EUniWell Open Lecture Series: Inflammation - An old flame to understand chronic metabolic and neurodegenerative diseases
Lecturer: Prof. Pablo Pelegrín
Related EUniWell Arena: 1) Health and Well-being
About this lecture:
Inflammatory diseases affect over 80 million people worldwide and accompany many diseases in industrialised countries, the majority of them infection-free conditions. We now know that innate immunity is the primary coordinator and driver of inflammation through the secretion of cytokines and other signalling proteins upon innate immune cell activation by pathogen-associated molecular patterns. The activation of purinergic P2X7 receptors in immune cells by extracellular ATP is a novel and increasingly validated “sterile” pathway to initiate inflammation. P2X7 receptor induces the activation of the NLRP3 inflammasome and caspase-1, leading to the unconventional release of IL-1β via plasma membrane permeabilization. In the last years, we have gained substantial insights into the release of IL-1β, and other cytosolic proteins through the formation of gasdermin D pores on the plasma membrane and the execution of a specific type of inflammatory cell death called pyroptosis. Extracellular ATP, the physiological P2X7 receptor agonist, is a crucial danger signal released by stressed or injured cells and one of the most important mediators of infection-free inflammation. We have recently translated this knowledge to human clinical pathology, where developing selective NLRP3 antagonists with a suitable clinical profile increases the therapeutic window to treat inflammatory, metabolic and degenerative diseases.
About the lecturer:
Dr. Pelegrín is a Researcher at the University of Murcia and the Biomedical Research Institute of Murcia (Spain). Dr. Pelegrín obtained his Ph.D. in 2003 in the field of comparative immunology, studying IL-1 cytokine in different fish species at the University of Murcia. Then Dr. Pelegrín moved to Prof. Surprenant’s lab at the University of Sheffield (Sheffield, UK) for a postdoc funded by AstraZeneca. There he specialised in P2X7 and purinergic signalling in innate immune cells. Then in 2007, he moved for a second postdoc at the University of Manchester (Manchester, UK), where he studied inflammasome regulation in response to danger signals. Then, in 2009, he established his independent lab focused on regulating the inflammasome in disease. He leads the Molecular Inflammation research group with two young PIs, two postdocs, 5 Ph.D. students, and two technicians. Dr. Pelegrín with an h index of 50 (Scopus), is the author of over 130 publications in leading top journals such as Immunity, Nature Immunology, EMBO J, Nature Communications or Nature Chemical Biology, some of them considered “classic” papers with over 8,000 citations. He has received funding from ERC at Consolidator and Proof of Concept programmes and the H2020 programme.
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