Yuanzhao Cao

1) Using stem cells to optimise cardiac disease modelling: I have advanced the field of stem cell-based disease modelling by developing optimised conditions for human induced pluripotent stem cell-derived cardiomyocytes (hiPSCs-CMs) to better and specifically model cardiac ischaemia. The outcomes resulted in important steps to developing valid and predictive human in vitro models of cardiac ischaemia, to achieve better predictive drug candidate testing and understand the disease mechanisms of ischaemic reperfusion injury (IRI). This work has resulted in a current preparation for publication in a high-impact journal in the fields of stem cells or cardiovascular development.

2) Developing preclinical models of diabetes in the co-morbidity of ischaemic heart disease: One of the primary reasons why has the drug development pipeline failed for ischaemic heart disease is that comorbidities (e.g., diabetes) may impact the efficacy of a new treatment in patients with myocardial infarction (MI) and reperfusion injury. I have developed new cell and mice co-morbidity models of diabetes and ischaemic heart disease, highlighting glycaemic variability as a significant cardiovascular disease risk in diabetes. This work has resulted in being prepared for publication in a high-impact heart research journal and formed the basis for funding from an MRFF Translation grant (MRFCDDM000033, under embargo). Due to the commercial value of my work, my protocol for modelling diabetes with hiPSCs has led to a collaborative effort and interest with companies such as Nanion Technologies, STEMCELL Technologies.

3) Drug discovery for ischaemic heart disease: There remain no clinically approved drugs that block cardiomyocyte cell death during acute IRI. A preliminary study revealed that a novel role for the acid-sensing ion channel 1a (ASIC1a) is identified as a new injury response mechanism governing cardiomyocyte death during acute ischaemic injuries. In subsequent studies, I have participated in studying the basis of and developing new therapies to treat heart disease. The outcomes (Heart, Lung and Circulation, Journal of Molecular and Cellular Cardiology) formed the funding from The Ian Potter Foundation Limited (31111380). I am leading another project will determine the role of an acid-sensitive chloride channel that is targeted as a novel therapy to promote rapid and more effective recovery in patients subjected to MI. This work resulted in a Phenomics Australia Pipeline Accelerator Award (Lead applicant, 2023-2024 Round 2) to advance these investigations into animal studies in the physiology and pathophysiology of the heart.