Address: Room 320,Administration Building,Shenzhen University,Nanshan District,Shenzhen, Guangdong, China, 518060
2004 Chongqing University of Medical Sciences, Department of Microbiology and Immunology, Ph.D.
1999 Chongqing University of Medical Sciences, B.S.Med
2008.9-2014.2 Duke University, Department of Immunology, Post-doctoral Association
2006.3–2008.8 Case Western Reserve University School of Medicine, Division of Hematology/Oncology, Post-doctoral Scholar
2004.8– 2006.2 Shanghai Institute of Immunology, Post-doctoral Fellow
Effective adaptive immune responses toward pathogens depend upon the proper differentiation of CD4 T cells into particular effector cell types. TH1 cells are responsible for clearance of intracellular infection and are implicated as the effectors in various autoimmune diseases; TH2 cells control extracellular microbe infection as well as mediate chronic inflammation and allergic responses; and a recently identified third subset, TH17 cells, has been linked to a growing list of autoimmune disorders.TCR and cytokines signaling is critical for downstream gene expression and T cell fate determination. While the signaling network in T cells has largely been described, the impact of non-coding RNAs (ncRNAs) on this network is largely unknown. miRNAs that affect mature T cell functional differentiation.
We revealed that miR-17 and miR-19b are the key players controlling TH1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activation-induced cell death, supporting IFN-γ production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (phosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGFβRII and the novel target CREB1. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell-based tumor therapy. (Blood. 2011 Nov 17;118(20):5487-97.)
We also revealed that Methyl CpG binding protein 2 (MeCP2) was indispensable for the differentiation of naïve CD4 (+) T cells into TH1 and TH17 cells. Loss of MeCP2 in CD4 (+) T cells impaired the expression of the miR-124 and consequently relieved miR-124-mediated repression of the translation of suppressor of cytokine signaling 5 (Socs5) mRNA. The resulting accumulation of SOCS5 inhibited the cytokine-dependent activation of signal transducer and activator of transcription 1 (STAT1) and STAT3, which are necessary for the differentiation of TH1 and TH17 cells, respectively. Meanwhile MeCP2 enforces Foxp3 expression to promote nTreg’s resilience to inflammation. (Sci Signal. 2014 Mar 11; 7 (316):ra25.)
Currently, we are studying in three directions:
1. To determine the immunotherapeutic efficacy of micorRNAs-modified CAR-T cells against human tumors.
2. To characterize the roles of microRNAs in the immune suppression of T cells in the tumor environment.
3. To characterize the roles of microRNAS in memory T cells generation.
2013, American immunology annual conference, Trainee Abstract Awards
2013, Duke University, The Outstanding Service Award
2012, Duke University, Bernard Amos Annual Poster Contest，First Prize
2005, Chongqing City, Technology Advancement Prize, Second Prize
1. Li C*, Jiang S*, Liu SQ, Lykken E, Zhao LT, Sevilla J, Zhu B, Li QJ.MeCP2 enforces Foxp3 expression to promote regulatory T cells' resilience to inflammation. Proc Natl Acad Sci U S A. 2014 Jun 23. pii: 201401505. [Epub ahead of print] (* co-first authorship)
3. Liu SQ, Jiang S, Li C, Zhang B, Li QJ. miR-17-92 cluster targets Phosphatase and Tensin Homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation. J Biol Chem. 2014 Mar 18. [Epub ahead of print]
4. Jiang S*, Li C*, McRae G, Lykken E, Sevilla J, Liu SQ, Wan Y, Li QJ.MeCP2 Reinforces STAT3 Signaling and the Generation of Effector CD4+ T Cells by Promoting miR-124-Mediated Suppression of SOCS5.Sci Signal. 2014 Mar 11;7 (316):ra25.(* co-first authorship)
5. Guo Q, Zhang J, Li J, Zou L, Zhang J, Xie Z, Fu X, Jiang S, Chen G, Jia Q, Li F, Wan Y, Wu Y. Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells. Blood. 2013 Jun 13;121(24):4875-83.
6. Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, Deng Y, Zhao J, Jiang S, Yuan Y, Wang HY, Cheng SQ, Xie D, Wang XF.TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012 Sep 11;22(3):291-303.
7. Shan Jiang*, Chaoran Li*, Virginie Olive, Erik Lykken, Feng Feng, Jose Sevilla, Lin He, Qi-Jing Li. Molecular dissection of the miR-17-92 cluster’s critical dual roles in promoting Th1 responses and preventing inducible Treg Differentiation. Blood. 2011 Nov 17;118(20):5487-97. (* co-first authorship)
8. Weiwen Fan, Zhe Tang, Lihong Yin, Bei Morrison, Said Hafez-Khayyata, Pingfu Fu Honglian Huang, Rakesh Bagai, Shan Jiang, Adam Kresak, Scott Howell, Amit Vasanji,Chris A. Flask, Balazs Halmos, Henry Koon, and Patrick C. Ma. MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents. Cancer Res. 2011 Jul 1;71(13):4494-505.
9. Ebert PJ, Jiang Shan, Xie J, Li QJ, Davis MM. An endogenous positively selecting peptide enhances mature T cells responses and becomes an antoantigen in the absebce of microRNA mir-181a. Nat Immunol. 2009 Nov; 10(11):1162-9.
10. Tang Z, Jiang S, Du R, Dietrich S, El Telbany AS, Chan PS, Petri ET, Boggon TJ, Halmos B, Kern JA. and Ma PC. Disruption of a conserved ion pair in EGFR differentially alters kinase inhibitor sensitivity. Oncogene. 2009 Jan 29; 28(40:518-33.
11. Tang Z, Du R, Jiang S, Wu C, Barkauskas DS, Richey J, Molter J, Lam M, Flask C, Gerson S, Dowlati A, Liu L, Lee Z, Halmos B, Wang Y, Kern JA, Ma PC. Dual MET-EGFR combinatorial inhibition against T790M-EGFR mediated erlotinib-resistant lung cancer. Br J Cancer. 2008 Sep 16; 99(6):911-22.
12. Tang Z, Jiang S, Du R and Ma PC. Mutational analysis of the lung cancer genome in novel therapy – era of high throughput sequencing. Book chapter, Tumorigenesis Research Focus.Editor, F. Columbus. Publisher, Nova Publishing, 2008.
13. Zhu DY, Jiang S, Luo XD. Therapeutic effects of Ag85B and MPT64 DNA vaccines in a murine model of Mycobacterium tuberculosis infection. Vaccine, 2005.23(37): 4619-4624.