A new study from The University of Texas at Arlington details a novel strategy for how the body clears out dead cells during stress, revealing unexpected roles for well-known stress-response genes—a discovery that could help scientists better understand diseases affecting the immune system, brain and metabolism.
"The body is constantly creating new cells and removing old cells once they die," said Aladin Elkhalil, lead author of the study and a third-year doctoral student in the lab of Piya Ghose, assistant professor of biology at UT Arlington. "This removal of dead cells is just as important as creating new ones, because if the body is unable to rid itself of dead cells, it can lead to various health problems"
Published in the peer-reviewed, open-access journal PLoS Genetics, the study was conducted on the roundworm C. elegans by Dr. Ghose, Elkhalil and Alec Whited, another graduate student in the Ghose lab. This tiny, transparent organism is a widely used tool in genetic research because its see-through body allows scientists to observe live cell behavior, including how cells die. The research team took advantage of these unique features in several innovative ways.
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"This has been an exciting study, where stress meets cell behavior," said Ghose. "It's fascinating to see how our cells adapt to changes in their surroundings and still perform their normal functions. Understanding that process is essential to our normal physiology and development."
The team examined stress-response genes—many of which have human counterparts—in a new context: how they help remove dying cells. Using tools like CRISPR/Cas9 gene-editing technology, they manipulated these genes to identify a specific stress-response pathway that activates to help in the removal of dying cells.
Using state-of-the-art live imaging, the researchers were able to characterize this stress-response pathway by observing key components of the cell clearance machinery in action. This allowed them to see when and how stress-related and clearance genes are switched on during the removal process.
A key gene was identified: The human version, known as lyst, is linked to Chediak-Higashi Syndrome, a rare disorder in which cells struggle clearing out debris, leading to immune system problems.
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"One of the novel findings in our study is that the worm version of this gene is controlled by classical stress-response genes, which was previously unknown," Elkhalil said. "An intriguing question is why this pathway needs to be in place at all. That leaves us with an exciting avenue for future research."
This work was supported by The Cancer Prevention Research Institute of Texas (CPRIT) (RR100091) and the National Institutes of Health–National Institute of General Medical Sciences (R35GM142489).
About The University of Texas at Arlington (UTA)
Celebrating its 130th anniversary in 2025, The University of Texas at Arlington is a growing public research university in the heart of the thriving Dallas-Fort Worth metroplex. With a student body of over 41,000, UTA is the second-largest institution in the University of Texas System, offering more than 180 undergraduate and graduate degree programs. Recognized as a Carnegie R-1 university, UTA stands among the nation's top 5% of institutions for research activity. UTA and its 280,000 alumni generate an annual economic impact of $28.8 billion for the state. The University has received the Innovation and Economic Prosperity designation from the Association of Public and Land Grant Universities and has earned recognition for its focus on student access and success, considered key drivers to economic growth and social progress for North Texas and beyond.
