91猫先生

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 & Awards

1. World′s Top 2% Scientists (2021~2025)
2. Field-Weighted Citation Impact: 5.16 (2021~2025)
3. 91猫先生 Teaching Excellence Award (2019)
4. Ministry of Science and Technology Grant Award for Cultivation of Outstanding Young Scholars Award (2015~2018)
5. National Health Research Institute Career Development Grant Award (2014~2017)
6. Ministry of Science and Technology Special Outstanding Talent Award (2015、2014)

Publication

1. Lin YJ, Huang LT, Ke PY, Chen GC, The deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B, Journal of Cell Biology, May, 2025, 224(5): e202407014.
2. Hsiao YC, Chang CW, Yeh CT and Ke PY*, Hepatitis C Virus NS5A Activates Mitophagy Through Cargo Receptor and Phagophore Formation, Pathogens, Dec, 2024, 13(12): 1139.
3. Ke PY* and Yeh CT, Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy, Pathogens, Nov, 2024, 13(11): 980.
4. Wu CC, Tam EH, Shih YY, Lin YR, Hsueh PC, Shen HY, Woung CH, Wang LT, Tsai JC, Lin SJ, Chang CR, Ke PY, and Kuo RL, Exploration of influenza A virus PA protein-associated cellular proteins discloses its impact on mitochondrial function, Virus Research, Jul, 2024, 345: 199387.
5. Ke PY*, Regulation of Autophagosome-Lysosome Fusion by Human Viral Infections, Pathogens, Mar, 2024, 13(3): 266.
6. Ke PY*, Molecular Mechanism of Autophagosome-Lysosome Fusion in Mammalian Cells, Cells, Mar, 2024, 13(6): 500. 
7. Ke PY*, Crosstalk between Autophagy and RLR Signaling, Cells, Mar, 2023, 12(6): 956.
8. 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.
9. Ke PY*, Chang CW, Hsiao YC, Baicalein Activates Parkin-Dependent Mitophagy through NDP52 and OPTN, Cells, Mar, 2022, 11(7): 1132.
10. Ke PY*, Autophagy and antiviral defense, IUBMB Life, Apr, 2022, 74(4): 317-338.
11. 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.
12. 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.

Research Grants & Support

1. Study on the molecular mechanism of lactate metabolism-regulated mitophagy and its physiological significance in metabolic dysfunction–associated steatotic liver disease (NSTC 114-2320-B-182-015)
2. Unraveling the physiological significance of the Kennedy pathway-regulated mitophagy in metabolic dysfunction-associated fatty liver disease (NSTC 113-2311-B-182-001)
3. Unraveling the physiological role of mitophagy in flaviviruses-host interactions (MOST 109-2320-B-182-010-MY3)
4. Study on the functional role of human DEAD-box helicase 3-mediated lipophagy in flaviviruses-host interactions (MOST 108-2320-B-182-011)
5. Study on the functional role of selective autophagy in the degradation of viral entry (co)receptors (MOST 105-2628-B-182-001-MY3)
6. Deciphering HCV-host interactions by identifying substrates of viral-induced selective autophagy (NHRI-EX103 ~106-10322SC)
7. Functional study of autophagic response in suppression of type I interferon response (MOST 102-2320-B-182-037-MY3)
8. Molecular mechanism of selective autophagy in regulation of RLR antiviral signaling (MOST 101-2320-B-182-043)