The liver occupies a strategic position for efficient metabolism throughout the body, receiving its supply of hydrophilic nutrients absorbed by the intestine via the portal vein and delivering metabolized products to the other organs via the central vein. It is the main detoxifying organ of the body, which removes wastes and xenobiotics by metabolic conversion and biliary secretion. Although adult hepatocytes are long lived and normally do not undergo cell division, they maintain the ability to proliferate in response to toxic injury and infection. The amazing regenerative capacity of the liver has already been described in Greek mythology (see Figure). Equally fascinating are the pathways that regulate liver development, metabolic function, liver size control, zonation or signaling to other organs. These pathways are controlled by several layers of overlapping mechanisms, whose understanding is a challenging task.
The main research interest of our group is to study the molecular mechanisms governing the transcriptional regulation of liver-specific genes. Our research is broadly centered around the analysis of the function of hepatic regulators and the general transcription machinery. We use biochemical, genetic and cell biology approaches to study the chromatin organization and the regulated assembly of the transcription machinery on hepatic genes involved in the regulation of various metabolic pathways and/or hepatocyte differentiation. Focus is on studies of epigenetic mechanisms with an ultimate goal to describe the complete Epigenomes matching the hepatocyte cell type at different stages of liver development and during hepatocarcinogenesis.
“Prometheus Bond by Pieter Paul Rubens, 1612”
The ancient Greeks knew that the liver possessed an unusual ability to regenerate in response to damage. According to Greek mythology, when Zeus hid fire from mortals, the Titan deity Prometheus stole it and retuned it to the mortals. This enraged Zeus, who then had Prometheus taken to the Caucasus Mountains and bound naked to a rock. Every morning an eagle came and pecked away at Prometheus' liver - here depicted by Rubens. Each night, though, Prometheus' liver regenerated.