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Caroline Jefferies, PhD

Caroline Jefferies, PhD





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

  • Undergraduate: Trinity College, 1993
  • Doctorate: Trinity College, 1997
  • Biomedical Sciences


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