Personal Introduction

Education

• 2011.09-2016.12, Ph.D, Bioinformatics, College of Life Science and Technology, Tongji University

• 2007.09-2011.06, B.S., Biotechnology, School of Biological Science and Engineering, Fuzhou University

Position

• 2020.01 -, PI of Cancer multi-modal integration and cancer therapy lab, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine

• 2016.08-2019.12, Postdoctoral Fellow, The University of Texas Health Science Center at Houston

Research summary

My research focuses on the spatial characteristics of the tumor boundary microenvironment and their regulatory mechanisms, pursuing a systematic framework spanning spatial feature characterization, immune evasion mechanisms, and therapeutic target discovery. We have developed a suite of original spatial omics algorithms and databases to delineate the spatial architecture of the tumor microenvironment, including methods for precise tumor boundary identification, multi-scale inference of cellular composition, and integration of spatial transcriptomics with histopathological imaging (Nat Commun 2023a; Adv Sci 2026), as well as comprehensive resources such as SpatialTME, scPanStroma, CTTIME, and SpatialToolDB (Can Res 2024a, 2024b; GPB 2025; Sci Bull 2026), thereby enabling systematic modeling of spatial cellular states. Building on these approaches, we have elucidated key mechanisms by which the tumor boundary microenvironment orchestrates immune evasion, including hypoxia-driven cellular organization and the hypoxia-ALCAMhigh macrophage-exhausted T cell axis (Nat Metab 2019; Adv Sci 2024), stromal-immune crosstalk mediated by SPP1⁺ macrophages and FAP⁺ CAFs that establishes immune exclusion barriers (Nat Commun 2022; J Hepatol 2023), and metabolic reprogramming pathways regulating T cell function (Cell Metab 2023; Immunity 2024a, 2024b). Furthermore, leveraging clinical cohorts, we have developed predictive models for immunotherapy response based on dynamic cytokine changes and RNA processing features (Innovation 2022; Can Res 2022; Nat Commun 2023b), and are advancing agent-guided spatial predictive frameworks integrating multi-modal data. Importantly, we have identified spatially defined therapeutic vulnerabilities, including the formation of immunosuppressive resistant niches during chemotherapy and the dual role of CD276 in promoting tumor cell state transition and immune suppression (Gastroenterology 2026). Collectively, our work aims to elucidate how the tumor boundary microenvironment governs tumor progression and therapeutic response, and to translate spatially informed mechanisms into actionable strategies for precision immunotherapy. To date, this research has resulted in dozens of publications in international peer-reviewed journals (Google Scholar H-index: 48; citations > 9,800). As last or co-corresponding author, I have published in journals including Gastroenterology, Immunity (2024a, 2024b), Cell Metabolism, Cancer Research (2022, 2024a, 2024b), Nature Communications (2022, 2023a, 2023b), Journal of Hepatology, and Advanced Science (2024, 2025, 2026). As first or co-first author, I have published in Nature Metabolism, Nature Immunology, Cancer Cell, and Cell Systems. I have also been invited to publish commentaries and review articles in journals such as Cell Reports Medicine (2024), Cancer Cell (2021), and Trends in Genetics (2020). In addition, I hold seven registered software copyrights and two patents, supporting the development and application of computational tools for spatial omics and cancer research.

I have been awarded the NSFC Young Scientists Fund (Category B, formerly the Excellent Young Scientists Fund), the Shanghai Overseas High-level Young Talents Program, the Pujiang Talent Program (Category A), the Second Prize of the 20th “Silver Snake Award”, and the Chinese Society for Immunology Academic Award-Young Scholar Award. They have led two NSFC General Program projects and a Shanghai Natural Science Foundation Original Innovation (Exploration) project, and served as a key investigator on two Ministry of Science and Technology Key R&D projects. I also provide significant academic service as Board Member and Deputy Secretary-General of the Shanghai Bioinformatics Society, Member of the Tumor Microenvironment Committee of the Chinese Anti-Cancer Association, and Vice-Chair of the Youth Committee of the Chinese Society of Pathology, demonstrating strong leadership in bioinformatics, TME research and spatial oncology.

Scientific Research Project

• PI, National Natural Science Foundation of China, Outstanding Youth Science Foundation, 32470959, 2025.1-2027.12, 100%, ¥2,000,000

• PI, National Natural Science Foundation of China, General Program, 82422058, 2025.1-2027.12, 100%, ¥500,000

• Co-PI, National Key Research and Development Program, 2024YFC3407700, 2024.10-2027.09, 50%, ¥2,000,000

• PI, National Natural Science Foundation of China, General Program, 82073145, 2021.1-2024.12, 100%, ¥580,000

• PI, Shanghai Jiao Tong University 2030 Initiative, WH510363001-4, ¥ 500,000/year

• PI, Shanghai Science and Technology Commission, 20JC1410100, 100%, ¥500,000

• PI, Shanghai Pujiang Program, 20PJ1412800, 2020.11-2022.10, 100%, ¥500,000

• Co-Investigator, 2.7%, National Key Research and Development Program, 2022YFC2504700, 11/2022-12/2025, ¥ 14,840,000, PI: Xiang Chen

• Co-Investigator, 20%, Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM, 2023IHM01032, 09/2023-8/2027, ¥ 3,000,000, PI: Yao Liu

• Co-Investigator(Yanhua Du), 2.7%, National Key Research and Development Program, 2022YFC2504700, 11/2022-12/2025, ¥ 14,840,000, PI: Xiang Chen

• PI(Yanhua Du), Natural Science Foundation of Shanghai, 23ZR1455300, 2023.04 -2026.03, 100%, ¥ 200,000.

• PI(Yanhua Du), National Natural Science Foundation of China, 32470715, 2025.01-2028.12, 100%, ¥ 500,000.

• Co-Investigator(Yanhua Du), National Major Science and Technology Project (New Organization Mode Project), Grant Number: 2025ZD0552307, 2025.01-2027.01, 11%,  ¥ 6,500,000.

Publications

• Zhang Y*, Du Y*, Wang J*, Wang D*, Li J, Zhang J, Zhao Y, Sun S, Sun H, Qi J, Bao R, Shao C, Zhang M, He X, Zhang L, Zhou C, Wang Dong, Su B#, Zou D#, Ye Y#. Single-cell analysis of chemotherapy-induced remodeling reveals CD276-driven basal-like chemoresistance in pancreatic cancer. Gastroenterology 2026 Feb 17:S0016-5085(25)06097-4

• Li W*, Zhang D*, Peng E, Shen S, Alinejad-Rokny H, Liu Y#, Zheng J#, Jiang C#, Ye Y#. HiST: Histological Images Reconstruct Tumor Spatial Transcriptomics via MultiScale Fusion Deep Learning. Advanced Science 2026, 0:e14351.

• Guo Z*, Wu R*, Li W, Yang K, Ying X, Alinejad-Rokny H#, Ye Y#. Mapping biology in space: from spatial transcriptomics platforms to analytical tools and databases. Science Bulletin 2026, 71:921-45.

• Zhang C*, Dong Y*, Liu Y, Shi J, Han L#, Ye Y#. CTTIME: A Database for Analyzing Cancer Therapy’s Impact on Tumor Immune Microenvironment. Genomics, Proteomics & Bioinformatics. qzaf086, https://doi.org/10.1093/gpbjnl/qzaf086.

• Du Y*, Zhao Y*, Li J*, Wang J, You S, Zhang Y, Zhang L, Yang J, Alinejad-Rokny H, Cheng S, Shao C#, Zou D#, Ye Y#. PLXDCl+ Tumor-associated Pancreatic Stellate Cells Promote Desmoplastic and Immunosuppressive Niche in pancreatic Ductal Adenocarcinoma. Advanced Science, 2025, 2415756.

• Ding X*, Wu Q*, Du Y, Ji M, Yang H#, Hu Q#, Ye Y#, CDK16+ Luminal Progenitor Cell-Like Tumor Cells Interacted with POSTN+ Cancer-Associated Fibroblasts Associate with Chemo-Resistance in Breast Cancer, Small Methods, 2025 (2401192)

• Miao S*, Li H*, Song H*, Liu L, Wang G, Kan C, Ye Y#, Liu R#, Li H#, tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells, Journal of Experimental Medicine, 2025, 222(3):NA

• Lu T*, Guo W*, Guo W, Meng W, Han T, Guo X, Li C, Gao S#, Ye Y#, Li H#, A novel computational model ITHCS for enhanced prognostic risk stratification in ESCC by correcting for intratumor heterogeneity, Briefings in Bioinformatics, 2025, 26(1):bbae631

• 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 Research, 2024, 84(8): 1210- 1220

• 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 Research, 2024, 84(2): 192-210

• Du Y, Ding X, Ye Y. The spatial multi-omics revolution in cancer therapy: Precision redefined. Cell Reports Medicne, 2024;5:101740.

• Ding, R., Yu, X., Hu, Z., Dong, Y., Huang, H., Zhang, Y., Han, Q., Ni, Z. #, Ye Y.#, Zou Q.#. Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells Article Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells. Immunity 2023, 57(3): 528-540

• 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, 57(5): 1087-1104

• Xun Z., Zhou H., Shen, M., Liu., Sun C., Du Y., Zhou J., Yang L., Zhang Q., Lin C., Ye Y. #, Han L. Identification of Hypoxia-ALCAMhigh Macrophage-Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance. Advanced Science 2024, 2309885.

• Lin S., Dai Y., Han C., Han T., Zhao L., Wu R., Liu J., Zhang B., Huang, N., Liu Y., Lai S., Shi J., Wang Y., Lou M., Xie J., Cheng Y., Tang, H., Yao H., Fang H., Zhang Y., Wu X., Shen L.#, Ye Y.#, Xue L.#, Wu Z.B.#. Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage–tumor interaction axes among different lineages of pituitary neuroendocrine tumors. Genome Medicine. 16, 1–22 (2024).

• 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(1): 933

• Dong Y., Qian G, 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, 2540 (2023).

• 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, 2022 82(19): 3474-3485.

• Shen M., Du Y.#, Ye Y.#. Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance. Medical Review. 2022;4710:1–22.

• 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 Medicine. 22, 1–19 (2024).

• Han D., Han Y., Guo W., Wei W., Yang S., Xiang J., Che J., Zhu L., Hang J., Van Den Ende T., Van Laarhoven H. W. M., Li B., Ye Y.#, Li H.#. High-dimensional single-cell proteomics analysis of esophageal squamous cell carcinoma reveals dynamic alterations of the tumor immune microenvironment after neoadjuvant therapy. J. Immunother. Cancer. 11, 1–14 (2023).

• Zhang Y., Yu X., Bao R., Huang H., Gu C., Lv Q., Han Q., Du X., Zhao X., Ye Y.#, Zhao R.#, Sun J.#, Zou Q.#, Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses. Cell Metabolism. 1–12 (2023)

• Liu, Y., Xun, Z., Ma K., Liang, S., Li, X., Zhou, S., Hu Q.#, Wang, J.#, Ye, Y.#, Liu, L. Identification of a tumor immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy. Journal of Hepatology (2023) 100358.

• 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.#, Su, B.#. Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer. Nature Communications (2022) 13:1742.

• 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 (2022) 268.

• 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 Advances. 8, 1–12 (2022).

• 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.

• 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.

• 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.

• 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 (2021) 3 (1) 100194.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Liu 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)

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

• 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

• 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.

• 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.

• 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.

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