Molecular Proteomics
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Division Head
David Greening03 8532 1585
Research Overview
We explore intercellular signalling and apply advanced omics in the context of the heart and circulation.
Our research program seeks to understand cell signalling through nanovesicles as a therapeutic strategy and integrate multi-disciplinary technologies to understand cardiac remodelling and its repair.
The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Production and release of EVs as biological messengers appears to be evolutionary conserved across all kingdoms of life. Our lab has pioneered the understanding and function of EVs, providing key insights into the physiological and therapeutic roles that EVs display depend on their cargos and their capacity to transfer proteins, to the target cells and organs. EVs released into blood mediate systemic cross talk to orchestrate essential life processes such as metabolic homeostasis, inflammation and immunity, and drive progression of life-threating disease such cardiovascular disease and cancer metastasis.
The Molecular Proteomics group uses a multi-disciplinary approach to understand the molecular composition and function of EVs incorporating proteomics, lipidomics, cell biology, stem cell models, nanomaterials, molecular biology, and physiology, with the goal of identifying new deliverable therapeutic targets. Our team employs direct and localised administration approaches incorporating biomaterials, and chemical labelling strategies to understand the cell surfaceome as a targetable platform for interaction and delivery. His team has also developed optimised workflows to capture precise and comprehensive proteome of EVs, especially from ultra-low sample quantities (sub-nanogram), an important challenge in the field where obtaining in-depth proteome information is essential.
Our aim is to study the complex signalling of heart including extracellular vesicles, to identify their form and function and engineer their utility for enhanced therapeutic application in cardiac disease and repair.
Key areas of ongoing research
- Assembly of a precise and comprehensive proteome blueprint of circulating extracellular vesicles
- Understand circulating EV surfaceome as interactive, tissue-specific vascular platform
- Bioengineer extracellular vesicles for cardiovascular therapeutics
- Integrate multi-omics to define mechanisms of extracellular vesicle function in heart
- Proteomics and machine learning strategies to decipher subcellular proteome of the heart
The team is internationally recognised in the field of extracellular vesicles and proteomics. To achieve our research goals, the laboratory uses advanced proteomics, phosphoproteomics, lipidomics, regenerative cell biology, and collaborative network in molecular therapies with the goal of identifying new deliverable therapeutic targets for next generation cell-free therapy.
Key areas of technical expertise
- Extracellular vesicle biology — including isolation (density, ultracentrifugation, IP-specific), biophysical and biochemical characterising, single particle tracking analyses, and confocal imaging.
- Advanced proteomics (mass spectrometry)— including discovery proteomics, high resolution/sensitivity approaches, phosphoproteomics, biofluid proteomics (plasma), and bioinformatics
- Subcellular proteomics – including machine learning, cell surface mapping, organelle profiling, secretome biology, bioinformatics
- Cell/in vivo biology — including the development of cell surface labelling tools, functional assays, in vivo mouse models (heart disease), histology and relating microscopy imaging.
Research projects are available to Honours and PhD students to join as part of their thesis and training. High level students with prior laboratory expertise suited to the areas of research are highly encouraged. Please contact the Research Group Leader to discuss your options.
Staff
Team members
Associate Professor David Greening (Division Head)
Dr Alin Rai (Senior Post-doctoral Fellow, Group Leader)
Dr Bethany Claridge (Post-doctoral Fellow)
Mr Jonathon Cross (Research Assistant)
Ms Auriane Drack (PhD Student)
Ms Haoyun Fang (PhD Student and Research Assistant)
Ms Iasmin Inocencio (PhD Student)
Mr Jonathan Lozano (PhD Student)
Ms Qi Hui Poh (PhD Student)
Mr Sadegh Eslami (PhD Student)
Funding
- NHMRC / MRFF
- Heart Foundation
- Tithon Biotechnology
- Prescient Therapeutics
- Takeda
- Various industry partnerships
Research Publications
- (2022) Scalable generation of nanovesicles from human-induced pluripotent stem cells for cardiac repair
- (2021) Proteome characterisation of extracellular vesicles isolated from heart Proteomics
- (2021) Secreted midbody remnants are a class of extracellular vesicles molecularly distinct from exosomes and microparticles Nature Commun Biol
- (2021) Development of extracellular vesicle therapeutics: challenges, considerations and opportunities Front Cell Dev Biol
- (2021) Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform Journal of Extracellular Vesicles
- (2021) Sustained subcutaneous delivery of secretome of human cardiac stem cells promotes cardiac repair following myocardial infarction Cardiac Research
- (2023) Estrogen receptor α deficiency in cardiomyocytes reprograms the heart-derived extracellular vesicle proteome and induces obesity in female mice ', Nature Cardiovascular Research
- (2023) Quantitative proteomic landscape of unstable atherosclerosis identifies molecular signatures and therapeutic targets for plaque stabilization. Nature Commun Biol
- (2023) Extracellular Vesicles as Next Generation Immunotherapeutics. Semin Cancer Biol.
- (2018) Extracellular vesicles in cancer—implications for future improvements in cancer care. Nature Reviews Clinical Oncology
- (2023) Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts. Journal of Extracellular Biology