Sarah Broders is a second-year PhD student in the department of bioengineering at the University of California, San Diego. She earned her BS in engineering in biomedical engineering from Duke University, where she conducted research in Dr. Nenad Bursac’s laboratory as a Pratt Research Fellow and Duke Cardiovascular Research Center CURE Fellow. Her undergraduate work focused on cardiac regeneration, including the study of cardiomyocyte proliferation in engineered heart tissues and in vivo mouse models. At UC San Diego, Sarah’s doctoral research centers on understanding how biological sex influences immune responses in cardiovascular disease. As an NHLBI T32 trainee co-mentored by Dr. Brian Aguado and Dr. Farah Sheikh, she leverages the Four Core Genotypes mouse model and high-dimensional immune profiling to disentangle the effects of sex chromosomes and sex hormones during myocarditis and the foreign body response. Her work aims to identify sex-specific immune drivers of cardiac inflammation and apply this knowledge to engineer next-generation immunomodulatory biomaterials for the injured heart. Sarah is a recipient of the Fronek Family WHISDEM Fellowship for Women’s Health Research and the SWHR Emerging Scholars in Women’s Health Research Award. Through her research and mentorship, she is committed to advancing sex-inclusive cardiovascular science and improving health outcomes for women and men alike.
Abstract: Dissecting Chromosomal and Hormonal Sex Effects on Immune Responses in Myocarditis
Myocarditis is an inflammatory heart disease affecting an estimated 1.8 million people worldwide each year and remains a major cause of acute heart failure, sudden cardiac death, and progression to dilated cardiomyopathy, particularly in young adults and athletes. Although myocarditis exhibits clear sex-based disparities, with an incidence ratio of approximately 1:2–4 female to male, how sex chromosomes and sex hormones independently shape cardiac inflammation and remodeling remains poorly defined. Here, we investigate how sex chromosomes and gonadal sex independently shape immune responses during myocarditis using the Four Core Genotypes (FCG) mouse model, which decouples chromosomal sex (XX vs. XY) from gonadal sex (ovaries vs. testes). Using high-dimensional spectral flow cytometry, we profile cardiac and systemic immune populations during experimental myocarditis to define sex-dependent immune signatures. At baseline, mice with ovaries exhibit significantly higher splenic (1.65-fold CD4⁺, 1.90-fold CD8⁺) and cardiac (2.32-fold CD4⁺, 2.88-fold CD8⁺) T cell populations compared to mice with testes, independent of sex chromosome complement. This difference persists following gonadectomy at four weeks of age, suggesting a role for sex-dependent developmental hormone exposure in regulating thymic egress and peripheral lymphocyte distribution. Ongoing studies in an experimental myocarditis model are examining whether XX mice exhibit amplified T cell activation and sustained inflammatory immune profiles relative to XY mice, consistent with a potential contribution of X chromosome dosage to heightened immune responses. These analyses include 24 markers for both lymphoid and myeloid lineages, as well as resident cardiac immune populations. Together, this work aims to define how sex chromosomes and hormones interact to regulate immune behavior during myocarditis. These findings underscore the importance of incorporating both chromosomal and hormonal sex as biological variables in inflammatory heart disease and may help explain sex-dependent differences in myocarditis progression and outcomes.