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Dr. Jim-Tong Horng

  1. Biographical Sketch

BIOGRAPHICAL SKETCH

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NAME: Horng, Jim-Tong

 

POSITION TITLE: Professor and Head of Biochemistry and Molecular Biology

EDUCATION/TRAINING  (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)

INSTITUTION AND LOCATION

DEGREE

(if applicable)

MM/YY

FIELD OF STUDY

National Taiwan University/College of Medicine

B.S.

06/1988

Medical Technology

National Taiwan University/College of Medicine

M.S.

01/1991

Biochemistry

University of Cambridge

Ph.D

12/1994

Biochemistry

University of California, San Francisco

Postdoctroal

06/1999

Biochemistry and Biophysics

         

A.    Personal Statement

I have been researching enterovirus (EV) A71 for many years, especially focusing on virus-host interaction and antiviral developments. My team has achieved important milestones such as the development of small molecules that successfully inhibit several RNA viruses, including EV71 and influenza viruses. I have published these findings in prestigious journals such as Antimicrob. Agents Chemother., J. Antimicrob. Chemother., J. Biol. Chem., J. Med. Chem., and J. Virol.

B.    Positions and Honors

Positions and Employment

1999-2007       Assistant Professor, Department of Biochemistry and Molecular Biology, Chang Gung University, Kweishan, Taoyuan, Taiwan

2007-2012       Associate Professor, Department of Biochemistry and Molecular Biology, Chang Gung University, Kweishan, Taoyuan, Taiwan

2012-               Professor, Department of Biochemistry and Molecular Biology, Chang Gung University, Kweishan, Taoyuan, Taiwan

 

Other Experience and Professional Memberships

1999-               Member, Taiwan Cell Biology Society

2012-               Member, American Society for Microbiology

2012-               Member, Taiwan Microbiology Society

2015-               Member, Taiwan Virology Society

2012-               Editorial Board Member, Antiviral Research

2016-               Editorial Board Member, Journal of Virological Methods

2018-               Editorial Board Member, Antimicrobial Agents and Chemotherapy

 

Honors

2010-2019       Talent Subsidy Incentives, Ministry of Science and Technology, Taiwan (科技部獎勵特殊優秀人才)

 

C.    Selected Peer-reviewed Publications

1. Horng, J. T., Behari, R., Burke, L. E., and Baker, A. (1995) Investigation of the energy requirement and targeting signal for the import of glycolate oxidase into glyoxysomes. European journal of biochemistry / FEBS 230, 157-163

2. Faundez, V., Horng, J. T., and Kelly, R. B. (1997) ADP ribosylation factor 1 is required for synaptic vesicle budding in PC12 cells. The Journal of cell biology 138, 505-515

3. Clift-O'Grady, L., Desnos, C., Lichtenstein, Y., Faundez, V., Horng, J. T., and Kelly, R. B. (1998) Reconstitution of synaptic vesicle biogenesis from PC12 cell membranes. Methods (San Diego, Calif 16, 150-159

4. Faundez#, V., Horng#, J. T., and Kelly, R. B. (1998) A function for the AP3 coat complex in synaptic vesicle formation from endosomes. Cell 93, 423-432

5. Pool, M. R., Lopez-Huertas, E., Horng, J. T., and Baker, A. (1998) NADPH is a specific inhibitor of protein import into glyoxysomes. Plant J 15, 1-14

6. Salem, N., Faundez, V., Horng, J. T., and Kelly, R. B. (1998) A v-SNARE participates in synaptic vesicle formation mediated by the AP3 adaptor complex. Nature neuroscience 1, 551-556

7. Horng*, J. T., and Tan, C. Y. (2004) Biochemical characterization of the coating mechanism of the endosomal donor compartment of synaptic vesicles. Neurochemical research 29, 1411-1416

8. Wong, W. R., Chen, Y. Y., Yang, S. M., Chen, Y. L., and Horng*, J. T. (2005) Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71. Life sciences 78, 82-90

9. Chang, Y. K., Horng, J. T., Huang, R. Z., and Lin, S. Y. (2006) Direct recovery of clotting factor IX from unclarified human plasma by expanded bed ion exchange chromatography. Biochemical Engineering Journal 30, 138-146

10. Chang, Y. K., Horng, J. T., Huang, R. Z., and Lin, S. Y. (2006) Direct capture of factor IX from unclarified human plasma by IMEBAC. Biochemical Engineering Journal 29, 12-22

11. Wei, J. R., Tsai, Y. H., Horng, Y. T., Soo, P. C., Hsieh, S. C., Hsueh, P. R., Horng, J. T., Williams, P., and Lai, H. C. (2006) A mobile quorum-sensing system in Serratia marcescens. Journal of bacteriology 188, 1518-1525

12. Tang, W. F., Yang, S. Y., Wu, B. W., Jheng, J. R., Chen, Y. L., Shih, C. H., Lin, K. H., Lai, H. C., Tang, P., and Horng*, J. T. (2007) Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication. The Journal of biological chemistry 282, 5888-5898

13. Tung, W. H., Sun, C. C., Hsieh, H. L., Wang, S. W., Horng, J. T., and Yang, C. M. (2007) EV71 induces VCAM-1 expression via PDGF receptor, PI3-K/Akt, p38 MAPK, JNK and NF-kappaB in vascular smooth muscle cells. Cellular signalling 19, 2127-2137

14. Wu, B. W., Pan, T. L., Leu, Y. L., Chang, Y. K., Tai, P. J., Lin, K. H., and Horng*, J. T. (2007) Antiviral effects of Salvia miltiorrhiza (Danshen) against enterovirus 71. The American journal of Chinese medicine 35, 153-168

15. Chen, Y. J., Zeng, S. J., Hsu, J. T., Horng, J. T., Yang, H. M., Shih, S. R., Chu, Y. T., and Wu, T. Y. (2008) Amantadine as a regulator of internal ribosome entry site. Acta pharmacologica Sinica 29, 1327-1333

16. Lin, J. Y., Li, M. L., Huang, P. N., Chien, K. Y., Horng, J. T., and Shih, S. R. (2008) Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5' untranslated region and participates in virus replication. The Journal of general virology 89, 2540-2549

17. Lin, T. Y., Liu, Y. C., Jheng, J. R., Tsai, H. P., Jan, J. T., Wong, W. R., and Horng*, J. T. (2009) Anti-enterovirus 71 activity screening of chinese herbs with anti-infection and inflammation activities. The American journal of Chinese medicine 37, 143-158

18. Jheng, J. R., Lau, K. S., Tang, W. F., Wu, M. S., and Horng*, J. T. (2010) Endoplasmic reticulum stress is induced and modulated by enterovirus 71. Cellular microbiology 12, 796-813

19. Shih#, S. R., Horng#, J. T., Poon, L. L., Chen, T. C., Yeh, J. Y., Hsieh, H. P., Tseng, S. N., Chiang, C., Li, W. L., Chao, Y. S., and Hsu, J. T. (2010) BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses. The Journal of antimicrobial chemotherapy 65, 63-71

20. Lin#, C. S., Horng#, J. T., Yang, C. H., Tsai, Y. H., Su, L. H., Wei, C. F., Chen, C. C., Hsieh, S. C., Lu, C. C., and Lai, H. C. (2010) RssAB-FlhDC-ShlBA as a major pathogenesis pathway in Serratia marcescens. Infection and immunity 78, 4870-4881

21. Yeh#, J. Y., Coumar#, M. S., Horng#, J. T., Shiao, H. Y., Kuo, F. M., Lee, H. L., Chen, I. C., Chang, C. W., Tang, W. F., Tseng, S. N., Chen, C. J., Shih, S. R., Hsu, J. T., Liao, C. C., Chao, Y. S., and Hsieh, H. P. (2010) Anti-influenza drug discovery: structure-activity relationship and mechanistic insight into novel angelicin derivatives. Journal of medicinal chemistry 53, 1519-1533

22. Shih, S. R., Chu, T. Y., Reddy, G. R., Tseng, S. N., Chen, H. L., Tang, W. F., Wu, M. S., Yeh, J. Y., Chao, Y. S., Hsu, J. T., Hsieh, H. P., and Horng*, J. T. (2010) Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. Journal of biomedical science 17, 13

23. Wu, M. S., Yen, H. R., Chang, C. W., Peng, T. Y., Hsieh, C. F., Chen, C. J., Lin, T. Y., and Horng*, J. T. (2011) Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. Journal of ethnopharmacology 134, 614-623

24. Hsu, J. T., Yeh, J. Y., Lin, T. J., Li, M. L., Wu, M. S., Hsieh, C. F., Chou, Y. C., Tang, W. F., Lau, K. S., Hung, H. C., Fang, M. Y., Ko, S., Hsieh, H. P., and Horng*, J. T. (2012) Identification of BPR3P0128 as an Inhibitor of Cap-Snatching Activities of Influenza Virus. Antimicrob Agents Chemother 56, 647-657

25. Chang, C. W., Leu, Y. L., and Horng*, J. T. (2012) Daphne Genkwa sieb. Et zucc. Water-soluble extracts act on enterovirus 71 by inhibiting viral entry. Viruses 4, 539-556

26. Hsieh, C. F., Lo, C. W., Liu, C. H., Lin, S., Yen, H. R., Lin, T. Y., and Horng*, J. T. (2012) Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus. Journal of ethnopharmacology 143, 57-67

27. Hung, H. C., Liu, C. L., Hsu, J. T., Horng, J. T., Fang, M. Y., Wu, S. Y., Ueng, S. H., Wang, M. Y., Yaw, C. W., and Hou, M. H. (2012) Development of an anti-influenza drug screening assay targeting nucleoproteins with tryptophan fluorescence quenching. Analytical chemistry 84, 6391-6399

28. Jheng, J. R., Lin, C. Y., Horng*, J. T., and Lau, K. S. (2012) Inhibition of enterovirus 71 entry by transcription factor XBP1. Biochemical and biophysical research communications 420, 882-887

29. Liu, C. H., Horng, J. T., Chang, J. S., Hsieh, C. F., Tseng, Y. C., and Lin, S. (2012) Localization and force analysis at the single virus particle level using atomic force microscopy. Biochemical and biophysical research communications 417, 109-115

30. Yeh, J. Y., Coumar, M. S., Shiao, H. Y., Lin, T. J., Lee, Y. C., Hung, H. C., Ko, S., Kuo, F. M., Fang, M. Y., Huang, Y. L., Hsu, J. T., Yeh, T. K., Shih, S. R., Chao, Y. S., Horng*, J. T., and Hsieh*, H. P. (2012) Anti-influenza Drug Discovery: Identification of an Orally Bioavailable Quinoline Derivative through Activity- and Property-Guided Lead Optimization. ChemMedChem 7, 1546-1550

31. Hsieh, C. F., Yen, H. R., Liu, C. H., Lin, S., and Horng*, J. T. (2012) Ching-fang-pai-tu-san inhibits the release of influenza virus. Journal of ethnopharmacology 144, 533-544

32. Mok, C. K., Chen, G. W., Shih, K. C., Gong, Y. N., Lin, S. J., Horng, J. T., Hsu, J. T., Chen, C. J., and Shih, S. R. (2013) Evolutionarily conserved residues at an oligomerization interface of the influenza A virus neuraminidase are essential for viral survival. Virology 447, 32-44

33. Hsu, K. C., Hung, H. C., Horng, J. T., Fang, M. Y., Chang, C. Y., Li, L. T., Chen, I. J., Chen, Y. C., Chou, D. L., Chang, C. W., Hsieh, H. P., Yang, J. M., and Hsu, J. T. (2013) Parallel screening of wild-type and drug-resistant targets for anti-resistance neuraminidase inhibitors. PloS one 8, e56704

34. Chen, L. L., Kung, Y. A., Weng, K. F., Lin, J. Y., Horng, J. T., and Shih, S. R. (2013) Enterovirus 71 infection cleaves a negative regulator for viral internal ribosomal entry site-driven translation. Journal of virology 87, 3828-3838

35. Ho, J. Y., Chang, H. W., Lin, C. F., Liu, C. J., Hsieh, C. F., and Horng*, J. T. (2014) Characterization of the anti-influenza activity of the Chinese herbal plant Paeonia lactiflora. Viruses 6, 1861-1875

36. Wu, M. J., Ke, P. Y., Hsu, J. T., Yeh, C. T., and Horng*, J. T. (2014) Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction. Cellular microbiology 16, 1603-1618

37. Jheng, J. R., Ho, J. Y., and Horng*, J. T. (2014) ER stress, autophagy, and RNA viruses. Frontiers in microbiology 5, 388

38. Wu, M. J., Ke, P. Y., and Horng*, J. T. (2014) RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication. Biochemical and biophysical research communications 454, 19-24

39. Weng, K. F., Hung, C. T., Hsieh, P. T., Li, M. L., Chen, G. W., Kung, Y. A., Huang, P. N., Kuo, R. L., Chen, L. L., Lin, J. Y., Wang, R. Y., Chen, S. J., Tang, P., Horng, J. T., Huang, H. I., Wang, J. R., Ojcius, D. M., Brewer, G., and Shih, S. R. (2014) A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic acids research 42, 12789-12805

40. Velu, A. B., Chen, G. W., Hsieh, P. T., Horng, J. T., Hsu, J. T., Hsieh, H. P., Chen, T. C., Weng, K. F., and Shih, S. R. (2014) BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71. Antiviral research 112, 18-25

41. Tang, W. F., Huang, R. T., Chien, K. Y., Huang, J. Y., Lau, K. S., Jheng, J. R., Chiu, C. H., Wu, T. Y., Chen, C. Y., and Horng*, J. T. (2016) Host MicroRNA miR-197 Plays a Negative Regulatory Role in the Enterovirus 71 Infectious Cycle by Targeting the RAN Protein. Journal of virology 90, 1424-1438

42. Jheng, J. R., Wang, S. C., Jheng, C. R., and Horng*, J. T. (2016) Enterovirus 71 induces dsRNA/PKR-dependent cytoplasmic redistribution of GRP78/BiP to promote viral replication. Emerg Microbes Infect 5, e23

43. Ho, J. Y., Chern, J. H., Hsieh, C. F., Liu, S. T., Liu, C. J., Wang, Y. S., Kuo, T. W., Hsu, S. J., Yeh, T. K., Shih, S. R., Hsieh, P. W., Chiu, C. H., and Horng*, J. T. (2016) In vitro and in vivo studies of a potent capsid-binding inhibitor of enterovirus 71. The Journal of antimicrobial chemotherapy 71, 1922-1932

44. Lin, T. J., Lin, C. F., Chiu, C. H., Lee, M. C., and Horng*, J. T. (2016) Inhibition of endosomal fusion activity of influenza virus by Rheum tanguticum (da-huang). Sci Rep 6, 27768

45. Hsieh, C. F., Chen, Y. L., Lin, C. F., Ho, J. Y., Huang, C. H., Chiu, C. H., Hsieh, P. W., and Horng*, J. T. (2016) An extract from Taxodium distichum targets hemagglutinin- and neuraminidase-related activities of influenza virus in vitro. Sci Rep 6, 36015

46. Chang, Y. H., Lau, K. S., Kuo, R. L., and Horng*, J. T. (2017) dsRNA Binding Domain of PKR Is Proteolytically Released by Enterovirus A71 to Facilitate Viral Replication. Front Cell Infect Microbiol 7, 284

47. Chen, S. G., Cheng, M. L., Chen, K. H., Horng, J. T., Liu, C. C., Wang, S. M., Sakurai, H., Leu, Y. L., Wang, S. D., and Ho, H. Y. (2017) Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo. Sci Rep 7, 935

48. Jheng, J. R., Lau, K. S., Lan, Y. W., and Horng, J. T. (2018) A novel role of ER stress signal transducer ATF6 in regulating enterovirus A71 viral protein stability. Journal of biomedical science 25, 9

49. Huang, C. G., Lee, L. A., Wu, Y. C., Hsiao, M. J., Horng, J. T., Kuo, R. L., Huang, C. H., Lin, Y. C., Tsao, K. C., Chen, M. C., Chen, T. C., and Shih, S. R. (2018) A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients' responses to H7N9 infection. Oncotarget 9, 14492-14508

50. Sethy, B., Hsieh, C. F., Yeh, C., Horng, J. T., and Hsieh, P. W. (2018) Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents. Future Med Chem 10, 1333-1347

51. Tang, W. F., Huang, R. T., Chien, K. Y., Tang, P., and Horng*, J. T. (2018) Large-Scale Proteomic Identification of Targets of Cellular miR-197 Downregulated by Enterovirus A71. Journal of proteome research

52. Sethy, B., Hsieh, C. F., Lin, T. J., Hu, P. Y., Chen, Y. L., Lin, C. Y., Tseng, S. N., Horng*, J. T., and Hsieh*, P. W. (2019) Design, Synthesis, and Biological Evaluation of Itaconic Acid Derivatives as Potential Anti-Influenza Agents. Journal of medicinal chemistry 62, 2390-2403

 

D.    Research Support

Ongoing Research Support

MOST106-2320-B-182-004-MY3          Horng (PI)      08/01/2017-07/31/2020

Inhibitory mechanistic study of enterovirus 71 entry by a natural compound isolated from Kudingcha leaves (Ilex kaushue).

To identify the detailed inhibitory mechanism of CGU-V007 and examine its in vivo anti-EV-A71 activity in mouse models.

Role: PI

 

Completed Research Support

MOST 105-2311-B-182 -001 -               Horng (PI)       08/01/2016-07/31/2017

in vivo efficacy evaluation and mechanistic study of broad spectrum inhibitors against enteroviruses

The goal of this study is to identify the antiviral mechanisms of the active imidazolidinone compounds and to test the in vivo activities of these compounds in animal models.

Role: PI

 

MOST 105-2632-B-182 -002 -               Shin-Ru Shih (PI)   08/01/2015-07/31/2018

Pathogenesis study of enterovirus infection using an authentic bioengineered human enteric system
The goal of this this study is to establish a bioengineered enteric system for enterovirus infection, which would provide valuable information to understand the pathogenesis of virus infection through gut entry - how enterovirus expand and traffic in host, and pave a way to develop effective therapeutic strategies.

Role: Co-Investigator

 

MOST 103-2325-B-182-009-        Chia-Ho Shih (PI)   08/01/2010-10/31/2013

In vitro and in vivo studies of enterovirus 71 virus-host interactions

The goal of the integrated project is to investigate the virus host interactions during EV71 infection.

Role: Co-Investigator

 

MOST101-2325-B-182-016-     Horng (PI)   05/01/2012-04/30/2015

Mechanistic study and in vivo efficacy test of BPR3P – a novel enterovirus 71 agent that may inhibit viral replication complex formation

The goal of this project is to find out compounds which against enterovirus 71 (EV71) infections.

Role: PI

 

Speech

  1. Celebration Series Academic Activities of College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 2015, Invited speech: Drug development against RNA viruses
  2. Hong Kong City University, Hong Kong 2016, Invited speech: Development of anti-enterovirus 71 agents that target the ER stress signaling pathway and capsid protein VP1.
  3. 6th International Symposium on Infectious Disease and Signal Transduction, National Cheng Kung University, 2016, invited speech: Identification of natural-based inhibitors targeting enterovirus 71 VP1-receptor interaction.
  4. Lessons Learned: 20th Anniversary of Enterovirus A71 Epidemic of 1998 in Taiwan (2018), Invited speech: Anti-enterovirus A71 inhibitors: current status and future perspectives.
  5. Keynote speaker invited by International Conference on Biology and Medical Sciences (ICBMS 2019) Asia Pacific Society for Biology and Medical Sciences       
  6. International Flu virus Symposium for celebrating IPM 47th Anniversary, March 6, 2019, invited speech: Identification of itaconic acid derivatives as potential anti-influenza agents.
  7. International Symposium on emerging infectious diseases-enterovirus and vector-borne diseases (2019), National Cheng Kung University, Invited speech: Development of anti-enterovirus A71 agents that target capsid protein VP1.

 

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