2024 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research (formerly the Seymour & Vivian Milstein Award from 1988 – 2020)
Yanick J. Crow, MD, PhD
University of Edinburgh, Edinburgh, Scotland
Université Paris, Paris, France
Programme lead at the MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, UK (https://www.ed.ac.uk/mrc-human-genetics-unit/research/crow-research-group), and the Institute Imagine, Université Paris Cité, France (https://www.institutimagine.org/en/yanick-crow-180).
Professor Yanick J. Crow has been selected as the 2024 ICIS-Pfizer Award for Excellence in Interferon and Cytokine Research in recognition for his ground-breaking research on type I Interferonopathies, work which has significantly impacted the fields of basic and clinical immunology. Professor Crow is recognized as a leader in the field of human inborn errors of immunity, and a founder of the rapidly growing field of “type I interferonopathies,” making him a most deserving recipient for the ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research.
2024 ICIS-Pfizer Award for Excellence in Cytokine & Interferon Research Presentation
Professor Crow will give his ICIS-Pfizer Award Presentation at Cytokines 2024 Joint Meeting KAI 2024 in the Opening Session on Sunday, October 20th at the COEX Conference Center in Seoul, Korea, an overview of the field of monogenic diseases associated with enhanced type I interferon signalling, with an emphasis on more recent points of interest.
Over a period of more than 20 years, Yanick has worked to define the molecular basis of Aicardi-Goutières syndrome (AGS), an inherited neurological condition that was intriguing because it mimicked (in neonates) the consequences of viral infection during foetal life, both clinically (e.g. brain calcification) and immunologically (e.g. enhanced type I interferon (IFN) activity in the cerebrospinal fluid). What began as a genetic study of an Mendelian phenocopy of foetal infection has developed into a most surprising and highly informative adventure in clinical immunology and cytokine biology.
First, AGS has helped to delineate a continually expanding novel group of human conditions, the “type I Interferonopathies”, which are characterized by excessive type I IFN production – where such type I interferon signalling is hypothesised to directly contribute to pathogenesis. Second, AGS contrasts beautifully with inborn errors characterized by impaired type I IFN (e.g. STAT1 deficiency, IFNAR1 deficiency). Together, these two groups of disorders have shown the deleterious consequences of too little or too much type I IFN immunity in humans – phenotypes that are sometimes but not always predicted in inbred mice. Third, the study of AGS and other type I interferonopathies has informed our understanding of more common disorders, most obviously systemic lupus erythematosus (SLE).
The single most important lesson deriving from the study of AGS and other type I interferonopathies is that essential anti-viral systems, sensing either viral DNA or RNA, can also be triggered by host-derived nucleic acid. Using screening tools that he developed and characterised for the identification of type I interferonopathies, Yanick’s work has helped to define multiple cell-intrinsic molecular programs, dysfunction of which can lead to a failure of self/non-self discrimination and the induction of inappropriate anti-viral signalling. Of particular note, these discoveries have highlighted the immunogenic potential of retroelements, ‘by-products’ of DNA transcription and repair, mitochondrial nucleic acid, and nuclear DNA as potential triggers of an anti-viral response against self. Importantly, Yanick has moved to translate these insights into novel ‘anti-interferon’ therapies – potentially also relevant to a larger group of non-Mendelian diseases.
As often with major breakthroughs, the above discoveries were generated at the crossroads of several fields, in this case neurology, paediatrics, human genetics and immunology. Yanick’s work illustrates the value of a human-focused approach in tackling complex biology, and the place of imaginative thinking in scientific research.
The Pfizer Award for Excellence in Interferon and Cytokine Research (formerly the Seymour & Vivian Milstein Award from 1988 – 2020), represents the pinnacle of scientific achievement in interferon and cytokine research since 1988, two years after interferon was first approved for the treatment of hairy cell leukemia. Since that time, it has been widely recognized that interferons and the larger class of cytokines play critical roles in the development and progression of many major diseases including cancer, viral diseases such as hepatitis and influenza, and autoimmune disorders like multiple sclerosis and lupus. For more details, list of Award Laureates, please click here.
