Personal Introduction

I got my bachelor’s degree in Fudan University majoring in Biochemistry in 1991 and joined Shanghai Institute of Immunology until now. In 2005 and 2006, I got Ph.D degrees from Shanghai Jiao Tong University School of Medcine in China and University of Mediterranean in Marseille in France respectively. I am now Professor of , Principle Investigator of Shanghai Institute of Immunology and Vice Dean of Graduate School of Medicine Shanghai Jiao Tong University School of Medicine. I was selected in Shanghai Pujiang Scholar Program in 2007 and Shanghai Academic Research Leader Project in 2018.

Disease-oriented immunological investigations are my most favorable researches. Through the collaborations with the clinicians, I have gradually set up my research directions to dissect aberrant immune regulation during the pathogenesis of lung-related diseases including tuberculosis, COVID-19 and lung cancer. From well-designed clinical study and sample collection to immune profiling of disease-related immune abnormality, I have tried to figure out key factors that can improve the diagnosis, efficacy predication as well as prevention of the diseases some of which are inclined to potentiate clinical applications in the future. To explore diagnostic biomarkers and development of novel preventive vaccines against tuberculosis (TB) and latent TB infection, my group has screened panels of novel mycobaceterial antigens with high immunogenencity both in active TB patients and mice, which facilitates their further expectation for vaccine development and biomarker determination. Among them, LppZ is identified with high immunogenicity and antigenicity, and induces both innate and adaptive immune responses with great potential values in both TB diagnosis and new TB vaccine development. My another research interest is investigations on efficacy prediction and improvement in non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor treatment. Since only ~20% of patients benefit from anti-PD-1/PD-L1 antibodies monotherapy, predictive biomarkers that facilitate patient selection and treatment decisions in ICIs therapy are necessary. Collaboration with Dr Shun Lu from Shanghai Chest Hospital affiliated to Shanghai Jiaotong University, we have serially collected blood, urea and fecal from the NSCLC enrolled in registered ICI clinical trials. By using omics techniques, we have identified microbiota, metabolites and immune signatures in the prediction and prognosis of ICI treatment for NSCLC. Subsequently, we have started to explore comprehensive strategies on “cold-to-hot” tumor transition for the sensitization of immune checkpoint inhibitors against advanced non-small cell lung cancer.

Scientific Research Projects

• Perspective clinical Investigations on Biomarker-oriented selection for lung cancer patients benefit from immune checkpoint inhibitors  Co-PI  (12/1/2021-11/30/2024)

Funding Source: Chinese National Mega Science and Technology Program on Infectious Diseases

Grant Number: 2021YFC2301502

• The mechanisms of NLRP4-mediated Type I interferon response in affecting PD-1/PD-L1 blockade treatment in lung cancer  PI  (10/1/2020-9/30/2023)

Funding Source: Basic Medicine Key Project, Shanghai Municipal Science and Technology Committee

Grant Number: 20JC1417500

• Exploration on immune compatibility of hydrogel biomaterials in the treatment of stroke  Participant  (1/1/2020-12/31/2024)

Funding Source: Key Project, National Natural Science Foundation of China

Grant Number: 81930051

• Perspective clinical Investigations on Biomarker-oriented selection for lung cancer patients benefit from immune checkpoint inhibitors  Co-PI

Funding Source: Medical Innovative Project, Shanghai Municipal Science and Technology Committee, Grant Number: 19411950500, 9/1/2019-5/30/2022. ￥500,000

• Metabolic reprogramming mycobacterial specific memory T cells and its clinical significance    PI  (1/1/2019-12/31/2022)

Funding Source: National Natural Science Foundation of China

Grant Number: 81873868

Publications

1. Wang H#, Xia L#, Yao CC, Dong H, Yang Y, Li C, Ji WX, Sun RM, Duan HQ, Mengzhou W, Xia WM, Wang SJ, Ji P, Li Z, Jiao L, Wang Y* and Lu S*. NLRP4 negatively regulates type I interferon response and influences the outcome in anti-programmed cell death protein (PD)-1/PD-ligand 1 therapy. Cancer Sci. 2021 Dec 20. doi: 10.1111/cas.15243. Online ahead of print

2. Liu S#, Li YM#, Li JZ, Wang SJ, Ji P, Zhang MY*, Wang Y*. CD4+ T Cells Promote IgG Production in MHC-Independent and ICAM-1-Dependent Manners in Pristane-Induced Lupus Mice. Mediators Inflamm. 2022 Jan 21;2022:9968847. doi: 10.1155/2022/9968847. eCollection 2022

3. Xia L#, Guo L#, Kang J#,# Yang Y, Yao Y, Xia W, Sun R, Zhang S, Li W, Gao Y, Chen H, Li Z, Yang J, Lu S*, Wang Y* (2021). Predictable Roles of Peripheral IgM Memory B Cells for the Responses to Anti-PD-1 Monotherapy Against Advanced Non-Small Cell Lung Cancer. Front. Immunol., 24 November 2021 | https://doi.org/10.3389/fimmu.2021.759217

4. Liu Z#*, Liu S#, Zhang Y, Zeng W, Wang S, Ji P, Pan M, Zhu C and Wang Y*. (2021) Distinct roles of ICOS and CD40L in human T-B cell adhesion and antibody production. Cell Immunol. 2021 Oct;368:104420

5. Luo, L.#, Liang, W.#, Pang, J.#, Xu, G.#, Chen, Y.#, Guo, X., Wang, X., Zhao, Y., Lai, Y., Liu, Y., Li, B., Su, B., Zhang, S., Bniyash, M., Shen, L., Chen, L., Ling, Y., Wang Y., Liang, Q., Lu, H.*, Zhang, Z.* and Wang, F.* (2021). Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals. Cell Discovery 7, 89.

6. Sam IK, Chen YY, Ma J, Li SY, Ying RY, Li LX, Ji P, Wang SJ, Xu J, Bao YJ, Zhao GP, Zheng HJ, Wang J*, Sha W*, Wang Y* (2021). TB-QUICK: CRISPR-Cas12b-assisted rapid and sensitive detection of Mycobacterium tuberculosis J Infect. 83(1):54-60. doi: 10.1016/j.jinf.2021.04.032.

7. Nie X, Xia L, Gao F, Liu L, Yang Y, Chen Y, Duan H, Yao Y, Chen Z, Lu S*, Wang Y*, and Yang C*. Serum Metabolite Biomarkers Predictive of Response to PD-1 Blockade Therapy in Non-Small Cell Lung Cancer. Front Mol Biosci. 2021 May 21;8:678753. eCollection 2021

8. Lai YD, Chen YY, Sun JP, Ling Y, Xu J, Ye YQ, Shen L, Lu HZ∗, Su B∗ and Wang Y∗. Immune profiles of a COVID-19 adolescent with mild symptoms and anti-viral antibody deficiency.  Fundamental Research (2021) 1:117–123

9. Xia LL, Wang H, Sun MJ, Yang Y, Yao CC, He S, Duan HQ, Xia WM, Sun RM, Yao YX, Chen ZW, Zhao Q, Li H, Lu S* and Wang Y*. Peripheral CD4+ T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer. Sci China Life Sci (2021)  doi.org/10.1007/s11427-020-1861-5

10. Yang QY#, Zhang YT#, Xiao JN, Liang YS, Ji P, Wang SJ, Wang Y* and Chen YY*. Age-related immunoreactivity profiles to diverse mycobacterial antigens in BCG vaccinated Chinese population. Front. Immunol. (2021) 11: 608220

11. Bao YJ #, Ling Y #, Chen YY #, Tian D, Zhao GP, Zhang XH, Hang H, Li Y, Su B, Lu HZ*, Xu J* and Wang Y*. Dynamic Anti-Spike Protein Antibody Profiles in COVID-19 Patients. Int J Infect Dis. (2021) 103:540–548

12. Wang C #, Ding Y #, Liu YY #, Zhang QC, Xu SQ, Xia LL, Duan HQ, Wang SJ, Ji P, Huang WR, Zhao GP, Cao ZW, Shen HB* and Wang Y*. Identification of Mutated Peptides in Bladder Cancer From Exomic Sequencing Data Reveals Negative Correlation Between Mutation-Specific Immunoreactivity and Inflammation. Front. Immunol. (2020) 11:Article 576603

13. Tian Y #, Lian CY #, Chen YY #, Wei D, Zhang XX, Ling Y, Wang Y* and Yeap LS*. Sensitivity and specificity of SARS-CoV-2 S1 subunit in COVID-19 serology assays. Cell Discovery. (2020) 6:75. doi: 10.1038/s41421-020-00224-3. eCollection 2020

14. Khanniche A, Zhou L, Jiang B, Song J, Jin YH, Yin J, Wang SJ, Ji P, Shen H, Wang Y* and Xu HJ*. Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment. Front. Immunol. (2019) 10: 887

15. Chen YY#, Xiao JN#, Li Y#, Xiao YJ#, Xiong YQ, Liu Y, Wang SJ, Ji P, Zhao GP, Shen H, Lu SH, Fan XY* and Wang Y*, Mycobacterial lipoprotein Z triggers efficient innate and adaptive immunity for protection against Mycobacterium tuberculosis infection. Front. Immunol., (2019) 9:3190.

16. Zhang MY#，Yao CC#，Cai J#，Liu S，Liu XN，Chen YY，Wang SJ，Ji P，Pan M, Kang ZZ* and Wang Y*. LRRK2 is involved in the pathogenesis of system lupus erythematosus through promoting pathogenic antibody production. J Translational Medicine, 2019.1.22, 17(1)

17. Zhang MY, Xia LL, Yang Y, Liu S, Ji P, Wang SJ, Chen YY, Liu ZD, Zhang YY, Lu S and Wang Y*. PD-1 blockade augments humoral immunity through ICOS-mediated CD4+ T cell instruction. International Immunopharma (2018).11.16, 66: 127-138

18. Yuan-yong Liu#, Wei Sha#, Shi-qiang Xu, Xu-Wei Gui, Li-liang Xia, Ping Ji, Shu-jun Wang, Guo-ping Zhao, Xiao Zhang*, Yingying Chen* and Ying Wang. Identification of HLA-A2-restricted mycobacterial lipoprotein Z peptides recognized by T Cells from patients with active tuberculosis infection, Front. Microbiol., (2018) 9:3131.

19. Xiao JN, XiongYQ, Chen YY, Xiao YJ, Ji P, Li Y, Wang SJ, Zhao GP, Cheng QJ, Lu SH* and Wang Y*. Determination of Lipoprotein Z-specific IgA in tuberculosis and latent tuberculosis infection. Front Cell Infect Mcrobiol. (2017) Nov 30; 7; 495. doi: 10.3389/fcimb.2017.00495

20. Yang X, Wu JB, Liu Y, Xiong Y, Ji P, Wang SJ, Chen Y, Zhao GP, Lu SH, Wang Y*. Identification of mycobacterial bacterioferritin B for immune screening of tuberculosis and latent tuberculosis infection. Tuberculosis (Edinb). 2017 Dec;107:119-125. doi: 10.1016/j.tube.2017.08.005. Epub 2017 Aug 31.

21. Liu Z, Zeng W, Huang X, Wang S, Zheng J, Pan M, Wang Y*. Peripheral CD19hi B cells exhibit activated phenotype and functionality in promoting IgG and IgM production in human autoimmune diseases. Sci Rep. 2017 Oct 24;7(1):13921. doi: 10.1038/s41598-017-14089-2.

Patent

• Applications of branched-chain amino acids in combinational therapy and predication of therapeutic efficacy in cancer immunotherapy. (National Application Number: 202111549291.6)

• HLA-A2 restricted neoantigen and its applications in bladder cancer. National Application Number: ZL 2019 1 0184858.0.  Patent Licensing Date: Sep 25 2020.

• A Kit for Detecting Mycobacterium tuberculosis Infection and Monitoring Clinical Effects of Anti-TB Treatment.  National Application Number: ZL 2014 1 0255419.1. Patent Licensing Date: December 7 2016.

• Preparation for Humanized Antibody against Avian Influenza H5N1 Hemagglutinin Antigen. National Application Number: ZL 2013 1 0693018.X. Patent Licensing Date: December 9 2015.

• Reagent for Detecting Mycobacterium tuberculosis Specific Immune Responses. National Application Number: ZL 2014 1 0028297.2. Patent Licensing Date: December 2 2015.

• SiRNA for Specific in vitro Interference LAT protein expression in human T cells. National Application Number: ZL 2010 1 0233433.3. Patent Licensing Date: March 6 2013.

• Preparation of VHH Heavy Chain Antibody against H5N1-type Avain Influenza Virus. National Application Number: ZL 2010 1 0148083.0. Patent Licensing Date: October 30 2013.

• Humanization of Antibody anti-Interferon alpha. National Application Number: 200910085232.0. Patent Licensing Date: November 18 2009.