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Contact information


arian.laurence@ndm.ox.ac.uk

Research groups

Arian Laurence

Visiting Researcher

I received my degrees in biochemistry and medicine from UMDS, London University, London UK and subsequently obtained my doctoral degree 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 subsequently pursued a post-doctoral fellowship at NIAMS, NIH, Bethesda USA in the laboratory of Dr John O' Shea where I worked on the role of JAK/ STAT signaling in T helper cell lineages. I continued as a research fellow during which time I discovered the roles of STAT3 and STAT5 in Th17 and T regulatory cell development,

I established my research programme at Oxford in collaboration with Prof..Uhlig in 2015. Here my discoveries include identifying the link between haploinsufficiency syndromes and genes that are regulated by complex enhancer structures known as superenhancers (Nat. Immunol. 2017). I have continued to work on the role of STAT5 in T helper cells, focusing on its role in cellular metabolism (Sci. Immunol, 2022).

I work as a consultant clinician at both the Immunology department, Royal Free hospital and Haematology department, University College Hospital with an interest in the treatment of patients with primary immunodeficiency using allogeneic bone marrow transplantation

Current projectS:

Investigation into the role of BACH2 in human T and B cell development and its relationship with colitis and chronic variable immunodeficiency.

Investigation of the IL6ST/ GP130/ JAK signalling complex through the study of patients with homozygous and heterozygous mutations of IL6ST

Investigation of the role of IL-18 in the pathophysiology of Haemophagocytic lympho-histiocytosis

Selected publications

  1. Chaganti S, Maycock S, McIlroy G, Jackson AE, Bishop R, Johnson S, Kanfer E, Kassam S, Cwynarski K, Wrench DJ, Arumainathan A, Fox CP, Johnson RJ, McKay P, Paneesha S, Rowntree C, Balotis C, Collins GP, Davies AJ, Wright J, Burns S Dr, Laurence ADJ, Wheatley K, Menne T. Ibrutinib as part of risk-stratified treatment for post-transplant lymphoproliferative disorder: The phase 2 TIDaL trial. Blood. 2024 Apr 21:blood.2024023847. doi: 10.1182/blood.2024023847. Online ahead of print. PMID: 38643491

  2. Castelo-Soccio L, Kim H, Gadina M, Schwartzberg PL, Laurence A, O'Shea JJ.
    Protein kinases: drug targets for immunological disorders. Nat Rev Immunol. Dec 2023 Dec;23(12):787-806. PMID: 37188939

  3. Cheminant M, Fox TA, Alligon M, Bouaziz O, Neven B, Moshous D, Blanche S, Guffroy A, Fieschi C, Malphettes M, Schleinitz N, Perlat A, Viallard JF, Dhedin N, Sarrot-Reynauld F, Durieu I, Humbert S, Fouyssac F, Barlogis V, Carpenter B, Hough RE, Laurence ADJ, Marçais A, Chakraverty R, Hermine O, Fischer A, Burns SO, Mahlaoui N, Morris EC, Suarez F. Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity. Blood. 2023 Jan 5;141(1):60-71. PMID: 36167031

  4. Villarino AV*, Laurence AD*, Davis FP, Nivelo L, Brooks SR, Sun HW, Jiang K, Afzali B, Frasca D, Hennighausen L, Kanno Y, O'Shea JJ. A central role for STAT5 in the transcriptional programing of T helper cell metabolism. Sci Immunol. 2022 Nov 25;7(77):eabl9467. doi: 10.1126/sciimmunol.abl9467. Epub 2022 Nov 25. PMID: 36427325

  5. Mackenzie S, Laurence A, O'Reilly M, Peggs KS, Roddie C. Progressive multifocal leukoencephalopathy in the era of chimeric antigen receptor T-cell therapy. Lancet Haematol. 2021 Dec;8(12):e870-e873. doi: 10.1016/S2352-3026(21)00316-1. PMID: 34826407

  6. Chauss D, Freiwald T, McGregor R, Yan B, Wang L, Nova-Lamperti E, Kumar D, Zhang Z, Teague H, West EE, Vannella KM, Ramos-Benitez MJ, Bibby J, Kelly A, Malik A, Freeman AF, Schwartz DM, Portilla D, Chertow DS, John S, Lavender P, Kemper C, Lombardi G, Mehta NN, Cooper N, Lionakis MS, Laurence A, Kazemian M, Afzali B. Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells. Nat Immunol. 2022 Jan;23(1):62-74. doi: 10.1038/s41590-021-01080-3. Epub 2021 Nov 11. PMID: 34764490

  7. Chen YH, Spencer S, Laurence A, Thaventhiran JE, Uhlig HH. Inborn errors of IL-6 family cytokine responses. Curr Opin Immunol. 2021 Oct;72:135-145. doi: 10.1016/j.coi.2021.04.007. Epub 2021 May 24.
  8. Chen YH, Grigelioniene G, Newton PT, Gullander J, Elfving M, Hammarsjö A, Batkovskyte D, Alsaif HS, Kurdi WIY, Abdulwahab F, Shanmugasundaram V, Devey L, Bacrot S, Brodszki J, Huber C, Hamel B, Gisselsson D, Papadogiannakis N, Jedrycha K, Gürtl-Lackner B, Chagin AS, Nishimura G, Aschenbrenner D, Alkuraya FS, Laurence A, Cormier-Daire V, Uhlig HH. Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome. J Exp Med. 2020 Mar 2;217(3). pii: e20191306. doi: 10.1084/jem.20191306. PMID: 31914175

  9. Li P, Deng X, Luo J, Chen Y, Bi G, Gong F, Wei Z, Liu N, Li H, Laurence A, Yang XP. ATP6V0d2 mediates leucine-induced mTORC1 activation and polarization of macrophages. Protein Cell. 2019 Aug;10(8):615-619. doi: 10.1007/s13238-019-0636-x

  10. Schwartz DM, Farley TK, Richoz N, Yao C, Shih HY, Petermann F, Zhang Y, Sun HW, Hayes E, Mikami Y, Jiang K, Davis FP, Kanno Y, Milner JD, Siegel R, Laurence A, Meylan F, O'Shea JJ. Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology. Immunity. 2019 Jan 15;50(1):106-120.e10. doi: 10.1016/j.immuni.2018.12.014.

  11. Liu N, Luo J, Kuang D, Xu S, Duan Y, Xia Y, Wei Z, Xie X, Yin B, Chen F, Luo S, Liu H, Wang J, Jiang K, Gong F, Tang ZH, Cheng X, Li H, Li Z, Laurence A, Wang G, Yang XP. Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression. J Clin Invest. 2019 Feb 1;129(2):631-646. doi: 10.1172/JCI123027. Epub 2019 Jan 7.

  12. Povoleri GAM, Nova-Lamperti E, Scottà C, Fanelli G, Chen YC, Becker PD, Boardman D, Costantini B, Romano M, Pavlidis P, McGregor R, Pantazi E, Chauss D, Sun HW, Shih HY, Cousins DJ, Cooper N, Powell N, Kemper C, Pirooznia M, Laurence A, Kordasti S, Kazemian M, Lombardi G, Afzali B. Human retinoic acid-regulated CD161+ regulatory T cells support wound repair in intestinal mucosa. Nat Immunol. 2018 Dec;19(12):1403-1414. doi: 10.1038/s41590-018-0230-z. Epub 2018 Nov 5.

  13. Stathopoulou C, Gangaplara A, Mallett G, Flomerfelt FA, Liniany LP, Knight D, Samsel LA, Berlinguer-Palmini R, Yim JJ, Felizardo TC, Eckhaus MA, Edgington-Mitchell L, Martinez-Fabregas J, Zhu J, Fowler DH, van Kasteren SI, Laurence A, Bogyo M, Watts C, Shevach EM, Amarnath S. PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells. Immunity. 2018 Aug 21;49(2):247-263.e7. doi: 10.1016/j.immuni.2018.05.006.

  14. Afzali B, Grönholm J, Vandrovcova J, O'Brien C, Sun HW, Vanderleyden I, Davis FP, Khoder A, Zhang Y, Hegazy AN, Villarino AV, Palmer IW, Kaufman J, Watts NR, Kazemian M, Kamenyeva O, Keith J, Sayed A, Kasperaviciute D, Mueller M, Hughes JD, Fuss IJ, Sadiyah MF, Montgomery-Recht K, McElwee J, Restifo NP, Strober W, Linterman MA, Wingfield PT, Uhlig HH, Roychoudhuri R, Aitman TJ, Kelleher P, Lenardo MJ, O'Shea JJ, Cooper N*, Laurence ADJ*. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat Immunol. 2017 Jul;18(7):813-823. doi: 10.1038/ni.3753. Epub 2017 May 22.

  15. Villarino A, Laurence A, Robinson GW, Bonelli M, Dema B, Afzali B, Shih HY, Sun HW, Brooks SR, Hennighausen L, Kanno Y, O'Shea JJ. Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions. Elife. 2016 Mar 21;5. pii: e08384. doi: 10.7554/eLife.08384.

  16. Yang XP, Jiang K, Hirahara K, Vahedi G, Afzali B, Sciume G, Bonelli M, Sun HW, Jankovic D, Kanno Y, Sartorelli V, O'Shea JJ, Laurence A. EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion. Sci Rep. 2015 Jun 19;5:10643. doi: 10.1038/srep10643.

  17. 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. Asymetric action of STAT transcription factors drives transcriptional outputs and cytokine specificity. Immunity 2015 May 19; 42(5):877-89. doi:10.1016/ j.immuni.2015.04.014.

  18. Steward-Tharp SM*, Laurence A*, Kanno Y, 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