Children’s Discovery Institute awards $3.1 million in pediatric research grants

Scientists researching pediatric lung disease, childhood cancer, malaria and short bowel syndrome will share $3.1 million in new grants from the Children’s Discovery Institute (CDI).

The CDI grants, announced earlier this year, will fund 10 research initiatives at Washington University School of Medicine in St. Louis and St. Louis Children’s Hospital.

Launched in 2006, CDI encourages unique collaborations among scientists at the School of Medicine, the university’s Danforth Campus and Children’s Hospital. Institute-funded projects constitute “discovery research” — preliminary studies that may point scientists down a path that eventually could yield new treatments.

“These 10 projects illustrate the CDI’s emphasis on giving investigators the opportunity to pursue bold questions in pediatric disease by building creative collaborations and daring to think outside the box,” said Mary Dinauer, MD, PhD, the CDI’s scientific director, the Fred M. Saigh Distinguished Chair in Pediatric Research at Children’s Hospital, and professor of pediatrics and of pathology and immunology at the School of Medicine.

The recipients of the grants are:

Jeffrey Magee, MD, PhD, an assistant professor of pediatrics and a 2014 Faculty Scholar. Magee, who joined the School of Medicine faculty last year, studies bone-marrow stem cells. His laboratory will investigate the relationship between stem cell regulation and leukemia at different ages. The aim is to identify age-specific mechanisms that alter bone-marrow stem cells and to develop more precise and effective therapies for childhood leukemia.

Todd Druley, MD, PhD, an assistant professor of pediatrics and of genetics. Druley’s grant will focus on leukemia in infants younger than a year old. In previous work, he identified damaging variants in genes of infant leukemia patients. The new award will enable Druley and his collaborators to expand the understanding of how these gene variants cause changes in immature blood cells that can lead to leukemia. The genomic tools developed to study infant leukemia also will help define how inherited genetic variation influences a variety of other complex diseases.

Vikas Dharnidharka, MD, associate professor of pediatrics. Dharnidharka and his collaborators will focus on newly available next-generation sequencing technologies. Their aim is to expand understanding of post-transplant lymphoproliferative disorder (PTLD). This malignant transformation of white blood cells can occur in recipients of solid-organ or tissue transplants and may lead to death. While many cases of PTLD are caused by the Epstein-Barr virus, others have no known cause. Dharnidharka hopes to reveal other viruses involved in PTLD, as well as to identify Epstein-Barr genome sequences associated with poorer outcomes.

Nicole Gilbert, PhD, postdoctoral fellow in the Department of Molecular Microbiology. Gilbert and her collaborators will investigate the interaction between the Group B Streptococcus (GBS) bacterium, a major cause of life-threatening infection and lung damage in newborns, and a related condition called bacterial vaginosis. GBS can invade the uterus during pregnancy, infect both mother and baby and lead to preterm delivery, fetal lung damage, pneumonia and other serious conditions. Women with both GBS and bacterial vaginosis are more likely than others to deliver preterm babies, who are at a greater risk of lung damage.

Amanda Lewis, PhD, assistant professor of molecular microbiology and of obstetrics and gynecology, and Warren Lewis, PhD, research instructor in medicine. The two are investigating the molecular mechanisms involved in GBS bacterial colonization of vaginal tissue. They are specifically studying the function of an enzyme that may play a key role in bacterial colonization of tissue and transition to invasive disease. Their work is aimed at identifying a biomarker for pregnancies at risk for preterm labor and delivery.

S. Celeste Morley, MD, PhD, assistant professor of pediatrics and of pathology and immunology. Morley and her collaborators will test her hypothesis that susceptibility to severe pneumococcal disease by some children may be the result of inherited defects in proteins that regulate immune responses. Morley will use her award to establish a database of patient DNA samples that will be used to define the kinds of pneumococcus that cause severe infection, and identify genetic differences that can impair immune response and predispose individuals to pneumococcal infection.

Thad Stappenbeck, MD, PhD, professor of pathology and immunobiology and of developmental biology, and Steven Brody, MD, professor of medicine and of radiology. The two will focus on the development of valuable tools for lung disease research. They hope to take advantage of a specific signaling molecule to expand stem cells isolated from various lung regions. If successful, their approach will provide new, efficient tools for lung stem-cell studies, better methods to investigate the mechanisms of childhood lung diseases, enable drug testing on cells relevant to these diseases and ultimately pave the way for personalized therapies.

Susan Dutcher, PhD, professor of genetics and of cell biology and physiology, and Brody, who leads the Airway Epithelial Cell Core funded by the CDI. The two will collaborate on a grant Dutcher has received to investigate the causes of inherited diseases of the cilia, the barrier that keeps the lungs clean of harmful substances inhaled into our lungs along with the air we breathe. By modeling genetic mutations involved in human cilia-related disease in algae and zebrafish, Dutcher’s research will provide new diagnostic tools and potentially reveal new treatments for children with ciliary dysfunction.

Audrey Odom, MD, PhD, a CDI faculty scholar and an assistant professor of pediatrics and of molecular microbiology, and Barani Raman, PhD, assistant professor of biomedical engineering. The two will research malaria, a parasitic disease that claims the lives of more than 1 million children each year. The new grant will enable them and their collaborators to develop and validate the use of a noninvasive device that detects malaria biomarkers in exhaled breath. Development of an inexpensive diagnostic tool will improve care of infected children and conserve antimalarial medications for children most in need.

Scott Saunders, MD, PhD, associate professor of
pediatrics and of developmental biology; Brad Warner, MD, the Jessie L.
Ternberg, MD, PhD, Distinguished Professor of Pediatric Surgery and professor of pediatrics; and
David Ornitz, MD, PhD, the Alumni Endowed Professor of Developmental Biology. The investigators will focus on short bowel syndrome, a condition in which a large part of the small intestine is missing. They will investigate the signaling pathways that regulate the growth of the small intestine during development to determine if certain signaling molecules previously identified can accelerate intestinal growth after birth. Their goal is to find new approaches for clinical management of short bowel syndrome in children.

Children’s Discovery Institute is a world-class center for pediatric research and innovation. The institute funds the collaborative, multidisciplinary work of creative scientists aimed at some of the most devastating childhood diseases and disorders.

St. Louis Children’s Hospital has provided specialized care for children for more than 130 years. The hospital is affiliated with Washington University School of Medicine. In 2013, St. Louis Children’s Hospital again made the elite U.S. News & World Report Honor Roll of the nation’s Best Pediatric Hospitals. It also has received Magnet re-designation from the American Nurses Credentialing Center, the nation’s highest honor for nursing excellence. St. Louis Children’s is a member of BJC HealthCare.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.