Biomedical Translational Research Group: Developing Therapies for Cardiovascular Disease

Research Overview

Academic site: Medicine, St Vincent's Hospital, Eastern Hill Campus

The Biomedical Translational Research Group is an internationally recognised team focused on the preclinical development of novel compounds for the treatment of pathological inflammation and fibrosis. Increasingly, low grade, subclinical inflammation is being recognised to contributed 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 inflammation and fibrosis. Our group adopts a “bench to bedside” approach to research, where we evaluate the efficacy of novel therapies on structural and functional aspects of heart, kidney, lung, liver and eye disease using robust in vivo animal models that display key aspects of human disease.

In collaboration with the academia and industry we have tested the efficacy of emerging pharmaceuticals in preclinical animal models of diabetic heart and kidney failure and eye disease. Fibrotech Therapeutics, a biotech company founded by our group and the University of Melbourne, successfully advanced our compound, FT011, into phase 1 clinical trials in humans which resulted in the sale of Fibrotech and its pre-clinical pipeline to Shire Pharmaceuticals to faciltate further clinical development for the treatment of diabetic kidney disease.

More recently our experience in research commercialisation has led to the establishment of another biotech company OccuRx, that is focussed on the development of innovative therapeutic strategies for the treatment of ophthalmic disorders associated with retinal inflammation and fibrosis. OccuRx has successfully secured funding from Uniseed, The Medical Research Commercialisation Fund and Brandon Capitol Partners and has a number of compounds in pre-clinical development.

Staff

Collaborators

  • Prof Robyn Langham, Head, Monash University School of Rural Health
  • Professor Richard Gilbert, St Michael's Hospital, Toronto, Canada
  • Dr Kim Connelly, St Michael's Hospital, Toronto, Canada
  • Professor Phil Poronnik, Professor of Biomedical Sciences, University of Sydney
  • Professor Duncan Campbell, St Vincent's Institute, Melbourne
  • Dr James Pearson, Director, Department of Cardiac Physiology
  • National Cerebral and Cardiovascular Center Research Institute, Osaka, JAPAN
  • Professor Jonathon Crowston, University of Melbourne and Centre for Eye Research Australia
  • Associate Professor Jennifer Wilkinson Berka, Head, Diabetic Retinopathy Laboratory, Alfred Medical Research and Education Precinct, Monash University
  • Professor Robyn Gumyer, Centre for Eye Research Australia
  • Dr Peter van Wijngaarden, Centre for Eye Research Australia

Funding

  • 2016 Program Grant CIs Kelly, Reid, Liew XXX details
  • OccuRx Pty Ltd
  • Fibrotech Therapeutics Pty Ltd
  • Neuprotect Pty Ltd
  • 546272 NHMRC Program Grant. CIs Henry Krum, Darren Kelly, Christopher Reid. Prevention and Treatment of Chronic Heart and Kidney Disease via Epidemiological, Pharmacological Device and Cell-Based Approaches (2010-2014). 5.4 million AUD.
  • 1004596 NHMRC Project Grant. CIs Darren Kelly and Amanda Edgley. Pre-clinical development of a novel anti-fibrotic, anti-inflammatory compound to treat diabetic heart disease (2011-2013). $471,706 AUD

    334008 2005 – 2009 NHMRC program grant. Novel therapeutic strategies to reduce the burden of chronic heart failure. H Krum, DJ Kelly, S Itescu:  $4.7 million AUD.

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

  1. Chen YC, Inagaki T, Fujii Y, Schwenke DO, Tsuchimochi H, Edgley AJ, Umetani K, Zhang Y, Kelly DJ, Yoshimoto M, Nagai H, Evans RG, Kuwahira I, Shirai M, Pearson JT.
    Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in insulin resistant Goto-Kakizaki rats.
    Am J Physiol Regul Integr Comp Physiol. 2016 Jun [Epub ahead of print
  2. Zhang Y, Sivakumaran P, Newcomb AE, Hernandez D, Harris N, Khanabdali R, Liu GS, Kelly DJ, P├ębay A, Hewitt AW, Boyle A, Harvey R, Morrison WA, Elliott DA, Dusting GJ, Lim SY.Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart.
    Stem Cells. 2015 Oct;33(10):3100-13.
  3. Waddingham MT, Edgley AJ, Astolfo A, Inagaki T, Fujii Y, Du CK, Zhan DY, Tsuchimochi H, Yagi N, Kelly DJ, Shirai M, Pearson JT.
    Chronic Rho-kinase inhibition improves left ventricular contractile dysfunction in early type-1 diabetes by increasing myosin cross-bridge extension.
    Cardiovasc Diabetol. 2015 Jul 22;14:92.
  4. Lee A, Slattery C, Nikolic-Paterson DJ, Hryciw DH, Wilk S, Wilk E, Zhang Y, Valova VA, Robinson PJ, Kelly DJ, Poronnik P.
    Chloride channel ClC-5 binds to aspartyl aminopeptidase to regulate renal albumin endocytosis.
    Am J Physiol Renal Physiol. 2015 Apr 1;308(7):F784-92
  5. Rana I, Kompa AR, Skommer J, Wang BH, Lekawanvijit S, Kelly DJ, Krum H, Charchar FJ
    Contribution of microRNA to pathological fibrosis in cardio-renal syndrome: impact of uremic toxins.
    Physiol Rep. 2015 Apr;3(4). pii: e12371
  6. Jenkin KA, McAinch AJ, Zhang Y, Kelly DJ, Hryciw DH.
    Elevated cannabinoid receptor 1 and G protein-coupled receptor 55 expression in proximal tubule cells and whole kidney exposed to diabetic conditions.
    Clin Exp Pharmacol Physiol. 2015 Mar;42(3):256-62.
  7. Tan CY, Weier Q, Zhang Y, Cox AJ, Kelly DJ, Langham RG.
    Thioredoxin-interacting protein: a potential therapeutic target for treatment of progressive fibrosis in diabetic nephropathy.
    Nephron. 2015;129(2):109-27. doi: 10.1159/000368238. Epub 2015 Jan 31.
  8. Deliyanti D, Zhang Y, Khong F, Berka DR, Stapleton DI, Kelly DJ, Wilkinson-Berka JL.
    FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy.
    PLoS One. 2015 Jul 29;10(7):e0134392
  9. Ayoub MA, Zhang Y, Kelly RS, See HB, Johnstone EK, McCall EA, Williams JH, Kelly DJ, Pfleger KD.
    Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif) receptor 2 with implications for chronic kidney disease.
    PLoS One. 2015 Mar 25;10(3):e0119803.

For a full list of publications, please visit Prof Kelly's Research Profile.

Research Projects



Key Contact

For further information about this research, please contact
Professor Darren Kelly.

Department / Centre

Medicine and Radiology