The immune system strikes a remarkably tight balance between controlling infections and limiting immunity to self. T cell-derived cytokines are a case in point: while critical for protecting against infectious disease, they also mediate pathology in autoimmunity. The Gaffen lab studies a cytokine called IL-17, which links innate and adaptive immunity through regulation of neutrophils and innate antimicrobial proteins. IL-17 and its receptor are unique in structure and sequence from other known cytokine families, and the Gaffen lab was among the first to study signaling mechanisms mediated by this novel protein. Dr. Gaffen’s group takes a variety of biochemical, molecular and in vivo approaches to defining IL-17 biology. In terms of infections, the Gaffen lab was the first to demonstrate that IL-17 is critical for immunity to mucosal fungal infection with the commensal fungus, Candida albicans, causative agent of oral and vaginal thrush and also of systemic candidiasis, a serious hospital-acquired infection with >50% mortality. Research in the Gaffen lab is focused on defining the biological function of IL-17 and its receptor in the context of the oral mucosa. Treatment of autoimmune diseases has been revolutionized by biologic drugs that neutralize cytokines, such as etanercept (a TNF receptor antagonist) and tocilizumab (an IL-6 receptor antagonist). Many of these drugs target the Th17/IL-17 pathway, and antibodies to IL-17 were approved in 2016 for psoriasis. Dr. Gaffen’s group aims to understand the physiological impact of cytokine blockade in humans, particularly with respect to the IL-17 signaling pathway.
- BS, Carnegie Mellon University, Pittsburgh, PA, 1988
- PhD, University of California at Berkeley, Berkeley CA, 1994
- Postdoctoral Fellow, UC San Francisco/Gladstone Institute of Virology & Immunology, 1999
Education & Training
Li Y, Dey I, Vyas SP, Synackova A, Li D, Lubberts E, Ascherman DP, Draber P, Gaffen SL. The RNA binding protein Arid5a is an activator of TNF signaling in rheumatoid arthritis. JCI Insight. 2026 Jan 23;11(2):e196411. PMID: 41574607.
Dey I, Li Y, Taylor TC, Peroumal D, Asada N, Panzer U, Biswas PS, Sterneck E, Gaffen SL. C/EBPδ Mediates Immunity to Renal Autoinflammatory Disorders in a Stage-specific Manner. J Immunol. 2024 Sep 15;213(6):767-778. PMID: 39082925.
Ponde NO, Shoger KE, Khatun MS, Sarkar MK, Dey I, Taylor TC, Cisney RN, Arunkumar SP, Gudjonsson JE, Kolls JK, Gottschalk RA, Gaffen SL. SARS-CoV-2 ORF8 Mediates Signals in Macrophages and Monocytes through MyD88 Independently of the IL-17 Receptor. J Immunol. 2023 Jul 15;211(2):252-260. PMID: 37265402.
Bechara R, Amatya N, Bailey RD, Li Y, Aggor FEY, Li DD, Jawale CV, Coleman BM, Dai N, Gokhale NS, Taylor TC, Horner SM, Poholek AC, Bansal A, Biswas PS, Gaffen SL. The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis. Sci Immunol. 2021 Jul 2;6(61):eabd1287. PMID: 34215679.
Taylor TC, Coleman BM, Arunkumar SP, Dey I, Dillon JT, Ponde NO, Poholek AC, Schwartz DM, McGeachy MJ, Conti HR, Gaffen SL. IκBζ is an essential mediator of immunity to oropharyngeal candidiasis. Cell Host Microbe. 2023 Oct 11;31(10):1700-1713.e4. PMID: 37725983.
Bechara R, Amatya N, Majumder S, Zhou C, Li Y, Liu Q, McGeachy MJ, Gaffen SL. The RNA-binding protein IMP2 drives a stromal-Th17 cell circuit in autoimmune neuroinflammation. JCI Insight. 2022 Feb 8;7(3):e152766. PMID: 34914635.
Li X, Bechara R, Zhao J, McGeachy MJ, Gaffen SL. IL-17 receptor-based signaling and implications for disease. Nat Immunol. 2019 Dec;20(12):1594-1602. PMID: 31745337.
Majumder S, Amatya N, Revu S, Jawale CV, Wu D, Rittenhouse N, Menk A, Kupul S, Du F, Raphael I, Bhattacharjee A, Siebenlist U, Hand TW, Delgoffe GM, Poholek AC, Gaffen SL, Biswas PS, McGeachy MJ. IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival. Nat Immunol. 2019 May;20(5):534-545. PMID: 30962593.
McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 Family of Cytokines in Health and Disease. Immunity. 2019 Apr 16;50(4):892-906. PMID: 30995505. Invited review for 25th anniversary collection.
Amatya N, Garg AV, Gaffen SL. IL-17 Signaling: The Yin and the Yang. Trends Immunol. 2017 May;38(5):310-322. PMID: 28254169.
Verma AH, Richardson JP, Zhou C, Coleman BM, Moyes DL, Ho J, Huppler AR, Ramani K, McGeachy MJ, Mufazalov IA, Waisman A, Kane LP, Biswas PS, Hube B, Naglik JR, Gaffen SL. Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Sci Immunol. 2017 Nov 3;2(17):eaam8834. PMID: 29101209.
- Hulda Irene Duggan Arthritis Investigator Award, Arthritis Foundation, 2001
- JuneAnn Murphy Women in Science Distinguished Lectureship, University of Oklahoma, 2017
- NIH MERIT award, 2017
- Chancellor's Senior Scholar Research Awards, 2018
- Fellow, American Academy of Microbiology, 2021
- Fellow, AAAS, 2022
- President, International Cytokine & Interferon Society, 2023-2025
- Distinguished Fellow, American Association of Immunologists, 2026
R37 DE022550, Host and Fungal Regulation of Type 17 Immunity to Oral Candidiasis, PI, 2022-2027.
R21 AI185365, Mucosal host defense against vaginal candidiasis, PI, 2024-2026.
