About Dr Xin-Ming Chen

Diabetic nephropathy is a leading cause of end-stage renal failure, accounting for 35-40% of all new cases requiring dialysis therapy or kidney transplantation throughout the world and diabetes mellitus is predicted to afflict up to 25% of the older population in western countries, representing a significant burden on the health system. It is increasingly being recognized that the burden of diabetic nephropathy is not limited to its implications on demands for organ transplantation, but has a major impact on the health of the overall population. Indeed, patients with reduced kidney function represent a population not only at risk for progression of kidney disease and for end-stage renal disease, but also at even greater risk for cardiovascular diseases. This suggests that patients with diabetic nephropathy who are progressing towards end-stage renal disease carry the heaviest burden of cardiovascular disease, and that this frequently leads to death before end-stage renal disease is reached. So, diabetic nephropathy, through their impact on cardiovascular morbidity, may directly contribute to increasing mortalities. At present, there is no specific cure for diabetic nephropathy. Renal transplantation is limited by organ shortage, a worldwide problem that is not likely to be resolved in the near or immediate future. Therapeutic strategies to delay or arrest the progression of kidney nephropathy are essential to the treatment of patients with diabetes mellitus. Therefore, the best therapeutic option at the present time is to understand the mechanisms of diabetic renal fibrosis and then develop new strategies to prevent the progression of the diseases.

Progressive renal interstitial fibrosis and tubular atrophy represent the final common injury pathway for the majority of insults that lead to chronic kidney disease, including diabetic nephropathy. It is now clearly recognised that tubulointerstitial pathology predicts progression of diabetic nephropathy. Tubulointerstitial fibrosis is characterized by excess accumulation of extracellular matrix (ECM) in the renal interstitium.

Dr. Chen is currently a senior lecturer and Senior Scientist in the Kolling Institute of Medical Research. Dr. Chen’s postdoctoral research projects in Johns Hopkins University aimed to examine the role of Kruppel-like factors in cellular and molecular biology. These projects continued after his accepting a faculty appointment in Emory University. The inducible KLF4 expression system Dr. Chen independently established has played a foundational role for these projects. Dr. Chen firstly identified the gene expression profile induced by KLF4 using this KLF4 expression system with cDNA microarray analysis. Subsequently siRNA-mediated KLF4 gene silencing has been developed. As a result of his research in Johns Hopkins and Emory Universities eight articles were published in highly respected-peer-reviewed journals such as J Biol Chem, J Mol Biol and Oncogene. Since 2003, Dr Chen has been working on several projects to understand the mechanisms of diabetic renal fibrosis in the Kolling Institute. To date, 21 manuscripts have been published in renal medicine. His research experience with KLF4 has created a new direction in the Kolling Renal Research Laboratories in the area of “Epithelial-mesenchymal transformation in diabetic nephropathy”. This was funded as an NHMRC project grant 2005 and led to the successful completion of a PhD project. He has also been successful in an NHMRC project grant in 2008 and an ARC-linkage grant 2005. With his supervision, four outstanding PhD students were awarded their PhDs in 2006 and 2008. He currently co-supervises 4 PhD students at the University of Sydney.

Our research interests including the following aspects:

  • The isoform specific effects of transforming growth factor β (TGFβ) in diabetic nephropathy.
  • Differentiating the inflammatory vs the profibrotic component of progressive renal disease in diabetic nephropathy.
  • The role of the Kruppel like transcription factors in mediating vascular disease and progressive renal fibrosis.
  • MicroRNA and regulation of renal inflammation and fibrosis.
  • Re-expression of fetal developmental markers of maturation in the epithelial to mesenchymal transformation observed in diabetic nephropathy.
  • Stimulation of the peroxisome proliferator agonist receptors as a strategy to reduce progressive renal disease in kidney disease due to, and independent of, diabetes mellitus.
  • Molecular differences in PPAR gamma agonists that underpin differences in clinical outcomes.
  • Mechanisms of renal repair with a focus on the BMP-7 signalling pathways.
  • The consequences of statins on renal tubular function.
  • Hypoxia inducible genes and diabetic nephropathy.
  • Toll-like receptors and diabetic nephropathy.
  • The thioredoxin pathway and diabetic vascular disease.

Selected publications

For a comprehensive list of Dr Chen's publicatons, please visit his Sydney Medical School profile page