Collaborating to Develop A New Roadmap for Personalized Medicine

THI’s Cardiomyocyte Renewal Laboratory takes a closer look at the gene expression landscape of congenital heart disease

Researchers in the Cardiomyocyte Renewal Laboratory at THI, directed by James F. Martin, MD, PhD, are working to understand how genetic pathways function in the heart. By obtaining an in-depth understanding of these pathways, Dr. Martin and his team of researchers hope to develop new techniques for preventing and treating heart disorders.

One area of ongoing research is the study of how cell growth and differentiation are regulated during early development and how these processes are related to heart disease.

“The development of the heart is a highly complex process that begins early in pregnancy,” explains Dr. Martin. “When errors occur in this process, the heart doesn’t develop properly. As a result, babies can be born with defects in the heart, which is known as congenital heart disease, or CHD.” CHD includes a wide spectrum of defects that commonly lead to pediatric heart failure—the leading cause of death in infants, children, and adolescents.

CHD affects an estimated 12,000 to 35,000 children under 19 years of age in the United States each year.


“Although more than 90% of patients born with CHD survive into adulthood, many often die prematurely from heart failure or noncardiac causes,” says Dr. Martin. “How this disease develops and progresses is poorly understood, so we are trying to better understand the molecular nature of CHD. Eventually, we hope our work can be used to develop individualized therapies for patients with CHD.”

Recently, Dr. Martin and his team published the results of a collaborative, innovative study in which they studied cells and their molecular makeup in heart tissues from pediatric donors and patients with various types of CHD (Hill, M.C., Kadow, Z.A., Long, H. et al. Integrated multiomic characterization of congenital heart disease. Nature, (2022).

They also studied blood samples and used other publicly available data from blood donors of various ages.

To gain insight into CHD at the molecular level, the research team used a complex “multi-omics” approach that involves combining different types of data from multiple cutting-edge techniques used to study genetic material and proteins in the body.

For the first aim of the investigation, the researchers examined gene expression in each heart sample.

Studying patterns of gene expression can be used to identify the types of cells and their functions. The researchers identified a total of 14 different cell types in donor and CHD heart samples. Furthermore, they found that gene expression patterns in these cells were unique to the type of CHD.

For another aim of the study, the researchers analyzed the expression of genes known to function in the heart. In CHD heart samples, they found evidence of cells active in regeneration. They observed stronger and more cell-to-cell interactions in CHD heart samples than in donor samples, which is a finding often observed in diseased tissues.

In addition to studying heart cells, the researchers also analyzed gene expression in the blood cells of donors and patients with CHD.

Interestingly, they uncovered evidence of a weakened immune response in the blood cells of patients with CHD. This finding supports those of other studies showing that patients with CHD often develop infection and cancer. The researchers also detected an increase in signals related to heart development and inflammation being sent from blood cells to heart cells of CHD patients.

When asked how this work will ultimately lead to individualized medicine for patients with CHD in the future, Dr. Martin’s was encouraging and enthusiastic.


“Now that we have a baseline picture of the patterns of gene expression in different types of CHD, we can perform more focused studies to directly compare heart tissues within the same class of CHD. In addition, we can distinguish between the influence of the underlying CHD and the resultant disruption in heart function. We hope our study will help to spur more studies that will continue to provide new mechanistic insights into CHD.”

Hill, M.C., Kadow, Z.A., Long, H. et al. Integrated multiomic characterization of congenital heart disease. Nature (2022).

By Nicole Stancel, PhD, ELS(D)