本课题组聚焦于肿瘤微环境中T细胞功能调控的营养代谢与表观遗传交叉机制， 我们将以小鼠为模型，结合蛋白组学、代谢组学、表观组学以及遗传学等多组学手段，系统解析肿瘤内T细胞营养感知的分子机制，并围绕以下两个核心科学问题展开研究：

（1）在肿瘤微环境中，T细胞如何选择性感知并响应不同类型的营养物质以调控其表观遗传图谱及功能？

（2）在系统代谢紊乱条件下，T细胞如何整合并协调局部与全身性代谢信号，以维持其抗肿瘤能力？

马世鑫博士长期聚焦于肿瘤微环境中T细胞命运与功能的代谢–表观遗传调控机制，在免疫代谢与表观遗传学交叉领域取得了一系列具有原创性的研究成果。截至目前，马博士共发表科研论文11篇，其中以第一作者发表Science与Journal of Experimental Medicine各一篇。

马世鑫博士博士毕业于中国科学院上海巴斯德研究所与苏州大学联合培养项目，曾在耶鲁大学及美国索尔克研究所从事博士后与副研究员工作，师从国际著名免疫学家、美国科学院院士Susan Kaech 教授。

马世鑫博士（1）提出并验证了“营养驱动的组蛋白乙酰化密码”这一新概念，揭示CD8⁺ T细胞可根据不同营养来源（如乙酸和葡萄糖）产生的乙酰辅酶A，构建差异化的组蛋白乙酰化图谱，从而驱动谱系特异性的转录程序与功能命运；（2）系统阐明了亚细胞器代谢分区在表观遗传调控中的核心作用，发现乙酰辅酶A在细胞核内的不同来源（ACLY与ACSS2）通过各自特异的组蛋白乙酰转移酶复合物，引导T细胞分化为效应型或耗竭型，奠定了营养代谢介导免疫命运决定的新机制；（3）构建了代谢–表观遗传重编程的普适性理论框架，为靶向代谢通路调控表观状态以增强T细胞抗肿瘤活性提供了理论基础与策略指导。

索尔克生物研究院创新博士后基金 （2019-2020）

Cancer research institute博士后基金 （2020-2023）

AAI 口头报告奖 （2024）

AAI 优秀墙报奖 （2025）

1.Shixin Ma; Michael S. Dahabieh; Thomas H. Mann; Steven Zhao; Bryan McDonald; Won-Suk Song; H. Kay Chung; Yagmur Farsakoglu; Lizmarie Garcia-Rivera; Filipe Araujo Hoffmann; Shihao Xu; Victor Y. Du; Dan Chen; Jesse Furgiuele; Michael A. LaPorta; Emily Jacobs; Lisa M. DeCamp; Brandon M. Oswald; Ryan D. Sheldon; Abigail E. Ellis; Longwei Liu; Peixiang He; Yingxiao Wang; Cholsoon Jang; Russell G. Jones; Susan M. Kaech ; Nutrient-driven histone code determines exhausted CD8 + T cell fates, Science, 2025, 387(6734)

2. Heleen H. Van Acker; Shixin Ma; Tommaso Scolaro; Susan M. Kaech; Massimiliano Mazzone; How metabolism bridles cytotoxic CD8+ T cells through epigenetic modifications, Trends in Immunology, 2021, 42(5): 401-41

3. Ma, Shixin; Wan, Xiaoling; Deng, Zihou; Shi, Lei; Hao, Congfang; Zhou, Zhenyuan; Zhou, Chun; Fang, Yiyuan; Liu, Jinghua; Yang, Jing; Chen, Xia; Li, Tiantian; Zang, Aiping; Yin, Shigang; Li, Bin; Plumas, Joel; Chaperot, Laurence; Zhang, Xiaoming; Xu, Guoliang; Jiang, Lubin; Shen, Nan; Xiong, Sidong; Gao, Xiaoming; Zhang, Yan; Xiao, Hui ; Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs, JOURNAL OF EXPERIMENTAL MEDICINE, 2017, 214(5): 1471-1491

4. Siva Karthik Varanasi; Shixin Ma; Susan M.Kaech ; T Cell Metabolism in a State of Flux,Immunity, 2019, 51(5): 783-785

5. Deng, Zihou; Ma, Shixin; Zhou, Hao; Zang, Aiping; Fang, Yiyuan; Li, Tiantian; Shi, Huanjing; Liu, Mei; Du, Min; Taylor, Patricia R.; Zhu, Helen He; Chen, Jiangye; Meng, Guangxun; Li, Fubin; Chen, Changbin; Zhang, Yan; Jia, Xin-Ming; Lin, Xin; Zhang, Xiaoming; Pearlman, Eric; Li, Xiaoxia; Feng, Gen-Sheng; Xiao, Hui ; Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses, NATURE IMMUNOLOGY, 2015, 16(6): 642-652

6. Irem Kaymak; McLane J. Watson; Brandon M. Oswald; Shixin Ma; Benjamin K. Johnson; Lisa M. DeCamp; Batsirai M. Mabvakure; Katarzyna M. Luda; Eric H. Ma; Kin Lau; Zhen Fu; Brejnev Muhire; Susan M. Kitchen-Goosen; Alexandra Vander Ark; Michael S. Dahabieh; Bozena Samborska; Matthew Vos; Hui Shen; Zi Peng Fan; Thomas P. Roddy; Gillian A. Kingsbury; Cristovão M. Sousa; Connie M. Krawczyk; Kelsey S. Williams; Ryan D. Sheldon; Susan M. Kaech; Dominic G. Roy; Russell G. Jones ; ACLY andACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses, Journal of Experimental Medicine, 2024, 221(9)

7. Bryan McDonald; Brent Y. Chick; Nasiha S. Ahmed; Mannix Burns; Shixin Ma; Eduardo Casillas; Dan Chen; Thomas H. Mann; Carolyn O’Connor; Nasun Hah; Diana C. Hargreaves; Susan M. Kaech; Canonical BAF complex activity shapesthe enhancer landscape that licenses CD8(+) T cell effector and memory fates, Immunity, 2023, 56(6): 1303-1319.E5

8. Dan Chen; Siva Karthik Varanasi; Toshiro Hara; Kacie Traina; Ming Sun; Bryan McDonald; Yagmur Farsakoglu; Josh Clanton; Shihao Xu; Lizmarie Garcia-Rivera; Thomas H. Mann; Victor Du; H. Kay Chung; Ziyan Xu; Victoria Tripple; Eduardo Casillas; Shixin Ma; Carolyn O’Connor; Qiyuan Yang; Ye Zheng; Tony Hunter; Greg Lemke; Susan M. Kaech ; CTLA-4 blockade induces a microglia-Th1 cell partnership that stimulates microglia phagocytosis and anti-tumor function in glioblastoma, Immunity, 2023, 56(9): 2086-2104.E8

9. Lei Shi; Xia Chen; Aiping Zang; Tiantian Li; Yanxiang Hu; Shixin Ma; Mengdie Lü; Huiyong Yin; Haikun Wang; Xiaoming Zhang; Bei Zhang; Qibin Leng; Jinbo Yang; Hui Xiao; TSC1/mTOR- controlled metabolic–epigenetic cross talk underpins DC control of CD8+ T-cell homeostasis, PLOS Biology, 2019, 17(8)

10. Chun Zhou; Xia Chen; Rosa Planells-Cases; Jiachen Chu; Li Wang; Limin Cao; Zhihong Li; Karen I. López-Cayuqueo; Yadong Xie; Shiwei Ye; Xiang Wang; Florian Ullrich; Shixin Ma; Yiyuan Fang; Xiaoming Zhang; Zhikang Qian; Xiaozheng Liang; Shi-Qing Cai; Zhengfan Jiang; Dongming Zhou; Qibin Leng; Tsan S. Xiao; Ke Lan; Jinbo Yang; Huabin Li; Chao Peng; Zhaozhu Qiu; Thomas J. Jentsch; Hui Xiao ; Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity, Immunity, 2020, 52(5): 767-781.e6

11. Cao L, Wang L, Li Z, Wei X, Ding J, Zhou C, Chen X, Huang Z, Shao Z, Shen J,Lou H, Zhao K, Huang Y, Yang Y, Liu H, Sun Y, Niu J, Jiang S, Lu R, Tang L, ZhangX, Zhang H, Xiao Y, Chen J, Ma S, Gao C, Meng G, Liu L, Qiu Z, Wang H, Deng L,Ye Y, Jia XM, Li H, Xiao H. 2025. Radiotherapy enhances anticancer CD8 T cell responses by cGAMP transfer through LRRC8A/C volume-regulated anion channels. Sci Immunol 10: eadn1630 

博士后