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Researchers at Memorial Sloan Kettering Cancer Center identified DHRS7 as the human gene for an enzyme studied since 1992. Using human cells and zebrafish, they found that the 5-oxoETE signaling pathway may help protect tissue from excessive inflammation; implications for disease treatment remain a research prospect, not a proven therapy.
Researchers at Memorial Sloan Kettering Cancer Center have identified DHRS7 as the human gene for an enzyme that scientists had been unable to trace for more than 30 years, and report that the enzyme is part of a signaling pathway that may help limit inflammation-related tissue damage. The study, published October 7 in Nature, used human cells and zebrafish to investigate 5-oxoETE, a chemical signal that attracts immune cells to sites of infection.
The enzyme in question can both produce and break down 5-oxoETE, a fatty molecule that helps direct immune cells toward threats. Researchers had described its chemical activity in 1992, but had not identified the human gene responsible. Without that genetic identity, experiments to manipulate the enzyme and examine its role in disease were difficult.
In cultured human cells, postdoctoral researcher Yanan Ma and former lab colleague King Lam Hui tested candidate genes by switching them off. When the researchers disabled DHRS7, the enzyme stopped functioning, identifying the gene linked to the activity. The team also found almost no comparable enzyme activity from the rodent version of the gene.
The researchers then used zebrafish to study the pathway in a living organism. According to the report, mice lack a known immune-cell receptor for 5-oxoETE, making them unsuitable for examining the complete signaling process. Zebrafish retain the relevant machinery, enabling the team to investigate how the signal operates in an intact animal.
A Possible Brake on Immune Damage
The findings connect a signal that recruits infection-fighting immune cells with a possible mechanism for limiting harm to nearby healthy tissue. Immune cells can release substances that attack pathogens, but those substances can also damage tissue if the response is excessive. Understanding how 5-oxoETE is made and broken down gives researchers a more specific way to study how the body balances defense with tissue protection.
The work could inform future research into cancer, inflammatory bowel disease and asthma, all areas named by the research report. It does not establish that changing DHRS7 or 5-oxoETE can treat or prevent these conditions. The significance at this stage is a newly identified gene and pathway that researchers can examine in further studies.
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The Search Began in 1992
The mystery dates to 1992, when researchers at McGill University investigated 5-oxoETE and observed an enzyme able to both make and break down the signal. The enzyme received a descriptive name based on its chemical function, but its human genetic identity remained unknown for decades. That gap limited scientists’ ability to test how the enzyme’s activity affected immune signaling.
Ma’s work took place in the laboratory of cell biologist Philipp Niethammer, which studies cellular responses to injury, infection and other forms of stress. The report says the lab had already been investigating the molecular reactions involved in 5-oxoETE signaling. Identifying DHRS7 also connected Ma’s research with a separate investigation in the lab led by postdoctoral researcher Miklos Lengyel, though the supplied report cuts off before detailing that work.
The choice of animal model mattered because, according to the researchers, mice and rats lack a known receptor needed to recognize 5-oxoETE. Zebrafish retain the pathway’s relevant components. The findings underline that a standard model organism may not be suitable for every biological question.
“They flood the site with toxic substances to kill the bacteria. But this can cause damage to healthy cells if it gets out of control.”
— Philipp Niethammer, cell biologist at Memorial Sloan Kettering Cancer Center
Questions Beyond Gene Identification
The report establishes that switching off DHRS7 stopped the enzyme’s activity in cultured human cells, and describes experiments using zebrafish. It does not provide enough detail to establish how the pathway’s protective effect was measured, how large that effect was, or whether the same mechanism has been demonstrated in people.
It also remains unclear whether DHRS7 or the 5-oxoETE pathway could be safely targeted as a treatment. The report describes possible relevance to cancer, inflammatory bowel disease and asthma, but does not present clinical results or evidence that a therapy is available. The supplied source text ends mid-sentence while describing a related project, so further details about that work are not available here.
From Pathway Findings to Further Tests
The next step is further research into how DHRS7 and 5-oxoETE regulate immune-cell recruitment and tissue injury, including whether the zebrafish findings translate to human biology. Researchers may also investigate the pathway in disease models and test whether altering its activity changes inflammation without weakening defenses against infection.
No treatment timeline or clinical trial is specified in the source material. For now, the confirmed development is the identification of DHRS7 and a clearer route for investigating an immune signaling system that had remained partly unexplained since 1992.
Key Questions
What did the researchers discover?
They identified DHRS7 as the human gene responsible for an enzyme that can produce and break down 5-oxoETE, an immune-cell signaling molecule.
What is 5-oxoETE?
It is a fatty chemical signal that helps attract immune cells to sites of infection. The study examines how its signaling pathway may also be involved in limiting damage to healthy tissue.
Why did the team use zebrafish instead of mice?
According to the report, mice lack a known immune-cell receptor for 5-oxoETE, so they cannot model the complete pathway. Zebrafish retain the relevant biological machinery.
Does this discovery provide a treatment for inflammation?
No. The findings identify a gene and a pathway for further study. The report does not describe a proven treatment, clinical trial or demonstrated benefit for patients.
Which diseases could this research relate to?
The report names cancer, inflammatory bowel disease and asthma as areas the findings could inform. It does not show that the discovery treats or prevents those conditions.
Source: sciencedaily.com
