Understanding Sex Differences in Deadly Heart Disease

What was the biomedical issue you addressed in your research and what did your studies find?

My Ph.D. research focused on studying myocarditis, a virus-initiated inflammation of the heart. Though rare, it's most prevalent in young males and can lead to a heart condition that may require a transplant or can even cause sudden death. Dr. Fairweather's lab has a long track record studying biological sex differences in heart disease. We studied sex differences in cardiac function and gene programming during acute stages of myocarditis.

Using state-of-the-art echocardiography, we were able to acquire highly detailed imaging of the disease process in mouse models. All mice showed reduced blood pumped out of the heart, the measure known as ejection fraction. We also measured the shortening motion that pushes blood up over the heart to the rest of the body, a motion known as global longitudinal strain. This sensitive technique lets us see subtle but important differences in heart contraction. Males showed worse function than females, and the differences in global longitudinal strain correlated with several immune cell populations in the heart, a sign of inflammation. The findings suggest that global longitudinal strain may be a useful clinical assessment of myocarditis, which can be hard to detect.

I was also interested in sex differences in gene programming and gene expression affecting heart energetics, particularly in mitochondria, organelles that produce energy for cells. My work revealed that females with myocarditis had gene signatures supporting mitochondrial function, but males with myocarditis had the same genes turned off. In addition, we identified sex differences in some key transcription factors that regulate gene programming, turning certain cell programs "on" or "off" like a light switch. Some of these sex differences have not yet been described in biomedical literature, and we're excited about our ongoing studies to understand why the differences exist.

What opportunities at Mayo did you take advantage of to further your leadership skills and your career path?

One area that was particularly exciting for me was the opportunity to teach others. I served as a TA (teaching assistant) in several classes. In teaching, I hope to help pass along necessary knowledge to future generations and to convey information in a way that inspires students to do good work. I also mentored several undergraduate and summer students during my Ph.D. It was rewarding to see several of my students win awards for the work that they had done and then presented at science fairs and conferences.

What aspects of Mayo's culture and approach to training helped you grow as a scientist and as a thinker?

The culture at Mayo — and within the Clinical and Translational Science graduate track — centers around the ongoing reminder that we're doing the work for patients. It's a great motivator when things are difficult at the bench and also helps us keep our research questions focused on studies that will one day improve patients' lives. I'm excited to continue my training as a postdoctoral research fellow at Mayo Clinic in Florida, studying mitochondria in the heart and building toward a career in academia.