Graffmann lab: Functional liver epigenetics

In our group, we apply human induced pluripotent stem cells (iPSCs) to model liver development and liver diseases.

A focus lies on the study of nonalcoholic fatty liver disease (NAFLD). In this condition, which affects up to 30% of the general population in the Western World, hepatocytes store fat as lipid droplets. While this is initially not harmful and reversible, many patients develop more severe forms of the disease, namely nonalcoholic steatohepatitis (NASH), cirrhosis and cancer. Although so many patients are affected by NAFLD, it is currently unknown why only some of them develop more severe forms while others even manage to reduce fat levels in the liver.

Also, we face a lack of approved medication for preventing and/or reverting hepatic fat storage. This is mainly due to the lack of suitable in vitro models, which we want to overcome with our research.

 

 

 

Fig. 1: Modelling of NAFLD with iPSC-derived hepatocyte like cells

 

In order to better understand the disease mechanisms, we recapitulate the essential steps in our iPSC based in vitro liver model. This enables us to study metabolic changes and test medication to prevent or revert fat storage.

In addition, we want to understand the role of epigenetics for NAFLD development and reversibility.

Epigenetic mechanisms control gene expression by regulating the accessibility of genomic regions to enzymes such as RNA-Polymerase. They are inherited during cell division but can also be influenced by the environment. This is especially true for hepatocytes as they are exposed to all our nutrients as well as drugs and toxins that are ingested. We want to decipher epigenetic factors that (I) foster fat storage, (II) are involved in the reversibility of fat storage, (III) might influence the action of anti-NAFLD drugs.

 

All current in vitro liver models have drawbacks regarding cell maturity and function. Therefore, we continuously strive to improve our system by applying 3D techniques in combination with relevant small molecules.   

 

Funding: Else-Kröner Fresenius Stiftung

https://www.ekfs.de/wissenschaftliche-foerderung/aktuelle-foerderungen/entschluesselung-der-epigenetischen-basis-der

 

 

Team

Dr. rer. nat. Nina Graffmann

 

M.Sc. Christiane Lörch

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