The 2018 Seymour & Vivian Milstein Award for Excellence in Interferon and Cytokine Research

The ICIS Awards Committee have chosen Thirumala-Devi Kanneganti, PhD, as one of the recipients of the 2018 Seymour & Vivian Milstein Award for Excellence in Interferon and Cytokine Research in recognition of her numerous contributions and impact on our understanding of immunology, inflammation, cytokine signaling and host-pathogen interactions. The field of innate immunity and inflammation has emerged as a central focus in biomedical research in recent years, and Dr. Kanneganti’s contributions are at an outstanding level and at the forefront of this research area.

Dr. Kanneganti is the Vice Chair of the Immunology Department and the Rose Marie Thomas Endowed Chair at St. Jude Children’s Research Hospital in Memphis, Tennessee. Her first major contribution to the field of innate immunity was the initial discovery of the role of the NLRP3 inflammasome in caspase-1 activation by microbial components (Nature 2006 Mar 9;440(7081):233-6). Her research identified the activation mechanisms of inflammasomes during infections and autoinflammatory diseases, and the crosstalk between several cell death pathways, namely pyroptosis, apoptosis and necroptosis. Using novel genetic mouse models and in-depth molecular and biochemical analyses, her lab has discovered distinct and previously unrecognized functions of the cytokines IL-1α, IL-1 and IL-33 and their signaling pathways in inflammatory diseases and cancer. Her lab has recently identified ZBP1/DAI as an innate sensor of influenza virus that triggers the NLRP3 inflammasome and programmed cell death pathways. Additionally, research from her lab discovered roles for NLRC3 in regulating PI3K signaling and for the cGAS-STING-IRF-GBP-IRGB10 pathway in liberating ligands that are eventually sensed by the AIM2 and NLRP3 inflammasomes. Her studies have contributed significantly to shaping our current understanding of the NLRs, inflammasomes, interferons, and cytokines of the IL-1 family in all areas of immunology. Dr. Kanneganti is well known for her many original and critically important contributions to our understanding of how the innate immune system recognizes and responds to pathogens and how genetic mutations in innate immunity affect the development of infectious, inflammatory, and autoimmune diseases in humans.

Dr. Kanneganti’s story is compelling and her achievements remarkable. Dr. Kanneganti grew up in modest circumstances in India. She was an exceptional student, ultimately receiving a Ph.D. and the Jawaharial Nehru Award for Outstanding Doctoral Thesis, a competitive award only conferred on 18 Ph.D. doctoral graduates in all of India. Her early efforts focused on understanding plant pathogens and toxins relevant to her region. This led her to question general principles related to how all organisms respond to pathogens, inflammation, and to move to one of the best laboratories in the United States to study this.

Dr. Kanneganti’s ascendance, as she has moved through her post-doctoral studies to a junior faculty position at St. Jude Children’s Research Hospital to her current position as the Vice-Chair of Immunology and Member (equivalent of Full Professor) in the Department of Immunology, has been phenomenal. Most recently, she received the Rose Marie Thomas Endowed Chair, the highest honor faculty at St. Jude can receive. She is currently the Chair of the NIH Innate Immunity and Inflammation study section and has received the 2015 Vince Kidd Mentor of the Year Award. The American Association of Immunologists (AAI) has recognized her contributions to the field of immunology by selecting her for the AAI-BD Biosciences Investigator Award in 2015, and she also received the Society for Leukocyte Biology (SLB) Dolph O. Adams award, the Eli Lilly and Company-Elanco Research Award from the American Association of Microbiology (ASM) and was recently elected to the Society of Mucosal Immunology Board of Councilors and Telengana Academy of Sciences.

Luke A.J. O’Neill, PhD, FRS is Professor & Chair of Biochemistry in the School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute at Trinity College Dublin, Ireland. Professor O'Neill is awarded the 2018 Seymour & Vivian Milstein Award for Excellence in Interferon & Cytokine Research in recognition for his seminal contributions to our understanding of the molecular basis of inflammation and immunity. He is one of the key figures whose research and publications are responsible for the major increase in interest amongst immunologists in innate immunity over the past 20 years and is listed by Thompson Reuters/ Clarivates in the top 1% of immunologists in the world, based on citations per paper. 

His interest in cytokines began in 1985 during his PhD at the Royal College of Surgeons in London on the recently cloned IL1. He worked on the mechanism whereby IL1 could increase production of prostaglandins, providing an early description of inducible cyclooxygenase. He continued investigating IL1 signaling as a postdoctoral scientist working with IL1 co-discoverer Jerry Saklatvala at the Strangeways Research Laboratory in Cambridge where he did work on IL1 signal transduction and NFkappaB. Establishing his own lab back in Dublin he continued to study NFkappaB, providing early descriptions of NFkappaB in brain and studying its redox regulation. His interest in IL1 signaling continued and he wrote a key review describing in detail the Toll-IL1 receptor- resistance (TIR) domain as a critical domain in innate immunity. This led to the discovery of viral proteins with TIR domains which he showed were inhibitors of Toll-like receptor (TLR) signaling, providing the first link between TLRs and viruses. This interest in the TIR domain led to the discovery of the protein Mal, a signaling adapter which he showed to be essential for signaling by the LPS receptor TLR4, which has more recently been shown to be critical for all TLRs (with the exception of TLR3) making it a central player in innate immunity and a key signal linking innate and adaptive immunity. O’Neill then carried out extensive characterization of signaling mechanisms for TLRs, uncovering negative regulatory mechanisms (including miRNAs) and  recent important work on metabolic changes in macrophages triggered by TLR4. His metabolic work also involved the NLRP3 inflammasome, which drives production of the key cytokines IL-1 and IL-18, investigating its role in Type 2 diabetes, uncovering control mechanisms and also reporting the first potent selective inhibitor of NLRP3 which has tremendous potential as a novel anti-inflammatory agent. 

His work on metabolic changes induced by TLR4 has made a pioneering contribution to the currently burgeoning field of Immunometabolism, whereby immune cells undergo metabolic reprogramming to elicit specific effector functions. O’Neill identified the metabolite succinate as a key inflammatory signal, driving IL1beta production. More recently he has uncovered a critical anti-inflammatory role for the citrate - derived metabolite itaconate, acting via Nrf2.

All of these contributions have helped to place the field of innate immunity center stage in the effort to understand host defense mechanisms and inflammation and are fundamental findings in biology of the immune system and are also important for efforts to develop new treatments of infectious and inflammatory diseases. In short, O’Neill is a world authority on signaling in inflammation and innate immunity.  

In 2013 he served as co-President of the newly inaugurated International Cytokine & Interferon Society with Chuck Samuel.

Professor O'Neill is founder director of three companies exploring innate immune targeting, Opsona, Inflazome and Sitryx. He is also a member of the External Immunology Network at GSK, where he has been a visiting scientist.

He was awarded the Royal Dublin Society / Irish Times Boyle Medal for scientific excellence, the Royal Irish Academy Gold Medal for Life Sciences, The Society for Leukocyte Biology (SLB) Dolph O. Adams award and the European Federation of Immunology Societies Medal. He is a member of the Royal Irish Academy, EMBO (European Molecular Biology Organisation) and a Fellow of the Royal Society.