Cardiac regeneration

Heart disease continues to be the leading cause of death worldwide. Our understanding of heart disease in humans is limited because human heart tissues are hard to come by. The human heart cells generated from stem cells can be used to grow human heart tissues in a dish. This pre-clinical human heart model has allowed us to test new drugs that have potential to protect the heart from injury, and to study genetic mutations that can cause heart disease.

Research Themes

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 diversity of heart tissue. We have established a novel cardiac organoid model with an integrated vasculature and sympathetic 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 secretome

Stem 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 morphology

Mitochondria 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 the heart damage is a change in the shape of the mitochondria. Mitochondria 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 and 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 that could be developed into an effective drug for humans. We have discovered new drugs that can bind specifically to the 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.

Student Projects


  • Dr Shiang (Max) Lim
  • Dr Jarmon Lees (Post-doctoral Fellow)
  • Dr Anne Kong (Post-doctoral Fellow, part-time)
  • Mr RenJie Phang (Jack) (Research Assistant)
  • Dr Ayeshah Rosdah (PhD student)
  • Ms Yali Deng (PhD student)
  • Mr Alex Parker (PhD student)
  • Mr Jonathan Lozano (PhD student)
  • Mr Haoxiang Zhang (Alan) (Masters student)

Publication Highlights

  1. Lees JG, Napierala M, Pébay A, Dottori M, Lim SY. Cellular pathophysiology of Friedreich’s ataxia cardiomyopathy. Int J Cardiol. 2022:346:71-78. 
  2. Kalkhoran SB, Kriston-Vizi J, Hernandez-Resendiz S, Crespo-Avilan GE, Rosdah AA, Lees JG, Da Costa JRS, Ling NXY, Holien JK, Samangouei P, Chinda K, Ping YE, Riquelme JA, Ketteler R, Yellon DM, Lim SY*, Hausenloy DJ*. Hydralazine protects the heart against acute ischemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission. Cardiovasc Res. 2022:118:282-294. *joint senior authors  
  3. Prakoso D, Lim SY, Erickson JR, Wallace RS, Lees JG, Tate M, Kiriazis H, Donner DG, Henstridge DC, Davey JR, Qian H, Deo M, Parry LJ, Davidoff AJ, Gregorevic P, Chatham JC, De Blasio MJ, Ritchie RH. Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart. Cardiovasc Res. 2022:118:212-225. 
  4. 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. 2021:117:91-929. 
  5. 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. 2020:2:391-398.  
  6. 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. 2020:107594.  
  7. Lozano O, Silva-Platas C, Chapoy-Villanueva H, Pérez BE, Lees JG, Ramachandra CJA, Contreras-Torres FF, Lázaro-Alfaro A, Luna-Figueroa E, Bernal-Ramírez J, Gordillo-Galeano A, Benitez A, Oropeza-Almazan Y, Castillo EC, Koh PL, Hausenloy DJ, Lim SY, García-Rivas G. Amorphous SiO2 nanoparticles promote cardiac dysfunction via the opening of the mitochondrial permeability transition pore through the modification of thiols and generation of oxidative stress. Part Fibre Toxicol. 2020:17:15. 
  8. Lees JG, Kong AM, Chen YC, Sivakumaran P, Hernández D, Pébay A, Harvey AJ, Gardner DK, Lim SY. Mitochondrial fusion by M1 promotes embryoid body cardiac differentiation of human pluripotent stem cells.  Stem Cells Int. 2019:6380135.  
  9. Fang L, Hung SSC, Yek J, El Wazen L, Nguyen T, Khan S, Lim SY, Hewitt AW, Wong RCB. A simple cloning-free method to efficiently induce gene expression using CRISPR/Cas9. Mol. Ther. Nucleic Acids. 2018:14:184.   
  10. 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.   
  11. Nie S, Wang X, Sivakumaran P, Chong MMW, Liu X, Karnezis T, Bandara N, Takov K, Nowell CJ, Wilcox S, Shambrook M, Hill AF, Harris NC, Newcomb AE, Strappe P, Shayan R, Hernández D, Clarke J, Hanssen E, Davidson SM, Dusting GJ, Pébay A, Ho JWK, Williamson N, Lim SY. Biologically active constituents of the secretome of human W8B2+ cardiac stem cells. Sci Rep. 2018:8(1):1579.   
  12. Zhang Y, Sivakumaran P, Newcomb AE, Hernandez D, Harris N, Khanabdali R, Liu GS, Kelly DJ, Pébay 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. 2015:33:3100-13.