中央研究院化學研究所－人員

化學生物學，這個令人振奮的領域，使我們能夠使用化學來觀察、研究，甚至和操控生物體內的生化反應。我們團隊的重點是開發創新的囊泡設計，例如表面裝飾有各種功能性多肽和智能生物分子的微脂體(Liposome)和脂質奈米粒子（lipid nanoparticle, LNPs）。這些奈米載具可以在對外部刺激（人工信號）或內部疾病信號做出反應的情況下，向活細胞傳遞藥物或重要的生物大分子(如遺傳物質核酸，或催化物質如酶)。我們還致力於設計和合成生物螢光回報傳感器，可以為了解活細胞的作用，以提供有價值的見解。我們的最終目標是獲得在生物體內實驗測試，和更好地理解生物化學反應的能力，以期在未來，能修復活細胞或組織。通過我們的研究，我們希望在對化學生物學和奈米醫學領域做出重大貢獻。
我們的研究團隊正在追求幾個化學生物學領域，特別關注開發對未來活細胞和組織進行修復的創新解決方案。我們關注的主要領域包括：

• 利用表面附着智能分子（如肽）的微脂體(Liposome)和脂質奈米粒子（lipid nanoparticle, LNPs），有效傳遞大分子到活細胞和組織，這對於細胞或組織修復至關重要。
• 研究細胞蛋白質化學修飾，創造對於活細胞和組織修復至關重要的新型蛋白質功能，這對於細胞或組織修復至關重要。
• 研究肽與細胞膜相互作用，這是發展智能脂質納米載體進行靶向藥物傳遞的基礎。
• 開發能提供有關活細胞和組織化學環境有價值信息的荧光報告生物傳感器，以更好地了解細胞過程並開發靶向治療方法。
• 探索上轉換(upconversion)奈米晶體和納米粒子在紅外生物醫學影像和紅外光釋放應用中的使用，這克服了在生物組織中，可見光穿透深度非常差的限制。

我們的實驗室一直在尋找有才華的研究生和博士後加入我們的團隊。如果您有興趣了解我們實驗是甚至加入我們實驗室，請隨時跟我連絡。我們可以隨時討論。我們實驗室相當多元化和國際化。除此之外，我們的學長學姊們不僅知識渊博，而且友好且易於親近。我們相信有好的學長學姊，與擁有優秀的指導教授一樣重要。

雖然我們在台灣尚未獲得任何獎項或榮譽，但這不表示我們在化學生物學研究方面的工作不值得認可。這只說明了伯樂尚未出現 (哈哈哈)。如果貴組織或基金會有興趣支持這一領域的創新和有影響力的研究，我們將不勝感激。歡迎瀏覽我們的研究成果。

1. Tzu-Ho Chen, Kevin Garnir, Chong-Yan Chen, Cheng-Bang Jian, Hua-De Gao, Bill Cheng, Mei-Chun Tseng, Cécile Moucheron, Andrée Kirsch-De Mesmaeker*, Hsien-Ming Lee* A Toolkit for Engineering Proteins in Living Cells: Peptide with a Tryptophan-Selective Ru-TAP Complex to Regioselectively Photolabel Specific Proteins. J. Am. Chem. Soc. 2022-09, 144 (39), 18117-18125. (IF= 16.383)
2. Cheng-Bang Jian, Xu-En Yu, Hua-De Gao, Huai-An Chen, Ren-Hua Jheng, Chong-Yan Chen, Hsien-Ming Lee* Liposomal PHD2 Inhibitors and the Enhanced Efficacy in Stabilizing HIF-1α. Nanomaterials 2022-01, 12(1), 163. (Feature Paper, IF=5.719)
3. Babu Eththilu, Bhuvaneswari Jayaraman, Muthu Mareeswaran Palpandiyan, Thanasekaran Pounraj, Lee Hsien-Ming*, Rajagopal Seenivasan* Transition metal complexes based aptamers as optical diagnostic tools for disease proteins and biomolecules. Coordination Chemistry Reviews 2019, 380 519-549. (IF= 22.06)
4. Thanasekaran Pounraj, Chu Chih-Hang, Wang Sheng-Bo, Chen Kuan-Yu, Gao Hua-De, Lee Mandy M., Sun Shih-Sheng, Li Jui-Ping, Chen Jiun-Yu, Chen Jen-Kun*, Chang Yu-Hsu*, Lee Hsien-Ming* Lipid-Wrapped Upconversion Nanoconstruct/Photosensitizer Complex for Near-Infrared Light-Mediated Photodynamic Therapy. ACS Applied Materials & Interfaces 2019, 11, 1, 84–95 . (IF= 10.38)
5. Zhang, S.; Chen, T.-H.; Lee, H.-M.; Bi, J.; Ghosh, A.; Fang, M.; Qian , Z.; Xie, F.; Ainsely, J.; Christov, C.; Luo, F.-T.; Zhao, F.; Liu, H. Luminescent Probes for Sensitive Detection of pH Changes in Live Cells through Two Near-infrared Luminescence Channels. ACS Sensors, 2017, 2, 924. (IF=9.618)
6. He, R.-Yu; Chao, S.-H.; Tsai, Y.-J.; Lee, C.-C.; Yu, C.-Y.; Gao, H.-D.; Huang, Y.-A.; Hwang, E.; Lee, H.-M.; Huang, J. J.-T. Photo-Controllable Probe Spatiotemporally Induces Neurotoxic Fibrillar Aggregates and Impairs Nucleocytoplasmic Trafficking. ACS NANO, 2017, 11, 6795. (IF=18.02)
7. Yadav, K.; Chou, A.-C.; Ulaganathan, R. K.; Gao, H.-D.; Lee, H.-M.; Pan, C.-Y.; Chen, Y.-T. Targeted and Efficient Activation of Channelrhodopsins Expressed in Living Cells Via Specifically-Bound Upconversion Nanoparticles. Nanoscale, 2017, 9, 9457. (IF=8.307)
8. Gao, H.-D. ; Chiang, C.-W.; Thanasekaran, P.; Hong, J.-L.; Liu, Y.-C.; Chang, Y.-H.; Lee, H.-M. Construction of a Near-Infrared-Activatable Enzyme Platform to Remotely Trigger Intracellular Signal Transduction Using an Upconversion Nanoparticle. ACS NANO 2015, 9, 7041. (IF=18.02)
9. He, R.-Y.; Huang, Y.-C.; Chiang, C.-W.; Tsai, Y.-J.; Ye, T.-J.; Gao, H.-D.; Wu, C.-Y.; Lee, H.-M.; Huang, J. J.-T. Characterization and real-time imaging of the FTLD-related protein aggregation induced by amyloidogenic peptides. Chem. Comm. 2015, 51, 8652. (IF=6.06)
10. Priestman, M. A.; Shell, T. A.; Sun, L.; Lee, H.-M.; Lawrence, D. S. Merging of Confocal and Caging Technologies: Selective Three-Color Communication with Profluorescent Reporters. Angew. Chem. Int. Ed. 2012, 51, 1. (IF=16.823)
    
    
JOURNAL ARTICLES (2011~2001): (Before Academia Sinica)
11. Lee, H.-M.; Xu, W.; Lawrence, D. S. Construction of a Photoactivatable Profluorescent Enzyme Via Propinquity Labeling. J. Am. Chem. Soc. 2011, 133, 2331. (IF=16.38)
12. Lee, H.-M.; Priestman, M. A.; Lawrence, D. S. Light-Mediated Spatial Control via Photolabile Fluorescently Quenched Peptide Cassettes. J. Am. Chem. Soc. 2010, 132, 1446. (IF=16.38)
13. Wakata, A.; Lee, H.-M.; Toutchkine, A.; Schmidt, M.; Lawrence, D. S. Simultaneous Fluorescent Monitoring of Proteasomal Subunit Catalysis. J. Am. Chem. Soc. 2010, 132, 1578. (IF=16.38)
14. Lee, H.-M.; Larson, D. R.; Lawrence, D. S. Illuminating the Chemistry of Life: Design, Synthesis, and Applications of “Caged” and Related Photoresponsive Compounds. ACS Chem. Biol. 2009, 4, 409. (IF=4.63)
    (Ranked # 3 of the “Most Read Articles in ACS Chemical Biology” in 2009)
15. Satish Nayak,; Lee, H.-M.; Chmielewski, J. A.; Lyon, A. Folate-Mediated Cell Targeting and Cytotoxicity Using Thermoresponsive Microgels. J. Am. Chem. Soc. 2004, 126, 10258. (IF=16.823)

JOURUAL PAPERS:
16. Bhaskarchand Gautam, Chun-Hao Luo, Hua-De Gao, Jye-Chian Hsiao, Hsian-Rong Tseng*, Hsien-Ming Lee*, Hsiao-hua Yu*, Nano-On-Nano: Responsive Nanosubstrate-Mediated Liposome Delivery with High Cellular Uptake Efficiency, ACS Appl. Bio Mater. 2023, doi.org/10.1021/acsabm.3c00029
17. Tzu-Ho Chen, Kevin Garnir, Chong-Yan Chen, Cheng-Bang Jian, Hua-De Gao, Bill Cheng, Mei-Chun Tseng, Cécile Moucheron, Andrée Kirsch-De Mesmaeker*, Hsien-Ming Lee* A Toolkit for Engineering Proteins in Living Cells: Peptide with a Tryptophan-Selective Ru-TAP Complex to Regioselectively Photolabel Specific Proteins.J. Am. Chem. Soc. 2022-09, 144 (39), 18117-18125.
18. P. Thanasekaran, B.-C Lin, A. Valaboju, C.-F. Lan, C.-H. Chang, C.-C. Lee, J.-Y. Wu, D. Battacharya, T.-W. Tseng, H.-M. Lee, C-P Hsu*,K-L Lu* Molecular mechanics of glove-like re(I) metallacycles: Toward light-activated molecular catchers. JOURNAL OF THE CHINESE CHEMICAL SOCIETY 2022-08-01, 69, 8-1392-1399.
19. Cheng-Bang Jian, Xu-En Yu, Hua-De Gao, Huai-An Chen, Ren-Hua Jheng, Chong-Yan Chen, Hsien-Ming Lee* Liposomal PHD2 Inhibitors and the Enhanced Efficacy in Stabilizing HIF-1α. Nanomaterials 2022-01, 12(1), 163.
20. Wang Jianbo, Xia Shuai, Bi Jianheng, Zhang Yibin, Fang Mingxi, Luck Rudy L., Zeng Yanbo, Chen Tzu-Ho, Lee Hsien-Ming*, Liu Haiying* Near-infrared fluorescent probes based on TBET and FRET rhodamine acceptors with different pKa values for sensitive ratiometric visualization of pH changes in live cells. Journal of Materials Chemistry B 2019, .
21. Babu Eththilu, Bhuvaneswari Jayaraman, Muthu Mareeswaran Palpandiyan, Thanasekaran Pounraj, Lee Hsien-Ming*, Rajagopal Seenivasan* Transition metal complexes based aptamers as optical diagnostic tools for disease proteins and biomolecules. Coordination Chemistry Reviews 2019, 380 519-549.
22. Thanasekaran Pounraj, Chu Chih-Hang, Wang Sheng-Bo, Chen Kuan-Yu, Gao Hua-De, Lee Mandy M., Sun Shih-Sheng, Li Jui-Ping, Chen Jiun-Yu, Chen Jen-Kun*, Chang Yu-Hsu*, Lee Hsien-Ming* Lipid-Wrapped Upconversion Nanoconstruct/Photosensitizer Complex for Near-Infrared Light-Mediated Photodynamic Therapy. ACS Applied Materials & Interfaces 2019, 11, 1, 84–95.
23. Chen Tzu-Ho, Zhang Shuwei, Jaishi Meghnath, Adhikari Rashmi, Bi Jianheng, Fang Mingxi, Xia Shuai, Zhang Yibin, Luck Rudy L., Pati Ranjit, Hsien-Ming Lee*, Luo Fen-Tair*, Tiwari Ashutosh*, Liu Haiying* New Near-Infrared Fluorescent Probes with Single-Photon Anti-Stokes-Shift Fluorescence for Sensitive Determination of pH Variances in Lysosomes with a Double-Checked Capability. ACS Applied Bio Materials 2018, 1(3) 549-560.
24. Kataria Monika, Yadav Kanchan, Haider Golam, Liao Yu Ming, Liou Yi-Rou, Cai Shu-Yi, Lin Hung-i, Chen Ying Huan, Paul Inbaraj Christy Roshini, Bera Krishna Prasad, Lee Hsein Ming, Chen Yit-Tsong*, Wang Wei-Hua, Chen Yang Fang* Transparent, Wearable, Broadband, and Highly Sensitive Upconversion Nanoparticles and Graphene-Based Hybrid Photodetectors. ACS Photonics 2018, 5(6) 2336-2347.
25. Hsieh Feng-Jen, Chen Yen-Wei, Huang Yao-Kuan, Lee Hsien-Ming, Lin Chun-Hung, Chang Huan-Cheng* Correlative Light-Electron Microscopy of Lipid-Encapsulated Fluorescent Nanodiamonds for Nanometric Localization of Cell Surface Antigens. Analytical Chemistry 2018, 90(3) 1566-1571.
26. Hua-De Gao, Pounraj Thanasekaran, Tzu-Ho Chen, Yu-Hsu Chang*, Yu-Ju Chen, Hsien-Ming Lee* An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation. Journal of Visualized Experiments 2017, (126), e55769.
27. Shuwei Zhang, Tzu-Ho Chen, Hsien-Ming Lee*, Jianheng Bi, Avik Ghosh, Mingxi Fang, Zichen Qian, Fei Xie, Jon Ainsley, Christo Christov, Fen-Tair Luo*, Feng Zhao*, Haiying Liu* Luminescent Probes for Sensitive Detection of pH Changes in Live Cells through Two Near-Infrared Luminescence Channels. ACS Sensors 2017, 2(7), 924-931.
28. Ruei-Yu He, Shu-Han Chao, Yu-Ju Tsai, Chi-Chang Lee, Chu-Yi Yu, Hua-De Gao, Yung-An Huang, Hwang Eric, Lee Hsien-Ming*, Joseph Jen-Tse Huang* Photocontrollable Probe Spatiotemporally Induces Neurotoxic Fibrillar Aggregates and Impairs Nucleocytoplasmic Trafficking. ACS Nano 2017, 11(7), 6795-6807.
29. Kanchan Yadav, Ai-Chuan Chou, Rajesh Kumar Ulaganathan, Hua-De Gao, Hsien-Ming Lee*, Chien-Yuan Pan*, Yit-Tsong Chen* Targeted and efficient activation of channelrhodopsins expressed in living cells via specifically-bound upconversion nanoparticles. Nanoscale 2017, 9(27), 9457-9466.
30. Hua-De Gao, Pounraj Thanasekaran, Chao-Wei Chiang, Jia-Lin Hong, Yen-Chun Liu, Yu-Hsu Chang, and Hsien-Ming Lee * Construction of a Near-Infrared-Activatable Enzyme Platform to Remotely Trigger Intracellular Signal Transduction Using an Upconversion Nanoparticle. ACS Nano 2015-06,  9(7), 7041–7051.
31. Cheng-Wei Hsieh, Chih-Hang Chu, Hsien-Ming Lee, and Wei-Yuan Yang Triggering Mitophagy with Far-Red Light. Scientific Reports 2015-05, 5, 10376.
32. He, R.-Y.; Huang, Y.-C.; Chiang, C.-W.; Tsai, Y.-J.; Ye, T.-J.; Gao, H.-D.; Wu, C.-Y.; Lee, H.-M.*; Huang, J. J.-T.* Characterization and real-time imaging of the FTLD-related protein aggregation induced by amyloidogenic peptides. CHEMICAL COMMUNICATIONS 2015-04, 51, 8652-8655.
33. Gerard Chun-Hao Liu , Bryan Po-Wen Chen , Nancy Ting-Juan , Chih-Hsien Wang , Wenlung Chen , Hsien-Ming Lee , Sunney I. Chan and Joseph Jen-Tse Huang  Delineating the membrane-disrupting and seeding properties of the TDP-43 amyloidogenic core. CHEMICAL COMMUNICATIONS 2013-10, 49, 11212-11214.
34. Priestman MA, Shell TA, Sun L, Lee HM, Lawrence DS Merging of confocal and caging technologies: selective three-color communication with profluorescent reporters.. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2012, 51(31), 7684-7.

Update： 2023-11-08

1. Tzu-Ho Chen, Kevin Garnir, Chong-Yan Chen, Cheng-Bang Jian, Hua-De Gao, Bill Cheng, Mei-Chun Tseng, Cécile Moucheron, Andrée Kirsch-De Mesmaeker*, Hsien-Ming Lee* A Toolkit for Engineering Proteins in Living Cells: Peptide with a Tryptophan-Selective Ru-TAP Complex to Regioselectively Photolabel Specific Proteins. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2022-09, 144 (39), 18117-18125.
2. P. Thanasekaran, B.-C Lin, A. Valaboju, C.-F. Lan, C.-H. Chang, C.-C. Lee, J.-Y. Wu, D. Battacharya, T.-W. Tseng, H.-M. Lee, C-P Hsu*,K-L Lu* Molecular mechanics of glove-like re(I) metallacycles: Toward light-activated molecular catchers. JOURNAL OF THE CHINESE CHEMICAL SOCIETY 2022-08-01, 69, 8-1392-1399.
3. Cheng-Bang Jian, Xu-En Yu, Hua-De Gao, Huai-An Chen, Ren-Hua Jheng, Chong-Yan Chen, Hsien-Ming Lee* Liposomal PHD2 Inhibitors and the Enhanced Efficacy in Stabilizing HIF-1α. Nanomaterials 2022-01, 12(1), 163.
4. Wang Jianbo, Xia Shuai, Bi Jianheng, Zhang Yibin, Fang Mingxi, Luck Rudy L., Zeng Yanbo, Chen Tzu-Ho, Lee Hsien-Ming*, Liu Haiying* Near-infrared fluorescent probes based on TBET and FRET rhodamine acceptors with different pKa values for sensitive ratiometric visualization of pH changes in live cells. Journal of Materials Chemistry B 2019, .
5. Thanasekaran Pounraj, Chu Chih-Hang, Wang Sheng-Bo, Chen Kuan-Yu, Gao Hua-De, Lee Mandy M., Sun Shih-Sheng, Li Jui-Ping, Chen Jiun-Yu, Chen Jen-Kun*, Chang Yu-Hsu*, Lee Hsien-Ming* Lipid-Wrapped Upconversion Nanoconstruct/Photosensitizer Complex for Near-Infrared Light-Mediated Photodynamic Therapy. ACS Applied Materials & Interfaces 2019, .
6. Babu Eththilu, Bhuvaneswari Jayaraman, Muthu Mareeswaran Palpandiyan, Thanasekaran Pounraj, Lee Hsien-Ming*, Rajagopal Seenivasan* Transition metal complexes based aptamers as optical diagnostic tools for disease proteins and biomolecules. Coordination Chemistry Reviews 2019, 380 519-549.
7. Chen Tzu-Ho, Zhang Shuwei, Jaishi Meghnath, Adhikari Rashmi, Bi Jianheng, Fang Mingxi, Xia Shuai, Zhang Yibin, Luck Rudy L., Pati Ranjit, Hsien-Ming Lee*, Luo Fen-Tair*, Tiwari Ashutosh*, Liu Haiying* New Near-Infrared Fluorescent Probes with Single-Photon Anti-Stokes-Shift Fluorescence for Sensitive Determination of pH Variances in Lysosomes with a Double-Checked Capability. ACS Applied Bio Materials 2018, 1(3) 549-560.
8. Kataria Monika, Yadav Kanchan, Haider Golam, Liao Yu Ming, Liou Yi-Rou, Cai Shu-Yi, Lin Hung-i, Chen Ying Huan, Paul Inbaraj Christy Roshini, Bera Krishna Prasad, Lee Hsein Ming, Chen Yit-Tsong*, Wang Wei-Hua, Chen Yang Fang* Transparent, Wearable, Broadband, and Highly Sensitive Upconversion Nanoparticles and Graphene-Based Hybrid Photodetectors. ACS Photonics 2018, 5(6) 2336-2347.
9. Hsieh Feng-Jen, Chen Yen-Wei, Huang Yao-Kuan, Lee Hsien-Ming, Lin Chun-Hung, Chang Huan-Cheng* Correlative Light-Electron Microscopy of Lipid-Encapsulated Fluorescent Nanodiamonds for Nanometric Localization of Cell Surface Antigens. Analytical Chemistry 2018, 90(3) 1566-1571.
10. Shuwei Zhang, Tzu-Ho Chen, Hsien-Ming Lee*, Jianheng Bi, Avik Ghosh, Mingxi Fang, Zichen Qian, Fei Xie, Jon Ainsley, Christo Christov, Fen-Tair Luo*, Feng Zhao*, Haiying Liu* Luminescent Probes for Sensitive Detection of pH Changes in Live Cells through Two Near-Infrared Luminescence Channels. ACS Sensors 2017, 2(7), 924-931.
11. Ruei-Yu He, Shu-Han Chao, Yu-Ju Tsai, Chi-Chang Lee, Chu-Yi Yu, Hua-De Gao, Yung-An Huang, Hwang Eric, Lee Hsien-Ming*, Joseph Jen-Tse Huang* Photocontrollable Probe Spatiotemporally Induces Neurotoxic Fibrillar Aggregates and Impairs Nucleocytoplasmic Trafficking. ACS Nano 2017, 11(7), 6795-6807.
12. Kanchan Yadav, Ai-Chuan Chou, Rajesh Kumar Ulaganathan, Hua-De Gao, Hsien-Ming Lee*, Chien-Yuan Pan*, Yit-Tsong Chen* Targeted and efficient activation of channelrhodopsins expressed in living cells via specifically-bound upconversion nanoparticles. Nanoscale 2017, 9(27), 9457-9466.
13. Hua-De Gao, Pounraj Thanasekaran, Tzu-Ho Chen, Yu-Hsu Chang*, Yu-Ju Chen, Hsien-Ming Lee* An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation. Journal of Visualized Experiments 2017, (126), e55769.
14. Hua-De Gao, Pounraj Thanasekaran, Chao-Wei Chiang, Jia-Lin Hong, Yen-Chun Liu, Yu-Hsu Chang, and Hsien-Ming Lee * Construction of a Near-Infrared-Activatable Enzyme Platform to Remotely Trigger Intracellular Signal Transduction Using an Upconversion Nanoparticle. ACS Nano 2015-06,  9(7), 7041–7051.
15. Cheng-Wei Hsieh, Chih-Hang Chu, Hsien-Ming Lee, and Wei-Yuan Yang Triggering Mitophagy with Far-Red Light. Scientific Reports 2015-05, 5, 10376.
16. He, R.-Y.; Huang, Y.-C.; Chiang, C.-W.; Tsai, Y.-J.; Ye, T.-J.; Gao, H.-D.; Wu, C.-Y.; Lee, H.-M.*; Huang, J. J.-T.* Characterization and real-time imaging of the FTLD-related protein aggregation induced by amyloidogenic peptides. CHEMICAL COMMUNICATIONS 2015-04, 51, 8652-8655.
17. Gerard Chun-Hao Liu , Bryan Po-Wen Chen , Nancy Ting-Juan , Chih-Hsien Wang , Wenlung Chen , Hsien-Ming Lee , Sunney I. Chan and Joseph Jen-Tse Huang  Delineating the membrane-disrupting and seeding properties of the TDP-43 amyloidogenic core. CHEMICAL COMMUNICATIONS 2013-10, 49, 11212-11214.
18. Priestman MA, Shell TA, Sun L, Lee HM, Lawrence DS Merging of confocal and caging technologies: selective three-color communication with profluorescent reporters.. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2012, 51(31), 7684-7.

1. Thanasekaran, P.; Gao, H.-D.; Lee, H.-M.*, 2016, “Upconversion Nanoparticle as a Platform for Photoactivation isbn”, editor(s): Liu, R.-S., Phosphors, Upconversion Nano Particles, Quantum Dots and Their Applications (Volume 2), pp. 391, SINGAPORE: SPRINGER.

• 用以偵測類澱粉沉積蛋白之探針及方法 PROBES AND METHODS FOR DETECTING AMYLOIDOGENIC PROTEINS
  Taiwan: I649091 2019