Kantharidis research group
Key terms: diabetic complications, nephropathy, atherosclerosis, microRNA, biomarkers, fibrosis
To understand the interplay between genetic, fibrotic and inflammatory factors in diabetes that contribute to diabetic complications.
2019 group L-R: Dr Madhura Bose, Dr Phillip Kantharidis, Mr Muthu Mohan.
To understand the interplay between genetic, fibrotic and inflammatory factors that contribute to development of diabetic complications, in particular diabetic kidney disease and atherosclerosis.
Diabetes is the leading cause of kidney disease with one-third of people with diabetes developing this disease, which in most case will progress to renal failure. People with diabetes and kidney disease have a much higher risk of developing cardiovascular disease as well. The main focus of our group has been on understanding the various factors contributing to the development of progression of these complications of diabetes.
Our research is focused on understanding the role of a number of cytokines, growth factors and chronic low grade inflammation that drive the development of diabetic complications. Our laboratory has demonstrated that several cytokines and growth factors are elevated in diabetes and this results in dysregulation of certain microRNA, which are important regulators of fibrotic and inflammatory pathways in the kidney and the aorta. Targeting of these factors and microRNA directly has remained difficult due to their normal physiological roles.
More recently, we have made an exciting discovery in that a family of small endogenous molecules known as “resolvins” are able to attenuate the pathological signaling in diabetes by dampening the signaling through both inflammatory and fibrotic pathways in tissues where complications occur. We have demonstrated that not only do resolvins protect against the development of kidney disease and atherosclerosis, but are also effective when used against pre-existing disease, appearing to reverse pathological processes. We are currently testing a number of resolvin analogues as novel treatments against diabetic kidney disease and atherosclerosis, with a focus on how they act on signaling pathways using both RNA-sequencing and proteomic profiling approaches.
Dr Phillip Kantharidis is a Senior Research Fellow in the Department of Diabetes. His main research focus is the identification of novel treatments to protect diabetic patients from micro and macrovascular complications. He is a molecular biologist who has worked for 10 years in the field of diabetic nephropathy publishing findings which have advanced our understanding of the important role of microRNAs in diabetic complications. He is interested is adapting his recent exciting results to the clinical setting.
Projects and Opportunities
Honours, Masters and PhD research projects are available in the laboratory. Please contact us to discuss the details of the projects and to see how they fit in your specific interests. Please refer to the following general description of our current projects.
Current project funding
- 2017-19 NHMRC project grant (APP1122176, Cooper ME, Kantharidis P) A novel endogenous inhibitor for the treatment of diabetic nephropathy.
- 2019-22 NHMRC project grant (APP1159460, Jandeleit-Dahm K, Kantharidis P, Godson C) Lipoxins protect against diabetes associated atherosclerosis.
Pubmed link [Kantharidis P]
- Hagiwara S, Sourris K, Ziemann M, Tieqiao W, Mohan M, McClelland AD, Brennan E, Forbes J, Coughlan M, Harcourt B, Penfold S, Wang B, Higgins G, Pickering R, El-Osta A, Thomas MC, Cooper ME, Kantharidis P: RAGE Deletion Confers Renoprotection by Reducing Responsiveness to Transforming Growth Factor-beta and Increasing Resistance to Apoptosis. Diabetes 2018;67:960-973
- Brennan EP, Mohan M, McClelland A, Tikellis C, Ziemann M, Kaspi A, Gray SP, Pickering R, Tan SM, Ali-Shah ST, Guiry PJ, El-Osta A, Jandeleit-Dahm K, Cooper ME, Godson C, Kantharidis P: Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease. J Am Soc Nephrol 2018;29:1437-1448
- Brennan EP, Mohan M, McClelland A, de Gaetano M, Tikellis C, Marai M, Crean D, Dai A, Beuscart O, Derouiche S, Gray SP, Pickering R, Tan SM, Godson-Treacy M, Sheehan S, Dowdall JF, Barry M, Belton O, Ali-Shah ST, Guiry PJ, Jandeleit-Dahm K, Cooper ME, Godson C, Kantharidis P: Lipoxins Protect Against Inflammation in Diabetes-Associated Atherosclerosis. Diabetes 2018;67:2657-2667
- Brennan E, Wang B, McClelland A, Mohan M, Marai M, Beuscart O, Derouiche S, Gray S, Pickering R, Tikellis C, de Gaetano M, Barry M, Belton O, Ali-Shah ST, Guiry P, Jandeleit-Dahm KAM, Cooper ME, Godson C, Kantharidis P: Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis. Diabetes 2017;66:2266-2277
- McClelland AD, Herman-Edelstein M, Komers R, Jha JC, Winbanks CE, Hagiwara S, Gregorevic P, Kantharidis P, Cooper ME: miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7. Clin Sci (Lond) 2015;129:1237-1249
- Wang B, Jha JC, Hagiwara S, McClelland AD, Jandeleit-Dahm K, Thomas MC, Cooper ME, Kantharidis P: Transforming growth factor-beta1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b. Kidney Int 2014;85:352-361