Sarah Gaffen, Ph.D.
Campus: Biomedical Science Tower South, 200 Lothrop St
Pittsburgh, PA 15261
- B.S., Carnegie Mellon University
- Ph.D., University of California at Berkeley
- Postdoc, University of California at San Francisco
- Gerald P. Rodnan Professor, Division of Rheumatology and Clinical Immunology
- Director, Basic Rheumatology Research
T cell derived cytokines are critical for mediating host defense against infectious disease, but they also mediate disease pathology in autoimmunity. A subset of CD4+ T cells, known as "Th17 cells" based on production of the cytokine IL-17, plays a key role in driving autoimmunity. Conversely, IL-17 and Th17 cells play important roles in fungal immunity, particularly in protection against opportunistic mucosal infections caused by the commensal yeast Candida albicans, first shown by Dr. Gaffen's group. IL-17 and its receptor are unique in structure and sequence from other known cytokines, and the Gaffen lab has been a leader in studying signaling pathways mediated by this this novel family of cytokines. In addition, antibodies against IL-17 and its receptor were recently approved by the FDA to treat autoimmune conditions, particularly psoriasis
The Gaffen lab studies three aspects of IL-17/Th17 cell biology: (1) mechanisms of molecular signal transduction mediated by IL-17 and its receptor (2) means by which IL-17 mediates host defense against mucosal Candida albicans fungal infections, and (3) mechanisms by which dysregulated IL-17/Th17 cells drive pathogenesis of autoimmunity.
Watch this video to hear Dr. Gaffen describe her lab's resaerch
Conti HR, Peterson AC, Huppler AR, Brane L, Hernández-Santos N, Whibley N, Garg AV, Simpson-Abelson MR, Gibson G, Mamo AJ, Osborne L, Bishu S, Ghilardi N, Siebenlist U, Watkins SC, Artis D, McGeachy MJ, Gaffen SL. Oral-resident ‘natural’ Th17 cells and gamma-delta-T cells control opportunistic Candida albicans infections. J Exp Med, 2014; 211:2075. (recommended by Faculty of 1000 Biology)
Garg AV, Amatya N, Chen K, Cruz JA, Whibley N, Grover P, Whibley N, Conti HR, Mir GH, Sirakova T, Childs EC, Smithgall TE, Biswas PS, Kolls JK, McGeachy MJ, Kollatukudy PE, Gaffen SL. MCPIP1/Regnase is a negative feedback inhibitor of IL-17-mediated signaling and inflammation. Immunity, 2015; 43:475-487.
Conti HR, Bruno VM, Childs EE, Daugherty S, Hunter JP, Mengesha BG, Saevig DL, Hendricks MR, Coleman BM, Brane L, Solis N, Cruz JA, Verma AH, Garg AV, Hise AG, Richardson JP, Naglik JR, Filler SG, Kolls JK, Sinha S, Gaffen SL. IL-17RA signaling in oral epithelium is necessary and sufficient for protection against oropharyngeal candidiasis. Cell Host & Microbe, 2016; 20:606-617. (recommended by Faculty of 1000)
Verma AH, Richardson JP, Moyes DL, Ho J, Huppler AR, Ramani K, Coleman BM, 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. Science Immunology, 2017; 2, eaam8834 (Featured Cover Art, Commentary by Illyan Iliev and colleagues)
-- Interview with authors: https://www.youtube.com/watch?v=57ifWIT8j_Q&feature=youtu.be
Amatya N, Cruz JA, Aggor FEY, Garg AV, Berman AJ, Atasoy U, Gaffen SL. IL-17 integrates multiple self-reinforcing, feed-forward signaling cascades through the RNA-binding protein Arid5a. Science Signaling, 2018; 11:eaat4617. (commentary by Puel and Casanova, "Arid5a makes the IL-17A/F pathway less arid")
Aggor FEY, Break TJ, Trevejo-Nunez G, Whibley N, Bailey R, Kaplan DH, Naglik JR, Shan W, Shettey AC, McCracken C, Durum SK, Biswas PS, Bruno VM, Kolls JK, Lionakis MS, Gaffen SL. Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Science Immunology, 2020; 5:eaba0570
-- interview with authors: https://www.youtube.com/watch?v=pSTKF4i1FTA&feature=youtu.be
Zhou C, Monin L, Gordon R, Aggor FEY, Behcar R, Edwards TN, Kaplan DH, Gingras S, Gaffen SL. An IL-17F.S65L knock-in mouse reveals similarities and differences in IL-17F function in oral candidiasis: A new tool to understand IL-17F. J Immunol. 2020; 205:720-730.
Bechara R, Amatya N, Bailey RD, Li Y, Aggor FEY, Li DD, Jawale C, Coleman BM, Dai N, Gokhale N, Taylor TC, Horner SM, Poholek A, Ansal B, Biswas PS, Gaffen SL. The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFalpha-dependent C/EBP transcription factor axis. Science Immunology, 2021; 6:eabd1287.