UC Irvine

Although it is widely acknowledged that heart disease is the number one killer of Americans, what may not be so commonly known is that genetic mutations can cause heart diseases. According to numerous studies, many mutated genes cause heart diseases such as cardiomyopathies, and arrhythmias, yet the practical diagnosis and treatment for them are scarce. Lamin A/C gene (LMNA) is one of the genes that can cause dilated cardiomyopathy, arrhythmia, and heart failure. This gene codes for proteins, which create a mesh-like layer under the nucleus envelope known as the nuclear lamina. Even though nuclear lamina exists in almost every nucleated cell in the body, there are individuals with LMNA splice site mutation (c.357-2A>G) who mainly have heart problems. The mechanisms by which LMNA mutations cause heart dysfunctions remain a mystery. In this project, human-induced Pluripotent Stem Cells (hiPSCs) derived cardiomyocytes have been used to develop an in vitro model of the consequences of the mutation on heart function. We demonstrated that it is possible to recapitulate the pathological phenotype in vitro by using patient-specific derived cells and tissue engineering techniques, even though the patients do not exhibit symptoms until later in life. Moreover, this in vitro model of cardiomyocytes tissues can be utilized to correlate gene profiles, structure, and function of the hiPSC-derived cardiomyocytes; thus, elucidating the disease-causing mechanisms.