Our multidisciplinary team of physician-scientists conducts various research projects to help promote patient care and better educate families. We participate in studies funded by the National Institute of Health (NIH), pharmaceutical companies and our own investigator-initiated studies. We hope our research efforts will improve treatment for children with hard-to-treat neonatal conditions.
Learn more about what we're investigating currently by reviewing the information below.
MicroRNAs and Perinatal Hypoxia-Ischemia
Maria Dizon, MD, MSCI, was recently awarded an R01 grant from the National Institute of Neurological Diseases and Stroke for a project entitled “MicroRNAs and Perinatal Hypoxia-Ischemia.” The goal of this funded project is to understand the role of microRNAs in regulating the response of the brain to a type of injury frequently encountered by newborns. Dr. Dizon is interested in preventing cerebral palsy following preterm and term birth. MicroRNAs are small RNAs that regulate the production of specific proteins. Previously, the Dizon lab showed that microRNAs in general may modulate the endogenous regenerative response following brain injury, particularly with regard to those brain cells that make white matter. (Read the article.) White matter injury causes cerebral palsy. Now, the Dizon lab will investigate the role of a particular microRNA, microRNA-21, in the development of this disease. MicroRNA-21 is induced in response to hypoxia-ischemia (decreased oxygen with decreased blood flow). It is not clear whether the effect of increased microRNA-21 is helpful or harmful to the developing brain. The Dizon lab will evaluate microRNA-21’s effects using novel tools including transgenic mouse lines, microRNA mimics and antagonists and diffusion tensor MRI.
In a separate project funded through the Friends of Prentice Foundation, the Dizon lab has documented perturbations in specific microRNAs known regulate white matter development following hypoxia-ischemia.
Through the generous support of these sponsors as well as the support of bridge funding from the Stanley Manne Research Center, Dr. Dizon has established an independent research program. Going forward, the central interest of Dr. Dizon’s lab continues to be whether neural injury induces changes in neural stem and progenitor cell lineages; that is, do cells that would ordinarily become one type of cell change to become a different cell type in order to meet a need following injury? This interest has resulted in an important new collaboration with Ed Gong, MD, Assistant Professor, Pediatric Urology. Together, the two labs will be studying changes to stem cell lineages following bladder denervation after spinal cord injury. This will involve the use of new mouse models the labs are developing together with the Transgenic and Targeted Mutagenesis Laboratory at Northwestern Feinberg School of Medicine. The hope here is to develop translational strategies to restore function to the bladder in patients with spinal cord injuries.
Persistent Pulmonary Hypertension Research
Persistent pulmonary hypertension (PPHN) is a serious clinical disorder that occurs in some newborn infants when the blood vessels in the lung do not adjust normally during the transition to breathing air at birth.
Although inhaled nitric oxide (NO) helps many newborns with PPHN, a substantial number of infants do not respond initially to this treatment, or do not continue responding. In addition, pulmonary hypertension may worsen considerably when NO is discontinued after as little as 24 hours of inhalation.
Researchers are only beginning to understand how and why NO works. Because NO is a potent oxidant that may damage the lung, it appears to work through increasing concentrations of a messenger molecule called cyclic GMP in the smooth muscle cell.
Scientists at Lurie Children's are examining whether the formation and breakdown of this messenger molecule occurs normally in PPHN. They are also evaluating the role of other oxidants in producing or aggravating PPHN and if they interact with NO.
The researchers' ultimate goal is to develop new therapies that safely work with NO, thereby allowing the blood vessels of the lung to relax more normally.
Fifty years ago, the diseases that threatened children and challenged scientists typically had isolated causes such as viral or bacterial infections. According to Xiaobin Wang, MD, MPH, ScD, today's health challenges such as preterm birth, asthma, obesity, diabetes, cancer and emotional and behavioral disabilities have broader and more complex origins.
"Unlike tetanus, polio and measles, which we now can control" she says, "today we confront disorders that have multiple causes including environmental and genetic factors.” These problems require a new model for treatment and prevention. As the former director of the Mary Ann and J. Milburn Smith Child Health Research Program at Ann & Robert H. Lurie Children’s Hospital of Chicago Research Center, Wang was excited to work with investigators from multiple disciplines to address the most challenging child health problems.
Wang's own research focuses on the interactions between genes and environment, and their effects on reproductive outcomes. "More than one in ten U.S. babies comes into the world either too early or too small," says Wang. "Both preterm and low-weight births are associated with high death rate in infants and high risk illness in children." In 1988, with funding from the March of Dimes and the National Institutes of Health (NIH), Wang and her team at Boston Medical Center began recruiting mothers and their newborns for a comprehensive study of the genetic and social-environmental factors that contribute to preterm births and low birth weight. With over 2,500 mother-infant pairs already enrolled, it is one of the largest studies of this kind in the country. At Lurie Children’s, Wang continues to recruit research subjects.
Wang, a molecular epidemiologist, also has extensively examined the link between genetic factors, maternal cigarette smoking and infant birth weight. She recently published her results in the Journal of the American Medical Association. While the dangers of smoking during pregnancy are fairly common knowledge, Wang points out that there are vast differences in a person's capacity to avoid the negative effects. "This capacity is largely determined by genes." Her study found that women who smoked and had two gene variants (CYP1A1 and GSTT1) had a markedly increased risk of having a baby with low birth weight than women who smoked and did not have these genetic variants.
Wang says the smoking-gene interaction study is just the beginning. "With a multidisciplinary team of investigators and our expertise in clinical medicine, epidemiology, molecular genetics, biostatistics and bioinformatics, we have a great potential to better understand the causes of preterm births and low birth weight, and to improve clinical practice and public health interventions.