Every 12 minutes, an Australian dies of cardiovascular disease. We’d like to change that. Our group conducts clinical research to understand how inflammation works together with altered blood lipid levels to promote cardiovascular disease.
This project opportunity is focused on Familial Hypercholesterolaemia (FH), which is an inherited genetic mutation that results in vastly elevated cholesterol levels. FH increases the risk of premature cardiovascular disease, heart attack, and stroke, with 7x increased risk of heart attack in the 25-39 year age group. The prevalence of FH is 1/250 people, but only ~10% of people with this condition are aware they have it. Research to improve diagnosis of this condition, and to better understand of the mechanisms linking FH to clinical cardiovascular events, is essential.
We are establishing an FH biobank, which is funded by OHMR. This biobank will expedite FH research by removing the need to collect samples prospectively. The collection will consist of ~500 samples from participants with FH. Blood-derived samples (plasma, serum, buffy coat, PBMCs and dried blood spots) will be obtained over ~ 3 years and stored at a dedicated biobanking facility. The student joining our team will aid in the collection, and utilise some banked specimens to address one of our aims; improving FH screening or understanding inflammation in FH. Our lab-based techniques include, but are not limited to, cell isolation, cell culture, flow cytometry, gene expression.
Westmead - Westmead Clinical School
We currently hold funding to support the collection, processing and storage of FH biospecimens at the NSW Health statewide biobank. A student working on this project will be involved in establishing this biobank, as well as utilising biobank samples for research.
There are two proposed broad aims that utilise these samples and could form the basis of a PhD. Firstly, we want to address the underdiagnosis of FH in Australia. We propose that dried blood spot samples (such as those collected from all newborns in Australia) could be used for universal FH screening to identify those with the disease, early in life. Secondly, we want to understand the inflammatory changes that occur in FH and how these may contribute to someone having a clinical event such as heart attack. The precise details of the PhD project would be determined based on student interest and experience.
Aim One: Here we will establish a method to measure lipoproteins and lipids using dried blood spot samples from people with FH. Techniques include proteomics/lipidomics. This is an important step in investigating the utility of dried blood spot samples for universal screening of FH in newborns.
Aim Two: Here we will determine (i) what inflammatory changes occur in FH, (ii) whether these differ with different genetic mutations, (iii) whether these are resolved in cases where substantial or target cholesterol reduction has been achieved (iv) whether unresolved inflammatory changes are linked to longer-term cardiovascular outcomes, such as heart attack.
At the Vascular Biology Research Centre, Westmead Hospital, our overarching aims are to understand the role of inflammation in cardiovascular/metabolic diseases. We conduct a range of clinical projects focusing on circulating monocytes and monocyte-derived cells. Considering cardiovascular disease is associated with numerous other disease states and risk factors, our interests extend to diabetes, dyslipidaemia, and the broader impact on health.
The opportunity ID for this research opportunity is 3418