About the Cardiac Cellular Systems laboratory
Heart failure is a leading cause of mortality worldwide. Resulting from a wide range of etiologies, heart failure is characterized 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 (Figure 1: Skelly et al. 2018, Pinto et al. 2016, Pinto et al. 2012). Based on these discoveries, new avenues of cardiovascular research involving the targeting and manipulation of specific cell types and networks are now possible. Today, virtually nothing is known about how the ecosystem of non-myocytes in the heart operate as a cell network.
tSNE plot displaying the diversity of cardiac non-myocytes in the adult mouse heart.
- 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 (Figure 2).
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.
Model of heart failure driven by pathological remodeling of cardiac cell networks. Factors promoting heart failure and reconfiguration of cardiac cellular constituents shown in red. Potential remedial strategies shown in blue.
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.
- 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 development of novel cell- and organ-specific genetic tools.