Institute of Chemistry, Academia Sinica

Using chemistry as a tool to observe, to probe and even to alter the biochemical reactions in the living organism is a very exciting topic in the area of chemical biology. We are very interested in any type of vesicle design that can deliver drugs or functional macromolecules into the living cells, such as surface functionalized liposomes, nanoparticles and cell penetrating peptides. Our lab also focuses on the design and the synthesis of many types of biosensor that can report to us what is going on in the living cells. These two directions will allow us, in the foreseeable future, to “run” or “test” our biochemical reactions in the living organisms.

• Development of IR biomedical imaging and IR photo-releasing applications based on upconversion nanocrystals / nanoparticles.
• Development of fluorescence-reporting biosensors.
• Protein chemical modifications for novel protein functions.
• Cellular drug delivery using peptides, liposomes, and nanoparticles.
• Development of cell-penetrating / organelle-targeting peptides as cellular delivery vesicles.

1. Wang, J.; Xia, S.; Bi, J.; Zhang, Y.; Fang, M.; Luck, R. L.; Zeng, Y.; Chen, T.-H.; Lee, H.-M.; Liu, H. 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. J. Mater. Chem. B. 2019 in press.
2. Babu, E.; Bhuavaneswari, J.; Muthumareeswaran, P.; Thanasejaran, P.; Lee, H.-M.; Rajagopal, S. Transition Metal Complexes Based Aptamers as Optical Diagnostic Tools for Disease Proteins. Coord. Chem. Rev. 2019, in press
3. Haider, G*; Lin, H,-I; Yadav, K.; Shen K.-C.; Liao, Y.-M.; Hu, H.-W.; Roy, P.K.; Bera, K.P; Lin, K.-S.; Lee, H.-M.; Chen, Y.-T.; Chen, F.-R.; Chen,Y.-F. A Highly-Efficient Single Segment White Random Laser. ACS Nano, 2018, 12, 12, 11847.
4. Chen, T.-H.; Zhang, S.; Jaishi, M.; Adhikari, R.; Bi, J.; Fang, M.; Xia, S.; Zhang, Y.; Luck, R. L.; Pati, R.; Lee, H.-M.; Luo, F.-T.; Tiwari, A.; Liu, H. 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 Appl. Bio Mater. 2018, 1, 549.
5. Kataria, M.; Yadav, K.; Haider, G.; Liao, Y.-M.; Liou, Y.-R.; Cai, S.-Y.; Li, H.-i.; Chen, Y.-H.; Inbaraj, C. R. P.; Bera, K.P.; Lee, H.-M.; Chen, Y.-T.; Wang, W.-H.; Chen, Y.-F. Transparent, Wearable, Broadband, and Highly Sensitive Upconversion Nanoparticles and Graphene-Based Hybrid Photodetectors. ACS Photonics, 2018, 5, 2336.
6. Hsieh, F. -J.; Chen, Y. -W.; Huang, Y.-K.; Lee, H.-M.; Lin, C.-H.; Chang, H.-C. Lipid-Encapsulated Fluorescent Nanodiamonds for Correlative Light-Electron Microscopy of Cell Surface Antigens. Anal. Chem. 2018, 90, 1566.
7. 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.
8. Gao, H.-D.; Thanasekaran, P.; Chen, T.-H.; Chang, Y.-H.; Chen, Y.-J.; Lee, H.-M. An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation. JoVE. 2017, (126), e55769, doi:10.3791/55769.
9. 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.
10. 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.
11. 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.
12. 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.
13. Hsieh, C.-W.; Chu, C.-H.; Lee, H.-M.; Yang, W.-Y. Triggering Mitophagy with Far-Red Light. Sci. Rep. 2015, 5, 10376.
14. Liu, G. C.-H.; Chen, B. P.-W.; Ye, N. T.-J.; Wang, C.-H.; Chen, W.; Lee, H.-M.; Chan, S. I., Huang, J. J.-T. Delineating the membrane-disrupting and seeding properties of the TDP-43 amyloidogenic core. Chem. Commun. 2013, 49, 11212.
15. 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.
    
    
JOURNAL ARTICLES (2011~2001): (Before Academia Sinica)
16. Lee, H.-M.; Xu, W.; Lawrence, D. S. Construction of a Photoactivatable Profluorescent Enzyme Via Propinquity Labeling. J. Am. Chem. Soc. 2011, 133, 2331.
17. 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.
18. 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.
19. 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.
    (Ranked # 3 of the “Most Read Articles in ACS Chemical Biology” in 2009)
    
20. Lee, H.-M.; Chmielewski, J. A. Liposomal Cargo Unloading Induced by pH-Sensitive Peptides. J. Peptide Res. 2005, 65, 355-363
21. 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.
22. Lee, H.-M.; Kim, Y. W.; Baird, J. K. Electrophoretic Mobility and Zeta-potential of Lysozyme Crystals in Aqueous Solutions of Some 1 : 1 Electrolytes. J. Cryst. Growth 2001, 232, 294.

BOOK CHAPTER:
1. Thanasekaran, P.; Gao, H.-D.; Lee, H.-M. Phosphors, Upconversion Nano Particles, Quantum Dots and Their Applications: Upconversion Nanoparticle as a Platform for Photoactivation; Liu, R.-S. (eds), Chapter 34, Springer Publication, China, 2015.

Update： 2019-01-18

1. 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, .
2. 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.
3. 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, .
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.