Lab Leader:WenxiangZhang

Lab Name: Laboratory oftranscriptional regulation mechanisms of adaptive immunity

Lab Info：Building on its existing research achievements, the research group is committed to addressing key questions in tumorigenesis and immune regulation. Leveraging the scientific and clinical resources of Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, and Ruijin Hospital, the group plans to investigate transcriptional regulatory mechanisms of genes in depth from molecular and biochemical perspectives through interdisciplinary approaches and the development of diverse research and analytical methods, with the ultimate goal of pursuing clinical translation:

1. To further explore the molecular mechanisms by which the transcription factor FOXP3 regulates Treg cells, as well as its dynamic regulatory roles in the tumor microenvironment and autoimmune diseases.

2. To investigate the regulatory mechanisms of other core transcription factors across the immune system, uncover novel and more complex regulatory patterns, and strive to identify universal regulatory principles.

3. To elucidate the functions of microsatellite sequences in the genome in immune regulation and genome stability, examine their associations with specific diseases, and conduct analyses integrated with epidemiological data.

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Lab Leader: Leng Siew Yeap

Lab Name: Laboratory of Antibody Diversification

Lab Info：The research in the Yeap laboratory focuses on understanding the mechanisms of antibody diversification, specifically on how rare mutational outcomes from programmed DNA lesion processes in B cells contribute to anti-viral broadly neutralizing antibody (bnAb) activities or B cell-related diseases. Rare mutational outcomes on antibody genes such as insertion-deletions (indels), long complementarity determining region 3 (CDR3) and improbable mutations on certain nucleotides are bottlenecks that hinder the elicitation of bnAbs in vaccine strategies, resulting in the inefficiency of the immune system in fighting a fast evolving virus during a pandemic. We are interested in dissecting the genetic pathways that generate these rare mutational outcomes during Immunoglobulin (Ig) Somatic Hypermutation processes. Our lab has generated more than 40 mouse genetic models based on an in vivo hypermutating passenger-immunoglobulin B cell system and performed ultra-deep profiling of the mutational outcomes on the passenger-Ig gene to elucidate the pathways that generate the rare mutational outcomes and the effect of DNA sequences on mutation rate. Our ultimate aim is to generate humanized antibody mouse models based on our knowledge of antibody diversification processes to screen bnAbs and test vaccines. As the mutational outcomes during B cell receptor diversification processes also cause diseases such as autoimmune diseases and B cell cancers, we are also interested in collaborating with clinicians to identify the antibodies and antigens that resulted in these diseases.

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Lab Leader: Lei Chen

Lab Name: Laboratory of Genomics and Microbiome

Lab Info：My lab study the complex immune system and its interaction with human microbiota through analysis of sequencing data. One focus is to use single cell RNA-seq to dissect immune cell heterogeneity, track their developmental lineages. Another focus is human gut microbiota, how their compositions are correlated with intestinal health or disease.

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Lab Leader: Lei Shen

Lab Name: Laboratory of Immunometabolism

Lab Info：We focus on the interaction between the immune system and metabolism in the context such as metabolic diseases where immune cells modulate whole-body metabolism, and immune cells development where cell-intrinsic metabolic programs control the fate and function of immune cells. Our lab current research directions include: 1. To define the immune mechanisms of obesity-induced insulin resistance;

2. To decipher the metabolic programs that control Innate Lymphoid Cells (ILC) development and function.

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Lab Leader: Huabing Li

Lab Name: Laboratory of RNA Epigenetics &Immunity

Lab Info：There are more than 100 types of different chemical RNA modification, among which m6A, m1A, m5C, pseudoUridine and APA are the major ones. HBL lab has made a series of pioneering discoveries in the m6A studies, won international reputations in the field, and laid solid experimental foundation. m6A research has been the frontier of the epigenetics field, but it is under explored for other types of RNA modifications, especially the cross-talks among those RNA modifications in response to environmental stimulation are unknown. Immune cells, especially T cells and macrophages in various inflammatory disease and tumor, provide an ideal perspective to explore this frontier.Combine mouse reverse genetics and state-of-art omics techniques, our research focuses on the following areas:

(1) Function of m1A modification in T cells and macrophages;

(2) Function of pseudouridine modification in T cells and macrophages;

(3) Function of APA modification in T cells and macrophages;

(4) Develop inhibitors to those RNA modification and apply to tumor immunotherapy;

(5) Cross-talks of those RNA modifications.  Our lab website：www.hua-binglilab.com.

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Lab Leader: Feng Wang

Lab Name: Laboratory of Immune Cell Signaling and Metabolism

Lab Info：Research Interests：The research in my laboratory focuses on the mechanism of antigen recognition, signaling transduction and metabolic regulation of T lymphocytes. Three research directions include: (1) Regulation of immune cell signaling by naturally occurring metabolites; (2) The role of TCR signaling and repertoire in anti-tumor immune response; (3) The mechanism of anti-tumor immunity and autoimmunity induced by immune checkpoint blockade.

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Lab Leader: Qiming Liang

Lab Name: Laboratory of Virus-host Interaction

Lab Info：Research in my laboratory focuses on the interactions between virus and host, specifically emphasizing the oncogenic virus Kaposi sarcoma-associated herpesvirus (KSHV) and emerging pathogen Zika virus (ZIKV) and SARS-CoV-2. We utilize mutiple apporaches to dissect the molecular mechanisms by which viruses evade our immune system and cause the disease. Our recent work is published on Nature Immunology (2022), Cell Stem Cell (2016, 2020), Med (2021), and PLOS Pathogens (2021, 2022).

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POSTDOCTORS

2016-2019    Changrun Guo, Ph.D. (Jilin University)

2017-2019    Xin Wang, Ph.D. (Nanjing Agricultural University)

2020-2022    Jingjiao Li, Ph.D. (Shanghai Jiao Tong University)

2021-present  Shupeng Dong, Ph.D. (Shanghai Jiao Tong University)

GRADUATE STUDENTS

2016-2021    Shupeng Dong, Ph.D.

2017-2021    Xing Yang, Ph.D.

2018-present   Yafei Qu, Ph.D. candidate

2019-present   Weili Wang, Ph.D. candidate

2020-present   Jingfan Zhou, Ph.D. candidate

2020-present   Biyao Chen, Ph.D. candidate

2020-present   Peixian Dong, Master candidate

2021-present   Xiaoqian Wang, Ph.D. candidate

2021-present   Qingyu Guo, Ph.D. candidate

2021-present   Xue Xu, Master candidate

Lab Leader: Nie Hong

Lab Name: Laboratory of Immunoregulation and Immune Intervention

Lab Info：The main research direction in my laboratory is the pathogenesis and immune intervention of autoimmune diseases, focusing on the relationship between inflammatory factors and immune cells. We are interested in traditional Chinese medicine and study the mechanism of natural small molecule compounds in the treatment of autoimmune diseases to explore new therapeutic targets. In addition, we investigate the key molecules of tumor development and their impact on the tumor microenvironment, focusing on the interaction between tumor cells and immune cells, and exploring the mechanism of tumorigenesis and immune intervention strategies.

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Lab Leader:Youqiong Ye

Lab Name:Laboratory of Tumor Multiomics and Immunotherapy

Lab Info：

Our group focuses on the spatial characteristics of the tumor boundary microenvironment and their regulatory mechanisms. We conduct systematic investigations along a progressive framework of spatial feature characterization-immune evasion mechanisms-identification of potential therapeutic targets. We have developed a series ofnovel spatial omics algorithms and databases to characterize the spatial architecture of the tumor microenvironment; elucidated the molecular mechanisms by which the tumor boundary microenvironment regulates immune evasion; and identified potential targets while constructing predictive models and analytical tools for immunotherapy response. Our overall goal is to systematically define the critical roles of the tumor boundary microenvironment in tumor initiation, progression, and therapeutic response. To achieve this, we pursue the following three research directions:

(i) Development of single-cell and spatial omics algorithms and databases for characterizing tumor microenvironment

Advances in single-cell and spatial multi-omics technologies have greatly enhanced our understanding of cellular heterogeneity in complex biological systems. To fully leverage these technologies, our group has developed a series of computational methods and databases to systematically dissect the spatial features of the tumor microenvironment. For example, Cottrazm enables precise identification of tumor boundaries, multi-scale inference of spatial cellular composition, and reconstruction of near single-cell resolution spatial gene expression maps (Nat Commun2023a). HiST integrates spatial transcriptomics with histopathological images through a multi-scale deep learning framework, enabling prediction of spatial expression profiles and supporting tumor localization, prognosis evaluation, and clinical subtyping from H&E images (Adv Sci2026).

In terms of resource development, we have established a multi-layered database system, including the pan-cancer tumor spatial microenvironment database SpatialTME (Can Res2024a), the pan-cancer stromal cell atlas scPanStroma (Can Res2024b), and the dynamic tumor immune microenvironment database CTTIME capturing pre- and post-treatment changes (GPB2025). We further developed SpatialToolDB, an integrated visualization platform that combines spatial transcriptomics technologies, analytical algorithms, and databases (Sci Bull2026). These resources substantially improve the accessibility and analytical power of single-cell spatial omics data and provide a foundation for computational modeling of cellular phenotypes under physiological and pathological conditions. Our group continues to advance methodological development, with particular emphasis on cross-modal integration and cross-sample modeling.

(ii) Mechanistic studies of tumor boundary microenvironment in immune evasion

We focus on the tumor boundary as a critical spatial niche regulating immune responses, aiming to systematically elucidate its role in T cell dysfunction and immune evasion. Based on single-cell and spatial multi-omics approaches, we have shown that hypoxic heterogeneity in the tumor microenvironment shapes spatial cellular organization and drives immunotherapy resistance through a “hypoxia-ALCAM^highmacrophage-exhausted T cell” axis (Nat Metab2019;Adv Sci2024). Further studies revealed that in the tumor–adjacent interface, interactions betweenSPP1⁺ macrophages andFAP⁺ cancer-associated fibroblasts (CAFs) promote extracellular matrix deposition, forming a physical and functional immune barrier that restricts T cell infiltration. Targeting SPP1 disrupts this interaction, enhances T cell infiltration, and improves immunotherapy efficacy (Nat Commun2022;J Hepatol2023). In addition, we demonstrated that CAFs in the interface region induce functional exhaustion of CD8⁺ T cells at the tumor boundary, contributing to immunotherapy resistance (Cancer Res2024b;Adv Sci2025). Moreover, collaborative studies revealed that metabolic reprogramming plays a crucial role in regulating T cell function (Cell Metab2023;Immunity2024a, 2024b). Collectively, our work systematically elucidates how the tumor boundary microenvironment regulates T cell migration and dysfunction through spatial organization, cellular interactions, and metabolic regulation, providing a theoretical foundation for understanding immune evasion and improving immunotherapy strategies.

(iii) Construction of predictive models based on clinical cohorts and identification of spatially associated therapeutic targets

Accurate prediction of immunotherapy response remains a major challenge, as traditional biomarkers such as tumor mutational burden and PD-L1 expression are insufficient for comprehensive patient stratification. Based on clinical treatment cohorts, our group has developed predictive models including an early immune activation model based on dynamic changes of plasma cytokines(Innovation2022), as well as models based on alternative polyadenylation and circRNA features (Can Res2022;Nat Commun2023b). Furthermore, by integrating multi-cancer spatial multi-modal data with immunotherapy outcomes, we are developing agent-guided spatial predictive models to improve the accuracy and generalizability of response prediction.

In terms of target discovery, we focus on spatially defined functional niches within the tumor boundary microenvironment. We found that during chemotherapy, tumor cells can transition from intermediate states to a drug-resistant basal-like phenotype, co-evolving with SPP1⁺ macrophages and exhausted CD8⁺ T cells to form an immunosuppressive resistant niche. Mechanistically, the immune checkpoint molecule CD276 plays a dual regulatory role by promoting basal-like transformation of tumor cells while enhancing immunosuppressive signaling (Gastroenterology2026). This research direction aims to identify key spatially associated regulatory molecules and facilitate their translation into potential therapeutic targets, ultimately improving treatment efficacy and patient outcomes.

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Lab Leader: Yan Zhang Ph.D.

Lab Name: Laboratory of Cancer Immunotherapy

Lab Info：Our laboratory has focused on the fundamental mechanism of immune recognition and cancer biology, including both mechanisms that uncover the link between autoimmunity and cancer immunity, and on translating the new concept for production of new generation of cancer immunotherapeutic. We will focus on the most pressing unanswered questions in cancer immunotherapy, including a deeper understanding of the mechanisms of 1) tumor immunity and autoimmunity 2) response and resistance to current immunotherapy strategies, to help develop safe and effective treatments to benefit more patients, including new antibodies, new targets, new compounds and combinational therapeutics.

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Prof. Yan Zhang’s research group currently has 2 Assistant Research Fellows, 3 enrolled PhD students, and 1 master’s candidate.

Lab Leader:Qiang Zou

Lab Name:Laboratory of Cancer Immunometabolism

Lab Info：Tumor immunotherapy has been clinically applied in the treatment of malignant tumors, with remarkable efficacy in some patients, but there is still a problem of low clinical response rate. The activity of immune cells is regulated by cell metabolism. Studying the metabolic regulation mechanism of tumor immunity will provide new ideas and strategies for further improving the efficacy of tumor immunotherapy. Our team mainlyfocuses on the metabolic regulation mechanism of tumor immune response and tolerance, using molecular, cellular, biochemical, animal model, clinical samples,etc., to study the key factors involved in the regulation of tumor immune metabolism and its mechanism, and explore the immunotherapy strategy to intervene tumor immune metabolism and improve tumor immune response.

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Lab Leader: Ying Wang

Lab Name: Laboratory of T cell Dysfunction in Human Diseases

Lab Info：Research interest in my lab is the study on immunological mechanism and preventive strategies against lung-related diseases including infectious tuberculosis (TB), COVID-19 and lung cancer. In the investigations on TB, we have been working on the exploration of diagnostic biomarkers and development of novel preventive vaccines against TB and latent TB infection. We have screened panels of novel mycobaceterial antigens with high immunogenencity both in active TB patients and mice, which facilitates their further expectation for vaccine development and biomarker determination. In addition, some new-identified mycobacterial antigens were subjected to the study on the mechanisms of their immune regulatory function. Another interesting field lies in the screening the biomarkers for the checkpoint inhibitors against lung cancer. Multi-omics strategies has been used in this study to model the predictive and prognositic biomarkers for the clinical efficacy as well as resistance, which will be optional for the development of new immune-targets. Accordingly, new strategies are explored to improve the clinical efficacy of immune checkpoint inhibitors. During COVID-19 pandemics, we have investigated immune profiles of COVID-19 patients as well as in BBIBP-CorV vaccinees. In the last five years, we have successfully got more than 10 grants and published more than 30 publications. At present we have two faculty members, 5 graduate students and 1 post-doc. Prof Ying Wang has been selected in Shanghai Pujiang Talent program and Shanghai Academic Leader Program.

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Lab Leader: Huang Chuanxin

Lab Name: Laboratory of B cell Response and Tumor

Lab Info：In response to antigens such as vaccines B cells are activated and form germinal center B cells in lymphatic follicles, and eventually differentiate into plasma cells that can produce a large number of protective antibodies to eliminate pathogenic bacteria. The germinal center response leads to the formation of immune memory and production of high-affinity antibodies, and is critical for the effective role of the vaccine. Deficient B cell response can easily lead to low immune function and even immunodeficiency. Deregulated B cell differentiation within germinal center is associated with many human diseases, including autoimmune, allergic diseases, and B-cell lymphoma. We use a variety of genetic, cell biological and high-throughput sequencing technologies to reveal the transcriptional network underlying B cell responses. The goal is to better understand how B cells are programmed to produce antibodies via cell-intrinsic mechanisms and environmental clues, helping to develop new vaccine and therapeutic strategies for human B cell-related diseases.

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Lab Leader:YAO Yufeng

Lab Name:Laboratory of Bacterial Pathogenesis

Lab Info：

Research interest of the lab:

Our research focuses onbacterial pathogenesis andpathogen-host interactions covering two main topics. The first one is bacterial pathogenesis. UsingSalmonellaTyphimurium,Pseudomonas aeruginosa, and other clinically relevant bacteria as models, we investigate the regulatory roles of protein post-translational modifications (e.g., acetylation,lactylation and methylation) in bacterial virulence, acid resistance, antibiotic tolerance, and intracellular survival. We also useS. Typhimurium as a model to explore the mechanisms by which persister cells contribute to chronic infections and antibiotic resistance. The second topic is the mechanisms of pathogen-host interactions. UsingS. Typhimurium,P. aeruginosaandFusobacterium nucleatum, etc. as models, we investigate how bacteria regulate host protein post-translational modifications (e.g., acetylation and lactylation) and how bacterial metabolites modulate host immunity. This allows us to elucidate the mechanisms by which pathogens influence host cell fate, tumor development and progression, as well as immune responses.

Our group is currently undertaking several projects funded by the National Natural Science Foundation of China, including Youth Programs, General Programs, and Key Programs.Our team consists of one group leader, two associate professors, one senior experimentalist, two postdoctoral fellows, and five graduate students. The group provides its members with a personalized learning and working environment, as well as ample space for future career development. We welcome diligent and dedicated students who are interested in bacterial pathogenesis and human health to applyto join our group.

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Lab Leader: Liming Lu

Lab Name: Laboratory of Immune Regulation Research

Lab Info：Our research areas include immune regulation in transplantation and tolerance induction, 109 academic papers were published, including 56 SCI papers, 3 patent authorization and 2 patent applications. We first reported: 1. Low doses of Chinese medicine drug Trichosanthin in the negative regulation of the immune system, and identification of functional domains of Trichosanthin in immune tolerance in transplantation; 2.Th1/Th2 subset conversion via mCIITA and NOD receptor, providing a basis for modulating type I immune response in transplantation and autoimmune diseases. The results have been published in Nature, Nature cell biology and other journals. PI has been selected into Shanghai Pujiang Talent Plan, Shanghai Dawning Scholar, Shanghai Science and Technology Bright Star Talent Plan and presided over 15 national and municipal projects, participated in more than 10 national 863 and 973 projects, Shanghai Municipal Fund and Ministry of Health projects.

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Lab Leader: Zhiduo Liu

Lab Name: Laboratory of Immune Microenvironment

Lab Info：Research interest of the lab:

1. Pathogenic mechanism of important pathogenic bacteria

2. Interaction between important pathogenic bacteria and the host.

This group is currently undertaking a number of Youth project, General Program, Key Program of National Natural Science Foundation of China. Our group has 1 group leader, 1 associate professor, 1 lecturer, 1 senior experimentalist, 1 postdoctoral fellow, and 8 graduate students. With the research leader as the core, young and middle-aged teachers take the lead, and graduate students as the main body, the laboratory is a young and energetic team. The research group provides team members with a personalized learning and working environment, sufficient space for their future development. We welcome honest and hard-working students who are interested in bacterial pathogenesis and human health to apply for our group. We also welcome researchers who are interested in pathogenic mechanism of bacteria and bacteria-host interaction to join us.

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