Our current research projects include:
1. Targeting inflammatory pathways known to be upregulated in kidney disease.
These studies are done in conjunction with ADALTA, an Australian Biotech company, using patented shark antibodies. They have been highly promising in preventing the development and treating established chronic kidney disease due to a variety of causes. A PhD student (Q Cao) and two post-doctoral researchers (XM Chen and C Huang) work on this project and we hope that our initial results will help take the compounds forward to the next stage of clinical trial.
2. Limiting kidney scarring in models of transplantation to ensure longevity of transplant kidney function.
These studies are done in collaboration with Pharmaxis, an Australian biotech company, and with the support of a generous donor. The experiments aim to test whether inhibiting the assembly of collagen fibres that form scar tissue can reduce the development of scarring after a kidney transplant. Drugs used to prevent rejection can have the adverse effect of causing kidney scarring. The experiments currently underway will determine whether new compounds developed by Pharmaxis and shown by our group to limit scarring in models of diabetes will limit transplant glomerulopathy. This is the most common cause of kidney failure after transplantation. If positive these studies will move to clinical trial. The studies are supported by early and more established post-doctoral scientists (Dr Nguyen and A/Prof Saad)
3. Non-invasive determination of patients at risk of progressive diabetic/non-diabetic kidney disease.
We recognise that only 30-40 per cent of patients with diabetes develop renal failure. This project studies the characteristics of kidney cells excreted into the urine of patients with diabetes and no kidney disease, stable or progressive kidney disease. It aims to determine whether specific characteristics detected by advanced microscopy techniques will avoid the need for renal biopsy and identify patients very early who are at risk of progressive kidney disease. The study is done in collaboration with the University of Sydney and UNSW with the support of the MAST and EMORGO Foundations. It is conducted by established and emerging researchers (A/Prof Saad, Dr Wong, Dr Nguyen)
4. Prevention of chronic kidney disease though limiting transmission of maternal to foetal risk of chronic kidney disease
Studies primarily undertaken by Dr Sarah Glastras and A/Prof Saad have demonstrated that maternal obesity and smoking lead to an increased risk of chronic kidney disease to the offspring. Studies are currently being undertaken to determine whether mothers taking a low dose of blood pressure lowering medication, currently used safely in pregnancy, will lower this risk. Validation of the changes in gene expression caused by obesity occur in both experimental models and obese people. Whether changes in gene expression persist in patients with diabetic kidney disease will be tested in large data bases accessible to Prof Pollock. These studies are partly supported by the EMORGO Foundation and also by PhD students Drs B Larkin and N Rodriguez.
5. Fibre supplements to improve glycaemic control and reduce chronic kidney disease
We hypothesise that fibre supplements may directly lower the blood glucose but secondarily modify the gut microbiome to increase short chain fatty acids that induce hormonal changes to decrease blood sugar levels and directly improve kidney function. These studies are undertaken by A/Prof Saad and PhD student A Zaky.
6. Metformin to reduce renal pathology
Metformin has long been used for glycaemic control. However, it is only recently recognised that it may have an independent effect in protecting the kidney. These studies are being undertaken by A/Prof Chen, Dr Huang and PhD student Hao Li.
7. Normalising the function of the mitochondria in progressive chronic kidney disease
Dr Huang has demonstrated that impaired function of the mitochondria contributes to the development of diabetic kidney disease. She has been primarily responsible for developing a collaboration between the USA based biotech Mitokinin to assess mitochondrial therapeutics in chronic kidney disease.
8. Development of therapeutics against promising targets in chronic kidney disease
Dr Shi demonstrated in her recently completed PhD, the receptor-interacting protein Kinase -3 was key in the development of progressive kidney disease (in diabetic and non-diabetic models). However, inhibiting receptor-interacting protein Kinase -3 is challenging. A/Prof Chen and Dr Shi have formed a collaboration with a small Australian biotech, Phylogica, and the Murdoch Institute to develop targeted gene therapy and new delivery systems to ensure the culprit genes are “turned off” in the kidney.
9. Targeting non-coding RNA to limit diabetic kidney disease
Non-coding RNA was until recently thought of as “junk”. We now recognise that although it doesn’t code for proteins, it significantly regulates the genes that do code for protein and hence can affect the development of kidney disease. A/Prof Panchapakesan has demonstrated that novel areas of long non-coding RNA affect genes that regulate the structure and function of kidney cells and hence targeting with gene therapy may prove fruitful.
10. The role of cilia in the development of non-cystic progressive kidney disease
The primary cilia on kidney cells are finger-like projections that serve as "antennae" to transmit abnormal signals in the flow and composition of the urine to influence kidney cell responses. These abnormalities occur in chronic kidney disease and lead to scarring and kidney failure. This proposal aims to investigate an important ciliary component called c2cd3 as a therapeutic target.
11. Diabetic kidney disease-early detection and potential treatment
Some patients progress to advanced chronic kidney disease and end stage kidney disease while others with seemingly similar clinical circumstances remain stable. Hence, new markers for early diagnosis and chronic kidney disease progression are critically needed. Using an animal model which reflects human disease, we have recently identified new potential markers for diabetic kidney disease progression. During this project we will confirm if those genes predict progressive kidney disease in a cross-sectional study of patients with T2D and advanced chronic kidney disease compared to T2D patients without chronic kidney disease. We have access to those samples from two recently completed clinical trials. Hence, the project will determine possible biomarkers to identify patients at risk of chronic kidney disease progression before the development of disease for early intervention. This will have a great impact on the diabetic population in Australia and worldwide.