Faculty Profile, National Health Research Institutes, Taiwan

Faculty Profiles


Andrew Yueh Yueh, Ph.D.

Associate Investigator
Institute of Biotechnology and Pharmaceutical Research
andrewyueh@nhri.org.tw

EDUCATION

Ph.D., Biochemistry, New York University School of Medicine, USA

PROFESSIONAL EXPERIENCES

Associate Investigator, Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan

Assistant Investigator, Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan

Postdoctoral Research Fellow, Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, USA

RESEARCH INTERESTS

The long-term objective of our lab is to develop small-molecule inhibitors for clinical use to treat Hepatitis C virus (HCV) or Dengue virus (DENV) infected patients through teaming up with experts with expertise in chemistry, pharmacology, and pharmacokinetics. HCV, a member of Flaviviridae family, is an important cause of acute and chronic liver disease worldwide (3 % of population). DENV, the other member of Flaviviridae family, causes one of the most serious anthropod-borne viral illnesses. Cases have been reported in over 100 countries, with estimated 2.5 billion people living in areas where dengue is epidemic. Although tremendous efforts have been invested in HCV and DENV research, there is still no effective vaccine available against HCV or DENV infection at this time. There is an urgent need to develop a cure for those globally transmitted viruses.
To achieve the goals, our lab have been investigating the molecular mechanism of small molecules that interfere with HCV or DENV replication, as well as understanding how HCV or DENV interacts with host cells. We intend to search for novel small molecules that can block virus replication and identify the molecular mechanism(s) by which they interrupt the HCV or DENV life cycle. We also seek for cellular factors that interact with HCV or DENV viral proteins during virus life cycle. By knowing how small molecules interfere with virus replication and how cellular factors facilitate virus replication, better drugs may thus be developed to prevent HCV or DENV epidemics. This knowledge can also be applied to other flavivirus pathogens such as the West Nile virus, Japanese encephalitis virus, Yellow Fever virus, in order to develop a broad range of anti-flaviviral therapy.
Dr. Yueh’s lab also jointed several protein drug projects targeting at virus, cancer, and neuron diseases. Phage display library and other protein drug platforms have been developing in Dr. Yueh’s lab and will be applied to screen potential monoclonal antibodies for antiviral, anticancer, or neuron diseases drug development.

RESEARCH ACTIVITIES & ACCOMPLISHMENTS

Dr. Yueh has published several high impact research articles, e.g. Cell, Genes & Development, and EMBO Journal. Some of papers are highly cited. Since 2003, Dr. Yueh focused on antiviral drug research and developed several novel systems for anti-HCV and -DENV drug discovery. Several novel antiviral tools and platforms have been developed and published in the prestigious antiviral journals. In particular, a novel, potent HCV NS5A inhibitor, DBPR110, has been successfully developed as an anti-HCV drug candidate for clinical development. On April, 2013, technology transfer of DBPR110 was signed and transferred to pharmaceutical company for further clinical development. Dr. Yueh received “Outstanding Technology Transfer Award in 2013”by Ministry of Science and Technology regarding the technology transfer of DBPR110.

SELECTED PUBLICATIONS

1. Scanning Mutagenesis Studies Reveal Potential Intramolecular Interaction within the C-terminal Half of Dengue Virus NS2A Involved in Viral RNA Replication and Virus Assembly/Secretion. Wu RH, Tsai MH, Chao DY, and Yueh A. J. Virol. 2015 (Accepted)

2. A novel approach to propagate flavivirus infectious cDNA clones in bacteria by introducing tandem repeat sequences upstream of virus genome. Szu-Yuan Pu, Ren-Huang Wu, Ming-Han Tsai, Chi-Chen Yang, Chung-Ming Chang, and Andrew Yueh. 2014 Jul. Journal of General Virology, 95:1493-1503.

3. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Moghaddam E, Teoh BT, Sam SS, Lani R, Hassandarvish P, Chik Z, Yueh A, Abubakar S, Zandi K. 2014 Jun. Scientific reports, 4:5452.

4. A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease. Yang CC, Hu HS, Wu RH, Wu SH, Lee SJ, Jiaang WT, Chern JH, Huang ZS, Wu HN, Chang CM, and Yueh A*. 2014 Jan. Antimicrobial Agents & Chemotherapy, 58(1), 110-9.

5. Characterization of an efficient dengue virus replicon for development of assays of discovery of small molecules against dengue virus. Yang CC, Tsai MH, Hu HS, Pu SY, Wu RH, Wu SH, Lin HM, Song JS, Chao YS, Yueh A. Antiviral Res. 2013 Mar 13;98(2):228-241.

6. Resistance studies of a di-thiazol analogue, DBPR110, as a potential Hepatitis C virus NS5A inhibitor in replicon systems. Lin HM, Wang JC, Hu HS, Wu PS, Wang WH, Wu SY, Yang CC, Wu CP, Yeh TK, Hsu TA, Jiaang WT, Chao YS, Chern JH, Yueh A. Antimicrobial Agents & Chemotherapy. 2013 Feb; 57(2):723-33

7. Large ribosomal protein 4 increases efficiency of viral recoding sequences. Green L, Houck-Loomis B, Yueh A, Goff SP. J. Virol. 2012 Sep;86(17):8949-58.

8. Resistance Analysis and Characterization of a Thiazole Analogue, BP008, as a potent Hepatitis C Virus NS5A Inhibitor. Lin HM, Wang JC, Hu HS, Wu PS, Yang CC, Wu CP, Pu SY, Hsu TA, Jiaang WT, Chao YS, Chern JH, Yeh TK, Yueh A. Antimicrobial Agents & Chemotherapy, 2012 Jan; 56: 44-53.

9. Successful propagation of flavivirus infectious cDNAs by a novel method to reduce the cryptic bacterial promoter activity of virus genomes. Pu SY, Wu RH,Yang CC, Jao TM, Tsai MH, Wang JC, Lin HM, Chao YS, Yueh A. J. Virol. 2011 Mar; 85:2927-2941.

10. Novel dengue virus-specific NS2B/NS3 protease inhibitor, BP2109, discovered by a high-throughput screening assay. Yang CC, Hsieh YC, Lee SJ, Wu SH, Liao CL, Tsao CH, Chao YS, Chern JH, Wu CP, Yueh A. Antimicrobial Agents & Chemotherapy, 2011 Jan; 55(1):229-38.

11. Synthesis, activity, and pharmacokinetic properties of a series of conformationally-restricted thiourea analogues as novel hepatitis C virus inhibitors. Kang IJ, Wang LW, Yeh TK, Lee CC, Lee YC, Hsu SJ, Wu YS, Wang JC, Chao YS, Yueh A, Chern JH. Bioorg. Med. Chem 2010 Sep; 18: 6414-21.

12. Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors. Kang IJ, Wang LW, Hsu SJ, Lee CC, Lee YC, Wu YS, Yueh A, Wang JC, Hsu TA, Chao YS, Chern JH. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6063-8.

13. Design and synthesis of indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives as novel HCV inhibitors. Kang IJ, Wang LW, Hsu SJ, Lee CC, Lee YC, Wu YS, Hsu TA, Yueh A, Chao YS, Chern JH. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4134-8.

14. A novel dengue vaccine candidate that induces cross-neutralizing antibodies and memory immunity. Leng CH, Liu SJ, Tsai JP, Li YS, Chen MY, Liu HH, Lien SP, Yueh A, Hsiao KN, Lai LW, Liu FC, Chong P, Chen HW. Microbes Infect. 2009 Feb;11(2):288-95..

15. Structure-based drug design of a novel family of PPARgamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities. Lu IL, Huang CF, Peng YH, Lin YT, Hsieh HP, Chen CT, Lien TW, Lee HJ, Mahindroo N, Prakash E, Yueh A, Chen HY, Goparaju CM, Chen X, Liao CC, Chao YS, Hsu JT, Wu SY. J Med Chem. 2006 May 4;49(9):2703-12.

16. Interaction of Moloney murine leukemia virus matrix protein with IQGAP. Leung J, Yueh A, Appah FS Jr, Yuan B, de los Santos K, Goff SP. EMBO J. 2006 May 17;25(10):2155-66.

17. Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. Yueh A, Leung J, Bhattacharyya S, Perrone LA, de los Santos K, Pu SY, Goff SP. J Virol. 2006 Jan;80(1):342-52.

18. Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Orlova M, Yueh A, Leung J, Goff SP. Cell. 2003 Oct 31;115(3):319-31.

19. Phosphorylated serine residues and an arginine-rich domain of the moloney murine leukemia virus p12 protein are required for early events of viral infection. Yueh A, Goff SP. J Virol. 2003 Feb;77(3):1820-9.

20. Characterization of Moloney murine leukemia virus p12 mutants blocked during early events of infection. Yuan B, Fassati A, Yueh A, Goff SP. J Virol. 2002 Nov;76(21):10801-10.

21. Translation by ribosome shunting on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S rRNA. Yueh A, Schneider RJ. Genes Dev. 2000 Feb 15;14(4):414-21.

22. Selective translation initiation by ribosome jumping in adenovirus-infected and heat-shocked cells. Yueh A, Schneider RJ. Genes Dev. 1996 Jun 15;10(12):1557-67.

23. The carboxyl-terminal transactivation domain of human serum response factor contains DNA-activated protein kinase phosphorylation sites. Liu SH, Ma JT, Yueh AY, Lees-Miller SP, Anderson CW, Ng SY. J Biol Chem. 1993 Oct 5;268(28):21147-54.

24. Properties of malate dehydrogenase isolated from the marine diatom Cylindrotheca fusiformis. Lai YK and Yueh AY. 1989. Phytochemistry 28: 1579-1583.

25. Purification and molecular properties of malate dehydrogenase from the marine diatom Nitzschia alba. Yueh AY, Chung CS, Lai YK. Biochem J. 1989 Feb 15;258(1):221-8.

PATENT

1. Jyh-Haur Chern, Tsu-An Hsu, Iou-Jiun Kang, Li-Wen Wang, Chung-Chi Lee, Yen-Chun Lee, Yen-Shian Wu, Sheng-Ju Hsu, Yueh Andrew Yueh, Yu-Sheng Chao: Imidazolidinone and imidazolidinethione derivatives. National Health Research Institutes May, 10 2011: US 7939523B2