The liver is a very slowly dividing organ but, when damaged by toxins present on the food or other environmental agents, it starts the machinery to regenerate itself and bring the organ back to its original resting state. Our aim is to understand the molecular mechanism by which liver or other adult cells sense the damage infringed to the tissue and start the repairing process. Understanding these mechanisms is crucial to improve our knowledge on the basics of cancer initiation, as during tumorigenesis, similar mechanisms have to be put in place to activate the resting cells to start proliferating.
We are also interested in developing tools to study human physiology and disease in vitro in a petri dish. Because of their numerous biomedical implications in studies of hepatitis, drug testing, as well as transplantation for chronic liver diseases, scientists around the world have unsuccessfully attempted for decades to regenerate primary liver cells.
We have recently achieved that challenge by establishing a novel liver culture system named 'liver organoid culture' that allows the massive and infinite expansion of mouse liver cells into 3D structures that resemble functional liver tissue in a dish. Of note, when these cells are grownin vitro and transplanted into a mouse model of an inherited liver disease, which resembles the Tyrosinemia type I human liver disease, the cultured and transplanted liver cells continued to grow in the recipient livers and alleviated the pathology of the disease by prolonging the survival of the transplanted mice, thus proving their therapeutic potential.