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SHEN Nan
Ph.D., Professor, Principal Investigator
Laboratory of Molecular Rheumatology
Email: nanshensibs@@gmail.com
nshen@@sibs.ac.cn
 

Research Interests or Current Research Focus
Our research focuses on the molecular dissection of the disease pathways in systemic autoimmune diseases by functional genomics approach and the development of novel biomarkers and therapeutic targets in the management of systemic lupus erythematosus. The major ongoing research projects described as below:

1. Functional dissection of human lupus positional candidate genes
Genetic predisposition has been firmly established as a key element in susceptibility to lupus . By targeted genome scan and LD fine mapping approaches , We have localized two SLE susceptibility loci on 1q23 and 16q12 in Chinese population and identified two novel positional candidate genes ( PBX1 and OAZ ) which also have been confirmed in other ethnic group .By high dense SNPs genotyping, we further defined the disease associated functional SNPs and hoplotypes which may have some significant impacts on these genes expression regulation . PBX1 as a transcription factor whose functions in immune pathways have not been fully elucidated. We found the dysregulation of PBX1 gene in lupus patients may have involved in SLE pathogenesis by its role on influence on several inflammatory molecule expression. We plan to explore further its biological properties on the immune-regulatory signaling pathways by systemic biology approach in conditional knockout and transgenic mice system. Discovery of these genes function will define disease novel pathway for developing new immune intervention for lupus.

2. Role of the IFN-α targeted gene in lupus autoimmunity
The microarray provides an appropriate high-throughput method of investigating gene regulation in SLE from an overall and relatively non-biased perspective. Several groups independently demonstrate that IFN-regulated genes are among the most significantly overexpressed in SLE patients’PBMC which implicated that activation of the type I interferon signaling pathway is a major molecular phenotype for human lupus .but most of those lupus related IFN-regulated genes’ functions are unknown. We think key question need to be addressed is what are biological function of interferon inducible genes in lupus disease process. By integrating functional genomics, proteomics and cellular immunological approaches , We defined several important interferon inducible genes function on the regulation of innate and adtive immune system. Our works showed Interferon-induced protein with tetratricopeptide repeats 3(IFIT3), associated with systemic lupus erythematosus, promotes differentiation of monocyte into DC-like cells and IFIT3 promotes Chemokines expression by enhancing the activation of NF-kB in TLRs pathway; Through combining gene expression profiling with proteomic strategy, we first described IFIT1 as a candidate gene for SLE and revealed its novel function on activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor and thus to participate in the pathogenesis of SLE. Our work provide some detailed molecular aspect of type I interferon biological function , which could be used to distinguish unique signaling pathway related to interferon immune defense or pro- inflammatory process. We plan to screen some small molecules or other inhibitor to selectively block these “harmful” type I interferon inducible genes for modulating lupus patients immune system and hope to decrease possible infections risk due to using whole type I interferon system blockade treatment.

3. Molecular mechanism of type I interferon pathway activation in lupus
Abundant data from several investigators including our group indicate that activation of the type I interferon (IFN) pathway is a feature of many people with SLE and is thought to account for many features of that disease. However, the mechanisms that result in induction of IFN have not been well characterized. Our preliminary data also showed the gene expression phenotype (IFN Signature) is characterized by familial aggregation in lupus families. According the clinical observations that only quite few person develop lupus like symptoms after they receive type I interferon treatment and it also has been documented that three different genetic strains of mice generate completely different phenotypes and prognosis after high-dose interferon exposure. We had make a hypothesis that genetic backgrounds may affect the sensitivity of interferon stimulation and downstream effects of IFN-α pathway activation and that may contribute to the role of IFN-α in inducing or perpetuating autoimmunity in lupus. We plan to comprehensive identify genetic polymorphisms confer to individual with interferon signature by deep sequencing of more candidate genes and would apply these genetic information to guide future interferon block trials.

4. MicroRNA and Lupus autoimmunity
The disorder of fine regulation of gene expression can cause complex diseases’ phenotypes. It was well-known that microRNAs as novel regulator can fine tune cellular gene expression programs to control diverse steps in cell development and physiology. Recently a bevy of discoveries suggest that miRNAs associate with human diseases. We hypothesize that some miRNAs expression is altered in SLE and may have unknown impacts on the some key lupus disease pathways. We are using cutting edge technology platform to study miRNA global expression profiling in our lupus cohort. We revealed the differential expression of multiple microRNA, including miR-146a, a negative regulator of innate immunity. Further analysis showed that underexpression of miR-146a negatively correlated with clinical disease activity and with interferon scores in lupus patients. Of note, overexpression of miR-146a reduced, while inhibition of endogenous miR-146a increased, the induction of type I IFNs in PBMCs. Furthermore, miR-146a directly repressed the transactivation downstream of type I IFN. At the molecular level, miR-146a could target several key signaling molecules including IRF5 and STAT-1. More importantly, introduction of miR-146a into the patients’PBMCs alleviated the coordinate activation of the type I IFN pathway. Our findings suggest that miR-146a levels could be manipulated to provide useful therapeutic interventions for SLE. future Studies in knockout and transgenic animal models would further identify the role of miR-146a in autoimmune diseases. Now We are also using same strategies and approaches to explore other lupus related microRNA function, manly focus on their molecular mechanism underlying controlling inflammatory cytokine and chemokine produce and also will try setup effective microRNA systemic in vivo delivery system to intervene lupus tissue damage process.

5. Development of novel biomarkers in human lupus
We have found more than half lupus patients had elevated type I interferon activity in their serum and that is high correlated with disease activity based on new developed high sensitivity assay (ISRE Report gene assay) and also we comfirmed IFN scores and levels of LY6E expression were elevated in patients with lupus nephritis, more notably in those with current renal flare in our large lupus cohort. Our recent data based on gene expression profile analysis of lupus kidney biopsies have documented prominent overexpression of type I IFN–inducible chemokines in the lupus major target tissue. Our further independent cohort study indicate that a composite score based on chemokine gene expression in peripheral blood leukocytes is significantly associated with lupus disease activity. The chemokine score showed a slightly greater degree of correlation with disease activity than did an IFN score and is more specific for SLE, as the IFN score was also elevated in RA patients. Among the promising data are those showing significantly higher chemokine scores in patients with active lupus nephritis compared with those with inactive lupus nephritis, the data suggest that the chemokine score might be a candidate for validation as a biomarker of those requiring aggressive immunosuppressive therapy for lupus nephritis. More importantly chemokine scores may be a useful measure of more generalized inflammation that suggests ongoing target organ damage. Using a long-term fellow-up lupus cohort with defined clinical data, we are undergoing to confirm our preliminary results and also explore other novel biomarkers for lupus disease assessment.

Major Research Achievement
1. Interferon (IFN) pathway was identified as disease key pathway of lupus
Microarray technology is applied to the study of pathways involved in the SLE pathogenesis, and is applied in efforts to identify the target for possible manipulations on the specific immune responses. Based on the studies of PBMC gene expression profiles in SLE patients, we have found Interferon related immune pathway may play an important role in the pathogenesis of SLE and the gene expression profile seems to be the molecular basis of diverse immune phenotype of SLE. High levels of interferon-inducible genes in lupus, termed as IFN signature, expresses as IFN score, which is positively correlated with disease activity and its order of severity. Recently, we found an interesting phenomena that chemokine score, defined as a composite score based on chemokine genes (such as RANTES, MCP-1, MIG, IP-10, CXCL11, IL-8, and CCL19) expression in peripheral blood leukocytes, was closely associated with lupus disease activity and degree of organ damage, and showed a slightly greater degree of correlation with disease activity than did an IFN score, indicating that the chemokine score may serve as a new biomarker for active and severe disease in SLE.
Recently, we defined a link between type I IFNs, vascular damage, and progression of atherosclerosis in SLE (Arthritis Rheum. 2011), providing novel insights into the mechanisms of and potential therapeutic approaches to premature atherosclerosis in patients with SLE. We also found IFN-α contributed to the pathogenesis of SLE by regulating the function of CD4+CD25+Foxp3+ cells. Increased circulating CD4+CD25+Foxp3+ cells positively correlated with disease activity (Arthritis Rheum. 2008. Evaluated by Faculty of 1000 medicine). By integrating functional genomics, proteomics and cellular immunological approaches, We defined several important interferon inducible genes function on the regulation of innate and adtive immune system. Our works showed Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), associated with systemic lupus erythematosus, promoted differentiation of monocyte into DC-like cells and IFIT3 promoted chemokines expression by enhancing the activation of NF-kB in TLRs pathway. Through combining gene expression profiling with proteomic strategy, we first described IFIT1 as a candidate gene for SLE and revealed its novel function on activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor and thus to participate in the pathogenesis of SLE.
Our preliminary data also showed the gene expression phenotype (IFN Signature) is characterized by familial aggregation in lupus families. So our recent experiments focus on addressing the hypothesis that activation of the interferon pathway reflects allelic variation within the pathway that predisposes to disease. We are screening and identifying the functional SNPs within genes from this pathway for association with SLE. we have found polymorphisms in IFNαreceptors are associated with lupus phenotype. Recently we did fine-mapping of the 23-kb TLR7 region in 1434 SLE cases of Eastern Asian (EA) descent vs. 1591 EA controls showed association of 2 TLR7 SNPs with SLE. These SNPs are located at promoter and 3UTR and functional assay showed individual carrying only the risk G allele had significantly higher mRNA level of TLR7 in PBMC than those carrying allele C only (PNAS, 2010).
2. The role of microRNA in the diagnosis and treatment of human lupus
We examined the involvement of miRNAs in human lupus and found that dysregulation of several miRNAs in lupus and some of which is correlated with clinical disease activity. We further dissected the contribution of miRNA to lupus pathogenesis and made achievement as followed. 1) In human plasmacytoid dendritic cells, the miR-155 and its star-form partner miR-155* can cooperatively regulate type I interferon production (Blood,2010). Overproduciton of IFN is thought to account for many features of human lupus; 2) Underexpression of miR-146a contributes to alterations in the type I IFN pathway in lupus patients by targeting the key signaling proteins (Arthritis Rheum. 2009. Evaluated by Faculty of 1000 medicine). Recently, we have found that a functional variant in miR-146a promoter confers disease risk for SLE (PLoS Genet. 2011); 3) We have demonstrated a critical functional link between upregulation of miR-21 and the aberrant DNA hypomethylation in lupus CD4+ T cells (J Immunol. 2010. The article was elected for ‘In This Issue of the Journal of Immunology’ by editor), and found the underexpression of miR-125a contributed to the elevated expression of RANTES in SLE (Arthritis Rheum. 2010), underexpression of miR-31 caused to the abnormal production of IL-2 in lupus T cells by targeting RhoA which resulted in altered nuclear NF-AT expression and IL-2 promoter activity (Arthritis Rheum. 2012); 4) Deregulated expression of miR-23b contributed tissue damage by targeting IL-17 pathway (Nature Medicine 2012). More importantly, we have demonstrated that in vitro manipulation of lupus-related miRNAs (such as miR-146a, miR-125a and miR-21) level in the patients’ immune cells can alleviate the coordinate activation of the type I IFN pathway; reduce inflammatory chemokine RANTES expression, and correct DNA methylation state of lupus T cells, respectively, suggesting miRNAs may have therapeutic potential for human lupus.

Education
1982-1988 Master of Medical Science from Shanghai Second Medical University (SSMU)
1988-1991 M.D. from college of clinical medicine, SSMU
1998-1999 Visiting Scholar, Division of Rheumatology, UCLA

Recent Publications

  1. Yan S, Xu Z, Lou F, Zhang L, Ke F, Bai J, Liu Z, Liu J, Wang H, Zhu H, Sun Y, Cai W, Gao Y, Su B, Li Q, Yang X, Yu J, Lai Y, Yu XZ, Zheng Y, Shen N, Chin YE, Wang H*. NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun. 2015 Jul 3;6:7652.
  2. Pan W#, Zhu S#, Dai D#, Liu Z, Li D, Li B, Gagliani N, Zheng Y, Tang Y, Weirauch MT, Chen X7, Zhu W, Wang Y, Chen B, Qian Y, Chen Y, Fang J, Herbst R, Richman L, Jallal B, Harley JB, Flavell RA, Yao Y*, Shen N*. MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis. Nat Commun. 2015 May 12;6:7096.
  3. Lu X, Zoller EE, Weirauch MT, Wu Z, Namjou B, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath SK, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya JM, James JA, Sivils KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Joo YB, Choi J, Bae SC, Boackle SA, Graham DC, Vyse TJ, Guthridge JM, Gaffney PM, Langefeld CD, Kelly JA, Greis KD, Kaufman KM, Harley JB, Kottyan LC. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. Am J Hum Genet. 2015 May 7;96(5):731-9.
  4. Wu Y, Zhang F, Ma J, Zhang X, Wu L, Qu B, Xia S, Chen S, Tang Y*, Shen N*. Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus. Arthritis Res Ther. 2015 May 21;17:131.
  5. Qin H, Guo Q*, Shen N*, Huang X, Wu H, Zhang M, Bao C, Chen S. Chest imaging manifestations in lupus nephritis. Clin Rheumatol. 2014 Jun;33(6):817-23.
  6. 陈兰芳, 唐元家, 沈南. NEAT1与系统性红斑狼疮发病的相关研究. 《现代免疫学》, 2014年第34卷第5期,363-367.
  7. 剌婷, 马健阳, 沈南, 唐元家*. 利用CRISPR/Cas9系统和TALEN技术干预XIST基因的表达. 中国细胞生物学学报. 2014, 36(12): 1652-1660.
  8. 周盈盈; 周桢源; 黄新芳; 沈南*. miR-363-3p促进人浆细胞样树突细胞干扰素α分泌的机制研究. 《诊断学理论与实践》, 2014年13卷3期,255-259.
  9. Zhou XJ, Nath SK, Qi YY, Cheng FJ, Yang HZ, Zhang Y, Yang W, Ma JY, Zhao MH, Shen N*, Zhang H*. Brief Report: Identification of MTMR3 as a Novel Susceptibility Gene for Lupus Nephritis in Northern Han Chinese by Shared-Gene Analysis With IgA Nephropathy. Arthritis Rheumatol. 2014 Oct;66(10):2842-8.
  10. Song X, Gao H, Lin Y, Yao Y, Zhu S, Wang J, Liu Y, Yao X, Meng G, Shen N, Shi Y, Iwakura Y, Qian Y*. Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity. 2014 Jan 16;40(1):140-52.
  11. Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y*. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Harmacol Ther. 2014 Feb;141(2):125-39.
  12. Wang SL, Wang FF, Chen SL, Shen N, Xue F, Ye P, Bao CD, Gu YY, Yu CZ, Wilson A, Wallace DJ, Weisman MH, Lu LJ*. Expression, localization and clinical application of exogenous Smith proteins D1 in gene transfected HEp-2 cells. Int J Rheum Dis. 2013 Jun;16(3):303-9.
  13. Luo X, Ranade K, Talker R, Jallal B, Shen N*, Yao Y*. microRNA-mediated regulation of innate immune response in rheumatic diseases. Arthritis Res Ther. 2013 Apr 9;15(2):210. doi: 10.1186/ar4194.(并列通讯作者)
  14. Lin YW, Ren LL, Xiong H, Du W, Yu YN, Sun TT, Weng YR, Wang ZH, Wang JL, Wang YC, Cui Y, Sun DF, Han ZG, Shen N, Zou W, Xu J, Chen HY, Cao W, Hong J, Fang JY*. Role of STAT3 and vitamin D receptor in EZH2-mediated invasion of human colorectal cancer. J Pathol. 2013 Jul;230(3):277-90.
  15. Shen N, Liang D, Tang Y, and Qin Y (2012) Dubois Lupus Erythematosus and Related Syndromes, "Epigenetics of Lupus", 8th ed., Saunders.
  16. Shen N*, Liang D, Tang Y, de Vries N, Tak PP. MicroRNAs-novel regulators of systemic lupus erythematosus pathogenesis. Nat Rev Rheumatol. 2012.
  17. Zhou ZY, Chen SL, Shen N*, Lu Y*. Cytokines and Behcet’s Disease. Autoimmun Rev. 2012 Aug;11(10):699-704.
  18. Qu B, Han X, Tang Y, Shen N*. A Novel Vector-Based Method for Exclusive Overexpression of Star-Form MicroRNAs. PLoS One. 2012;7(7):e41504.
  19. Liang D, Shen N*. MicroRNA involvement in lupus: the beginning of a new tale. Curr Opin Rheumatol. 2012 Sep;24(5):489-98.
  20. Guo Q, Shen N, Yuan K, Li J, Wu H, Zeng Y, Fox J 3rd, Bansal AK, Singh BB, Gao H, Wu M. Caveolin-1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity. Eur J Immunol. 2012 Jun;42(6):1500-11. doi: 10.1002/eji.201142051.
  21. Wang FF, Zhu LA, Zou YQ, Zheng H, Wilson A, Yang CD, Shen N, Wallace DJ, Weisman MH, Chen SL, Lu LJ. New insights into the role and mechanism of macrophage migration inhibitory factor in steroid-resistant patients with systemic lupus erythematosus. Arthritis Res Ther. 2012 May 2;14(3):R103.
  22. Du F, Lü LJ, Teng JL, Shen N, Ye P, Bao CD. T-614 alters the production of matrix metalloproteinases (MMP-1 andMMP-3) and inhibits the migratory expansion of rheumatoid synovial fibroblasts, in vitro. Int Immunopharmacol. 2012 May;13(1):54-60.
  23. Wang JL, Lin YW, Chen HM, Kong X, Xiong H, Shen N, Hong J, Fang JY. Calcium prevents tumorigenesis in a mouse model of colorectal cancer. PLoS One. 2011;6(8):e22566.
  24. Zhu S, Pan W, Song X, Liu Y, Tang Y, Wang H, Liu W, Shi Y, He D, Harley JB, Shen N*, Qian Y*. MiR-23b suppresses IL-17 associated autoimmune pathogenesis. Nat Med. 2012 Jul;18(7):1077-86.
  25. Fan W, Liang D*, Tang Y, Qu B, Cui H, Luo X, Huang X, Chen S, Higgs BW, Jallal B, Yao Y, Harley JB, Shen N*. Identification of microRNA-31 as a novel regulator contributing to impaired IL-2 production in T cells from patients with systemic lupus erythematosus. Arthritis Rheum. 2012 Jun 26. doi: 10.1002/art.34596. [Epub ahead of print]
  26. Yang D, Li T, Wang Y, Tang Y, Cui H, Tang Y, Zhang X, Chen D, Shen N, Le W. miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression. J Cell Sci. 2012 Apr 1;125(Pt 7):1673-82.
  27. Wang J, Cao N, Yuan M, Cui H, Tang Y, Qin LJ, Huang X, Shen N, Yang H*. MicroRNA-125b/Lin28 pathway contributes to the mesendodermal fate decision of embryonic stem cells. Stem Cells Dev. 2012 Jun 10;21(9):1524-37.
  28. Li J, Bao C, Shen N*. Reply. Arthritis Rheum. 2012 Jan;64(1):324.
  29. Zhou XJ, Lu XL, Nath SK, Lv JC, Zhu SN, Yang HZ, Qin LX, Zhao MH, Su Y, International Consortium on the Genetics of Systemic Lupus Erythematosus, Shen N, Li ZG, Zhang H. Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis Rheum. 2012 Jan;64(1):222-31.
  30. Li R, Yang W, Zhang J, Hirankarn N, Pan HF, Mok CC, Chan TM, Wong RW, Mok MY, Lee KW, Wong SN, Leung AM, Li XP, Avihingsanon Y, Lee TL, Ho MH, Lee PP, Wong WH, Wong CM, Ng IO, Yang J, Li PH, Zhang Y, Zhang L, Li W, Baum L, Kwan P, Rianthavorn P, Deekajorndej T, Suphapeetiporn K, Shotelersuk V, Garcia-Barceló MM, Cherny SS, Tam PK, Sham PC, Lau CS, Shen N, Lau YL, Ye DQ. Association of CD247 with systemic lupus erythematosus in Asian Populations. Lupus. 2012 Jan;21(1):75-83.
  31. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Truedsson L, Andersson BA, Dahle C, Ortqvist E, Gregersen PK, Behrens TW, Hammarström L. Selective IgA deficiency in autoimmune diseases. Mol Med. 2011;17(11-12):1383-96.
  32. Zhao J, Wu H, Khosravi M, Cui H, Qian X, Kelly JA, Kaufman KM, Langefeld CD, Williams AH, Comeau ME, Ziegler JT, Marion MC, Adler A, Glenn SB, Alarcón-Riquelme ME; BIOLUPUS Network; GENLES Network, Pons-Estel BA, Harley JB, Bae SC, Bang SY, Cho SK, Jacob CO, Vyse TJ, Niewold TB, Gaffney PM, Moser KL, Kimberly RP, Edberg JC, Brown EE, Alarcon GS, Petri MA, Ramsey-Goldman R, Vilá LM, Reveille JD, James JA, Gilkeson GS, Kamen DL, Freedman BI, Anaya JM, Merrill JT, Criswell LA, Scofield RH, Stevens AM, Guthridge JM, Chang DM, Song YW, Park JA, Lee EY, Boackle SA, Grossman JM, Hahn BH, Goodship TH, Cantor RM, Yu CY, Shen N, Tsao BP*. Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. PLoS Genet. 2011 May;7(5):e1002079.
  33. Liao LH, Zhang H, Lai MP, Chen SL, Wu M, Shen N*. Single-nucleotide polymorphisms and haplotype of CYP2E1 gene associated with systemic lupus erythematosus in Chinese population. Arthritis Res Ther. 2011 Jan 31;13(1):R11. [Epub ahead of print]
  34. Huang X, Guo Y, Bao C, Shen N*. Multidimensional Single Cell Based STAT Phosphorylation Profiling Identifies a Novel Biosignature for Evaluation of Systemic Lupus Erythematosus Activity. PLoS One. 2011;6(7):e21671. Epub 2011 Jul 22. doi:10.1371/journal.pone.0021671.
  35. Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, de Vries N, Tak PP, Tsao BP, Shen N*. A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus. PLoS Genet. 2011, 30 Jun;7(6): e1002128.
  36. Li J, Fu Q, Cui H, Qu B, Pan W, Shen N*, Bao C*. Interferon-α Priming Promotes Lipid Uptake and Macrophage-Derived Foam Cell Formation: A Novel Link between Interferon-α and Atherosclerosis in Lupus. Arthritis Rheum. 2011, Feb;63(2):492-502.
  37. Wang S, Tang Y, Cui H, Zhao X, Luo X, Pan W, Huang X, Shen N*. Let-7/miR-98 regulate Fas and Fas-mediated apoptosis. Genes Immun. 2011, 12(2):149-54.
  38. Fu Q, Zhao J, Qian X, Wong JL, Kaufman KM, Yu CY, Hwee Siew Howe, Tan Tock Seng Hospital Lupus Study Group, Mok MY, Harley JB, Guthridge JM, Song YW, Cho SK, Bae SC, Grossman JM, Hahn BH, Arnett FC, Shen N, Tsao BP*. Association of a functional IRF7 variant with systemic lupus erythematosus. Arthritis Rheum. 2011 Mar;63(3):749-54.
  39. Maiti AK, Kim-Howard X, Viswanathan P, Guillén L, Qian X, Rojas-Villarraga A, Sun C, Cañas C, Tobón GJ, Matsuda K, Shen N, Cherñavsky AC, Anaya JM, Nath SK. Non-synonymous variant (Gly307Ser) in CD226 is associated with susceptibility to multiple autoimmune diseases. Rheumatology (Oxford). 2010 Jul;49(7):1239-44.
  40. Zhou H, Huang X, Cui H, Luo X, Tang Y, Chen S, Wu L, Shen N*. miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. Blood. 2010, 116(26): 5885-5894.
  41. Shen N*, Fu Q, Deng Y, Qian X, Zhao J, Kaufman KM, Wu YL, Yu CY, Tang Y, Chen JY, Yang W, Wong M, Kawasaki A, Tsuchiya N, Sumida T, Kawaguchi Y, Howe HS, Mok MY, Bang SY, Liu FL, Chang DM, Takasaki Y, Hashimoto H, Harley JB, Guthridge JM, Grossman JM, Cantor RM, Song YW, Bae SC, Chen S, Hahn BH, Lau YL, Tsao BP*. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2010, 107(36): 15838-15843.
  42. Zhao X, Tang Y, Qu B, Cui H, Wang S, Wang L, Luo X, Huang X, Li J, Chen S, Shen N*. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum. 2010, 62 (11): 3425-3435.
  43. Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, Li J, Zhou H, Tang Y, Shen N*. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010 Jun 15;184(12):6773-81.
  44. Yang W, Shen N, Ye DQ, Liu Q, Zhang Y, Qian XX, Hirankarn N, Ying D, Pan HF, Mok CC, Chan TM, Wong RW, Lee KW, Mok MY, Wong SN, Leung AM, Li XP, Avihingsanon Y, Wong CM, Lee TL, Ho MH, Lee PP, Chang YK, Li PH, Li RJ, Zhang L, Wong WH, Ng IO, Lau CS, Sham PC, Lau YL; Asian Lupus Genetics Consortium. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet. 2010 Feb 12;6(2):e1000841.
  45. Luo X, Tsai LM, Shen N, Yu D. Evidence for microRNA-mediated regulation in rheumatic diseases. Ann Rheum Dis. 2010 Jan;69 Suppl 1:i30-36.
  46. Tang YJ, Luo XB, Cui HJ, Ni XM, Yuan M, Guo YZ, Huang XF, Zhou HB, Vries N, Tak P, Chen SL, Shen N. MicroRNA-146a Contributes to Abnormal Activation of the Type I Interferon Pathway in Human Lupus by Targeting the Key Signaling Proteins. Arthritis Rheum. 2009 Apr;60(4):1065-75.
  47. Du F, Lü LJ, Fu Q, Dai M, Teng JL, Fan W, Chen SL, Ye P, Shen N, Huang XF, Qian J, Bao CD. T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis. Arthritis Res Ther. 2008;10(6):R136.
  48. Fu Q, Chen XQ, Cui HJ, Guo YZ, Chen J, Shen N, Bao CD. Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients. Arthritis Res Ther. 2008;10(5):R112. Epub 2008 Sep 15.
  49. Tang J, Gu Y, Zhang M, Ye S, Chen X, Guo Q, Qian J, Bao C, Chen S, Shen N. Increased expression of the type I interferon-inducible gene, lymphocyte antigen 6 complex locus E, in peripheral blood cells is predictive of lupus activity in a large cohort of Chinese lupus patients. Lupus. 2008;17(9):805-13.
  50. Huang XY, Shen N, Bao CD, Gu YY, Wu L, Chen SL. Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into dendritic cell-like cells. Arthritis Res Ther. 2008;10(4):R91. Epub 2008 Aug 15.
  51. Yan B, Ye S, Chen GJ, Kuang M, Shen N, Chen SL. Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum. 2008;58(3):801-12.
  52. Wu H, Boackle SA, Hanvivadhanakul P, Ulgiati D, Grossman JM, Lee Y, Shen N, Abraham LJ, Mercer TR, Park E, Hebert LA, Rovin BH, Birmingham DJ, Chang DM, Chen CJ, McCurdy D, Badsha HM, Thong BY, Chng HH, Arnett FC, Wallace DJ, Yu CY, Hahn BH, Cantor RM, Tsao BP. Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2007;104 (10):3961-6. Epub 2007 Feb 22.
  53. Feng XG, Ye S, Lu Y, Xu XJ, Gu YY, Shen N, Ye P, Cheng FP, Wang AM, Chen SL.Antikinectin autoantibody in Behçet´s disease and several other autoimmune connective tissue diseases. Clin Exp Rheumatol. 2007 ;25(4 Suppl 45):S80-5.
  54. Lu Q, Shen N, Li XM, Chen SL. Genomic view of IFN-alpha response in pre-autoimmune NZB/W and MRL/lpr mice. Genes Immun. 2007;8(7):590-603. Epub 2007 Aug 30.
  55. Ye S, Guo Q, Tang JP, Yang CD, Shen N, Chen SL. Could 2´5´-oligoadenylate synthetase isoforms be biomarkers to differentiate between disease flare and infection in lupus patients? A pilot study. Clin Rheumatol. 2007, 26(2): 186-90.
  56. Huang XF, Hua J, Shen N,Chen SL. ysregulated expression of interleukin-23 and interleukin-12 subunits in systemic lupus erythematosus patients. Modern Rheumatology. 2007;17(3):220-223.
  57. Feng XB, Shen N, Qian J, Sun L, Hua J, Chen SL. Single nucleotide polymorphisms of deoxyribonuclease I and their expression in Chinese systemic lupus erythematosus patients. Chin Med J (Engl). 2004;117(11):1670-6.
  58. Shen N, Tsao BP. Current advances in the human lupus genetics. Curr Rheumatol Rep. 2004;6(5):391-8. Review.
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