Faculty | Xuebin LIAO, Ph. D
Xuebin Liao, PI
Tenure-Track Associate Professor, School of Pharmaceutical Science, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University. Prof. Xuebin Liao obtained his B.S. degree from Peking University in 1995. Then he did his Ph.D work on natural product synthesis with Prof. James M. Cook at the University of Wisconsin at Milwaukee from 1998-2004. After that, from 2005-2008, he was a postdoctoral associate with Prof. John F. Hartwig at Yale and later at UIUC. In 2009, he held a position of Research Investigator I at GNF (the Genomics Institute of the Novartis Research Foundation). At GNF, his research was centered on discovering new drug candidates for pharmaceutical optimization. In September of 2012, he joined the Department of Pharmacology and Pharmaceutical Science, School of Medicine, Tsinghua University.
Research Interests
Currently Prof. Liao's research at Tsinghua University focuses on three major areas: (1) Bioactive natural product oriented synthesis and new synthetic method development; (2)Develop new approaches to cancer immunotherapy, including: discovering new TLRs agonists and exploring combined cancer immunotherapy ; (3) Structure-based drug discovery, in particular, we focus on discovering of inhibitors for HPK1 and KMO.
Major scientific contributions
One of major interests in Prof. Liao's group is to develop a variety of small molecule tool compounds to study innate immunity on anti-cancer activities. Cancer immunotherapy includes treatments that work in different ways. Some treatments involve boosting of the body's immune system in a very general way. Others help train the immune system to attack cancer cells specifically. Among these treatments, the blockade of immune checkpoints approach and the adoptive cell transfer such as CAR-T therapy have held a lot of promise as cancer treatment. However, recent studies suggest that immune checkpoint blockade such as PD-1 pathway blockade as a monotherapy will only succeed in the setting of pre-existing antitumor immune response in such patients. CAR-T monotherapy also exhibited very poor efficacies for the treatments of solid tumors during the pre-clinic studies. To expand efficacy of monotherapy, the combined therapies such as PD-1 monoclonal antibody with TLRs agonists or CAR-T with other immune modulators were extensively attempted in Prof. Liao’s lab. The “synergistic effects” were observed and the detailed mechanistic studies are ongoing.
1) Completed several total syntheses of biologically active indole alkaloids based on the novel methods developed in our group; Developed some useful methods for medicinal chemistry, for example: a nickel-catalyzed methylation of aryl halides with deuterated methyl iodide was recently developed in our lab.
2) With our newly developed TLR7/8 small molecule dual agonists and HPK1 inhibitors, different combination studies showed “synergistic effects”.
Honors and Awards
Tsinghua-Janssen Investigator Award (2013-2015)
Selected Publications
1. “Transition-Metal-Free Synthesis of N-hydroxy Oxindoles via an Aza-Nazarov Type Reaction involving Aza-Oxyallyl Cations” Ji, W.; Liu, Y. Liao, X.* Angew. Chem., Int. Ed. 2016, accepted. (*corresponding author)
2. “Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides” Chen, S.; Zhang, M.; Liao, X. *; Weng, Z. * J. Org. Chem. 2016, ASAP. (*corresponding author)
3. “Nickel-catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide”Hu, L.; Liu, X. Liao, X.* Angew. Chem., Int. Ed. 2016, 55, 9743. (*corresponding author)
4. “Access to the Pyrroloindoline Core via [3 + 2] Annulation as well as the Application in the Synthetic Approach to (±)-Minfiensine ”Ji, W.; Yao, L.; Liao, X. * Org. Lett. 2016, 18, 628.(*corresponding author)
5. “Enantioselective and Diastereoselective Azo-coupling/Iminium-Cyclization: A Unified Strategy for the Total Synthesis of (-)-Psychotriasine and (+)-Pestalazine B ”Li, Q.; Xia, T.; Yao, L.; Deng, H.*; Liao, X. * Chem. Sci. 2015, 6, 3599.(*corresponding author)
6. “Fluorescent Probes for the Detection of Hydrogen Peroxidein Biological Systems”Liu, Y.*, Liao,X.* Curr. Org. Chem. 2013, 17, 654.(*corresponding author)
7. “Stereospecific Approach to the Synthesis of Ring‑A Oxygenated Sarpagine Indole Alkaloids. Talent Total Synthesis of the Dimeric Indole Alkaloid P‑(+)-Dispegatrine and Six Other Monomeric Indole Alkaloids” Edwankar, C. R.; Edwankar, R. V.; Namjoshi, O. A.; Liao, X.; Cook, J. M. J. Org. Chem. 2013, 78, 6471.
8. “2‑Bromopalmitate Analogues as Activity-Based Probes To Explore Palmitoyl Acyltransferases” Zheng, B.; DeRan, M.; Li, X.; Liao, X.; Fukata, M.; Wu, X. J. Am. Chem. Soc. 2013, 135, 7082.
9. “Enantioselective Total Syntheses of (–)-Taiwaniaquinone H and (–)-Taiwaniaquinol B by Iridium-Catalyzed Borylation and Palladium-Catalyzed Asymmetric α-Arylation” Liao, X.; Stanley, L. M.; Hartwig, J. F.; J. Am. Chem. Soc.2011, 133, 2088.
10. “ Small Molecule Antagonists in Distinct Binding Modes Inhibit Drug Resistant Mutant of Smoothened” Tao, H.; Jin, Q.; Koo, D.; Liao, X.; Englund, N. P.; Wang, Y.; Ramamurthy, A.; Schultz, P. G.; Dorsch, M.; Kelleher, J.; Wu, X. Chem. Biol. 2011, 18, 432.
11. “Cyanation of Arenes via Iridium-catalyzed Borylation” Liske, C. W.; Liao, X.; Hartwig, J. F.; J. Am. Chem. Soc. 2010, 132, 11389.
12. “Enantioselective -Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel” Liao, X.; Weng, Z.; Hartwig, J. F.; J. Am. Chem. Soc. 2008, 130, 195.(published and highlighted in SYNFACTS issue 04/08)
13. “General Approach to the Total Synthesis of 9-Methoxy-Substituted Indole Alkaloids: Synthesis of Mitragynine, as well as 9-Methoxygeissoschizol and 9-Methoxy-Nb-methylgeissoschizol” Ma, J.; Yin, W.; Zhou, H.; Liao, X; Cook, J. M. J. Org. Chem. 2009, 74, 264.
14. “Synthesis and structure-activity relationship studies on tryprostatin A, an inhibitor of breast cancer resistance protein” Jain, H. D.; Zhang, C.; Zhou, S.; Zhou, H.; Ma, J.; Liu, X.; Liao, X.; Deveau, A. M.; Dieckhaus, C. M.; Johnson, M. A.; Smith, K. S.; Macdonald, T. L.; Kakeya, H.; Osada, H.; Cook, J. M. Bioorg. Med. Chem. 2008, 16, 4626.
15. “meta-Halogenation of 1,3-Disubstituted Arenes via Iridium-catalyzed Arene Borylation” Murphy, J. M.; Liao, X.; Hartwig, J. F.; J. Am. Chem. Soc. 2007, 129, 15434.
16. “Palladium-Catalyzed α-Arylation of Trimethylsilyl Enol Ethers with Aryl Bromides and Chlorides: The Synergistic Effect of Two Metal Fluorides as Additives” Su, W †; Raders, S; † Verkade, J. G.;*,†Liao, X.;‡ and Hartwig, J. F.*,‡ Angew. Chem., Int. Ed. 2006, 45, 5852. a VIP paper and highlighted at the cover. (two group’s work)
17. “A Cascade Approach Toward the Core Structure of Neosarpagine” Liao, X.; Huang, S.; Zhou, H.; Parrish, D.; Cook, J. M. Org Lett. 2007, 9, 1469.
18. “An Improved Total Synthesis of (+)-Macroline and Alstonerine as well as the Formal Total Synthesis of (-)-Talcarpine and (-)-Anhydromacrosalhine-methine” Liao, X.; Zhou, H.; Cook, J. M.; J. Org. Chem. 2006, 71, 8884. (most-accessed articles: October-December, 2006)
19. General Approach for the Synthesis of 12-Methoxy-Substituted Sarpagine Indole Alkaloids Including (-)-12-Methoxy-Nb-methylvoachalotine, (+)-12-Methoxy-Na-methylvellosimine, (+)-12-Methoxyaffinisine, and (-)-Fuchsiaefoline” Zhou, H.; Liao, X.; Yin, W.; Ma, J.; Cook, J. M. J. Org. Chem. 2006, 71, 251.
20. “The First Regiospecific, Enantiospecific Total Synthesis of 6-Oxoalstophylline and an Improved Total Synthesis of Alstonerine and Alstophylline as well as the Bisindole Alkaloid Macralstonine” Liao, X.; Zhou, H.; Wearing, X.; Ma, J.; Cook, J. M. Org. Lett. 2005,7, 3501.
2. “Copper-Catalyzed 2,2,2-Trifluoroethylthiolation of Aryl Halides” Chen, S.; Zhang, M.; Liao, X. *; Weng, Z. * J. Org. Chem. 2016, ASAP. (*corresponding author)
3. “Nickel-catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide”Hu, L.; Liu, X. Liao, X.* Angew. Chem., Int. Ed. 2016, 55, 9743. (*corresponding author)
4. “Access to the Pyrroloindoline Core via [3 + 2] Annulation as well as the Application in the Synthetic Approach to (±)-Minfiensine ”Ji, W.; Yao, L.; Liao, X. * Org. Lett. 2016, 18, 628.(*corresponding author)
5. “Enantioselective and Diastereoselective Azo-coupling/Iminium-Cyclization: A Unified Strategy for the Total Synthesis of (-)-Psychotriasine and (+)-Pestalazine B ”Li, Q.; Xia, T.; Yao, L.; Deng, H.*; Liao, X. * Chem. Sci. 2015, 6, 3599.(*corresponding author)
6. “Fluorescent Probes for the Detection of Hydrogen Peroxidein Biological Systems”Liu, Y.*, Liao,X.* Curr. Org. Chem. 2013, 17, 654.(*corresponding author)
7. “Stereospecific Approach to the Synthesis of Ring‑A Oxygenated Sarpagine Indole Alkaloids. Talent Total Synthesis of the Dimeric Indole Alkaloid P‑(+)-Dispegatrine and Six Other Monomeric Indole Alkaloids” Edwankar, C. R.; Edwankar, R. V.; Namjoshi, O. A.; Liao, X.; Cook, J. M. J. Org. Chem. 2013, 78, 6471.
8. “2‑Bromopalmitate Analogues as Activity-Based Probes To Explore Palmitoyl Acyltransferases” Zheng, B.; DeRan, M.; Li, X.; Liao, X.; Fukata, M.; Wu, X. J. Am. Chem. Soc. 2013, 135, 7082.
9. “Enantioselective Total Syntheses of (–)-Taiwaniaquinone H and (–)-Taiwaniaquinol B by Iridium-Catalyzed Borylation and Palladium-Catalyzed Asymmetric α-Arylation” Liao, X.; Stanley, L. M.; Hartwig, J. F.; J. Am. Chem. Soc.2011, 133, 2088.
10. “ Small Molecule Antagonists in Distinct Binding Modes Inhibit Drug Resistant Mutant of Smoothened” Tao, H.; Jin, Q.; Koo, D.; Liao, X.; Englund, N. P.; Wang, Y.; Ramamurthy, A.; Schultz, P. G.; Dorsch, M.; Kelleher, J.; Wu, X. Chem. Biol. 2011, 18, 432.
11. “Cyanation of Arenes via Iridium-catalyzed Borylation” Liske, C. W.; Liao, X.; Hartwig, J. F.; J. Am. Chem. Soc. 2010, 132, 11389.
12. “Enantioselective -Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel” Liao, X.; Weng, Z.; Hartwig, J. F.; J. Am. Chem. Soc. 2008, 130, 195.(published and highlighted in SYNFACTS issue 04/08)
13. “General Approach to the Total Synthesis of 9-Methoxy-Substituted Indole Alkaloids: Synthesis of Mitragynine, as well as 9-Methoxygeissoschizol and 9-Methoxy-Nb-methylgeissoschizol” Ma, J.; Yin, W.; Zhou, H.; Liao, X; Cook, J. M. J. Org. Chem. 2009, 74, 264.
14. “Synthesis and structure-activity relationship studies on tryprostatin A, an inhibitor of breast cancer resistance protein” Jain, H. D.; Zhang, C.; Zhou, S.; Zhou, H.; Ma, J.; Liu, X.; Liao, X.; Deveau, A. M.; Dieckhaus, C. M.; Johnson, M. A.; Smith, K. S.; Macdonald, T. L.; Kakeya, H.; Osada, H.; Cook, J. M. Bioorg. Med. Chem. 2008, 16, 4626.
15. “meta-Halogenation of 1,3-Disubstituted Arenes via Iridium-catalyzed Arene Borylation” Murphy, J. M.; Liao, X.; Hartwig, J. F.; J. Am. Chem. Soc. 2007, 129, 15434.
16. “Palladium-Catalyzed α-Arylation of Trimethylsilyl Enol Ethers with Aryl Bromides and Chlorides: The Synergistic Effect of Two Metal Fluorides as Additives” Su, W †; Raders, S; † Verkade, J. G.;*,†Liao, X.;‡ and Hartwig, J. F.*,‡ Angew. Chem., Int. Ed. 2006, 45, 5852. a VIP paper and highlighted at the cover. (two group’s work)
17. “A Cascade Approach Toward the Core Structure of Neosarpagine” Liao, X.; Huang, S.; Zhou, H.; Parrish, D.; Cook, J. M. Org Lett. 2007, 9, 1469.
18. “An Improved Total Synthesis of (+)-Macroline and Alstonerine as well as the Formal Total Synthesis of (-)-Talcarpine and (-)-Anhydromacrosalhine-methine” Liao, X.; Zhou, H.; Cook, J. M.; J. Org. Chem. 2006, 71, 8884. (most-accessed articles: October-December, 2006)
19. General Approach for the Synthesis of 12-Methoxy-Substituted Sarpagine Indole Alkaloids Including (-)-12-Methoxy-Nb-methylvoachalotine, (+)-12-Methoxy-Na-methylvellosimine, (+)-12-Methoxyaffinisine, and (-)-Fuchsiaefoline” Zhou, H.; Liao, X.; Yin, W.; Ma, J.; Cook, J. M. J. Org. Chem. 2006, 71, 251.
20. “The First Regiospecific, Enantiospecific Total Synthesis of 6-Oxoalstophylline and an Improved Total Synthesis of Alstonerine and Alstophylline as well as the Bisindole Alkaloid Macralstonine” Liao, X.; Zhou, H.; Wearing, X.; Ma, J.; Cook, J. M. Org. Lett. 2005,7, 3501.
