51st BrJAC Webinar скачать в хорошем качестве

51st BrJAC Webinar

Quantitative Approaches to Understand the Role of Zinc Dyshomeostasis on Thrombotic Risk Dr. Alan James Stewart Professor in Molecular Medicine at the School of Medicine, University of St Andrews, Scotland, United Kingdom Abstract: This webinar will explore how zinc speciation, modulated by serum albumin and fatty acids, influences vascular and metabolic health. Using a multidisciplinary approach—spanning structural biology, proteomics, lipidomics, cellular assays, and mathematical modelling—our recent studies reveal that fatty acid binding disrupts albumin’s zinc coordination, enhancing zinc availability and promoting platelet aggregation and dense fibrin clot formation. These effects are particularly pronounced in type 2 diabetes, where elevated non-esterified fatty acid (NEFA) levels exacerbate thrombotic risk. Proteomic and lipidomic analyses following bariatric surgery show systemic improvements, including reduced NEFA concentrations and restored zinc buffering, suggesting a mechanistic link to improved haemostasis. Cellular uptake studies demonstrate that zinc transport is tightly regulated by albumin concentration and fatty acid loading, with implications for endothelial function and zinc toxicity. Structural and biochemical assays further show that zinc modulates the neutralisation of anticoagulant glycosaminoglycans, affecting heparin efficacy. Together, these findings highlight a regulatory axis—zinc, albumin, and fatty acids—that connects metabolic dysfunction to vascular pathology. By integrating molecular, cellular, and systemic data, this work opens new avenues for therapeutic intervention in diabetes, obesity, and cardiovascular disease. Biography Alan James Stewart, BSc (Hons), PhD, FRSB, FRSC, is currently a Reader in Molecular Medicine at School of Medicine, University of St Andrews, St Andrews, Scotland, United Kingdom. Education/Qualifications: PhD in Chemistry, School of Chemistry, University of Edinburgh, Edinburgh, UK (1999-2003). BSc(Hons) in Biochemistry, University of Edinburgh, Edinburgh, UK (1995-1999). Professional history: Senior Lecturer, University of St Andrews (2016-2021); Lecturer, University of St Andrews (2009-2016); MRC Career Development Fellow, Queen’s Medical Research Institute, Edinburgh, Edinburgh, UK (from 2006-2009); Postdoctoral Fellow, Roslin Institute, Midlothian, UK (from 2003-2005). Other Appointments and Affiliations: Deputy Chair and Executive Board Member of Scottish Universities Life Sciences Alliance (SULSA; since 2023). Deputy Chair of the Int. Union of Crystallography (IUCr) Commission on Biol. Macromolecules (since 2023). Tenovus Scotland National Scientific Advisory Committee (since 2023). Honours and Awards: Elected Fellow of the Royal Society of Chemistry (2022); Elected Fellow of the Royal Society of Biology (2020); Guest Professor at Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, China (2017); BBSRC New Investigator Award (2012). Publication summary and metrics (Source: Google Scholar (accessed 2/10/2025): Total publications: 105; Citations: 7,092; h-index: 42; i10-index: 82.