Sarah Gaffen, Ph.D.
Campus: 200 Lothrop Street
Office: S702 BST South
Lab: BST S737
Pittsburgh, PA 15261
- BS, Carnegie Mellon University
- PhD, University of California at Berkeley
- Postdoc, University of California at San Francisco
- Gerald P. Rodnan Professor, Division of Rheumatology & 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.
Pub Med link:
Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Ho AW, Hai JH, Yu JJ, Jung JW, Filler SG, Masso-Welch P, Edgerton M, Gaffen SL. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med, 2009; 206:299-311 (recommended by Faculty of 1000 Biology and Faculty of 1000 Medicine).
Garg A, Ahmed M, Vallejo A, Ma A, Gaffen SL. The deubiquitinase A20 mediates feedback inhibition of Interleukin-17 receptor signaling. Science Signaling, 2013; 6:ra44.
Gaffen SL, Jain R, Garg AV, Cua D. IL-23-IL-17 immune axis: Discovery, mechanistic understanding and clinical therapy. Nature Rev Immunol, 2014; 14:585-600.
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)
Monin L, Gudjonsson JE, Childs EE, Amatya N, Xing X, Verma AV, Coleman BM, Killeen M, Mathers A, Ward NL, Gaffen SL. MCPIP1/Regnase-1 restricts IL-17A- and IL-17C-dependent skin inflammation. J Immunol, 2017; 198:767-775.
Amatya N, Garg AV, Gaffen SL. The Yin and the Yang of IL-17 signaling. Trends Immunol. 2017; 38:310+322 (Featured Cover Art)
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
Verma AH, Zafar H, Ponde NO, Hepworth O, Sihra D, Aggor FEY, Ainscough JS, Ho J, Richardson JP, Coleman B, Hube B, Stacey M, McGeachy MJ, Naglik JR, Gaffen SL*, Moyes DL*. IL-36 and IL-1/IL-17 drive immunity to oral candidiasis via parallel mechanisms. J Immunol. 2018; 201:627-634. (Featured in "In This Issue")
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")