Professor YAO Shao Qin
B.Sc., Ohio State University (USA) PhD, Purdue University (USA) Post-doc., UC Berkeley/ Scripps Research Institute (USA)
| Department of Chemistry, NUS
3 Science Drive 3
| Office: S5-03-05
Research Fellow (RF) and Research Associate/Assistant (RA) Positions in Chemical Biology & Drug Discovery Available:
Positions are available immediately in the areas of chemical biology, chemical proteomics, drug discovery and delivery, bioimaging and material chemical biology. For more background on our research, please visit our group website at https://blog.nus.edu.sg/yaolab/ as well as our recent publications at https://blog.nus.edu.sg/yaolab/publications/
Requirement: Recent graduates with a PhD, MSc, or BSc with Honors, in chemistry/life sciences related fields. Prior research experience in organic synthesis/medicinal chemistry, protein chemistry, molecular biology or cell biology is preferred. Good communication and interpersonal skills would be essential. The candidate should be motivated and eager to learn.
Interested candidates are to send in their CV, research statement and three recommendation letters to:
Prof Shao Q Yao
Department of Chemistry
National University of Singapore
3 Science Drive 3
For more information, please see https://blog.nus.edu.sg/yaolab/
Organic & Bioorganic Chemistry/Chemical Biology
A key step towards the biological characterization of enzymes, as well as their adoption as drug targets, is the development of global solutions that bridge the gap in understanding these proteins and their interactions. We herein present technological advances that facilitate the study of enzymes and their properties both in vitro and in living organisms (e.g. live mammalian cells/tissues). This is an emerging area we called “Catalomics”, which involves the development of powerful strategies in Chemical Biology and Chemical Proteomics that enable organism-wide, high-throughput studies of enzymes.
Over the years, our group has introduced and developed a variety of such enabling platforms for many classes of enzymes, including kinases, phosphatases and proteases, as well as proteins that engage in interactions with them leading to modulating their biological activities. For each of these different types of enzymes, specific design considerations are required to develop the appropriate chemical tools to characterize each class. These tools include activity-based probes and chemical compound libraries, which in many cases are rapidly assembled using efficient combinatorial synthesis or “click chemistry” strategies. The resulting molecular assortments may then be screened against the target enzymes in high-throughput using microplates or microarrays. Once “hits” are identified, they will be further studied in live mammalian cells/disease tissues. In cases where compounds are not cell-permeable and/or possess unfavorable cytotoxicity, they will be delivered into cells/tissues in cell/tissue type-specific manner, and their intracellular release is done in a “smart” manner that is highly controllable and directly dependent upon the disease state of the intracellular settings. These techniques offer powerful means to study, profile, and discover potent small molecules that can modulate enzyme activity. Specific foci in “Catalomics” are:
- Organic synthesis, combinatorial & medicinal chemistry; Solid-phase synthesis of natural product-like and bioactive compounds; Click chemistry; Multicomponent reactions
- Proteomics/functional Genomics & catalomics; Developing next-generation microarray technologies; Developing new strategies for large-scale proteomics and drug profiling; Microarrays for disease diagnostics
- Protein engineering & directed evolution; Protein- and peptide-based biosensors; In vitro and in-cell evolution of proteins with diverse functions; protein-protein interaction and post-translational modifications
- Small molecule bioimaging of cellular events; Developing novel strategies for biomolecule labeling in living cells; Developing novel fluorescent molecules; Developing strategies for transporting macromolecules across cell membranes
- Wang, D.; Du, S.; Cazenave-Gassiot, A.; Ge, J.; Lee, J.-S.; Wenk, M.; Yao, S.Q.* “Global Mapping of Protein-Lipid Interactions by Using Modified Choline-Containing Phospholipids Metabolically Synthesized in Live Cells”, Angew. Chem. Int. Ed., 2017, in press.
- P. Yuan, X. Mao, K. C. Chong, J. Fu, S. Pan, S. Wu, C. Yu*, S. Q. Yao*, “Simultaneous Imaging of Endogenous Survivin mRNA and On-Demand Drug Release in Live Cells by Using a Mesoporous Silica Nanoquencher”, Small., 2017, in press.
- Peng, B.; Thorsell, A.-G.; Karlberg, T.; Schüler*, H.; Yao, S.Q.*, Small Molecule Microarray (SMM)-Based Discovery of PARP14 Inhibitors”, Angew. Chem. Int. Ed., 2017, 56, 248-253.
- Xie, Y.; Ge, J.; Lei, H.; Peng, B.; Zhang, H.; Wang, D.; Pan, S.; Chen, G.; Chen, L.; Wang, Y.; Hao, Q.; Yao, S. Q.; Sun, H.; “Fluorescent Probes for Single-Step Detection and Proteomic Profiling of HDACs”. J. Am. Chem. Soc., 2016, 138, 15596-15604.
- Yu, C.; Qian, L.; Ge, J.; Fu, J.; Yuan, P.; Yao, S. C. L.; Yao, S. Q.*, “Cell-Penetrating Poly(disulﬁde)-Assisted Intracellular Delivery of Mesoporous Silica Nanoparticles for Inhibition of miR-21 Functions and Detection of Subsequent Therapeutic Effects”, Angew. Chem. Int. Ed., 2016, 55, 9272-9276.
- Ge, J.; Zhang, C.-W.; Ng, X.W.; Peng, B.; Pan, S.; Du, S. Wang, D.; Li, L.; Lim, K.-L.; Wohland, T.; Yao, S.Q.*, “A Suite of Puromycin Analogs Capable of Multiplexed Imaging and Profiling of Protein Synthesis and Dynamics in Live Cells and Neurons”, Angew. Chem. Int. Ed., 2016, 55, 4933-4937.
- Li, Z.; Qian, L.; Li, L.; Bernhammer, J. C.; Huynh, H. V.; Lee, J.-S.; Yao, S. Q.*, “Tetrazole Photoclick Chemistry: Reinvestigating Its Suitability as a Bioorthogonal Reaction and Potential Applications”, Angew. Chem. Int. Ed., 2016, 55, 2002-2006.
- Zhang, H.; Liu, R.; Liu, J.; Li, L.; Wang, P.; Yao, S.Q.; Xu, Z.; Sun, H., “A Minimalist Fluorescent Probe for Differentiating Cys, Hcy and GSH in Live Cells”, Chem. Sci., 2016, 7, 256-260.
- Fu, J.; Yu, C.; Li, L.; Yao, S.Q.*, “Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s”, J. Am. Chem. Soc., 2015, 137, 12153-12160.
- Yu, C.; Qian, L.; Uttamchandani, M.; Li, L.; Yao, S.Q.*, “Single Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR-122 Function in Hepatocellular Carcinoma Cells with “Smart” Mesoporous Silica Nanoparticles’, Angew. Chem. Int. Ed., 2015, 54, 10574-10578.
- Li, L.; Zhang, C.-W.; Ge, J.; Qian, L.; Chai, B-H.; Zhu, Q.; Lee, J.-S.; Lim, K.-L.; Yao, S.Q.*, “A small molecule probe capable of selective profiling and imaging of monoamine oxidase B activities in Parkinson’s disease models”, Angew. Chem. Int. Ed., 2015, 54, 10821-10825.
- Na, Z.; Peng, B.; Ng, S.; Pan, S.; Lee, J.-S.; Shen, H.M.; Yao, S.Q.* “A Small Molecule Protein-Protein Interaction Inhibitor Of PARP1 That Targets Its BRCT Domain”, Angew. Chem. Int. Ed., 2015, 54, 2515-2519.
- Li, Z.; Wang, D.; Li, L.; Pan, S.; Na, Z.; Tan, C.Y.J.; Yao, S.Q.*, “Minimalist” Cyclopropene-Containing Photo-Cross-Linkers Suitable for Live-Cell Imaging and Affinity-Based Protein Labeling”, J. Am. Chem. Soc., 2014, 136, 9990-9998.
- Na, Z.; Pan, S.; Uttamchandani, M.; Yao, S.Q.*, “Discovery of Cell-Permeable Inhibitors That Target the BRCT Domains of BRCA1 Protein by Using Small Molecule Microarray”, Angew. Chem. Int. Ed., 2014, 53, 8421-8426.
- Li. L.; Zhang, C.-W.; Chen, G.Y.J.; Zhu, B.; Chai, C.; Xu, Q.-H., Tan, E.-K.; Zhu, Q.; Lim, K.-L.*; Yao, S.Q.*, “A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models.”, Nat. Commun., 2014, 5:3276
- Zhang, C.; Tan, C.Y.J.; Ge, J.; Na, Z.; Chen, G.Y.J.; Uttamchandani, M.; Sun, H.; Yao, S.Q.*, “Preparation of Small Molecule Microarrays by Using trans-Cyclooctene Tetrazine ligation and Their Applications in High-Throughput Screening of Potential Protein-Protein-Interaction Inhibitors of Bromodomains”, Angew. Chem. Int. Ed., 2013, 52, 14060-14064.
- Li, Z.; Li, L.; Hao, P. Tan, C.Y.J.; Cheng, X.; Chen, G.Y.J.; Sze, S.K.; Shen, H.-M.; Yao, S.Q.*, “Design and Synthesis of “Minimalist” Terminal Alkyne-Containing Diazirine Photo-Cross-Linkers and Their Incorporation into Kinase Inhibitors for Cell- and Tissue-Based Proteome Profiling”, Angew. Chem. Int. Ed., 2013, 52, 8551-8556.
- Li, L.; Shen, X.; Xu, Q.-H.; Yao, S. Q.*, “A Switchable Two-photon Membrane Tracer Capable of Imaging Membrane-Associated Protein Tyrosine Phosphatase Activities:, Angew. Chem. Int. Ed., 2013, 52, 424-428.
- Li, L.; Ge, J.; Wu, H.; Xu, Q.H.; Yao, S.Q.* “Organelle-Specific Detection of Phosphatase Activities with Two-Photon Fluorogenic Probes in Cells and Tissues”, J. Am. Chem. Soc., 2012, 134, 12157-12167.
- Shi, H.; Zhang, C.; Chen, G.Y.J.; Yao, S.Q.* “Cell-Based Proteome Profiling of Potential Dasatinib™ Targets Using Affinity-Based Probes (AfBPs)”, J. Am. Chem. Soc., 2012, 134, 3001-3014.
- Liu, K.; Yang, P.-Y.; Na, Z.; Yao, S.Q.* “Dynamic Monitoring of Newly Synthesized Proteomes: Up-Regulation of Myristoylated Protein Kinase A During Butyric Acid Induced Apoptosis”, Angew. Chem. Int. Ed., 2011, 50, 6776-6781.
- Hu, M.; Li, L.; Wu, H.; Su, Y.; Yang, P.-Y.; Uttamchandani, M.; Xu, Q.-H.; Yao, S.Q.* “Multi-Color, One- and Two-Photon Imaging of Enzymatic Activities in Live Cells with Novel Fluorescently Quenched Activity-Based Probes (qABPs)”, J. Am. Chem. Soc., 2011, 133, 12009-12020.
- Wu, H.; Ge, J.; Yang, P.-Y..; Wang, J.; Uttamchandani, M.; Yao, S.Q.* “A Peptide Aldehyde Microarray for High-Throughput Detection of Cellular Events”, J. Am. Chem. Soc., 2011, 133, 1946-1954.
- Wu, H.; Ge, J.; Yao, S.Q.* “Microarray-Assisted High-Throughput Identification of a Cell-Permeable Small Molecule Binder of 14-3-3 Proteins”, Angew. Chem. Int. Ed., 2010, 49, 6528-6532.
- Yang, P-Y.; Liu, K.; Ngai, M.H.; Lear, M.J..; Wenk, M.; Yao, S.Q.* “Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat – An FDA-Approved Drug with Anti-Tumor Activities”, J. Am. Chem. Soc., 2010, 132, 656-666.
- Liu, K.; Shi, H.; Xiao, H.; Chong, A.G.L.; Bi, X.; Chang, Y.T., Tan, K.; Yada, R.Y.; Yao, S.Q.* “Functional Profiling, Identification and Inhibition of Plasmepsins in Intra-erythrocytic Malaria Parasites”, Angew. Chem. Intl. Ed., 2009, 48, 8293-8297
- Lu, C.H.S.; Sun, H.; Bakar, F.B.A.; Uttamchandani, M.; Zhou, W.; Liou, Y.-C.; Yao, S.Q.* “Rapid Affinity-Based Fingerprinting of 14-3-3 Isoforms Using A Combinatorial Peptide Microarray”, Angew. Chem. Int. Ed., 2008, 47, 7438-7441.
- Sun, H.; Lu, C.H.S.; Uttamchandani, M.; Xia, Y.; Liou, Y.-C.; Yao, S.Q.* “Peptide Microarray for High-throughput Determination of Phosphatase Specificity and Biology”, Angew. Chem. Intl. Ed., 2008, 47, 1698-1702.
- Uttamchandani, M.; Lee, W.L.;Wang, J.; Yao, S.Q.* “Quantitative Inhibitor Fingerprinting of Metalloproteases using Small Molecule Microarrays”,”, J. Am. Chem. Soc., 2007, 129, 13110-13117.
- Uttamchandani, M.; Wang, J.; Li, J.; Hu, M.; Sun, H.; Chen, K. Y.-T.; Liu, K.; Yao, S.Q.* “Inhibitor Fingerprinting of Matrix Metalloproteases Using a Combinatorial Peptide Hydroxamate Library”, J. Am. Chem. Soc., 2007, 129, 7848-7858.
- Hu, Y.; Chen, G.Y.J.; Yao, S.Q.* “Activity-based high-throughput screening of enzymes using DNA microarray”, Angew. Chem. Intl. Ed. 2005, 44, 1048-1053.
- Chan, E.W.S.; Chattopadhaya, S.; Panicker, R.C.; Huang, X.; Yao, S.Q.* “Developing photo-active affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases”, J. Am. Chem. Soc. 2004, 126, 14435-14446.
- Lue, R.Y.P., Chen, G.Y.J., Hu, Y., Zhu, Q., Yao, S.Q.* “Versatile protein biotinylation strategies for potential high-throughput proteomics”, J. Am. Chem. Soc. 2004, 126, 1055-1062.
- Lesaicherre, M.L., Lue, R.Y.P., Chen, G.Y.J., Zhu, Q., Yao, S.Q.* “Intein-mediated biotinylation of proteins and its application in a protein microarray”, J. Am. Chem. Soc. 2002, 124, 8768-8769.