Po-Yuan Ke

Appointment: Associate Professor

Lab：Stress Response & Molecular Mechanism Laboratory

Education: Ph.D.

University/Nation：National Taiwan University, College of Medicine /Taiwan

Tel: 03-211-8800#5115

E-mail: pyke0324@mail.cgu.edu.tw

Research website:

Laboratory personnel:

Postdoctoral fellow:  ; Ph.D. student: 1 ; Master student: 1 ; Res. Assistant: 1 ; undergraduate: 2022/08/04  

Research interests:：

Autophagy is a stress-responsive process (such as nutrient starvation) that catabolizes cytoplasmic components to maintain the cellular homeostasis. Autophagy initiates with the rearrangement of membranous structures and coordinates with the cascades of signal transduction. Then, the cytoplasmic components are initially sequestered by a membrane-constituted structure, named isolation membrane (IM) or phagophore, which then expands and the two ends meet to form a double-membraned vesicle termed autophagosome. Finally, autophagosome fuses with a lysosome, forming the autolysosome where the engulfed cytoplasmic contents are degraded. The autophagic machinery has long been known to act as a stress response that promotes cell survival, mainly by regulating the energy availability and maintaining the organelle quality. Nevertheless, emerging evidence indicates that autophagy may function in regulating multiple defensive responses to microbial infections, such as degrading the invading microorganisms including bacteria, viruses, and protozoa, activating the host immune response against these infecting pathogens, or suppressing host innate immunity to help replication of the invading virus. On the other hand, autophagy is also activated by virus infection to promote the viral life cycle. Therefore, study on how autophagy is regulated is important will promote our understanding of how cell counteracts stresses. In the future, we set up three goals as the follows,

1. Several viral infections have shown to activate autophagy. Our recent study demonstrates that HCV induces autophagic process via unfolded protein response (UPR) (Journal of Clinical Investigation). Our results reveal that HCV-induced autophagy suppresses innate antiviral immunity to promote viral RNA replication in the infected cells. However, how autophagy promotes HCV escape from immune surveillance is largely unknown. To answer this question, we will employ molecular biology, proteomics, and transmission electron microscopy to investigate how autophagy represses antiviral immunity by altering signal transduction and protein trafficking of innate immunity-associated molecules.

2. Virus infection often activates autophagy via UPR. Current studies indicate that virus replication within the endoplasmic reticulum-associated membranous structure may trigger stress response to induce UPR, thus activate autophagy. However, the detailed molecular mechanism underlying how UPR promotes autophagy is thus far poorly understood. In the future, we will utilize the siRNA interference technology and transcriptional genomics to investigate the functional role of UPR in the activation of autophagic process. The regulation of gene transcription, protein synthesis, and post-translational modifications of proteins involved in this process will be analyzed.

3. Autophagy plays a promoting and/or repressive role in tumorigenesis. So far, the related studies regarding the function of autophagy in the progress of tumor formation is still controversial. In the future, our study will focus on investigation of the physiological significance of autophagy in the pathogenesis of liver cancer.

Current position:

Assistant Professor

Department of Biochemistry & Molecular Biology and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taiwan, Republic of China

Liver Research Center, Chang Gung Memorial Hospital, LinKuo, Taiwan, Republic of China

Contact information:

Tumor Research Laboratory

The 6th Floor, 1st Medicine Building

No. 259 Wen-Hwa 1st Road, Kwei-Shan Tao-Yuan,Taiwan33302, R.O.C

Tel: +886-3-2118800 ext 5115

Education:

Ph.D.    Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taiwan, Republic of China

Relevant experience:

Postdoctoral Research Fellow in Institute of Biomedical Sciences, Academia Sinica (2007/3~ 2012/2)

Postdoctoral Research Fellow in Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University (2005/7~2005/11)

Fields of specialty:

Protein degradation, Autophagy, Selective autophagy, Hepatitis C virus, and Liver-associated diseases, Molecular virology

HONORS & ACADEMIC SERVICE

(I) AWARDS

1. World’s Top 2% Scientist 2020 (2021).
2. Chang Gung University Teaching Excellence Award (2019)
3. Ministry of Science and Technology Grant Award for Cultivation of Outstanding Young Scholars (2015~2018)
4. National Health Research Institute Career Development Grant Award (2014~2017)
5. Ministry of Science and Technology Special Outstanding Talent Award (2015)
6. Ministry of Science and Technology Special Outstanding Talent Award (2014)
7. Outstanding Paper Award on Hepatitis C Virus Research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C. (2011)
8. International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses (2011)
9. Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica (2010)
10. Poster Outstanding Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology (2010)
11. Poster Outstanding Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology (2009)
12. The President Award in Medicine and Technology, Tien-Te Lee Biomedical
13. Foundation, Yung Shin PHARM. IND. CO., LTD (2005)
14. Post-doctoral Fellowship Award, National Health Research Institute (2005)
15. Outstanding Student Award in Academy, National Taiwan University (2004)
16. Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology (2004)
17. International Conference Travel Award, The Chinese Society of Cell and Molecular Biology (2003)
18. Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine (2003)

(II) ACADEMIC SERVICE

1. The editorial board member of Scientific Reports (SCI) (2019~)
2. The editorial board member of Pathogens (SCI) (2019~)
3. The editorial board member of Frontier in Microbiology (SCI) (2021~)
4. The reviewer board member of International Journal of Molecular Sciences (SCI) (2020~)
5. The reviewer board member of Cells (SCI) (2020~)
6. The reviewer board member of Microorganisms (SCI) (2020~)
7. The review board member of Welcome Trust Investigator Grant Award 2020 (UK) (2020)
8. The 9th International Symposium on Autophagy (2019) Organization Committee and Section Chair
9. The peer reviewer of research journals (SCI): Autophagy; Viruses; Apoptosis; Scientific Reports; Journal of Biomedical Sciences; Brain Research; Cell cycle; Biomedical Journal; Cellular Microbiology; IJMS; Cells; Cancers; Journal of Virology; PLoS ONE; BioMed Research International
10. The peer reviewer of research proposal and funding grant: Ministry of science and technology (MOST) research proposal; Chang Gung Memorial Hospital (CGMH) research proposal; Taipei Veterans General Hospital (TVGH) research proposal; Cheng Hsin General Hospital (CHGH) research proposal

(III) MEMBERSHIP

1. The Chinese Society of Cell and Molecular Biology (2001-present)
2. The American Society of Cell Biology (2004-present)
3. The International Conference of Hepatitis C Virus and Related Virus (2010-present)
4. The Gordon Research Conference: Autophagy (2014-present)
5. The International Symposium of Autophagy, Asia (2014-present)
6. Keystone Symposium in Molecular and Cellular Biology (2015-present)
7. Cold Spring Harbor Conferences, Asia (2015-present) 

GRNAT SUPPORT

1. Unraveling the physiological role of mitophagy in flaviviruses-host interactions (MOST 109-2320-B-182-010-MY3) (2020/8/1~2023/7/31) NTS$ 5,760,000, supported by Ministry of Science and Technology, Taiwan, ROC
2. Study on the functional role of human DEAD-box helicase 3-mediated lipophagy in flaviviruses-host interactions (MOST 108-2320-B-182-011) (2019/8/1~2020/7/31) (NT$ 1,309,000), supported by Ministry of Science and Technology, Taiwan, ROC
3. Study on the functional role of selective autophagy in the degradation of viral entry (co)receptors (MOST 105-2628-B-182-001-MY3) (2016/8/1~2019/7/31) (NT$ 4,295,000), supported by Ministry of Science and Technology, Taiwan, ROC
4. Deciphering HCV-host interactions by identifying substrates of viral-induced selective autophagy (NHRI-EX103 ~106-10322SC) (2014/1/1~2017/12/31) (7,000,000), supported by National Health Research Institute, Taiwan, ROC
5. Functional study of autophagic response in suppression of type I interferon response (MOST 102-2320-B-182-037-MY3) (2013/8/1~2016/7/31) (NT$ 6,528,000), supported by Ministry of Science and Technology, Taiwan, ROC
6. Molecular mechanism of selective autophagy in regulation of RLR antiviral signaling (MOST 101-2320-B-182-043) (2012/8/1~2013/7/31) (NT$1,050,000), supported by Ministry of Science and Technology, Taiwan, ROC

Publications:

Journal articles:

1. Liou LB, Wang TY, Liu IJ, Wu HC, Ke PY, Fang YF, Chen YF, α-2,6-sialic acid/IgG anti-dsDNA ratios correlate with human lupus disease activity and possible mechanisms: A pilot study, LUPUS, Jul, 2022, 31(8): 927-938.
2. Ke PY, Chang CW, Hsiao YC, Baicalein Activates Parkin-Dependent Mitophagy through NDP52 and OPTN, Cells, Mar, 2022, 11(7): 1132.
3. Ke PY, Autophagy and antiviral defense, IUBMB Life, Apr, 2022, 74(4): 317-338.
4. Peng HH, Wu CY, Hsiao YC, Martel J, Ke PY, Chiu CY, Liau JC, Chang IT, Su YH, Ko YF, Young JD, Ojcius DM, Ganoderma lucidum stimulates autophagy-dependent longevity pathways in Caenorhabditis elegans and human cells, Aging-us, May, 2021, 13(10): 13474-13495.
5. Klionsky DJ et al, and Ke PY, and 2290 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition), Autophagy, Jan, 2021, 17(1): 1-382.
6. Lin CL, Chien RN, Chu YD, Liang KH, Huang YH, Ke PY, Lin KH, Lin YH, Yeh CT, Hepatitis B virus X gene mutants emerge during antiviral therapy and increase cccDNA levels to compensate for replication suppression, Hepatology International, Dec, 2020, 14(6): 973-984.
7. Ke PY, Mitophagy in the Pathogenesis of Liver Diseases, Cells, Mar, 2020, 9(4): 831.
8. Martel J, Ojcius DM, Ko YF, Ke PY, Wu CY, Peng HH, Young JD, Hormetic Effects of Phytochemicals on Health and Longevity, Trends in Endocrinology & Metabolism, Jun, 2019, 30(6): 335-346.
9. Lai MW, Chu YD, Lin CL, Chien RN, Yeh TS, Pan TL, Ke PY, Lin KH, Yeh CT, Is there a sex difference in postoperative prognosis of hepatocellular carcinoma?, BMC Cancer, Mar, 2019, 19(1): 250.
10. Ke PY, Diverse Functions of Autophagy in Liver Physiology and Liver Diseases, International Journal of Molecular Sciences, Jan, 2019, 20(2): 300.
11. Ke PY, The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions. International Journal of Molecular Sciences, Dec, 2018, 19(12): 3940.
12. Lai JH, Wang MY, Huang CY, Wu CH, Hung LF, Yang CY, Ke PY, Luo SF, Liu SJ, Ho LJ, Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells, EMBO Reports, Aug, 2018, 19(8): e46182.
13. Liang KH, Ahn SH, Lee HW, Huang YH, Chien RN, Hu TH, Lin KH, Yeh CS, Hsu CW, Lin CL, Pan TL, Ke PY, Chang ML, Yeh CT, A novel risk score for hepatocellular carcinoma in Asian cirrhotic patients: a multicentre prospective cohort study, Scientific Reports, Jun, 2018, 8(1): 8608.
14. Lin CL, Chien RN, Liang KH, Ke PY, Huang YH, Yeh CT, Intrahepatic HCV RNA Level and Genotype 1 Independently Associate with Hepatic Reticulon 3 Expression, Anticancer Research, Jun, 2017, 37(6): 2885-2891.
15. Ke PY, Horning cell self-digestion: Autophagy wins the 2016 Nobel Prize in Physiology or Medicine, Biomedical Journal, Feb, 2017, 40(1): 5-8.
16. Huang YH, Liang KH, Chien RN, Hu TH, Lin KH, Hsu CW, Lin CL, Pan TL, Ke PY, Yeh CT, A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients. Scientific Reports, Mar, 2017, 7(1): 523.
17. Klionsky DJ et al, and Ke PY, and 1296 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd Edition), Autophagy, Jan, 2016, 12(1): 1-222.
18. Wu MJ, Ke PY, Horng JT, RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication, Biochemical and Biophysical Research Communications, Nov, 2014, 454(1): 19-24.
19. Wu MJ, Ke PY, Hsu JT, Yeh CT, and Horng JT, Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction, Cellular Microbiology, Nov, 2014, 16(11): 1603-1618.
20. Ke PY, Chen SS, Autophagy in hepatitis C virus-host interactions: Potential roles and therapeutic targets for liver-associated diseases, World Journal of Gastroenterology, May, 2014, 20(19): 5773-5793.
21. Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, Chen CY, Lin Y H, and Lin KH, Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism, Autophagy, Jan, 2014, 10(1): 20-31.
22. Ke PY, Chen SS, Active RNA replication of hepatitis C virus downregulates CD81 expression, PLoS ONE, Jan, 2013, 8(5): e54866.
23. Ke PY, Chen SS, Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases, Viruses, Oct, 2012, 4(10): 2251-2290.
24. Klionsky DJ et al, and Ke PY, and 1296 authors, Guidelines for the use and interpretation of assays for monitoring autophagy (2nd Edition), Autophagy, Apr, 2012, 8(4):445-544.
25. Ke PY, Chen SS, Autophagy: a novel guardian of HCV against innate immune response, Autophagy, May, 2011, 7(5): 533-535.
26. Ke PY, Chen SS, Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro, Journal of Clinical Investigation, Jan, 2011, 121(1): 37-56.
27. Chen SS, Yang P, Ke PY, Li HF, Chan WE, Chang DK, Chuang CK, Tsai Y, Huang SC, Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection, Journal of Virology, Jan, 2009, 83(2): 870-883.
28. Ke PY, Hu CM, Chang YC, Chang ZF, Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding, FASEB Journal, Apr, 2007, 21(4): 1276-1284.
29. Ke PY, Kuo YY, Hu CM, Chang ZF, Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability, Genes & Development, Aug, 2005, 19(16): 1920-1933.
30. Ke PY, Chang ZF, Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway, Molecular and Cellular Biology, Jan, 2004, 24(2): 514-526.
31. Li CL, Lu CY, Ke PY, Chang ZF, Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site, Biochemical and Biophysical Research Communications, Jan, 2004, 313(3): 587-593.
32. Ke PY, Yang CC, Tsai IC, Chang ZF, Degradation of human thymidine kinase is dependent on serine-13 phosphorylation: involvement of the SCF-mediated pathway, Biochemical Journal, Feb, 2003, 370(Pt 1): 265-273.

BOOK CHAPTERS

1. Chen SS and Ke PY, Suppression of innate antiviral immunity after hepatitis C virus infection: role of the unfolded protein response and autophagy. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging: Volume 2 - Role in General Diseases Chapter 9. (ISBN: 9780124058774). Amsterdam, Netherlands: ELSEVIER. Dec, 2013.
2. Ke PY and Chen SS, Multifaceted Roles of Autophagy in the Life Cycle of Flaviviridae. Recent Research Developments in Virology, Vol. 8. Chapter 1. (ISBN: 978-81-7895-563-6). Kerala, India: Transworld Research Network. Apr, 2012.