PROFESSIONAL EXPERIENCE

Transcription

1 EDUCATION Doctor of Philosophy, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University Master of Science, Division of Organic Chemistry, Chemistry, National Taiwan University, Taiwan. Bachelor of Science, Chemistry, National Chung-Hsing University, Taiwan. PROFESSIONAL EXPERIENCE 2015 Professor, Institute of Biopharmaceutical Sciences, National Yang-Ming University Associate professor, Institute of Biopharmaceutical Sciences, National Yang- Ming University Assistant professor, Institute of Biopharmaceutical Sciences, National Yang- Ming University Postdoctoral Fellow, Apoptosis and Cell Death Program, The Burnham Institute for Medical Research RESEARCH 1. New drugs design and synthesis. 2. Pharmacology of novel agents for anticancer research AWARDS 國家新創獎 California Breast Cancer Research Program Postdoctoral Fellowship Albert H. Soloway Graduate Student Award in Pharmacy and Cancer Research Scholarship offered by Ministry of Education of Taiwan. PATENTs Ø Small molecule Bcl-xL/Bcl-2 binding inhibitors. USA Ø Agonists of SRC homology-2 containing protein tyrosine phoshpastase-1 and treatment methods using the same. USA. Provisional Ø Agonists of SRC homology-2 containing protein tyrosine phoshpastase-1 and treatment methods using the same (USA, Canada, Taiwan, New Zealand, China) Ø Aryl Amine Substituted Pyrimidine and Quinazoline and Their Use as Anticancer Drugs PUBLICATIONS (2011-) 1. Huang CY, Tai WT, Wu SY, Shih CT, Chen MH, Tsai MH, Kuo CW, Shiau CW, Hung MH, Chen KF. Dovitinib Acts As a Novel Radiosensitizer in Hepatocellular Carcinoma by Targeting SHP-1/STAT3 Signaling. Int J Radiat Oncol Biol Phys. 2016; in press 2. Tai WT, Hung MH, Chu PY, Chen YL, Chen LJ, Tsai MH, Chen MH, Shiau CW, Boo YP, Chen KF. SH2 domain-containing phosphatase 1 regulates pyruvate kinase M2 in hepatocellular carcinoma. Oncotarget. 2016, in press 3. Hung MH, Chen YL, Chu PY, Shih CT, Yu HC, Tai WT, Shiau CW, Chen KF. Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential. Oncogene. 2016; in press.

2 4. Tai WT, Chen YL, Chu PY, Chen LJ, Hung MH, Shiau CW, Huang JW, Tsai MH, Chen KF. Protein tyrosine phosphatase 1B dephosphorylates PITX1 and regulates p120rasgap in hepatocellular carcinoma. Hepatology. 2016; in press 5. Liu CY, Hu MH, Hsu CJ, Huang CT, Wang DS, Tsai WC, Chen YT, Lee CH, Chu PY, Hsu CC, Chen MH, Shiau CW, Tseng LM, Chen KF. Lapatinib inhibits CIP2A/PP2A/p-Akt signaling and induces apoptosis in triple negative breast cancer cells. Oncotarget, 2016; in press 6. Chao TI, Tai WT, Hung MH, Tsai MH, Chen MH, Chang MJ, Shiau CW, Chen KF. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy. Cancer letters. 2016; 371, Chang HC, Huang YT, Chen CS, Chen YW, Huang YT, Su JC, Teng LJ, Shiau CW, Chiu HC. In vitro and in vivo activity of a novel sorafenib derivative SC5005 against MRSA. J Antimicrob Chemother. 2016; 71, Hung MH, Wang CY, Chen YL, Chu PY, Hsiao YJ, Tai WT, Chao TT, Yu HC, Shiau CW*, Chen KF. SET antagonist enhances the chemosensitivity of non-small cell lung cancer cells by reactivating protein phosphatase 2A. Oncotarget. 2016; 7, Fan LC, Teng HW, Shiau CW, Tai WT, Hung MH, Yang SH, Jiang JK, Chen KF. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer. NEOPLASIA. 2015; 17: Chao TT, Wang CY, Chen YL, Lai CC, Chang FY, Tsai YT, Chao CH, Shiau CW, Huang YC, Yu CJ, Chen KF. Afatinib induces apoptosis in NSCLC without EGFR mutation through Elk-1- mediated suppression of CIP2A. Oncotarget, 2015; 6, Wang SH, Yeh SH, Shiau CW, Chen KF, Lin WH, Tsai TF, Teng YC, Chen DS, Chen PJ. Sorafenib Action in Hepatitis B Virus X-Activated Oncogenic Androgen Pathway in Liver through SHP-1. JNCI J Natl Cancer Inst, 2015; 107: djv Su TH, Shiau CW, Jao P, Liu CH, Liu CJ, Tai WT, Jeng YM, Yang HC, Tseng TC, Huang HP, Cheng HR, Chen PJ, Chen KF, Kao JH, Chen DS. Sorafenib and its derivative SC-1 exhibit antifibrotic effects through signal transducer and activator of transcription 3 inhibition. Proc Natl Acad Sci U S A. 2015; 112, Fan LC, Shiau CW, Tai WT, Hung MH, Chu PY, Hsieh FS, Lin H, Yu HC, Chen KF. SHP-1 is a negative regulator of epithelial-mesenchymal transition in hepatocellular carcinoma. Oncogene. 2015; 34: Su JC, Chang, JH, Huang JW, Chen P, Chen KF, Tseng PH, Shiau CW*. Copper obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma. Chemico-biological interaction. 2015; 228: Hung MH, Tai WT, Shiau CW, Chen KF. Downregulation of signal transducer and activator of transcription 3 by sorafenib: A novel mechanism for hepatocellular carcinoma therapy. World J Gastroenterol. 2014; 20: Su JC, Chiang HC, Tseng PH, Tai WT, Hsu CY, Li YS, Huang JW, Ko CH, Lin MW, Chu PY, Liu CY, Chen KF, Shiau CW*. RFX-1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells. Carcinogenesis. 2014;35: Tai WT, Chu PY, Shiau CW, Chen YL, Li YS, Hung MH, Chen LJ, Chen PL, Su JC, Lin PY, Yu HC, Chen KF. STAT3 Mediates Regorafenib-Induced Apoptosis in Hepatocellular Carcinoma. Clin Cancer Res. 2014;20: Liu CY, Hung MH, Wang DS, Chu PY, Su JC, Teng TH, Huang CT, Chao TT, Wang CY, Shiau CW, Tseng LM, Chen KF. Tamoxifen induces apoptosis through cancerous inhibitor of protein

3 phosphatase 2A dependent phospho-akt inactivation in estrogen-receptor negative human breast cancer cells. Breast Cancer Res. 2014;16:431 Chao TT, Wang CY, Lai CC, Chen YL, Tsai YT, Chen PT, Lin HI, Huang YC, Shiau CW*, Yu CJ, Chen KF. TD-19, an erlotinib derivative, induces EGFR wild-type NSCLC apoptosis through CIP2A-mediated pathway. J Pharmacol Exp Ther. 2014; 351:352-8 Yu HC, Hung MH, Chen YL, Chu PY, Wang CY, Chao TT, Liu CY, Shiau CW*, Chen KF*. Erlotinib derivative inhibits hepatocellular carcinoma by targeting CIP2A to reactivate protein phosphatase 2A. Cell Death and Disease. 2014; 31: e1359. Fan LC, Teng HW, Shiau CW, Lin H, Hung MH, Huang JW, Tai WT, Yu HC, Chen KF. SHP-1 is a target of regorafenib in colorectal cancer. Oncotarget. 2014; 30: Su JC, Tseng PH, Hsu CY, Tai WT, Huang JW, Ko CH, Lin MW, Liu CY, Chen KF, Shiau CW*. RFX1 dependent activation of SHP-1 induces autophagy by a novel obatoclax derivative in hepatocellular carcinoma cells Oncotarget. 2014; 15: Liu CY, Su JC, Ni MH, Tseng LM, Chu PY, Wang DS, Tai WT, Kao YP, Hung MH, Shiau CW*, Chen KF. Obatoclax analog SC-2001 inhibits STAT3 phosphorylation through enhancing SHP-1 expression and induces apoptosis in human breast cancer cells. Breast Cancer Res Treat. 2014; 146: Wang CY, Chao TT, Chang FY, Chen YL, Chen YT, Lin HI, Huang, YC, Shiau CW, Yu CJ, Chen KF. CIP2A mediates erlotinib-induced apoptosis in non-small cell lung cancer cells with no EGFR mutation. Lung cancer. 2014;85: Su JC, Tseng PH, Wu SH, Hsu CY, Tai WT, Li YS, Liu CY, Chen KF, Shiau CW*. SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma. Neoplasia. 2014; 16: Huang CY, Tai WT, Hsieh CY, Hsu WM, Lai YJ, Chen LJ, Shiau CW*, Chen KF. A sorafenib derivative and novel SHP-1 agonist, SC-59, acts synergistically with radiotherapy in hepatocellular carcinoma cells through inhibition of STAT3. Cancer Lett. 2014; 28: Tai WT, Shiau CW, Li YS, Chang CW, Huang JW, Hsueh TT, Chen KF. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. J Hepatol. 2014; 61: CY Wang, Chao TT, Tai WT, Chang FY, Su WP, Chen YL, Chen PT, Weng CY, Yuan A, Shiau CW, Yu CJ, Chen KF. Signal Transducer and Activator of Transcription 3 as Molecular Therapy for Non-small Cell Lung Cancer. Journal of Thoracic Oncology. 2014; 9: Tai WT, Shiau CW, Chen PJ, Chu P-Y, Huang HP, Liu CY, Huang JW, Cheng AL, Chen KF. Discovery of novel SHP-1 agonists from sorafenib for the treatment of HCC. Hepatology. 2014; 59: Tai WT, Shiau CW, Li YS, Chen YL, Chu PY, Huang JW, Hsu CY, Hsu YC, Chen PJ, Chen KF. SC-60, a dimer-based sorafenib derivative, shows a better anti-hcc effect than sorafenib in a preclinical HCC model. Mol Cancer Ther. 2014; 13: Hou DR, Huang AC, Shiau CW, Wang CY, Yu HC, Chen KF. Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition. Molecules 2013; 18: Liu CY, Tseng LM, Su, JC, Chang, KC, Chu, PY, Tai WT, Shiau CW*, Chen KF*. Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells. Breast Cancer Res : R68. Yu HC, Lin CS, Tai WT, Liu CY, Shiau CW, Chen KF. Nilotinib induces autophagy in hepatocellular carcinoma through AMPK activation. J Biol Chem. 2013; 288: Hunag CY, Lin CS, Tai WT, Hsieh CY, Shiau CW, Cheng AL, Chen KF. Sorafenib enhances

4 radiation-induced apoptosis in hepatocellular carcinoma by inhibiting STAT3. Int J Radiat Oncol Biol Phys. 2013;86: Yu HC, Hou DR, Liu CY, Lin CS, Shiau CW, Cheng AL, Chen KF. Cancerous inhibitor of protein phosphatase 2A mediates bortezomib-induced autophagy in hepatocellular carcinoma independent of proteasome. PLoS One. 2013; 8:e Tai WT, Shiau CW, Chen HL, Liu CY, Lin SL, Cheng AL, Chen PJ, Chen KF.Mcl-1 dependent activation of beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells. Cell Death and Disease. 2013; 4: e Yu HC, Chen HJ, Chang YL, Liu CY, Shiau CW, Cheng AL, Chen KF. Inhibition of CIP2A determines erlotinib-induced apoptosis in hepatocellular carcinoma. Biochem Pharmacol. 2013; 85: Liu CY, Shiau CW*, Ko, HY, Huang HP, Chen MH, Tzeng CH, Chen KF*. Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in acute leukemia cells. Haematologica. 2013; 98: Chen KF*, Chen HL, Shiau CW, Liu CY, Chu PY, Tai WT, Ichikawa K, Chen PJ, Cheng AL. Sorafenib and its derivative SC-49 sensitize hepatocellular carcinoma cells to CS-1008, a humanized anti-dr5 antibody. Br. J. Pharmacol. 2013;168: Wang CT, Lin CS, Shiau CW, Chu PY, Hsiao CC, Chiang YL, Tai WT, Chen KF. SC-1, a Sorafenib derivative, shows anti-tumor effects in osteogenic sarcoma cells. J. Orthopaedic Res. 2013; 31: Su JC, Chen KF, Chen WL, Liu CY, Huang JW, Tai WT, Chen PJ, Kim I, Shiau CW*. Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists. Eur J Med Chem. 2012; 56: Chen KF, Tai WT, Hsu CY, Huang JW, Liu CY, Chen PJ, Kim I, Shiau CW*. Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity. Eur J Med Chem. 2012; 55: Chen KF, Pao KC, Su JC, Chou YC, Liu CY, Chen HJ, Huang JW, Kim I, Shiau, CW*. Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity. Bioorg. Med. Chem. 2012; 20: Chen KF, Lin JP, Shiau CW, Tai WT, Liu CY, Yu HC, Chen PJ, Cheng AL. Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells. Biochem Pharmacol. 2012; 84: (Co-first author) 45. Tseng LM, Liu CY, Chang KC, Chu PY, Shiau CW, Chen KF. CIP2A is a target of bortezomib in human triple negative breast cancer cells. Breast Cancer Res. 2012; 14: R Chen KF, Su JC, Liu CY, Huang JW, Chen KC, Chen WL, Tai WT, Shiau CW*. A novel obatoclax derivative, SC-2001, induces apoptosis in hepatocellular carcinoma cells through SHP- 1-dependent STAT3 inactivation. Cancer Lett. 2012; 321: Tai WT, Cheng AL, Shiau CW, Liu CY, Ko CH, Lin MW, Chen PJ, Chen KF. Dovitinib induces apoptosis and overcomes sorafenib resistance in hepatocellular carcinoma through SHP-1- mediated inhibition of STAT3. Mol Cancer Ther. 2012; 11: Shih KC, Shiau CW, Chen TS, Ko CH, Lin CL, Lin CY, Hwang CS, Tang CY, Chen WR, Huang JW. Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors. Bioorg Med Chem Lett. 2011; 21: Chen KF, Tai WT, Huang JW, Hsu CY, Chen WL, Cheng AL, Chen PJ, Shiau CW*. Sorafenib derivatives induce apoptosis through inhibition of STAT3 independent of Raf. Eur J Med Chem. 2011; 46:

5 50. Tai WT, Cheng AL, Shiau CW, Huang HP, Huang JW, Chen PJ, Chen KF. Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma. J Hepatol. 2011; 55: