张飞飞-上海市免疫学研究所

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张飞飞研究员博士生导师
肿瘤免疫与基因编辑课题组课题组长
国家高层次青年人才
上海市高层次青年人才

研究方向

肿瘤免疫治疗，包括免疫检查点抑制剂和细胞治疗等，近年来显著改变了肿瘤治疗模式。然而，仍有相当一部分患者对免疫治疗缺乏响应，或在初始治疗有效后出现获得性耐药和肿瘤复发。其重要原因之一在于肿瘤与免疫系统之间存在复杂而动态的相互作用：在肿瘤进展及治疗选择压力下，肿瘤细胞可通过细胞状态转变和表型可塑性获得新的免疫逃逸能力，同时肿瘤免疫微环境也会发生适应性重塑，最终影响治疗响应、治疗耐药及转移复发。

肿瘤微环境并非由固定细胞类型和分子标志物组成的静态体系，而是一个在时间和空间上不断变化的动态免疫生态系统。肿瘤细胞、免疫细胞及基质细胞之间持续发生相互作用，并在肿瘤进展和治疗选择压力下形成不同的功能状态、空间组织及演化轨迹。传统基于单一基因、单一细胞群或静态分子特征的研究策略，难以全面揭示决定免疫治疗响应与耐药的复杂生物学机制。因此，从动态、空间和功能的角度理解肿瘤免疫微环境的变化，并进一步建立从机制发现到精准干预的研究体系，是发展下一代肿瘤免疫治疗的重要方向。

课题组聚焦肿瘤免疫治疗驱动的肿瘤-免疫互作与免疫生态演化，整合基因编辑、CRISPR功能筛选（CRISPR screening）、空间扰动组学（spatial perturbation omics）、单细胞与空间多组学、AAV基因治疗、细胞治疗、人工智能及生物信息学分析等前沿技术，系统解析免疫治疗压力下肿瘤细胞与免疫微环境的动态变化规律，揭示免疫逃逸、治疗耐药和转移复发的关键分子与细胞机制；在此基础上发现新的免疫调控靶点，发展肿瘤免疫微环境精准重塑及新型免疫治疗策略。

主要研究方向

1. 基因编辑与CRISPR筛选解析肿瘤免疫逃逸与转移复发机制

2. 空间CRISPR基因扰动多组学解析肿瘤免疫微环境演化

3. 体内基因编辑与肿瘤免疫微环境精准重塑，开发新型免疫治疗

岗位招聘！！！

课题组现处于快速发展阶段，科研经费充足，诚邀对肿瘤免疫、基因编辑、CRISPR功能筛选、单细胞与空间组学、细胞与基因治疗以及AI与生物医学交叉研究感兴趣的青年人才加入。长期招聘助理研究员、博士后、科研助理及实习生，同时欢迎优秀博士、硕士及本科生加入课题组开展科研训练。有意者请将个人简历、自荐信（Cover Letter）及相关材料发送至 feifei.zhang@sjtu.edu.cn，邮件及附件请注明“姓名+应聘岗位”。工作地点：上海市黄浦区重庆南路280号，上海交通大学医学院。本招聘长期有效。

代表性论文

1. Feifei Zhang^#, Chuanpeng Dong^#, Ryan D. Chow^#, Shan Xin^#, Emily He, Yanzhi Feng, Lvyun Zhu, Daniyal Mirza, Xiaolong Tian, Luojia Yang, Liqun Zhou, Xinyu Ling, Qin Han, Rong Fan, Sidi Chen*, Guangchuan Wang*. Rational Design of Immune Gene Therapy Combinations via In Vivo CRISPR Activation Screen of Tumor Microenvironment Modulators. Cancer Discovery. 2026;16(6):1222–1244. doi:10.1158/2159-8290.CD-25-0545.

2. Luojia Yang, Paul A. Renauer, Kaiyuan Tang, Josh Saskin, Liqun Zhou, Charles Zou, Seok-Hoon Lee, Madison Fox, Samuel Johnson-Noya, Benedict Weiss, Stephanie Deng, Paris Fang, Binfan Chen, Giacomo Sferruzza, Saba Fooladi, Kai Zhao, Daniel Park, Feifei Zhang, Jiayi Tu, Jing Chen, Jennifer Moliterno, Murat Gunel, Lei Peng, Sidi Chen. OR7A10 GPCR engineering boosts CAR-NK therapy against solid tumours. Nature. 2026;652(8110):740–751. doi:10.1038/s41586-026-10149-8.

3. Alev Baysoy^#, Xiaolong Tian^#, Paul Renauer^#, Feifei Zhang^#, Zhiliang Bai, Hao Shi, Mingyu Yang, Dingyao Zhang, Miao Liu, Haikuo Li, Bo Tao, Archibald Enninful, Yao Lu, Fu Gao, Guangchuan Wang, Wanqiu Zhang, Thao Tran, Nathan Heath Patterson, Jie Sheng, Shuozhen Bao, Chuanpeng Dong, Shan Xin, Binfan Chen, Mei Zhong, Sherri Rankin, Cliff Guy, Yan Wang, Jon P. Connelly, Shondra M. Pruett-Miller, Daifeng Wang, Mina Xu, Mark B. Gerstein, Hongbo Chi, Sidi Chen*, Rong Fan*. Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT. Nature Biotechnology. 2026. doi:10.1038/s41587-026-03127-y.

4. Yinghua Wang, Weiwei Hu, Rui Xia, Xianfa Yang, Yange Gu, Zihan Ning, Tiange Yang, Chune Yu, Lulu Zhang, Dun Li, Yitian Jin, Jianhua Li, Feifei Zhang, Yaochen Xu, Chenqi Xu, Zhengxin Wang, Naihe Jing, Luonan Chen, Guangchuan Wang. CLIM-TIME identifies metastatic microenvironment modulators for T cell therapy response. Cell. 2026;189(5):1555–1572.e23. doi:10.1016/j.cell.2025.12.042.

5. Chuanpeng Dong, Feifei Zhang, Kaiyuan Tang, Nipun Verma, Xinxin Zhu, Di Feng, James Cai, Hongyu Zhao, Sidi Chen*. TCPGdb: A Comprehensive T-cell Perturbation Genomics Database for the Identification of Critical T-cell Regulators. Cancer Immunology Research. 2026;14(2):219–227. doi:10.1158/2326-6066.CIR-25-0168.

6. Feifei Zhang^#, Ryan D. Chow^#, Emily He, Chuanpeng Dong, Shan Xin, Daniyal Mirza, Yanzhi Feng, Xiaolong Tian, Nipun Verma, Medha Majety, Yueqi Zhang, Guangchuan Wang*, Sidi Chen*. Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology. 2025;43(12):2054–2067. doi:10.1038/s41587-024-02535-2.

7. Chuanpeng Dong^#, Feifei Zhang^#, Emily He, Ping Ren, Nipun Verma, Xinxin Zhu, Di Feng, James Cai, Hongyu Zhao, Sidi Chen*. Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs. Patterns. 2025;6(3):101184. doi:10.1016/j.patter.2025.101184.

8. Feifei Zhang^#, Chen Jiang^#, Dong-ping Jiang^#, Yu-zhu Cui, Xin-yue Wang, Liang-zhan Sun, Miao Chen, Ka-On Lam, Sha-yi Wu, Krista Verhoeft, Dora Lai-wan Kwong*, Xin-Yuan Guan*. ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway. PLOS Genetics. 2023;19(2):e1010640. doi:10.1371/journal.pgen.1010640.

9. Liangzhan Sun, Shaoyan Xi, Zhengdong Zhou, Feifei Zhang, Pengchao Hu, Yuzhu Cui, Shasha Wu, Ying Wang, Shayi Wu, Yanchen Wang, Yuyang Du, Jingyi Zheng, Hui Yang, Miao Chen, Qian Yan, Dandan Yu, Chaoran Shi, Yu Zhang, Dan Xie, Xin-Yuan Guan*, Yan Li*. Elevated expression of RIT1 hyperactivates RAS/MAPK signal and sensitizes hepatocellular carcinoma to combined treatment with sorafenib and AKT inhibitor. Oncogene. 2022;41(5):732–744. doi:10.1038/s41388-021-02130-8.

10. Shayi Wu, Miao Chen, Jiao Huang, Feifei Zhang, Zhaojie Lv, Yongxu Jia, Yu-Zhu Cui, Liang-Zhan Sun, Ying Wang, Ying Tang, Krista R. Verhoeft, Yan Li, Yanru Qin, Xiang Lin, Xin-Yuan Guan*, Ka-On Lam*. ORAI2 Promotes Gastric Cancer Tumorigenicity and Metastasis through PI3K/Akt Signaling and MAPK-Dependent Focal Adhesion Disassembly. Cancer Research. 2021;81(4):986–1000. doi:10.1158/0008-5472.CAN-20-0049.

11. Guangchuan Wang, Ryan D. Chow, Lvyun Zhu, Zhigang Bai, Lupeng Ye, Feifei Zhang, Paul A. Renauer, Matthew B. Dong, Xiaoyun Dai, Xiaoya Zhang, Yaying Du, Yujing Cheng, Leilei Niu, Zhiyuan Chu, Kristin Kim, Cun Liao, Paul Clark, Youssef Errami, Sidi Chen*. CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade. Cancer Discovery. 2020;10(12):1912–1933. doi:10.1158/2159-8290.CD-19-1448.

12. Shuo Fang, Ming Liu, Lei Li, Feifei Zhang, Yun Li, Qian Yan, Yu-Zhu Cui, Ying-Hui Zhu, Yun-Fei Yuan, Xin-Yuan Guan*. Lymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway. Oncogene. 2019;38(21):4061–4074. doi:10.1038/s41388-019-0704-y.

13. Yuzhu Cui^#, Feifei Zhang^#, Yongxu Jia, Liangzhan Sun, Miao Chen, Shayi Wu, Krista Verhoeft, Yan Li, Yanru Qin, Xinyuan Guan*, Ka-On Lam*. The BMP antagonist, SOSTDC1, restrains gastric cancer progression via inactivation of c-Jun signaling. American Journal of Cancer Research. 2019;9(11):2331–2348.

14. Feifei Zhang^#, Lingling Wu^#, Jie Qian^#, Bo Qu, Shiwei Xia, Ting La, Yanfang Wu, Jianyang Ma, Jing Zeng, Qiang Guo, Yong Cui, Wanling Yang, Jiaqi Huang, Wei Zhu, Yihong Yao, Nan Shen*, Yuanjia Tang*. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. Journal of Autoimmunity. 2016;75:96–104. doi:10.1016/j.jaut.2016.07.012.

15. Bo Qu^#, Jianchang Cao^#, Feifei Zhang^#, Huijuan Cui, Jialin Teng, Jia Li, Zheng Liu, Chris Morehouse, Bahija Jallal, Yuanjia Tang, Qiang Guo, Yihong Yao, Nan Shen*. Type I Interferon Inhibition of MicroRNA-146a Maturation Through Up-Regulation of Monocyte Chemotactic Protein–Induced Protein 1 in Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2015;67(12):3209–3218. doi:10.1002/art.39398.

16. Yanfang Wu, Feifei Zhang, Jianyang Ma, Xiaoyan Zhang, Lingling Wu, Bo Qu, Shiwei Xia, Shunle Chen, Yuanjia Tang*, Nan Shen*. Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus. Arthritis Research & Therapy. 2015;17(1):131. doi:10.1186/s13075-015-0632-3.

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