91猫先生

赵清贵

职称：组主任/讲座教授

研究室名称：肿瘤细胞研究室

最高学歷：Ph.D.

学校/国家：德州大学西南医学院/美国

分机号码：5157

电子邮件帐号： ?cckchao@mail.cgu.edu.tw

个人网页网址：

研究室现有：博士后研究员0人；博士班研究生2人；硕士班研究生1人；专任研究助理2人；大学部专题生0人

研究方向及研究室特色：

1.癌症抗药机制与凋亡（Modulating chemotherapeutic resistance and apoptosis）：
本研究室主要目标是探讨癌症之化学及辐射治疗失效的分子机制及改进癌疗的研发。运用基因科技修改DNA修补及细胞凋亡?(modulation of DNA repair &?apoptosis)?可以克服癌细胞的抗药、抗辐射现象。利用蛋白生化及基因选殖技术，我们发现数种受基因毒损坏DNA?的辨识及修补蛋白，譬如HMG (high-mobility group)、DDB1及?DDB2?蛋白，其活性在细胞内可明显地修饰药物反应。此外，我们更进一步运用基因晶片?(DNA microarray)?配合基因转殖?(transgenics)?或剔除?(genetic knockout)?及蛋白体?(proteomics)，发现一些”抗药基因”。有些基因功能还受?p53?抑癌蛋白及ubiquitin-mediated proteasome?蛋白分解的调控。B?型肝炎病毒?HBx?蛋白或鼻咽癌EB病毒LMP-1蛋白所引起的细胞感染反应(譬如细胞生长及细胞死亡)。此外，我们更进一步运用RNAi配合基因转殖?(transgenics)?或剔除?(genetic knockout)?及蛋白体學?(proteomics)，探讨是否提升药效及筛选新药。???

2.细胞分化、发育与疾病（Cell differentiation, development and diseases）：
本研究室另一个目标是探讨细胞分化与个体发育及疾病的调控。藉由致癌，抑癌与凋亡基因(oncogene, tumor suppressor and apoptotic genes)?的遗传操作，来分析細胞生长分化与移动，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长?(growth arrest)，在这个抑长?阶段特别表现的抑长基因?(growth-arrest-specific gene，简称?Gas)，可能决定细胞是否能够顺利分化，否则就会凋亡?(apoptosis)。我们与德国科学家分别发现了多个的抑长基因，其中我们发现的?Gas7?(growth-arrest-specific 7)?对小鼠及斑马鱼脑神经细胞及骨骼生成是必要的。?Gas7?也与细胞骨干?(cytoskeleton)?譬如?F-actin及microtubulin?结合，可以调节其?assembly，可能参与细胞骨干的相关功能。我们的目的在藉此动物模式进一步探讨该关键分子，在神经与骨骼肌肉系统的发育?(development)?恆定?(maintenance)，以及人类脑神经退化及骨骼疏鬆的相关病理角色。

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最近五年所发表论文： (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

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