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The Cardiac Precision Group and The Aortic Research Group

Dr Cassandra Malecki

BMedSc (Hons), PhD

Since starting in my postdoctoral position, I have assisted with the progression of multiple projects within the cardiac precision group and the aortic group, overseen the collection of tissue and management of the Sydney Heart Bank and initiated my own research project and research questions.

Coming from a background in molecular biology, I was first able to assist in helping students in executing techniques in the lab to examine the level of expression of relevant genes in heart failure samples and how these levels compare to those in healthy hearts. I have also been involved in helping prepare samples for large-scale analysis of human aortic and cardiac samples, which have allowed for the investigation over 4500 proteins and genome-wide RNA expression in different types of heart failure and aortic disease, contributing to the findings of multiple projects, with some currently being written up for publication.

I was given the chance to the take the lead on an exciting project investigating the changes that occur in the heart as we age. Age is one of the biggest risk factors of heart failure, and therefore understanding the changes that occur in the heart as we age will assist in the development of preventative and therapeutic options for heart failure. We are currently looking at levels of proteins, metabolites, and lipids and the expression of thousands of genes in hearts of individuals over the age of 50 and comparing these to hearts of individuals 20 and younger. This is the first ever study to characterise the molecular changes that occur in normal ageing of the human heart.  We have found very interesting and novel results including changes in levels of contractile proteins and seen how the heart changes its ability to utilise energy as we age. We are currently writing up the results of this study, with the aim to submit it for publication before the end of 2022, to a highly prestigious scientific journal.

Most of this research is made possible due to the utilisation of the unique resource that is the Sydney Heart Bank. A major part of my role has involved collecting precious human heart and aortic tissue samples from RPAH, processing the tissue, managing the Sydney Heart Bank database, and preparing samples for other members of the lab and collaborators around the world who are using the tissue for their own research projects. I have also optimised protocols for tissue collection and processing and have put systems in place to keep thorough track of samples coming in and out of the heart bank and tracking sample information.

To expand on the cardiac ageing project mentioned earlier, I have taken a particular interest in developing a project that examines how the aorta changes at a molecular level with age, and how these changes may impact the heart. The aorta naturally becomes stiff as we age. The stiffer the aorta is, the harder the heart must work to pump blood into the aorta and around the body.  If the heart is under these higher stresses for an extended period, this can lead to heart disease. Therefore, understanding the relationship between the aorta and heart in ageing may bring to light new therapeutic options for heart disease. After thoroughly examining the Sydney Heart bank database, I identified healthy heart tissue and healthy aorta that were from the same individual, with samples covering a wide age range.  I have used these samples to examine the molecular relationship between the aorta and the heart as we age. Currently, genome-wide RNA expression and protein levels of the tissue samples have been completed, with the data to be analysed in the next few months and future experiments in the planning process.

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