Top 7 Discoveries from Cincinnati Children's Featured in 2019 Research Annual Report

Wednesday, February 05, 2020

Improving sickle cell disease care in Africa. Developing new esophageal organoids. Advancing the field of circadian medicine in ways that could affect how thousands of medications are prescribed. These are just some of the many outcome-improving discoveries made by scientists at Cincinnati Children’s in the past year.

Our 2019 Research Annual Report features the most significant discoveries from more than 50 research divisions, including cancer, heart care, developmental biology, human genetics, surgery, brain sciences, and more. The featured works were chosen from more than 2,200 published findings in FY19 (ended June 30), including many that appeared in the world’s top medical and science journals.

This scientific progress was fueled by another record year for research funding, from sources including the National Institutes of Health, a variety of federal and state agencies, non-profit foundations, private donors, and industry.

“At the close of fiscal 2019, our faculty established yet another all-time record for extramural support, with a total surpassing $242 million for extramural grants and contracts—an unquestionable victory in an era when dollars available for NIH grants have not increased. Our research performance continues to place us in the top three pediatric departments in the country,” says Margaret Hostetter, MD, Chair, Department of Pediatrics, and Director of the Cincinnati Children’s Research Foundation.

In this year's report, research leaders at Cincinnati Children's named seven discoveries as our most significant breakthroughs of the year:

Hydroxyurea Sharply Reduces Sickle Cell Burden in Study Touching Four Nations in Africa

“From Nothing to Gangbusters.” That’s how the New York Times described the REACH study led by Russell Ware, MD, PhD, from Cincinnati Children’s and Leon Tshilolo, MD, PhD, a scientist based in the Democratic Republic of the Congo (DRC).  The study, published in The New England Journal of Medicine, suggests a practical, affordable way to prevent so many children in resource-poor African nations from dying of sickle cell complications before age 5.

First Human Esophagus Grown from Pluripotent Stem Cells

Infants born with esophageal atresia, children who develop eosinophilic esophagitis, and others coping with throat diseases stand to benefit from the latest breakthrough in organoid development from Cincinnati Children’s. For now, these tiny-but-functional organs in a dish will help researchers explore how organ formation goes wrong, and in testing the safety and effectiveness of experimental medications. Eventually, experts hope to grow personalized tissues in large enough volume to use in transplants that would not require anti-rejection medications.  This breakthrough, led by graduate student Stephen Trisno, and senior author James Wells, PhD, was published in the journal Cell Stem Cell.

Is Your Child Sick With a ‘Stomach Bug’? Don’t Bother with Probiotics…

Hype abounds about the wonders of probiotics. So it comes as little surprise that many parents hope a dose of “good bugs” might help their children recover faster from the “bad bugs” that cause the diarrhea and vomiting of gastroenteritis.  But when scientists took a careful look at whether probiotics made any difference in outcomes for these sick children, the evidence was clear: Probiotics did not help. This myth-busting finding was led by David Schnadower, MD, and was published in The New England Journal of Medicine.

Meanwhile, a ‘Prebiotic’ Might Someday Help Children with Painful, Damaged Colons…

Up to 26% percent of children diagnosed with ulcerative colitis (UC) fail to respond to standard treatments and wind up needing major surgery. But a new trove of data gathered in the 29-center PROTECT study has revealed that some children may avoid such surgery through a fundamental shift in treatment. By analyzing tissue samples and the mix of gut bacteria in 400 young patients with UC, a research team led by senior author Lee (Ted) Denson, MD, found 33 genes whose activity was changed when children had UC. This gene signature, described in The Lancet, may help doctors determine which children are most likely to need early, intense therapy. Meanwhile, uncovering these gene associations suggests that a ‘prebiotic’ known as 2’-fucosyllactose may help restore healthy microbiomes in many of these children. A clinical trial is underway to evaluate this potential therapy.

And Adjusting Your Gut Bacteria Mix Might Boost Metabolism and Promote Weight Loss

Several years ago, scientists learned that obese mothers can pass along a mix of gut bacteria to their children that puts them at increased risk of growing up obese themselves. Now, after studying how these bacteria interact with the gut at a molecular level, researchers at Cincinnati Children’s led by Theresa Alenghat, VMD, PhD, have discovered a possible way to control the process. The team learned that blocking the activity of the enzyme HDAC3 allowed lab mice to consume high-fat, high-calorie diets without becoming obese. Before this approach can be tested in humans, however, scientists need to develop methods to inhibit this enzyme only in the intestine, and not elsewhere in the body, where it has other beneficial functions. The team’s findings appear in the journal Gastroenterology.

Your Skin Tells Time in Ways That Could Redefine How Doctors Prescribe Medicine

Regardless of your ethnicity, sex, or age, your body’s internal clock regulates half of your entire genome. That means genetic activity rises and falls according to a 24-hour rhythm. And that means taking a medication at the right time of day—for you—can maximize the benefits. Or, taking a drug at the wrong time could maximize unwanted side effects. In a potentially far-reaching study, Cincinnati Children’s experts Marc Ruben, PhD, David Smith, MD, and John Hogenesch, PhD, identified 900 “cycling genes” in 13 tissue types that either regulate how our bodies absorb medications or are themselves the targets of treatment. Best of all, many of these cycles can be tracked through low-cost skin testing rather than more complex blood tests or invasive biopsies, the researchers say. Eventually, this information could help doctors give patients more precise instructions on when to take medications—and patients could experience much better outcomes. The details appear in Science Translational Medicine.

How Light Therapy Might Prevent Vision Problems in Preterm Infants

Even inside the womb, light exposure matters. It turns out that normal eye development depends in part on exposure to a specific wavelength of violet light that influences how blood vessels grow. However, when infants are born prematurely, they can spend weeks, even months under hospital lighting that happens to lack this wavelength.  In mice, light therapy supports healthy vision development, according to a groundbreaking study in Nature Cell Biology, led by researchers Minh-Thanh Nguyen, PhD, and Richard Lang, PhD. Now, as part of a large building expansion, Cincinnati Children’s is installing a special lighting system in the future home of its neonatal intensive care unit that can be calibrated to evaluate the effectiveness of light therapy for preterm infants.