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, assistant professor of pediatrics, 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 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,” says 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 the School of Medicine. “Collectively, this research could ultimately benefit millions 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 the School of Medicine that has awarded nearly $29 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,” Dinauer says. “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.”
- Carlos Bernal-Mizrachi, MD, assistant professor of medicine and of cell biology and physiology, 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, postdoctoral research scholar in developmental biology, 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, instructor in pediatrics, 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, associate professor of medicine and of cell biology and physiology, 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, assistant professor of pediatrics, 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, assistant professor of genetics and of pediatrics, and Christina Gurnett, MD, PhD, assistant professor of neurology, of pediatrics and of orthopaedic surgery, 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, associate professor of pediatrics and of cell biology and physiology, and Katherine Henzler-Wildman, PhD, assistant professor of biochemistry and molecular biophysics, 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, instructor of pediatrics, 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, assitant professor of pediatrics and of medicine, 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, associate professor of pediatrics, of neurology and of neurobiology, and David Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology, 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, research associate in the Department of Mechanical Engineering & Materials Science, 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, assistant professor of medicine and of cell biology and physiology, and David Piwnica-Worms, MD, PhD, professor of developmental biology, of cell biology and physiology and of radiology, 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.
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 fourth 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.
The Children’s Discovery Institute is a world-class center for pediatric research and innovation. The Institute funds the collaborative, multi-disciplinary work of creative scientists aimed at some of the most devastating childhood diseases and disorders. For more information about the Children’s Discovery Institute, visit ChildrensDiscovery.org.
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, ranked the number four medical school in the country by US News & World Report. In 2011, St. Louis Children’s Hospital again made the elite US News Honor Roll of the nation’s Best Pediatric Hospitals, in addition to receiving Magnet re-designation from the American Nurses Credentialing Center, the nation’s highest honor for nursing excellence. In 2009, Parents magazine ranked St. Louis Children’s Hospital #5 on its list of the 10 Best Children’s Hospitals in America.. St. Louis Children’s Hospital is a member of BJC HealthCare. For more information visit StLouisChildrens.org; or visit us on Facebook
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