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
The main focus of the Gaffen lab centers around the cytokine Interleukin-17. 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 IL-17, plays a key role in driving autoimmunity. Conversely, IL-17 plays important roles in fungal immunity particularly in protection against opportunistic infections caused by the commensal yeast Candida albicans. The Gaffen lab studies mechanisms of signal transduction mediated by IL-17, as well as its role in mediating host defense against fungi. 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 are in clinical trials to treat various autoimmune conditions. Studies in Dr. Gaffen's lab also focus on the consequences of anti-IL-17 therapy with respect to infection.
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.
Hernández-Santos N, Huppler AR, Peterson AC, Khader S, McKenna K, Gaffen SL. IL-17-producing T cells confer long term adaptive immunity to Candida albicans. Mucosal Immunol, 2013; 6:900-910.
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)
Whibley N, Jaycox JR, Reid D, Garg AV, Taylor JA, Clancy CJ, Nguyen MH, Biswas PS, McGeachy MJ, Brown GD, Gaffen SL. Delinking CARD9 and IL-17: CARD9 protects against Candida tropicalis infection through a TNFa-dependen, IL-17-independent mechanism. J Immunol, 2015; 195:3781-92. (featured in the "In This Issue" section of J Immunology)
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)