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Immunity and Liver Disease
2024-04-09 10:17     (点击: )

Establishment and Development:

Immunity and Liver disease was born from a shared vision and passion for the liver immune microenvironment in both physiological and pathological conditions. Considering the huge burden of liver diseases and the significant roles of immune disorders, our founders decided to establish a laboratory dedicated to identify the novel immune subsets and key regulators responsible for liver immune homeostasis and relate diseases, to illustrate the molecular mechanism and regulatory network, to develop new strategies for multiple liver diseases. The journey of Immunity and Liver disease began with the same research interests and long term close cooperation focusing on liver immunology. With a small but dedicated team, we set out to establish a research laboratory that would be recognized for its excellence and impact. Since its inception, Immunity and liver disease has gone through a remarkable journey of growth and development. We have expanded our team to include five professors, two associate professors, three postdoctors and one research assistant. Our research has evolved to address the cell interaction, metabolic and functional homeostasis of liver immune microenvironment (such as macrophages, NK cells, T cells) in both physiological and pathological conditions to investigate the important immune regulatory molecules in liver homeostasis and chronic liver diseases, to reveal the crosstalk among liver, gut, fat and other tissues and its effect in whole body homeostasis, to develop novel intervention strategies for related liver diseases. Additionally, we have carried out valuable collaborations and partnerships with Dr. Brett T Spear in University of Kentuky, Dr. Kazuya Yamagata in University of Tokyo and Dr. Nailin Li in Karolinska Institute to further enhance our research capabilities.


Team Members:

Our team is composed of four doctoral supervisors. Dr. Chunhong Ma received her Ph.D degree in Immunology from Shandong University in 2002. Dr. Ma is the winner of the National Science Fund for Distinguished Young Scholars, National special support program for high-level personnel recruitment. Dr. Ma’s interests are focused on investigating immune microenvironment and gene regulation in liver diseases. She has strong interests in exploring the action of important immune mediators such as Tim-3 and ZHX2 in innate and adaptive immunity, and identifying novel strategies to improve antitumor immunity.

Dr. Xiaohong Liang’s research interest focuses on regulation of cancer immune microenvironment. The goal is to explore the novel strategies of tumor immunotherapy. Much of the focus is on how innate immune cells, including macrophages and NK cells, is manipulated in tumor microenvironment and involves in tumor development.

Dr. Lifen Gao is mainly engaged in the investigation of macrophage, CAR-T, metabolic related diseases and tumor immunity, and is committed to exploring the regulatory mechanism of macrophage homeostasis in related diseases, developing novel CAR-T cells for liver cancer.

Dr. Xuetian Yue’s major research interest is the response of tumors to nutrient stress, including glucose, glutamine and lipids. Together, we dedicate to explore the mechanism maintaining liver immune homeostasis and related diseases and develop new intervention strategies.


Research Areas:

Immunity and liver disease focuses on investigating liver immune microenvironment regulation and developing intervention strategy, systematically exploring the liver inflammation induced by viral infection, metabolism and other environmental factors and its malignant transformation mechanism. We are especially interested in the cell interaction among macrophages, NK cells, T cells and hepatocytes, as well as immune metabolism and immunosenescence in liver homeostasis and related diseases.


Research Achievements:

We have made significant contributions in delineating immune microenvironment and their interaction network during HBV infection, metabolic liver diseases and the malignant transformation of non-resolving liver inflammation. Some research work have been published in J Hepatol, Cell Mol Immunol, Gastroenterology, etc. These studies revealed an important mechanism of NK dysfunction, macrophage polarization, identified the key role of Tim-3, ZHX2 and Tipe1 in chronic viral infection mediating non-resolving inflammation and liver cancer pathogenesis, opening up a new field for HCC diagnosis and intervention. Recently, we focused on liver immune microenvironment regulation and intervention strategy research. We systematically explored the liver inflammation induced by viral infection, metabolism and other environmental factors and its malignant transformation mechanism. We identified the crucial roles of several important checkpoints including Tim-3, ZHX2, Siglec-9, Tipe1, Tim-4 in regulating T cells, NK cells, macrophages or hepatocytes, which provides new targets and strategies for liver cancer and virus infection (Sci Transl Med. 2023, J Exp Med. 2021, J Hepatol. 2024, Cancer Res. 2023, Cell Death Differ. 2023, Cell Rep. 2022, Nat Commun. 2023, etc.). We documented the regulatory mechanisms of nutrient deprivation and metabolic reprogramming in driving liver cancer progression and inducing exhaustion of hepatic NK cells (Redox biol.2023, Hepatology 2023, Cell Rep. 2023, Nat Commun. 2023, Mol Ther. 2022). In addition, we elucidated the potential target for HBV related liver disease and multiple human coronaviruses (Signal Transduct Target Ther. 2023, Signal Transduct Target Ther. 2021, Cell Mol Gastroenterol Hepatol. 2022, Adv Sci (Weinh). 2022, Cell Mol Immunol. 2021).


Main Publications:

Selected publications in last 5 years (*represents the corresponding authors).

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Kong Y, Wu M, Wan X, Sun M, Zhang Y, Wu Z, Li C, Liang X, Gao L, Ma C, Yue X*. Lipophagy-mediated cholesterol synthesis inhibition is required for the survival of hepatocellular carcinoma under glutamine deprivation. Redox Biol. 2023 Jul;63:102732.

  6. 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.

  7. Wang Y, Wang Y, Ding L, Ren X, Wang B, Wang L, Zhao S, Yue X, Wu Z, Li C, Liang X, Ma C, Gao L*. Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. Cell Rep. 2022 Nov 29;41(9):111738.

  8. Guo X, Tan S, Wang T, Sun R, Li S, Tian P, Li M, Wang Y, Zhang Y, Yan Y, Dong Z, Yan L, Yue X, Wu Z, Li C, Yamagata K, Gao L, Ma C, Li T*, Liang X*. NAD+ salvage governs mitochondrial metabolism, invigorating natural killer cell antitumor immunity. Hepatology. 2023 Aug 1;78(2):468-485.

  9. Cheng Y, Bai F, Ren X, Sun R, Guo X, Liu W, Wang B, Yang Y, Zhang X, Xu Y, Li C, Yang X, Gao L, Ma C, Li X*, Liang X*. Phosphoinositide-Binding Protein TIPE1 Promotes Alternative Activation of Macrophages and Tumor Progression via PIP3/Akt/TGFβ Axis. Cancer Res. 2022 Apr 15;82(8):1603-1616.

  10. 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 Sep 6;218(9):e20210009.

  11. 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 May;9(16):e2103135.

  12. 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 Aug;18(8):1871-1882.


Facilities & Resources:

Our state-of-the-art facilities and cutting-edge technology enable us to conduct research that is both rigorous and innovative. Our team is supported by the Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity. We boast multi-color fluorescence flow cytometry, real-time quantitative PCR instrument, laser confocal microscope, single crystal X-ray diffractometer, small animal micro CT imaging analysis system, fluorescence microscope, laser confocal microscope, laser confocal high content imaging analysis system, scanning electron microscope, transmission electron microscope, two-photon microscope, atomic force microscope, live cell workstation, panoramic tissue multispectral imaging and quantitative analysis system, biacore biomolecular interaction analysis system, mass spectrometry instrument, single crystal X-ray diffractometer, 400 MHz fully digital superconducting nuclear magnetic resonance spectrometer, cryo-electron microscopy, Seahorse Cell Energy Analysis System XFe96, small animal Metabolism System, small animal nuclear magnetic resonance Imaging instrument, SPF grade IVC mouse feeding system and other related facilities. In addition, several national key laboratories and open laboratories available in our university. Generally, our team is equiped with many large equipments and basic instruments required for performing above studies.


Collaborations & Partnerships:

We believe in the power of collaboration. That's why we have carried out collaborations with Dr. Brett T Spear from University of Kentuky, Dr. Kazuya Yamagata from University of Tokyo, Dr. Nailin Li from Karolinska Institute, Dr. Zhigang Tian from University of Science and Technology of China, Prof. Youhai Chen from Shenzhen University of Technology, Prof. Jianwei Wang from Chinese Academy of Medical Sciences and Peking Union Medical College, Dr. Jinming Yu from Shandong First Medical University, etc. In addition, we have established stable cooperative relations with professors of different disciplines in Shandong Unversity including Hong Liu and Yuanhua Sang (State Key Laboratory of Crystal Materials), Xinyong Liu and Minyong Li (Key Laboratory of Chemical Biology of Ministry of Education), Jiwei Cui (School of Chemistry and Chemical Engineering) to further advance our research.


Recreational Activities:

There are many types of outdoor and indoor activities in our university. We have modern gymnasium, concert hall and various social groups such as badminton, basketball, running. Our university often holds interesting sports, sets up a number of sports and entertainment and competitions suitable for all teachers and students to participate, strengthens the physical exercise, and improves the physical health. In addition, variety show is regularly held in Baotu Spring Campus to inherit the fine tradition of Qilu Medicine of the century-old "Broad Wisdom and Truth-seeking". Many types of professional development workshops are held to communicate with famous researchers in different fields.


Other Features:

Totally, there are more than 60 master and doctoral graduates in our team. In our lab, joint lab meeting is held each week. Journal club is organized by graduates actively to learn the lastest references. Christmas symponium is regularly held during Christmas to talk about the achievements and projects. In order to better relax, we usually hold a spring outing or autumn outing every year. We go hiking and skiing together.



For more information or inquiries, please contact us at, or visit our website at


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