Dr Jinhua Li - Researcher Profile

Dr Jinhua Li

Address

Dept of Anatomy & Developmental Biology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

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-β1). 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-β1molecules 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 β1, 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.”

Qualifications

DOCTOR OF PHILOSOPHY
Institution: Monash University
Year awarded: 2006
MASTER DEGREE OF INTERNAL MEDICINE
Institution: Sun Yat-Sen University of Medical Sciences, Guangzhou, PR China
Year awarded: 1998
MEDICINE
Institution: Sun Yat-Sen University of Medical Sciences-
Year awarded: 1990

Publications

Journal Articles

Sun, Y.Y., Qu, X., Zhang, X., Caruana, G., Bertram, J.F., Li, J., 2013, Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy, PLoS ONE [P], vol 8, issue 1, Public Library of Science, USA, pp. 1-12.

Iqbal, J., Tonta, M.A., Mitsui, R., Li, Q., Kett, M.M., Li, J., Parkington, H.C., Hashitani, H., Lang, R.J., 2012, Potassium and ANO1/ TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis, British Journal of Pharmacology [P], vol 165, issue 7, John Wiley & Sons Ltd, UK, pp. 2389-2408.

Qu, X., Zhang, X., Yao, J., Song, J., Nikolic-Paterson, D.J., Li, J., 2012, Resolvins E1 and D1 inhibit interstitial fibrosis in the obstructed kidney via inhibition of local fibroblast proliferation, Journal Of Pathology [P], vol 228, issue 4, John Wiley & Sons Ltd, UK, pp. 506-519.

Walker, K., Sims-Lucas, S., Caruana, G., Cullen-McEwen, L., Li, J., Sarraj, M., Bertram, J., Stenvers, K., 2011, Betaglycan is required for the establishment of nephron endowment in the mouse, PLoS ONE [P], vol 6, issue 4 (Art. No: e18723), Public Library of Science, USA, pp. 1-10.

Chen, H., Huang, X.R., Wang, W., Li, J., Heuchel, R.L., Chung, A.C., Lan, H., 2011, The protective role of Smad7 in diabetic kidney disease: Mechanism and therapeutic potential, Diabetes [P], vol 60, issue 2, American Diabetes Association, USA, pp. 590-601.

Li, J., Qu, X., Yao, J., Caruana, G., Ricardo, S.D., Yamamoto, Y., Yamamoto, H., Bertram, J.F., 2010, Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy, Diabetes [P], vol 59, issue 10, American Diabetes Association, USA, pp. 2612-2624.

Li, J., Qu, X., Ricardo, S.D., Bertram, J.F., Nikolic-Paterson, D.J., 2010, Resveratrol inhibits renal fibrosis in the obstructed kidney: Potential role in deacetylation of Smad3, American Journal Of Pathology [P], vol 177, issue 3, American Society for Investigative Pathology, USA, pp. 1065-1071.

Li, J., Bertram, J.F., 2010, Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosis, Nephrology [P], vol 15, issue 5, Wiley-Blackwell Publishing Asia, Australia, pp. 507-512.

Zhuang, J., Deane, J.A., Yang, R., Li, J., Ricardo, S.D., 2010, SCUBE1, a novel developmental gene involved in renal regeneration and repair, Nephrology Dialysis Transplantation [P], vol 25, Oxford University Press, UK, pp. 1421-1428.

Li, J., Qu, X., Bertram, J.F., 2009, Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice, American Journal Of Pathology [P], vol 175, issue 4, American Society for Investigative Pathology, USA, pp. 1380-1388.

Li, J., Deane, J.A., Campanale, N.V., Bertram, J.F., Ricardo, S.D., 2007, The contribution of bone marrow-derived cells to the development of renal interstitial fibrosis, Stem Cells, vol 25, issue 3, Alphamed Press, Durham USA, pp. 697-706.

Li, J., Deane, J.A., Campanale, N.V., Bertram, J.F., Ricardo, S.D., 2006, Blockade of p38 mitogen-activated protein kinase and TGF-beta1/Smad signaling pathways rescues bone marrow-derived peritubular capillary endothelial cells in adriamycin-induced nephrosis, Journal of the American Society of Nephrology, vol 17, issue 10, American Society Nephrology, Washington USA, pp. 2799-2811.

Li, J., Campanale, N.V., Liang, R., Deane, J.A., Bertram, J.F., Ricardo, S.D., 2006, Inhibition of p38 mitogen-activated protein kinase and transforming growth factor-beta1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy, The American Journal of Pathology, vol 169, issue 5, American Society for Investigative Pathology, Bethesda USA, pp. 1527-1540.

Li, H., Xu, D., Li, J., Berndt, M.C., Liu, J., 2006, Transforming growth factor beta suppresses human telomerase reverse transcriptase (hTERT) by Smad3 interactions with c-Myc and the hTERT gene, Journal of Biological Chemistry, vol 281, issue 35, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 25588-25600.

Wang, W., Huang, X.R., Li, A.G., Liu, F., Li, J., Truong, L.D., Wang, X.J., Lan, H.Y., 2005, Signaling mechanism of TGF-beta1 in prevention of renal inflammation: Role of Smad7, Journal of the American Society of Nephrology, vol 16, Lippincott Williams & Wilkins, USA, pp. 1371-1383.

Li, H., Pinto, A.R.I., Duan, W., Li, J., Toh, B., Liu, J., 2005, Telomerase down-regulation does not mediate PC12 pheochromocytoma cell differentiation induced by NGF, but requires MAP kinase signalling, Journal of Neurochemistry, vol 95, issue 3, Blackwell Publishing Ltd, UK, pp. 891-901.

Li, J., Huang, X.R., Zhu, H., Oldfield, M.D., Cooper, M.E., Truong, L.D., Johnson, R.J., Lan, H.Y., 2004, Advanced glycation end products activate Smad signaling via TGF--dependent and -independent mechanisms: implications for diabetic renal and vascular disease, FASEB Journal, vol 18, issue 1, Federation of American Societies for Experimental Biology, United States, pp. 176-178.

Li, J., Wang, W., Huang, X.R., Oldfield, M.D., Schmidt, A.M., Cooper, M.E., Lan, H.Y., 2004, Advanced glycation end products induce tubular epithelial-myofibroblast transition through the RAGE-ERK 1/2 MAP kinase signaling pathway, American Journal of Pathology, vol 164, issue 4, American Society of Investigative Pathology, USA, pp. 1389-1397.

Nakagawa, T., Li, J., Garcia, G., Mu, W., Piek, E., Bottinger, E.P., Chen, Y., Zhu, H.J., Kang, D., Schreiner, G.F., Lan, H.Y., Johnson, R.J., 2004, TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways, Kidney International, vol 66, issue 2, Nature Publishing Group, United Kingdom, pp. 605-613.

Lan, H.Y., Mu, W., Tomita, N., Huang, X.R., Li, J., Zhu, H., Morishita, R., Johnson, R.J., 2003, Inhibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model, Journal of the American Society of Nephrology, vol 14, issue 6, Lippincott, Williams & Wilkins, United States, pp. 1535-1548.

Li, J., Huang, X.R., Zhu, H., Johnson, R.J., Lan, H.Y., 2003, Role of TGF-beta signaling in extracellular matrix production under high glucose conditions, Kidney International, vol 63, Nature Publishing Group, United Kingdom, pp. 2010-2019.

Kanellis, J., Watanabe, S., Li, J., Kang, D.H., Li, P., Nakagawa, T., Wamsley, A., Sheikh-Hamad, D., Lan, H.Y., Feng, L., Johnson, R.J., 2003, Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2, Hypertension, vol 41, issue 6, Lippincott, Williams & Wilkins, United States, pp. 1287-1293.

Li, J., Zhu, H., Huang, X.R., Lai, K.N., Johnson, R.J., Lan, H.Y., 2002, Smad7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking Smad2 activation, Journal of the American Society of Nephrology, vol 13, issue 6, Lippincott, Williams & Wilkins, United States, pp. 1464-1472.

Grants

Title:
Contribution of bone marrow-derived cells to renal fibrosis and elucidation of cell signalling mechanisms.
Investigators:
Li, J
Funding:
(2007 - 2011). National Health & Medical Research Council (NHMRC).
Title:
New insights into the role of renal endothelial dysfunction in the pathogenesis of glomerular injury and renal fibrosis.
Investigators:
Li, J, Bertram, J
Funding:
(2010 - 2013). National Health & Medical Research Council (NHMRC).
Title:
New insights into the role of renal endothelial dysfunction in the pathogenesis of glomerular injury and renal fibrosis.
Investigators:
Li, J
Funding:
(2010 - 2013). National Health & Medical Research Council (NHMRC).
Title:
Resolvin E1 is a novel anti-inflammatory and anti-fibrotic lipid mediator for the treatment of chronic kidney desease.
Investigators:
Li, J, Nikolic-Paterson, D
Funding:
(2010 - 2013). National Health & Medical Research Council (NHMRC).
Title:
The role of bone marrow-derived endothelial-myofibroblast-transdifferentiation in renal injury and regeneration in the mouse.
Investigators:
Li, J
Funding:
(2007 - 2010). Kidney Health Australia.
Title:
Contribution of bone marrow-derived cells to renal fibrosis and elucidation of cell signalling mechanisms.
Investigators:
Li, J
Funding:
(2007 - 2010). National Health & Medical Research Council (NHMRC).
(2010 - 2014). National Health & Medical Research Council (NHMRC).

Postgraduate Research Supervisions

Completed Supervision

Student:
Yousef, J.
Program of Study:
Pharmacological investigation of nephrotoxicity of colistin: the potential for nephro-protection afforded by co-administration of antioxidants. (PHD) 2012.
Supervisors:
Li, J (Joint-Co), Nation, R (Joint), Li, J (Associate).