About Our Lab
Heart disease is a major health and economic burden worldwide and the leading cause of death in the United States. Although much progress has been made in understanding the causes of genetic heart disease, ischemic heart disease and heart failure, the molecular underpinnings that contribute to injury have yet to be fully elucidated. Unfortunately, the result is current treatments that are largely ineffective.
Our lab aims to better understand the molecular mechanisms responsible for heart injury and the progression to heart failure using a systems-based approach. Our long-term goal is translating these findings to improved therapeutic approaches for patients.
Mechanisms of ischemic heart injury
A major focus of the lab is to understand how the signaling cascade known as the Hippo pathway – a fundamental and conserved growth control mechanism – influences heart injury, within cardiomyocytes and fibroblasts, as well as in extra-cardiac cell types. Our research group previously reported that Hippo signaling exhibits cell-type specificity, and can influence paracrine interactions between cardiomyocytes and other cell types within the heart. We use a combination of complementary approaches including tissue-specific gene targeting, adoptive transfer and primary cell culture, to elucidate injury mechanisms that contribute to myocardial infarction.
Overview of the Hippo pathway. (Wackerhage et al, Sci. Signal. 2014; 7(337))
Mechanisms of cardiac remodeling and heart failure
We routinely leverage both ischemic (permanent coronary artery ligation) and non-ischemic (LV pressure overload) stress to model human pathology, and induce cardiac remodeling and eventual heart failure in mice. Our studies seek to understand the mechanisms that necessitate cardiac fibrosis, hypertrophy and decompensation in response to chronic stress, with the goal of identifying novel targets for treatment of heart failure.
Myocardial infarct and remodeling in mice (Del Re et al, J. Biol. Chem. 2013; 288(6))
Understanding fundamental principles of inflammation
We are interested in potential crosstalk between Hippo signaling and innate immune function, both as a basic mechanism of biology, and as it relates to cardiovascular disease. To this end, we use proteomics and genomics based approaches in combination with genetically targeted knockout mice to investigate these pathways.
Cardiac transcriptome analysis by RNAseq, with assistance from Rutgers NJMS Genomics Center.