廖学斌实验室利用药物化学、各种筛选技术和结构生物学等手段理性设计工具小分子化合物研究先天免疫系统。例如：利用蛋白结构信息及新的筛选体系，课题组发现了新的TLR7和8的小分子激动剂以及TLR7小分子拮抗剂；并利用新的TLR7小分子激动剂开展了与PD-1抗体的癌症免疫组合治疗，不仅验证了“协同机制”，还发现了与PD-1抗体治疗效果密切相关的基因；另外，课题组基于新的蛋白结构信息，理性设计了造血祖蛋白激酶的小分子抑制剂，此抑制剂在癌症免疫治疗中极具前景；课题组还利用KMO的相关结构开展了小分子抑制剂的研究，这类小分子抑制剂将可能被用于对老年痴呆症和急性胰腺炎的治疗。

研究成果

2.发现了组蛋白去甲基化酶KDM5A与PD-1抗体治疗的协同机制，此项研究不仅找到了一种可以预测PD-1抗体治疗效果的潜在生物标记物，还揭示了一种新的免疫组合疗法，这种组合疗法将大大提高免疫检验点阻断疗法的效果。

清华大学-杨森研究员（Janssen-Tsinghua Investigator）（2013-2015）

Roche Chinese Investigator Award（2018）

The Thieme Chemistry Journals Award （2020）

1. “Structure-Based Drug Design of Highly Potent Toll-Like Receptor 7/8 dual Agonists for Cancer Immunotherapy”, Wang, Z.; ^# Gao, Y.; ^# He, L.; ^# Sun, S.; Xia, T.; Hu, L.; Yao, L.; Wang, L.; Li, D.; Shi, H.; Liao, X. ^* J. Med. Chem. 2021, ASAP.

2. “Tumor Immunological Phenotype Signature-based High Throughput Screening for the Discovery of Combination Immunotherapy Compounds”, Wang, H.; Li, S.; Wang, Q.; Jin, Z.; Shao, W.; Gao, Y.; Li, L.; Lin, K.; Zhu, L.; Wang, H.; Liao, X.; Wang, D.* Sci Adv. 2021, 7(4), eabd7851.

3. “Recent Progress in Radical Decarboxylative Functionalizations Enabled by Transition Metal (Ni, Cu, Fe, Co or Cr) Catalysis”, Chen, H.; Liu, Y.; ^* Liao, X. ^* Synthesis 2021, 53, 1–29.

4. “Hematopoietic progenitor kinase1 (HPK1) mediates T cell dysfunction and is a druggable target for T-cell based immunotherapies”, Si, J.; ^# Shi, X.; ^# Sun, S.; ^# Zou, B.; ^# Li, Y.; An, D.; Lin, X.; Gao, Y.; Long, F.; Pang, B.; Liu, X.; Liu, T.; Chi, W.; Chen, L.; Dimitrov , D. S.; Sun, Y.; Du, X.; Yin, W.; Gao, G.; Min, J.; Wei, L.; ^* Liao, X.^* Cancer Cell 2020, 38, 551.

5. “Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade”, Wang, L.; ^# Gao, Y.; ^# Zhang, G.; ^# Li, D.; ^# Wang, Z.; Zhang, J.; Hermida, L. C.; He, L.; Wang, Z.; Si, J.; Geng, S.; Ai, R.; Ning, F.; Cheng, C.; Deng, H.; Dimitrov, D. S.; Sun, Y.; Huang, Y.; Wang, D.; Hu, X.; ^* Wei, Z.; ^* Wang, W.; ^* Liao, X.^* Sci Trans Med. 2020, 12, Issue 560, eaax2282.

6. “Neural regulation of humoral immune responses amenable to behavioral modulation”, Zhang, X.; Lei, B.; Yuan, Y.; Zhang, L.; Hu, L.; Jin, S.; Kang, B.; Liao, X.; Sun, W.; Xu, F.; Zhong, Y.; ^* Hu, J.; ^* Qi, H. ^* Nature 2020, 581, 204.

7. “Nickel-Catalyzed Cyanation of Aryl Halides and Hydrocyanation of Alkynes via C-CN Bond Cleavage and Cyano Transfer”, Chen, H.; Sun, S.; Liu, Y.; Liao, X. ^* ACS Catal. 2020, 10, 1397.

8. “A newly designed heterodiene and its application to construct six-membered heterocycles containing an N–O bond” Ji, W.; ^# Li, C.; ^# Chen, H.; Yu, Z.; ^* Liao, X. ^* Chem. Comm. 2019, 55, 12012.

9. “Nickel-Catalyzed Decarboxylative Alkenylation of Vinyl Triflates or Halides with Anhydrides”, Chen, H.; Sun, S.; Liao, X. ^* Org Lett 2019, 21, 3625.

10. “Nickel catalyzed decarboxylative alkylation of aryl triflates with anhydrides”, Chen, H.; Liao, X. ^* Tetrahedron 2019, 75, 4186. ( Special issue in honor of Prof. John F Hartwig’s Tetrahedron Award)

11. “Nickel-Catalyzed Decarboxylative Alkylation of Aryl Iodides with Anhydrides”, Chen, H.; Hu, L.; Ji, W.; Yao, L.; Liao, X.^* ACS Catal. 2018, 8, 10479.

12. “Enantioselective and Divergent Syntheses of Alstoscholarisines A, E and Their Enantiomers”, Hu, L.; ^# Li, Q.; ^# Yao, L.; ^# Chen, H.; Wang, X.; Liao, X.^* Org. Lett. 2018, 20, 6202 .

13. “Total synthesis of (±)minfiensine via a formal [3+2] cycloaddition”, Zhang, C.; Ji, W.; Liu, Y. A.; Song, C. ^*; Liao, X.^* J. Nat. Prod. 2018, 81, 1065.

14. “Recent Progress in Methylation of (Hetero)Arenes”, Hu, L.; Liu, Y. A.; Liao, X.^* Syn Lett. (SYNPACTS) 2018, 29, 375.

15. “Synthesis of Withasomnine and Pyrazole Derivatives via Intramolecular Dehydrogenative Cyclization, as well as Biological Evaluation of Withasomnine-based Scaffolds”, Xia, T.; Hu, Z.; Ji, W.; Zhang, S.; Shi, H.; Liu, C.; Pang, B.; Liu, G.; Liao, X.^* Org. Chem. Fron. 2018, 5, 850.

16. “ In situ generation of N-unsubstituted imines from alkyl azides and their applications for imine transfer via copper catalysis”, Hu, L.; Liu, Y. A.; Liao, X.^* Sci. Adv. 2017, 3, e1700826 (Highlighted by Synform).

17. “Palladium-Catalyzed Cross-Coupling of Ethyl Bromodifluoroacetate with Aryl Bromides or Triflates and Cross-Coupling of Ethyl Bromofluoroacetate with Aryl Iodides”, Xia, T.; He, L.; Liu, Y. A.; Hartwig, J. F. ^*; Liao, X.^* Org. Lett. 2017, 19, 2610.

18. “The Novel Toll-like Receptor 2 Agonist SUP3 Enhances Antigen Presentation and T cell Activation by Dendritic cells”, Guo, X.; Wu, N.; Shang, Y.; Liu, X.; Wu, T.; Zhou, Y.; Liu, X.; Huang, J.; Liao, X.^*; Wu, L. ^* Front. Immunol. 2017, 8, 158/1-158/15.

19. “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, 55, 13286.

20. “Copper-Catalyzed 2, 2, 2-Trifluoroethylthiolation of Aryl Halides”, Chen, S.; Zhang, M.; Liao, X.^*; Weng, Z. ^* J. Org. Chem. 2016, 81, 7993.

21. “Nickel-catalyzed Methylation of Aryl Halides with Deuterated Methyl Iodide”, Hu, L.; Liu, X.; Liao, X.^* Angew. Chem. Int. Ed. 2016, 55, 9743.

22. “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.

23. “Enantioselective and Diastereoselective Azo-coupling/Iminium-Cyclization: A Unified Strategy for the Total Synthesis of (-)-Psychotriasine and (+)-Pestalazin

e B”, Li, Q.; Xia, T.; Yao, L.; Deng, H. ^*; Liao, X.^* Chem. Sci. 2015, 6, 3599.