Our objective
Our mission is to better understand the therapeutic mechanisms of cardiovascular-protective natural supplements in platelets and the heart, and use this knowledge to develop next-generation precision medicine for the prevention and treatment of life-threatening thrombosis and ischaemic stroke.
Despite the global burden of cardiovascular disease, the development of new cardiovascular drugs has stalled for over two decades. The primary reason is intolerance to drug-related side effects. Recently, there has been considerable interest in the development of natural supplements for cardiovascular-protective therapeutics, due to their inherent safety profiles and the clinical evidence for ameliorating chemotherapy-induced cardiovascular complications. However, it remains a huge challenge to understand the cardiovascular-protective mechanisms at the molecular level, which impedes pharmacological optimisation of these bioactive agents for therapeutic use. Therefore, we aim to apply cutting-edge chemoproteomics platforms to understand the intricate signalling interplay in cardiomyocytes in response to different natural products and to construct a comprehensive chemotype database for cardiovascular-protective drug discovery.
Our research aims to determine the protective mechanisms underlying heart-healthy diets and herbs, and apply this knowledge to design and develop safer and more effective cardiovascular therapeutics.
To this end, we focus on the development of new proteomic platforms to enable genome-wide understanding of how natural supplements and drugs perform in the context of cardiovascular complications, and on constructing a comprehensive chemical-proteomics database to reveal the therapeutic impacts on thrombosis at the cellular and molecular level.
We also focus on adopting new drug discovery technologies – PROTAC and ABPP that have led to a tremendous achievement in anti-cancer drug discovery – to accelerate the development of precision medicine to tackle thrombosis and ischaemic stroke. In particular, leukocytes, ie, neutrophil and macrophage, have been strongly implicated in the pathogenesis of thrombosis. We aim to develop new PROTAC molecules to tackle the challenge of severe thromboinflammation that leads to the poor prognosis of cardiovascular disease and COVID-19.
Our impact
Thrombotic complication is the leading cause of mortality and accounts for one in four deaths worldwide. Despite intense investigation over the past decades, the discovery of novel cardiovascular drugs has remained disappointingly low. Novel antithrombotic drugs entering clinical testing have stalled due to the large attrition in investment and increasing demand in risk assessment. However, the existing antithrombotic drugs such as aspirin and clopidogrel are ineffective, with less than 15 per cent of diabetic patients taking these medicines avoiding a fatal thrombotic event. This situation is likely to worsen in the near future due to the rapidly growing incidence of obesity and diabetes.
The chemical biology research approach adopted by our group is designed to identify effective and durable antithrombotic therapy inspired by natural supplements, and to repurpose anti-cancer and anti-inflammatory drugs for thrombotic conditions.
Selected grants
2019 USYD Cardiovascular Initiative Catalyst Award – Project: A PROTAC-based bioengineering platform for novel anti-platelet drug discovery
2020 USYD Cardiovascular Initiative Catalyst Award – Project: Towards the development of safer and more effective antithrombotics for the treatment of stroke
2020 Therapeutic Innovation Australia: Pipeline Accelerator COVID-19 Rapid Response Funding – Project: Towards the development of more effective and safer high-affinity ACE2 variants for the treatment of COVID-19