NAME: Xing, Shaojun

POSITION TITLE: Professor of pathology and immunology; Shenzhen University School of Medicine

EDUCATION/TRAINING

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A.?? Personal Statement

My research interests focus on the immune response to infection.? I have been studied the function and development of T cells using mouse model and human immune cells. Based on the previous work, I will further study the regulation of immune response to infection and underlying molecular mechanism: 1). Regulatory Follicular helper T cells response to infection. 2). Epigenetic modification of multiple immune cells.

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B.?? Positions and Honors

Positions and Employment

08/2010–03/2013??????? Assistant Professor, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

05/2018 – present????? Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China

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Other Experience and Honors

1.??? Member of American Association of Immunologists (AAI)? (2017)

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C.?? Contributions to Science

1.??? T cell development: Epigenetic modification function of transcription factor:

CD4+ and CD8+ T cell dichotomy is essential for effective cellular immunity. How individual T cell identify is established remains poorly understood. TCF1/LEF1 are transcription factors downstream of Wnt signaling, and regulate the development of T cells in the thymus. Using Cd4-cre mediated conditional gene knockout mouse, I investigated the function of TCF1/LEF1 at the late stage of T cell development. We found that, TCF1/ LEF1 determined the CD4+ T cells fate, and specific ablation of TCF1/LEF1 at double positive (DP) stage results in the deficiency of CD4+T cell. On the other hand, TCF1/ LEF1 regulate the integrity of CD8+ T cells by repressing the expression of CD4+ T cell lineage-associated genes. More important,? ?hyper-acetylation of? histone H3K9 and H3K27 exhibit in TCF1/LEF1 deficient CD8 T cells and correlated with TCF1 binding sites. Furthermore, by in vitro analysis of enzymic activity, we identified the histone deacetylase (HDAC) function of TCF1/LEF1.

TCF1 is essential for T cell development. As a result of differential promoter usage and alternative splicing, multiple TCF1 isoforms can be detected in T cells- p45/p42 and p33/p30. All isoforms contain a C-terminal DNA binding domain and a newly discovered HDAC domain(Steinke et al 2014). Among all the isoforms, long isoform contains a unique N-terminal β-catenin binding domain more than short isoform. ?however, it remains controversial β-catenin whether play a role in the regulation function of TCF1. By comparing the function of long isoform and short isoform, we found that β-catenin binding domain is dispensable for T cell maturation, but essential for ?the thymocytes survival.

1)??? Zhe Xu*, Shaojun Xing*, Qiang Shan et al Cutting Edge: beta-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions. J Immunol. 2017 Mar 27. pii: 1602139. doi: 10.4049/jimmunol.1602139.? (co-first author).

2)??? Shaojun Xing*, Fengyin Li*, Zhouhao Zeng*, Yunjie Zhao, Shuyang Yu, et al Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity. Nat Immunol. 2016 Jun;17(6):695-703.

2.??? Infection and immunity: dynamic enhancer repertoires and regulatory networks of CD8+ T cells ?in response to infections

CD8+ T cell-mediated immune response are essential for controlling infection. The differentiation of na?ve to effector and subsequently to memory is accompanied by extensive changes in the transcriptome. Core transcriptional signatures of effector and memory CD8+ T cells are relatively conserved regardless of infection types (Best et al, 2013). Regulation of gene transcription is mediated by dynamic activation and interaction of promoters and enhancers (Ong and Corces,2011). Enhancers exhibit higher cell-type specificity and contribute to spatial and temporal gene regulation to a greater extent than promoters. We employed well-established infection models and profiled the epigenomics during CD8+ T cell response. Using histone mark signatures, we uncovered a highly dynamic repertoire of enhancers and super enhancers. We further constructed T cell response stage-specific transcriptional regulatory networks, providing an enhancer-centric, global view of the regulatory circuitry in antigen-responding CD8+ T cells, serving as a blueprint for in-depth delineation of molecular mechanisms underlying functional differentiation of CD8+ T cells.

1)??? Bing He*, Shaojun Xing*, Changya chen et al CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections. Immunity. 2016 Dec 20;45(6):1341-1354. (co-first author).

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3.??? TCF1/ LEF1 regulate differentiation of follicular helper T cells ：

Follicular helper T cells (Tfh cells) are specialized effector CD4+ T cells that help B cells develop germinal centers(GCs) and memory. However, the transcription factors that regulate the differentiation of Tfh remain incompletely understood. In collaboration with Shane Crotty group, we reported that selective loss of TCF1 and LEF1 resulted in Tfh cell defects. Mechanistically, TCF1/LEF1 established the responsiveness of na?ve CD4+ T cells to Tfh cell signals and they promoted early Tfh differentiation via regulating multiple interacting mechanisms upstream of Bcl6 during Tfh differentiation.?

1)??? Choi YS, Gullicksrud JA, Xing S et al? LEF-1 and TCF-1 orchestrate T(FH) differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6 Nat Immunol. 2015 Sep;16(9):980-90.

4.??? Human immunity: CD4+ cytotoxic T cell (CTL) in HBV-related hepatocellular carcinoma (HCC) patients and immune deficiency during chronic HIV-1 infection

Hepatocellular carcinoma (HCC) is characterized by a progressive development and poor prognosis. The role of CD4+ CTL in HCC remains obscure. We defined CD4+ CTL in HBV-related HCC patients and correlated with disease progression.??

HIV-1 infection is associated with immune deficiency. We analyzed the hyperactivation of cytotoxic T cells and FoxP3+ regulatory T cells during chronic HIV-1 infection. In addition, we found follicular cytotoxic T cells are correlated with chronic HIV-1 infection.

1)??? Fu J, Zhang Z, Zhou L, Qi Z, Xing S, et al Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma. Hepatology. 2013 Jul;58(1):139-49. doi: 10.1002/hep.26054. Epub 2013 Feb 15.

2)??? Xing S*, Fu J*, Zhang Z et al Increased turnover of FoxP3high regulatory T cells is associated with hyperactivation and disease progression of chronic HIV-1 infection.? J Acquir Immune Defic Syndr. 2010 Aug;54(5):455-62.

3)??? Jiao Y-M, Yang H-G, Huang H-H, Tu B, Xing S-J, Mao L, Xia W, He R, Zhang J-Y, Xu R-N, Jin L, Shi M, Xu Z, Qin E-Q, Wang X-C, Wu H, Ye L and Wang F-S (2017) Dichotomous Roles of Programmed Cell Death 1 on HIV-Specific CXCR5⁺ and CXCR5^? CD8⁺ T Cells during Chronic HIV Infection. Front. Immunol. 8:1786.

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D.??? Peer-reviewed publications

1.??????????????????? Jiao Y-M, Yang H-G, Huang H-H, Tu B, Xing S-J, Mao L, Xia W, He R, Zhang J-Y, Xu R-N, Jin L, Shi M, Xu Z, Qin E-Q, Wang X-C, Wu H, Ye L and Wang F-S (2017) Dichotomous Roles of Programmed Cell Death 1 on HIV-Specific CXCR5⁺ and CXCR5^? CD8⁺ T Cells during Chronic HIV Infection. Front. Immunol. 8:1786. doi: 10.3389/fimmu.2017.01786

2.??????????????????? Shan Q, Zeng Z, Xing S, Li F, Hartwig SM,et al . The transcription factor Runx3 guards cytotoxic CD8(+)effector T cells against deviation towards follicular helper T cell lineage. Nat Immunol. 2017 Jun 12. doi: 10.1038/ni.3773. [Epub ahead of print] PubMed PMID:28604718. IF=21.506

3.??????????????????? Zhe Xu*, Shaojun Xing*, Qiang Shan et al Cutting Edge: beta-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions.J Immunol. 2017 Mar 27. pii: 1602139. doi: 10.4049/jimmunol.1602139.? PMID: 28348272 ?IF=4.856 ?(co-first author).

4.??????????????????? Bing He*, Shaojun Xing*, Changya chen et al CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections. Immunity. 2016 Dec 20;45(6):1341-1354. PMID:27986453? IF=22.845 (co-first author).

5.??????????????????? Shaojun Xing*, Fengyin Li*, Zhouhao Zeng*, Yunjie Zhao, Shuyang Yu, et al Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity. Nat Immunol. 2016 Jun;17(6):695-703. PMID: 27111144 ?IF=21.506? ?(F1000 prime recommended by Salvatore Spicuglia; Commentary by Charles P Ng and Dan R Littman )

6.??????????????????? Yu S, Li F, Xing S et al Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1 Transcription Factors. J Biol Chem. 2016 May 20;291(21):11148-60. PMID: 27044748 ?IF=4.125

7.??????????????????? Yang Q, Li F, Harly C, Xing S, Ye L, et al TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow. Nat Immunol. 2015 Oct;16(10):1044-50. doi: 10.1038/ni.3248. Epub 2015 Aug 17. PMID: 26280998 IF=21.506 (commentary by Kaye J.)?

8.??????????????????? Choi YS, Gullicksrud JA, Xing S et al? LEF-1 and TCF-1 orchestrate T(FH) differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6 Nat Immunol. 2015 Sep;16(9):980-90. PMID:26214741 IF=21.506 (cited by Nature, commentary by Masato Kubo)

9.??????????????????? Fu J, Zhang Z, Zhou L, Qi Z, Xing S, et al Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma. Hepatology. 2013 Jul;58(1):139-49. doi: 10.1002/hep.26054. Epub 2013 Feb 15. PMID: 22961630 IF=13.246 (commentary by Gyongyi Szabo)

10.??????????????? Xing S*, Fu J*, Zhang Z et al Increased turnover of FoxP3high regulatory T cells is associated with hyperactivation and disease progression of chronic HIV-1 infection.? J Acquir Immune Defic Syndr. 2010 Aug;54(5):455-62. PMID: 20585263 IF=3.935

11.??????????????? Jiao Y, Fu J, Xing S, et al? The decrease of regulatory T cells correlates with excessive activation and apoptosis of CD8+ T cells in HIV-1-infected typical progressors, but not in long-term non-progressors. Immunology. 2009 Sep;128(1 Suppl):e366-75. PMID:19016904 ?IF=3.701

Contact:

Email: shaojun-xing@szu.edu.cn

Office Tel:?0755-26935621