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Student research project

Supervisor(s): Professor Karlheinz Peter, Dr Smriti Murali Krishna and Dr Yung-Chih (Ben) Chen

Project summary

The main objective of this project is to understand the molecular mechanisms that drive atherosclerotic plaque formation and rupture in CVDs.

Cardiovascular diseases (CVDs), principally ischaemic heart disease including myocardial infarction (MI) and stroke, are the leading cause of global mortality and a major contributor to disability. The underlying cause of most CVDs is the formation of lipid-laden atherosclerotic plaques in medium and large arteries, such as those that supply the heart and brain with blood. Stable plaques grow slowly over several decades until they may cause stenosis or occlusion. Unstable or “vulnerable” plaques are prone to spontaneous erosion, fissure, or rupture, causing acute thrombosis (blood clots), occlusion, and infarction long before they cause hemodynamically significant stenosis. Most clinical events and CVD mortality result from unstable plaques. Thus, plaque stabilisation is a promising approach to reduce morbidity and mortality.

We aim to deeply characterise the fundamental molecular pathways underlying plaque formation and rupture using novel translational disease models and cutting-edge technologies. Based on novel genomic data from polygenic risk score predictions, we identified novel targets that will be assessed to validate their causative role and therapeutic potential. We will use novel theranostic agents for diagnosis and targeted delivery of therapeutics to stabilise the vulnerable plaques. With a particular focus on translational relevance, we will assess the potential of novel therapies such as stem cell-derived exosomes and novel small-molecule inhibitors preventing plaque rupture.

Related methods, skills or technologies

This project is suitable for a Masters, Honours or PhD student and and would involve the use of translational animal models, confocal microscopy, multiphoton microscopy, flow cytometry, cell culture, immunohistochemistry and molecular assays. The student will join a skilled research team in the field of platelet function and cardiovascular disease.

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