教育背景
2005-2009 山东大学生物科学专业 学士
2009-2015 中国科学院生物物理研究所 博士
工作经历
2014-2015 美国芝加哥大学 公派联合培养
2016-2018 中国科学院生物物理研究所 博士后
2018-2019 清华大学药学院 助理研究院
2019-2022 美国得州大学西南医学中心 博士后
2022-2024 清华大学医学院 副研究员
2024-至今 清华大学基础医学院 副研究员
研究领域
癌症是人类健康的重大挑战。近年来癌症免疫治疗在临床上取得了突破性进展，但在大多数肿瘤患者身上无响应。利用蛋白质和核酸工程技术、小鼠动物肿瘤模型、分子和细胞免疫学分析等方法和手段研究肿瘤微环境中免疫调控机制，开发新一代免疫治疗分子。具体研究包括1）新型肿瘤靶向性抗体药物和治疗性细胞因子蛋白药物的设计和开发，并研究其抗肿瘤机制； 2）研究肿瘤微环境免疫逃逸机制，探索有效的联合治疗策略。
科学贡献
结合免疫学和细胞生物学知识探究免疫检查点治疗的细胞和分子学机制，设计开发靶向肿瘤组织的免疫治疗分子用于克服外周毒性，增强肿瘤免疫治疗效果。发现肿瘤组织内宿主髓系细胞表达更高的PD-L1，PD-L1/PD-1抗体治疗肿瘤主要依赖于宿主细胞尤其是髓系细胞表达的PD-L1。进而首次提出并验证了了anti-PDL1抗体可以作为肿瘤特异性抗体运载细胞因子到肿瘤组织用于肿瘤免疫治疗。近年来与合作者设计开发了基于MMP-14可切割底物多肽linker的特定靶向肿瘤组织的pro-IFN和pro-IL15细胞因子前药，避免细胞因子和外周组织受体结合导致的外周毒副作用。其主要研究成果以第一作者或共第一作者身份发表在Cell Research, Journal of Clinical Investigation，Clinical Cancer Research, Nature Communications等学术期刊；与他人合作参与多篇文章发表在Immunity、Sci Transl Med等期刊上。
代表性论文
1.Liang, Y, and Fu YX. LIGHTing CAR T in the tumor microenvironment. Mol Ther. 2023;31(9):2570-1.
2.Cao, X.Z.*, Liang, Y.*, Hu, Z.X., Li, H.Y., Yang, J.M., Hsu, E.J., Zhu, J.K., Zhou J., Y.X. Fu. Next generation of tumor-activating type I IFN enhances antigen presentation to improve treated-resistance inside tumor micro-environment. [*co-first author] Nat Communications 12, 5866 (2021). https://doi.org/10.1038/ s41467-021-26112-2
3.Guo, J.Y. *, Liang, Y.*#, Xue, D.Y., Shen, J., Cai, Y.Q., Zhu, J.K., Fu, Y.X. #, H. Peng#. Tumor-conditional IL-15 pro-cytokine reactivates anti-tumor immunity with limited toxicity. [*co-first author] Cell Research (2021). https://doi.org/10.1038/s41422-021-00543-4
4.Liang, Y., R. Hannan, and Y.-X. Fu. Type I IFN Activating Type I Dendritic Cells for Antitumor Immunity. Clinical Cancer Research 2021;27(14):3818-24.
5.Liang, Y.*, Tang, H. *, Guo, J.Y. *, Qiu X.Y., Yang, Z.C., Ren, Z.H., Sun, Z.C., Bian, Y.J., Xu, H.R., Shen, J., Han, Y.F., Dong, H.D., Peng, H., Y.X. Fu. Targeting type I interferon tumor entry by anti-PD-L1 creates feedforward antitumor responses to overcome innate and adaptive resistance. Nat Communications 2018 Nov 2; 9(1):4586.
6.Tang, H.*, Liang, Y.*, Liu, X., Qiu, X., Mulgaonkar, A., Harrington, S., Guo, J., Peng, H., Sun, X., Qiao, J., Dong, H., Y.X. Fu. PD-L1 on host cells is essential for tumor regression mediated by PD-L1 blockade. [*co-first author] J. Clin. Invest. 2018; 128(2):580-8.
7.Liang, Y. and H. Peng. STING-cytosolic DNA sensing: the backbone for an effective tumor radiation therapy. Ann Transl Med, 2016. 4(3): p. 60.
8.Liang, Y. and H. Peng. LIGHTing tumor up for checkpoint blockade. Oncotarget, 2016. 7(31): p. 48857-48858.
9.Liang, Y., Yang, K.T., Guo, J.Y., Wroblewska, J., Fu, Y.X., H. Peng. Innate lymphotoxin receptor mediated signaling promotes HSV-1 associated neuroinflammation and viral replication. Scientific Reports, 2015.5:10406.
10.Meng CY, Sun S, Liang Y, Xu H, Zhang C, Zhang M, Wang FS, Fu YX, Peng H. Engineered anti-PDL1 with IFNα targets both immunoinhibitory and activating signals in the liver to break HBV immune tolerance. Gut. 2023 Aug;72(8):1544-1554. doi: 10.1136/gutjnl-2022-327059.
11.Shen J, Zou Z, Guo J, Cai Y, Xue D, Liang Y, Wang W, Peng H, Fu YX. An engineered concealed IL-15-R elicits tumor-specific CD8+T cell responses through PD-1-cis delivery. J Exp Med. 2022 Dec 5;219(12):e20220745. doi: 10.1084/jem.20220745.
12.Ren Z, Zhang A, Sun Z, Liang Y, Ye J, Qiao J, Li B, Fu YX. Selective delivery of low-affinity IL-2 to PD-1+ T cells rejuvenates antitumor immunity with reduced toxicity. J Clin Invest. 2022 Feb 1;132(3):e153604. doi: 10.1172/JCI153604.
13.Lu, C., J. Guan, S. Lu, Q. Jin, B. Rousseau, T. Lu, D. Stephens, H. Zhang, J. Zhu, M. Yang, Z. Ren, Y. Liang, Z. Liu, C. Han, L. Liu, X. Cao, A. Zhang, J. Qiao, K. Batten, M. Chen, D.H. Castrillon, T. Wang, B. Li, L.A. Diaz, G.-M. Li, and Y.-X. Fu. DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity. Cancer Cell 2021;39(1):96-108.e6.
14.Deng, S., Z. Sun, J. Qiao, Y. Liang, L. Liu, C. Dong, A. Shen, Y. Wang, H. Tang, Y.-X. Fu, and H. Peng. Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3–CD8+ T cells. JCI Insight. 2020;5(7).
15.Peng, Q., X. Qiu, Z. Zhang, S. Zhang, Y. Zhang, Y. Liang, J. Guo, H. Peng, M. Chen, Y.-X. Fu, and H. Tang. PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade. Nature Communications 2020;11(1).
16.Sun, Z., Z. Ren, K. Yang, Z. Liu, S. Cao, S. Deng, L. Xu, Y. Liang, J. Guo, Y. Bian, H. Xu, J. Shi, F. Wang, Y.-X. Fu, and H. Peng. A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8+ T-cell response and effective tumor control. Nature Communications 2019;10(1).
17.Yang, K., Liang, Y., Sun, Z.C., Xue, D.Y., Xu, H.R., Zhu, M.Z., Fu, Y.X., H. Peng. T Cell-Derived Lymphotoxin Is Essential for the Anti-Herpes Simplex Virus 1 Humoral Immune Response. J Virol. 2018. 92. 14e00428-18
18.Ren, Z., J. Guo, J. Liao, Y. Luan, Z. Liu, Z. Sun, X. Liu, Y. Liang, H. Peng, and Y.-X. Fu. CTLA-4 Limits Anti-CD20–Mediated Tumor Regression. Clinical Cancer Research 2017;23(1):193-203.
19.Pu, Y., Xu, M., Liang, Y., Yang, K.T., Guo, Y.J., Yang, X.M. and Y.X. Fu. Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse. Sci Transl Med, 2016. 8(333):333ra347.
20.Guo, X.H., Liang, Y., Zhang, Y., Lasorella, A., Kee, B.L., Y.X. Fu. Innate Lymphoid Cells Control Early Colonization Resistance against Intestinal Pathogens through ID2-Dependent Regulation of the Microbiota. Immunity, 2015. 42, 731–743.
21.Kumar, V., Dasoveanu, D.C., Chyou, S., Tzeng, T.C., Rozo, C., Liang, Y., Stohl, W., Fu, Y.X., Ruddle, N.H., Lu, T.T. 2015. A Dendritic-Cell-Stromal Axis Maintains Immune Responses in Lymph Nodes. Immunity, 2015. 42, 719-730.
22.Okwor, I., G. Xu, H. Tang, Y. Liang, Y.-X. Fu, and J.E. Uzonna. Deficiency of CD40 Reveals an Important Role for LIGHT in Anti-Leishmania Immunity. The Journal of Immunology 2015;195(1):194-202.
Complete list of publications: https://scholar.google.com/citations?hl=zh-CN&user=Px7slAUAAAAJ
