Presentation Title

Using iPSC-derived Cardiomyocytes to Evaluate the Pathogenicity of a MYH14 Knockout in Causing Hypertrophic Cardiomyopathy

Faculty Mentor

Jessica Wang

Start Date

23-11-2019 10:00 AM

End Date

23-11-2019 10:45 AM

Location

63

Session

poster 3

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Myosin heavy chain 14 (MYH14) is a non-muscle myosin involved in mechanotransduction (Levy et al., 2016). In humans, familial MYH14 mutations are documented as affecting sensorineural hearing loss and not much is known about its role in the heart. Myh14 is a candidate gene that protects against heart failure identified by Dr. Jessica Wang in a novel approach to discover genes associated with cardiac remodeling using the Hybrid Mouse Diversity Panel (HMDP). By applying isoproterenol (ISO), a chemical agonist of the beta-adrenergic system, to the HMDP and measuring heart structure and function by echocardiography, Dr. Wang discovered several genomic loci that were associated with the increase of left ventricle mass (LV mass hypertrophy).

Studies on the Myh14 knockout mouse line in our laboratory have shown that the loss of the gene can exacerbate the ISO-induced LV mass hypertrophy (Wang et al., 2016). This shows the important protective role of Myh14 in heart failure. We are interested in the role of MYH14 in human cardiomyocytes. I hypothesize that knocking out MYH14 in human induced pluripotent stem cells (iPSCs) by clustered regularly interspaced short palindromic repeats (CRISPR) genomic editing will cause phenotypic aberrations in cardiomyocytes after differentiation.

In order to test the hypothesis, I will be establishing MYH14 knockout iPSC lines with confirmed guide RNAs and a differentiating them into cardiomyocytes. Once these lines are established, I will be designing assays in order to determine the role of MYH14 knockout in iPSC-derived cardiomyocytes.

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Nov 23rd, 10:00 AM Nov 23rd, 10:45 AM

Using iPSC-derived Cardiomyocytes to Evaluate the Pathogenicity of a MYH14 Knockout in Causing Hypertrophic Cardiomyopathy

63

Myosin heavy chain 14 (MYH14) is a non-muscle myosin involved in mechanotransduction (Levy et al., 2016). In humans, familial MYH14 mutations are documented as affecting sensorineural hearing loss and not much is known about its role in the heart. Myh14 is a candidate gene that protects against heart failure identified by Dr. Jessica Wang in a novel approach to discover genes associated with cardiac remodeling using the Hybrid Mouse Diversity Panel (HMDP). By applying isoproterenol (ISO), a chemical agonist of the beta-adrenergic system, to the HMDP and measuring heart structure and function by echocardiography, Dr. Wang discovered several genomic loci that were associated with the increase of left ventricle mass (LV mass hypertrophy).

Studies on the Myh14 knockout mouse line in our laboratory have shown that the loss of the gene can exacerbate the ISO-induced LV mass hypertrophy (Wang et al., 2016). This shows the important protective role of Myh14 in heart failure. We are interested in the role of MYH14 in human cardiomyocytes. I hypothesize that knocking out MYH14 in human induced pluripotent stem cells (iPSCs) by clustered regularly interspaced short palindromic repeats (CRISPR) genomic editing will cause phenotypic aberrations in cardiomyocytes after differentiation.

In order to test the hypothesis, I will be establishing MYH14 knockout iPSC lines with confirmed guide RNAs and a differentiating them into cardiomyocytes. Once these lines are established, I will be designing assays in order to determine the role of MYH14 knockout in iPSC-derived cardiomyocytes.