The De Plaen laboratory investigates the pathogenesis of necrotizing enterocolitis (NEC), a devastating disease of the intestine affecting premature infants, leading to chronic problems and sometimes death. Infants with NEC require much longer hospitalization and have a higher rate of neurodevelopmental delay, significantly impacting their quality of life. Even today, the causes of NEC are not well understood and specific treatments are lacking.
Animal models offer a unique avenue for deciphering disease pathogenesis. In our lab, we model NEC in neonatal mice and study the molecular mechanisms which lead to this disease in the neonatal intestine.
Inflammation is a key step to NEC development. Our laboratory has found that inhibiting the activity of an important inflammation-controlling molecule called Nuclear Factor kappa B (NF-KB) prevented NEC in a neonatal mouse NEC model. Currently we are investigating the role of the NF-KB-dependent inflammation in cells lining the lumen of the intestine versus myeloid cells, which are immune cells. By learning precisely which cell types play a key role in NEC we can develop interventions to prevent or treat NEC in premature infants in the future.
In premature infants, the microvessels of several organs have not completely developed, which predispose these infants to several diseases such as retinopathy of prematurity and bronchopulmonary dysplasia. VEGF is a protein that has an important role in the proliferation and growth of blood vessels. VEGF receptors are present in the intestine of fetuses and infants and VEGF is found in breast milk. Genetic studies have shown that newborns carrying certain mutations of the VEGF gene causing a lower production of VEGF are more susceptible to NEC. However, the role of VEGF in NEC has not been well studied.
Using a neonatal mouse model of NEC developed in our laboratory, which mimics the disease process occurring in premature babies, we found that VEGF protein is significantly diminished in animals exposed to the NEC protocol compared to dam fed controls. We are now exploring the role of VEGF in NEC. The determination of whether VEGF plays a role in the disease process of NEC is an important step that might lead to the development of a new treatment strategy to prevent NEC in premature babies.
We have previously found that changes in intestinal permeability precede the injury in NEC and are associated with the redistribution of tight junction proteins, which are proteins that help connect cells to each other. We now are studying the role of one of these proteins that we have found to be significantly increased in NEC.
List of publications indexed in PubMed by the De Plaen Laboratory
Isabelle De Plaen, MD