My main research goal is to develop effective and translatable treatments for heart disease and functionally validate and translate my findings. My research vision is driven by three significant medical challenges, namely (1) extreme difficulty to translate from bench to bedside, (2) limited effective medicines to treat heart disease, and (3) lack of safe and effective long-term delivery vehicle for biologics. To achieve this goal, I have creatively combined stem cell biology, bioengineering and pharmacology in my multidisciplinary research program.
My team has made some seminal discoveries, including identifying a novel population of stem cells in human hearts (Zhang et al. Stem Cells 2015; Nie et al. Sci Rep 2018). My team has also innovatively employed an immunoisolation device to transplant stem cell in vivo and address the unmet need for sustained release of the stem cell secretome for cardiac repair (Kompa et al. Cardiovasc Res 2020). In 2022, we received a Federal Government’s NHMRC MRFF grant to translate this approach using clinically relevant disease models and a stem cell type with improved translatability.
To facilitate clinical translation, my team has invented a novel method to fabricate a novel multicellular human cardiac organoid using human induced pluripotent stem cells. This pre-clinical human heart model contains cardiomyocytes and non-cardiomyocytes cell populations that better recapitulate the cellular heterogeneity of native heart tissue for disease modelling, therapeutic discovery, and screening.
Another key research focus is developing cardioreparative strategies, which specifically target mitochondrial morphology that plays an important role in cell survival and metabolism. My team is currently developing new small molecule therapeutics that target mitochondrial fission protein Drp1 for cardiovascular disease and to formulate a nanoparticle-based system for cardiac-targeted drug delivery of these compounds
Key achievements
2023-current Council member of the International Society for Heart Research (Australasian Section)
2021 Shirley Keon Hummingbirds Fellowship
2018-2022 Chair of Conference and Awards committee, Australasian Society for Stem Cell Research
2018-2023 Peer review panel member for NHMRC Grant Review Working Committee
2016 European Society of Cardiology/FCVB travel award
2012 APSH Young Investigator Fellowship
2012 HBPRCA Young Investigator Award
Selected 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
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
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(1):282-294 *joint senior authors
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
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
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. doi: 10.1002/stem.2101
Lim SY, Hausenloy DJ, Arjun S, Price AN, Davidson SM, Lythgoe MF, Yellon DM. Mitochondria cyclophilin-D as a potential therapeutic target for post-myocardial infarction heart failure. J Cell Mol Med. 2011:15(11):2443-51
Lim SY, Hausenloy DJ, Yellon DM. The neural and humoral pathways in remote limb ischaemic preconditioning. Basic Res Cardiol. 2010:105(5):651-5
Ong SB, Subrayan S, Lim SY, Yellon DM, Davison SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia reperfusion injury. Circulation. 2010:121(18):2012-22. doi: 10.1161/CIRCULATIONAHA.109.906610
ORCID profile: https://orcid.org/0000-0002-0442-3655
Google Scholar profile: https://scholar.google.com/citations?user=-F_g4SQAAAAJ&hl=en