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Department of Medicine

Department of Medicine

  Division of Rheumatology and Clinical Immunology

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photo Sarah L. Gaffen, PhD

Gerald P. Rodnan Endowed Chair, Professor of Rheumatology

Email: sarah.gaffen@pitt.edu

Phone: 412-383-8903

Contact
Office: S702 Biomedical Science Tower
200 Lothrop St
Pittsburgh, PA 15261
 
Phone: 412-383-8903
Fax: 412-383-8864
E-mail: sarah.gaffen@pitt.edu
Administrative Assistant:
Linda Sadej
Education and Training
Education
BS, Carnegie Mellon University, Pittsburgh, PA, 1988
Ph.D., University of California at Berkeley, Berkeley CA, 1994
Training
Postdoctoral Fellow, UC San Francisco/Gladstone Institute of Virology & Immunology, 1999
Assistant/Associate Professor, University at Buffalo, SUNY, 1999
Research Interest
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 heavily 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.
Publications
For my complete bibliography, Click Here.
Selected Publications:
A Maitra, F Shen, W Hanel, K Mossman, J Tocker, D Swart, SL Gaffen. Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc. Natl. Acad. Sci., USA. 2007; 104: 7506.
F Shen, N Li, P Gade, D Kalvakolanu, B Doble, J Woodgett, SL Gaffen. IL-17 receptor signaling inhibits C/EBPß by sequential phosphorylation of the regulatory 2 domain. Science Signaling. 2009; 2: 8.
HR Conti, F Shen, N Nayyar, E Stocum, JM Sun, MJ Lindemann, AW Ho, M Edgerton, SL Gaffen. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. Journal of Experimental Medicine. 2009; 206: 299.
AV Garg, M Ahmed, A Vallejo, A Ma, SL Gaffen. The deubiquitinase A20 mediates feedback inhibition of Interleukin-17 receptor signaling. Science Signaling. 2013; 6: ra44.
S Bishu, EW Su, ER Wilkerson, KA Reckley, DM Jones, MJ McGeachy, SL Gaffen, MC Levesque. Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses. Arthritis Research and Therapy. 2014; 16(1): R50.
Heather Conti, AC Peterson, AR Huppler, Luke Brane, Nydiaris Hernandez-Santos, Natasha Whibley, ...., Mandy McGeachy, Sarah Gaffen. Oral-resident ‘natural’ Th17 cells and ?d-T cells control opportunistic Candida albicans infections. J Exp Med. 2014; 211: 2075.
Gaffen, SL, Jain, R, Garg, AV, Cua, D. IL-23-IL-17 immune axis: Discovery, mechanistic understanding and clinical therapy. Nature Reviews Immunology. 2014; 14: 585.
Garg, AV, Amatya, N, Chen, K, Cruz, JA, Whibley, N, Grover, P, Conti, HR, Mir, GH, Sirakova, T, Childs, EC, Smithgall, T, Biswas, PS, Kolls, JA, McGeachy, MJ, Kollatukudy, PE, Gaffen, SL. MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity. 2015; 43: 475.
Whibley, N, Tritto, E, Traggiai, E, Kolbinger, F, Moulin, P, Brees, D, Coleman, BM, Mamo, AJ, Garg, AV, Jaycox, J, Siebenlist, U, Kammüller, M, Gaffen, SL. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral candidiasis. Journal of Leukocyte Biology. 2016; 99: 1153.
Monin, L, Gudjonsson, JE, Childs, EE, Amtya, N, Xing, X, Veram, AV, Coleman, BM, Killeen, M, Mathers, A, Ward, NL, Gaffen, SL. MCPIP1/Regnase-1 restricts IL-17A- and IL-17C-dependent skin inflammation. Journal of Immunology. 2017; 198: 767.
Sponsored Research/Activities
Title: IL-17 Isoforms in Organ Specific Autoimmunity
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R21 AI128991
Start Year: 2016
End Year: 2018
Title: Cytokine Synergy in Control of Fungal Infections
Role: Principal Investigator
Funding Agency: Janssen Pharm
Start Year: 2015
End Year: 2017
Title: Negative Control of IL-17R Signaling: Implications for Fungal Immunity
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R01 AI107825
Start Year: 2014
End Year: 2018
Title: IL-23 STAT3 Driven Oral Immune Responses to Candida Albicans
Role: Principal Investigator
Funding Agency: National Institute of Dental/Craniofacial Research
Grant Number: R01 DE023815
Start Year: 2013
End Year: 2018
Title: IL-17 Receptor Signaling in the Oral Mucosa
Role: Principal Investigator
Funding Agency: National Institute of Dental/Craniofacial Research
Grant Number: R01 DE022550
Start Year: 2012
End Year: 2017
Title: IL-17 Blockade in Opportunistic Candida Albicans Infections
Role: Principal Investigator
Funding Agency: Novartis Pharmaceutical
Grant Number: DRUG IL-17 BLOCK
Start Year: 2012
End Year: 2016
Title: Structure Function Relationships in the IL-17 Receptor
Role: Principal Investigator
Funding Agency: National Institute of Arthristis, Muscoskel, & Skin Disease
Grant Number: R01 AR054389
Start Year: 2009
End Year: 2014
Title: T Helper Cell Responses in Tanerella Forsythia-Induced Alveolar Bone Destruction
Role: Principal Investigator
Funding Agency: SUNY at Buffalo/National Institute of Dental/Craniofacial Research
Grant Number: R01 DE019424
Start Year: 2008
End Year: 2013
Notable Achievements
Hulda Irene Duggan Arthritis Investigator Award, Arthritis Foundation, 2001
Associate Editor, Cytokine, 2006-pres.
Young Investigator Award, International Cytokine Society, 2004
Faculty of 1000, 2009
Member, Immunity and Host Defense (IHD) study section, NIH, 2013-19
Section Editor, Journal of Immunology, 2014-18
Reviewing Editor, Journal of Biological Chemistry, 2015-20
NIH MERIT award, 2017