学习与工作经历：

教育经历

1987.09-1991.07  山东师范大学生物学系 本科

1991.09-1994.07  华中师范大学昆虫学研究所 硕士

1999.09-2002.07  山东大学医学院免疫学研究生 博士

工作经历

1994.07-2000.07  山东医科大学基础部微生物教研室助教、讲师             

2000.09-2003.09  山东大学医学院免疫学研究所副教授              

2003.09-2016.07  山东大学医学院免疫学教授

2016.09-至今     山东大学基础医学院免疫学教授

研究方向：

主要从事肝病与免疫研究，致力于研究HBV、代谢等环境因素诱发肝脏炎症及其恶性转化机制，并探索新型免疫干预策略。发现了肝癌免疫微环境重塑新机制，鉴定获得了促进免疫治疗效应的新策略。

学术/社会兼职：

实验畸形学教育部重点实验室主任，中国免疫学会理事、第七届中国免疫学会肿瘤免疫与生物治疗分会委员、山东省免疫学会副理事长

获奖荣誉：

获得国家自然科学基金杰出青年基金、中组部“万人计划”领军人才、教育部“新世纪优秀人才支持计划”、霍英东基金会高等院校青年教师基金、山东省泰山攀登计划及山东省杰出青年基金、山东省杰出青年基金获得者、全国三八红旗手，享受国务院政府特殊津贴。

本科生课程：

医学免疫学、感染与免疫、感染免疫与相关疾病

研究生课程：

医学分子免疫学、消化诊疗新概念全英文课、分子与细胞免疫学新进展

1. 国家自然科学基金委员会，重点项目，82230056，代谢-线粒体轴失调介导NK细胞衰老在肝癌免疫逃逸中的作用及机制研究，2023.01-2027.12，261万元，在研，主持

2. 科技部重点研发计划，HBV慢性感染与肝脏免疫耐受和耗竭机制（2021YFC2300600）课题三：介导HBV 肝脏免疫耐受/耗竭的关键卡控点分子的发现与验证（2021YFC2300603），2021.12-2024.11，527万，在研，主持

3. 山东省自然科学基金重大基础研究项目，No.ZR2020ZD12，肿瘤免疫逃逸关键抑制分子的鉴定及多靶向纳米抗体制备，2021.01-2023.12，250万，在研，主持

4. 泰山攀登计划 (No.tspd20181201) 

5. 国家自然科学基金委员会，重点项目，81830017，肠道菌群调控肝脏免疫微环境阻断HBV慢性感染进程的作用与机制研究，2019.01-2023.12，293万，在研，主持

6. 国家重点研发计划“政府间国际科技创新合作重点专项”，中日政府间科技合作联委会联合研究项目，2016YFE0127000，射频消融改造肿瘤相关巨噬细胞在肝癌免疫治疗中的意义，2017.01-2019.12，284万元，已结题，主持

7. 国家自然科学基金杰出青年基金，81425012，HBV 感染、免疫与肝病研究，2015.01-2019.12，400万元，已结题，主持

8. 国家自然科学基金，面上项目，81370527，新型抑癌基因ZHX2调节脂质代谢参与非酒精性脂肪肝的作用研究 ，2014.01-2017.12，70万元，已结题，主持

9. 国家自然科学基金委员会，重大研究计划培育项目，91129704，Tim-3介导的NK及其调节网络异常在非可控性乙型肝炎向肝癌恶性转化进程中的作用，2012.01-2014.12，60万元，已结题，主持

10. 国家自然科学基金委员会，面上项目，81172353，HBV上调Foxp3表达促进肝癌细胞恶性增殖和免疫逃逸的分子机制研究 ，2012.01-2015.12，63万元，已结题，主持

1.Zhang Z, Ren C, Xiao R, Ma S, Liu H, Dou Y, Fan Y, Wang S, Zhan P, Gao C, Yue X, Li C, Gao L, Liang X, Wu Z**,Ma C**. Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity.Sci Immunol. 2024 Nov 15;9(101):eadp7302. doi: 10.1126/sciimmunol.adp7302.

2.Wang T^##, Fan Y^##, Tan S, Wang Z, Li M, Guo X, Yu X, Lin Q, Song X, Xu L, Li L, Li S, Gao L, Liang X**, Li C**,Ma C**. Probiotics and their metabolite spermidine enhance IFN-γ+CD4+ T cell immunity to inhibit hepatitis B virus.Cell Rep Med. 2024 Nov 19;5(11):101822. doi: 10.1016/j.xcrm.2024.101822.

3.Chen C^##, Zhao F^##, Peng J^##, Zhao D^##, Xu L, Li H, Ma S, Peng X, Sheng X, Sun Y, Wang T, Dong H, Ding Y, Wu Z, Liang X, Gao L, Wang H,Ma C**, Li C**. Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8+ T cell exhaustion and anti-PD-1 resistance.Cell Rep Med. 2024 Aug 20;5(8):101686. doi: 10.1016/j.xcrm.2024.101686.

4.Ren C, Zhang Z, Dou Y, Sun Y, Fu Z, Wang L, Wang K, Gao C, Fan Y, Sun S, Yue X, Li C, Gao L, Liang X,Ma C**, Wu Z**. DNA Sensor ABCF1 Phase Separates With cccDNA to Inhibit Hepatitis B Virus Replication.Adv Sci(Weinh). 2024 Dec;11(48):e2409485. doi: 10.1002/advs.202409485.

5.Ma S^##, Wu Q^##, Wu W^##, Tian Y, Zhang J, Chen C, Sheng X, Zhao F, Ding L, Wang T, Zhao L, Xie Y, Wang Y, Yue X, Wu Z, Wei J, Zhang K, Liang X, Gao L, Wang H, Wang G**, Li C**,Ma C**. Urolithin A hijacks ERK1/2-ULK1 cascade to improve CD8+ T cell fitness for antitumor immunity.Adv Sci. 2024 Mar 6:e2310065.

6.Xiao R^##, Tian Y^##, Zhang J, Li N, Qi M, Liu L, Wang J, Li Z, Zhang J, Zhao F, Wang T, Tan S, Li C, Wu Z, Yu M, Jiang X, Zhan P, Gao L, Han B**, Liu X**, Liang X**,Ma C**. Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy.J Hepatol. 2024 Feb 7:S0168-8278(24)00106-5.

7.Ma S^##, Tian Y^##, Peng J^##, Chen C, Peng X, Zhao F, Li Z, Li M, Zhao F, Sheng X, Zong R, Li Y, Zhang J, Yu M, Zhu Q, Tian X, Li Y, Neckenig MR, Liu H, Zhan P, Yue X, Wu Z, Gao L, Liang X, Liu X**, Li C**,Ma C**. Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models.Sci Transl Med. 2023 Nov 15;15(722):eadg6752. (IF=16.9).国际期刊Trends in Molecular Medicine (IF = 14.5)为该论文配发热点推荐（spotlight）文章“TIM-3 inhibitors: a promising strategy for tumor immunotherapy”

8.Zhang Y, Fan Y, Hu H, Zhang X, Wang Z, Wu Z, Wang L, Yu X, Song X, Xiang P, Zhang X, Wang T, Tan S, Li C, Gao L, Liang X, Li S, Li N, Yue X**,Ma C**ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nat Commun. 2023 Nov 18;14(1):7527.

9.Tan S^##, Wang Z^##, Li N, Guo X, Zhang Y, Ma H, Peng X, Zhao Y, Li C, Gao L, Li T, Liang X**,Ma C**. Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.Cell Death Differ. 2023 Sep;30(9):2104-2119.

10.Tian P, Yang W, Guo X, Wang T, Tan S, Sun R, Xiao R, Wang Y, Jiao D, Xu Y, Wei Y, Wu Z, Li C, Gao L,Ma C**, Liang X**. Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis.Nat Commun. 2023 Mar 27;14(1):1710.

11.Jiao D, Sun R, Ren X, Wang Y, Tian P, Wang Y, Yuan D, Yue X, Wu Z, Li C, Gao L,Ma C**, Liang X**. Lipid accumulation-mediated histone hypoacetylation drives persistent NK cell dysfunction in anti-tumor immunity.Cell Rep. 2023 Oct 31;42(10):113211.

12.Wu Z^##, Lei X^##, Wang X^##, Zhang Z, Li Y, Gao L, Liang X, Wang P, Wang J**,Ma C**. Peptide targeting the interaction of S protein cysteine-rich domain with Ezrin restricts pan-coronavirus infection.Signal Transduct Target Ther.2023 Jan 18;8(1):19.

13.Wang L^##, Zhang G^##, Sun Y, Wu Z, Ren C, Zhang Z, Peng X, Zhang Y, Zhao Y, Li C, Gao L, Liang X, Sun H, Cui J**,Ma C**. Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure.ACS Appl Mater Interfaces. 2022 Oct 19;14(41):46176-46187. (IF=9.6)

14.Ding Y^##, Chen C^##, Ma S, Sheng X, Zhao F, Peng J, Dong H,Ma C**, Li C**. Intrinsic PD-L1 promotes antitumor activity of CD8+ cytotoxic T lymphocytes via in cis interaction with CD80.Cancer Commun(Lond). 2022 Aug;42(8):784-788.

15.Wu Z, Wang L, Wang X, Sun Y, Li H, Zhang Z, Ren C, Zhang X, Li S, Lu J, Xu L, Yue X, Hong Y, Li Q, Zhu H, Gong Y, Gao C, Hu H, Gao L, Liang X,Ma C*:Mapping cccDNA-host interactome identifies cohesin complex as a novel HBV restriction factor.Cell Mol Gastroenterol Hepatol. 2022; S2352-345X(22)00180-1.

16.Sun Y^##, Teng Y^##, Wang L, Zhang Z, Chen C, Wang Y, Zhang X, Xiang P, Song X, Lu J, Li N, Gao L, Liang X, Xia Y**, Wu Z**,Ma C**. LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1.Adv Sci(Weinh). 2022 Apr 10:e2103135.

17.Wang T, Zhang J, Li N, Li M, Ma S, Tan S, Guo X, Wang Z, Wu Z, Gao L,Ma C**, Liang X**. Spatial distribution and functional analysis define the action pathway of Tim-3/Tim-3 ligands in tumor development.Mol Ther. 2022 Mar 2;30(3):1135-1148.（封面文章）

18.Yang X^##, Li M^##, Qin X, Tan S, Du L,Ma C**, Li M**. Photophosphatidylserine Guides Natural Killer Cell Photoimmunotherapy via Tim-3.J Am Chem Soc. 2022 Mar 9;144(9):3863-3874

19.Tan S, Guo X, Li M, Wang T, Wang Z, Li C, Wu Z, Li N, Gao L, Liang X,Ma C*. Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity.J Exp Med. 2021, 218(9):e20210009.

20.Wu Z^##**, Zhang Z^##,Wang X^##, Zhang J^##, Ren C, Li Y, Gao L, Liang X, Wang P**,Ma C**. Palmitoylation of SARS-CoV-2 S protein is essential for viral infectivity.Signal Transduct Target Ther. 2021, 6(1): 231.

21.Wang L, Sun Y, Song X, Wang Z, Zhang Y, Zhao Y, Peng X, Zhang X, Li C, Gao C, Li N, Gao L, Liang X, Wu Z**,Ma C**.Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes.Cell Mol Immunol. 2021, 18(8):1871-1882.

22.Chen C, Peng J, Ma S, Ding Y, Huang T, Zhao S, Gao L, Liang X, Li C**,Ma C**. Ribosomal protein S26 serves as a checkpoint of T-cell survival and homeostasis in a p53-dependent manner.Cell Mol Immunol. 2021, 18(7):1844-1846.

23.Wang Z, Kong L, Tan S, Zhang Y, Song X, Wang T, Lin Q, Wu Z, Xiang P, Li C, Gao L, Liang X**,Ma C**. Zhx2 Accelerates Sepsis by Promoting Macrophage Glycolysis via Pfkfb3.J Immunol. 2020, 204(8):2232-2241.

24.Yu X, Lin Q, Wu Z, Zhang Y, Wang T, Zhao S, Song X, Chen C, Wang Z, Xu L, Li C, Gao L, Liang X, Yue X**,Ma C**. ZHX2 inhibits SREBP1c-mediated de novo lipogenesis in hepatocellular carcinoma via miR-24-3p.J Pathol. 2020 Dec;252(4):358-370.

25.Lin Q, Wu Z, Yue X, Yu X, Wang Z, Song X, Xu L, He Y, Ge Y, Tan S, Wang T, Song H, Yuan D, Gong Y, Gao L, Liang X,Ma C*. ZHX2 restricts hepatocellular carcinoma by suppressing stem cell-like traits through KDM2A-mediated H3K36 demethylation.EBioMedicine. 2020, 53:102676.

26.Tan S^##, Xu Y^##, Wang Z, Wang T, Du X, Song X, Guo X, Peng J, Zhang J, Liang Y, Lu J, Peng J, Gao C, Wu Z, Li C, Li N, Gao L, Liang X**,Ma C**. Tim-3 hampers tumoral surveillance of liver-resident and conventional NK cells by disrupting PI3K pathway.Cancer Res. 2019 Dec 17.

27.Wu Z^##, Ma H^##, Wang L, Song X, Zhang J, Liu W, Ge Y, Sun Y, Yu X, Wang Z, Wang J, Zhang Y, Li C, Li N, Gao L, Liang X, Yue X**,Ma C**. Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake.Cell Death Differ. 2019 Nov 18.

28.Du X, Wu Z, Xu Y, Liu Y, Liu W, Wang T, Li C, Zhang C, Yi F, Gao L, Liang X,Ma C*.Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.Cell Mol Immunol. 2019 Nov;16(11):878-886

29.Zhang H, Song Y, Yang H, Liu Z, Gao L, Liang X**,Ma C**.Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-κB/IL-6/STAT3 axis.Oncogene. 2018 May;37(18):2456-2468.

30.Liu Y, Cheng Y, Xu Y, Wang Z, Du X, Li C, Peng J, Gao L, Liang X,Ma C*.Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers.Oncogene. 2017 Nov 2;36(44):6143-6153.

31.Yan W, Liu X, Ma H, Zhang H, Song X, Gao L, Liang X,Ma C*.Tim-3 fosters HCC development by enhancing TGF-β-mediated alternative activation of macrophages.Gut. 2015 Oct;64(10):1593-604.

32.Yue X, Zhang Z, Liang X, Gao L, Zhang X, Zhao D, Liu X, Ma H, Guo M, Spear BT, Gong Y,Ma C*. Zinc Fingers and Homeoboxes 2 Inhibits Cell Proliferation and Represses Cyclin A and Cyclin E expression.Gastroenterology. 2012 Jun;142(7):1559-1570.e2.

33.Ju Y, Hou N, Meng J, Wang X, Zhang X, Zhao D, Liu Y, Zhu F, Zhang L, Sun W, Liang X, Gao L,Ma C*.T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B.J Hepatol. 2010 Mar;52(3):322-9.

34.Luan F, Liu H, Gao L, Liu J, Sun Z, Ju Y, Hou N, Guo C, Liang X, Zhang L, Sun W,Ma C*.Hepatitis B virus protein preS2 potentially promotes HCC development via its transcriptional activation of hTERT.Gut.2009 Nov;58(11):1528-37.