chemical biology, fluorescent probe, protein folding and aggregation, amyloidosis, cardiomyopathy

2010-2015, PhD in Chemistry, The Scripps Research Institute, USA

​2006-2010, B. Appl. Sci in Applied Chemistry (1^st class honours), National University of Singapore, Singapore

• 07/2017 --- 01/2019, Assistant Research Professor with Professor Xin Zhang

The Pennsylvania State University, University Park, PA, USA

• 10/2015 --- 07/2017, Postdoctoral Fellow with Professor Xin Zhang

The Pennsylvania State University, University Park, PA, USA

• 08/2010 --- 09/2015, Graduate Student with Professor Jeffery W. Kelly

The Scripps Research Institute, La Jolla, CA, USA

• 08/2009 --- 04/2010, Undergraduate Thesis with Professor Hardy Chan Sze On

National University of Singapore, Singapore

• 05/2009 --- 08/2009, Summer Internship with Professor Jianwei Xu

Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), Singapore

• 06/2008 --- 12/2008, Research Assistant with Professor David Perrin

University of British Columbia, Canada

(1) Suh, E. H.*; Liu, Y.*; Connelly, S.; Genereux, J. C.; Wilson, I. A.; Kelly, J. W., Stilbene vinyl sulfonamides as fluorogenic sensors of and traceless covalent kinetic stabilizers of transthyretin that prevent amyloidogenesis. Journal of the American Chemical Society 2013, 135 (47), 17869-80;

(2) Baranczak, A.*; Connelly, S.*; Liu, Y.*; Choi, S.; Grimster, N. P.; Powers, E. T.; Wilson, I. A.; Kelly, J. W., Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging--what we know and what we need to learn. Biopolymers 2014, 101 (5), 484-95;

(3) Liu, Y.*; Tan, Y. L.*; Zhang, X.*; Bhabha, G.; Ekiert, D. C.; Genereux, J. C.; Cho, Y.; Kipnis, Y.; Bjelic, S.; Baker, D.; Kelly, J. W., Small molecule probes to quantify the functional fraction of a specific protein in a cell with minimal folding equilibrium shifts. Proceedings of the National Academy of Sciences of the United States of America 2014, 111 (12), 4449-54; (highlighted in ACS Chem. Biol.)

(4) Liu, Y.*; Zhang, X.*; Tan, Y. L.; Bhabha, G.; Ekiert, D. C.; Kipnis, Y.; Bjelic, S.; Baker, D.; Kelly, J. W., De novo-designed enzymes as small-molecule-regulated fluorescence imaging tags and fluorescent reporters. Journal of the American Chemical Society 2014, 136 (38), 13102-5;

(5) Zhang, X.; Liu, Y.; Genereux, J. C.; Nolan, C.; Singh, M.; Kelly, J. W., Heat-shock response transcriptional program enables high-yield and high-quality recombinant protein production in Escherichia coli. ACS Chem. Biol. 2014, 9 (9), 1945-9; 1. (ACS Editor’s Choice, highlighted in C&EN News, and ACS Chem. Biol.).

(6) Baranczak, A.; Liu, Y.; Connelly, S.; Du, W. G.; Greiner, E. R.; Genereux, J. C.; Wiseman, R. L.; Eisele, Y. S.; Bradbury, N. C.; Dong, J.; Noodleman, L.; Sharpless, K. B.; Wilson, I. A.; Encalada, S. E.; Kelly, J. W., A fluorogenic aryl fluorosulfate for intraorganellar transthyretin imaging in living cells and in Caenorhabditis elegans. Journal of the American Chemical Society 2015, 137 (23), 7404-14;

(7) Cho, Y.; Zhang, X.; Pobre, K. F.; Liu, Y.; Powers, D. L.; Kelly, J. W.; Gierasch, L. M.; Powers, E. T., Individual and collective contributions of chaperoning and degradation to protein homeostasis in E. coli. Cell reports 2015, 11 (2), 321-33;

(8) Liu, Y.*; Zhang, X.*; Chen, W.; Tan, Y. L.; Kelly, J. W., Fluorescence Turn-On Folding Sensor To Monitor Proteome Stress in Live Cells. Journal of the American Chemical Society 2015, 137 (35), 11303-11;

(9) Chen, W.; Dong, J.; Li, S.; Liu, Y.; Wang, Y.; Yoon, L.; Wu, P.; Sharpless, K. B.; Kelly, J. W., Synthesis of Sulfotyrosine-Containing Peptides by Incorporating Fluorosulfated Tyrosine Using an Fmoc-Based Solid-Phase Strategy. Angew Chem Int Ed Engl 2016, 55 (5), 1835-8;

(10) Chen, W.; Dong, J.; Plate, L.; Mortenson, D. E.; Brighty, G. J.; Li, S.; Liu, Y.; Galmozzi, A.; Lee, P. S.; Hulce, J. J.; Cravatt, B. F.; Saez, E.; Powers, E. T.; Wilson, I. A.; Sharpless, K. B.; Kelly, J. W., Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. Journal of the American Chemical Society 2016, 138 (23), 7353-64;

(11) Chen, W.; Kong, L.; Connelly, S.; Dendle, J. M.; Liu, Y.; Wilson, I. A.; Powers, E. T.; Kelly, J. W., Stabilizing the CH2 Domain of an Antibody by Engineering in an Enhanced Aromatic Sequon. ACS Chem. Biol. 2016, 11 (7), 1852-61;

(12) Liu, Y.; Fares, M.; Dunham, N. P.; Gao, Z.; Miao, K.; Jiang, X.; Bollinger, S. S.; Boal, A. K.; Zhang, X., AgHalo: A Facile Fluorogenic Sensor to Detect Drug Induced Proteome Stress. Angew Chem Int Ed Engl 2017, 56, 8672-8676; (Highlighted by F1000Prime)

(13) Liu, Y.; Miao, K.; Dunham, N. P.; Liu, H.; Fares, M.; Boal, A. K.; Li, X.; Zhang, X., The Cation-pi Interaction Enables a Halo-Tag Fluorogenic Probe for Fast No-Wash Live Cell Imaging and Gel-Free Protein Quantification. Biochemistry 2017, 56 (11), 1585-1595. (ACS Editor’s Choice)

(14) Fares, M.; Li, Y.; Liu, Y.; Miao, K.; Gao, Z.; Zhai, Y.; Zhang, X., A molecular rotor-based Halo-tag ligand enables a fluorogenic proteome stress sensor to detect protein misfolding in mildly stressed proteome. Bioconjugate Chem. 2018, 29 (1), pp 215–224.

(15) Liu, Y.; Miao, K; Li, Y; Fares, M; Chen, S; Zhang, X. A HaloTag-Based Multicolor Fluorogenic Sensor Visualizes and Quantifies Proteome Stress in Live Cells Using Solvatochromic and Molecular Rotor-Based Fluorophores. Biochemistry 2018, DOI: 10.1021/acs.biochem.8b00135.

(16) Liu, Y.; Zhang, X., Heat Shock Protein Reports on Proteome Stress, Biotechnol. J. 2018, 13, 1800039.

(17) Liu, Y.; Wolstenholme, C. H.; Carter, G. C.; Liu, H.; Hu, H.; Grainger, L. S.; Miao, K; Fares, M;Hoelzel, C. A.; Yennawar, H. P.; Ning, G.; Du, M.; Bai, L.; Zhang, X., Modulation of Fluorescent Protein Chromophores to Detect Protein Aggregation with Turn-on Fluorescence. Journal of the American Chemical Society 2018, 140(24), 7381-7384. (Highlighted by F1000Prime)

(18) Jung, K. H.; Fares, M.; Grainger, L. S.; Wolstenholme, C. H.; Hou, A.; Liu, Y.; Zhang, X., A SNAP-tag fluorogenic probe mimicking the chromophore of the red fluorescent protein Kaede. Org. Biomol. Chem., 2018, DOI: 10.1039/C8OB01483C.

(19) Liu, Y.; Fares, M.; Zhang, X., Monitoring Proteome Stress in Live Cells Using HaloTag-Based Fluorogenic Sensor. Book Chapter, Protein Misfolding Diseases, 2019, Page 171-182.

(20) Jung, K. H.; Kim, S. F.; Liu, Y.; Zhang, X.*, A Fluorogenic AggTag Method Based on Halo- and SNAP-Tags to Simutaneously Detect Aggregation of Two Proteins in Live Cells. ChemBioChem. 2019, 20, 1078-1087.

(21) Kim, S. H.; Liu, Y.; Hoelzel, C.; Zhang, X.*; Lee, T. H.*, Super-Resolution Optical Lithography with DNA. Nano Lett. 2019, 19, 9, 6035-6042.

(22) Hoelzel, C., Hu, H., Wolstenholme, C. H.; Karim, B. A.; Munson, K. T.; Jung, K. H.; Zhang, H.; Liu, Y.; Yennawar, H. P.; Asbury, J. B.; Li, X.*; Zhang, X.*; A General Strategy to Enhance Donor‐Acceptor Molecules Using Solvent-Excluding Substituents. Angew. Chem. Int. Ed. Engl., 2020, 59, 2-10. (Hot Paper)

(23) Yu, J.; Li, T.; Liu, Y.; Wang, X.; Zhang, J.*; Wang, X.; Shi, G.; Lou, J; Wang, L.; Wang, C. C.; Wang, L.*; Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress. EMBO J., 2020, e103841

(24) Wolstenholme, C.; Hu, H.; Ye, S.; Funk, B. E.; Jain, D.; Hsiung, C. H.; Ning, G.; Liu, Y.*; Li, X.*; Zhang, X.*; AggFluor: Fluorogenic Toolbox Enables Direct Visualization of the Multi-Step Protein Aggregation Process in Live Cells. J. Am. Chem. Soc., 2020, 142(41), 17515-17523.

(25) Wan, W.; Jin, W.; Huang, Y.; Xia, Q.; Bai, Y.; Lyu, H.; Liu, D.; Dong, X.; Li, W.*; Liu, Y.*; Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores. Anal. Chem., 2021, 93(3), 1717-1724.

(26) Wan, W.;  Huang, Y.; Xia, Q.; Bai, Y.;Jin, W.;Wang, M.; Lyu, H.; Tang, Y.; Dong, X.; Gao, Z.; Zhao, Q.; Zhang, L.; Liu, Y.*; Covalent Probes for Aggregated Protein Imaging via Michael Addition. 2021, Angew. Chem. Int. Ed. Engl., 2021, 60, 11335-11343.(Hot paper)

(27) Shen, D.; Jin, W.; Bai, Y.; Huang, Y.; Lyu, H.; Zeng, L.; Wang, M.; Tang, Y.; Wan, W.; Dong, X.; Gao, Z.; Piao, H.; Liu, X.; Liu, Y.*; Rational Design of Crystallization Induced Emission Probes to Detect Amorphous Protein Aggregation in Live Cells. Angew. Chem. Int. Ed. Engl., 2021, DOI:10.1002/anie.202103674.

We are a group interested in developing chemical biology tools to visualize misfolded and aggregated pathogenic proteins and dissect the mechanism of protein conformational diseases. In particular, we focus on two amyloidogenic serum proteins, light chain and transthyretin, whose misfolding, aggregation, and deposition cause human amyloidosis diseases, including polyneuropathy and cardiomyopathy.

现指导学生

白玉龙  博士研究生  070303-有机化学  

张怀月  硕士研究生  070303-有机化学  

冯焕  博士研究生  070303-有机化学  

王梦蝶  博士研究生  070303-有机化学  

肖永全  硕士研究生  070303-有机化学  

高蕊  硕士研究生  070303-有机化学  

孙瑞  博士研究生  070303-有机化学  

夏秋璇  博士研究生  070303-有机化学