Trained immunity and childhood risk factors of cardiovascular and metabolic disease

Inflammatory Origins, Murdoch Children’s Research Institute, Royal Children’s Hospital, and Department of Paediatrics, University of Melbourne, Parkville, Australia

 

Research topic

 

We apply a range of epidemiological, clinical and immunological techniques to a unique collection of longitudinal human cohorts and clinical trials in order to understand the relationship between environmental exposures and molecular mediators in modifying the risk of cardiovascular and metabolic risk and disease. We have several exposures of interest, including exposures in pregnancy, childhood infections and antibiotic use, childhood obesity, chronic inflammatory conditions, as well as Kawasaki disease, cystic fibrosis and dental health. Two projects in which we study trained immunity specifically are detailed below.

Trained immunity in childhood obesity

The prevalence of obesity in young children has increased markedly in the last 20 years and childhood obesity is robustly associated with an increased risk for metabolic and cardiovascular disease in adulthood. We are currently investigating the inflammatory phenotype of human monocytes and NK-cells as well as performing cardiovascular measurements in the COBRA cohort, a large cohort of obese children. In collaboration with the group of Professor Richard Saffery, we will study not only phenotypical but also transcriptomic and epigenetic changes in PBMCs from these children in comparison with healthy children to understand the mechanisms of obesity, inflammation and the subsequent cardiovascular risk.

Trained immunity in childhood infections

Inflammation is central to atherosclerosis pathogenesis and infections are a major inflammatory stimulus, especially in children. There are considerable epidemiological, clinical and animal data that infections increase CVD risk and events. Clinical translation of these observations into effective prevention and interventions requires an understanding of which infections are most deleterious and the biological mechanisms by which infections increase CVD risk.

In two major human cohort studies, we aim to investigate how common, well-characterised inflammation/infections in pregnancy and childhood impact on changes in the immune phenotype with subsequent increased CVD. (1) In the VASCFIND (VAascular Changes Following Infectious Diseases) study, the macro- and microvasculature will be analysed for preclinical vascular phenotypes at 2 weeks, 2 months and 6 months following well-defined severe infection presenting to hospital. We will also study the phenotype of monocytes and NK-cells and study whether severe infections induce a TRIM phenotype associated with adverse CV phenotypes. (2) In collaboration with A/Prof Jeff Craig and Prof Richard Saffery, we also study samples from the PETS (twin) cohort and PIES (preterm) cohort, two longitudinal cohorts studying inflammation during pregnancy  and how this could contribute to the early development of atherosclerosis by activating early immune responses.

 

Group leaders

David Burgner, PhD, Professor and Group Leader

 

Group members

  • Jessica Miller, PhD, Postdoctoral Fellow
  • Mihiri Silva, PhD, Postdoctoral Fellow
  • Siroon Bekkering, PhD, Postdoctoral Fellow
  • Christoph Saner, Paediatrician and PhD student
  • Tom Saunders, Paediatrician and PhD student
  • Cerys Chau, Honours Student
  • Meg Kaegi, Research Assistant
  • Peter Vuillermin, Professor of Paediatrics and Researcher

 

Selected publications

 

Funding

  • NHMRC GTN1064629 (research fellowship)
  • NHMRC GTN1065494 (project grant)
  • NHMRC GTN1164212 (project grant)
  • NHMRC GTN1149047 (project grant)
  • NHMRC GTN1109355 (project grant)
  • National Blood Authority, (Australia) (project grant)
  • Royal Children’s Hospital Foundation
  • DHB Trustees
  • Jam and Jelly Foundation

We welcome enquiries from prospective postgraduate students and post docs.

Please email david.burgner@mcri.edu.au

David Burgner