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Caroline Jefferies, PhD

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Caroline Jefferies, PhD

The research of Caroline Jefferies, PhD, focuses on systemic lupus erythematosus (SLE). This complex disease encompasses a broad spectrum of clinical symptoms ranging from skin and joint manifestations to a severely debilitating kidney disease, lupus nephritis. Her key focus is on understanding the role of RNA/DNA sensing pathways and the estrogen receptor system in the pathogenesis of the disease and how they contribute to the immune dysregulation observed. This has led to the identification of TRIM21 as a key regulator of type I interferon and IL-23 production via its ability to target the transcription factors IRF3, IRF5 and IRF7. Translating these findings to understanding how a lupus patient's immune cells are regulated, Jefferies' work has shown that TRIM21 regulates IL-23 expression via its ability to degrade IRF3. In addition, the work has shown that TRIM21 activity and levels are dysregulated in lupus patient monocytes and that the estrogen system plays an important role in regulating the levels of this key protein. The transition to the Cedars-Sinai Division of Rheumatology has allowed Jefferies to extend her earlier work to investigate how these pathways may be differentially regulated in different manifestations of SLE in an effort to uncover novel targets for subtype-specific disease intervention. One example of this approach is to investigate how microRNA profiles and mRNA profiles correlate with clinical phenotypes. A number of estrogen-regulated microRNAs associate with lung disease, for example, and Jefferies and her colleagues are investigating these as potential therapeutic targets for the treatment of disease. This work is funded by the Alliance for Lupus Research under its Targets in Lupus program.

View NIH Biographical Sketch as a PDF

  • Undergraduate: Trinity College, 1993
  • Doctorate: Trinity College, 1997
  • Senior Editor: American Journal of Clinical and Experimental Immunology, 2013-present
  • Editor: Clinical Immunology, 2011-present
  • Science Foundation Ireland Principal Investigator Award, 2009
  • Science Foundation Ireland Principal Investigator Career Advancement Award, 2004
  • International Cytokine Society Sheldon Wolff Prize In Cytokine Research Award, 2001
  • Enterprise Ireland Fellowship, 2001
  • International Cytokine Society Outstanding Scholar Award, 1999

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Click here for a list of peer-reviewed publications.

  • Smith S, Ní Gabhann J, McCarthy E, Coffey B, Mahony R, Byrne JC, Stacey K, Ball E, Bell A, Cunnane G, Doran MF, Molloy ES, Lee RZ, Harvey B, Kearns G, Jefferies CA. Estrogen receptor α regulates tripartite motif-containing protein 21 expression, contributing to dysregulated cytokine production in systemic lupus erythematosus. Arthritis Rheumatol. 2014;66 (1):163-172.
  • Jefferies C, Wynne C, Higgs R. Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease? Nat Rev Immunol. 2011;11(9):617-625.
  • Byrne JC, Ní Gabhann J, Stacey KB, Coffey BM, McCarthy E, Jefferies CA. Btk is required for apoptotic cell uptake via regulating the phosphorylation and localisation of Calreticulin. J Immunol. 2013;190(10):5207-5215.
  • Smith S, Gabhann JN, Higgs R, Stacey K, Wahren-Herlenius M, Espinosa A, Totaro MG, Sica A, Ball E, Bell A, Johnston J, Browne P, O'Neill L, Kearns G, Jefferies CA. Enhanced interferon regulatoryfactor 3 binding to the IL-23p19 promoter correlates with enhanced IL-23 expression in systemic lupus erythematosus. Arthritis Rheum. 2012;64(5):1601-1609.
  • Higgs R, Ní Gabhann J, Ben Larbi N, Breen EP, Fitzgerald KA, Jefferies CA. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J Immunol. 2008;181(3):1780-1876.

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