Megan Randolph
Research Mentor: Andre Monteiro Da Rocha
Mentor Department: Cardiology – CVC Cardiovascular Regeneration Core, Medicine
Author(s): Megan Randolph, Natalie Bienkowski, Maryam Khan, Julia Vallier, Alexander Visconti, Sasha Cai Lesher-Perez, Laurie Svoboda, Andre Monteiro Da Rocha
Session: Session 5 (2:00 PM – 2:50 PM)
Presentation Type: Poster 86
Abstract
It is established that sex differences in cardiovascular function, drug response, disease risk and management, and therapeutic outcomes exist. However, there remains limited and conflicting information on whether the mechanisms of the differences observed are due to sex chromosome differences and/or are a product of hormone milieu. One reason for this is that it is challenging to obtain the information needed to study the function and gene expression of human cardiomyocytes due to limitations in accessing healthy adult cardiomyocytes in a serial and timed manner. Another is because there is not a reliable and established in vitro model that captures the dynamic physiological changes throughout the ovarian cycle that occur due to hormonal oscillations. This project is based on interdisciplinary research that is conducted in three main phases – 1: development of the microfluidics model; 2: maintenance and differentiation of cardiomyocytes from reprogrammed human induced pluripotent stem cells (hiPSCs); 3: evaluation of effects of environmental contamination on the cardiomyocytes utilizing the microfluidics model. The central hypothesis is that hormonal milieu exerts a predominant role in changing cardiomyocyte electrophysiology and susceptibility to drug induced arrhythmogenesis/environmental contaminants. The second phase of the project is interested in how hormone treatment affects the expression of steroid hormone receptors in the cardiomyocytes. This will be investigated through treatment of the cardiomyocytes with the appropriate corresponding hormone concentrations, followed by immunofluorescent staining with specific interest in transcription factors Estrogen Receptor Alpha and Beta (ERa and ERß) and Progesterone Receptor Alpha and Beta (PRa and PRß), and finally, confocal imaging of the immunofluorescent cardiomyocytes. The long term goal of this project is to develop a micro-fluidic simulated in vitro ovarian cycle model which will be used to generate data to determine if this model could be established as a reliable option for future studies regarding sex differences on susceptibility to disease, drug induced adverse effects, and environmental contamination.
