Looking Beyond: We Need Extensive Insights into Gene Regulatory Mechanisms to Better Diagnose and Treat NAFLD | Danish Diabetes and Endocrine Academy
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Looking Beyond: We Need Extensive Insights into Gene Regulatory Mechanisms to Better Diagnose and Treat NAFLD

Looking Beyond: We Need Extensive Insights into Gene Regulatory Mechanisms to Better Diagnose and Treat NAFLD -

by Mie Tomzak

A review recently published in ‘Cells’ from DDA-funded researcher Trine Vestergaard Dam and her associates discusses insights into the cis-regulatory genome in NAFLD and highlights emerging technologies enabling single-cell resolved analysis of the cis-regulatory genome of the liver.

NAFLD (non-alcoholic fatty liver disease) is an ever-rising problem found in people with obesity and diabetes. The condition is often associated with a modern western lifestyle influenced by sedentary work and high consumption of processed food. An estimated 25 % of all adults has some degree of NAFLD. Up to 20 % of these will develop the most severe type called NASH, characterized by inflammation and scar tissue.

A great need for research
PhD student Trine Vestergaard Dam received funding by the Danish Diabetes Academy in 2019. She is based at ATLAS (Center for Functional Genomics and Tissue Plasticity) at the Department of Biochemistry and Molecular Biology, the University of Southern Denmark. Her PhD project focuses on NAFLD.

“Targeted treatment for NAFLD is practically non-existent, relying standardly on a significant change in lifestyle. Likewise, diagnosing the condition is associated with comprehensive methods where one of the most effective ones is a liver biopsy, which is more than a little invasive. As such, there is a great need for research leading to improved detection methods and treatment,” says Trine Vestergaard Dam.

A possibility for new discoveries
Trine Vestergaard Dam and her associates recently had a review published in the international journal ‘Cells’ from the open access publisher MDPI. The review was part of the Special Issue ‘Cellular and Molecular Mechanisms Governing Liver Pathophysiology’. Trine and her co-authors direct focus to the potential of making new discoveries in the largely unexplored cis-regulatory genome of NAFLD livers, meaning not in the protein-coding genes, but in the non-coding DNA sites that interact with genes to regulate their expression.

“Our hope is that it might be possible to identify new drug targets among the non-coding DNA regions in livers with NAFLD, thereby enabling the creation of targeted medicine. Maybe there are dysfunctions in the regulatory non-coding sequences, which then push to regulate the genes differently than in a healthy body. By focusing on this deeper level beyond gene expression itself, it may be possible to further map out the issues at the root of the problem,” explains Trine Vestergaard Dam.

Potential in emerging technologies
In their review, Trine and her co-authors, Nicolaj I. Toft and Lars Grøntved, highlight the technologies used in single-cell analysis of NAFLD. Singe-cell sequencing makes it possible to isolate not just the different cell types, but also the individual cells within each type population. Most of these techniques, however, currently focus on RNA-sequencing, i.e. gene expression, which is why the review concludes that there might be a huge potential in looking beyond and focusing more on the cis-regulatory genome.

“We look forward to seeing more of these techniques focusing on the regulatory aspect of gene expression. Some of these techniques already exists and become more and more prevalent, but we have yet to see them utilized in the context of NAFLD,” says Trine Vestergaard Dam.

Cell-Type Resolved Insights into Cis-Regulatory Genome of NAFLD
Trine V. Dam, Nicolaj I. Toft, Lars Grøntved

Cells 2022 11(5), 870: Cells | Free Full-Text | Cell-Type Resolved Insights into the Cis-Regulatory Genome of NAFLD | HTML (mdpi.com)
Published 3 March 2022 

Trine Vestergaard Dam

PhD student, ATLAS, University of Southern Denmark
Trine V. Dam (0000-0003-1148-0591) (orcid.org)
Email: trinevd@bmb.sdu.dk