Chuck C.-K. Chao

Appointment : Division Director / Professor

Lab：Tumor Biology Laboratory

Education : Ph.D.

University/Nation：Univ. Texas Southwestern Med. Ctr, USA

Tel: 5157

E-mail : cckchao@mail.cgu.edu.tw

Research website : http://cckchao1.wix.com/chao-lab

Research interests:

Chemoresistance gene & target therapy

We are interested in cancer formation and treatment, with focus on the mechanism of anticancer resistance -- how chemotherapy resistant cells have changed their biology to escape cell death. Using transcriptomic analysis, we have identified numerous resistance genes and pathways against tranditional therapeutic agents, e.g., ER vesicular protein NAPA and chromatin modifying protein p300/Cited2 in cisplatin resistance; hormone androgen receptor (AR) and immunophilin FKBP5 in taxol resistance. We also engaged in studying the molecular mechanism of target therapy agents such as sorafenib, and ways to overcome resistance. Additionally, we work on the regulation of drug resistance genes by viral proteins mimetic chronic infection of clinically relevance viruses. e.g., hepatitis B X protein (HBx) and NPC derived EBV LMP1. Basic molecular methods and new genome-wide analysis are applied to these studies, in cell culture as well as in animal models, in hope that elucidation of molecular mechanism of drug resistance will shed light on improvement of clinical use.

Differentiation gene & metabolic disorder

We are also interested in the control of cell differentiation, development and metabolism. Cell differentiation is preceded by cell growth arrest. Failure in differentiation, arrested cells undergo apoptosis (a genetically programmed cell death). Numerous genes engaged in cell growth arrest, named growth-arrest-specific (gas) genes, were identified. Gas7, a PCH family evolved in vertebrates, for example is preferentially expressed in brain and known to play a role in the proliferation (and/or anti-apoptosis) and differentiation of precursor cells of neuronal and other tissue types. Transcript variants of gas7 via alternative splicing and physical interaction with cytoskeletons were found. However, the function and mechanism of Gas7 in cell differentiation and development remains uncharacterized. In addition, DNA damage may cause cell senescence and metabolic dysfunction. Silencing of Cited2, a regulator of CBP/p300 on chromatin, results in severe DNA damage and mis-regulation of a sub-group of genes. It may have a novel role at epigenetic in cell development. We currently work on: (i) gas7 and cited2 in development and homeostasis of fat, muscle and bone using primary cells (e.g., mesenchymal stroma cells, MEF and preadipocytes), precursor cell lines and transgenic animals (mouse and zebrafish); (ii) transcriptomic alterations associated learning/memory deficiency using gas7 gene disrupted mice. Basic molecular methods, cell culture and transgenic animal analysis are applied to these studies, in hope that outcome of this study will lead to better understanding of the mechanism of development/homeostasis of specific tissue and coordination with others, and the cause and prevention/improvement of related diseases.

Publications:  (among 110 peer-reviewed papers)

1. Wu, Z.-Z., Lu, H.-P. and Chao, C.C.-K. Identification and functional analysis of genes which potentially confer resistance to cisplatin in tumor cells. Biochem. Pharmacol. 80: 262-276, 2010 SCI IF=5.009

2. Sun, N.-K.*, Sun, C.-L.*, Lin, C.-H., Pai, L.-M. and Chao, C.C.-K. Damaged DNA-binding protein 2 (DDB2) protects against UV irradiation in human cells and Drosophila. J. Biomed. Sci., 2010 (*equal contribution) IF=2.763

3. Wu, Z.-Z. and Chao, C.C.-K. Knockdown of NAPA using short-hairpin RNA sensitizes cancer cells to cisplatin: implications to overcome chemoresistance. Biochem. Pharmacol. 80: 827-837, 2010 IF=5.009

4. Kuo, T.-C. and Chao, C.C.-K. Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression. Biochem. Pharmacol. 80: 1093-1102, 2010IF=5.009

5. Hung, F.-C. and Chao, C.C.-K. Knockdown of growth-arrest-specific 7b gene (gas7b) using short-hairpin RNA desensitizes neuroblastoma cells to cisplatin: implications to prevent apoptosis of neurons. J. Neurosci. Res. 88: 3578-3587, 2010  IF=2.594

6. Wu, Z.-Z., Sun, N.-K. and Chao, C.C.-K. Knockdown of CITED2 using short-hairpin RNA sensitizes cancer cells to cisplatin through stabilization of p53 and enhancement of p53-dependent apoptosis. J. Cell. Physiol.226: 2415-2428, 2011 IF=3.839

7. Chao, C.C.-K. A Search for the genes involved in resistance to cisplatin chemotherapy: Review of the experimental evidence. Curr. Top. Pharmacol. 14: 47-54, 2011 January [invited review article]

8. Chao, C.C.-K. The role of DDB2 in regulating cell survival and apoptosis following DNA damage - a mini-review. In DNA Repair (ed., Kruman, I.), InTech: 2011 July (ISBN 978-953-307-697-3) [invited review]

9. Hung, F.-C., Chang, Y.-H., Lin-Chao, S. and Chao, C.C.-K. Gas7 mediates the differentiation of human bone marrow-derived mesenchymal stem cells into functional osteoblasts by enhancing Runx2-dependent gene expression. J. Orthopaedic Res. 29: 1528-1535, 2011 IF=2.986

10. Kuo, T.-C.*, Lu, H.-P.* and Chao, C.C.-K. The tyrosine kinase inhibitor sorafenib sensitizes hepatocellular carcinoma cells to taxol by suppressing the HURP protein. Biochem. Pharmacol. 82: 184-194, 2011 (*equal contribution) IF=5.009

11. Wu, Z.-Z., Sun, N.-K., Chien, K.-Y. and Chao, C.C.-K. Silencing of the SNARE protein NAPA sensitizes cancer cells to cisplatin by inducing ERK1/2 signaling, synoviolin ubiquitination and p53 accumulation. Biochem Pharmacol. 82: 1630-1640, 2011 IF=5.009

12. Wu, Z.-Z.*, Chow, K.-P.N.*, Kuo, T.-C., Chang, Y.-S., Chao, C.C.-K. Latent membrane protein 1 of Epstein–Barr virus sensitizes cancer cells to cisplatin by enhancing NF-kB p50 homodimer formation and downregulating NAPA expression. Biochem. Pharmacol. 82: 1860-1872, 2011 (*equal contribution) IF=5.009

13. Kuo, T.-C., Chang, P.-Y., Huang, S.-F., Chou, C.-K. and Chao, C.C.-K. Knockdown of HURP inhibits the proliferation of hepatocellular carcinoma cells via downregulation of gankyrin and accumulation of p53. Biochem Pharmacol. 83: 758- 768, 2012 IF=5.009

14. Chao, C.C.-K. Adapting new ways to escape attacks by anti-cancer drugs: Epigenetic changes and alternative splicing. Adaptive Medicine 4: 64-68, 2012 [invited review]

15. Sun, N.-K., Huang, S.-L., Chien, K.-Y. and Chao, C.C.-K. Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28/MDM2/p53 complexes and by preventing the ubiquitination and degradation of p53.Biochem. J. 444: 303-314, 2012 IF=4.396

16. Huang, B.-T., Chang, P.-Y., Su, C.-H., Chao, C.C.-K. and Lin-Chao, S. Deficiency of Gas7 in mice reveals motor coordination defects due to abnormal motor neuron function and muscle fiber composition during aging.PLoS ONE 7(5): e37702. DOI:10.1371/journal.pone.0037702, 2012 IF=3.234

17. Lu, H.-P. and Chao, C.C.-K. Cancer cells acquire resistance to anticancer drugs: An update. Biomed. J. 35: 479-491, 2012 [invited review]

18. Hung, F.-C., Cheng, Y.-C., Sun, N.-K. and Chao, C.C.-K. Identification and characterization of zebrafish gas7 gene in early development. J, Neurosci. Res. 91:51-61, 2013  IF=2.594

19. Chao, C.C.-K., Hung, F.C. and Chao, J.J. Gas7 is required for mesenchymal stem cell-derived bone development. Stem Cells Int. vol. 2013, Article ID 137010, 6 pages, 2013. DOI:10.1155/2013/137010 [invited review] IF=2.813

20. Sun, N.-K., Huang, S.-L., Chang, T.-C. and Chao, C.C.-K. Sorafenib induces apoptosis in endometrial carcinoma cells by inhibiting Elk-1-dependent Mcl-1 gene expression and by inducing Akt/GSK3β-dependent Mcl-1 protein degradation. J. Cell. Biochem. 114: 1819-1831, 2013 IF=3.263

21. Chang, P.-Y.*, Wu, Z.-Z.*, Sun, N.-K. and Chao, C.C.-K. EBV-encoded LMP-1 sensitizes nasopharyngeal carcinoma cells to genotoxic drugs by down-regulating Cabin1 expression. J. Cell. Physiol. 229: 309-322, 2014(*equal contribution) IF=3.839

22. Sun, N.-K.*, Huang, S.-L.*, Chang, P.-Y., Lu, H.-P. and Chao, C.C.-K. Transcriptomic profiling of taxol-resistant ovarian cancer cells identifies FKBP5 and the androgen receptor as critical markers of chemotherapeutic response. Oncotarget 5: 11939-11956, 2014 (*equal contribution) IF=6.359

23. Chao, C.C.-K. Mechanisms of p53 degradation. Clinica Chimica Acta 438: 139-147, 2015 (online: Aug. 13, 2014, doi: 10.1016/j.cca.2014.08.015) [invited review] IF=2.824

24. Huang, S.-L. and Chao, C.C.-K. Linking immunophilin FKBP5 to taxol resistance in ovarian cancer. Cancer Cell & Microenviron. 2015; 2: e692. doi: 10.14800/ccm.692 [invited research highlight]

25. Lin, Y.-T., Lu, H.-P. and Chao, C.C.-K. Oncogenic c-Myc and prothymosin-alpha protect hepatocellular carcinoma cells against sorafenib-induced apoptosis. Biochem. Pharmacol. 93: 110-124, 2015 (first online: 3 Nov. 2014, DOI:10.1016/j.bcp.2014.10.012) IF=5.009

26. Lin, Y.-T. and Chao, C.C.-K. Sorafenib induces apoptosis in hepatocellular carcinoma Cells by inhibiting c-Myc and prothymosin-alpha. Cancer Cell & Microenviron. 2015; 2: e788. doi: 10.14800/ccm.788 [invited research highlight]

27. Huang, S.-L. and Chao, C.C.-K. Silencing of taxol-sensitizer genes in cancer cells: Lack of sensitization effects. Cancers 7: 1052-1071, 2015; doi:10.3390/cancers7020824 (special issue - Cancer Cell Proliferation) [invited article].

28. Ho, C.H., Hsu, J.L., Liu, S.P., Hsu, L.C., Chang, W.L., Chao, C.C.-K., Guh, J.H. Repurposing of phentolamine as a potential anticancer agent against human castration-resistant prostate cancer: A central role on microtubule stabilization and mitochondrial apoptosis pathway. Prostate 75 (13):1454-1466, 2015 IF=3.565

29. Sun, N.-K.*, Huang, S.-L.*, Lu, H.-P., Chang, T.-C. and Chao, C.C.-K. Integrative transcriptomics-based identification of cryptic drivers of taxol-resistance genes in ovarian carcinoma cells: analysis of the androgen receptor. Oncotarget 6: 27065-27082, 2015 (*equal contribution) IF=6.359

30. Liu, Y.-C., Chang, P.-Y. and Chao, C.C.-K. CITED2 silencing sensitizes cancer cells to cisplatin by inhibiting p53 trans-activation and chromatin relaxation on the ERCC1 DNA repair gene. Nucleic Acids Res. 43: 10760-10781, 2015 IF=9.112

31. Lin, Y.-T. and Chao, C.C.-K. Identification of the  β-catenin/JNK/prothymosin-alpha axis as a novel target of sorafenib in hepatocellular carcinoma cells. Oncotarget 6: 38999-39017, 2015 IF=6.359

32. Hung, F.-C.*, Shih, H.-Y.*, Cheng, Y.-C. and Chao, C.C.-K. Growth-arrest-specific 7 gene regulates neural crest formation and craniofacial development in zebrafish. Stem Cells Dev. 24: 2943-2951, 2015 (*equal contribution) IF=3.727