The heart can regenerate, but it’s not enough to reverse or fix damage caused by a heart attack or limited blood flow. We’re trying to figure out how to help a patient’s own heart muscle cells (cardiomyocytes) improve their own ability to repair the injured area. In addition, we’re studying the underlying genetics of heart disease (cardiovascular disease) in order to develop new therapies to correct mutations or stop the progression of disease. 

Heart disease: regeneration and repair

We focus on two primary approaches to understanding heart disease: stimulation of endogenous heart muscle repair (helping a patient’s own heart repair itself), and studying the genetics underlying heart disease.

Kick-starting more heart muscle cells into action

Ischemic heart disease is lack of blood flow to the heart, and often leads to a heart attack, which results in the death of heart muscle cells (cardiomyocytes). Interestingly, there is a very small number of cardiomyocytes that start to replicate and make new healthy cardiomyocytes, but unfortunately, it’s not enough for the heart to fully recover.

We’re searching for factors and genes that can stimulate a patient’s own heart to better repair itself. Using novel techniques including Tomo-Seq (genome-wide sequencing that includes spatial relationships of genes) and single cell sequencing, we can look at genes that regulate cardiomyocyte damage and study the function of these genes. So far, we’ve identified a few transcription factors that that may be able to trigger more cardiomyocytes to also replicate in response to injury or disease. 

Heart disease in a dish

Another aspect of our work investigates the molecular pathways of genetic and inherited heart disease. For obvious ethical reasons, it’s difficult to get heart muscle cells from human patients, so we’re using an alternative cell source called induced pluripotent stem cells (iPS cells) to model genetic heart diseases. iPS cell technology can reprogram an adult cell back into an immature state. We can then direct these cells to become any type of cell we want. For example, we can take a skin biopsy from a patient with a genetic heart disease and reprogram the cells to become cardiomyocytes. What’s unique about these cardiomyocytes is that they carry the exact genetic flaws of the patient. We can use these cells to generate an in-depth view of the patient’s disease and hopefully develop new therapies that either correct the mutation or slow or halt disease progression.

Research with a strong translational push         

Although I’m a basic science researcher at heart, I’ve always focused on being able to use research to improve human health. For a number of years, I worked in a very different sector – I’m the scientific co-founder of miRagen Therapeutics, a company developing microRNA technology for treatments (microRNAs are important for regulating gene expression); several programs are now in clinical trials. I’ve moved back to academia, and the infrastructure within the Circulatory Health program greatly supports our vision of translating our scientific findings into patient benefit.