Exploring the role of MLIP in LMNA-Cardiomyopathy in iPSC-based human cardiac models

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2022

LMNA-Cardiomyopathy (LMNA-CMP) is a rare genetic disease caused by mutations in the Lamin A and C proteins (Lamin A/C). Affected patients present with diverse cardiac dysfunctions, that manifest without a clear correlation between the genotype (the specific DNA sequence variation) and the clinical phenotype, with severity and progression of the disease displaying a marked variability among individual (variable symptoms even in patients carrying the same mutation). Despite the intensive research in this field, knowledge on mechanisms underlying the clinical variability in LMNA-CMP is still very limited.
This project aims to explore the role of a Lamin A/C-interacting protein, called MLIP, in LMNA-CMP; indeed, although its function in the heart is almost unknown, the few available studies suggest a potential involvement of MLIP in regulation of Lamin A/C functions, thus potentially contributing to the clinical variability typically observed in the patients affected with this disease.
From the experimental point of view, we will integrate cutting edge technologies, namely induced pluripotent stem cells, gene-editing systems and organs-on-chip, to develop advanced in vitro cardiac models in which functional and molecular roles of MLIP can be comprehensively studied.
In the first instance, results from this project will increase our knowledge on the function of MLIP in the heart and in LMNA-CMP, providing insights into the mechanisms that control the manifestation of symptoms, that, in the long run, could potentially improve patients’ management and care.