ABSTRACT

During early cardiac development, blood flow and genetic processes influence each other to ensure formation of an efficient heart. However, how exactly genes and blood flow interact with one another during formation and growth of the heart remains largely unknown. This collaborative research between the University of California at Irvine (UCI) and the Oregon Health & Science University (OHSU) will use advanced imaging methods together with computational simulations to unravel how altered blood flow affects programmed genetic processes, and conversely how altering genetic processes changes blood flow, leading to hearts with defects. Results from this project will ultimately guide approaches to treat heart defects before a baby is born. To further broaden the impact of this project to the society, outreach activities involving rising high school sophomores, juniors, and seniors in California and Oregon, will engage the students in scientific activities with the goal of learning about heart development and cultivate team science skills.

Although both blood flow and genetic processes contribute to heart development, how exactly they interact and affect each other, and the synergistic roles that blood flow and genetics play to predispose the heart to malformations are yet undetermined. The project?s intellectual merit is to elucidate interlinked connections between blood flow and genetic processes during heart development. More specifically, the project will study early changes in gene expression in response to altered blood flow, and early changes in blood flow in response to altered signaling, using two complementary avian models of heart development. The project will focus on three main objectives: (1) Determine blood flow and flow-induced stresses during normal and aberrant cardiac formation through advanced engineering methods; (2) Identify and quantify cellular responses to normal and perturbed heart development by generating spatiotemporal maps of cardiac adaptation; and (3) Determine the genetic and epigenetic adaptations in cardiac tissues due to early perturbations by DNA methylation and RNA sequencing. As the broader impact, results from this project will ultimately guide fundamental knowledge on embryonic heart development and help devise strategies to improve diagnosis of heart defects, prevent heart malformations, and eventually guide early fetal interventions to ameliorate the adverse effects of cardiac defects.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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