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Graduate Institute of Biomedical Sciences

:::

柯博元

Po-Yuan Ke

Appointment: Assistant Professor

LabStress Response & Molecular Mechanism Laboratory

Education: Ph.D.

University/NationNational Taiwan University, College of Medicine /Taiwan

Tel: 03-211-8800#5115

E-mail: pyke0324@mail.cgu.edu.tw

Laboratory personnel:

Postdoctoral fellow:  ; Ph.D. student: 1 ; Master student: 1 ; Res. Assistant: 1 ; undergraduate:2019/2/25

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 investigatehow 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

Division of Allergy, Immunology, and Rheumatology, Chang Gung Memorial Hospital, Linkou, 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

Cell phone: +886-975260923

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                                                       

Peer reviewer:

1. Journal reviewer:

Autophagy; Viruses; Apoptosis; Scientific Reports; Journal of Biomedical Sciences; Brain Research; Cell cycle; PLoS ONE; International Journal of Molecular Sciences; Biomedical Journal

2. Proposal reviewer:

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

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-present0                                 

Publications:

Journal articles:

1. Diverse Functions of Autophagy in Liver Physiology and Liver Diseases. Ke PY Int J Mol Sci. 13;20(2), 2019

2. The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions. Ke PY Int J Mol Sci. 7;19(12), 2018

3. Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells. Lai JH, Wang MY, Huang CY, Wu CH, Hung LF, Yang CY, Ke PY, Luo SF, Liu SJ, Ho LJ EMBO Reports 19: e46182, 2018

4. A novel risk score for hepatocellular carcinoma in Asian cirrhotic patients: a multicentre prospective cohort study. 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 Scientific Reports 8: 8608, 2018

5. Intrahepatic HCV RNA Level and Genotype 1 Independently Associate with Hepatic Reticulon 3 Expression. Lin CL, Chien RN, Liang KH, Ke PY, Huang YH, Yeh CT Anticancer Research 37: 2885-2891, 2017

6. Horning cell self-digestion: Autophagy wins the 2016 Nobel Prize in Physiology or Medicine. Ke PY Biomedical Journal 40: 5-8, 2017

7. A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients. Huang YH, Liang KH, Chien RN, Hu TH, Lin KH, Hsu CW, Lin CL, Pan TL, Ke PY, Yeh CT. Scientific Reports 7: 523, 2017

8. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd Edition) Daniel J. Klionsky et al., and Ke PY, and 1269 authors. Autophagy 12; 1-222, 2016.

9. Autophagy in hepatitis C virus-host interactions: Potential roles and therapeutic targets for liver-associated diseases. Ke PY and Chen SSL World Journal of Gastroenterology 20: 5773-5793, 2014

10. RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication. Wu MJ, Ke PY, Horng JT Biochemical Biophysical Research Communications 454: 19-24, 2014

11. Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction. Wu MJ, Ke, PY, Hsu JT, Yeh CT, and Horng JT Cellular Microbiology 16: 1603-1618, 2014.

12. Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism. Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, Chen CY, Lin Y H, and Lin KH Autophagy 10: 20-31, 2014.

13. Active RNA replication of hepatitis C virus downregulates CD81 expression. Ke PY and Chen SS PLoS ONE 8: e54866, 2013.

14. An occult hepatitis B-derived hepatoma cell line carrying persistent nuclear viral DNA and permissive for exogenous hepatitis B virus infection. Lin CL, Chien RN, Lin SM, Ke PY, Lin CC, and Yeh CT PLoS ONE 8: e65456, 2013. 

15. Hepatitis C virus and cellular stress response: implications to molecular pathogenesis of liver diseases. Ke PY and Chen SS Viruses 4: 2251-2290, 2012.

16. Guidelines for the use and interpretation of assays for monitoring autophagy (2nd Edition). Daniel J. Klionsky et al., and Ke PY, and 1269 authors. Autophagy 8:1-100, 2012.

17. Autophagy: a new guardian of HCV against innate immune response. Ke PY and Chen SS Autophagy 7: 533-535, 2011.

18. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. Ke PY and Chen SS Journal of Clinical Investigation 121: 37-56, 2011.

19. Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane go41 protein as a distinct determinant for viral infection.   Chen SS, Yang P, Ke PY, Li HF, Chan WE, Chang DK, Chuang CK, Tsai Y, and Huang SC Journal of Virology 83: 870-883, 2009.

20. Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding. Ke PY, Hu CM, Chang YC, and Chang ZF FASEB Journal 21: 1276-1284, 2007. 

21. Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability. Ke PY, Kuo YY, Hu CM, and Chang ZF Genes & Development 19: 1920-1933, 2005.

22. Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site. Li CL, Lu CY, Ke PY, and Chang ZF Biochemical Biophysical Research Communications 313: 587-593, 2004.

23. Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway. Ke PY and Chang ZF Molecular and Cellular Biology 24: 514-526, 2004.

24. Degradation of human thymidine kinase is dependent on serine-13 phosphorylation: involvement of the SCF-mediated pathway. Ke PY, Yang CC, Tsai IC, and Chang ZF Biochemical Journal 370: 265-273, 2003.

Books:

1. Suppression of innate antiviral immunity after hepatitis C virus infection: role of the unfolded protein response and autophagy. Chen SS and Ke PY  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. Multifaceted Roles of Autophagy in the Life Cycle of Flaviviridae. Ke PY and Chen SS Research Developments in Virology, Vol. 8. (ISBN: 978-81-7895-563-6). Kerala, India: Transworld Research Network. Apr, 2012.

Presentations:

1. Exclusion of homologous superinfection of hepatitis C virus by autophagic degradations of viral entry (co)receptors. Chang CW and Ke PY Poster presentation: Keystone Symposia on Molecular and Cellular Biology: Selective Autophagy, Kyoto, Japan (2018)

2. Deregulation of Wnt-beta-catenin signaling by hepatitis C virus infection-induced autophagic degradations of Dishevelled family proteins. Chang CW and Ke PY Poster presentation: The 8th International Symposium on Autophagy, Nara, Japan (2017)

3. Degradation of hepatitis C virus entry (co)receptors by selective autophagy. Chang CW and Ke PY Poster presentation: Cold Spring Harbor Asia: Ubiquitin Family, Autophagy & Disease, Suzhou, China (2016)

4. Activation of selective autophagy by hepatitis C virus infection. Chang CW and Ke PY Poster presentation: The 7th International Symposium on Autophagy, Huangshan, China (2015)

5. Degradation of cargo receptors by hepatitis C virus infection. Chang CW and Ke PY Poster presentation: Gordon Conference: Autophagy in Stress, Development & Disease, Lucca, Italy (2014)

6. Emergence of a host cellular restriction mechanism on propagation of hepatitis C virus. Ke PY and Chen SS. Poster presentation: The 18th International Meeting on Hepatitis C Virus and Related Viruses, Seattle, USA (2011)

7. A role of autophagy in emergence of a host cellular restriction mechanism on propagation of hepatitis C virus. Ke PY and Chen SS Poster presentation: The 19th symposium on recent advances in cellular and molecular biology, Taiwan, R.O.C. (2011)

8. Autophagic control of hepatitis C virus RNA replication through repression of the innate immune response. Ke PY and Chen SS Oral presentation: The 17th International Meeting on Hepatitis C virus and Related Viruses, Yokohama, Japan (2010)

9. Autophagy controls hepatitis C virus RNA replication through suppression antiviral innate immunity. Ke PY and Chen SS Poster presentation: The 18th symposium on recent advances in cellular and molecular biology, Taiwan, R.O.C. (2010)

10. Stable growth of hepatitis C virus in cell culture: a novel model for study of host-virus interactions and screening of anti-viral agents. Ke PY, Shih C, and Chen SS Poster presentation: The 17th symposium on recent advances in cellular and molecular biology, Taiwan, R.O.C. (2009)

11. Stable growth of hepatitis C virus in cell culture: a novel model for study of host-virus interactions and screening of anti-viral agents. Ke PY, Shih C, and Chen SS Poster presentation: The 17th symposium on recent advances in cellular and molecular biology, Taiwan, R.O.C. (2009)

12. Stable growth of hepatitis C virus: a new cell model for study of host-virus interaction. Ke PY and Chen SS Poster presentation: The 48th annual meeting of American Society of Cell Biology, San Francisco, USA (2008)

13. Proteomic and Functional analysis of Hepatitis C virus NS5A protein. Ke PY, Shih C., and Chen SS Poster presentation: The 8th conference on biomedical sciences, National Defense Medical Center, Taiwan, R.O.C. (2008)

14. Stabilization of human thymidine kinase 1 and thymidylate kinase by substrate binding. Ke PY and Chang ZF Poster presentation: The 4th symposium on signal transduction, National Health research Institute, Taiwan, R.O.C. (2005)

15. Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway. Ke PY and Chang ZF Oral presentation: The 12th symposium on recent advances in cellular and molecular biology, Taiwan, R.O.C. (2004)

16. Cell Cycle-Regulated Degradation of Human Thymidine Kinase is Dependent on the APC/CCDH1- Mediated Proteolytic Pathway in Mammalian Cells. Ke PY and Chang ZF Poster presentation: The 43th annual meeting of American Society of Cell Biology, San Francisco, USA (2003)

Awards & Honors:

1. 國家衛生研究院 (NHRI)103年度Career Development Grant (CDG,支持103-107四年期研究計畫)獲獎人。

2. 科技部傑出學者養成計畫 (MOST grant award for cultivation of outstanding young scholars,支持105~108三年期研究計畫)獲獎人。

3. 2015  科技部補助大專校院獎勵特殊優秀人才

4. 2014  科技部補助大專校院獎勵特殊優秀人才

5. 2011  Outstanding Paper Award on hepatitis C virus research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C.

6. 2010  International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses

7. 2010  Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica

8. 2010  Poster Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology

9. 2009  Poster Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology

10. 2005  The President Award in Medicine and Technology, Tien-Te Lee Biomedical Foundation, Yung Shin PHARM. IND. CO., LTD

11. 2005  Post-doctoral Fellowship Award, National Health Research Institute

12. 2004  Outstanding Student Award in Academy, National Taiwan University

13. 2004  Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology

14. 2003  International Conference Travel Award, The Chinese Society of Cell and Molecular Biology

15. 2003  Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine

Grants & Funding:

1. 專一細胞自噬反應引發之選擇性分解作用於調控病毒接受體分子與病毒感染力交互作用之功能性分析, 補助機構: 科技部, 2016/8/1~2019/7/31 (MOST 105-2628-B-182-001-MY3)

2. 細胞自噬分解作用於負向調控第一型干擾素反應之功能性分析, 補助機構: 科技部, 2013/8/1~2016/7/31 (MOST 102-2320-B-182-037-MY3)

3. 探討selective autophagy調控RLR抗病毒訊息傳遞之分子機轉, 補助機構: 科技部, 2012/8/1~2013/7/31 (MOST 101-2320-B-182-043)

4. 探索C型肝炎病毒引發之專一選擇性細胞自噬作用降解的分子以研究病毒與宿主細胞之交互作用, 補助機構: 國家衛生研究院, 2014/1/1~2017/12/31 (NHRI-EX103~106-10322SC)

 

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