Personal profile

Biography

Dr. O'Sullivan is the head of the Translational Kidney Therapies Group within the Centre for Inflammatory Diseases (CID) based at the Monash Health Translational Precinct. Kim completed her undergraduate studies and Master’s Degree in Anatomy and Structural Biology at the University of Otago, New Zealand. In 2002 Kim joined the Autoimmune Kidney Disease and Vasculitis Research Group and completed a staff PhD in Immunology under the supervision of Prof. Stephen Holdsworth and Prof. Richard Kitching-world leaders in the study of glomerulonephritis and immune mediated kidney diseases. Since completion of a PhD Kim has obtained competitive funding from the National Health and Medical Research Council (2x NHMRC Ideas Grant as CIA and CIB) a Medical Research Future Fund grant (MRFF, as a CI) and Industry funding. 

Research Interests:

Kims main research is centred around finding new therapies for autoimmune diseases. In particular: Anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), a rare disease characterized by inflammation of the small blood vessels. In particular the delicate network of capillaries in the kidney are susceptible to injury. If left untreated this can develop into glomerulonephritis (GN) a major cause of kidney disease. AAV is a debilitating autoimmune disease of unknown etiology, current treatment has multiple side effects and 30% of patients relapse and become dialysis dependent within 3 years. Patients are left severely immunocompromised and at risk of death from infection in the first year of diagnosis. They also often fail to sustain remission. While treatments have reduced AAV from an acute life-threatening illness to one of a chronic disease, patients still experience multiple relapses and side effects from long term immunosuppression. There is a significant need for new therapies with fewer side effects. Kim's main research area is investigating the pro-inflammatory role of Neutrophil Extracellular Traps (NETs) in MPO-ANCA vasculitis with a particular focus on looking for potential therapeutics which will prevent NET formation and ameliorate disease-without compromising host defence.  In addition to this work Kim has great interest in the role of the gut microbiome and how it may be harnessed to reduce inflammation in autoimmune diseases.

Research programmes going on in the lab at the moment are:

1. Characterizing therapeutics that inhibit neutrophil extracellular traps (NETs) without diminishing host defence mechanisms

Current treatment for autoimmune kidney diseases consists of therapies which render patients severly immunocompromised. This arm of our research involves testing therapeutics that target different pathways that lead to NET formation. Importanly once these therapeutics are determined to be efficacious at preventing the development of NET driven pathogenesis in the kidney we aim to test them in common models of infection to see if treatment renders the host more susceptible to infection.

2. Adeno associated viral vector gene therapy for treatment of autoimmune kidney diseases

Autoimmune kidney diseases, particularly lupus nephritis and ANCA associated vasculitis are associated with low expression of DNase I a critical enzyme for degrading Extracellular DNA released from pro inflammatory cell death. Administration of exogenous DNase I can therapeutically treat ANCA associated vasculitis in animal models- however it has a short half life and requires twice daily treatment intravenously a cumbersome form of treatment for patients. We are using gene therapy targeting the liver so we can use one shot of an adeno associated viral vector that enable hepatocytes from the liver to release super physiological amounts of DNase I overcoming the short half life. 

3. Bugs as drugs: Bacterial exosomes for therapeutic immunododulation of autoimmune kidney diseases

Exosomes are secreted by most cells and have untapped immunomodulatory activity. Cell therapy can be toxic and generate a lower degree of therapeutic efficacy. Exosomes due to their small size offer an alternative with less associated toxicity. Harnessing exosomes to deliver treatment has great potential as a new therapeutic. In particular bacterial Exosomes from gut bacteria can be used to modulate NFkB a key transcription factor in initiating inflammatory pathways. It is becoming increasingly apparent that host-gut interactions have a critical role in maintaining self tolerance. Exosomes from bacteria can promote immune tolerance, in particular secretion of IL-10 from PBMCs, inducing T regulatory cells, and tolerogenic dendritic cells. This project aims to use bacterial Exosomes to induce tolerance in animal models of ANCA associated vasculitis, anti GBM disease and Lupus nephritis all diseases with suboptimal treatment options

4. Bugs as drugs: Harnessing the gut microbiome to improve treatment for autoimmune vasculitis

The gut microbiome is a critical factor influencing immune homeostasis and inflammatory diseases. Reduced microbial diversity in the gut has been associated with the increasing prevalence of autoimmune diseases. Notably, the family Muribaculaceae has declined within the human microbiome in the industrialised world, and studies have linked its reduced abundance to disease.  We are investigating the role of the declining Muribaculaceae family in ANCA-associated vasculitis. We are using dietary supplementation with resistant starch (RS) a fermentable substrate for gut bacteria to enhance the growth of short chain fatty acid (SCFA) producing bacteria (including Muribaculaceae), and using oral administration of anti-inflammatory SCFAs acetate, propionate and butyrate to mitigate neutrophil activation and ameliorate kidney inflammation in ANCA vasculitis. 

Student supervision: Kim is taking enquiries for Honours and PhD Projects for 2023/2024 on the role of neutrophil extracellular traps in perpetuating inflammation in vasculitis, gene therapy to release therapeutic levels fof DNase I, Bugs as Drugs investigating the therapeutic role of the gut microbiome to alleviate inflammation in autoimmune diseases.

Service to the scientific community: In 2020/2021 Kim served as the chair of the ImmuMON committee responsible for organising a symposia to highlight the research from ECR and Mid-Career researchers across departments/schools with an Immunology theme at Monash. Nationally Kim is on the Australian Society for Immunology Day of Immunology Committee, an event to communicate immunological concepts to the general public. Locally, Kim is the convenor of the Centre for Inflammatory Diseases weekly seminar series, which involves inviting guest speakers and local researchers to present their research.

Kim is a passionate supporter of women in STEM, she is a brainstem mentor for year 9 high school students and a member of the Australian and New Zealand Society of Nephrology's Equity, Diversity and Inclusion Committee.

Kim serves as a Review Editor for Frontiers Immunology and serves an editorial board member for the International Journal of Molecular Sciences and the Journal of Integrated Medicine in Nephrology and Andrology.

Kim is a member of the Australian Society of Immunology, the Australian and New Zealand Society of Nephrology, the Society of Leukocyte Biology, and the American Society of Nephrology. Her expertise in pathology and immunology is evident in her invited participation in peer review for the Journals: Journal of Clinical Investigation (JCI), Journal of Clinical Investigation Insight, (JCI Insight) Frontiers Immunology, Nephrology, Xenotransplantation, Pathology, Clinical and Experimental Immunology, Kidney International, and the Journal of Immunology and Cell Biology.

 

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Education/Academic qualification

Immunology, PhD, Defining novel targets and biological interventions in human and experimental glomerulonephritis, MONASH UNIVERSITY

External positions

Review Editor, Frontiers in Immunology

Editorial Board Member, Integrative Medicine in Nephrology and Andrology

Editorial Board Member, International Journal of Molecular Sciences

Research area keywords

  • Neutrophil Extracellular Traps
  • ANCA Vasculitis
  • Autoimmunity
  • Kidney Disease
  • Neutrophils
  • Inflammatory disease
  • Macrophage extracellular traps
  • Gender Equity
  • Glomerulonephritis
  • Lung Disease

Collaborations and top research areas from the last five years

Recent external collaboration on country/territory level. Dive into details by clicking on the dots or