Specialized Lab Aims to Advance Liver Disease Research
Kirsten Sadler Edepli, associate professor of biology, says NYU Abu Dhabi's "beautiful genomics center" is vital to the promising liver research projects she will be pursuing on campus.
"What's really great about doing the projects in Abu Dhabi," she said, "is the genomics facility and the bioinformatics team. It's all about genome-wide studies ... having the bioinformatics expertise has really been helpful, and the genomics center is essential."
One project aims at steatosis, better known as fatty liver disease, an alarmingly widespread ailment that can lead to cirrhosis and death. Steatosis can be caused by obesity, toxins including alcohol, type II diabetes, or other factors.
Living cells, she explained, contain a "quality control pathway, to ensure that the proteins, the building blocks of cells, are folded in the right shape to do the right job. When these proteins are not folded properly, there's a pathway that is activated to help fold them back in the right shape."
Studying this "unfolded protein response" has revealed an adaptive process, analagous to an immune response: Give a cell a small quantity of toxin, and the cell can re-fold its proteins, undoing the damage. If you then apply a larger toxin dose, a previously-exposed cell will handle it better than a "naïve" cell that has never experienced the toxin.
(Zebrafish) are a great system to study this; their liver looks just like that in a human, it functions the same … we can give the fish toxins and they get fatty liver, just like people.
Edepli is examining how this happens. If she can "understand what is mediating this … maybe we could tweak this adaptive response in people prone to fatty liver disease."
Her research uses mainly zebrafish (Danio rerio). These 1.5-inch long creatures "are a great system to study this; their liver looks just like that in a human, it functions the same … we can give the fish toxins and they get fatty liver, just like people," Edepli said.
"One of the big benefits of doing this work in Abu Dhabi is that we have a zebrafish facility, one of the few in the whole region, in the basement of the Experimental Research Building."
Zebrafish are also used in Edepli's other project, which involves epigenetic regulation in the liver.
"The liver in mammals has this amazing capacity to regenerate," she added. "It's an adaptive response, evolutionarily acquired because the liver gets injured, it's the first stop for detoxification. A driving theory of my lab is that the processes that regulate the proliferation and development of the liver in embryo might be the same as those that regulate proliferation and development of the liver in adults, when it regenerates.
The liver in mammals has this amazing capacity to regenerate ... A driving theory of my lab is that the processes that regulate the proliferation and development of the liver in embryo might be the same as those ... in adults.
"And as cells from the liver get transformed to become cancer, maybe some of those processes that control development and regeneration might be co-opted by tumor cells."
This study, she pointed out, is "really focused on one gene … UHRF1; it's a central regulator of the epigenome" – the way individual genes in DNA can be activated or de-activated.
"We focus on one epigenetic mechanism, DNA methylation, which people have studied for a long time and assumed it regulates many aspects of the epigenome, but we don't really understand what it does … We know that this one gene Uhrf1 is in all vertebrates we've looked at, and in zebrafish we've learned that it's required for liver development and liver regeneration, and when it's expressed at very high levels it causes liver cancer."
Understanding this mechanism, Edepli noted, would "advance our long-term goal of improving regenerative potential to treat liver disease."
Both of Edepli's two projects come with research grants from the U.S. National Institutes of Health, which she said are a first for NYUAD. She is working with three postdoctoral researchers transferred from New York; another is participating from there.