Principal Investigator

Zhenke Wen, MD., Ph.D.

Distinguished Professor at Soochow University

Executive Dean of Institutes of Biology and Medical Sciences (IBMS)

Dr. Zhenke Wen is recognized as a National Overseas High-Level Talent (Youth), a Distinguished Professor and Outstanding Scholar in Jiangsu Province, and a Suzhou Innovation Leading Talent. He earned his Bachelor's degree in Clinical Medicine from Shandong First Medical University in 2004, followed by a Master’s degree in Immunology from Fudan University in 2007. From 2007 to 2010, Dr. Wen worked as a physician and deputy director at the Blood Transfusion Research Institute of Qingdao Blood Center. He completed his PhD in Immunology at Fudan University in 2013. Between 2014 and 2019, he conducted postdoctoral research and served as a Research Scientist at Stanford University School of Medicine. In September 2019, Dr. Wen joined the Institutes of Biology and Medical Sciences (IBMS) at Soochow University as a professor and principal investigator. He currently holds the positions of Executive Dean of IBMS and Director of the Jiangsu Key Laboratory of Infection and Immunity.

Research Interests

Current understanding of nucleic acid antigens predominantly focuses on their role in innate immunity, leaving their function in adaptive immunity as a fundamental and unresolved issue in immunology. Our research centers on the adaptive immune response to nucleic acid antigens, specifically self-DNA, and has led to original discoveries demonstrating that self-DNA functions as a T cell-dependent antigen. We are conducting comprehensive studies using clinical patient and control cohorts, humanized disease models, tissue organoids, and disease-related cell interaction platforms to investigate:

1. The cellular and molecular mechanisms underlying adaptive immune recognition and response to self-DNA.

2. How self-DNA regulates T and B cell differentiation and function.

3. The role of self-DNA in modifying tissue and organ regional immunity in human diseases.

Selected publications（^#Corresponding）

1. Wu T, Su D, Zhang L, Liu T, Wang Q, Yan C, Liu M, Ji H, Lei J, Zheng M, Wen Z^#. Mitochondrial control of proteasomal Psmb5 drives the differentiation of tissue-resident memory T cells in patients with rheumatoid arthritis. Arthritis Rheumatol 2024 Jul 22. doi: 10.1002/art.42954.

2. Zhang J, Ji H, Liu M, Zheng M, Wen Z^#, Shen H^#. Mitochondrial DNA Programs Lactylation of cGAS to Induce IFN Responses in Patients with Systemic Lupus Erythematosus. J Immunol 2024 Aug 2: ji2300758. doi: 10.4049/jimmunol.2300758.

3. Yuan Z, Liu M, Zhang L, Jia L, Hao S, Su D, Tang L, Wang C^#, Wang M^#, Wen Z^#. Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2024 Apr 23: keae231.

4. Lei J, Wen Z^#. DRP1 bridges complement component C5a and podocyte injury in lupus nephritis. Mol Ther 2024; 32(5):1199-1201.

5. Hu C, Qiao W, Li X, Ning ZK, Liu J, Dalangood S, Li H, Yu X, Zong Z^#, Wen Z^#, Gui J^#. Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8+T cells. Cell Metab 2024; 36(3):630-647.e8.

6. Wang Y, Liu M, Zhang L, Liu X, Ji H, Wang Y, Gui J^#, Yue Y^#, Wen Z^#. Cancer CD39 drives metabolic adaption and mal-differentiation of CD4+ T cells in patients with non-small-cell lung cancer. Cell Death Dis 2023; 14(12):804.

7. Qiao W, Hu C, Ma J, Dong X, Dalangood S, Li H, Yuan C, Lu B, Gao WQ, Wen Z^#, Yin W^#, Gui J^#. Low-dose metronomic chemotherapy triggers oxidized mtDNA sensing inside tumor cells to potentiate CD8⁺T anti-tumor immunity. Cancer Lett 2023; 216370.

8. Liu Z, Lei J, Wu T, Hu W, Zheng M, Wang Y, Song J, Ruan H, Xu L, Ren T^#, Xu W^#, Wen Z^#. Lipogenesis promotes mitochondrial fusion and maintains cancer stemness in human NSCLC. JCI Insight 2023; 8(6):e158429.

9. Liu Z, Shan S, Yuan Z, Wu F, Zheng M, Wang Y, Gui J, Xu W, Wang C^#, Ren T^#, Wen Z^#. Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells. EMBO Rep 2023; 24(2):e54006.

10. Jiang W, Sun M, Wang Y, Zheng M, Yuan Z, Mai S, Zhang X, Tang L, Liu X^#, Wang C^#, Wen Z^#. Critical Role of Notch-1 in Mechanistic Target of Rapamycin Hyperactivity and Vascular Inflammation in Patients With Takayasu Arteritis. Arthritis Rheumatol 2022; 74(7):1235-1244.

11. Wen Z^#, Xu L, Xu W, Xiong S^#. Retinoic Acid Receptor-Related Orphan Nuclear Receptor γt Licenses the Differentiation and Function of a Unique Subset of Follicular Helper T Cells in Response to Immunogenic Self-DNA in Systemic Lupus Erythematosus. Arthritis Rheumatol 2021; 73(8):1489-1500.

12. Zhang J, Zhao L, Wang J, Cheng Z, Sun M, Zhao J, Liu B, Liu X^#, Wen Z^#, Li Z^#. Targeting Mechanistic Target of Rapamycin Complex 1 Restricts Proinflammatory T Cell Differentiation and Ameliorates Takayasu Arteritis. Arthritis Rheumatol 2020; 72(2):303-315.

13. Wen Z, Jin K, Shen Y, Yang Z, Li Y, Wu B, Tian L, Shoor S, Roche NE, Goronzy JJ, Weyand CM. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation. Nat Immunol 2019; 20:313-325.

14. Wen Z, Shen Y, Berry G, Shahram F, Li Y, Watanabe R, Liao YJ, Goronzy JJ, Weyand CM. The microvascular niche instructs T cells in large vessel vasculitis via the VEGF-Jagged1-Notch pathway. Sci Transl Med 2017; 9(399). pii: eaal3322.

15. Wen Z^*, Shimojima Y^*, Shirai T, Li Y, Ju J, Yang Z, Tian L, Goronzy JJ, Weyand CM. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs. J Clin Invest 2016; 126:1953-67.