Redox Biology Lab

About us

The Redox Biology Laboratory aims to understand how fundamental biochemical events called reduction and oxidation (redox) reactions control cardiovascular and immune cell function and how dysfunction of these redox processes contribute to cardiovascular and immune-based diseases.  The lab focusses on two major research areas of relevance to redox biology and disease: 
 

1. Oxidative stress and cardiovascular disease


Myeloperoxidase, oxidative stress and cardiovascular disease
This project aims to define how oxidative stress promotes cardiovascular disease. At present we focus on understanding the oxidative mechanisms by which the leukocyte-derived heme enzyme myeloperoxidase (MPO) promotes endothelial dysfunction and drives arterial disease states including atherosclerosis and aortic aneurysm. We are also testing new classes of therapeutic agents for their ability to combat MPO-catalysed oxidative reactions and prevent inflammatory cardiovascular disease. 

Redox control of endothelial cell phenotype
Redox reactions represent important transducers of cell signalling pathways. This project studies how the production of redox-active signalling species by different intracellular enzymatic sources control cell signalling pathways to alter endothelial cell function and phenotype. Currently we are studying how redox reactions in the mitochondria control intracellular calcium signalling to promote the phenotypic modulation of endothelial cells into pro-inflammatory mesenchymal cells via a process called endothelial-to-mesenchymal transition (EndMT).

 

2. Roles and Regulation of the immune regulatory enzyme Indoleamine 2, 3-Dioxygenase


Indoleamine 2, 3-dioxygenase (IDO) is an intracellular heme enzyme that catalyses the catabolism of L-tryptophan (L-Trp). IDO represents a central immune regulatory enzyme. Thus, expression of IDO in professional antigen presenting cellsinhibits T cell activation to promote immune suppression and tolerance during inflammation, transplantation, auto-immunity and cancer. 

IDO and Vascular Disease
Atherosclerosis and aortic aneurysm are a chronic inflammatory diseases of the artery in which T cell-mediated immune reactions play an important role. We are currently testing if selectively upregulating IDO activityin antigen presenting cells inhibits arterial disease by limiting T cell activation and cardiovascular inflammation. We are also examining a potential link between IDO, gut microbiome dysbiosis and cardiovascular disease.

 

IDO and Viral Infection

Increased IDO expression is a feature of viral infection where it can exhibit anti-microbial or immune regulatory functions. With Prof. Nicholas King at the University of Sydney we are studying the role of IDO in coordinating immune responses during influenza, West Nile virus and dengue infection.    

Biochemical regulation of IDO activity
In light of the important immune regulatory roles of IDO it is important to understand how the enzyme is controlled. Our previous studies were the first to describe post-translational regulation of IDO and our recent data indicate a link between fundamental cellular metabolic processes and IDO activity. This project aims to characterize the post-translational mechanisms and metabolic pathways governing IDO expression/activity and the immune regulatory actions of antigen presenting cells. Identification of how IDO is regulated can facilitate the development of novel drug strategies to modulate immune responses in vivo.

Team

Collaborators

Dr Jacqueline Ku (Post-Doctoral Researcher)

Students

  • Bentotage (Sam) Fernando (Scientia PhD Scholar)
  • Idris Bello (PhD Scholar)
  • Calum Macarthur (Honours Student)