Prof. Marco Rasponi of the Department of Electronics, Information and Bioengineering of the Politecnico di Milano and Prof. Elisa Di Pasquale of the CNR and IRCCS Humantias Clinical Institute conduct a study of the role of MLIP in LMNA-Cardiomyopathy in iPSC-based human 3D-cardic models funded by Fondazione Cariplo and Fondazione Telethon.
LMNA- Cardiomyopathy is a form of inherited cardiomyopathy caused by mutations in the Lamin A/C encoding gene, LMNA. It is characterized by left ventricular dilatation and systolic dysfunctions, usually associated with various conduction abnormalities and arrhythmias, which manifest with variable penetrance and expressivity, leading to diverse patterns of clinical phenotypes. Mechanisms behind such clinical variability are still largely unknown.
The project focuses on MLIP, a binding partner of Lamin A/C proteins, whose function in the heart is still largely unknown. Specifically, while deepening its physiological action in the heart, the goal is to determine whether MLIP plays a role in the pathogenesis of LMNA-cardiomyopathy (LMNA-CMP), as a “modifier” of disease, contributing to the clinical heterogeneity typical of the disease.
From an experimental point of view, breakthrough technologies will be integrated, namely CRISPR/Cas9 system, induced pluripotent stem cells (iPSCs) and organs-on chip (mHeart), to generate 3D human cardiac microtissue models, in which functional and molecular roles will be comprehensively investigated.
The project outputs will bring knowledge about the functional and molecular roles of MLIP in the onset and progression of LMNA-CMP, filling some gaps in the understanding of its clinical heterogeneity. In the long term, this increased knowledge could contribute to improve clinical management of patients.