(一)Michael P. Snyder
Our present healthcare system focuses on treating people when they are ill rather than keeping them healthy. We have been using big data and remote monitoring approaches to monitor people while they are healthy to keep them that way and detect disease at its earliest moment presymptomatically. We use advanced multiomics technologies (genomics, immunomics, transcriptomics, proteomics, metabolomics, microbiomics) as well as wearables and microsampling for actively monitoring health. Following a group of 109 individuals for over 13 years revealed numerous major health discoveries covering cardiovascular disease, oncology, metabolic health and infectious disease. We have also found that individuals have distinct aging patterns that can be measured in an actionable period of time. Finally, we have used wearable devices for early detection of infectious disease, including COVID-19 as well as microsampling for monitoring and improving lifestyle. We believe that advanced technologies have the potential to transform healthcare and keep people healthy.
(二)Michael Karin
Damage associated molecular patterns (DAMP) elicit inflammation and provide co-stimulatory signals to adaptive immune cells1, but whether recurring innate stimulation circumvents self-tolerance2,3 to establish maldaptive and long-lasting autoimmunity is unknown. We adressed this question using the NLRP3 inflammasome activator alum4, which induces the circulatory release of oxidized mitochondrial DNA (Ox-mtDNA)5, a DAMP associated with diverse metabolic6 and autoimmune disorders, including systemic lupus erythematosus (SLE) where it correlates with dysregulated type I interferon (IFN-I) production7-10. Yet, whether Ox-mtDNA is the cause of autoimmunity remained unknown. We show that by inducing Ox-mtDNA release repetitive alum injections triggered germinal center reactions, autoantibody production and renal pathology. The same reactions were induced by in-vitro prepared Ox-mtDNA, while non-oxidized mtDNA was non-pathogenic. Both mtDNA forms were preferentially taken up by plasmacytoid dendritic cells (pDC) and induced IFN-I but only Ox-mtDNA triggered NLRP3-dependent IL-1β production, resulting in autocrine induction of IL-21 that together with IL-1β, but independently of IFN-I, enabled pDC to convert naïve CD4+ T cells into follicular helper cells that support autoantibody production. Highlighting Ox-mtDNA as a uniquely immunogenic DAMP and IL-1β as key orchestrator of autoantibody induction, these findings may pertain to the origins of SLE, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA)11 and related diseases, while providing new preventive and therapeutic targets.
嘉宾介绍

Michael P. Snyder
Stanford W. Ascherman Professor, Chair, Department of Genetics and Director, Center for Genomics and Personalized Medicine
Michael Karin
Distinguished Professor of Pharmacology and Pathology Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic DiseasesProfessor Michael Karin is highly regarded in the signal transduction community, he pioneered the JNK signaling pathway research, and the first cloning of the IKK gene. Professor Karin’s research interests focus on basic biochemical and cell biological processes that control innate immunity and inflammation and their contribution to cancer and metabolic disease. His group also investigates the interaction between chronic inflammation and immunity during tumor development and therapy.
Professor Karin has served on the editorial board of several international academic journals, including Molecular Cell, Immunity, Cell Metabolism, and Cell Death & Differentiation. He has published more than 490 papers in Nature, Cell, Nature Medicine, Immunity and many other prestigious journals, and the number of paper citations ranks top in the world in the field of molecular biology and genetic research. He has won numerous honors including Harvey Prize, The Brupbacher Prize for Cancer Research, The William B. Coley Award for Distinguished Research in Basic and Tumor Immunology, The Anthony Dipple Carcinogenesis Award, AAACR GHA Clowes Award for Outstanding Basic Cancer Research, Fellow of the AACR Academy and has been an Einstein Professorship, Chinese Academy of Sciences in 2009.