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人才隊(duì)伍

趙祥
研究員，研究組長(zhǎng)，博士生導(dǎo)師
E-mail: xiang.zhao@sibcb.ac.cn
實(shí)驗(yàn)室主頁: https://zhaoxianglab.sibcb.ac.cn

個(gè)人簡(jiǎn)介：

2009-2013年，復(fù)旦大學(xué)生命科學(xué)學(xué)院，生物科學(xué)學(xué)士
2013-2018年，新加坡國立大學(xué)醫(yī)學(xué)院，免疫學(xué)博士
2018-2023年，斯坦福大學(xué)醫(yī)學(xué)院，博士后
2023年6月起任中國科學(xué)院分子細(xì)胞科學(xué)卓越創(chuàng)新中心（生物化學(xué)與細(xì)胞生物學(xué)研究所）研究員，研究組長(zhǎng)，博士生導(dǎo)師

社會(huì)任職：

研究方向：

T細(xì)胞免疫與T細(xì)胞受體

研究工作：

T細(xì)胞受體（TCR）結(jié)合配體peptide-MHC，是免疫系統(tǒng)識(shí)別多種多樣抗原的分子基礎(chǔ)。課題組綜合運(yùn)用生物化學(xué)、細(xì)胞生物學(xué)、免疫學(xué)、蛋白質(zhì)工程、結(jié)構(gòu)生物學(xué)、遺傳學(xué)、生物物理學(xué)等方法，以T細(xì)胞與T細(xì)胞受體為主要研究對(duì)象，深入研究T細(xì)胞受體的抗原識(shí)別與信號(hào)轉(zhuǎn)導(dǎo)機(jī)制，發(fā)展針對(duì)實(shí)體腫瘤的TCR-T細(xì)胞療法。
具體方向包括：
　　1.T細(xì)胞受體抗原識(shí)別與信號(hào)轉(zhuǎn)導(dǎo)的新機(jī)制;
　　2.T細(xì)胞受體等免疫受體的蛋白質(zhì)工程改造新技術(shù);
　　3.T細(xì)胞抗原識(shí)別與信號(hào)轉(zhuǎn)導(dǎo)的結(jié)構(gòu)基礎(chǔ);
　　4.多學(xué)科賦能的實(shí)體腫瘤特異TCR-T細(xì)胞療法;
　　5.鑒定新型的免疫受體-配體。
主持項(xiàng)目：
　　國家自然科學(xué)基金委員會(huì)原創(chuàng)探索計(jì)劃(主持，2024-2026)
　　中國科學(xué)院率先行動(dòng)(主持，2024-2026)
　　上海市白玉蘭人才計(jì)劃浦江項(xiàng)目(主持，2023-2025)

承擔(dān)科研項(xiàng)目情況：

代表論著：

1. Wang, Y., Wang, Y., Yuan, W., Fan, M., Wang, X., Wang, A., Bao, Y., Zhang, Y., Tan, J.C., Wang, J., Liu, J., Huang T., Han Z., Pei B., Chen L., Ren Z., Wang X., Hu L., Wu S., Pang M., Wang S., Yang Z., Li J., Huang D., Shao S., Yuan H., Wu L., Feng Y., Zhou P., Li G., Sun B., Xu C., Gascoigne N., Zhao*, X. (2026). Tuning the sensitivity of mechanosensory receptors through histidine scanning. Cell. https://doi.org/10.1016/j.cell.2025.12.050.
2. Fan, M., and Zhao*, X. (2025). Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy. Acta Biochim. Biophys. Sin. https://doi.org/10.3724/abbs.2025216
3. Zhao*, X., Shao, S., and Hu, L. (2024). The recent advancement of TCR-T cell therapies for cancer treatment. Acta Biochim. Biophys. Sin. https://doi.org/10.3724/abbs.2024034.
4. Ren, F., Wang, F., Baghdasaryan, A., Li, Y., Liu, H., Hsu, R., Wang, C., Li, J., Zhong, Y., Salazar, F., et al. (2024). Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses. Nat. Biomed. Eng. 8, 726–739. https://doi.org/10.1038/s41551-023-01083-5.
5. Yang, X., Nishimiya, D., L?chte, S., Jude, K.M., Borowska, M., Savvides, C.S., Dougan, M., Su, L., Zhao, X., Piehler, J., et al. (2023). Facile repurposing of peptide–MHC-restricted antibodies for cancer immunotherapy. Nat Biotechnol, 1–12. https://doi.org/10.1038/s41587-022-01567-w.
6. Chan, W., Cao, Y.M., Zhao, X., Schrom, E.C., Jia, D., Song, J., Sibener, L.V., Dong, S., Fernandes, R.A., Bradfield, C.J., et al. (2023). TCR ligand potency differentially impacts PD-1 inhibitory effects on diverse signaling pathways. J. Exp. Med. 220, e20231242. https://doi.org/10.1084/jem.20231242.
7. Zhao, X., Kolawole, E.M., Chan, W., Feng, Y., Yang, X., Gee, M.H., Jude, K.M., Sibener, L.V., Fordyce, P.M., Germain, R.N., et al. (2022). Tuning T cell receptor sensitivity through catch bond engineering. Science (New York, N.Y.) 376, eabl5282. https://doi.org/10.1126/science.abl5282.Nat Rev Drug Discov綜述點(diǎn)評(píng)Nat Rev Clin Oncol綜述點(diǎn)評(píng)F1000推薦美國授權(quán)PCT專利PCT/US2022/018975
8. Yang, X., Garner, L.I., Zvyagin, I.V., Paley, M.A., Komech, E.A., Jude, K.M., Zhao, X., Fernandes, R.A., Hassman, L.M., Paley, G.L., et al. (2022). Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides. Nature, 1–7. https://doi.org/10.1038/s41586-022-05501-7.
9. Yen, M., Ren, J., Liu, Q., Glassman, C.R., Sheahan, T.P., Picton, L.K., Moreira, F.R., Rustagi, A., Jude, K.M., Zhao, X., et al. (2022). Facile discovery of surrogate cytokine agonists. Cell. https://doi.org/10.1016/j.cell.2022.02.025.
10. Feng, Y., Zhao, X., White, A.K., Garcia, K.C., and Fordyce, P.M. (2022). A bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation. Nat Methods, 1–11. https://doi.org/10.1038/s41592-022-01592-2.
11. Wu, L., Balyan, R., Brzostek, J., Zhao, X., and Gascoigne, N.R.J. (2022). Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response. Embo Rep, e54969. https://doi.org/10.15252/embr.202254969.
12. Zhao, X., Wu, L.-Z., Ng, E.K.Y., Leow, K.W.S., Wei, Q., Gascoigne, N.R.J., and Brzostek, J. (2021). Non-Stimulatory pMHC Enhance CD8 T Cell Effector Functions by Recruiting Coreceptor-Bound Lck. Frontiers in immunology 12, 721722. https://doi.org/10.3389/fimmu.2021.721722.
13. Brzostek, J., Gautam, N., Zhao, X., Chen, E.W., Mehta, M., Tung, D.W.H., Chua, Y.L., Yap, J., Cho, S.H., Sankaran, S., et al. (2020). T cell receptor and cytokine signal integration in CD8+ T cells is mediated by the protein Themis. Nature immunology 21, 186–198. https://doi.org/10.1038/s41590-019-0570-3.
14. Wei, Q., Brzostek, J., Sankaran, S., Casas, J., Hew, L.S.-Q., Yap, J., Zhao, X., Wojciech, L., and Gascoigne, N.R.J. (2020). Lck bound to coreceptor is less active than free Lck. Proceedings of the National Academy of Sciences of the United States of America 117, 15809–15817. https://doi.org/10.1073/pnas.1913334117.
15. Zhao, X., Hamidinia, M., Choo, J.A.L., Too, C.T., Ho, Z.Z., Ren, E.C., Bertoletti, A., MacAry, P.A., Gould, K.G., Brzostek, J., et al. (2019). Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation. J. Vis. Exp. https://doi.org/10.3791/59126-v.
16. Zhong, Y., Ma, Z., Wang, F., Wang, X., Yang, Y., Liu, Y., Zhao, X., Li, J., Du, H., Zhang, M., et al. (2019). In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles. Nature biotechnology 37, 1322–1331. https://doi.org/10.1038/s41587-019-0262-4.
17. Zhao, X., Sankaran, S., Yap, J., Too, C.T., Ho, Z.Z., Dolton, G., Legut, M., Ren, E.C., Sewell, A.K., Bertoletti, A., et al. (2018). Nonstimulatory peptide-MHC enhances human T-cell antigen-specific responses by amplifying proximal TCR signaling. Nature communications 9, 2716. https://doi.org/10.1038/s41467-018-05288-0.

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