Jason Choi, PhD

Mutations in the LMNA gene, encoding nuclear lamins A and C, cause a diverse range of diseases collectively called laminopathies. Although expressed in most differentiated mammalian somatic cells, specific mutations in LMNA lead to tissue-specific diseases, the most common of which is dilated cardiomyopathy. The pleiotropic nature of laminopathies, as well as their molecular pathogenic mechanisms, is poorly understood. Our goal is to understand how specific mutations in LMNA cause tissue-specific diseases and leverage new insights into therapeutic strategies. Two areas of investigation are currently under way:

Defining the cardiac microenvironment during LMNA-mediated cardiomyopathy pathogenesis.The heart consists of several stromal cell populations, the most notable being cardiac fibroblasts. Despite this fact, cardiac fibroblasts have traditionally been overlooked in favor of cardiomyocytes in the investigation of cardiac biology and disease pathogenesis. By employing in vitro co-cultures and in vivo mouse models, we aim to unravel the complex interrelationship between cardiomyocytes and cardiac fibroblasts at the incipient phase of disease pathogenesis.

Elucidating pathogenic mechanisms of LMNA mutation in adipocytes. The most intriguing aspect of lamin A/C biology is that LMNA mutations cause a pleiotropy of tissue-specific pathologies. Although patients with LMNA mutation most prevalently display muscular dystrophy and cardiomyopathy or lipodystrophy, concomitant clinical manifestations are common. By using conditional knockout mice, we will elucidate whether LMNA mutations engender tissue-specific pathologies by convergent or divergent mechanisms.