About 14 years have passed since the Human Genome Project completed its map of our genes, and the final count is in: Human beings have between 20,000 and 20,500 genes, every one of which is made of DNA—the stuff of heredity.
DNA provides instructions to proteins, the worker bees in our cells that make our bodies run. But there’s another molecular player whose role and importance remains a little less well understood: RNA.
Roughly defined, RNA relays instructions between genes and proteins, telling our cells which proteins to build and how to build them.
According to Dr. Enikö Sonkoly, senior author of a study focusing on the link between psoriasis and a particular RNA component, “Scientists used to think that large regions of DNA and RNA were little more than junk, mainly because they didn’t seem to match up with specific proteins. Now, we know that’s not true. Instead of defining single proteins, some components of RNA—especially those categorized as microRNAs—seem to regulate entire pathways of molecules.”
NPF grant winner Dr. Enikö Sonkoly
Tiny but potent
MicroRNAs were discovered in the 1990s. There are 2,500 of these tiny, potent RNA fragments, and they’re implicated in all kinds of biological processes from stem cell differentiation to intercellular communication.
Sonkoly and her team in the Karolinska Institute’s Dermatology and Venereology Unit in Stockholm, Sweden, have been studying one such fragment: microRNA-146a.
In their studies of a mouse model of psoriasis—a mouse who’s been given a disease resembling psoriasis in humans—the researchers observed that microRNA-146a blocks communication between inflammation-promoting immune cells and skin cells.
When microRNA-146a is working properly, it helps skin stay healthy by keeping inflammation in check. But when it goes awry, as it does in psoriasis, the result is unbridled inflammation and the out-of-control build-up of skin cells that characterizes the disease.
The Karolinska Institute team published its findings in the February 2017 issue of the Journal of Allergy and Clinical Immunology, with Sonkoly as senior author.
Sonkoly’s research has been made possible in part by two grants from the National Psoriasis Foundation, a $50,000 grant in 2008 and a $200,000 Translational Research Grant in 2012.
Sonkoly is optimistic about the potential of microRNAs as biomarkers, which are substances in the blood or tissues that can measured to detect the presence of a disease or predict a patient’s response to treatment.
Sonkoly and her colleagues hope to advance their genetic candidates—microRNA-146a and other microRNAs—from promising performers to full-fledged biomarkers that can be used in medical practices to monitor and fine-tune the treatment of psoriasis in individual patients.
However, the road is long between the discovery of a promising RNA fragment and its validation as a biomarker. Do its levels in the blood tend to fluctuate, or are they stable? What level is optimal for keeping psoriasis at bay? How many samples are needed to get reproducible results in the lab?
For Sonkoly, these kinds of questions are part of science as usual. In fact, she welcomes them.
Opportunities and challenges
“I’m fortunate to be able to study the causes of psoriasis at a time of such rapid change,” she said. “In the past five to 10 years, we’ve seen an explosion of new treatments for psoriasis, and that means we can manage its symptoms in a majority of patients. Our understanding of the disease, too, has continued to deepen.”
She’s hopeful that valuable insights will come from a large, prospective study known as the Stockholm Psoriasis Cohort. Researchers have been following close to 800 patients enrolled in the study for more than 10 years.
Moreover, they’re gaining a picture of psoriasis that’s becoming clearer and clearer over time—a picture that’s revealing which patients are at risk for severe disease and which ones aren’t.
Having completed her medical degree and her Ph.D. in her native Hungary, Sonkoly has found a congenial professional home in Sweden—and not just because her husband Dr. Andor Pivarcsi, a biologist whom Sonkoly calls her “best collaborator,” is in the same unit at Karolinksa.
“It’s common in Scandinavia for physician-scientists like me to be able to spend half of my time in research and the other half treating patients. My dual identity suits me very well!” she said.
The phrase “from bench to bedside” has special meaning for Sonkoly, who is able to bring the benefits of scientific insight directly to the patients she sees in her medical practice.
In turn, her patients help ground her research, reminding her that there are real and often urgent reasons for her to push the envelope and take her discoveries to the next level…and the one after that…and the one after that.
Driving Discovery, Creating Community
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