Molecular Pathways of Development

As scientists who care about the health of smallest and sickest babies, we seek to understand normal development to inform our studies of the abnormal. To bridge critical gaps in understanding, we have built a direct line between our work in the Neonatal Intensive Care Unit and experiments at the bench.

Our laboratories are dedicated to studying fetal and perinatal development, exploring the molecular conversation that exists between mother and baby during pregnancy with the placenta serving as the interface. There are signals that initiate birth, and although we know some of the key players, many of them remain unknown. In normal development we are looking to discover those regulatory molecules that indicate the completion of pregnancy. When development goes awry, gaps in communication or inappropriate signaling may convey the wrong message, leading to profound anatomic or functional consequences for the fetus and/or mother. The abnormalities may be wholly due to factors intrinsic to this process, or may be impacted by extrinsic factors such infection, chemical exposure, and stress. In our division we study the full breadth of what influences fetal health and development. It’s especially important that we do because birth defects and preterm delivery originate from these anomalies along the molecular pathways.

Key regulators of development include heme oxygenases (HO), the metabolic proteins HO-1 and HO-2. Present in organisms from bacteria to man, these proteins have deep evolutionary origins and help the body maintain homeostasis. We benefit from having a very strong history of laboratory science using animal models to evaluate mammalian development as it pertains to HO-1 production as well as other enzymatic pathways. We have reliable mouse models for most of the vexing obstetrical and perinatal issues like preterm birth, stillbirth, low birth weight and failure to thrive. Using state-of-the-art in vivo imaging and sensing technologies, we can look at cells, both in humans and animals

Much of the laboratory work in neonatology is aimed at helping us spot clinical problems early when intervention is possible. For example, often mothers are infected at a low level and do not show significant outward symptoms; however, infection of even a few thousand cells in the placenta may have a profound effect on the developing fetus. The signals that regulate the migration of immune cells are called cytokines or chemokines, and are the same cells that direct cell migration in the developing fetus. Elevated or otherwise altered secretion of these molecules by the mother may substantially impact fetal development.

Exploring this response is possible through our transdisciplinary program in developmental biology which calls upon experts in neurodevelopment, psychology, microbiology, immunology and environmental biology. Integration is one of our strengths and paramount to our operation of the March of Dimes Prematurity Research Center. With generous support from the March of Dimes, we are heavily invested in studying developmental biology as it relates to the causes of prematurity and its long-term consequences on a child born preterm.

To learn about our laboratories, click here


Faculty

Professor (Research) of Pediatrics (Neonatology), Emeritus
The Harold K. Faber Professor of Pediatrics, Senior Associate Dean, Maternal and Child Health and Professor, by courtesy, of Obstetrics and Gynecology
Sr Res Scientist-Basic Ls, Pediatrics - Neonatology