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  • 张晓燕

    研究员,复旦大学校聘教授,博士生导师,复旦大学生物医学研究院免疫治疗课题组PI
    邮箱:zhangxiaoyan@fudan.edu.cn
    实验室主页:http://www.hiv.fudan.edu.cn

工作经历
研究员,复旦大学,生物医学研究院(2009-今)
双聘教授,复旦大学, 上海市公共卫生临床中心(2009-今)
创始所长,上海市新发与再现传染病研究所 (2010-2019)
执行主任,中山医院中山南院生物治疗中心(2019-2021)
双聘教授,复旦大学附属中山医院(2021-今)
副研究员/研究员,中国疾病预防控制中心艾滋病预防控制中心(2002-2007、2009)
博士后,美国纽约大学医学院(2000–2002)
助理教授,日本东北大学医学部(1999–2000)
教育经历
医学博士/内科,日本京都大学(1995-1999)
医学微生物学/硕士,哈尔滨医科大学(1990-1995)
医学/学士,哈尔滨医科大学(1984-1990)
所获人才项目
2010,上海市优秀学科带头人
2011,上海市医学领军人才
所获奖项
2011,黏膜潜在免疫损伤预测的新技术,上海医学科技奖三等奖(第一完成人)
2019,上海市巾帼建国标兵
研究方向
张晓燕教授聚焦病毒感染的免疫保护机制的研究,研发多项针对病毒感染或肿瘤的免疫疗法和治疗性疫苗。作为临床研究PI,张教授先后发起了NKT、CAR-T等免疫治疗的IIT临床研究。先后承担国家自然科学基金、国家科技重大专项、科技部重点研发计划等课题。在Nature, Nature Microbiology, Nature Communications, J Immunother Cancer, PNAS, CID等杂志发表论文160余篇。申报国家发明专利60余项,获得授权32项,实现技术成果转化6项。
1)解析病毒感染,特别是粘膜感染的免疫保护机制(Dissecting immune protective mechanisms against viral infection, particularly mucosal infection): 包括确定对寨卡病毒生命周期至关重要的宿主因素,揭示I型干扰素途径的早期抑制对病毒存活至关重要(Nat Microbiol,2018)证明I型IFN途径的缺陷导致严重的H7N9感染重症化(PNAS,2014);发现IFN-κ可以通过IFNAR-MAPK-Fos-CHD6轴发挥其功能来抑制甲型流感病毒(the coverage story,Science Signaling,2020)。证明T细胞免疫反应在预防流感疾病(Nature Communication,2015/2018;Front Immunol,2022),HIV进展(Nature,2016;J Immunol,2015;Front Immunol,2020)方面也起着至关重要的作用。2)研发病毒感染的免疫干预技术与转化医学的研究(Developing immunopreventive or immunotherapeutic approaches against viral infection and implementing translational research): 包括针对直肠HIV/SIV感染的预防剂(Emerg Infect Dis,2017;Plos one,2012)、新型雾化吸入技术(IFN/TFF2)(Antiviral Research,2024)并在临床研究中证明其对COVID-19治疗的安全性与有效性(EClinicalMedicine,2020a/2020b;Front Pharmacol。2022)。近年来作为研究者共同发起的一项HIV特异性CAR-T的IIT试验,证明了一种从潜伏细胞中清除功能性HIV基因组的新概念(Cell Discovery,2024)。3)研发实体瘤的免疫治疗技术与转化医学研究(Developing immunotherapeutic approaches against solid tumor and implementing translation research):她开发了一种在体外扩增PD-1+CD8+T细胞的新方法(Front Bioeng Biotechnol. 2022).。重要的是,她提出了NKT与抗体或PD1+CD8 T细胞的创新组合,显着增强了癌症控制和患者生存 (Immunotherapy. 2022; Clin Immunol. 2022; Cancer Res Commun. 2023).。最近,她进一步开发了针对实体瘤的新CAR-T和溶瘤病毒方法,包括新的动物模型(J Adv Res, 2023),几种新的CAR-T模式(Biomark Res. 2020a/2020b; J Immunother Cancer. 2021a) 和一种新型溶瘤病毒(J Immunother Cancer, 2021b).
招生专业
医学系统生物学
代表论文

Selected Publications in the past 5 years (*indicated the corresponding author) More than 160 scientific papers have been published in total.  Her publications have been cited over 3000 times on Research Gate. (https://www.researchgate.net/profile/Xiaoyan-Zhang-94/publications )

1.Yunyu Mao#, Qibin Liao#, Youwei Zhu#, Mingyuan Bi#, Jun Zou#, Nairong Zheng, Lingyan Zhu, Chen Zhao, Qing Liu, Li Liu, Jun Chen, Ling Gu, Zhuoqun Liu, Xinghao Pan, Ying Xue, Meiqi Feng, Tianlei Ying, Pingyu Zhou, Zhanshuai Wu, Jian Xiao, Renfang Zhang*, Jing Leng*, Yongtao Sun*, Xiaoyan Zhang*, Jianqing Xu*. Efficacy and Safety of Novel Multifunctional M10 CAR-T Cells in HIV-1-Infected Patients: A Phase I, Multicenter, Single-Arm, Open-Label Study. Cell Discovery. 10, 49 (2024). https://doi.org/10.1038/s41421-024-00658-z

2.Wang J, Cheng X, Jin Y, Xia B, Qin R, Zhang W, Hu H, Mao X, Zhou L, Yan J, Zhang X*, Xu J*, Safety and clinical response to combined immunotherapy with autologous iNKT cells and PD-1+CD8+ T cells in patients failing first-line chemotherapy in stage IV pancreatic cancer. Cancer Research Communications,2023 Jun 7;3(6):991-1003. doi: 10.1158/2767-9764. CRC-23-0137. eCollection 2023 Jun. PMID: 37377605 

3.Rongrong Gao#, Ang Li#, Sen Li, Xiangrong Li, Shuye Zhang, Xiaoyan Zhang*, Jianqing Xu*.Induced regulatory T cells modified by knocking down T-bet in combination with ectopic expression of inhibitory cytokines effectively protect Graft-versus-Host Disease. American Journal of Transplantation, 2023Jul;23(7):946-956.  doi: 10.1016/j.ajt.2023.04.017.

4.Shimeng Bai, Tianhan Yang, Cuisong Zhu, Meiqi Feng, Li Zhang, Ziling Zhang, Xiang Wang, Rui Yu, Xinghao Pan, Chen Zhao*, Jianqing Xu* and Xiaoyan Zhang*. A single vaccination of nucleoside-modified Rabies mRNA vaccine induces prolonged highly protective immune responses in mice. Frontiers in Immunology-. 2023 Jan 17;13:1099991. doi: 10.3389/fimmu.2022.1099991.

5.Chenli Qiu, Jing Wang, Lingyan Zhu, Xiaobo Cheng, Bili Xia, Yanling Jin, Qin Ran, Linxia Zhang, Huiliang Hu, Jia Yan, Chen Zhao, Xiaoyan Zhang* and Jianqing Xu* Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting Toll-like receptors, Frontiers in Bioengineering and Biotechnology, 31 October 2022https://doi.org/10.3389/fbioe.2022.1027619

6.Qibin Liao*, Zhuoqun Liu*, Cuisong Zhu*, Huan He*, Meiqi Feng, Lang Jiang, Xiangqing Ding, Rongxun Sun#, Xiaoyan Zhang#, Jianqing Xu#. Rapid generation of a mouse model for evaluating on-target normal tissue toxicity of human CAR-T cells using replication-defective recombinant adenovirus. Journal of Advanced Research. 2022 Aug 20:S2090-1232(22)00189-8. doi: 10.1016/j.jare.2022.08.008. PMID:35995414

7.Jing Wang*, Renfang Zhang*, Xiangqing Ding*, Yanling Jin, Ran Qin, Bili Xia, Qibin Liao, Huiliang Hu, Wei Song, Zhenyan Wang, Xiaoyan Zhang#, Jianqing Xu#. Pathologically complete remission to combination of invariant NK T cells and anti-CD20 antibody in a refractory HIV+ diffuse large B-cell lymphoma patient. Immunotherapy. 2022 Apr 20. doi: 10.2217/imt-2021-0247.

8.Xiaobo Cheng*, Jing Wang*, Chenli Qiu, Yanling Jin, Bili Xia, Ran Qin, Huiliang Hu, Jia Yan, Xiaoyan Zhang#, Jianqing Xu#. Feasibility of iNKT cell and PD-1+CD8+ T cell-based immunotherapy in patients with lung adenocarcinoma: Preliminary results of a phase I/II clinical trial. Clin Immunol. 2022 Mar 30;238:108992. doi: 10.1016/j.clim.2022.108992.

9.Jiang Lang†, Liu Lu†, Zhang Miaomiao, Zhang Linxia, Zhu Cuisong, He Qian, Ye Lilin, Zhao Chen*, Li Zejun*, Xu Jianqing*, Zhang Xiaoyan*. Prompt Antiviral Action of Pulmonary CD8+ TRM Cells Is Mediated by Rapid IFN-γ Induction and Its Downstream ISGs in the Lung. Frontiers in Immunology. 2022. https://www.frontiersin.org/article/10.3389/fimmu.2022.839455

10.Jian Chen#, Jun Fan#, Zhilu Chen#, Miaomiao Zhang#, Haoran Peng#, Jian Liu, Longfei Ding, Mingbin Liu, Chen Zhao, Ping Zhao*, Shuye Zhang*, Xiaoyan Zhang*, Jianqing Xu*. Nonmuscle myosin heavy chain IIA facilitates SARS-CoV-2 infection in human pulmonary cells. Proc. Natl Acad. Sci. USA. 2021 Dec 14;118(50): e2111011118.

11.Xiangchuan He#, Longfei Ding#, Kangli Cao#, Haoran Peng#, Chenjian Gu, Yutang Li, Duoduo Li, Lanlan Dong, Xiujing Hong, Xiangwei Wang, Meilan Fu, Chenli Qiu, Cuisong Zhu, Ziling Zhang, Shu Song, Chenguang Wang, Zhengfan Jiang, Youhua Xie, Zhongtian Qi, Chen Zhao*, Ping Zhao*, Xiaoyan Zhang*, Jianqing Xu*. A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge. Emerging Microbes & Infections. 2021,10(1):1555-1573.

12.Huan He#, Qibin Liao#,Chen Zhao,Cuisong Zhu,Meiqi Feng,Zhuoqun Liu,Lang Jiang,Linxia Zhang,Xiangqing Ding,Min Yuan*,Xiaoyan Zhang, Jianqing Xu*. Conditioned CAR-T cells by hypoxia-inducible transcription amplification (HiTA) system significantly enhances systemic safety and retains antitumor efficacy. Journal for ImmunoTherapy of Cancer. 2021 Oct;9 (10) : e002755.  doi: 10.1136/jitc-2021-002755.

13.Tianyue Chen#, XiangqingDing#, Qibin Liao, Nan Gao, Ye Chen, Chen Zhao*, Xiaoyan Zhang*, JianqingXu*. IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy. Journal for ImmunoTherapy of Cancer. 2021 Jan;9(1):e001647.doi: 10.1136/jitc-2020-001647.

14.Ang Li#, Yun Lin#, Zhigang Song#, Xiaobo Cheng, Weihui Fu, Yan Liu, Huiliang Hu, Songhua Yuan, Jian Chen, Jun Fan, Min Wang, Jing Wang, Yanling Jin, Miaomiao Zhang, Lingyan Zhu, Peng Sun, Linxia Zhang, Ran Qin, Wei Zhang, Chenli Qiu, Yinzhong Shen, Lin Zhang, Tongyu Zhu*, Hongzhou Lu*, Xiaoyan Zhang*, Jianqing Xu1*.Early plasma IL-37 responses accompanied with low inflammatory cytokines  correlate with benign clinical outcomes during SARS-CoV-2 infection. The Journal of Infectious Diseases, 2020 Nov 17:jiaa713. doi: 10.1093/infdis/jiaa713.

15.Qibin Liao, Yunyu Mao, Huan He, Xiangqing Ding, Xiaoyan Zhang*, Jianqing Xu* . PD-L1 chimeric costimulatory receptor improves the efficacy of CAR-T cells for PD-L1-positive solid tumors and reduces toxicity in vivo. Biomark Res, 2020 Nov 2;8(1):57. doi: 10.1186/s40364-020-00237-w. PMID: 33292688; PMCID: PMC7607631.

16.Qibin Liao#, Huan He#, Yunyu Mao, Xiangqing Ding, Xiaoyan Zhang*, Jianqing Xu*. Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing. Biomark Res, 2020. 8: 56. doi: 10.1186/s40364-020-00238-9.

17.Qian He , Lang Jiang, Kangli CaoLinxia ZhangXinci XieShuye ZhangXiangqing DingYongquan HeMiaomiao ZhangTianyi QiuXuanxuan JinChen Zhao*, Xiaoyan Zhang*, Jianqing Xu*. A Systemic Prime-Intrarectal Pull Strategy Raises Rectum-Resident CD8+ T Cells for Effective Protection in a Murine Model of LM-OVA Infection. Frontiers in Immunology. 2020 Sep 24;11:571248.doi: 10.3389/ fimmu. 2020.571248. eCollection 2020.

18.Weihui Fu, Yan Liu, Li Liu, Huiliang Hu; Xiaobo Cheng, Ping Liu; Zhigang Song; Lijun Zha; Shimeng Bai; Tingting Xu; Songhua Yuan; Fengru Lu; Zhiying Shang; Yihong Zhao; Jing Wang, Jun Zhao; Longfei Ding; Jun Chen, Lin Zhang; Tongyu Zhu*, Xiaoyan Zhang*, Hongzhou Lu*, Jianqing Xu*.  An open-label, randomized trial of the combination of IFN-κ plus TFF2 with standard care in the treatment of patients with moderate COVID-19. E Clinical Medicine. 2020 Oct;27:100547.doi: 10.1016/j.eclinm.2020.100547Web feature article.

19.Yongquan He, Weihui Fu, Kangli Cao, Qian He, Xiangqing Ding, Jian Chen, Lingyan Zhu, Tianyue Chen, Longfei Ding, Yu YangCuisong Zhu, Songhua Yuan, Zejun Li, Chen Zhao*, Xiaoyan Zhang*, Jianqing Xu*. IFN-κ suppresses the replication of influenza A virus through IFNAR-MAPK-Fos-CHD6 axis. Science Signaling 7 April 2020.13(626): eaaz3381. doi: 10.1126/scisignal.aaz3381.

20.Jian Chen#, Yi-feng Yang#, Yu Yang, Peng Zou, Yongquan He, Sai-lan Shui, Jun Chen, Ru Bai, Ya-jun Liang, Yunwen Hu, Biao Jiang, Lu Lu, Xiaoyan Zhang*, Jia Liu*, Jianqing Xu*.  AXL Promotes Zika Virus Infection in Astrocytes by Antagonizing Type I Interferon Signaling Pathway. Nature microbiology. 2018 Jan 29. 3: 302–309.

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