Grant: Operating Grant

Nucleotides (e.g. ATP) and nucleosides (e.g. adenosine) act as hormones by activating a variety of functions in all systems and cells. In the liver, these small molecules regulate a number of metabolic functions as well as inflammation and therefore a number of liver diseases. The level of these molecules is regulated by enzyme at the cell surface that break them down and therefore these enzymes regulate in the mean time the functions played by nucleotides and nucleosides. Interestingly, these enzymes transform the former molecule, ATP, into adenosine which has often opposite effect to the former molecule showing the importance of these regulatory enzymes. We have discovered a novel form of these enzymes that is almost exclusively present in this tissue and that it is the most important enzyme to regulate the level of these molecules. We will evaluate whether this and other similar enzymes in the liver regulate the functions of these molecules and therefore if they can regulate liver functions and diseases such as cirrhosis. To address this goal we will generate a mouse that is invalidated for this enzyme. This mouse will help us to understand the function and importance of this enzyme in liver diseases and functions. We anticipate that these studies will help define new molecular mechanisms that could be targeted as novel pathways to control liver diseases.