Name：Yi Cai

Position：Tenured Associate Professor

E-mail：caiyi0113@szu.edu.cn

Personal Statement:

Dr. Yi Cai is a tenured Associate Professor at the Department of Pathogen Biology, Shenzhen University Medical School. His research centers on host–Mycobacterium tuberculosis (Mtb) interactions, with the goal of identifying new therapeutic targets and host-directed therapies (HDT) for tuberculosis. He has systematically uncovered mechanisms by which Mtb evades host immune responses, particularly macrophage-mediated killing, and identified key host molecules such as CD157, SIRT7, MFN1, HRH1, and TRIM21 that contribute to Mtb clearance or persistence  (mBio, 2019, 2020, 2023, 2024; J Clin Invest 2023, Autophagy 2023). His team has screened over 1,500 FDA-approved compounds and identified several HDT candidates, including sulfasalazine, which has advanced to a Phase III clinical trial in China for MDR-TB. This represents one of the first HDT drugs for TB to reach this stage of development nationally.

Beyond therapeutic discovery, Dr. Cai investigates Mtb’s metabolic adaptation to immune pressure, including its use of cytochrome bd oxidase to resist IFNγ-induced acidification (PLoS Pathogens, 2021). He also employs single-cell RNA sequencing to uncover immune cell heterogeneity in TB. His studies revealed dynamic shifts in NK and CD8+ T cell populations during disease progression and at local infection sites, providing novel insights into TB immunopathogenesis (EbioMedicine, 2020; JEM, 2022; JCI Insight, 2024). Dr. Cai’s work bridges basic immunology with clinical application, offering new avenues for TB control.

Research Interests:

 • Host-pathogen interactions in Mtb infection

 • Mechanisms of immune evasion and immunopathogenesis

 • Discovery of host-directed therapeutics (HDT) for tuberculosis

 • Single-cell transcriptomics and immune heterogeneity in TB

Ongoing Research Projects:

1. NSFC (China)：The mechanism by which Mycobacterium tuberculosis downregulates Sirt7 to disrupt actin cytoskeleton rearrangement for immune evasion, 2025/1-2028/12 490,000 RMB; Yi Cai, PI

2. General Project of Shenzhen Institute of Advanced Medical Sciences: Molecular mechanism of iron metabolism dysregulation induced by Mycobacterium tuberculosis infection and its regulatory role in tuberculosis pathogenesis, 2024/1-2026/12, 3 million RMB, Yi Cai, PI

3. Shenzhen "Champion Project" for Technological Innovation: Development and application of new biomarkers and detection technologies for major diseases, 2022.11-2027.10, 30 million RMB Yi Cai, Co-PI. (6 million RMB allocated to the cooperating unit under my leadership)

Selected Peer-reviewed Publications:

1. Dai, Y., Zhu, C., Xiao, W., Huang, K., Wang, X., Shi, C., Lin, D., Zhang, H., Liu, X., Peng, B., Gao, Y., Liu, C. H., Ge, B., Kaufmann, S. H., Feng, C. G., Chen, X. *,& Cai, Y. * (2023). Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth. The Journal of clinical investigation, 133(8), e159941.

2. Cai, Y. #, Wang, Y. #, Shi, C. #, Dai, Y., Li, F., Xu, Y., Zhang, P., Kong, F., Deng, G., Wen, Z., Zhou, Q., Kang, B. C., Singhal, A., Yang, Q., Feng, C. G.*, & Chen, X*. (2022). Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion. The Journal of experimental medicine, 219(3), e20211777.

3. Li F, Zhang X, Xu J, Zhang Y, Li G, Yang X, Deng G, Dai Y, Liu B, Kosan C*, Chen X*, Cai Y*. SIRT7 remodels the cytoskeleton via RAC1 to enhance host resistance to Mycobacterium tuberculosis. mBio. 2024 Oct 16;15(10):e0075624

4. Yang Q#, Liao M#, Wang W, Zhang M, Chen Q, Guo J, Peng B, Huang J, Liu H, Yahagi A, Xu X, Ishihara K, Cooper A, Chen X*, Cai Y*. CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production. mBio. 2019 Aug 27;10(4). pii: e01949-19.

5. Li F, Zhu C, Zhang Y, Kong F, Zhang X, Pan L, Jia H, Fu L, Hu Y, Deng G, Yang Q, Chen X*, Cai Y*. (2024). Granzyme A as biomarker for diagnosis in tuberculous pleural effusion. JCI Insight, 6;9(23):e185307.