趙清貴

職稱：組主任/講座教授

研究室名稱：腫瘤細胞研究室

最高學歷：Ph.D.

學校/國家：德州大學西南醫學院/美國

分機號碼：5157

電子郵件帳號：  cckchao@mail.cgu.edu.tw

個人網頁網址：http://cckchao1.wix.com/chao-lab

研究室現有：博士後研究員0人；博士班研究生2人；碩士班研究生1人；專任研究助理2人；大學部專題生0人

研究方向及研究室特色：

1.癌症抗藥機制與凋亡（Modulating chemotherapeutic resistance and apoptosis）：
本研究室主要目標是探討癌症之化學及輻射治療失效的分子機制及改進癌療的研發。運用基因科技修改DNA修補及細胞凋亡 (modulation of DNA repair & apoptosis) 可以克服癌細胞的抗藥、抗輻射現象。利用蛋白生化及基因選殖技術，我們發現數種受基因毒損壞DNA 的辨識及修補蛋白，譬如HMG (high-mobility group)、DDB1及 DDB2 蛋白，其活性在細胞內可明顯地修飾藥物反應。此外，我們更進一步運用基因晶片 (DNA microarray) 配合基因轉殖 (transgenics) 或剔除 (genetic knockout) 及蛋白體 (proteomics)，發現一些”抗藥基因”。有些基因功能還受 p53 抑癌蛋白及ubiquitin-mediated proteasome 蛋白分解的調控。B 型肝炎病毒 HBx 蛋白或鼻咽癌EB病毒LMP-1蛋白所引起的細胞感染反應(譬如細胞生長及細胞死亡)。此外，我們更進一步運用RNAi配合基因轉殖 (transgenics) 或剔除 (genetic knockout) 及蛋白體學 (proteomics)，探討是否提升藥效及篩選新藥。   

2.細胞分化、發育與疾病（Cell differentiation, development and diseases）：
本研究室另一個目標是探討細胞分化與個體發育及疾病的調控。藉由致癌，抑癌與凋亡基因(oncogene, tumor suppressor and apoptotic genes) 的遺傳操作，來分析細胞生長分化與移動，可以 找出關鍵的細胞分子以瞭解癌症及腦神經等疾病的部分成因，及有助於發展新的治療藥物。細胞分化必需先抑止生長 (growth arrest)，在這個抑長 階段特別表現的抑長基因 (growth-arrest-specific gene，簡稱 Gas)，可能決定細胞是否能夠順利分化，否則就會凋亡 (apoptosis)。我們與德國科學家分別發現了多個的抑長基因，其中我們發現的 Gas7 (growth-arrest-specific 7) 對小鼠及斑馬魚腦神經細胞及骨骼生成是必要的。 Gas7 也與細胞骨幹 (cytoskeleton) 譬如 F-actin及microtubulin 結合，可以調節其 assembly，可能參與細胞骨幹的相關功能。我們的目的在藉此動物模式進一步探討該關鍵分子，在神經與骨骼肌肉系統的發育 (development) 恆定 (maintenance)，以及人類腦神經退化及骨骼疏鬆的相關病理角色。

 

最近五年所發表論文： (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 protecthepatocellular 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