Cytoprotection Pharmacology Research
Our research in Cytoprotection Pharmacology encompasses research into new treatments for vision threatening retinal disease, as well as stem cells and tissue engineering in heart repair. We explore cellular signalling that regulates survival and proliferation of crucial cells (where cells divide and multiply) and stem cell differentiation (where a stem cell develops into a more specialised cell). Angiogenesis (growth of new blood vessels) is a particular focus, both for exploring its potential in tissue regeneration, and treating diseases in the retina. By understanding the underlying mechanisms, we aim to develop new approaches for the treatment of growing eye diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity and ocular tumours, all of which result at least partly from pathological neovascularisation (excessive blood vessel growth). We are also working on the development of viral-based gene therapies for these eye diseases. This includes in vivo gene editing in the eye by game-changing technologies such as CRISPR.
Diabetic macular edema (DME) follows vascular leakage and accompanying swelling of the macula in the eye, and is the more common form of advanced diabetic retinopathy, which is becoming a major healthcare challenge. Anti-vascular endothelial growth factor (VEGF) treatments for diabetic macular edema have been shown to preserve and restore vision. Whilst anti-VEGF therapeutics provide some benefit, they can cause small but significant side-effects in patients, and place a burden on the healthcare system due to the need for frequent intraocular injections. In this project, we will validate a new, controllable gene therapy that targets VEGF directly. By preventing the leakage of retinal vessels, with less off target effects, it will be a safer and less-invasive therapeutic alternative to conventional drug injections for management of DME. This approach might reduce the need for multiple intraocular injections, and most importantly, minimize the side-effects associated with chronic suppression of vasculature and neurones in the retina.
We also collaborate with St Vincents Institute (Dr Max Lim) on regenerative repair of the heart with stem cells. Heart disease remains the leading cause of death in the world. Stem cells have the potential to treat heart diseases by transforming into heart cells and blood vessels or by producing protective factors. We grow human heart cells produced from stem cells into whole tissues of human heart. These engineered human heart tissues might then be developed to replace and support damaged hearts through surgical transplantation and to test new drugs for heart attack, and a particular application we are developing is in pediatric surgery to improve outcomes for blue babies.
We have recently found a new type of stem cell that grows in human hearts and are investigating its potential to treat heart attack. We have also successfully generated human heart tissue with induced pluripotent stem cells using our unique in vivo vascularised tissue engineering chamber. In order to utilize human stem cells to treat heart disease effectively, we have a multidisciplinary approach to identify an ideal stem cell source, enhance stem cell cardiomyogenesis, improve survival and functionality of stem cell-derived heart cells, and optimise their delivery to the damaged heart.
Dr Rick Guei-Sheung Liu, Research Fellow,
Sloan Jiang-Hui Wang, PhD student
Leilei Tu, PhD student
Amy Fan Li, PhD student
Damian Ling, Masters student
Prof Tien Wong, Singapore Eye Research Institute
Prof Ian Alexander, Children’s Medical Research Institute, Westmead
Prof Balamurali Ambati, University of Utah
Prof Fan Jiang, Shandong University
Prof Ming-Hong Tai, National Sun Yat-Sen University, Taiwan
Prof Shyh-Ming Kuo, Department of Biomedical Engineering, I-Shou University, Taiwan
Prof Rob Shepherd, Bionics Institute, University of Melbourne
A/Prof Bang Bui, Department of Optometry & Vision Sciences, University of Melbourne
A/Prof Alex Hewitt and Dr Anna King, University of Tasmania
A/Prof Geraldine Mitchell and Dr Max Lim, St Vincent’s Institute of Medical Research
Dr Hsinhui Shen, Monash University
Dr Hitesh Peshavariya, Centre for Eye Research Australia
Dr Peter van Wijngaarden, Centre for Eye Research Australia
NHMRC Project grant "New treatment to block retinal blood vessel growth avoiding eye surgery"
Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease. Khanabdali R, Rosdah AA, Dusting GJ, Lim SY. Biochem Pharmacol 2016: doi: 10.1016/j.bcp.2016.02.012. [Epub ahead of print] Review.
NADPH oxidase 2 plays a role in experimental corneal neovascularisation. Chan EC, Van Wijngaarden P, Chan E, Ngo D, Wang JH, Peshavariya HM, Dusting GJ, Liu GS. Clinical Science (Lond) 2016, 130(9):683-696. doi: 10.1042/CS20150103. Epub 2016 Jan 26.
Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells. Hernández D, Millard R, Sivakumaran P, Wong RC, Crombie DE, Hewitt AW, Liang H, Hung SS, Pébay A, Shepherd RK, Dusting GJ, Lim SY. Stem Cells Int. 2016;2016:1718041. doi: 10.1155/2016/1718041. Epub 2015 Dec 14.
Gene Delivery by Subconjunctival Injection of Adenovirus in Rats: A Study of Local Distribution, Transgene Duration and Safety. Liu GS, Wang JH, Lee JH, Tsai PJ, Tsai HE, Sheu SJ, Lin HC, Dusting GJ, Tai MH, Bee YS. PLoS One. 2015 Dec 7;10(12):e0143956. doi: 10.1371/journal.pone.0143956. eCollection 2015.
Cardiac repair with a novel population of mesenchymal stem cells resident in the human heart. Zhang Y, Dusting GJ, Lim SY: Stem Cells 2015, 33:3100-3113.doi: 10.1002/stem.2101. Epub 2015 Jul 29
Prostacyclin signalling boosts NADPH oxidase 4 in the endothelium promoting cytoprotection and angiogenesis. Peshavariya HM, Liu GS, Chang CWT, Jiang F, Chan EC, Dusting GJ: Antioxid Redox Signal 2014, 20: 2710-2725. doi: 10.1016/j.bbrc.2012.11.138. Epub 2012 Dec 19.
Involvement of Nox2 NADPH oxidase in retinal neovascularization. Chan EC, van Wijngaarden P, Liu GS, Jiang F, Peshavariya HM, Dusting GJ: . Invest Ophth Vis Sci 2013, 54:7061-7067. doi: 10.1167/iovs.13-12883.
Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose and dermal tissue. Hsiao STF, Asgari, Lim SY, Dusting GJ, Dilley RJ: Stem Cells Dev 2012, 21: 2189-2203. doi: 10.1089/scd.2011.0674. Epub 2012 Feb 3.
NADPH oxidase-mediated redox signaling: roles in cell stress response, stress tolerance, and tissue repair. Jiang F, Zhang Y, Dusting GJ: Pharmacol Reviews 2011, 63:218-242. doi: 10.1124/pr.110.002980. Epub 2011 Jan 12. Review.