FCF Funded Projects

CRISPR-engineering of human liver organoids to study fibrolamellar carcinoma

Status: Active

Goal: Model development

Principal Investigator: Benedetta Artegiani, PhD, Artegiani Group, Princess Maxima Center

Research into FLC is complicated because of the limited experimental tools that can be used to study this rare cancer. While tests in laboratory animals such as mice are useful tools, they do not reflect the human disease due to inherent differences between mice and humans. To date, experimental models that can provide insights into human disease development and progression are highly sought after.

In this research project, the researchers will build new models using human cells to study FLC. The researchers will make use of lab-grown three-dimensional human mini-livers, so-called “organoids”. These organoids can be grown from the two most important cells in the liver: the ductal cells and the hepatocytes. The researchers will then precisely modify the DNA of the organoids using CRISPRCas9 technology, also called molecular scissors, to mimic the mutations (changes in the DNA) that have been found in FLC. The researchers will also try to identify from which particular liver cell type the cancer is initiated.

With these newly built human FLC models the researchers hope to increase our current understanding of FLC, which may lead in the future to the discovery and testing of novel therapeutic strategies.