课题组致力于探究疾病组织微环境中细胞膜动态重塑调控T细胞功能的机制解析，并据此开发新一代靶向细胞膜的工程化免疫疗法。我们建立了涵盖小鼠模型、人源化模型及多组学分析的研究体系，结合合成生物学手段，重点开展以下研究方向：

（1）T细胞新型膜蛋白的功能解析与功能重塑： 鉴定在肿瘤微环境或慢性炎症中起关键作用的膜蛋白，揭示其介导T细胞功能调控机制。

（2）新型细胞免疫治疗策略的开发： 基于上述膜生物学新发现，设计并优化新型细胞治疗方案，通过精准干预实现T细胞功能的重编程。

顾博士长期聚焦T细胞抗肿瘤免疫的机制研究与免疫治疗转化。其研究系统性地阐明了T细胞内信号网络与代谢重编程的协同调控机制，并进一步拓展至细胞膜界面，揭示了膜转运功能障碍在T细胞功能失调中的关键作用。在此基础上，围绕T细胞膜功能开展工程化改造，发展了面向实体肿瘤治疗的新型CAR-T细胞策略。相关工作为膜信号调控在免疫治疗中的应用提供了重要参考。

*代表共同第一作者，#代表共同通讯作者。

1.Meidi Gu*, Kaitlin A. Read, Vipin Bhardwaj, Edmund J. Carvalho, David Padron Nardo, Justin C. Shayne, Divanshu Shukla, Wei Liu, Donald L. Siegel, Neil C. Sheppard, Michael C. Milone, Adam D. Cohen, Alfred L. Garfall, and James L. Riley*. Rab5 Improves CAR T Cell Efficacy via Reducing Fratricide and Maintaining Surface CAR Levels. (*first and co-corresponding author, accepted, Journal of Experimental Medicine, 2026).

2.Meidi Gu ^#, Xiaofei Zhou ^#, Jee Hyung Sohn, Lele Zhu, Zuliang Jie, Jin-Young Yang, Xiaofeng Zheng, Xiaoping Xie, Jie Yang, Yaoyao Shi, Hans D Brightbill, Jae Bum Kim, Jing Wang, Xuhong Cheng, Shao-Cong Sun. NF-κB-inducing kinase maintains T cell metabolic fitness in antitumor immunity. Nat Immunol. 22, pages193–204 (2021).

3.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

Jul;24(7):1165-1176.

4.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. Microglia promote autoimmune inflammation via the noncanonical NF-κB pathway. Sci Adv. 2021 Sep 3;7(36):eabh0609.

5.Lele Zhu, Yanchuan Li, Xiaoping Xie, Xiaofei Zhou, Meidi Gu, Zuliang Jie, Chun-Jung Ko, Tianxiao Gao, Blanca E Hernandez, Xuhong Cheng, Shao-Cong Sun. TBKBP1 and TBK1 form a growth factorsignaling axis mediating immunosuppression and tumorigenesis. Nat Cell Biol. 02 Dec.2019, 21(12):1604-1614.

6.Zuliang Jie, Jin-Young Yang, Meidi Gu, Hui Wang, Xiaoping Xie, Yanchuan Li, Ting Liu, Lele Zhu, Jianhong Shi, Lingyun Zhang , Xiaofei Zhou, Donghyun Joo, Hans D Brightbill, Yingzi Cong, Daniel Lin, Xuhong Cheng, Shao-Cong Sun. NIK signaling axis regulates dendritic cell function in intestinal immunity and homeostasis. Nature Immunology. volume 19, pages1224–1235 (2018).

7.Meidi Gu, Zhiyong Liu, Rongrong Lai, Si Liu, Wenlong Lin, Chuan Ouyang, Sheng Ye, He Huang, Xiaojian Wang. RKIP and TBK1 form a positive feedback loop to promote type I interferon production in innate immunity. EMBO J. 2016 Oct 17.4. C 

8.Meidi Gu, Ting Zhang , Wenlong lin , Zhiyong Liu, Rongrong Lai, Dajing Xia, He Huang, Xiaojian Wang. Protein phosphatase PP1 negatively regulates the Toll-like receptor- and RIG-I-like receptor-triggered production of type I interferon by inhibiting IRF3 phosphorylation at serines 396 and 385 in macrophage. Cell Signal. 2014 Dec;26(12):2930-9.

9.Chuan Ouyang*, Li Nie*, Meidi Gu*, Ailing Wu, Xu Han, Xiaojian Wang, Jianzhong Shao, Zongping Xia. TGF-β-activated kinase 1 (TAK1) Activation Requires Phosphorylation of Serine 412 by Protein Kinase A Catalytic Subunit α (PKACα) and Protein Kinase X (PRKX). J Biol Chem. 2014 Aug 29;289(35):24226-37. 

课题组正在招聘博士后、博士生、研究助理。