITION TITLE:

Director, Cancer Genome Research Center
Distinguished Chair Professor

EDUCATION/TRAINING:

National Taiwan University, Taipei, Taiwan, MD, 1983, Medicine

HONORS:

1994-1997 Fellow, Leukemia Society of America

2009           Outstanding research award of National Science Council, Taiwan

2009     4th TienTe Lee Award- Outstanding (4th TienTe Lee Award- Outstanding), TienTe Lee Biomedical Foundation

 

RESEARCH INTERESTS:

Dr. Wu is a physician-scientist with training in gene regulation and tumor biology. HIs research includes the molecular mechanism of epithelial-mesenchymal transition (EMT) mediated by hypoxia. Research projects will focus on the identification of HIF-1α and Twist1 target genes and their relationship to EMT and metastasis. Other aspects of biology including epigenetics, post-translational modification, protein stability and angiogenesis related to HIF-1α and Twist1 will be explored too.

PUBLICATIONS:

1. Selected peer-reviewed publications

 

1. Shyu, Y.C., Cho, R.L., Liao, P.C., Huang, T.S., Yang, C.J., Lu, M.J., Huang, S.M., Lin, X.Y., Liou, C.C., Kao, Y.H., Lu, C.H., Peng, H.L., Chen, J.R., Cherng, W.J., Yang, N.I., Chen, Y.C., Pan, H.C., Jiang, S.T., Hsu, C.C., Lin, G.G., Yuan, S.S., Wu, K.J., Lee, T.L., Shen, C.J. (2022) Genetic disruption of KLF1-K74 Sumoylation in hematopoietic system promotes healthy longevity in mice. Advanced Science, accepted for publication.

2. Wu, H.T., Lin, Y.T., Chew, S.H., and Wu, K.J. (2022) Organ defects of Usp7K444R mutant mouse indicate the essential role of K-63 polyubiquitination of Usp7 in organ formation. Biomedical J., accepted for publication.

3. Huang, Y.C., Lai, J.C.Y., Peng, P.H., Wei, K.C. and Wu, K.J. (2021) Chromatin accessibility analysis identifies GSTM1 as a prognostic marker in human glioblastoma patients. Clinical Epigenetics, 13, 201.

4. Peng, P.H., Hsu, K.W., and Wu, K.J. (2021) Liquid-liquid phase separation (LLPS) in cellular physiology and tumor biology. Am. J. Cancer Res., 11,3766-3776.

5. Peng, P.H., Lai, J.C.Y., Hsu, K.W. and Wu, K.J. (2021) Induction of epithelial-mesenchymal transition (EMT) by hypoxia-induced lncRNA RP11-367G18.1 through activating the histone 4 lysine 16 acetylation (H4K16Ac) mark. Am. J. Cancer Res., 11, 2618-2636.

6. Peng, P.H., Hsu, K.W., Lai, J.C.Y., and Wu, K.J. (2021) The role of hypoxia-induced long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis. Biomed. J., 44,521-533.

7. Wu, K.J. (2020) The epigenetic roles of DNA N6-methyladenine (6mA) modification in eukaryotes. Cancer Letters, 494, 40-46 (review article).

8. Peng, P.H., Lai, J.C.Y., Hsu, K.W. and Wu, K.J. (2020) Hypoxia-induced lncRNA RP11-300F4.3 promotes epithelial-mesenchymal transition and metastasis through upregulating EMT regulators. Cancer Letters, 483, 35-45.

9. Wu, K.J. (2020) The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness. Biomedical J. 43, 107-114 (review article).

10. Hao, Z., Wu, T., Cui, X., Zhu, P., Tan, C., Dou, X., Hsu, K.W., Lin, Y.T., Peng, P.H., Zhang, L.S., Gao, Y., Hu, L., Sun, H.L., Zhu, A., Liu, J, Wu, K.J., and He, C. (2020) N6-deoxyadenosine methylation in mammalian mitochondrial DNA. Molecular Cell, 78, 382-395 (doi: 10.1016/j.molcel.2020.02.018.)

11. Lin, Y.T. and Wu, K.J. (2020) Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling. J. Biomed. Sci. 27, 39 (review article).

12. Wang, J.Q., Yan, F.Q., Wang, L.H., Yin, W.J., Chang, T.Y., Liu, J.P., and Wu, K.J. (2020) Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation. Genes, Chromosomes, and Cancer, 59, 73-83.

13. Kao, S.H., Cheng, W.C., Wang, Y.T., Yeh, H.Y., Chen, Y.J., Wu, H.T., Tsai, M.H. and Wu, K.J. (2019) Regulation of miRNA Biogenesis and Histone Modification by K63-polyubiquitinated DDX17 Controls Cancer Stem-like Features. Cancer Research, 79, 2549-2563.

14. Kao, S.H., Wu, H.T., and Wu, K.J. (2018) Ubiquitination by Huwe1 in tumorigenesis and beyond. J. Biomedical Sciences, 25, 67 (invited review).

15. Wu, M.Z., Cheng, W.C., Chen, S.F., Nieh, S., O'Connor, C., Liu, C.L., Tsai, W.W., Wu, Martin, L., Lin, Y.S., Wu, K.J., Lu, L.F and Izpisua Belmonte, J.C. (2017) miR25/93 mediates hypoxia-induced immunosuppression by repressing cGAS. Nature Cell Biology, 19, 1286-1296.

Wu, H.T., Kuo, Y.C., Huang, C.H., Hung, J.J., Chen, W.Y., Chou, T.Y., Chen, Y., Y.J. Chen, Y.J. Chen, Cheng, W.C., Teng, S.C., and Wu, K.J. (2016) K63-polyubiquitinated HAUSP deubiquitinates HIF-1 and

1. dictates H3K56 acetylation to promote hypoxia-induced tumor progression. Nature Communications, 7, 13644.

2. Wang, J.Q., Wu, M.Z., and Wu, K.J. (2016) Analysis of Epigenetic Regulation of Hypoxia-induced Epithelial-Mesenchymal Transition in Cancer Cells by Quantitative Chromatin Immunoprecipitation. Methods in Molecular Biology, 1436, 23-9 (invited book chapter).

3. Chen, S.Y., Teng, S.C., Cheng, T.H. and Wu, K.J. (2016) MiR-1236 regulates hypoxia-induced epithelial-mesenchymal transition and cell migration/invasion through repressing SENP1 and HDAC3. Cancer Letters, 378, 59-67 (2016).

4. Kuo, Y.C., Wu, H.T., J.J. Hung, T.Y. Chou, Teng, S.C., and Wu, K.J. (2015) Nijmegen breakage syndrome protein 1 (NBS1) modulates hypoxia inducible factor-1a (HIF-1a) stability and promotes in vitro migration and invasion under ionizing radiation. Int. J. Biochemistry & Cell Biology, 64, 229-238.

5. Chen, H.F., Huang, C.H., Liu, C.J., Hung, J.J., Hsu, C.C., Teng, S.C., and Wu, K.J. (2014) Twist1 induces endothelial differentiation of tumor cells through the Jagged1-KLF4 axis. Nature Communications, 5, 4697.

6. Tsai, Y.P., Chen, H.F., Chen, S.Y., W.C. Cheng, H.W. Wang, Z.J. Shen, Teng, S.C., Chuan, H., and Wu, K.J. (2014) TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator. Genome Biology, 15, 513.

7. Tsai, Y.P. and Wu, K.J. (2014) Epigenetic regulation of hypoxia-responsive gene expression: focusing on chromatin and DNA modifications. Int. J. Cancer, 134, 249-256. (Review article)

8. Wu, C.Y., Tsai, Y.P., Wu, M.Z., Teng, S.C., and Wu, K.J. (2012) Epigenetic reprogramming and post-transcriptional regulation during the epithelial-mesenchymal transition. Trends in Genetics, 28, 454-463. (Review article) 

9. Tsai, Y.P., and Wu, K.J. (2012) Hypoxia-regulated target genes implicated in cancer metastasis. J. Biomed. Sci. 19, 102. (Review article)

10. Yang, W.H., Lan, H.Y., Huang, C.H., Tai, S.K., Tzeng, C.H., Kao, S.Y., Wu, K.J., Hung, M.C., and Yang, M.H. (2012) Rac1 activation mediates Twist1-induced cancer cell migration. Nature Cell Biology, 14, 366-374.

11. Wu, M.Z., Tsai, Y.P., Yang, M.H., Huang, C.H., Chang, S.Y., Chang, C.C., Teng, S.C., and Wu, K.J. (2011) Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition. Molecular Cell, 43, 811-822.

24.Yang, M.H., Hsu, D.S., Wang, H.W., Yang, W.H., Kao, S.Y., Tzeng, C.H., Tai, S.K., Chang, S.Y., O.K. Lee, and Wu, K.J. (2010) Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. (co-corresponding author) Nature Cell Biology, 12, 982-992.

25. Hung, J.J., Yang, M.H., Hsu, H.S., Hsu, W.H., Liu, J.S. and Wu, K.J. (2009) Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1, and Snail expression in resectable non-small cell lung cancer. Thorax, 64, 1082-1089.

26.Tsai, Y.P., Yang, M.H., Huang, C.H., Chang, S.Y., Liu, C.J., Chen, P.M., Teng, S.C., and Wu, K.J. (2009) Interaction between HSP60 and β-catenin promotes metastasis. Carcinogenesis, 30, 1049-1057.

27.Yang, M.H, and Wu, K.J. (2008) TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle, 7, 2090-2096 (Review article).

28.Yang, M.H., Wu, M.Z., Chiou, S.H., Chang, S.Y., Chen, P.M., Liu, C.J., Teng, S.C., and Wu, K.J. (2008) Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nature Cell Biology, 10, 295-305.

29. Yang, M.H., Chang, S.Y., Chiou, S.H., Liu, C.J., Chi, C.W., Chen, P.M., Teng, S.C., and Wu, K.J. (2007) Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene, 26, 1459-1467.

30.Yang, M.H., Chiang,W.C., Chou, T.Y., Chang, S.Y., Chen, P.M., Teng, S.C., and Wu, K.J. (2006) Increased NBS1 Expression Is a Prognostic Marker of Aggressive Head And Neck Cancer And Overexpression of NBS1 Contributes to Transformation. Clin. Cancer Res., 12, 507-515.

31.Chen, Y.C., Su, Y.N., Chou, P.C., Chiang, W.C., Chang, M.C., Wang, L.S., Teng, S.C., and Wu, K.J. (2005) Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J. Biol. Chem. 280, 32505-32511.

32. Chiang, Y.C., Teng, S.C., Su, Y.N., Hsieh, F.C. and Wu, K.J. (2003) c-MYC directly regulates the transcription of NBS1 gene involved in DNA double-strand break repair. J.Biol.Chem. 278, 19286-19291.

33. Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J. and Dalla-Favera, R. (1999). Direct activation of TERT transcription by c-MYC. Nature Genet. 21, 220-224.