Professor Darren Kelly
Academic site: Medicine, St Vincent's Hospital, Eastern Hill Campus
Our research looks to understand the mechanisms driving aberrant inflammation and fibrosis that underlies the decline in organ function in disease. Increasingly, low grade, subclinical inflammation is recognised to contribute to pathological fibrosis in multiple organs irrespective of the aetiology of the disease.
Pathological inflammation and fibrosis in heart, kidney, lung, liver and eye ultimately leads to end organ failure. As yet, there are few, and only poorly effective drugs on market that directly target the inflammatory and fibrotic processes and as such, there is a clear unmet need for treatments that directly modulate pathological fibrosis. Working collaboratively as a team with diverse expertise in medicinal chemistry, receptor biology and functional physiology and pharmacology, we are building a collective understanding of the mechanisms driving fibrosis, looking at innovative ways to map disease mechanisms of fibrosis and finally design and evaluate novel treatments to prevent the decline in organ function.
Our end goal is to advance these novel therapeutics through clinical development to provide precision medicine treatments and improve lives for patients living with inflammatory and fibrotic disease.
- Professor Darren Kelly, Director of Biomedical Research
- Dr Amanda Edgley, Senior Research Fellow
- Dr Andrew Kompa, Research Fellow
- Dr Roy Kong, Research Fellow
- Dr Fay Khong, Research Fellow
- Dr Elsa Chan, Senior Research Officer
- Ms Mariana Pacheco, Manager of Animal House
- Ms Jemma Court, Technical Officer
Our team is proud to have strong links to:
- Prof David O'Neal, University of Melbourne
- Professor Bernard Flynn, Monash University
- Professor Richard Gilbert, St Michael's Hospital Toronto Canada
- Professor Mathias Kreztler Department of Internal Medicine, Division of Nephrology, & Department of Computational Medicine and Bioinformatics, Michigan Medicine, Ann Arbor, MI.
- Professor Robyn Langham, University of Melbourne & Therapeutic Goods Association, Australia
- Dr Max Lim, St Vincents Institute of Medical Research
This research project is available to PhD students, Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
Professor Darren Kelly
Zammit, S.C., Cox, A.J., Gow, R., Zhang, Y., Gilbert, R.E., Krum, H., Kelly, D.J. and Williams, S.J. (2009) Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates. Bioorganic and Medicinal Chemistry Letters 19:7003-7006.
Gilbert, R. E., Zhang, Y., Williams, S. J., Zammit, S. C., Stapleton, D. I., Cox, A. J., Krum, H., Langham, R. G. and Kelly, D. J. (2012) A purpose-synthesised anti-fibrotic agent attenuates experimental kidney diseases in the rat. Plos One 7 (10): e47160.
Zhang, Y., Edgley, A.J., Cox, A.J., Powell, A.K., Wang, B., Kompa, A.R., Stapleton, D.I., Zammit, S.C., Williams, S.J., Krum, H., Gilbert, R.E. and Kelly, D.J. (2012) FT011, a new anti-fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy. European Journal of Heart Failure 14 (5) 549-562.
Zhang, Y., Elsik, M., Edgley, A.J., Cox, A.J., Kompa, A.R., Wang, B., Tan, C.Y., Khong, F.L., Stapleton, D.I., Zammit, S., Williams, S.J., Gilbert, R.E., Krum, H. and Kelly, D.J. (2013) A new anti-fibrotic drug attenuates cardiac remodeling and systolic dysfunction following experimental myocardial infarction. International Journal of Cardiology 168 (2):1174-1185.
Brandli, A., Khong F.L., Kong R.C.K., Kelly D.J., Fletcher E.L. (2022) Transcriptomic analysis of choroidal neovascularization reveals dysregulation of immune and fibrosis pathways that are attenuated by a novel anti-fibrotic treatment. Scientific Reports 12(1):859. doi: 10.1038/s41598-022-04845-4.
Wilkinson-Berka J.L., Kelly, D.J., and Gilbert R.E. (2001) The interaction between the renin-angiotensin system and vascular endothelial growth factor in the pathogenesis of retinal neovascularization in diabetes. Journal of Vascular Research 38(6):527-535.
Kelly D.J., Wilkinson-Berka J.L., Allen T.J., Cooper M.E. and Skinner S.L. (1998) A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). Kidney International 54(2):343-352.
Mifsud S*., Kelly D.J*., Weier Q., Zhang Y., Pollock C, Wilkinson-Berka J.L. and Gilbert, R.E. (2003) Intervention with tranilast attenuates renal pathology and albuminuria in advanced experimental diabetic nephropathy. Nephron Physiology 95:83-91. *Equal first author
PCT/AU2008/001868 (WO 2009/079692), PCT/AU2010/001398 (WO 2011/047432), PCT/AU2011/001455.
Dr Andrew Kompa
Kompa A.R., Greening, D.W., Kong, A, McMillan P.J., Fang, H., Saxena R., Wong R.C.B., Lees J.G., Sivakumaran P, Newcomb A.E., Tannous B.A., Kos C., Mariana L., Loudovaris T., Hausenloy D.J., Lim S.Y. (2021) Sustained subcutaneous delivery of secretome of human cardiac stem cells promotes cardiac repair following myocardial infarction. Cardiovascular Research. 117, 918-929.
Savira F., Wang B.H., Edgley A.J., Jucker B.M., Willette R.N., Krum H., Kelly D.J., Kompa A.R. (2020) Inhibition of apoptosis signal-regulating kinase 1 ameliorates left ventricular dysfunction by reducing hypertrophy and fibrosis in a rat model of cardiorenal syndrome. International Journal of Cardiology, 310, 128-136.
Von Lueder T.G., Wang B.H., Kompa A.R., L Huang, Webb R., Jordaan P., Atar D., Krum H. (2015) The angiotensin receptor neprilysin inhibitor LCZ-696 attenuates cardiac remodelling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circulation: Heart Failure, 8, 71-78.
Lekawanvijit S., Kompa A.R., Wang B.H., Kelly D.J., Krum H. (2012) Cardiorenal Syndrome: The emerging role of protein-bound uremic toxins. Circular Research, 111, 1470-83.
Lekawanvijit S., Kompa A,R., Manabe M, Wang BH, Langham RG, Nishijima F, Kelly DJ, Krum H. (2012) Chronic kidney disease-induced cardiac fibrosis is ameliorated by reducing circulating levels of a non-dialysable uremic toxin, indoxyl sulfate. PlosOne 7 (7) e41281.
Dr Amanda Edgley
Waddingham M.T., Edgley A.J., Tsuchimochi H., Kelly D.J., Shirai M., Pearson J.T. (2015) Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy. World Journal of Diabetes 6(7): p. 943-60.
Jenkins M.J., Pearson J.T., Schwenke D.O., Edgley A.J,. Sonobe T., Fujii Y., Ishibashi-Ueda H., Kelly D.J., Yagi N., Shirai M. (2013) Myosin heads are displaced from actin filaments in the in situ beating rat heart in early diabetes.Biophysical Journal, 2013. 104(5): p. 1065-72
Jenkins M.J., Edgley A.J., Sonobe T., Umetani K., Schwenke D.O., Fujii Y., Brown R.D., Kelly D.J., Shirai M., Pearson J.T. (2012) Dynamic synchrotron imaging of diabetic rat coronary microcirculation in vivo. Arterioscler Thrombosis and Vascular Biology 32(2): p. 370-7.
Edgley, A.J., Krum H, and Kelly D.J. (2012) Targeting fibrosis for the treatment of heart failure: a role for transforming growth factor-beta. Cardiovascular Therapies 30(1): p. e30-40.
Kelly D.J., Edgley A.J., Zhang Y., Thai K., Tan S.M., Cox A.J., Advani A., Connelly K.A., Whiteside C.I., Gilbert R,E. (2009) Protein kinase C-beta inhibition attenuates the progression of nephropathy in non-diabetic kidney disease. Nephrol Dial Transplant 24(6): p. 1782-90.
Wernstedt I, Edgley A.J., Berndtsson A., Fäldt J., Bergström G., Wallenius V., Jansson J.O. (2006) Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291(3): p. R551-7.
Edgley A.J., Thalén P.G., Dahllöf B., Lanne B., Ljung B., Oakes N.D (2006) PPARgamma agonist induced cardiac enlargement is associated with reduced fatty acid and increased glucose utilization in myocardium of Wistar rats. Euroupean Jounral of Pharmacology 538(1-3): p. 195-206.
Edgley A.J, Kett M., and Anderson W. (2001) 'Slow pressor' hypertension from low-dose chronic angiotensin II infusion. Clin Exp Pharmacol Physiology 28(12): p. 1035-9.
Dr Roy Kong
Fan Gaskin, J.C. et al. (2022) Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Mouse Model of Glaucoma Filtration Surgery and TGFbeta1-Induced Responses in Human Tenon's Fibroblasts. Transl Vis Sci Technol 11, 18
Brandli, A., Khong, F.L., Kong, R.C., Kelly, D.J. & Fletcher, E.L. (2022) Transcriptomic analysis of choroidal neovascularization reveals dysregulation of immune and fibrosis pathways that are attenuated by a novel anti-fibrotic treatment. Sci Rep 12, 859
Kong, R.C. et al. (2014) Mapping key regions of the RXFP2 low-density lipoprotein class-A module that are involved in signal activation. Biochemistry 53, 4537-4548
Bruell, S. et al. (2013) Chimeric RXFP1 and RXFP2 Receptors Highlight the Similar Mechanism of Activation Utilizing Their N-Terminal Low-Density Lipoprotein Class A Modules. Front Endocrinol (Lausanne) 4, 171
Kong, R.C. et al. (2013).The relaxin receptor (RXFP1) utilizes hydrophobic moieties on a signaling surface of its N-terminal low density lipoprotein class A module to mediate receptor activation. J Biol Chem 288, 28138-28151
Kong, R.C., Shilling, P.J., Lobb, D.K., Gooley, P.R. & Bathgate, R.A. (2010) Membrane receptors: structure and function of the relaxin family peptide receptors. Mol Cell Endocrinol 320, 1-15
- Novel therapies for the treatment of cardiorenal disease
- Developing novel therapies for the treatment of retinal disease
- Novel therapies for the treatment of cardiovascular disease
School Research Themes
For further information about this research, please contact Director of Biomedical Research Professor Darren Kelly
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St Vincent's Hospital
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