Life-threatening bacterial infections and brain tumors are just some of the serious health issues affecting children. Now, 12 Washington University School of Medicine research teams are preparing to ask – and answer – critical questions about these and other pediatric health problems with help from $3 million in new grants from the Children’s Discovery Institute. 

In one of the funded projects, Stephanie Fritz, MD, will follow 135 pediatric patients and their households for one year to identify genetic and environmental factors that influence the spread of methicillin-resistant Staphylococcus aureus (MRSA), a common strain of bacteria that doesn’t respond to some antibiotics. MRSA is the most frequent cause of skin infections and invasive, life-threatening infections of the muscles and bones in children. Over the last decade, there has been a dramatic increase in the number of MRSA infections in healthy children in the community, but combating these infections has been limited by the lack of effective preventive measures. This research could lead to the development of novel methods to interrupt the spread of MRSA and to prevent infections. 

Newly funded cancer-related projects will explore strategies to prevent nerve damage resulting from a commonly prescribed chemotherapy drug; genetic risk factors for brain tumors; and the ways by which an important cellular defense mechanism goes awry in brain tumors. Research projects focusing on cardiovascular disease will examine the link between congenital heart disease and brain development in infants, as well as the genetic basis of cardiovascular disease and metabolic syndrome — a disease characterized by obesity, diabetes and high blood pressure. 

Projects related to lung diseases will explore the genes responsible for excessive airway narrowing associated with asthma and mechanical structures in the cells that line the airways important for clearance of mucus.  Other newly funded Institute projects will examine genetic defects associated with autoimmune diseases; approaches to prevent sudden deaths related to insulin therapy; the genetic underpinnings of scoliosis in adolescents; and the characteristics of proteins implicated in type 2 diabetes.

“These projects represent the broad range of important pediatric diseases that the Institute tackles each year,” said Mary Dinauer, MD, PhD, Scientific Director of the Children’s Discovery Institute, the Fred M. Saigh Distinguished Chair of Pediatric Research at St. Louis Children’s Hospital and professor of pathology and immunology at Washington University School of Medicine. “Collectively, this research could ultimately benefit thousands of children in the United States.”

The Children’s Discovery Institute is a multi-disciplinary, innovation-based research partnership between St. Louis Children’s Hospital and Washington University School of Medicine that has awarded nearly $28 million in scientific grants since its launch. The Institute encourages unique, productive 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 could yield new treatments in the future.

To date, Institute awards have resulted in significant progress in children’s health research. Awardees have leveraged their initial “seed funding” to gain $69 million in additional funding resources from the National Institutes of Health (NIH) and other national organizations.

“Through a unique and extensive set of collaborations, Institute researchers have already made tremendous progress in advancing research on pediatric diseases,” Dr. Dinauer said. “There is still a long way to go, and the newest round of funding will help these investigators provide important insights that have the potential to lead to new treatments."

Children’s Discovery Institute Awards
February 2012

• Carlos Bernal-Mizrachi, MD, will investigate the contribution of fetal vitamin D deficiency to the development of metabolic syndrome and identify genes that predict the onset of metabolic syndrome and cardiovascular disease.
• Martha Bhattacharya, PhD, will receive a fellowship to develop molecular strategies to prevent the chemotherapy drug vincristine from causing peripheral nerve damage, which results in pain and loss of nerve function.
• Megan Cooper, MD, PhD, will use next-generation gene sequencing to determine whether genetic defects in abnormal immune cells lead to the development of a range of pediatric autoimmune diseases associated with serious long-term health problems.
• Simon Fisher, MD, PhD, will study the mechanisms by which high insulin doses in children with type 1 diabetes can cause sudden death, and test novel therapeutic approaches to prevent this potential deadly side effect.
• Stephanie Fritz, MD, will receive a Faculty Scholar Award to track pediatric patients and their households to identify genetic and environmental factors that influence the spread of MRSA.
• Matthew Goldsmith, MD, and Christina Gurnett, MD, PhD, will examine the genetic basis of adolescent idiopathic scoliosis, the most common pediatric spinal deformity, to gain biological insights that could lead to the development of non-surgical therapeutic strategies.
• Paul Hruz, MD, PhD, and Katherine Henzler-Wildman, PhD, will study the structure and movements of glucose transport proteins, which carry the blood sugar glucose into cells, to provide a basis for designing drugs that improve the function of these proteins in type 2 diabetes.
• Cynthia Ortinau, MD, will use advanced neuroimaging techniques to test whether changes in blood flow to the brain associated with congenital heart disease impair brain development and neurologic outcome in infants, and assess the impact of neonatal heart surgery on brain development.
• Anand Patel, MD, will identify genes and molecular pathways responsible for excessive airway narrowing in response to allergen exposure or viral infection to offer insights that could lead to the discovery of novel treatments for asthma, the most common chronic childhood disease.
• Joshua Rubin, MD, PhD, and David Gutmann, MD, PhD, will examine genetic variations that increase the risk for brain tumors in children with the genetic disease neurofibromatosis 1, and investigate why these tumors are more common in boys than in girls, in order to improve diagnostic and therapeutic strategies for children with brain cancer.
• Gang Xu, DSc, will receive a fellowship to measure the mechanical properties of important structural components found in cilia — whip-like appendages on cells that propel fluid and materials in the airways — to understand abnormalities in the movements of cilia that are associated with pulmonary diseases.
• Zhongsheng You, PhD, and David Piwnica-Worms, MD, PhD, will investigate the role of nonsense-mediated messenger ribonucleic acid decay (NMD), a cellular surveillance system that blocks the production of defective proteins, in pediatric brain cancer.