尹航 - 清华大学

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尹航教授收藏完善纠错
清华大学药学院
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个人简介

尹航，清华大学校学术委员会委员、校科技伦理委员会委员，药学院原副院长，兼任Bioorganic & Medicinal Chemistry Letters (Elsevier)主编、Journal of Extracellular Vesicle (Wiley)责任主编、Cell Chemical Biology (Cell Press)编委、中国细胞外囊泡研究与应用学会顾问、中国生物医药产业链创新与转化联盟常务理事及重大需求专委会主任委员、全国中药标准化技术委员会委员等。尹航教授团队在本领域一流期刊发表研究论文超过150篇(H-Index=61，总引用超2万次)；科研成果已申请专利超20项，并有多项成果转化。尹航教授先后入选国家和中国科协海智计划特聘专家、获得国家自然基金委杰出青年科学基金、北京市卓越青年科学家奖、吴阶平-保罗·杨森医学药学奖、中国药学会科学技术一等奖、教育部自然科学二等奖、美国化学学会大卫·罗伯特森杰出药物化学家奖、美国国家科学基金会杰出青年教授奖、美国癌症研究学会格特魯德·B·埃利恩奖、中美化学及化学生物学教授联合会OKeanos-CAPA资深科学家奖、悉德尼·金梅尔学者奖等奖项。

研究领域

Drug Discovery: Potential Therapeutics that Inhibit Toll-like Receptors. Pain remains a significant public health issue with two-thirds of patients achieving little to no pain relief from the myriad of currently available pharmacotherapies and dosing regimens. The use of opioid pharmacotherapies produces several rewarding and reinforcing side effects, which result in their diversion to abuse settings. Glial cells have been found to play a critical role in initiating and maintaining increased nociception in response to peripheral nerve injury. The opioids-induced glial cell activation attenuates opioid-induced pain suppression and enhances the development of opioid tolerance and dependence, the drug reward, and other negative side effects such as respiratory depression. We are interested in employing structure-based drug design and high-throughput screening techniques to identify novel small-molecule inhibitors of TLR4 that regulates glial cell activation. The identified agents will potentially serve as therapeutics that can suppress opioid-dependence and tolerance. Using these methods, we also successfully identified small molecule inhibitors that disrupt the TLR3-dsRNA interaction. This is significant because the protein-RNA complex is a challenging target for small molecule probes. Our goal is to develop a generally applicable method to provide small molecule probes for the protein-protein and protein-RNA interactions of these clinically relevant TLRs. Protein Engineering: Peptides Targeting Transmembrane Domains of Proteins. Protein transmembrane domains (TMDs) regulate many pivotal biological processes, including cell signal transduction, cancer development, ion transmission, and membrane protein folding. However, the nature of molecular recognition in membranes is little understood due to the lack of available probes with high affinity and specificity. Conventional tools such as antibodies are unable to bind to the transmembrane regions of membrane proteins. A goal in our lab is to develop exogenous peptide and small-molecule agents that target transmembrane helices. Using these agents, we can study these important membrane protein-protein interactions, thereby further our understanding of molecular recognition in membranes. As a proof-of-principle, we developed novel peptide/peptidomimetic reagents to recognize the TMDs of latent membrane proteins 1 (LMP-1) found in the human Epstein-Barr herpesvirus lymphomas and syndromes. These designed peptides will be used to study TMD-mediated LMP-1 activation. The findings from these studies will lay the groundwork for the discovery of new pharmaceutical agents with which we can prevent, diagnose, and treat herpesvirus-dependent cancers. Biotechnology Development: Non-invasive Cancer Biomarkers. Elevated microvesicle (MV) shedding is an indication of cancer metastasis. Selectively sensing the highly curved membrane of MVs may provide a novel strategy for their detection, which renders the potential of developing diagnostic, prognostic, and therapeutic agents. We employed a multidisciplinary approach, utilizing our expertise in computational modeling, membrane biophysics, and cellular assay development to rationally design novel tools that sense and regulate membrane curvature and lipid components. These rationally designed agents not only help us to understand the critical protein-lipid interactions but also provide prototypes that may eventually lead to novel cancer biomarkers. Fig: Schematic of using fluorescently labeled peptide to detect shed MVs. (A) Cancerous cells shed MVs into body fluid; (B) Collection body fluid from a patient suspected to have metastatic cancers; (C) Unstructured peptide labeled with a fluorophore via a flexible linker was added into the collected body fluid specimen; (D) Curvature/lipid-sensing detects MVs by selectively binding to their highly curved surfaces or a specific lipid component, resulting in (E) the fluorescence enhancement due to the elevated hydrophobic environment of the fluorophore; (F) MV detection by fluorescently labeled curvature/lipid-sensing peptides

近期论文

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Su, C.; Cheng, T.; Huang, J.; Zhang, T.; *Yin, H. “4-Octyl Itaconate Restricts STING Activation by Blocking Its Palmitoylation”, Cell Rep. 2023, 42, e113040. Jin, X.; Xia, T.; Luo, S.; Zhang, Y.; Xia, Y.; *Yin, H. “Exosomal Lipid PI4P Regulates Small Extracellular Vesicle Secretion by Modulating Intraluminal Vesicle Formation”, J. Extracell. Vesicles 2023, 12, e12319. Liang, J.; *Yin, H. “STAM Transports STING Oligomers into Extracellular Vesicles Down-Regulating the Innate Immune Response”, J. Extracell. Vesicles 2023, 12, e12316. "USP15 Promotes cGAS Activation through Deubiquitylation and Liquid Condensation", Shi, S.; Yang, X.; Hou, Y.; Jin, X.; Guo, L.; Zhou, Y.; Zhang, C.; *Yin, H. ; Nucleic Acid Res 2022, 50, 11093-11108 "Protein Phosphatase 1 Regulates Phosphorylation of Gasdermin D and Pyroptosis", Li, Y.; Pu, D.; Huang, J.; Zhang, Y.; *Yin, H. ; Chem. Comm 2022, 58, 11965-11968 "ZDHHC18 Negatively Regulates cGAS-Mediated Innate Immunity Through Palmitoylation", Shi, S.; Yang, X.; Liu, Y.; Li, H.; Chu, H.; Li. G.; *Yin, H. ; EMBO J 2022, 41, e109272 "MARCH8 attenuates cGAS-mediated innate immune responses through ubiquitylation", Yang X.; Shi C.; Li H.; Shen S.; Su C.; *Yin, H. ; Sci Signal 2022, 15(732):eabk3067 "sn-1 Specificity of Lysophosphatidylcholine Acyltransferase-1 Revealed by a Mass Spectrometry-Based Assay", Zhao, X.; Liang, J.; Chen, Z.; Jian, R.; Qian, Y.; Wang, Y.; Guo, Z.; Zhang, W.; Zhang, Y.; Yin, H.; Xia, Y. ; Angew. Chem. Int. Ed 2022, e202215556 "Small Molecule SMU-CX24 Targeting TLR3 Counteracts Inflammation: A Novel Approach to Atherosclerosis Therapy", Cen, X.; Wang, B.; Liang, Y.; Chen, Y.; Xiao, Y.; Du, S.; Nandakumar, K. S.; Yin, H.; Liu, S.; Cheng, K. ; Acta Pharm. Sin. B 2022, 12, 3667-3681 "Extracellular Vesicle-Associated MicroRNA-30b-5p Activates Macrophages through the SIRT1/NF-kB Pathway in Cell Senescence", Xiao, Y.; Liang, J.; Witwer, K. W.; Zhang, Y.; Wang, Q.; *Yin, H. ; Front. Immunol 2022, 13, e955175 "Photoactivation of Innate Immunity Receptor TLR8 in Live Mammalian Cells by Genetic Encoding of Photocaged Tyrosine", Yang, Y.; Luo, S.; Huang, J.; Xiao, Y.; Fu, Y.; Liu, W.; *Yin, H. ; ChemBioChem 2022, 23, e202100344 "Summary of Pro. Yin’s CSEMV-EVCNA Award Lecture 2021", Zhang, Y.; *Yin, H. ; Extracell. Vesicles. Circ. Nucleic Acids 2022, 3, 87-92 "Protocol for Evaluation and Validation of TLR8 Antagonists in HEK-Blue Cells via Secreted Embryonic Alkaline Phosphatase Assay", Hu, Z.; Zhang, T.; Jiang, S.; *Yin, H. ; STAR Protoc 2022, 3, e101061 "SARS-CoV-2 Spike Protein Interacts with and Activates TLR4", Zhao, Y.; Kuang, M.; Li, J.; Zhu, L.; Jia, Z.; Guo, X.; Hu, Y.; Kong, J.; Yin, H.; Wang, X.; You, F. ; Cell Res 2021, 31, 818-820 "Design and Optimisation of a Small-Molecule TLR2/4 Antagonist for Anti-Tumour Therapy", Xu, Q.; Li, T.; Chen, H.; Kong, J.; Zhang, L.; *Yin, H. ; RSC Med. Chem 2021, 12, 1771-1779 "Harnessing the Therapeutic Potential of Extracellular Vesicles for Cancer Treatment", Zhang, Y.; Xiao, Y.; Sun, G.; Jin, X.; Guo, L.; Li, T.; *Yin, H. ; Semin. Cancer Biol 2021, 74, 92-104 "SARS-CoV-2 Nucleocapsid Protein Undergoes Liquid-Liquid Phase Separation into Stress Granules through Its N-Terminal Intrinsically Disordered Region", Wang, J.; Shi, C.; Xu, Q.; *Yin, H. ; Cell Discov 2021, 7, 5 "Design, Synthesis, and Structure–Activity Relationship of N-Aryl-N′-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy", Chen, Z.; Zhang, L.; Yang, J.; Zheng, L.; Hu, F.; Duan, S.; Nandakumar, K. S.; Liu, S.; *Yin, H.; *Cheng, K. ; J. Med. Chem 2021, 64, 7371-7389 "TLR4 Biased Small Molecule Modulators", Lin, C.; Wang, H.; Zhang, M.; Mustafa, S.; Wang, Y.; Li, H.; Yin, H.; Hutchinson, M.; Wang, X. ; Pharmacol. Ther 2021, 228, 107918 "Orthosteric-Allosteric Dual Inhibitors of PfHT1 as Selective Anti-Malarial Agents", Huang, J.; Yuan, Y.; Zhao, N.; Pu, D.; Tang, Q.; Zhang, S.; Luo, S.; Yang, X.; Wang, N.; Xiao, Y.; Zhang, T.; Liu. Z.; Sakata-Kato, Y.; Hirata, K.; *Jiang, X.; *Kato, N.; *Yan, N.; *Yin, H. ; Proc. Natl. Acad. Sci. U. S. A 2021, 118, e2017749118 "Tetrasubstituted Imidazoles as Incognito Toll-like Receptor 8 A(nta)gonists", Yang, Y.; Csakai, A.; Jiang, S.; Smith, C.; Tanji, H.; Huang, J.; Jones, T.; Sakaniwa, K; Broadwell, L.; Shi, C.; Soti, S.; Ohto, U.; Fang, Y.; Shen, S.; Deng, F.; Shimizu, T.; *Yin, H. ; Nat. Commun 2021, 12, 4351 "TLR8 and Complement C5 Induce Cytokine Release and Thrombin Activation in Human Whole Blood Challenged with Gram-Positive Bacteria", Ehrnstr?m, B.; Kojen, J.; Giambelluca, M.; Ryan, L.; Moen, S.; Hu, Z.; Yin, H.; Mollnes, T. E.; Dam?s, J.; Espevik, T.; Stenvik, J. ; J. Leukoc. Biol 2020, 107, 673-683 "Discovery of Small Molecule Cyclic GMP-AMP Synthase Inhibitors", Padilla-Salinas, R.; Sun, L; Anderson, R.; Yang, X.; Zhang, S.; Chen, Z.; *Yin, H. ; J. Org. Chem 2020, 85, 1579-1600 "Switch off Parallel Circuit: Insight of New Strategy of Simultaneously Suppressing Canonical and Non-canonical Inflammation Activation in Endotoxemic Mice", Yan, L.; Liang, J.; Zhou, Y.; Huang, J.; Zhang, T.; Wang, X.; *Yin, H. ; Adv. Biosyst 2020, 4, e2000037 "Nuclear Molecular Imaging–Guided Bioorthogonal System Reveals the Antitumor Immune Function of Pyroptosis", *Yin, H. ; Acta. Phys.-Chim. Sin 2020, 36, 2004056 "Regulation of Aerobic Glycolysis to Decelerate Tumor Proliferation by Small Molecule Inhibitors Targeting Glucose Transporters", Gao, M.; Huang, J.; Jiang, X.; Yuan, Y.; Luo, S.; Wang, N.; Pang, H.; Deng, D.; Yao, C.; Lin, Z.; Pu, D.; Liu, Z.; Hu, Z.; *Yin, H. ; Protein Cell 2020, 11, 446-451 "Sensing of HIV-1 by TLR8 Activates Human T cells and Reverses Latency", Meas, H. Z.; Haug, M.; Beckwith, M. S.; Louet, C.; Ryan, L.; Hu, Z.; Landskron, J.; Nordb?, S. A.; Taskén, K.; Yin, H.; Dam?s, J. K.; Flo, T. H. ; Nat. Commun 2020, 11, 147 "Rationally Designed Small-Molecule Inhibitors Targeting an Unconventional Pocket on the TLR8 Protein-Protein Interface", Jiang, S.; Tanji, H.; Yin, K.; Zhang, S.; Sakaniwa, K.; Huang, J.; Yang, Y.; Li, J.; Ohto, U.; Shimizu, T.; *Yin, H. ; J. Med. Chem 2020, 63, 4117-4132 "Small Molecule Modulators of Toll-Like Receptors", Wang, Y.; Zhang, S.; Li, H.; Wang, H.; Zhang, T.; Hutchinson, M.; *Yin, H.; *Wang, X. ; Acc. Chem. Res 2020, 53, 1046-1055 "How Does an RNA Selfie Work? EV-Associated RNA in Innate Immunity as Self or Danger", Xiao, Y.; Driedonks, T.; Witwer, K.; Wang, Q.; *Yin, H. ; J. Extracell. Vesicles 2020, 9, e1793515 "Immune Profiling Before Treatment is Predictive of TLR9-Induced Antitumor Efficacy", Xu, Q.; Dai, C.; Kong, J.; Chen, H.; Feng, J.; Zhang, Y.; *Yin, H. ; Biomaterials 2020, 263, 120379 "Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum", Jiang, X.; Yuan, Y.; Huang, J.; Zhang, S.; Luo, S.; Wang, N.; Pu, D.; Zhao, N.; Tang, Q.; Hirata, K.; Yang, X.; Jiao, Y.; Sakata-Kato, Y.; Wu, J.; Yan, C.; Kato, N.; *Yin, H.; *Yan, N. ; Cell 2020, 183, 258-268 "Focusing on the Influenza Virus Polymerase Complex: Recent Progress in Drug Discovery and Assay Development", Zhang, J.; Hu, Y.; Musharrafieh, R. G.; Yin, H.; Wang, J. ; Curr. Med. Chem 2019, 26, 2243-2263 "Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): a Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines", Thery, C. et al. ; J. Extracell. Vesicles 2019, 8, e1535750 "Photoactivatable Prodrug of Doxazolidine Targeting Exosomes", Tamura, R.; Balabanova, A.; Frakes, S. A.; Bargmann, A.; Koch, T. H.; *Yin, H. ; J. Med. Chem 2019, 62, 1959-1970 "TLR1/2 Specific Small-Molecule Agonist Suppresses Leukemia Cancer Cell Growth by Stimulating Cytotoxic T Lymphocytes", Cen, X.; Zhu, G.; Yang, J.; Yang, J.; Guo, J.; Jin, J.; Nandakumar, K.; Yang, W.; Yin, H.; Liu, S.; Cheng, K. ; Adv. Sci 2019, 6, e1802042 "Human TLR8 is an Important Sensor of Pyogenic Bacteria and is Attenuated by Cell Surface TLR Signaling", Moen, S. H; Ehrnstr?m, B.; Kojen, J. F.; Beckwith, K. S.; Afset, J. E.; Dam?s, J. K.; Hu, Z.; Yin, H.; Espevik, T.; Stenvik, J. ; Front. Immunol 2019, 10, 1209 "Lovastatin Inhibits TLR4 Signaling in Microglia by Targeting Its Co-Receptor MD2 and Attenuates Neuropathic Pain", Peng, Y.; Zhang, X.; Zhang, T.; Grace, P. M.; Li, H.; Wang, Y.; Chen, H.; Watkins, L. R.; Hutchinson, M. R.; Yin, H.; Wang, X. ; Brain Behav. Immun 2019, 82, 432-444 "Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptor 7 and 8", Padilla-Salinas, R.; Anderson, R.; Sakaniwa, K.; Zhang, S.; Nordeen, P.; Lu, C.; Shimizu, S.; *Yin, H. ; J. Med. Chem 2019, 62, 10221-10244 "Extracellular Vesicles Derived from ODN-Stimulated Macrophages Promote Their Cellular Uptake by the Transfer and Activation of Cdc42", Zhang, Y.; Jin, X.; Liang, J.; Guo, Y.; Sun, G.; Zeng, X.; *Yin, H. ; Sci. Adv 2019, 5, eaav1564 "Focusing on the Influenza Virus Polymerase Complex: Recent Progress in Drug Discovery and Assay Development", Zhang, J.; Hu, Y.; Musharrafieh, R.; Yin, H.; Wang, J.; Curr. Med. Chem. 2018. "An Iterative Computational Design Approach to Increase the Thermal Endurance of a Mesophilic Enzyme", Sammond, D.; Kastelowitz, N.; Donohoe, B.; Alahuhta, M.; Lunin, V.; Sarai, N.; Yin, H.; Mittal, A.; Himmel, M.; Guss, A.; Bomble, Y.; Biotechnol Biofuels. 2018, 11:189. "Small Molecule TLR8 Antagonists via Structure-Based Rational Design", Hu, Z.; Tanji, H.; Jiang, S.; Zhang, S.; Koo, K.; Chan, J.; Sakaniwa, K.; Ohto, U.; Candia, A.; Shimizu, T.; Yin, H.; Cell Chem. Biol. 2018, 25, 1286-1291. "Discovery of Novel Small Molecule Inhibtors of NF-κB Signaling with Anti-Inflammatory and Anti-Cancer Properties", Zhang, L.; Shi, L.; Soars, S.; Kamps, J.; Yin, H.; J. Med. Chem. 2018, 61, 14, 5881-5899. "TLR4-Dependent Fibroblast Activation Drives Persistent Organ Fibrosis in Skin and Lung", Bhattacharyya, S.; Wang, W.; Qin, W.; Cheng, K.; Coulup, S.; Chavez, S.; Jiang, S.; Raparia, K.; De Almeida, L. M.; Stehlik, C.; Tamaki, Z.; Yin, H.; Varga, J.; JCI Insight 2018, 3(13), e98850. "Small Molecule Inhibition of TLR8 through Stabilization of Its Resting State", Zhang, S.; Hu, Z.; Tanji, H.; Jiang, S.; Das, N.; Li, J.; Sakaniwa, K.; Jin, J.; Bian, Y.; Ohto, U.; Shimizu, T.; Yin, H.; Nat. Chem. Biol. 2018, 14, 58-64.[C&EN][CU Boulder Today] "DREADDed Microglia in Pain: Implications for Spinal Inflammatory Signaling in Male Rats", Grace, P. M.; Wang, X.; Strand, K. A.; Baratta, M. V.; Zhang, Y.; Galer, E. L.; Yin, H.; Maier, S. F.; Watkins, L. R.; Exp. Neurol. 2018, 304, 125-131. “Summary of the ISEV Workshop on Extracellular Vesicles as Disease Biomarkers, Held in Birmingham, UK, During December 2017”, Clayton, A.; Buschmann, D.; Byrd, J. B.; Carter, D. R. F.; Cheng, L.; Compton, C.; Daaboul G.; Devitt, A.; Falcon-Perez, J. M.; Gardiner, C.; Gustafson, D.; Harrison, P.; Helmbrecht, C.; Hendrix, A.; Hill, A.; Hoffman, A.; Jones, J. C.; Kalluri, R.; Kang, J. Y.; Kirchner, B.; L?sser, C.; Lawson, C.; Lenassi, M.; Levin, C.; Llorente, A.; Martens-Uzunova, E. S.; M?ller, A.; Musante, L.; Ochiya, T.; Pink, R. C.; Tahara, H.; Wauben, M. H. M.; Webber, J. P.; Welsh, J. A.; Witwer, K. W.; Yin, H.; Nieuwland, R.; J. Extracell. Vesicles 2018, 7, e1473707.

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