Department of Biochemistry and Molecular Biology

Chang Chung University Academic Capacity Ensemble

Research Directions and Laboratory Features

Redefining Mitochondrial Quality Control in Infection and Metabolic Disease

Our laboratory is driven by a central question: How does mitochondrial quality control shape human disease, and can it be therapeutically harnessed?

We investigate the dynamic regulation of autophagy, particularly mitophagy, as a fundamental mechanism governing cellular adaptation to stress, infection, and metabolic imbalance. By integrating molecular biology, advanced ultrastructural imaging, and translational disease models, we seek to uncover how mitochondrial turnover determines cellular fate across diverse pathological contexts.

(1) Virus–Host Interactions: Mitochondria at the Frontline

Viruses such as hepatitis C virus, dengue virus, and Zika virus reprogram host cells to support their replication. We explore how these pathogens manipulate autophagy and mitophagy to reshape mitochondrial function, evade innate immunity, and optimize viral propagation. By dissecting the molecular circuitry linking mitochondria to antiviral signaling and metabolic remodeling, we aim to uncover new antiviral intervention strategies.

(2) Mitochondrial Dysfunction in MASLD and Liver Cancer

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a rapidly growing global health crisis and a major precursor to hepatocellular carcinoma. We investigate how breakdown of mitochondrial quality control drives disease progression from steatosis to inflammation, fibrosis, and malignancy. Through clinically relevant animal models and cutting-edge ultrastructural imaging platforms, we define the dynamic remodeling of mitochondria during MASLD progression and identify actionable therapeutic targets.

(3) Therapeutic Activation of Mitophagy

Restoring mitochondrial turnover represents a promising strategy to combat metabolic and degenerative diseases. We employ high-throughput screening platforms and validated mitophagy reporter systems to discover small-molecule activators that enhance mitochondrial quality control. Our long-term vision is to translate these discoveries into safe, mechanism-based therapies for diseases driven by mitochondrial dysfunction.

Our Mission
To uncover the fundamental biology of mitochondrial quality control and translate mechanistic insight into innovative therapies for viral infection, metabolic liver disease, and beyond.

HONORS & ACADEMIC SERVICE

(I) Awards

• Recipient of the World’s Top 2% Scientists recognition, 2021.

• Outstanding Teacher Award, Chang Gung University, 2019.

• Recipient of the MOST Grant Award for Cultivation of Outstanding Young Scholars, Ministry of Science and Technology, supporting a three-year research project from 2016 to 2019.

• Recipient of the Career Development Grant (CDG), National Health Research Institutes (NHRI), supporting a four-year research project from 2014 to 2018.

• Incentive Award for Special Outstanding Talent in Colleges and Universities, Ministry of Science and Technology, 2015.

• Incentive Award for Special Outstanding Talent in Colleges and Universities, Ministry of Science and Technology, 2014.

• Outstanding Paper Award on Hepatitis C Virus Research, Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C., 2011.

• International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses, 2011.

• Research Article Competition Award for Postdoctoral Research Fellow, Institute of Biomedical Sciences, Academia Sinica, 2010.

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

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

• The President Award in Medicine and Technology, Tien-Te Lee Biomedical Foundation, Yung Shin Pharm. Ind. Co., Ltd., 2005.

• Postdoctoral Fellowship Award, National Health Research Institutes, 2005.

• Outstanding Student Award in Academics, National Taiwan University, 2004.

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

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

• Excellent Publication Award for Graduate Student, College of Medicine, National Taiwan University, 2003.
  
  
  
  (II) Academic Service

• Editorial Board Member, Scientific Reports (SCI), 2019–present.

• Editorial Board Member, Pathogens (SCI), 2019–present.

• Editorial Board Member, Frontiers in Microbiology (SCI), 2021–present.

• Reviewer Board Member, International Journal of Molecular Sciences (SCI), 2020–present.

• Reviewer Board Member, Cells (SCI), 2020–present.

• Reviewer Board Member, Microorganisms (SCI), 2020–present.

• Review Board Member, Wellcome Trust Investigator Grant Award 2020, United Kingdom, 2020.

• Organizing Committee Member and Section Chair, The 9th International Symposium on Autophagy, 2019.

• Peer reviewer for SCI journals, including Autophagy, Viruses, Apoptosis, Scientific Reports, Journal of Biomedical Science, Brain Research, Cell Cycle, Biomedical Journal, Cellular Microbiology, International Journal of Molecular Sciences, Cells, Cancers, Journal of Virology, PLOS ONE, and BioMed Research International.

• Peer reviewer for research proposals and funding grants, including proposals from the Ministry of Science and Technology (MOST), Chang Gung Memorial Hospital (CGMH), Taipei Veterans General Hospital (TVGH), and Cheng Hsin General Hospital (CHGH).
  
  
  
  
  (III) Membership

• The Chinese Society of Cell and Molecular Biology, 2001–present.

• The American Society for Cell Biology, 2004–present.

• International Conference on Hepatitis C Virus and Related Viruses, 2010–present.

• Gordon Research Conference: Autophagy, 2014–present.

• International Symposium of Autophagy, Asia, 2014–present.

• Keystone Symposia on Molecular and Cellular Biology, 2015–present.

• Cold Spring Harbor Conferences Asia, 2015–present.

Grant Support

Publication

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.
    
33. Lin, Y.J., Huang, L.T., Ke, P.Y., Chen, G.C. (2025, May). The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B. Journal of Cell Biology, 224(5), e202407014. (SCI, 48/204, CELL BIOLOGY).
    
34. Hsiao, Y.C., Chang, C.W., Yeh, C.T. and Ke, P.Y. (2024, Dec). Hepatitis C Virus NS5A Activates Mitophagy Through Cargo Receptor and Phagophore Formation. Pathogens, 13(12), 1139. (SCI, 74/163, MICROBIOLOGY). 
    
35. Ke, P.Y. (2024, Mar). Molecular Mechanism of Autophagosome-Lysosome Fusion in Mammalian Cells. Cells, 13(6), 500. (SCI, 59/204, CELL BIOLOGY).
36. Ke, P.Y. (2023, Mar). Crosstalk between Autophagy and RLR Signaling. Cells, 12(6), 956. (SCI, 59/204, CELL BIOLOGY)

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.