Research interests

Anti-Tumor immunity and Tumor immune Microenvironment

In recent years, metabolism and immune evasion have been added to cancer hallmarks contributing to cancer formation. This highlights the crucial role of the immune system in cancer progression. The tumor microenvironment in cancer is extremely complex, consisting of various factors, including cancer cells, immune cells, and stromal tissues. During the development of tumors, cancer cells often create an immunosuppressive microenvironment, enabling them to evade the antitumor immune response. Our previous research has revealed that the E3 ligase Peli1 regulates the metabolic pathways of T cells, thereby influencing T cell's antitumor response. Additionally, we have found that Peli1 can regulate inflammasome activation in macrophages. These studies illustrate the significance of Peli1 in immune cells and its involvement in the regulation of antitumor immunity. In the future, we will continue to explore in-depth the role of Peli1 in immune system regulation and develop therapeutic strategies targeting Peli1.

Regulation of Immune Cell Differentiation, Activation, and Function

T cells play a crucial role in the immune system, as they can eliminate foreign pathogens or cancer cells. Abnormal T cell responses are often observed in diseases like cancer and autoimmune diseases. Therefore, a deeper understanding of T cell regulation can contribute to the development of therapeutic strategies. We have employed high-throughput analysis to examine the changes in gene expression patterns during T cell activation and macrophage polarization. In the future, we will focus on these potentially important genes with unclear functions and investigate their roles in immune cell activation, function, and differentiation.

The Impact of Targeted Therapies on the Immune System

Repurposing existing drugs has always been a hot research topic, and the combination of immunotherapy with drugs is currently a significant focus in the scientific community. Furthermore, the relationship between drug resistance and the immune system remains poorly understood. In the future, we will investigate the effects of currently important targeted drugs and potential medications on the immune response. This research will contribute to the development of combination therapies, aiming to enhance their efficacy in cancer patients. It will significantly advance our understanding of targeted drugs and provide essential insights for future drug development.

1. Li Y, Zhu L, Ko CJ, Yang JY, Wang H, Manyam G, Wang J, Cheng X, Zhao S, Jie Z. TRAF3-EWSR1 signaling axis acts as a checkpoint on germinal center responses. J Exp Med (2023) 220 (8): e20221483
2. Lele Zhu, Xiaofei Zhou, Meidi Gu, Jiseong Kim, Yanchuan Li, Chun-Jung Ko, Xiaoping Xie, Tianxiao Gao, Xuhong Cheng, Shao-Cong Sun. Dapl1 controls NFATc2 activation to regulate CD8+ T cell exhaustion and responses in chronic infection and cancer. Nat Cell Biol 2022, 24(7):1165-1176.
3. Hsin-Ying Lin, Chun-Jung Ko, Tzu-Yu Lo, Shang-Ru Wu, Shao-Wei Lan, Chen-An Huang, Yi-Chin Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Cheng-Fan Lee, Pei-Wen Hsiao, Hsiang-Po Huang, Mei-Jou Chen, Kai-Hsiung Chang, Ming-Shyue Lee. Matriptase-2/NR4A3 axis switches TGF-β action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis. Oncogene 2022, 41(20): 2833-2845.
4. Tianxiao Gao, Ting Liu, Chun-Jung Ko*, Lingyun Zhang, Donghyun Joo, Xiaoping Xie, Lele Zhu, Yanchuan Li, Xuhong Cheng and Shao-Cong Sun*. Myeloid cell TBK1 restricts inflammatory responses. Proc Natl Acad Sci U S A. 2022: 119, e2107742119, Jan 25 (co-corresponding author and co-first author)
5. Yanchuan Li, Xiaoping Xie, Zuliang Jie, Lele Zhu, Jin-Young Yang, Chun-Jung Ko, Tianxiao Gao, Antrix Jain, Sung Yun Jung, Natalia Baran, Marina Y Konopleva, Xuhong Cheng, Shao-Cong Sun (2021, Dec). DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and Bcell leukemogenesis. Blood, 138(23):2360-2371.
6. Lingyun Zhang, Chun-Jung Ko, Yanchuan Li, Zuliang Jie, Lele Zhu, Xiaofei Zhou, Xiaoping Xie, Tianxiao Gao, Ting Liu, Xuhong Cheng, Shao-Cong Sun (2021, Oct). Peli1 facilitates NLRP3 inflammasome activation by mediating ASC ubiquitination. Cell Reports, 37(4):109904. (co-first author)
7. Xie X, Zhu L, Jie Z, Li Y, Gu M, Zhou X, Wang H, Chang JH, Ko CJ, Cheng X, Sun SC (2021, Sep). TRAF2 regulates T cell immunity by maintaining a Tpl2- ERK survival signaling axis in effector and memory CD8 T cells. Cell Mol Immunol, 18(9):2262-2274.
8. Zuliang Jie, Chun-Jung Ko, Hui Wang, Xiaoping Xie, Yanchuan Li, Meidi Gu, Lele Zhu, Jin-Young Yang, Tianxiao Gao, Wenjuan Ru, Shao-Jun Tang, Xuhong Cheng, Shao-Cong Sun (2021, Sep). Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway. SCIENCE ADVANCES, 7(36):eabh0609. (co-first author)
9. Hsin-Fang Tu, Chun-Jung Ko, Ching-Tai Lee, Cheng-Fan Lee, Shao-Wei Lan, Hsin-Hsien Lin, Hsin-Ying Lin, Chia-Chi Ku, Der-Yen Lee, I-Chun Chen, Ya- Hui Chuang, Francisco Del Caño-Ochoa, Santiago Ramón-Maiques, Chao-Chi Ho, Ming-Shyue Lee, Geen-Dong Chang (2021, Jun). Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD. Cancer Research, 81(12):3270-3282.
10. Ko CJ, Zhang L, Jie Z, Zhu L, Zhou X, Xie X, Gao T, Yang JY, Cheng X, Sun SC (2021, Jan). The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses. EMBO Journal, 40(2):e104532.
11. Yang JY, Jie Z, Mathews A, Zhou X, Li Y, Gu M, Xie X, Ko CJ, Cheng X, Qi Y, Estrella JS, Wang J, Sun SC (2020, Nov). Intestinal Epithelial TBK1 Prevents Differentiation of T-helper 17 Cells and Tumorigenesis in Mice. Gastroenterology, 159(5):1793-1806.
12. Ko CJ, Hsu TW, Wu SR, Lan SW, Hsiao TF, Lin HY, Lin HH, Tu HF, Lee CF, Huang CC, Chen MM, Hsiao PW, Huang HP, Lee MS (2020, Sep). Inhibition of TMPRSS2 by HAI-2 reduces prostate cancer cell invasion and metastasis. Oncogene, 39(37):5950-5963. (co-first author)
13. Zhu L, Li Y, Xie X, Zhou X, Gu M, Jie Z, Ko CJ, Gao T, Hernandez BE, Cheng X, Sun SC (2019, Dec). TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis. Nat Cell Biol, 21(12):1604- 1614.
14. Lee CF, Dang A, Hernandez E, Pong RC, Chen B, Sonavane R, Raj G, Kapur P, Lin HY, Wu SR, Ko CJ, Lo UG, Lee HY, Hsieh JT, Lee MS (2019, Jul). Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase. Oncogene, 38(28):5580-5598.
15. Wu SR, Lin CH, Shih HP, Ko CJ, Lin HY, Lan SW, Lin HH, Tu HF, Ho CC, Huang HP, Lee MS (2019, Mar). HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis. . Br J Cancer, 120(5):499-511.
16. Wu SR, Teng CH, Tu YT, Ko CJ, Cheng TS, Lan SW, Lin HY, Lin HH, Tu HF, Hsiao PW, Huang HP, Chen CH, Lee MS (2017, Nov). The Kunitz Domain I of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells. . Sci Rep, 7(1):15101.
17. Ko CJ, Lan SW, Lu YC, Cheng TS, Lai PF, Tsai CH, Hsu TW, Lin HY, Shyu HY, Wu SR, Lin HH, Hsiao PW, Chen CH, Huang HP, Lee MS (2017, Aug). Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis. oncogene, 36(32):4597-4609. (co-first author)