De Plaen Laboratory
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.
Isabelle G. De Plaen, MD
THE ROLE OF DEFECTIVE INTESTINAL MICROVASCULATURE DEVELOPMENT IN THE PATHOGENESIS OF NECROTIZING ENTEROCOLITIS (NEC)
In this project, we study the critical role of intestinal mucosal microvascular development in the pathogenesis of necrotizing enterocolitis using a neonatal mouse NEC model. Our overall hypothesis is that, in premature infants, the oxygen-mediated downregulation of intestinal pro-angiogenic signaling pathways due to birth occurs before the intestinal microvasculature sufficiently develops. Perinatal stresses (such as inflammation) further reduce pro-angiogenic signaling and endothelial cell proliferation and subsequent vascular development. Therefore, the underdeveloped intestinal microvasculature, while sufficient for a “sterile” fasted intestine, becomes inadequate to meet the metabolic demand of postnatal stresses such as enteral feeding and bacterial colonization, which results in intestinal ischemia and necrosis, and NEC.
THE ROLE OF SPECIFIC GROUP OF INTESTINAL MACROPHAGES TO PROMOTE INTESTINAL VASCULAR DEVELOPMENT
In this project, we study how the intestinal macrophage compartment is affected by NEC stresses. We recently found that, in the neonatal intestine at birth, insulin-like-growth factor-1 (IGF-1) derived from embryonically-derived macrophages plays a critical role in promoting intestinal microvasculature development. We are now characterizing this embryonic macrophage population and define how this population is affected by NEC stresses, so we can define interventions that can preserve the paracrine role of these macrophages in premature infants to prevent NEC development.
A NOVEL NON-INVASIVE APPROACH TO PREDICT RETINOPATHY OF PREMATURITY (ROP) IN PREMATURE INFANTS
In this translational project, with the collaboration of Dr. Dina Arvanitis, the Head of the Center for Advanced Microscopy at Northwestern University, Dr. Hao Zhang, Professor of Biomedical Engineering at Northwestern University, and Dr. Hawke Yoon, a pediatric ophthalmologist at Ann & Robert H. Lurie Children’s Hospital of Chicago, we are examining whether nailfold capillary network density parameters can be used to predict vascular complications in preterm infants such as ROP. Indeed, beside NEC, abnormal microvascular development plays a critical role in several other diseases of prematurity, including ROP and pulmonary hypertension complicating bronchopulmonary dysplasia. However, there is a lack of non-invasive approaches to assess microvasculature development in premature infants.
Isabelle De Plaen, MD, is a Professor of Pediatrics at Northwestern University Feinberg School of Medicine. She is a Physician-Scientist and an Attending Physician in the Division of Neonatology at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. De Plaen’s lab focuses on deciphering the mechanisms leading to necrotizing enterocolitis (NEC), a leading cause of morbidity and mortality amongst premature infants. Their studies have identified a critical role for defective intestinal mucosal microvascular development in the pathogenesis of necrotizing enterocolitis. Specifically, their work focuses on defining how perinatal stress affects the developing intestinal microvasculature to increase premature infants’ susceptibility to NEC.