Dr Kim O’Sullivan is a Research Fellow in the Autoimmune Kidney Disease and Vasculitis Research Group at Monash University. Kim has authored/co-authored 37 publications with >1000 citations in the top tier Renal Journals (JASN, KI, and AJRP) as well as top tier general Journals (Nature Communications, PNAS, Blood). Kim’s main research area is investigating the pro-inflammatory role of Neutrophil Extracellular Traps (NETs) in anti-neutrophil cytoplasmic antibody vasculitis (AAV), with a particular focus on looking for potential therapeutics which will prevent NET formation and ameliorate disease. Current research is concentrated on modulating the function of neutrophils to keep their phagocytotic function whilst preventing injurious NET formation.
Kim authored the first description of Macrophage Extracellular Traps (METs) in human AAV (Kidney International 2015), and has co-authored several papers on the role of METs in Lung disease. Kim utilizes advanced confocal microscopy and image analysis using advanced machine learning to identify kidney immune cells implicated in the pathogenesis of AAV. In 2016 she won the prestigious Young Investigator Basic Science award at the Annual ANZSN scientific meeting for her work on NETs in AAV. Kim currently leads the NET research programme in the Autoimmune Kidney Disease and Vasculitis research group at Monash.
Compelling experimental evidence demonstrates neutrophils are pathogenic in anti-neutrophil cytoplasmic antibody vasculitis (AAV). The primary function of neutrophils is to eliminate bacteria through: degranulation, phagocytosis and the formation of neutrophil extracellular traps (NETs). In the context of AAV erroneous activation of neutrophils results in the extracellular deposition of the key antigenic molecules myeloperoxidase (MPO) and proteinase 3 (PR3).
Current therapy for AAV renders patients severely immunocompromised. There is an unmet need for new specific therapies for AAV. Therapeutically targeting neutrophils is a delicate balancing act between maintaining neutrophil function for host defence whilst preventing the injurious expulsion of inflammatory mediators. Recent discoveries indicate that targeting neutrophil activation (C5a, C5aR, ANCA) neutrophil enzymes (MPO, PR3, NE) or neutrophil cell death (NETs, Necroptosis) may provide potential new therapies. NET formation is of particular interest therapeutically as NETs eject highly injurious molecules including enzymes: peptidyl arginine deiminase 4 (PAD4), Neutrophil Elastase (NE), MPO, reactive oxygen species (ROS), and pro-inflammatory DNA/ mitochondrial (mt) DNA fragments. Inhibition of molecules required for NET formation have the potential to prevent the release of inflammatory mediators but also keep intact phagocytotic function of neutrophils. Unlike conventional treatment these therapies are also able to be withdrawn immediately if the patient is compromised by infection. Hence, blockade or inhibition of NETs will prevent extracellular deposition of a number of known autoantigens critical in the perpetuation of inflammation in AAV but also in other chronic and debilitating autoimmune conditions.