The exciting field of chemical biology allows us to use chemistry to observe, investigate, and manipulate biochemical reactions within living organisms. Our team's focus is on developing innovative vesicle designs, such as liposomes and lipid nanoparticles (LNPs) that are surface decorated with various functional peptides and smart biomolecules. These vesicles can deliver drugs or macromolecules to living cells in response to cues externally (artificial signal) or internally from disease signals. We are also working on designing and synthesizing biosensors that can provide valuable insights into the workings of living cells. Our ultimate goal is to gain the ability to experimentally test and better understand biochemical reactions in living organisms, as well as repair living cells or tissues in vivo. Through our research, we aim to make significant contributions to the fields of chemical biology and biomedicine.
Our research team is pursuing several areas of chemical biology with a particular focus on developing innovative solutions for living cell and tissue repair. Our key areas of interest include:

• Utilizing liposomes and nanoparticles with surface-anchored smart molecules, such as peptides, for efficient delivery of macromolecules to living cells and tissues, which is critically important for tissue repair.
  
• Investigating cellular protein chemical modifications to create novel protein functions that are essential for living cell and tissue repair.
  
• Studying peptide-membrane interaction, which is fundamental to the development of smart lipid nanocarriers for targeted drug delivery.
  
• Developing fluorescence-reporting biosensors that provide valuable information about the chemical environment in living cells and tissues to better understand cellular processes and develop targeted therapies.
  
• Exploring the use of upconversion nanocrystals and nanoparticles for IR biomedical imaging and IR photo-releasing applications, which overcomes the limitation of visible light that has very poor tissue penetrating depth.
  

Our lab is always looking for talented graduate students and postdocs to join our team. If you're interested in working with us, please don't hesitate to send me an email. I'm always available to chat and answer any questions you may have. We pride ourselves on having a diverse and international team, and our senior group members are not only knowledgeable but also approachable and friendly. We believe that having a supportive and collaborative research environment is just as important as having an excellent research advisor.

Although we haven't received any awards or honors in Taiwan, our work in chemical biology research deserves recognition. If your organization or foundation is interested in supporting innovative and impactful research in this field, we would be grateful for your consideration. Please check our track records in the Selected Publications.

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. 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.
6. 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, .
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. 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.
11. 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.
12. 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.
13. 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.
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