Heart disease continues to be the leading cause of death worldwide. However, our understanding of this disease remains limited because human heart tissues are hard to come by. Human heart cells generated from stem cells can be used to grow human heart tissues in a lab dish. This pre-clinical human heart model has allowed us to test new drugs with the potential to protect the heart from injury, as well as to study genetic mutations that can cause heart disease.
Current research projects
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Engineered heart tissue for disease modelling and novel target discovery
Development of effective new drug candidates that are specific and effective for humans has been severely limited and detailed characterisation of human heart disease is urgently needed. However, this has been largely impeded by the limited access to viable human heart samples and by the cellular heterogeneity of heart tissue. We have established a multicellular cardiac organoid model with an integrated vasculature and autonomic neuronal network. We hypothesise that this multicellular human cardiac organoid, constructed with human induced pluripotent stem cell derivatives, can recapitulate the cellular and microenvironment changes during cardiac injury. This study will establish a pre-clinical human heart tissue model for cardiac disease modelling and drug development that will facilitate animal-to-human translation.
Stem cell secretomeStem cells have the potential to treat heart disease by producing beneficial soluble factors and membrane-bound particles. This project aims to accelerate the development of a new, safe and minimally invasive method to deliver the beneficial proteins of stem cells to patients, using a retrievable encapsulation device that protects the transplanted cells, to allow long-term treatment for effective cardiac repair.
Therapeutic potential of targeting mitochondrial morphologyMitochondria are the powerhouses of cells. They are membrane-bound compartments, within the cell, that use nutrients to produce chemical energy to power the cell’s biochemical reactions. One of the processes involved in heart damage is a change in the shape of the mitochondria, which can either join together by the process of fusion or divide into smaller pieces by the process of fission. A protein called Drp1 is needed for mitochondrial fission; blocking Drp1-mediated mitochondrial fission can protect against heart damage. However, until recently, there has not been a specific and potent enough inhibitor of Drp1 to develop into an effective drug for humans. We have discovered new drugs that can bind specifically to human Drp1, inhibit mitochondrial division and protect animals from heart damage after heart attack. In this project, we will continue to improve the potency and specificity of these new drugs for heart protection and repair.
People
- Dr Andrew Kompa, Research Fellow
- Mr RenJie (Jack) Phang, Research Assistant
- Ms Ashley Nowland, Research Assistant
- Ms Yali Deng, PhD student
- Mr Alex Parker, PhD student
- Mr Jonathan Lozano, PhD student
- Mr Haoxiang (Alan) Zhang, Masters student
- Ms Anny Nan Su, Masters student
- Ms Li Li, Honours student
Student projects
Modelling cardiovascular diseases using human cardiac organoids
Lab: Cardiac Regeneration
Supervisor(s): Associate Professor Shiang (Max) Lim Dr Jarmon G Lees
Diseases focus: Regenerative MedicineDeveloping novel therapies for type 2 diabetic heart disease using human iPSC-derived multicellular cardiac organoids
Lab: Cardiac Regeneration
Supervisor(s): Associate Professor Shiang (Max) Lim Dr Jarmon G Lees
Diseases focus: Regenerative MedicineTreating cardiac vascular dysfunction in Friedreich ataxia using human iPSC-derived multicellular cardiac organoids
Lab: Cardiac Regeneration
Supervisor(s): Associate Professor Shiang (Max) Lim Dr Jarmon G Lees
Diseases focus: Regenerative MedicineInvestigating cardiometabolic disease using human induced pluripotent stem cells
Lab: Cardiac Regeneration
Supervisor(s): Associate Professor Shiang (Max) Lim
Diseases focus: Regenerative MedicineDeveloping novel biomarker for Friedreich ataxia heart disease
Lab: Cardiac Regeneration
Supervisor(s): Associate Professor Shiang (Max) Lim Dr Jarmon G Lees
Diseases focus: Regenerative MedicineSelected publications
Rosdah AA, Abbott BM, Langendorf CG, Deng Y, Truong JQ, Waddell HMM, Ling NXY, Smiles WJ, Delbridge LMD, Liu GS, Oakhill JS, Lim SY*, Holien JK*. A novel small molecule inhibitor of human Drp1. Scientific Reports 2022:12:21531 *joint senior authors
Lyu Q*, Gong S*, Lees JG*, Yin J, Yap LW, Kong AM, Shi Q, Fu R, Zhu Q, Dyer A, Dyson J, Lim SY, Cheng W. A Soft and Ultrasensitive Force Sensing Diaphragm for Probing Cardiac Organoids Instantaneously and Wirelessly. Nat Commun 2022:13(1):7259 *joint first authors
Deng Y, Ngo DTM, Holien JK, Lees JG, Lim SY. Mitochondrial dynamin-related protein Drp1: A new player in cardio-oncology. Current Oncology Reports 2022:24(12):1751-63.
Phang RJ, Ritchie RH, Hausenloy DJ, Lees JG, Lim SY. Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy. Cardiovasc Res 2023:119(3):668-690.
Lees JG, Napierala M, Pébay A, Dottori M, Lim SY. Cellular pathophysiology of Friedreich’s ataxia cardiomyopathy. Int J Cardiol 2022:346:71-78.
Rosdah AA, Smiles WJ, Oakhill JS, Scott JW, Langendorff CG, Delbridge LMD, Holien JK, Lim SY. New perspectives on the role of Drp1 isoforms in regulating mitochondrial pathophysiology. Pharmacol. Ther. 2020:213:107594.
Hernández D, Millard R, Kong AM, Burns O, Sivakumaran P, Shepherd RK, Dusting GJ, Lim SY. A tissue engineering chamber for continuous pulsatile electrical stimulation of vascularised cardiac tissues in vivo. Bioelectricity. 2020:2(4):391-398.
Kompa AR, Greening DW, Kong AM, McMillan PJ, Fang H, Saxena R, Wong RCB, Lees JG, Sivakumaran P, Newcomb AE, Tannous BA, Kos C, Mariana L, Loudovaris T, Hausenloy DJ, Lim SY. Sustained subcutaneous delivery of secretome of human cardiac stem cells promotes cardiac repair following myocardial infarction. Cardiovasc Res. 2021:117(3):918-929
Hoque A, Sivakumaran P, Bond ST, Ling NXY, Kong AM, Scott J, Bandara N, Hernández D, Liu GS, Wong RCB, Ryan MT, Hausenloy DJ, Kemp BE, Oakhill JS, Drew BG, Pébay A, Lim SY. Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells. Cell Death Discov. 2018:4:39
ORCID profile: https://orcid.org/0000-0002-0442-3655
Google Scholar profile: https://scholar.google.com/citations?user=-F_g4SQAAAAJ&hl=en