Cardiac Cellular Systems
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Laboratory Head
Dr Alexander Pinto8532 1275
Research Overview
Heart failure is a leading cause of mortality worldwide. Resulting from a wide range of etiologies, heart failure is characterised by deleterious cardiac remodeling and decline in heart function, ultimately leading to organ failure and death. Currently, there are no effective treatments for heart failure, and fundamental questions remain unanswered regarding the ways in which cardiac remodeling occurs and how it may be reversed.
Until recently the cellular composition of the heart was poorly defined. Using advanced genetic, flow cytometric, and single-cell transcriptomic approaches, our lab has shed new light on the cellular constituents of the heart by demonstrating that the heart is comprised of a complex and diverse ecosystem of non-myocytes. Based on these discoveries, new avenues of cardiovascular research involving the targeting and manipulation of specific cell types and networks are now possible. Today, very little is known about how the ecosystem of non-myocytes in the heart operate as a cell network.
Our aim is to study the complex ecosystem of cells that form the heart to identify novel genetic and cellular drivers of cardiac disease and ageing.
Overarching aims
- Determine how pathological changes in cardiac cell networks contribute to the development of heart failure.
- Determine whether manipulating the cell network can influence cardiac remodeling and thus be used to prevent or treat cardiac pathologies
Using single-cell, data science, micro-anatomy and traditional mouse genetics approaches our research uses and integrative systems biology approach for uncovering fundamental processes governing cell networks in the heart.
Key areas of ongoing research
- Determining the plasticity and elasticity of cardiac cell networks in the context of physiological stressors such as obesity and hypertension.
- Determining the molecular and cellular drivers of these processes.
- Determine sex differences in cardiac development, homeostasis, and disease.
- Development of unique genetic, computational biology, and imaging approaches to precisely study diverse cell populations in the heart.
Key areas of technical expertise
- Single-cell biology — including single-cell RNA sequencing, high-dimensional flow cytometry, and image cytometry.
- Multidimensional imaging — including 3D imaging and spatial mapping of cellular interactions.
- Mouse genetics — including the development of novel cell- and organ-specific genetic tools.
Staff
- Ms Gabriella Farrugia, Research Assistant
- Dr Malathi Imiyage Dona, Computational Biologist
- Mr Ian Hsu, Data Scientist
- Taylah Gaynor, Graduate Research Student
- Crisdion Krstevski, Graduate Research Student
- Charlie Cohen, Graduate Research Student
Funding
- NHMRC
- Diabetes Australia
Research Opportunities
This research project is available to Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
Research Outcomes
(2021) Diastolic dysfunction in a pre-clinical model of diabetes is associated with changes in the cardiac non-myocyte cellular composition. Cardiovasc. Diabetol
(2020). High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy. Circulation CIRCULATIONAHA.119.045115.
(2020). Cardiac Cellularity is Dependent upon Biological Sex and is Regulated by Gonadal Hormones. Cardiovasc. Res.
(2020). New perspectives of the cardiac cellular landscape: mapping cellular mediators of cardiac fibrosis using single-cell transcriptomics. Biochem. Soc. Trans.
(2018). Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart. Cell Reports 22, 600-610.
Research Publications
- High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy
Circulation 2020
- Cardiac cellularity is dependent upon biological sex and is regulated by gonadal hormones
Cardiovasc. Res. 2020
- Revisiting Cardiac Cellular Composition. Circulation Research, 2016