Starkey - Urinary Tract Immunology
Mucosal cytokines, innate lymphoid cells, urinary tract infection, cystinuria, kidney stone disease, kidney disease
The Urinary Tract Immunology research group studies the immune mechanisms of organ repair and regeneration with a recent focus on the urinary tract. Our team is particularly interested in the early-life infectious origins of chronic diseases and the role of tissue resident immune cells and mucosal cytokines. We employ a range of cutting-edge experimental models and tools to answer fundamental immunological questions for translational outcomes in human diseases.
Starkey group L-R: , Dr Jennifer Ngo, Dr Bernadette Jones-Freeman, Dr Malcolm Starkey, Mr Nirmal Bhatt, Ms Kate Leyden, Ms Theresa Nguyen
A/Prof Aniruddh Deshpande
Dr Bernadette Jones-Freeman
Dr Jennifer Ngo
Mr Gabriel Rodriguez
Mr Nirmal Bhatt
Department of Immunology and Pathology
Level 6, 89 Commercial Road
Melbourne Victoria 3004
Research projects available
Repurposing of immunotherapies for severe urinary tract infection and associated renal complications
Urinary tract infections are a common cause of bacterial infection, especially in females. These infections are often chronic and can cause long-term damage to the urinary tract, especially when they occur in children. In some cases, the bacteria can ascend to the kidney and cause kidney scarring, a key precursor to the development of chronic kidney disease, which predisposes to systemic health complications including cardiovascular disease and diabetes. The most common cause of urinary tract infection is uropathogenic Escherichia coli, which accounts for >80% of infections. Importantly, this pathogen is becoming increasingly resistant to existing antibiotic therapies. Therefore, there is an unmet need for alternative strategies to treat these infections and prevent deleterious sequela in susceptible individuals. Our approach involves targeting the host immune system rather than the bacteria, which we propose will reduce the burden of the bacterial infection and limit the severity of the associated renal complications. Our idea is to target the immune cytokine interleukin-22 (IL-22), which is known to protect against bacterial infections at other mucosal sites and to regenerate damaged tissue in other organs. However, its function during urinary tract infection is unknown. We have established a complete toolbox of genetically modified mice, in vivo models, techniques, human patients and analysis platforms to enable us to determine the role of IL-22 in urinary tract infection and associated renal complications. We aim to use these established tools to provide crucial evidence for the re-purposing of emerging immunotherapies that target IL-22 that have been developed for other diseases. This is likely to provide a much-needed alternative therapy to antibiotics to combat the bacterial resistance in urinary tract infections, promote tissue repair to limit the severity of renal complications and reduce the likelihood of progression to chronic kidney disease.
Harnessing the immune system for organ repair in kidney stone diseases
Kidney stones are a common urinary tract problem that disproportionally affects men. Stones can cause obstructions in the urinary system and are a significant risk factor for development of chronic kidney disease later in life. Current treatments for stones focus on removal of the stones, often with multiple invasive procedures. There is a lack in understanding of the reasons why stones reoccur and the reasons why individuals with stones are at increased risk of developing chronic disease. Therefore, there is a clear need for novel approaches to prevent stone recurrence and their deleterious consequences. Our immune system is known to be pivotal in controlling the severity of inflammation and in regulating the repair of our organ systems after insults such as stone formation or infection. However, as our understanding of the immune system grows and becomes more complex, new cells are identified that may hold the key to understanding the “switch” that controls whether an insult is appropriately dealt with or not, and whether the affected organ system is appropriately repaired. Incomplete repair may lead reoccurring stones and chronic disease. This project aims to improve our understanding of how our immune system protects against stone recurrence and its role in preventing long-term consequences such as impaired kidney function.