17 June 2020

Delilah Hendriks receives international postdoc grant to study liver disease

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Delilah Hendriks has received an international postdoc fellowship from the Swedish Research Council (Vetenskapsrådet) to extend her research stay in the Netherlands. The goal of this grant is to enable researchers with a PhD from Sweden to gain experience abroad and to develop an independent line of research. She will use this three-year grant to follow up on her studies in the group of Hans Clevers, where she combines genetic engineering techniques with human organoid models to study liver disease.

Hendriks obtained her PhD from Karolinska Institutet in Stockholm, Sweden, in 2018, after which she moved to the Netherlands to start her postdoctoral research in the group of Hans Clevers. During this period, she developed a new CRISPR-Cas based tool to label specific genes in various human organoid models. Thanks to the international postdoc grant, she will be able to now apply this method combined with other strategies to study liver disease.

Fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) is one of the most common type of chronic liver disease. This disease currently affects about one in four people globally, but its incidence is expected to keep growing. NAFLD encompasses a spectrum of liver disease ranging from simple steatosis (fat accumulation in liver cells, or hepatocytes) to severe inflammatory non-alcoholic steatohepatitis (NASH). Eventually, NASH can then progress to liver cancer or liver failure, after which patients require an organ transplant.

A liver organoid that shows the network of bile collecting tubes in red, and liver cells in green. Credit: Delilah Hendriks

Lack of experimental models
To date, no approved drug therapies for NAFLD exist due to the limited molecular understanding of the disease. This is in part due to the lack of reliable experimental models. Results from animal models are not directly translatable to humans, because of differences in diet, metabolism, and genetics. At the same time, representative human-based models remain scarce. Hendriks aims to fill this gap by using human liver organoids, or hepatocyte organoids – tiny versions of the liver that she can grow in the lab, a novel platform to model and study fatty liver disease.

Disease modelling in human organoids
With the help of the international postdoc fellowship, Hendriks will continue her work to establish a human fatty liver disease model. To this end, she will apply different methods to the hepatocyte organoids, including CRISPR-Cas genetic engineering, co-culture establishment with other liver cell types, and state-of-the-art sequencing techniques. This engineered model will allow her to bring insight into the cellular and molecular mechanisms that underlie fatty liver disease in model that is relevant to the human disease. The results from these studies may lead to the identification of novel disease biomarkers and new therapeutic targets.