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Keith Elkon, M.D.
Keith B. Elkon, M.D.
Professor, Medicine and Head, Division of Rheumatology
Dr. Elkon received his medical degree from the University of Witwatersrand, Johannesburg South Africa in 1974 and membership to the Royal College of Physicians (MRCP) in 1978. He received postdoctoral training at the Hammersmith Hospital, London and at the Weill Medical College of Cornell University, New York. Dr. Elkon was formerly Director of the Graduate Program in Immunology and Professor of Medicine at Cornell. He was appointed as Head, Division of Rheumatology, at UW in August, 2001.
Department of Medicine,
Division of Rheumatology
University of Washington
750 Republican Street
Seattle, WA 98109
Dr. Elkon's research objective is to better define the molecular and genetic basis for autoimmune diseases such as lupus and arthritis. Current areas of investigation include the following:
Cell Death, Nucleic Acids and the Immune Response
Loss of tolerance leads to autoantibody production in systemic autoimmune disorders such as systemic lupus erythematosus (SLE). There is considerable evidence to support the concept that autoimmunity is stimulated by exposure to nucleic acids. This may results from impaired clearance of dying cells, enhanced necrosis - for example through the process of NETosis, or intracellular abnormalities of nucleic acid processing. and / or increased exposure of nucleic acid sensors.
Current research projects address the following questions:
- What are the cell death abnormalities that provoke an immune response?
- How does the cell debris released from dying cells stimulate inflammation - especially the Type 1 interferon response?
- Which interferon pathways are specifically abnormal in lupus and related autoimmune disorders? The laboratory focuses on TLRs as well as the cGAS-STING pathway
- Can environmental triggers such as sunlight be used to uncover differences in the interferon response in lupus versus controls?
- Can we develop therapies to attenuate key pathways leading to Type I interferon production. Based on our mechanistic understanding, we created a biologic in Phase 2 clinical trials and a small molecule inhibitor of cGAS which is in preclinical studies.
- Inhibition of Cyclic GMP-AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1-Deficient Mice. An J, Woodward JJ, Lai W, Minie M, Sun X, Tanaka L, Snyder JM, Sasaki T, Elkon KB. Arthritis Rheumatol. 2018 May 21. doi: 10.1002/art.40559. [Epub ahead of print] PMID: 29781188
- Review: Cell Death, Nucleic Acids, and Immunity: Inflammation Beyond the Grave. Elkon KB. Arthritis Rheumatol. 2018 Jun;70(6):805-816. doi: 10.1002/art.40452. Epub 2018 Apr 18. Review. PMID: 29439290
- TLR7/8 activation in neutrophils impairs immune complex phagocytosis through shedding of FcgRIIA. Lood C, Arve S, Ledbetter J, Elkon KB. J Exp Med. 2017 Jul 3;214(7):2103-2119. doi: 10.1084/jem.20161512. Epub 2017 Jun 12. PMID: 28606989
- Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. An J, Durcan L, Karr RM, Briggs TA, Rice GI, Teal TH, Woodward JJ, Elkon KB. Arthritis Rheumatol. 2017 Apr;69(4):800-807. doi: 10.1002/art.40002. Epub 2017 Mar 7. PMID: 27863149
- Ultraviolet B Irradiation Causes Stimulator of Interferon Genes-Dependent Production of Protective Type I Interferon in Mouse Skin by Recruited Inflammatory Monocytes. Sontheimer C, Liggitt D, Elkon KB. Arthritis Rheumatol. 2017 Apr;69(4):826-836. doi: 10.1002/art.39987. PMID: 27863141
- Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs. An J, Minie M, Sasaki T, Woodward JJ, Elkon KB. Annu Rev Med. 2017 Jan 14;68:317-330. doi: 10.1146/annurev-med-043015-123453. Epub 2016 Oct 21. Review. PMID: 27813878
- Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus. Doedens JR, Jones WD, Hill K, Mason MJ, Gersuk VH, Mease PJ, Dall'Era M, Aranow C, Martin RW, Cohen SB, Fleischmann RM, Kivitz AJ, Burge DJ, Chaussabel D, Elkon KB, Posada JA. J Immunol. 2016 Oct 1;197(7):2854-63. doi: 10.4049/jimmunol.1601142. Epub 2016 Aug 17. PMID: 27534558
- Digestion of Chromatin in Apoptotic Cell Microparticles Prevents Autoimmunity. Sisirak V, Sally B, D'Agati V, Martinez-Ortiz W, Özçakar ZB, David J, Rashidfarrokhi A, Yeste A, Panea C, Chida AS, Bogunovic M, Ivanov II, Quintana FJ, Sanz I, Elkon KB, Tekin M, Yalçınkaya F, Cardozo TJ, Clancy RM, Buyon JP, Reizis B. Cell. 2016 Jun 30;166(1):88-101. doi: 10.1016/j.cell.2016.05.034. Epub 2016 Jun 9. PMID: 27293190
- Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ. Nat Med. 2016 Feb;22(2):146-53. doi: 10.1038/nm.4027. Epub 2016 Jan 18. PMID: 26779811
M.D., University of Witwatersrand