Dr. Po-Yuan Ke
Appointment: Assistant Professor
Lab：Stress Response & Molecular Mechanism Laboratory
University/Nation：National Taiwan University, College of Medicine /Taiwan
Postdoctoral fellow: ; Ph.D. student: 1 ; Master student: 2 ; Res. Assistant: 1 ; undergraduate:
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.
Ke, P.Y. and Chen, S,S-L.
World Journal of Gastroenterology 20: 5773-5793, 2014
Wu MJ, Ke P.Y., Horng J.T.
Biochem Biophys Res Commun. 454: 19-24, 2014
Wu, M.J., Ke, P.Y., Hsu, J.T., Yeh, C.T., and Horng, J.T.
Cellular Microbiology 16: 1603-1618, 2014.
Tseng, Y.H., Ke, P.Y., Liao, C.J., Wu, S.M., Chi, H.C., Tsai, C.Y., Chen, C.Y., Lin, Y. H., and Lin, K.H.
Autophagy 10: 20-31, 2014.
5. Active RNA replication of hepatitis C virus downregulates CD81 expression.
Ke, P.Y. and Chen, S.S-L.
PLoS ONE 8: e54866, 2013.
6. An occult hepatitis B-derived hepatoma cell line carrying persistent nuclear viral DNA and permissive for exogenous hepatitis B virus infection.
Lin, C.L., Chien, R.N., Lin, S.M., Ke, P.Y., Lin, C.C., and Yeh, C.T.
PLoS ONE 8: e65456, 2013.
Ke, P.Y. and Chen, S.S.L.
Viruses 4: 2251-2290, 2012.
8. Guidelines for the use and interpretation of assays for monitoring autophagy.
Daniel J. Klionsky et al., and Ke, P.Y., and 1269 authors.
Autophagy 8; 4:1-100, 2012.
9. Autophagy: a new guardian of HCV against innate immune response.
Ke, P.Y. and Chen, S.S-L.
Autophagy 7: 533-535, 2011.
10. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro.
Ke, P.Y. and Chen, S.S-L.
Journal of Clinical Investigation 121: 37-56, 2011.
u SciBX editorial board recommended
u Journal of Hepatology editorial board recommended
11. Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane go41 protein as a distinct determinant for viral infection.
Chen, S.S-L., Yang, P., Ke, P.Y., Li, H.F., Chan, W.E., Chang, DK., Chuang C.K., Tsai, Y., and Huang, S.C.
Journal of Virology 83: 870-883, 2009.
12. Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding.
Ke, P.Y., Hu, C.M., Chang, Y.C., and Chang, Z.F.
FASEB Journal 21: 1276-1284, 2007.
13. Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability.
Ke, P.Y., Kuo, Y.Y., Hu, C.M., and Chang, Z.F.
Genes & Development 19: 1920-1933, 2005.
14. Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site.
Li, C.L., Lu, C.Y., Ke, P.Y., and Chang, Z.F.
Biochem. Biophys. Res. Commun. 313: 587-593, 2004.
15. Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway.
Ke, P.Y. and Chang, Z.F.
Molecular and Cellular Biology 24: 514-526, 2004.
16. Degradation of human thymidine kinase is dependent on serine-13 phosphorylation: involvement of the SCF-mediated pathway.
Ke, P.Y., Yang, C.C., Tsai, I.C., and Chang, Z.F.
Biochemical Journal 370: 265-273, 2003.
1. Suppression of innate antiviral immunity after hepatitis C virus infection: role of the unfolded protein response and autophagy.
Chen, S.S-L. and Ke, P.Y.
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, P.Y. and Chen, S.S-L.
Recent Research Developments in Virology, Vol. 8. (ISBN: 978-81-7895-563-6). Kerala, India: Transworld Research Network. Apr, 2012.
Awards & Honors:
l 2003 Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine
l 2003 International Conference Travel Award, The Chinese Society of Cell and Molecular Biology
l 2004 Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology
l 2004 Outstanding Student Award in Academy, National Taiwan University
l 2005 Post-doctoral Fellowship Award, National Health Research Institute
l 2005 The President Award in Medicine and Technology, Tien-Te Lee Biomedical Foundation, Yung Shin PHARM. IND. CO., LTD
l 2009 Poster Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology
l 2010 Poster Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology
l 2010 Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica
l 2010 International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses
l 2011 Outstanding Paper Award on hepatitis C virus research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C.
l 2014 科技部補助大專校院獎勵特殊優秀人才
l 2015 科技部補助大專校院獎勵特殊優秀人才
Peer Reviewer: Autophagy; Viruses; Apoptosis
1. Functional study of autophagic response in suppression of type I interferon response (NSC102-2320-B-182-037-MY3, 102/8/1~105/7/30)
2. Deciphering HCV-host interactions by identifying substrates of viral-induced selective autophagy (NHRI-EX103-10322SC, 103/1/1~106/12/30)
3. Study on the Functional Role of Selective Autophagy in Hepatitis C Virus Life Cycle (CMRPD1D0021, 103/1/1~105/12/30)