Research

Mechanisms of 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 underlying mechanisms and identify novel potential target molecules that contribute to both ischemic and non-ischemic injury.

Mechanisms of Cardiac Remodeling and Heart Failure

We routinely leverage both ischemic (permanent coronary artery ligation) and non-ischemic (left ventricular 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 inflammation, fibrosis, hypertrophy, and decompensation in response to chronic stress, with the goal of identifying novel targets for treatment of heart failure.

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 are using single cell RNA sequencing and flow cytometry approaches in combination with genetically targeted knockout mice to investigate pathways that modulate sterile inflammation within the injured myocardium.

Investigating Metabolic Dysfunction

The heart requires a massive amount of ATP in order to maintain function, and an important contributing factor to heart decompensation and failure is an insufficient energy supply due to impaired energy production in heart muscle cells. We seek to understand how impaired mitochondrial respiration develops in the stressed heart, with the goal of preventing energetic collapse and progression to heart failure. We leverage next-generation sequencing, metabolomics profiling, real-time O₂ consumption measurements, and proteomics-based approaches to understand signaling networks and to identify new potential therapeutic targets for restoring proper metabolism.