91猫先生

长庚大学學術能量集萃

研究方向及研究室特色

探讨感染与代谢疾病中的粒线体品质管控分子机制

本实验室以一个核心科学问题作為研究主题：
粒线体品质管控如何参与人类疾病的发生与进展？我们是否能将其转化為可行的治疗策略？

我们致力於探讨自噬作用，尤其是粒线体自噬（mitophagy）的动态调控机制，并将其视為细胞因应压力、感染与代谢失衡之关键基础机制。透过整合分子生物学、先进超微结构影像技术以及转译医学疾病模型，我们旨在阐明粒线体周转如何在不同病理情境下决定细胞命运与功能状态。

(一) 病毒与宿主交互作用：粒线体自噬作為前线调控枢纽

如C型肝炎病毒、登革病毒与兹卡病毒等病原体，会重塑宿主细胞内在环境以支持其复製与存活。我们聚焦於解析这些病毒如何操控自噬与粒线体自噬，藉以改变粒线体功能、逃避免疫监控并优化病毒增殖。透过剖析粒线体在抗病毒讯号传递与代谢重塑中的分子调控网络，我们期望揭示病毒感染致病机制的新层面，并开发崭新的抗病毒介入策略。

(二) MASLD与肝癌中的粒线体功能与粒线体自噬的失衡

代谢功能异常相关脂肪性肝病（MASLD）已成為全球迅速上升的重大公共卫生挑战，亦是肝细胞癌的重要前驱疾病。我们致力於探讨粒线体品质管控崩解如何驱动疾病从脂肪堆积进展至发炎、纤维化乃至恶性转化。透过具临床相关性的动物模型以及尖端超微结构影像平台，我们描绘MASLD进程中粒线体的动态重塑过程，并鑑定具有治疗潜力的关键分子标的。

(叁) 粒线体自噬活化於临床治疗上的应用性

恢復粒线体周转与品质管控，被视為对抗代谢性与退化性疾病的关键策略。本实验室运用高通量筛选平台与可靠的粒线体自噬分析系统，寻找能促进粒线体品质管控的小分子活化剂。我们的长期愿景，是将这些基础发现转化為安全且具机制导向的治疗方法，用以改善由粒线体功能失衡所驱动的人类疾病。

我们的使命

阐明粒线体品质管控的基础生物学机制，并将其转化為创新的治疗策略，以应对病毒感染、代谢性肝病及其他相关疾病。

獲獎 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)

最近五年所发表论文

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)