CID seminar: Linking red cell disorders to immune dysregulation, 15 May

15 May, 12-1pm, seminar room 1, TRF

Presented by Dr Jim Vadolas, Hudson Institute of Medical Research

The β-haemoglobin disorders such β-thalassaemia, haemoglobin E (HbE), and sickle cell disease are the most prevalent inherited disorders worldwide. It is estimated that at least 300,000 children affected by these conditions are born annually, leading to a global patient population numbering in the tens of millions. Caused by mutations in the b‑globin gene, β‑haemoglobinopathies exhibit extreme clinical heterogeneity, ranging from nearly asymptomatic to life threatening, thus complicating patient management and treatment.

One feature of these conditions is the increased frequency of infectious complications such as pneumonia and sepsis, which are significantly associated with an increased rate of morbidity and mortality, particularly in developing countries. The increased susceptibility to pathogenic organisms has been attributed to multiple deficiencies affecting both innate and adaptive immune systems. What has become evident, is that iron overload may direct defective neutrophil effector functions resulting in increased susceptibility to infection and inflammation-related organ damage. This knowledge, combined with the emergence of novel immunomodulatory function and phenotypes for neutrophils has help to re-invigorate interest in the field. Understanding, and targeting the mechanisms that regulate these functions may provide therapeutic benefits to b‑haemoglobinopathy patients.

Jim Vadolas received his PhD from the University of Melbourne, Department of Microbiology and Immunology, researching in DNA vaccine technologies. In 1999, Jim undertook postdoctoral studies at the Murdoch Children’s Research Institute where he acquired expertise in genetic and molecular technique utilising bacterial artificial chromosome (BACs) and homologous recombination systems. In 2005, Dr Vadolas became group leader of the Cell and Gene Therapy group primarily interested in the development of novel therapeutic strategies for β-thalassaemia and related β-haemoglobinopathies. There he established several unique cell-based assay systems and clinically relevant animal models of β-thalassaemia.  These innovations enabled investigations that provided important insights into the epigenetic mechanism(s) involved in globin gene regulation throughout development and disease. A major aspect of his research is the development and evaluation of genetic-based approaches involving lentiviral gene therapy and genome editing. More recently, his expertise in β‑haemoglobinopathies enabled his group to establish a new research program investigating aberrant innate immune responses in β‑thalassaemia. In 2017, Jim relocated his research program to the Hudson Institute of Medical Research, Immunohaematology Group at the Centre for Cancer Research.