Sarah Gaffen, Ph.D.
Contact
Campus: Biomedical Science Tower East, 200 Lothrop St
Office: BST East 1552
Lab: 15th floor - Starzl Transplant Institute
Pittsburgh, PA 15261
Ph: 412-383-8903
Education
- B.S., Carnegie Mellon University
- Ph.D., University of California at Berkeley
- Postdoc, University of California at San Francisco
Academic Affiliation
- Gerald P. Rodnan Professor, Division of Rheumatology and Clinical Immunology
- Director, Basic Rheumatology Research
About 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
Selected Publications
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
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.
Aggor FEY, Bertolini M, Zhou C, Taylor TC, Abbott DA, Musgrove J, Bruno VM, Hand TW, Gaffen SL. A gut-oral microbiome axis controls oral candidiasis through retinoic acid. JCI Insight, 2022; e160348. (cover art)
Ponde NO, Shoger KE, Khatun MS, Sarkar MK, Dey I, Taylor TC, Cisney RN, Arunkumar SP, Giudjonsson JE, Kolls JK, Gottschalk RA, Gaffen SL. SARS-CoV-2 PRF8 mediates sigansl in macrophages and monocytes through MyD88 independently of the IL-17 reeptor. J Immunol. 2023; 211: 252-60. (Top Read, Journal of Immunology)
Taylor TC, Coleman BM, Arunkumar SP, Dey I, Dillon JT, Ponde NO, Poholek AC, Schwartz DM, McGeachy MJ, Conti HR, Gaffen SL. IkappaBzeta is an essential mediator of immunity to oropharyngeal candidiasis. Cell Host Microbe. 2023; 31:1700-13. (commentary by G. Hajishengallis, "Delving into the adytum of the IL-17 defense pathway")