Our lab focuses on the intersection of nutrient metabolism and epigenetic regulation in shaping T cell function within the tumor microenvironment. Using mouse models, we integrate multi-omics approaches, including proteomics, metabolomics, epigenomics, and genetics, to systematically dissect the molecular mechanisms by which T cells sense and respond to nutritional signals in tumors. Our research centers around two fundamental scientific questions:

1.How do T cells selectively sense and respond to different types of nutrients in the tumor microenvironment to shape their epigenetic landscape and functional states?

2.Under conditions of systemic metabolic dysregulation, how do T cells integrate and coordinate local and systemic metabolic signals to maintain their anti-tumor capacity?

Dr. Shixin Ma has long focused on the metabolic–epigenetic regulatory mechanisms that govern T cell fate and function within the tumor microenvironment. She has made a series of original contributions at the intersection of immunometabolism and epigenetics. To date, Dr. Ma has published 11 research articles, including two first-author papers in Science and Journal of Experimental Medicine.

Dr. Ma received her Ph.D. through a joint training program between Soochow University and the Institut Pasteur of Shanghai, Chinese Academy of Sciences. She subsequently conducted postdoctoral and associate research at Yale University and the Salk Institute, under the mentorship of renowned immunologist and National Academy of Sciences member, Professor Susan Kaech.

Her key scientific contributions include: (1) Proposing and experimentally validating the novel concept of a “nutrient-driven histone acetylation code,” demonstrating that CD8⁺ T cells selectively utilize acetyl-CoA derived from distinct nutrients (e.g., acetate and glucose) to establish distinct histone acetylation landscapes, thereby directing lineage-specific transcriptional programs and functional states; (2) Elucidating the critical role of subcellular compartmentalized metabolism in epigenetic regulation, revealing that nuclear acetyl-CoA generated by different enzymes (ACLY vs. ACSS2) associates with distinct histone acetyltransferase complexes, driving T cell differentiation toward effector or exhausted fates and establishing a new mechanism by which nutrient metabolism directs immune cell fate; (3) Developing a generalizable framework for metabolic–epigenetic reprogramming of immune cells, providing both theoretical insight and strategic guidance for targeting metabolic pathways to modulate epigenetic states and enhance the anti-tumor efficacy of T cells.

Salk Institute Innovation Postdoctoral Fellowship (2019–2020)

Cancer Research Institute Postdoctoral Fellowship (2020–2023)

AAI Oral Presentation Award (2024)

AAI Outstanding Poster Award (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 

Postdoc