Summary OVERALL; PD – Pascual, V. The Autoimmunity Center of Excellence based at Weill Cornell Medicine (WCM) in New York, NY aims at 1) advancing the knowledge of pathways and mechanisms that contribute to the development and amplification of Human Systemic Autoimmune Disease (SAD), and 2) developing tools and identifying biomarkers to monitor these dysfunctional pathways. Ultimately, we aim to be able to stratify patients towards personalized approaches to treatment. The Center will apply state-of-the-art technologies in immune profiling, cell biology and the field of nanoparticles to gain insight into disease contribution of two major and complementary compartments contributing to systemic disease: Immune Cells and Extra-Cellular Nanoparticles. The appropriate infrastructure is in place to support patient-based studies. In particular, we emphasize the following key conceptual and technological innovations adding to our strengths, that include access to an established pediatric SLE cohort followed by experienced clinical collaborators with an exceptional record of participation in translational research While the initial focus will be the study of children with Systemic Lupus Erythematosus (SLE), extrapolation of the Center findings to adult SLE as well as other SAD scenarios will be pursued, particularly in the context of the ACE Collaborative efforts. The Drukier Institute for Children’s Health Research at Weill Cornell Medicine has gathered a multidisciplinary team of pediatric basic and patient-oriented investigators with expertise in immunology, autoimmunity, cancer biology, molecular biology, and bioinformatics. This team works alongside clinical experts in autoimmunity, cancer, allergy and infectious diseases—bench-to-bedside and back—to understand and treat these diseases. The Institute and current WCM ACE investigators have also established strong local, national and international collaborations, many of whom are part of the larger ACE community. Dr. Pascual’s team has a long history of productive research in the fields of human autoinflammatory and autoimmune diseases. Dr. Lyden’s group has pioneered the study of exosomes and exomeres and how these particles horizontally transfer their cargo to recipient cells, thereby acting as vehicles of intercellular communication in both physiological and pathological conditions. The proposed Center is a natural result of the very complementary expertise of these groups and is well-poised to work collaboratively to advance clinical and basic discoveries in the field of human autoimmunity. .

Narrative OVERALL; PD – Pascual, V. A major problem in the field of human autoimmunity is the diversity of clinical manifestations and pathways leading to disease. The ACE at Weill Cornell Medicine aims to 1) better understand pathways and mechanisms that contribute to development and amplification of Human Systemic Autoimmune Diseases, 2) develop tools and identify biomarkers to monitor these pathways in patients, and 3) share expertise with colleagues across all basic and clinical ACE Programs.The proposed Center will employ state-of-the-art technologies to gain insight into how two major and complementary compartments contribute to systemic disease: Immune cells and extra- cellular nanoparticles that can modulate the function of cells that uptake them.