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The relentless pursuit of a likely suspect

Dr Jinhua Li has travelled a long road in search of an early treatment for kidney disease, an illness which often strikes diabetics, Australia's fastest-growing community of chronic disease sufferers. His search has taken him from China to the US and now Monash, a world leader in kidney research, where he has discovered how healthy kidney cells can turn bad.

Jinhua sees himself as kind of detective, looking for the tiniest clue to help solve a major medical crime - end-stage kidney disease.

'Patients with end-stage kidney disease need replacement therapy, such as dialysis or a transplant, which is expensive and places a huge burden on them, their families and the community.'

In much the same manner as a detective, Jinhua knew he had to identify the rogue elements that caused kidney damage and understand their modus operandi before he could hope to find a cure.

He has known the identity of one suspect for some time - a molecule known as transforming growth factor beta one (TGF-?1). It contributes to fibrosis - or scarring - in kidneys and other organs, but he only recently discovered how.

When Jinhua enrolled as a PhD student at Monash in 2003 - having spent 11 years as a doctor in China and Hong Kong, and two-and-a-half years as a researcher at the Baylor College of Medicine in Houston, Texas - he began investigating stem cells in bone marrow.

He found that endothelial cells, which occur naturally in large numbers in healthy kidneys and help remove toxins from our blood, are derived in small quantities from bone marrow when a kidney is damaged. These cells seemed to cause fibrosis.

Jinhua wondered if good endothelial cells in the presence of TGF-?1molecules were turning bad. By adding markers to healthy and unhealthy endothelial cells taken from mice, he found that this is exactly what was happening.

He knew the markers in healthy endothelial cells would glow green under laser light, while those in scar-producing endothelial cells, affected by TGF ?1, would glow red. But he found cells with markers that glowed yellow. This meant they contained green and red markers - in other words, he was looking at good kidney cells in the process of turning bad.

That discovery meant he had identified a cell pathway along which you might apply a special-purpose drug - which he hopes to design - to stop kidney disease before it causes serious damage.

Before starting the long and expensive task of designing a potential drug, Jinhua needs to establish if the process, identified in mice, occurs in humans in the same way.

He first needs to secure adequate supplies of diseased human kidney tissue, which isn't easy. Doctors usually don't order biopsies on diabetics with kidney disease since they know what has caused the disease.

Biopsies are done when non-diabetics present with kidney disease symptoms. Such cases are less common in Australia than in China (given its large population), which is why Jinhua is looking to Chinese doctors for help.

To design his drug, he must choose from thousands of likely candidates, test them for efficacy and side effects, discard those with severe effects and arrange funding to conduct experiments on cells and animals ahead of clinical trials, which are only approved for the most promising and important treatments.

Jinhua knows he has a long way to go, but, undeterred, his search continues, aided by a National Health and Medical Research Council Career Development Award and two NHMRC project grants.

'My job is like being a detective,' he says. 'I try to detect the bad guy, the bad pathway he follows, and find solutions. But if you like it, it's not hard work. It's really interesting.'

Research interests

I am studying diabetic kidney disease.

Research area keywords

  • Diabetic Kidney Disease (DKD)
  • Chronic kdiney disease
  • small molecule inhibitor

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Research Output

Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance

Sun, Y. B. Y., Qu, X., Howard, V., Dai, L., Jiang, X., Ren, Y., Fu, P., Puelles, V. G., Nikolic-Paterson, D. J., Caruana, G., Bertram, J. F., Sleeman, M. W. & Li, J., Aug 2015, In : Kidney International. 88, 2, p. 286 - 298 13 p.

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS

Li, J., Sun, Y. B. Y., Chen, W., Fan, J., Li, S., Qu, X., Chen, Q., Chen, R., Zhu, D., Zhang, J., Wu, Z., Chi, H., Crawford, S., Oorschot, V., Puelles, V. G., Kerr, P. G., Ren, Y., Nilsson, S. K., Christian, M., Tang, H. & 4 others, Chen, W., Bertram, J. F., Nikolic-Paterson, D. J. & Yu, X., 5 Feb 2020, In : EMBO Reports. 21, 2, 20 p., e48781.

Research output: Contribution to journalArticleResearchpeer-review

Combined Blockade of Smad3 and JNK Pathways Ameliorates Progressive Fibrosis in Folic Acid Nephropathy

Jiang, M., Fan, J., Qu, X., Li, S., Nilsson, S. K., Sun, Y. B. Y., Chen, Y., Yu, D., Liu, D., Liu, B-C., Tang, M., Chen, W., Ren, Y., Nikolic-Paterson, D. J., Jiang, X., Li, J. & Yu, X., 9 Aug 2019, In : Frontiers in Pharmacology. 10, 17 p., 880.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
1 Citation (Scopus)

Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury

Zhou, T., Zheng, Y., Sun, L., Badea, S. R., Jin, Y., Liu, Y., Rolfe, A. J., Sun, H., Wang, X., Cheng, Z., Huang, Z., Zhao, N., Sun, X., Li, J., Fan, J., Lee, C., Megraw, T. L., Wu, W., Wang, G. & Ren, Y., Mar 2019, In : Nature Neuroscience. 22, 3, p. 421-435 15 p.

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

MTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans

Puelles, V. G., van der Wolde, J. W., Wanner, N., Scheppach, M. W., Cullen-McEwen, L. A., Bork, T., Lindenmeyer, M. T., Gernhold, L., Wong, M. N., Braun, F., Cohen, C. D., Kett, M. M., Kuppe, C., Kramann, R., Saritas, T., Van Roeyen, C. R., Moeller, M. J., Tribolet, L., Rebello, R., Sun, Y. B. Y. & 13 others, Li, J., Müller-Newen, G., Hughson, M. D., Hoy, W. E., Person, F., Wiech, T., Ricardo, S. D., Kerr, P. G., Denton, K. M., Furic, L., Huber, T. B., Nikolic-Paterson, D. J. & Bertram, J. F., 19 Sep 2019, In : JCI Insight. 4, 18, 18 p., e99271.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
1 Citation (Scopus)