柯博元 / Po-Yuan Ke
職稱: 副教授
現職: 長庚大學
電話: 03-2118800#5115 ( 實驗室位置: 第一醫學大樓 6 樓 B 區 腫瘤共同研究室 )
學歷: 台灣大學博士
專長領域: 細胞生物學、細胞自噬暨胞器品質管控、肝臟疾病、分子病毒學、高階細胞影像學
長庚大學學術能量集萃
https://pure.lib.cgu.edu.tw/zh/persons/po-yuan-ke-2/研究方向及研究室特色
探討感染與代謝疾病中的粒線體品質管控分子機制
本實驗室以一個核心科學問題作為研究主題:
粒線體品質管控如何參與人類疾病的發生與進展?我們是否能將其轉化為可行的治療策略?
我們致力於探討自噬作用,尤其是粒線體自噬(mitophagy)的動態調控機制,並將其視為細胞因應壓力、感染與代謝失衡之關鍵基礎機制。透過整合分子生物學、先進超微結構影像技術以及轉譯醫學疾病模型,我們旨在闡明粒線體周轉如何在不同病理情境下決定細胞命運與功能狀態。
(一) 病毒與宿主交互作用:粒線體自噬作為前線調控樞紐
如C型肝炎病毒、登革病毒與茲卡病毒等病原體,會重塑宿主細胞內在環境以支持其複製與存活。我們聚焦於解析這些病毒如何操控自噬與粒線體自噬,藉以改變粒線體功能、逃避免疫監控並優化病毒增殖。透過剖析粒線體在抗病毒訊號傳遞與代謝重塑中的分子調控網絡,我們期望揭示病毒感染致病機制的新層面,並開發嶄新的抗病毒介入策略。
(二) MASLD與肝癌中的粒線體功能與粒線體自噬的失衡
代謝功能異常相關脂肪性肝病(MASLD)已成為全球迅速上升的重大公共衛生挑戰,亦是肝細胞癌的重要前驅疾病。我們致力於探討粒線體品質管控崩解如何驅動疾病從脂肪堆積進展至發炎、纖維化乃至惡性轉化。透過具臨床相關性的動物模型以及尖端超微結構影像平台,我們描繪MASLD進程中粒線體的動態重塑過程,並鑑定具有治療潛力的關鍵分子標的。
(三) 粒線體自噬活化於臨床治療上的應用性
恢復粒線體周轉與品質管控,被視為對抗代謝性與退化性疾病的關鍵策略。本實驗室運用高通量篩選平台與可靠的粒線體自噬分析系統,尋找能促進粒線體品質管控的小分子活化劑。我們的長期願景,是將這些基礎發現轉化為安全且具機制導向的治療方法,用以改善由粒線體功能失衡所驅動的人類疾病。
我們的使命
闡明粒線體品質管控的基礎生物學機制,並將其轉化為創新的治療策略,以應對病毒感染、代謝性肝病及其他相關疾病。
獲獎 Honors & Awards
- World′s Top 2% Scientists (2021~2025)
- Field-Weighted Citation Impact: 5.16 (2021~2025)
- Chang Gung University Teaching Excellence Award (2019)
- Ministry of Science and Technology Grant Award for Cultivation of Outstanding Young Scholars Award (2015~2018)
- National Health Research Institute Career Development Grant Award (2014~2017)
- Ministry of Science and Technology Special Outstanding Talent Award (2015、2014)
最近五年所發表論文
- 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.
- 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.
- Ke PY* and Yeh CT, Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy, Pathogens, Nov, 2024, 13(11): 980.
- 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.
- Ke PY*, Regulation of Autophagosome-Lysosome Fusion by Human Viral Infections, Pathogens, Mar, 2024, 13(3): 266.
- Ke PY*, Molecular Mechanism of Autophagosome-Lysosome Fusion in Mammalian Cells, Cells, Mar, 2024, 13(6): 500.
- Ke PY*, Crosstalk between Autophagy and RLR Signaling, Cells, Mar, 2023, 12(6): 956.
- 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.
- Ke PY*, Chang CW, Hsiao YC, Baicalein Activates Parkin-Dependent Mitophagy through NDP52 and OPTN, Cells, Mar, 2022, 11(7): 1132.
- Ke PY*, Autophagy and antiviral defense, IUBMB Life, Apr, 2022, 74(4): 317-338.
- 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.
- 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
- 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)
- Unraveling the physiological significance of the Kennedy pathway-regulated mitophagy in metabolic dysfunction-associated fatty liver disease (NSTC 113-2311-B-182-001)
- Unraveling the physiological role of mitophagy in flaviviruses-host interactions (MOST 109-2320-B-182-010-MY3)
- Study on the functional role of human DEAD-box helicase 3-mediated lipophagy in flaviviruses-host interactions (MOST 108-2320-B-182-011)
- Study on the functional role of selective autophagy in the degradation of viral entry (co)receptors (MOST 105-2628-B-182-001-MY3)
- Deciphering HCV-host interactions by identifying substrates of viral-induced selective autophagy (NHRI-EX103 ~106-10322SC)
- Functional study of autophagic response in suppression of type I interferon response (MOST 102-2320-B-182-037-MY3)
- Molecular mechanism of selective autophagy in regulation of RLR antiviral signaling (MOST 101-2320-B-182-043)