Xiaoyan Zhang MD& PhD

Education

• MBA, Peking University, July 2004 to June 2007

• PhD, Kyoto University, April 1995 to March 1999

• MD, Harbin Medical University, Sept.1984 to June 1990

• MM，Harbin Medical University, Sept.1990 to  June 1993

Work experience

• Professor /Ph.D. Supervisor, at Institutes of Biomedical Sciences, Fudan University School of Medicine, July 2009 to present

• PI at Biotherapy Center of Zhongshan Hospital affiliated with Fudan University, Nov. 2021 to present

• PI Ph.D. Supervisor, China CDC, Aug.2007 to July 2009

• CO-PI, China CDC, Aug.2002 to July 2007

• Program manager of CIPRA project jointly supported by USA-China (US$15 millions).  Aug. 2002 to July 2007.

• Post-doc./Research Scientist New York University, Jan.2000 to July 2002.

• Assistant professor, Department of Internal Medicine, Medical School of Tohoku University, April 1999 to Jan.2000

• Assistant professor, Department of Microbiology, Harbin Medical University, July 1993 to March 1995

Contact

Institutes of Biomedical Sciences, Fudan University, Shanghai 200032

Biotherapy Center of Zhongshan Hospital affiliated with Fudan University

Tel: +86-18930084760

Email: zhangxiaoyan@fudan.edu.cn

Lab homepage: http://www.hiv.fudan.edu.cn

Biography

Professor Zhang’s research has been focusing on dissecting the immune protective mechanisms against viral infection, and developing immunotherapy and therapeutic vaccine against viral infection or cancers. In addition to the new technology development, she also engaged in the clinical trials on tumor immunotherapy. She has become a distinguished leader in the translational research.

Professor Zhang’s research have been recognized by more than RMB ¥50 million from entities like the Natural Science Foundation of China and the USA National Institute of Health, and over 160 publications in prestigious journals including Nature, Nature Microbiology, and the PNAS, and filed 66 patents, 32 are authorized. 22 top publications have been cited over 3000 times on Research Gate. (https://www.researchgate.net/profile/Xiaoyan-Zhang-94/publications )

Prof. Zhang was awarded the honorary titles of both Shanghai Excellent Academic Leader 0n 2010 and Shanghai Leading Medical Talent in 2011. In 2019, she obtained the Honorary of Outstanding Women Leader in Shanghai.

Research Areas

• Viral infection and the immune protective mechanism

• Tumor immunotherapy and therapeutic vaccine

Research interest

1. Dissecting immune protective mechanisms against viral infection, particularly mucosal infection:  Her notable work includes identifying host factors critical to the Zika virus lifecycle and disclosing that the early suppression of type I interferon pathway is vital for viral survival (Nat Microbiol, 2018), and revealing how deficiencies in the type I IFN pathway could lead to severe H7N9 infections (PNAS, 2014); Interestingly, IFN-kappa could exert its function through IFNAR-MAPK-Fos-CHD6 axis to suppress influenza A viruses, which was highlighted as the coverage story (Science Signaling, 2020). T-cell immune responses have been also playing critical role in protect from influenza diseases (Nature Communication, 2015/2018; Front Immunol, 2022), HIV progression (Nature, 2016; J Immunol, 2015; Front Immunol, 2020)

2. Developing immunopreventive or immunotherapeutic approaches against viral infection and implementing translational research:  Professor Zhang was one of the pioneer to develop preventive agents against intrarectal HIV/SIV infection (Emerg. Infect. Dis, 2017; Plos One, 2012). She led the development of a novel aerosol inhalation technology that combines IFN/TFF2 (Antiviral Research, 2024), and tested against COVID-19 (EClinicalMedicine, 2020a/2020b) and for safety (Front Pharmacol. 2022) in clinic. Recently, she implemented a phase I trial of HIV-specific CAR-T and proved a novel concept to clear functional HIV genome from latent cells (Cell Discovery, 2024).

3. Developing immunotherapeutic approaches against solid tumor and implementing translation research: She has developed a novel approach to expand PD-1+CD8+ T cells in vitro (Front Bioeng Biotechnol. 2022). Importantly, she proposed an innovative combination of NKT with antibodies or PD1+ CD8 T cells, significantly enhancing cancer control and patient survival (Immunotherapy. 2022; Clin Immunol. 2022; Cancer Res Commun. 2023). Recently, she has further developed new CAR-T and oncolytic virus approaches against solid tumors, including a new animal model (J Adv Res, 2023), several new CAR-T modalities (Biomark Res. 2020a/2020b; J Immunother Cancer. 2021a) and a novel oncolytic virus (J Immunother Cancer, 2021b). Most importantly, she has deeply involved in the development of several therapeutic vaccines against lung cancer, liver cancer and prostatic cancer (Patents filed)

Selected Publications

Selected Publications in the past 5 years (*indicated the corresponding author)

More than 160 scientific papers have been published in total.

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 2022，https://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 Cao, Linxia Zhang, Xinci Xie, Shuye Zhang, Xiangqing Ding, Yongquan He, Miaomiao Zhang, Tianyi Qiu, Xuanxuan Jin, Chen 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. Chen J#, Chen Z#, Liu M, Qiu T ,Zhao C, Zhang S*, Zhang X*,Xu J*. Placental alkaline phosphatase promotes Zika virus replication by stabilizing viral proteins through BIP. mBio.2020. 11: e01716-20. doi: 10.1128/mBio.01716-20.

19. Linxia Zhang†, Anli Zhang†, Jun Xu†, Chao Qiu, Lingyan Zhu, Chenli Qiu, Weihui Fu, Ying Wang, Lilin Ye, YangXin Fu, Chen Zhao*, Xiaoyan Zhang*, Jianqing Xu*. CD160 plays a protective role during chronic infection by enhancing both functionalities and proliferative capacity of CD8+ T cells. Frontiers in Immunology 11, 10.3389/fimmu.2020.02188

20. 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.2020.100547（Web feature article）.

21. Yongquan He, Weihui Fu, Kangli Cao, Qian He, Xiangqing Ding, Jian Chen, Lingyan Zhu, Tianyue Chen, Longfei Ding, Yu Yang，Cuisong 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.

22. 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.