Baker Department of Cardiometabolic Health

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Projects Title Research Node (Project Site) Department Project Description Number of Places Available (Masters) Number of Places Available (Honours) Primary Supervisor UoM Staff ID Number Primary Supervisor Title Primary Supervisor First Name Primary Supervisor Surname Primary Supervisor Email Co-Supervisor 1 Title Co-Supervisor 1 First Name Co-Supervisor 1 Surname Co-Supervisor 2 Title Co-Supervisor 2 First Name Co-Supervisor 2 Surname Co-Supervisor 3 Title Co-Supervisor 3 First Name Co-Supervisor 3 Surname Additional Supervisors (Please include the title and full name) Opportunity
: Unravelling the role of breast milk ether lipids in modulating immune function in early life Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health In this project we will combine our lipidomics expertise with our unique mouse models of ether lipid modification to define the role of breast milk ether lipids in modulating immune function in infants. Professor Peter Meikle peter.meikle@baker.edu.au Dr Sudip Paul n/a PhD students; Honours students
A novel approach in improving lipidomics throughput for population profiling Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health This study aims to generate a novel approach in comprehensive lipidomic profiling using high resolution mass spectrometry approaches in conjunction with computational biology. Professor Peter Meikle peter.meikle@baker.edu.au Dr Kevin Huynh n/a PhD students
Activated platelets targeted drug therapy Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Developing a novel targeted fibrinolytic drug that is directed against activated platelets. Fibrinolysis is a valuable alternative for treating myocardial infarction when an invasivesurgical procedure is not available in a timely fashion. Dr Xiaowei Wang xiaoweiw@unimelb.edu.au Professor Karlheinz Peter Dr Laura Bienvenu n/a PhD students; Masters by Research
Assessing the therapeutic effects of plasmalogen supplementation in a mouse model of heart failure Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Cardiovascular disease remains the leading cause of death worldwide. Approximately 60% of men and 45% of women with heart failure die within five years of diagnosis. Additional therapies are required to address this major unmet need. Lipids are a major component of all cell membranes including heart muscle cells. Recent studies have shown that lipids (molecules such as fats) are altered in various pathologies, such as cardiovascular disease. Plasmalogens are a specific type of lipid that are enriched in the heart. Previous studies have demonstrated that plasmalogen levels were reduced in settings of type 2 diabetes. I have recently published results that demonstrate an association of reduced plasmalogen levels to heart failure in mice. The role of plasmalogens in the heart however, is currently unclear. This study aims to assess the potential of treating a surgical mouse model of heart failure(Ischemia reperfusion) by using a dietary supplement that increases plasmalogens levels in the heart. 1 Dr Yow Keat Tham yowkeat.tham@baker.edu.au Prof Julie McMullen n/a Honours students
Brain storming therapeutics for neurodegeneration with novel research models Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Our current understanding as to the pathways that cause and progress neurodegenerative conditions such as Alzheimer's and Parkinson's disease is poorly understood. Much information stands to be gained from studying preclinical models of these conditions, in which we can study the early and late changes that occur in the brain that associate with disease severity. This project will use several novel preclinical models to identify novel therapeutic targets that may be used in the future to treat these conditions 1 A/Prof Brian Drew brian.drew@baker.edu.au n/a PhD students; Honours students
Developing nanoparticles for targeted theranostics delivery of drug and gene therapeutics Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Research in the Molecular Imaging and Theranostics lab focus on translational research that links the findings from basic science to the practical applications that enhance human health and well-being in clinical settings. Developing new bio-compatible nanoparticles that can be used for targeted delivery and localize the drugs/genetic therapy to the site of disease, thereby eliminating reduce side effects. 1 Dr Xiaowei Wang xiaoweiw@unimelb.edu.au Dr Laura Bienvenu n/a PhD students; Masters by Research
Developing platelet derived nanoparticles for targeted thrombolysis Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Stroke is one of the leading causes of death and major morbidity worldwide. Despite this, the current thrombolytic (clot busting) therapies remain largely ineffective and many patients are resistant to therapy. There is a need for improved thrombolytic drugs and strategies for overcoming thrombolysis resistance. One strategy for achieving this is using targeted drug delivery to deliver high local concentrations of thrombolytic drugs to the thrombus to improve the efficacy of drug treatment. To achieve this, we are proposing using platelet derived nanoparticles loaded with thrombolytic drugs to achieve targeted thrombolysis. Prof Karlheinz Peter karlheinz.peter@unimelb.edu.au Dr Mitchell Moon n/a PhD students; Masters by Research; Honours students
Development and validation of a high throughput clinical lipidomics platform Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health This project will work to develop a Clinical Lipidomic Platform, which would measure several hundred different plasma lipids via LC/MS in a rapid and cost-effective manner, designed for clinical use. Professor Peter Meikle peter.meikle@baker.edu.au Dr Thomas Meikle n/a PhD students; Masters by Research
Diagnosis and therapy of inflammatory diseases using molecular ultrasound imaging Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health With steadily increasing health care expenses, a promising translational imaging application using ultrasound can fulfil the need for a cost-effective and non-invasive diagnostic tool. This project aims to investigate whether VCAM-1 targeted microbubbles will locate inflamed vessels using molecular ultrasound imaging, thereby providing a better diagnostic technology Dr Xiaowei Wang xiaoweiw@unimelb.edu.au Professor Karlheinz Peter n/a PhD students; Masters by Research
Do short chain fatty acids prevent gut leakiness and enhanced haematopoiesis induced by a high salt diet? Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Our laboratory has discovered that a high salt diet promotes a breakdown of the intestinal barrier in the gut which causes activation of the immune system and changes within the bone marrow microenvironment, altering blood production. This project will explore the hypothesis that supplementation of butyrate, an anti-inflammatory short chain fatty acid, will prevent high salt diet-induced gut leakiness, immune cells activation and protect the bone marrow microenvironment from being destructed. This will allow for the retention of haematopoietic stem cells and normal blood production. This project will employ a variety of assays and experimental readouts to address this hypothesis and give the student a valuable insight into immune and stem cell biology within a highly successful world class research laboratory. Prof Andrew Murphy andrew.murphy@baker.edu.au Dr. Sam Lee n/a PhD students; Masters by Research; Honours students
Does epicardial adipose tissue contribute to atrial fibrillation in endurance athletes? Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Exercise has substantial health benefits with pleomorphic vascular, metabolic, psychological and anti-neoplastic actions resulting in improved quality of life and longevity. Despite these many benefits, numerous studies have shown that endurance athletes are more likely to develop atrial fibrillation (AF) than non-athletes. The type, intensity and amount of sport appears to influence the risk of developing AF. Several endurance sport activities have been shown to increase the risk of developing AF but an excess in AF has not been shown in non-endurance sports. Furthermore, lifetime hours of participation appear to increase the risk of developing AF. Intriguingly, women appear relatively protected and an association between endurance sport and AF has not been clearly demonstrated amongst female endurance athletes. The mechanisms by which endurance sport promotes the development of AF are unclear. There are, however, a number of pathophysiological mechanisms which are known to increase the risk of AF in non-athletes which have correlates in athletes. This project will investigate the relationship between epicardial fat and atrial fibrillation in endurance trained athletes. 1 Dr Erin Howden erin.howden@baker.edu.au A/Prof Andre La Gerche n/a Honours students
Exploring how a high salt diet promotes bone destruction through immune cell activation Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Diets rich in salt have been linked to bone pathologies. This has generally been attributed to mineral exchange, causing weaker bones. However, our group hypothesized that this process is biologically driven. We have made initial discoveries to show that specific immune cells are produced and activated by a high salt diet that is linked with bone destruction. This project will focus on the novel mechanisms contributing to this discovery. Specifically, this project will determine how the immune cells interact and activate osteoclasts within the bone and will explore where these immune cells are first activated. We anticipate these findings being important across several age groups and will explore ways to offset these detrimental effects of high salt intake. The student will be exposed to a world class research environment and cutting-edge techniques, with excellent supervision. Techniques will include flow cytometry, sectioning of tissues (including bones), immunofluorescence, micro CT and multiphoton microscopy. Prof Andrew Murphy andrew.murphy@baker.edu.au Dr. Sam Lee n/a PhD students; Masters by Research; Honours students
Exploring how diabetes causes increased proliferation of haematopoietic stem cells carrying a mutation in DNMT3A Baker Department of Cardiometabolic Health Clonal haematopoiesis of indeterminant potential (CHIP), caused by somatic mutations in haematopoietic stem cells (HSCs) causes a growth advantage in these cells causing them to outcompete non-mutated HSCs. CHIP was commonly thought to be a prerequisite to leukaemia, the disease ultimately responsible for death in these individuals. However, it was recently shown that people with CHIP more frequently die of cardiovascular disease. Interestingly, there is an association with CHIP and diabetes, but this has not been explored experimentally. We discovered that diabetes enhances the proliferation of HSCs carrying the most common mutation in CHIP (DNMT3A). This project will explore mechanism behind this using a variety of unique animal models and experimental techniques. This project will give the student a valuable insight into stem cell biology within a highly successful world class research laboratory. Prof Andrew Murphy andrew.murphy@baker.edu.au Dr. Dragana Dragoljevic n/a PhD students; Masters by Research; Honours students
Exploring the therapeutic potential of protein phosphatases in cardiometabolic disease Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Heart failure is a debilitating condition in which the ability of the heart to meet the body's demands for oxygenated blood is compromised. Prognosis is poor, with approximately 50 per cent of patients with heart failure dying within 5 years of diagnosis. There is a clear need for new therapeutic strategies for the treatment of heart failure. This project will explore the role of a family of proteins known as ‘protein phosphatases’ in the development of heart failure, and whether phosphatases can be selectively targeted to improve outcome in mouse models of heart failure. 1 1 Dr Kate Weeks kate.weeks@baker.edu.au n/a Masters by Research; Honours students
Heart Health in Women: Role of Physical Activity to Prevent Cardiovascular Disease Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Gender plays a major role in modulating the development of cardiovascular disease (CVD). Yet, women are underrepresented in clinical trials that aim to prevent heart disease, and outcomes are rarely specified in sex-specific terms. Physical activity levels play a key role in preventing the development of many chronic diseases like diabetes, cancer and cardiovascular disease. In a broader context, physical activity levels in women could produce different long-term CVD outcomes to men. Our group has extensively studied female athletes and physiological remodelling in response to lifetime exercise training. Extending work into physical activity rates and physiological response in a population-based cohort would enable our work to extend beyond physiological mechanism, to a translatable population-based approach. Our research has two separate aims: • Gender-specific risk factors (e.g disorders of pregnancy, high parity) accelerate CVD development in women. We aim to determine how physical activity acts as a modifier for CVD events after a pregnancy-based event. • Vigorous exercise produces a pronounced central and peripheral physiological adaptations. Female gender may have a protective effect during vigorous exercise. Dr Erin Howden erin.howden@baker.edu.au Dr Leah Wright A/Prof Andre La Gerche n/a PhD students
Identification of additional markers of ferroptosis with mass spectrometry Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Interrogate the role of ether lipids (with antioxidant properties) in ferroptosis and their potential to mediate and regulate the process in various biological settings. 1 1 Professor Peter Meikle peter.meikle@baker.edu.au Dr Kevin Huynh n/a PhD students; Masters by Research; Honours students
Immunity, Chronic Inflammation and Cardiovascular Disease Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Our research focuses on understanding the immunological mechanisms that drive inflammation in cardiovascular diseases. In doing so, we aim to facilitate the development and implementation of effective anti-inflammatory and immune-modulating therapies for patients with cardiovascular disease. Professor Karlheinz Peter karlheinz.peter@unimelb.edu.au Dr Jonathan Noonan n/a PhD students; Masters by Research
Integration of population level ‘omics data to target cardiometabolic disease Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Development of a plasma lipid profiling test to enable the early detection of patients at increased risk of type 2 diabetes and coronary artery disease. In addition we will develop methods to monitor treatment. Identification of individuals prior to the development of disease will enable early intervention and will have a profound effect on the health of the Australian population. Professor Peter Meikle peter.meikle@baker.edu.au Dr Corey Giles n/a PhD students; Honours students
Lipidomic Profiling of Atrial Fibrillation Progression in a Murine Model Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Atrial Fibrillation (AF) is a growing epidemic which is expected to double in prevalence by 2030. It is the most common rhythm disorder of the heart with series clinical implications, most notably stroke, where the risk can increase five-fold. Current treatments for AF have limited efficacy and/or have potentially dangerous side effects. New therapeutic targets therefore are required to address this unmet need. The area of lipidomic profiling has seen major advances due to the improvements in mass spectrometry technology in the past decade. Our lab and others have demonstrated the benefits of harnessing large scale (~800 individual lipids) lipidomic profiling in uncovering new potential therapeutic targets and/or biomarkers for the treatment/detection of various diseases, including heart failure. This study aims to comprehensively track changes in the lipidomic profile of the circulation, heart and surrounding tissues in a murine model as it develops AF. 1 Dr Yow Keat Tham yowkeat.tham@baker.edu.au Prof Julie McMullen n/a Honours students
Mechanotransduction in blood cells and consequences for thrombosis and inflammation Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health This project will determine the effects of blood flow on immune cell function and identify receptors that control such effects. Professor Karlheinz Peter karlheinz.peter@unimelb.edu.au Dr Sara Baratchi n/a PhD students; Masters by Research
Novel regenerative therapies in cardiovascular diseases Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Cardiovascular regenerative medicine is an exciting new approach that promises to change the current care of million people world-wide. The main objective of this project is to study the molecular mechanisms that result in promoting regeneration in damaged tissues. We will employ various experimental approaches to focus on different regenerative strategies including a broad spectrum of techniques such as stem cell derived exosomes. 1 Prof Karlheinz Peter Karlheinz.Peter@baker.edu.au Dr SMRITI MURALI KRISHNA Dr Xiaowei Wang n/a PhD students; Masters by Research
Novel therapies for atherosclerotic plaque stabilization Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Our research focuses on understanding the molecular mechanisms that drive atherosclerotic plaque formation and plaque rupture in cardiovascular diseases. We aim to deeply characterise the fundamental molecular pathways underlying plaque formation and rupture using translational disease models and novel therapeutic agents. 1 Prof Karlheinz Peter Karlheinz.Peter@baker.edu.au Dr Smriti MURALI KRISHNA Dr Yung-Chih (Ben) Chen n/a PhD students; Masters by Research
Plasmalogen modulation as a therapeutic approach for fatty liver disease Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health In this project we will combine our lipidomics expertise with our unique mouse models of plasmalogen modification as well as established mouse models of fatty liver diseases to define the therapeutic potential of plasmalogen modulation against fatty liver diseases. Identification of the mechanisms operating to attenuate disease pathogenesis will provide a clear rationale for the subsequent translation and commercialisation of this new prophylactic therapy. Professor Peter Meikle peter.meikle@baker.edu.au Dr Sudip Paul n/a PhD students; Honours students
Prefrontal cortex, sympathetic activity and blood pressure regulation Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health There is a need to improve our understanding of how the brain interacts with other systems in the body to control blood pressure, so as to tailor more effective treatments. The sympathetic nervous system is known to play a critical role in blood pressure regulation. We have shown that activity in the prefrontal cortex is functionally coupled to bursts of muscle sympathetic nerve activity (MSNA), indicating that it could contribute to sympathetic outflow and, hence, the control of blood pressure. In this study, we will test the direct effect of prefrontal cortex stimulation on modulation of MSNA and blood pressure modification. 1 Dr Tye Dawood tye.dawood@baker.edu.au Professor Vaughan Macefield n/a Honours students
Sympathetic activation in adults with inadequate sleep Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health This proposed study will assess the effect of inadequate sleep on the neural control of blood pressure to determine the role of sleep in hypertension. Dr Stephanie Yiallourou stephanie.yiallourou@baker.edu.au Professor Vaughan Macefield n/a PhD students; Masters by Research
Targeting Pyroptosis to improve diabetic cardiovascular disease. Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Cardiovascular complications associated with Type 2 diabetes (T2D) lead to significant morbidity and mortality, for which standard treatment options are insufficient to halt or reduce this clinical burden. Recent clinical evidence from the successful CANTOS trial suggests that targeting the cytokine IL-1b lessens inflammation and reduces the burden of cardiovascular disease. IL-1b is matured on the NLRP3-inflammasome along with IL-18 and GasderminD, the pyroptosis (a specific form of cell death) regulating protein. Pyroptosis and release of detrimental cytokines is hypothesized to propagate cardiovascular disease. This proposal will investigate the role of pyroptosis in mediating diabetes-driven cardiomyopathy. 1 1 Prof Judy de Haan judy.dehaan@baker.edu.au Dr Arpeeta Sharma n/a Honours students
The effect of ageing and sex differences on heart recovery following a heart attack Baker Department of Cardiometabolic Health There are currently no treatments for survivors of a heart attack to support their heart healing and to reduce their high risk of developing severe complications such as heart failure. Most preclinical studies investigating cardiac protection post-heart attack were conducted on young male animals, equivalent to a teenager; however, 90% of Australian victims of heart attack were above 55 years and, importantly, 40% of them were women. Our study will establish for the first time, the age- and sex-specific differences in heart recovery after a heart attack, with a particular focus on cardiac function and remodelling. This study will provide support for further studies on treatments adapted for aged males and females following a heart attack. 1 Associate Professor Anna Calkin anna.calkin@baker.edu.au Dr Adele Richart n/a Honours students
Type I interferon as a novel endogenous trigger of trained immunity Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Trained immunity is a form of innate immune memory resulting in a “high-alert” immune state. We will explore whether type I interferon can build immunological memory in vivo and whether this exerts harmful effects in the setting of chronic inflammation, such as atherosclerosis. Dr Andrew Fleetwood andrew.fleetwood@unimelb.edu.au A/Professor Andrew Murphy n/a PhD students
Unravelling the causes of persistent exercise intolerance in cancer survivors Baker Heart and Diabetes Institute Baker Department of Cardiometabolic Health Persistent exercise intolerance is a common side effect experienced by cancer survivors treated with chemotherapy, and may predispose cancer survivors to cardiovascular disease and poor quality of life. This project aims to utilise novel imaging techniques (MRI, ultrasound, DEXA) to understand the causes of exercise intolerance in cancer survivors previously treated with chemotherapy. 1 Dr Steve Foulkes steve.foulkes@baker.edu.au Dr Nicholas Saner Dr Erin Howden n/a Honours students
Validation of 4D Flow with Exercise using CMR Baker Department of Cardiometabolic Health Cardiac magnetic resonance imaging (CMR) is a powerful tool for assessing heart function. Advanced CMR techniques include functional assessment during exercise, and three dimensional flow assessment over the cardiac cycle. We aim to assess the validity of 4D flow during exercise, at low, medium and high intensity in a group of trained athletes. 2 Doctor Ben Costello ben.costello@baker.edu.au A/Prof Andre La Gerche n/a Honours students