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Arian Laurence

Visiting Researcher

I received my degrees in biochemistry (1990) and medicine (1993) from UMDS, London University, London UK and subsequently obtained my doctoral degree in 2004 in Immunology and hematology at University College London while working at the London research (now Crick) institute, Cancer research UK at the laboratory of Dr Doreen Cantrell. I have eight year’s post-doctoral research training at NIAMS in the laboratory of Dr John O'Shea where I worked on the role of JAK/ STAT signaling in T helper cell lineages.

Current project:

I currently work on the role of BACH2 in human T and B cell development and its relationship with colitis and chronic variable immunodeficiency.

Publications

1. Hirahara K, Onodera A, Villarino AV, Bonelli M, Sciumè G, Laurence A, Sun HW, Brooks SR, Vahedi G, Shih HY, Gutierrez-Cruz G, Iwata S, Suzuki R, Mikami Y, Okamoto Y, Nakayama T, Holland SM, Hunter CA, Kanno Y, O'Shea JJ. Asymmetric Action of STAT Transcription Factors Drives Transcriptional Outputs and Cytokine Specificity. Immunity. 2015 May 19;42(5):877-889. doi: 10.1016/j.immuni.2015.04.014.

2. Villarino AV, Laurence A. IL-1 watches the watchmen. Nat Immunol. 2015 Mar;16(3):226-7. doi: 10.1038/ni.3105.

3. Amarnath S, Foley JE, Farthing DE, Gress RE, Laurence A, Eckhaus MA, Métais JY, Rose JJ, Hakim FT, Felizardo TC, Cheng AV, Robey PG, Stroncek DE, Sabatino M, Battiwalla M, Ito S, Fowler DH, Barrett AJ. Bone Marrow Derived Mesenchymal Stromal Cells Harness Purinergenic Signaling to Tolerize Human Th1 Cells In Vivo. Stem Cells. 2015 Apr;33(4):1200-12. doi: 10.1002/stem.1934.

4. Steward-Tharp SM*, LaurenceA*, KannoY, Kotlyar A, Villarino AV, Sciume G, Kuchen S, Resch W, Wohlfert EA, Jiang K, Hirahara K, Vahedi G, Sun HW, Feigenbaum L, Milner JD, Holland SM, Casellas R, Powrie F and O'Shea JJ. A mouse model of HIES reveals pro and anti-inflammatory functions of STAT3 Blood. 2014 May 8;123(19):2978-87.

5. Adamson A, Ghoreschi K, Rittler M, Chen Q, Sun HW, Vahedi G, Kanno Y, Stetler-Stevenson WG, O’Shea JJ, Laurence A. Tissue inhibitor of metalloproteinase 1 is preferentially expressed in Th1 and Th17 T-helper cell subsets and is a direct Stat target gene. PLoS ONE. 2013 Mar 26; 8(3): e59367.

6. Sciumé G, Hirahara K, Takahashi H, Laurence A, Villarino AV, Singleton KL, Spencer SP, Wilhelm C, Poholek AC, Vahedi G, Kanno Y, Belkaid Y, O'Shea JJ. Distinct requirements for T-bet in gut innate lymphoid cells. J Exp Med. 2012 Dec 17;209(13):2331-8.

7. Laurence A*, Amarnath S*, Mariotti J, Kim YC, Foley J, Eckhaus M, O’Shea JJ, Fowler DH. STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft versus host disease. Immunity. 2012 Aug 24;37(2):209-22.

8.Hirahara K, Ghoreschi K, Yang XP, Takahashi H, Laurence A, Vahedi G, Sciumè G, Hall AO, Dupont CD, Francisco LM, Chen Q, Tanaka M, Kanno Y, Sun HW, Sharpe AH, Hunter CA, O'Shea JJ. Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via Induction of the Ligand PD-L1. Immunity. 2012 Jun 29;36(6):1017-30.

9. Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, Roychoudhuri R, Ferreyra GA, Shen W, Durum SK, Feigenbaum L, Palmer DC, Antony PA, Chan CC, Laurence A, Danner RL, Gattinoni L, Restifo NP. Th17 cells are long lived and retain a stem cell-like molecular signature. Immunity. 2011 Dec 23;35(6):972-85.

10. Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O'Shea JJ, Laurence A. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol. 2011 Mar;12(3):247-54.

11. Ghoreschi K, Laurence A*, Yang XP*, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O'Shea JJ. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature. 2010 Oct 21;467(7318):967-71.

12. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O'Shea JJ. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity. 2010 May 28;32(5):605-15.

13. McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O'Shea JJ, Cua DJ. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009 Mar;10(3):314-24.

14. Cecchinato V*, Trindade CJ*, Laurence A*, Heraud JM*, Brenchley JM, Ferrari MG, Zaffiri L, Tryniszewska E, Tsai WP, Vaccari M, Parks RW, Venzon D, Douek DC, O'Shea JJ, Franchini G. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol. 2008 Jul;1(4):279-88.

15. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O'Shea J, Holland SM, Paul WE, Douek DC. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008; 452 (7188), pp. 773-776

16. Elias KM*, Laurence A*, Davidson TS, Stephens G, Kanno Y, Shevach EM, O'Shea JJ. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood. 2008; 111 (3), pp. 1013-1020

17.   Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O'Shea JJ, Hunter CA. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007 Dec;8(12):1363-71.

18. Wei L, Laurence A, Elias KM, O'shea JJ.  IL-21 is produced by TH17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem. 2007; 282 (48), pp. 34605-34610

19. Laurence A*, Tato CM*, Davidson TS*, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O'shea JJ. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity. 2007 Mar;26(3):371-81.

20. Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O'Shea JJ, Hennighausen L, Ernst M, Hunter CA. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006 Sep;7(9):937-45.

21. Chen Z*, Laurence A*, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8137-42.