A healthy teenager suddenly collapses during soccer practice and dies. After his death, physicians find he was harboring a silent killer known as hypertrophic cardiomyopathy, a condition in which the heart muscle becomes thickened, making it harder to pump blood out of the heart.

The condition generally has no symptoms, but it is the most common killer of adolescents who are otherwise healthy and is the leading reason for heart transplants in children.

Despite its prevalence, very little is known about the genetic and molecular makeup or the electrical phenotypes of the hearts of children with hypertrophic cardiomyopathy. New research funded by the Children’s Discovery Institute may change that.

Jeanne M. Nerbonne, PhD, the Alumni Endowed Professor of Molecular Biology and Pharmacology in Developmental Biology, and her colleagues received a large initiative grant from the Institute to develop the Translational Cardiovascular Tissue Core, a centralized system for acquiring, banking, annotating with clinical data, and distributing tissue from diseased hearts. It is directed by Kathryn A. Yamada, PhD, professor of medicine in the Cardiovascular Division.

“As individuals develop heart failure,” says Nerbonne, “we do not know how to predict who is going to have the fatal sudden death incident. It has become increasingly clear that detailed electrophysiological and molecular analyses of diseased and non-diseased human hearts are urgently needed to advance the field.”

Nerbonne, professor of medicine, and her team take tissue samples from the diseased hearts of children at the time they get a ventricular-assist device, which helps the heart pump blood and is often used as a bridge to a heart transplant. Investigators then perform various studies on these tissues, looking at the proteins, RNA, cellular and whole tissue physiology, as well as bank tissue for genetic and epigenetic analyses. They also collect diseased hearts at the time of transplant and perform similar studies, comparing what they find with non-diseased heart tissue.

Notably, the banked tissue and associated data will be available to all Washington University investigators for further types of analysis.

“As the science moves forward,” Nerbonne says, “other researchers will be able to take a different look at the data for new discoveries.”

Internationally, there are 250 million to 350 million cases of malaria each year, resulting in about 1 million deaths. Most of those deaths are children under age 5.

Audrey R. Odom, MD, PhD, wants to cure malaria. The pediatric infectious disease specialist has been working toward that goal since she came to the School of Medicine in 2008 with a Children’s Discovery Institute Faculty Scholars Award.

Odom’s background in cell signaling in eukaryotic organisms, or microbes that have a nucleus and organelles like human cells, led her to apply that knowledge to a eukaryotic pathogen in child health. An assistant professor of pediatrics and of molecular microbiology, Odom says malaria is hard to control because the parasite has become resistant to nearly all currently available anti-malarial drugs.

“Chloroquine, a mainstay drug for nearly 100 years, is resistant to malaria worldwide,” Odom says. “Every time we develop a new drug, we’re going to encounter resistance, so we need to establish a continual pipeline of new drugs.”

With funding from a separate grant from the Children’s Discovery Institute, Odom has made progress with that pipeline. She has identified a metabolic pathway that is present in the malaria parasite and is required for it to grow, but that is not present in humans.

“In theory, we can create a safe antimalarial drug,” she says. “What makes this pathway even more exciting is that it’s also present in the mycobacteria that cause tuberculosis, and there’s also a real need for new drugs for TB.”

Odom and her colleagues are testing new compounds to see if they inhibit the enzyme and kill the malaria parasite. Her research team also is screening a large number of existing compounds to determine if they have any effect.

But that’s not her ultimate goal.

“I want to identify a small molecule inhibitor that we can pitch to pharmaceutical companies to treat bacterial infections in the United States and that they can then give away to treat malaria and TB in the developing world,” Odom says.

But the malaria parasite also likely will become resistant to that drug, she says, so her strategy is to pair it with another compound.

“Combination therapy,” Odom says, “will be the way forward.”

Cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Among major childhood cancers, leukemia and brain and other central nervous system tumors make up more than half of new cases.

A child with leukemia — a cancer of the blood cells — has a 90 percent chance of long-term survival. But only two of three children with a malignant brain or central nervous system tumor will live beyond five years.

According to researchers Jeffrey R. Leonard, MD, and Joshua B. Rubin, MD, PhD, that needs to change.

Part of the reason pediatric brain tumors are so deadly is the lack of samples on which to do research. With funding from the Children’s Discovery Institute, Leonard, associate professor of neurosurgery and of pediatrics, and Rubin, associate professor of pediatrics, of neurology and of neurobiology, have developed a pediatric brain tumor data bank. It contains tissue samples from brain tumors in children they have treated, along with individual patient data such as age, sex, type of tumor and type of treatment. New data is automatically entered into the databank.

Leonard and Rubin implant the brain tumor samples into mouse brains. By studying how the tumors grow in the mice, they can screen thousands of existing compounds to determine if any work to slow the tumor’s growth or eliminate the tumor.

Rubin says that current treatments can be effective, but they also can cause long-term damage to children’s brains. “So,” he says, “even when tumors are cured, we are still looking for new treatments with less toxicity.”

Data from the tumor bank also is available to other researchers to study brain tumors, perform genetic screens or test for new drugs.

“We have a large number of resources here,” Leonard says. “We want people around the country to view Washington University as the place to come for pediatric and adult brain tumor research.

The Children’s Discovery Institute provides a unique mechanism to support innovative ideas and collaborative efforts among departments and across campuses, Rubin says.

“What’s smart about setting it up that way is it requires people to come up with a novel, collaborative approach to pediatric disease,” he says. “That prompts research that might not have happened without support from the Institute.”

Painful middle ear infections are among the most common infections seen in toddlers and young children. Many children find relief in a course of antibiotics, but others experience recurrent ear infections.

To find answers to what causes these and other pediatric respiratory infections, the Children’s Discovery Institute awarded a large initiative grant to Thomas W. Ferkol, MD, the Alexis Hartmann, MD, Professor in Pediatrics. Ferkol, also professor of cell biology and physiology, is a world-renowned expert on primary ciliary dyskinesia (PCD), a rare, inherited lung disease that results in chronic infections of the respiratory tract.

Despite its prevalence, very little is known about the genetic and molecular makeup or the electrical phenotypes of the hearts of children with hypertrophic cardiomyopathy. New research funded by the Children’s Discovery Institute may change that.

He and his team are studying the functional, structural and genetic characteristics of cilia diseases in children using a single-celled algae model that is structurally identical to a human cilium. Ultimately, they will learn more about common childhood diseases that could lead to better care, prevention and identification of new treatments.

The cilia are tiny, hair-like structures in the lungs, nose, sinuses and ears that help clear out mucus, foreign particles, fluids and bacteria. When the cilia don’t function correctly, children develop respiratory, sinus and ear infections.

In PCD, which occurs in about one in every 12,000 to 20,000 births, cilia are unable to clear out bacteria-filled mucus from the lungs, sinuses and ears, resulting in persistent infections. Ferkol and the research team suspect a link between common ear infections and the relatively rare PCD.

“Children who get chronic ear infections, requiring repeated treatment with antibiotics and sometimes surgeries, also may have genetic and functional defects of the cilia, similar to children with PCD, but much less severe,” he says.

The team has found genetic mutations that may impact cilia and flagella, another hair-like structure that functions much like cilia. The mutations disrupt the biochemical pathways of motor proteins that surround each cilium and make it move.

“Our goal is to connect specific abnormalities of cilia motion with a child’s genetic profile, then connect that with a child’s disease,” Ferkol says. “One day, we could potentially personalize treatment to the genetics and cilia motion abnormalities present in each child.”

Ferkol says the collaboration and support from the Children’s Discovery Institute have been instrumental in bringing about these insights.

Since its launch in 2006, the Children’s Discovery Institute has awarded nearly $29.5 million to researchers tackling deadly pediatric diseases ranging from cancer to malaria. The targeted effort has united clinicians and investigators from all corners of Washington University, reaching across 16 departments in three schools.

“In seeking new answers to questions about pediatric disease, we need to collaborate and think in bold new ways,” says Mary C. Dinauer, MD, PhD, scientific director of the Children’s Discovery Institute and professor of pediatrics and of pathology and immunology at the School of Medicine.

Institute-funded projects in four areas — childhood cancer, musculoskeletal and metabolic diseases, pulmonary disease and congenital heart disease — are “discovery research,” preliminary studies that may eventually yield new treatments.

“The Children’s Discovery Institute is an interesting concept developed to fund early-stage research that will lead to a better understanding of childhood disease and treatment, and in some cases, even prevention,” says Dinauer, who also serves as the Fred M. Saigh Distinguished Chair in Pediatric Research at St. Louis Children’s Hospital.

Of the 92 grants awarded to researchers since the Institute’s inception, 55 percent were to researchers outside the Department of Pediatrics. According to Dinauer, that’s unique among children’s disease research.

“We want these grants to bring people from multiple disciplines together to study in this research area,” she says. “Other institutions have in-house funding for research, but it stays within the department.”

The Children’s Discovery Institute also funds a Faculty Scholars Award that provides three years of support to junior faculty, allowing them to set up their laboratories, as well as a summer research opportunities program for undergraduate students.

“In the end, we want to establish new areas of pediatric research,” Dinauer says. “Creative collaborations will allow us to conduct outstanding investigations that otherwise wouldn’t have been possible.”