本课题组主要聚焦肿瘤微环境（TME）和免疫治疗，围绕肿瘤（边界）微环境，以生物大数据为驱动，构建算法、结合生信创新方法、基础实验、临床队列等多尺度手段阐释TME中调控因子对肿瘤进展和免疫逃逸机制、并利用多维数据构建免疫治疗疗效预测模型，为免疫治疗提供新治疗策略（Cancer cell，2020；Nature Metabolism， 2019；Nature Immunology， 2019；Nature Communications, 2020, 2022; etc.）。主要研究内容为 1）利用单细胞组学、空间组学和病理图片等多尺度数据构建精准研究肿瘤边界微环境的工具，以研究肿瘤边界微环境在不同肿瘤免疫微环境分型、肿瘤转移、免疫治疗耐受中调控机制，及开放基于边界微环境调控因子的新肿瘤治疗策略；2）基于临床队列的单细胞等组学揭示肿瘤微环境相关特征以辅助肿瘤免疫治疗。

本课题组更多研究方向和科研成果讯息详见实验室网站：http://www.yelab.site/

代表性论文

以*（共同）一作/#共同通讯发表的期刊

2024

1. Du Y#, Shi J#, Wang J, Xun Z, Yu Z, Sun H, Bao R, Zheng J, Li Z, Ye, Y. Integration of Pan-Cancer Single-Cell and Spatial Transcriptomics Reveals Stromal Cell Features and Therapeutic Targets in Tumor Microenvironment. Cancer Res 2024 Jan 16;84(2):192-210.

2. Shi J#, Wei X#, Xun Z, Ding X, Liu Y, Liu L, Ye, Y. The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment Cancer Res 2024 Apr 15;84(8):1210-1220.

3. Chen W, He Y, Zhou G, Chen X *, Ye, Y *, Zhang G *, Liu H *. Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma. BMC Med 2024 Jan 17;22(1):24.

4. Ding R, Yu X, Hu Z, Dong Y, Huang H, Zhang Y, Han Q, Ni ZY *, Zhao R *, Ye, Y *, Zou Q *. Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells. Immunity 2024 Mar 12;57(3):528-540.e6.

5. Xiao J, Wang S, Chen L, Ding X, Dang Y, Han M, Zheng Y, Shen H, Wu S, Wang M, Yang D, Li N, Dong C, Hu M, Su C, Li W, Hui L, Ye, Y *, Tang H *, Wei B *, Wang H *. 25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages. Immunity 2024 Apr 12:S1074-7613(24)00142-0.

2023

1. Dong Y, Gao Q, Chen Y, Zhang Z, Du Y, Liu Y, Zhang G, Li S, Wang G, Chen X#, Liu H#, Han L#, Ye Y#. Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy. Nature Communications(2023) 14(1):2540.

2. Xun, Z., Ding, X., Yao Zhang, Zhang, B., Lai, S., Zou, D., Zheng, J., Chen, G., Su, B., Han, L.# & Ye, Y.# Reconstruction of the tumor spatial microenvironment along the malignant- boundary-nonmalignant axis. Nature Communications(2023) 14: 933.
   

3. Sun, C. *, Ye, Y. *, Tan, Z., Liu, Y., Li, Y., Hu, W., Liang, K., Egranov, S. D., Huang, L. A., Zhang, Z., Zhang, Y., Yao, J., Nguyen, T. K., Zhao, Z., Wu, A., Marks, J. R., Caudle, A. S., Sahin, A. A., Gao, J., et al. Tumor-associated nonmyelinating Schwann cell - expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion. Science Advances 6995, 1–17 (2023).
   

4. Liu Y., Xun Z., Ma K.,Liang S., Li X., Zhou S., Sun L., Liu Y., Du Y., Guo X., Cui T., Zhou H., Wang J., Yin D., Song R., Zhang S., Cai W., Meng F., Guo H., Zhang B., Yang D., Bao R., Hu Q., Wang J., Ye, Y#., Liu L#. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy. Journal of hepatology S0168-8278(23)00023-5. doi: 10.1016/j.jhep.2023.01.011.

2022

1. Mo J., Tan K., Dong Y., Lu W., Liu F., Mei Y., Huang H., Zhao K., Lv Z.#, Ye Y.#, Tang Y.#. Therapeutic targeting the oncogenic driver EWSR1::FLI1 in Ewing sarcoma through inhibition of the FACT complex. Oncogene(2022) 42(1):11-25.

2. Zhang, C., Wang, H., Yang, X., Fu, Z., Ji, X., Shi, Y., Zhong, J., Hu, W., Ye Y.#, Wang, Z.# & Ni, D#. Oral zero-valent-molybdenum nanodots for inflammatory bowel disease therapy. Science Advances8, 1–12 (2022).

3. Wang G., Xie Z., Su J., Chen M., Du Y., Gao Q., Zhang G., Zhang H., Chen X.#, Liu H.#, Han L.# & Ye Y#. Characterization of immune-related alternative polyadenylation events in cancer immunotherapy. Cancer Research CAN-22-1417 (2022) doi:10.1158/0008-5472.CAN-22-1417.

4. He, Y., Dong, Y., Chen, Y., Zhang, G., Zhang, H., Lei, G., Du, Y., Chen, X.#, Ye, Y#. & Liu, H#. Multi-omics characterization and therapeutic liability of ferroptosis in melanoma. Signal Transduction and Targeted Therapy. 7, (2022).

5. Qi J., Sun H., Zhang Y., Wang Z., Xun Z., Li, Z., Ding X., Bao R., Hong L., Ji W., Fang, F., Li H., Chen L., Zhong J., Zou D., Liu L., Han L., Ginhoux F., Ye, Y.# (lead contact), Su, B.#. Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer. Nature Communications (2022) 13:1742.

6. Shen M., Du Y.#, Ye Y.# . Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance. Medical Review 2022;4710:1-22Liu Z.*, Ye Y.# , Liu Y., Liu Y., Chen H., Shen M., Wang Z., Huang S., Han L., Chen Z., He X. RNA helicase DHX37 facilitates liver cancer progression by cooperating with PLRG1 to drive super enhancer-mediated transcription of cyclin D1. Cancer Research (2022)

7. Ye Y.* , Zhang Y. *, Yang N. *, Gao Q. *, Ding X., Kuang X., Bao R., Zhang Z., Sun C., Zhou B., Wang L., Hu Q., Lin C., Gao J., Lou Y., Lin S.H., Diao L., Liu H., Chen X., Mills G.B., Han L. Profiling of immune features to predict immunotherapy efficacy. The Innovation (2022) 3 (1) 100194.

8. Wang F; Zhang Y; Yu X; Teng X-L; Ding R; Hu Z; Wang A; Wang Z; Ye Y.# , Zou Q#. ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells. Journal of Clinical Investigation (2021) 131.

9. Chen, H., Yao, J., Bao, R., Dong, Y., Zhang, T., Du, Y., Wang, G., Ni, D., Xun, Z., Niu, X., Ye Y.#, Li H#. Cross-talk of four types of RNA modification writers defines tumor microenvironment and pharmacogenomic landscape in colorectal cancer. Molecular Cancer (2021) 20, 1-21.

10. Shen L#, Ye Y#, Sun H#, Su B. ILC3 plasticity in microbiome-mediated tumor progression and immunotherapy. Cancer Cell (2021) 39, 10:1308-1310.

2021

1. Ye Y. *#, Kuang X. *, Xie Z. *, Liang L., Zhang Z., Zhang Y., Ma F., Gao, Q., Chang R., Zhao S., Su J., Li, H., Peng, J., Chen H., Yin M., Peng C., Yang N., Liu J., Liu H.#, Han L.#, Chen X#. Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1. Genome Medicine (2020) 12:83.

2. Ye Y., Jing Y., Li L., Mills G.B., Diao L., Liu H., Han L. Sex-associated molecular differences for cancer immunotherapy. Nature Communications (2020). 11.

3. Chang G. *, Shi L. *, Ye Y. *, Shi H., Zeng L, Tiwary S., Chang G., Huse J.T., Huo L., Ma L., Ma Y., Zeng L., Zhang S., Zhu J., Han L., He C. & Huang S. Genetic and Epigenetic Changes in YTHDF3 Promote Multiple Steps of Breast Cancer Brain Metastasis. Cancer Cell (2020) 38:1-15

4. Ye Y.*, Zhang Z.*, Liu Y., Han L. A multi-omics perspective for quantitative trait loci in precision medicine. Trends in Genetics (2020). 318-336.

5. Hui L.*, Kuang X. *, Liang, L. *,Ye Y. *, Zhang Y, Li J., Ma F., Tao J., Lei G., Zhao S., Su J., Yang N., Peng C., Xu X., Hung.-C., Han., Liu H., Liu J., & Chen X. The beneficial role of Sunitinib in tumor immune surveillance by regulating tumor PD-L1. Advanced Science (2020)6, 1-16.

Before

1. Ye Y.*, Hu Q.*, Chen H., Liang K., Yuan Y., Xiang Y., Ruan H., Zhang Z., Song A., Zhang H., Liu L., Diao L., Lou Y., Zhou B., Wang L., Zhou S., Gao J., Jonasch E., Lin S.H. et al. Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy. Nature Metabolism (2019). 1, 431-444. (Featured as Cover Story) (Included in Nature Research Collection on "Nobel Prize in Physiology or Medicine 2019")

2. Hu Q.*, Ye Y.*, Chan L.-C., Li Y., Liang K., Lin A., Egranov S.D., Zhang Y., Xia W., Gong J., Pan Y., Chatterjee S.S., Yao J., Evans K.W., Nguyen T.K., Park P.K., Liu J., Coarfa C., Donepudi S.R. et al. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature Immunology (2019). 20, 835-851.

3. Xiang Y.*, Ye Y.*, Lou Y., Yang Y., Cai C., Zhang Z., Mills T., Chen N., Kim Y., Ozguc F.M., Diao L., Karmouty-quintana H., Xia Y., Kellems R., Chen Z., Yoo S., Shyu A., Mills G.B. & Han L. Comprehensive characterization of alternative polyadenylation in human cancer. Journal of the National Cancer Institute (2018). 110, 379-389.

4. Ye Y., Xiang Y., Ozguc F.M., Kim Y., Liu C.J., Park P.K., Hu Q., Diao L., Lou Y., Lin C., Guo A.Y., Zhou B., Wang L., Chen Z., Takahashi J.S., Mills G.B., Yoo S.H. & Han L. The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy. Cell Systems (2018). 6, 314-328.E2. (Highlighted by preview from Cell Systems)

5. Xiang Y.*, Ye Y.*, Zhang Z. & Han L. Maximizing the utility of cancer transcriptomic data. Trends Cancer (2018). 4, 823-837.

6. Zhang Z.*, Ye Y.*, Gong J., Ruan H., Liu C., Xiang Y., Cai C., Guo A., Ling J., Diao L., Weinstein J.N. & Han L. Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers. Communications Biology (2018). 1, 234.

7. Ye Y.*, Li M.*, Gu L., Chen X., Shi J., Zhang X. & Jiang C. Chromatin remodeling during in vivo neural stem cells differentiating to neurons in early Drosophila embryos. Cell Death and Differentiation (2017). 24, 409-420.

专著章节(#: 共同通讯)

1. Tan P.#, Ye Y.#, Mao J., He L: Autophagy- and Immune-Related Diseases. In: Cui J Ed. Autophagy Regulation of Innate Immunity, Advances in Experimental Medicine and Biology. 2019.

2. Liu Y., Ye Y., Gong J., Han L: Expression Quantitative Trait Loci (eQTL) Analysis in Cancer. In Walker J Ed. Methods in Molecular Biology ISSN: 1064-3745. 2019.

办公室地址： 上海市重庆南路280号5号楼607室

办公室电话： 021-63846590-776772

实验室地址： 上海市重庆南路280号5号楼607室

实验室电话： 021-63846590-776772

邮            箱： youqiong.ye@shsmu.edu.cn