At LIAN we study different aspects of cardiac differentiation from pluripotent stem cells. The human heart has a limited capacity for repair and regeneration. Ischemic damage during myocardial infarction causes cardiomyocyte death, followed by an inflammatory response and subsequent replacement of the myocardium by non-contractile fibrous tissue. As a consequence of this, myocardial infarction usually leads to heart failure, the main cause of death both in our country and worldwide.

One of our main objectives at LIAN is to understand the molecular mechanisms that guide cardiac development to contribute to the development of regenerative therapies that can eventually be brought to the clinic. We have various research topics in this area:

GENE REGULATION OF CARDIAC DIFFERENTIATION

Cardiac differentiation from pluripotent stem cells recapitulates the processes that occur during human embryonic development. This sequential succession of cellular states is finely regulated by a regulatory network of RNAs. Our laboratory is actively working to determine what these networks are, studying short-chain RNAs (microRNAs) and long-chain RNAs (long non-coding RNAs). To do this, we use massive sequencing techniques, as well as manipulating these RNA networks through the use of gene editing with CRISPR / Cas9 or microRNA sponges.

RE-ENTRY OF CARDIOMYOCYTES TO THE CELL CYCLE

Human adult cardiomyocytes and those of other mammals are unable to proliferate under normal conditions, which among other things determines the low regenerative capacity of this organ against injuries such as myocardial infarction. However, it was recently determined that during the first postnatal days the heart retains a high capacity to regenerate, where cardiomyocytes retain their proliferative capacity. Knowing the mechanisms by which these cells can re-enter the cell cycle is key when thinking about future therapies. At LIAN we are actively working on this issue, studying the mechanisms of exit and re-entry into the cell cycle of cardiomyocytes derived from pluripotent stem cells.

MODULATION OF CARDIAC DIFFERENTIATION THROUGH EXTRACELLULAR SIGNALS

The transition from the pluripotent state to a specific tissue such as the mesoderm and cardiac cells are regulated by the extracellular signals with which the cells communicate. In our laboratory we work with some of them, such as integrins and cadherins.