Gerald P. Rodnan Professor of Rheumatology Director of Basic Rheumatology Research University of Pittsburgh School of Medicine Department of Medicine, Division of Rheumatology and Clinical Immunology Pittsburgh, USA
Professor Sarah Gaffen is a world leader in the field of IL-17 biology and function and has become virtually synonymous with this cytokine within the broad scientific community. Dr. Gaffen is recognized for her role on IL-17-producing T cells (TH17 cells). Her laboratory first showed the role of Th17 cells in fighting yeast infections with candida albicans. 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 novel family of cytokines. Dr. Gaffen started working on IL-17 back in 1999, at the time IL-17 was still an obscure and poorly understood cytokine, showing impressive foresight in working on this cytokine long before it was on anyone else’s radar. In remarkably short order, Dr. Gaffen became a leading expert on IL-17 biology, which is now widely recognized as a major axis of immune signaling in biomedicine, and she made major headway in establishing systems for its investigation. Her group described the “IL-17 signature” that is now widely used in the field as a measure of IL-17 activity. Many early IL-17 researchers were stymied by the surprisingly weak activities of this cytokine. Undaunted, Dr. Gaffen demonstrated that, while IL-17 acts in a modest capacity on its own, IL-17 synergizes with other cytokines and microbial stimuli. Indeed, the concept of IL-17/TNFα synergy is now the basis for clinical approaches to treat refractory autoimmune disease, and she received a grant from Janssen to pursue the clinical implications of this synergy (J Immunol 2018). Her group’s early analyses of the IL-17 receptor accurately predicted its 3-dimensional architecture and led to a patent (with Amgen) for methods to block IL-17 signaling activity (PNAS 2007; Science Signaling 2009; JBC 2010; J Immunol 2010; US Patent #8,460,647). Today, many groups use tools and systems that her lab developed to understand IL-17 biology. In recent years her group has discovered mechanisms by which IL-17 signal transduction is constrained to limit inflammation (Science Signaling [2013, 2018]; Immunity ; Journal of Immunology [(2017]). Undeniably, Dr. Gaffen has a unique talent for recognizing areas of science that have been overlooked but are critically important, clinically relevant, and ripe for influential discoveries; these include IL-17 but extend far beyond IL-17 to other fields such as oral mucosal immunity and fungal immunity.
Presently, Sarah is internationally recognized for her groundbreaking work on oral mucosal immunity. Her signaling studies led her to recognize that mucosal epithelial cells are responsive to IL-17, but the oral mucosa remained neglected in this regard. Recognizing this gap, Dr. Gaffen was the first to show that IL-17 is host-protective in the oral mucosa, using a model of anaerobic periodontal bacterial infection (Blood 2007; Infect Immun 2008; Science Immunol 2020); importantly, this work inspired others in the dental field to evaluate IL-17 in this setting. Additionally, she showed IL-17 signaling is critical for immunity to the opportunistic fungus Candida albicans (JEM 2009). The latter paper is widely considered a seminal paper in the fungal field, with almost 900 citations, two Faculty of 1000 recommendations and an accompanying commentary in J Exp Med. Strikingly, these findings were validated in humans, as rare mutations in the IL-17R pathway cause oral mucosal candidiasis but surprisingly few other infections. One prediction from her work was that oral candidiasis would be a side effect of anti-IL-17 biologic therapy, which is indeed the case.
Work from her team in the candidiasis system revealed that not just Th17 cells, but also novel subsets of innate immune lymphocytes, are vital mediators of immunity to candidiasis (Mucosal Immunol 2013; J Exp Med 2014; Science Immunology 2017). Dr. Gaffen has used these concepts to develop a strain of C. albicans expressing IL-17 for use as a probiotic (Infect Immun 2015; US Patent # 10,160,974). Recognizing the paucity of tools to study events in the oral cavity, her group created a new mouse system to allow conditional gene deletion in the oral/esophageal mucosa. She used this system to show that IL-17 in oral epithelial cells is necessary for immunity to oral candidiasis (Cell Host Microbe 2016). Thus, Dr. Gaffen’s group has pioneered studies of IL-17 in oral immunology and continues to lead the field with novel findings and innovative approaches.
Dr. Gaffen’s research program has impressive momentum. In the last few years she has published in Immunity, Cell Host & Microbe, Science Signaling, JEM, Nature Immunology, Nature Communications and Science Immunology. In 2016 she took advantage of a sabbatical leave at King’s College London to develop expertise in epithelial cell biology, a logical extension of her work on IL-17 in the oral mucosa. This led to her exciting work on Candidalysin, a virulence factor for invasive Candida. Gaffen’s publication record is stellar, with over 129 publications, many in the top journals of the field. She has also written many high impact reviews, including Nature Immunology (2019), Nature Reviews Immunology (2009, 2014) and the 25th Anniversary Edition of Immunity (2019). She is regularly called upon to write commentaries about articles in the field, which have appeared in Science Signaling, Immunity and Nature Reviews Immunology. Dr. Gaffen has been elected to leadership roles in professional societies (e.g., ICIS Secretary and Councilor). She chaired a standing NIH study section, organized major conferences (including the 2013 inaugural meeting of the ICIS), and is on several journal editorial boards, notably Deputy Editor at the Journal of Immunology and member of the Advisory Board of Science Immunology. She won a Young Investigator Prize from the International Cytokine Society in 2004; in 2008 she was named to the prestigious Henry Kunkel Society; and in 2009 she was invited to join the Faculty of 1000. On the strength of her many accomplishments, she was awarded the Gerald P. Rodnan Endowed Chair in Rheumatology in 2015, one of only 3 endowed chairs in her Division and the only PhD or woman to be so honored. Dr. Gaffen received the 2018 University of Pittsburgh Chancellor’s Senior Scholar Research award, one of the highest honors the University bestows, and one which is competitive across disciplines. Sarah’s stature is the field is also evidenced by her having received the top score at the 2001 Arthritis Foundation grant application (Hulda Irene Duggan Arthritis Investigator Award). Dr. Gaffen rapidly obtained NIH R01 funding, which she has maintained continuously to this day. She holds R21 and R03 grants and a Senior Investigator grant from the Rheumatology Research Foundation. Dr. Gaffen is currently PI of three R01 grants. Notably, the R01 renewal grant based on her sabbatical research was given a MERIT award, an honor given to fewer than 5% of NIH investigators, to “provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner.”
Dr. Sarah Gaffen received her BS in Biological Sciences from Carnegie Mellon University and her PhD in Molecular and Cellular Biology from the University of California at Berkeley. After a postdoctoral fellowship at the Gladstone Institute for Virology and Immunology at UC San Francisco working on IL-2 and JAK-STAT signaling in T cells, she joined the faculty at the University at Buffalo, State University of New York Dental School. In 2008 she re-located to the University of Pittsburgh, Division of Rheumatology and Clinical Immunology, where she holds the Gerald P. Rodnan Endowed Chair in the Department of Medicine, Division of Rheumatology and Clinical Immunology.