Patient specific heart muscle for testing new heart therapies in vitro – UROP Spring Symposium 2021

Patient specific heart muscle for testing new heart therapies in vitro

Bianca Angela Gunawan

Bianca Angela Gunawan

Pronouns: she/her

Research Mentor(s): Todd Herron, Research Assistant Professor
Research Mentor School/College/Department: Internal Medicine and Cardiology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 6 (4pm-4:50pm)
Breakout Room: Room 7
Presenter: 3

Event Link

Abstract

Hypertrophic Cardiomyopathy (HCM) is one of the most prevalent heart diseases in the world. In HCM, gene mutations lead to abnormal thickening of the heart muscles and makes it harder for the heart to pump blood. Previous research also indicated that abnormal structure and function of mitochondria is common in HCM. One of the biological pathways in the cell signaling network that contributes to HCM is the ERK1/2 pathway that consists of a series of proteins activation and signals for cell growth. Mutations that cause abnormally high activity of this pathway causes excessive cell growth. One of the proteins in this pathway is called MEK, and lately, there have been several highly-specific inhibitors studied for this protein. This research uses human stem cell-derived cardiomyocytes with MYH7 mutation-caused HCM to study the effect of MEK inhibition in relation to hypertrophic cardiomyopathy. The stem cell was cultured into cardiomyocytes monolayers and treated with 6 different doses of MEK inhibitor PD0325901 (0.1, 0.5, 1.0, 5.0, and 10 ┬ÁM. Afterwards, we studied the cells shape and sizes by staining the cells with Wheat Germ Agglutinin that binds with cell membrane, and Phalloidin that binds with actin. Another focus in this research is also observing the mitochondria structure and health using mitotracker red dye to get a clear picture of the organelle. We also separated the cell proteins and performed Western blotting to observe the effect of the MEK inhibitor on the ERK1/2 pathway. We hope to find that MEK inhibitors are effective in restoring the mitochondria in cardiomyocytes and improving overall heart cells condition. The results of this study could potentially advance heart-related research and public health.

Authors: Bianca Gunawan, Nicholas Peck-Dimit, Noah Poulin, Jefery Creech, Andre Monteiro da Rocha, Todd Herron
Research Method: Laboratory Research

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