Aarti Sridhar
Pronouns: She/Her
Research Mentor(s): Alison Vander Roest
Research Mentor School/College/Department: Biomedical Engineering / Engineering
Program: UROP
Session: Session 1 (9:00am – 9:50am)
Authors: Aarti Sridhar, Alison Vander Roest
Abstract
Hypertrophic Cardiomyopathy (HCM) is the most common genetic heart disease, which afflicts around 1 in every 200 to 500 people. HCM is noted for thickening of the heart muscles and increased contraction, which prevents blood flow from occurring at normal rates. In a previous study done by Dr. Vander Roest, they were able to identify the P710R mutation in the MYH7 gene that increases the hypercontractility of beta myosin in heart muscle (Vander Roest, PNAS 2021). The mutation caused a statistically significant increase in force production in stem cell derived cardiomyocytes; however, the data did have a large spread of points, and this study seeks to understand why by accounting for a specific confounding variable: alpha myosin. The human induced pluripotent stem cell (hiPSC) derived cardiomyocytes contained variable amounts of two types of cardiac myosin, beta and alpha myosin. We hope to quantify different ratios of the cardiac myosin types and assess whether a correlation exists between myosin type and variability in myofibril alignment and cell size. We then plan to knock out alpha myosin using the CRISPR-Cas9 gene editing approach. This will enable any future experiments to more accurately define a relationship between the mutations in beta myosin and force generation.
