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生化暨分子生物學科

生化暨分子生物學科
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簡昆鎰老師

柯博元

職稱： 副教授

現職： 長庚大學

信箱： pyke0324@mail.cgu.edu.tw

電話： 5115

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

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。

榮譽及學術服務 HONORS & ACADEMIC SERVICE

(I) AWARDS

  1. 全球前 2% 頂尖科學家(World’s Top 2% Scientists) 獲獎人(2021).
  2. 長庚大學108年度優良教師獎(2019)
  3. 科技部傑出學者養成計畫 (MOST grant award for cultivation of outstanding young scholars，支持105~108三年期研究計畫)獲獎人
  4. 國家衛生研究院 (NHRI)103年度Career Development Grant (CDG，支持103-107四年期研究計畫)獲獎人
  5. 科技部補助大專校院獎勵特殊優秀人才(2015)
  6. 科技部補助大專校院獎勵特殊優秀人才(2014)
  7. Outstanding Paper Award on Hepatitis C Virus Research of Liver Disease Prevention & Treatment Research Foundation, Taiwan, R.O.C. (2011)
  8. International Travel Fellowship and Invited Oral Presentation Award, 17th International Meeting on Hepatitis C Virus and Related Viruses (2011)
  9. Research Article Competition Award for Post-Doctoral Research Fellow, Institution of Biomedical Sciences, Academia Sinica (2010)
  10. Poster Outstanding Award, 18th Symposium on Recent Advances in Cellular and Molecular Biology (2010)
  11. Poster Outstanding Award, 17th Symposium on Recent Advances in Cellular and Molecular Biology (2009)
  12. The President Award in Medicine and Technology, Tien-Te Lee Biomedical
  13. Foundation, Yung Shin PHARM. IND. CO., LTD (2005)
  14. Post-doctoral Fellowship Award, National Health Research Institute (2005)
  15. Outstanding Student Award in Academy, National Taiwan University (2004)
  16. Dr. Chien-Tien Hsu Award in 12th Symposium on Recent Advances in Cellular and Molecular Biology (2004)
  17. International Conference Travel Award, The Chinese Society of Cell and Molecular Biology (2003)
  18. Excellent Publication Award for Graduate Student, National Taiwan University, College of Medicine (2003)

 

(II) ACADEMIC SERVICE

  1. The editorial board member of Scientific Reports (SCI) (2019~)
  2. The editorial board member of Pathogens (SCI) (2019~)
  3. The editorial board member of Frontier in Microbiology (SCI) (2021~)
  4. The reviewer board member of International Journal of Molecular Sciences (SCI) (2020~)
  5. The reviewer board member of Cells (SCI) (2020~)
  6. The reviewer board member of Microorganisms (SCI) (2020~)
  7. The review board member of Welcome Trust Investigator Grant Award 2020 (UK) (2020)
  8. The 9th International Symposium on Autophagy (2019) Organization Committee and Section Chair
  9. The peer reviewer of research journals (SCI): Autophagy; Viruses; Apoptosis; Scientific Reports; Journal of Biomedical Sciences; Brain Research; Cell cycle; Biomedical Journal; Cellular Microbiology; IJMS; Cells; Cancers; Journal of Virology; PLoS ONE; BioMed Research International
  10. The peer reviewer of research proposal and funding grant: Ministry of science and technology (MOST) research proposal; Chang Gung Memorial Hospital (CGMH) research proposal; Taipei Veterans General Hospital (TVGH) research proposal; Cheng Hsin General Hospital (CHGH) research proposal

 

(III) MEMBERSHIP

  1. The Chinese Society of Cell and Molecular Biology (2001-present)
  2. The American Society of Cell Biology (2004-present)
  3. The International Conference of Hepatitis C Virus and Related Virus (2010-present)
  4. The Gordon Research Conference: Autophagy (2014-present)
  5. The International Symposium of Autophagy, Asia (2014-present)
  6. Keystone Symposium in Molecular and Cellular Biology (2015-present)
  7. Cold Spring Harbor Conferences, Asia (2015-present) 

GRNAT SUPPORT

  1. 探索專一性粒腺體自噬作用在黃熱病毒與宿主交互作用之生理角色(MOST 109-2320-B-182-010-MY3) (2020/8/1~2023/7/31) (NT$ 5,760,000), 補助機構: 科技部
  2. 探討人類DEAD-box helicase 3所導引之細胞自噬脂質分解作用於黃熱病毒感染與宿主細胞交互作用之生理功能性角色(MOST 108-2320-B-182-011) (2019/8/1~2020/7/31) (NT$ 1,309,000), 補助機構: 科技部
  3. 專一細胞自噬反應引發之選擇性分解作用於調控病毒接受體分子與病毒感染力交互作用之功能性分析(MOST 105-2628-B-182-001-MY3) (2016/8/1~2019/7/31) (NT$ 4,295,000), 補助機構: 科技部
  4. 探索C型肝炎病毒引發之專一選擇性細胞自噬作用降解的分子以研究病毒與宿主細胞之交互作用, (NHRI-EX103 ~106-10322SC) (2014/1/1~2017/12/31) (NT$ 7,000,000), 補助機構: 國家衛生研究院
  5. 細胞自噬分解作用於負向調控第一型干擾素反應之功能性分析, (MOST 102-2320-B-182-037-MY3) (2013/8/1~2016/7/31) (NT$ 6,528,000), 補助機構: 科技部
  6. 探討selective autophagy調控RLR抗病毒訊息傳遞之分子機轉, (MOST 101-2320-B-182-043) (2012/8/1~2013/7/31) (NT$ 1,050,000), 補助機構: 科技部

發表論文

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.