2020 BioLegend William E. Paul Award for Excellence in Cytokine Research

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 [2015]; 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.

Professor Vijay K. Kuchroo is recognized for his impact on many of the fundamental discoveries related to cytokine research over the past decade. In particular, he was instrumental in defining the IL-17 producing Th17 cells and their role in autoimmunity and how their modulation effects immune function and tissue inflammation. His work contributed to the development of immunotherapeutics that target both Tim-3 in cancer and IL-17 for autoimmune diseases. Dr. Kuchroo is also recognized for his seminal and original contributions to our understanding of the basic mechanisms of T cell differentiation and tolerance.

Dr. Kuchroo is recognized as one of the major forces in the MS research community. Many of the reagents and tools generated by his laboratory are willingly shared with the research community including multiple TcR transgenic mice, specific for myelin proteolipid protein and Myelin Oligodendrocyte Glycoprotein (MOG), which are used widely in every laboratory working in the field of Experimental Autoimmune Encephalomyeltis (EAE) and multiple sclerosis (MS). These transgenic mice are used by immunologists all over the world and have become a gold standard for studies with EAE. He has utilized EAE in mice as a tractable system to understand how autoimmunity develops and causes disease that is relevant to patients with MS. His initial work embraced the new technology of animal transgenesis to develop animal models for human autoimmune diseases. The journal Nature Immunology judged two of Dr. Kuchroo’s papers as “classics in autoimmunity” and he received The Jacob Javits Neuroscience Investigator Award from the National Institutes of Health for this work in 2002. In addition, he was invited to give the prestigious Newsom-Davis lecture by the International Society of Neuroimmunology in 2016 and in 2019 was the recipient of the MileStones in Research Award from the National Multiple Sclerosis Society.

He has made enormous contributions to our understanding of autoimmunity, T cell differentiation and tolerance. His 400 studies have been cited more than 87,000 times and he has an H-index of 140. One of his papers on Th17 differentiation is one of the highly cited papers in Immunology. He is a pioneering T cell biologist who has made critical discoveries in the area of co-stimulation discovering TIM-3 and TIM family of genes in 2002.  He has also made an important contribution to the field of innate lymphoid cells, most recently in relation to neuroimmune aspects and T cell subset differentiation, where he uncovered pathways for differentiation of Th17, Tr1 and Th9 cells. Thus, Dr. Kuchroo’s work has had enormous impact not only the basic understanding of the immune system but his basic observations have had clinical impact.

As the field of Th17 biology has matured, Dr. Kuchroo has been at the forefront of adopting the parallel advances in the technologies that allow systems biology approaches to be applied to the analysis of immune populations. He has undertaken a temporal high-density transcriptomic analysis in collaboration with Aviv Regev at the Broad Institute, that has defined the circuitry of Th17 development. In addition to Th17 cells, Dr. Kuchroo also undertook single cell RNAseq analysis of ILC2 from the lung and identified the neuropeptide receptor- Neuromidine U receptor 1 (NMUR1), as uniquely expressed on ILC2. This study also showed that the cytokine IL-25 and the Neuropeptide NMU converts homeostatic ILC2 into pro-inflammatory allergenic ILC2 and contributes to lung inflammation.

Vijay Kuchroo is the first incumbent of the Samuel L. Wasserstrom Professor of Neurology in Inflammatory Diseases at Harvard Medical School and senior scientist at Brigham and Women’s Hospital. He is founding director of the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital. He is an institute member of the Broad Institute and a participant in a Klarman Cell Observatory project that focuses on T cell differentiation. Dr. Kuchroo came to the United States in 1985 and was at the National Institutes of Health, Bethesda as Fogarty International Fellow for a year before joining the Department of Pathology, Harvard Medical School as a Research Fellow in the fall of 1986. Dr. Kuchroo joined the Center for Neurologic Diseases, Brigham and Women’s Hospital in 1992 where he was promoted to the rank of Associate Professor in 1996 and full Professor in 2004.

He obtained his degree in veterinary medicine from the College of Veterinary Medicine, Hisar, India. Subsequently, he specialized in veterinary pathology at the University of Queensland, Brisbane (Australia), where he obtained a Ph.D. in 1985. He received the Fred Z. Eager Research prize and medal for his Ph.D. research work at the University of Queensland. Based on his contributions, he was awarded the Javits Neuroscience Award by the National Institutes of Health in 2002 and the Ranbaxy prize in Medical Research from the Ranbaxy Science Foundation in 2011 for discovery of Th17 cells. He was named Distinguished Eberly lecturer in 2014, Garber Lecturer by the French Society of Immunology in 2014 and was recipient of Nobel Laureate Peter Doherty lecture/prize in 2014.

Dr. Kuchroo has been on the Editorial Boards of the journals Autoimmunity, Journal of Immunology, Scandinavian Journal of Immunology, International Journal of Immunology and Journal of Experimental Medicine and an ad hoc reviewer for a number of Immunology related journals. He was a permanent member of the grants review boards of the Juvenile Diabetes Research Foundation, New York and is currently on the scientific review board of the National Multiple Sclerosis Society, New York. Dr. Kuchroo is also an ad hoc reviewer for the research grants for various study sections at the National Institutes of Health. 

Dr. Kuchroo has over 25 patents and has founded 6 different biotech companies. He also serves on the scientific advisory boards of a number of big pharmaceutical companies including Pfizer, Novartis, Sanofi/Genzyme and Glaxo-Smith-Klein (GSK). He is also on the boards of Biocon Pharmaceuticals, Syngene International and Bicara Inc.