Researchers at Monash University are investigating a novel approach to treating urinary tract infections (UTIs), focusing on the role of type 2 immunity in the bladder. The project, led by Dr. Malcolm Starkey, aims to identify potential new therapies for persistent and recurrent UTIs, a growing concern due to increasing antimicrobial resistance.
UTIs are a common indication for antibiotic treatment, but recurrence is a significant problem, hindering the establishment of effective non-antibiotic strategies. Dr. Starkey’s team, based in the Department of Immunology at the School of Translational Medicine, is studying how the bladder responds to bacterial pathogens, specifically examining the function of group 2 innate lymphoid cells (ILC2s).
The bladder, often overlooked in immunological research, possesses a unique mucosal environment. When exposed to bacteria, the bladder sheds epithelial cells as a defense mechanism. Maintaining the integrity of the bladder epithelium is crucial, as insufficient repair can lead to infection, while an exaggerated response can cause tissue remodeling and fibrosis. The research seeks to understand how ILC2s regulate this epithelial barrier function.
The team will utilize ILC2-deficient mice to determine the functional role of these immune cells during both normal bladder function and in response to uropathogenic E. Coli infection. Advanced imaging techniques, including 3-dimensional confocal imaging of optically transparent tissue and high-parameter flow cytometry, will be employed to pinpoint the location and activity of these immune cells within the bladder. RNA sequencing will be used to analyze the unique genetic profile of ILC2s in the urinary tract.
Dr. Starkey’s research extends beyond basic science, with a focus on translating findings into clinical applications. The project will explore the possibility of repurposing existing or emerging type 2 immunotherapies as a new treatment option for chronic UTIs. Dr. Starkey is also the Founding Director of the Bladder and Kidney Health Discovery Program, a multidisciplinary platform dedicated to developing new treatments and diagnostics for urinary tract conditions.
Dr. Starkey’s team also investigates rare genetic causes of kidney stone formation and how microbial challenges can predispose individuals to chronic diseases. He serves as a lead scientific advisor to Chronic UTI Australia and maintains connections with the Urinary Tract Infection Global Alliance and Travere Therapeutics. His research group is currently accepting PhD students for projects focused on urinary tract infection, mucosal immunity, and the interplay between the brain, bladder, and immune system.
The Monash Biomedicine Discovery Institute, where Dr. Starkey’s research is based, emphasizes systems immunology, integrating genomic, biochemical, and metabolic technologies to study immune responses to infection, autoimmunity, and cancer.
