In her PhD project, Kamilla Holtmann Hejn will set out to investigate whether activation of G protein-coupled receptors can counteract activation of the liver’s stellate cells and improve blood circulation in the diseased liver. If successful, it could ultimately be a potential treatment for cirrhosis of the liver.

Cirrhosis of the liver is a widespread disease that causes numerous deaths every year. Cirrhosis of the liver can be caused by both alcoholic and non-alcoholic fatty liver inflammation, the latter being abbreviated as NASH (non-alcoholic steatohepatitis).

“When NASH sets in, the small blood vessels of the liver are restricted, scar tissue forms, and the patient develops high blood pressure in the portal circulation, which supplies the liver with blood from the intestine. This impairs the function of the liver and can result in potentially fatal consequential diseases or acute liver failure,” says Kamilla Holtmann Hejn, a recent biomedicine graduate from University of Southern Denmark.

She has now been awarded a grant by the Danish Diabetes Academy for a PhD and is investigating a particular type of cell in the liver known as stellate cells, the activation of which may cause the heightened blood pressure.

“The stellate cells are believed to regulate the blood flow to the liver. However, during the development of NASH and cirrhosis the cells change, and instead of supporting the functions of the liver, they form the above-mentioned scar tissue. The cells are ‘activated’,” says Kamilla Holtmann Hejn.

“Effective treatment of patients with these diseases could save thousands of lives every single year and could increase the quality of life of many more”

Investigating problematic activation of liver cells – and discovering if it can be avoided
When stellate cells are activated, a group of receptor proteins called stimulant G protein-coupled receptors (GSPCRs) is downregulated. The hope is that stimulation of these receptors may counteract the activation of the stellate cells and prevent the formation of scar tissue in NASH.

“For the investigation, I will thoroughly map the composition of G protein-coupled receptors in stellate cells in patients with NASH, and apply this knowledge in the laboratory to treat liver tissue taken from cirrhotic patients. I will also use experimental disease models to study the mechanisms behind the functions of the GsPCRs,” explains Kamilla Holtmann Hejn.

The G protein-coupled receptors are particularly interesting, because we know they can be stimulated with medical treatment.

“In my project, I will explore the possibilities of treating NASH, cirrhosis and high blood pressure in the liver through the targeted stimulation of GsPCRs expressed in the stellate cells. The effective treatment of patients with these diseases could save thousands of lives every single year and could increase the quality of life of many more,” says Kamilla Holtmann Hejn.

Interdisciplinary cooperation between hospitals and universities ensures high-quality research
The project will be carried out under the direction of Kim Ravnskjaer, an Associate Professor at University of Southern Denmark, with whom Kamilla Holtmann Hejn already established positive collaboration as an undergraduate and postgraduate student.

Early on in the project, she will also work with Zachary Gerhart-Hines, Associate Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research at University of Copenhagen. In Gerhart-Hines’s lab, she aims to isolate human liver cells from biopsies and conduct the first analyses. She will obtain the biopsies through a collaboration with Professor Lise-Lotte Gluud, a gastroenterologist and hepatologist at Hvidovre Hospital.

Last but not least, in the middle of the project Kamilla Holtmann Hejn will spend three weeks in Groningen in the Netherlands, working with Professor Peter Olinga. His research group is a world leader in methods for studying slices of liver biopsies while the tissue is still alive.

“With the proposed project, I anticipate continuing my path towards becoming an independent researcher in the area of chronic liver disease,” concludes Kamilla Holtmann Hejn, who is looking forward to a project that involves different sectors and disciplines.

Contact
Kamilla Holtmann Hejn
E-mail: kamillahejn@gmail.com
Tel: +45 26 22 63 00

Danish Diabetes Academy
Managing Director Tore Christiansen
E-mail: tore.christiansen@rsyd.dk
Tel: +45 29 64 67 64

/By Project Manager Nina Jensen, Danish Diabetes Academy