Penn Lab In The Department of Pediatrics

Research Interests

Placental Hormones and Fetal Brain Development

Developing novel mouse models to change individual placental hormones: one hormone at a time!

We are developing a novel series of mice in which individual hormones are specifically removed from the placenta at precise times during development.  The vectors to engineer these mice are currently in production in my lab.  This system will allow the first direct, definitive tests of the placenta as a key regulator of fetal brain development.   Techniques have recently been developed to change gene expression specifically in the placenta and to create mice where genes can be turned on and off at specific times.  We will combine these new techniques in mouse engineering to change the expression of hormones either in the placenta alone or in the mother mouse and the placenta to test to placental and maternal hormonal contributions to fetal brain development.   Well-known placental hormones, such as progestins and oxytocin, are being targeted.  In a parallel series of experiments, we are identifying placental hormones not previously that may change neural connections.

 

Investigating sex differences in newborn brain damage: why can’t boys be more like girls?

Male sex is a well-established risk factor for poor neurodevelopmental outcome following premature birth.  The mechanisms that underlie this sex-related difference are unknown.  We have discovered that we can mimic this sex-linked differential damage in rodents either in vivo or in vitro, particularly in the hippocampus.  We are investigating the role of sex steroids-- to which the brain is exposed in high amounts during fetal development-- in this sex difference in terms of long-term anatomical and behavioral changes.  We are also exploring the potential use of sex steroids or temporary steroid blockade for neuroprotection.

 

AppleMark Linking hormone levels in newborns to later neurodevelopment

We are launching a new area of translational research to identify hormones in human preterm infants and ex-preterm children that are associated with cognitive disorders, particularly autism and developmental delay.  Using highly sensitivity mass spectroscopy protocols that we and our collaborators have developed for use on tiny fluid volumes, we will measure steroid and peptide hormone levels in left over infant cerebrospinal (CSF) and blood that has been obtained for clinical purposes. Neurodevelopmental outcomes will be assessed in collaboration with Developmental Medicine and the Autism Center at Stanford.

 

 

Establishing new resources for understanding the molecular biology of the placenta

The Stanford Placental Working Group is a multi-disciplinary group of physicians and scientists. Stanford delivers more than 5,000 babies per year; an estimated 300 of these are born early as a result of preeclampsia with 300 additional preterm births due to other causes. Over the next two years, we plan to collect more than 1000 placentas-- normal term, preterm, and preeclamptic placentas.

 

 

Dynamic models of neonatal physiology to predict risk and onset of adverse events in the NICU

In collaboration with Daphne Koller’s group in Computer Science and Jeff Gould, MD, MPH, we are capturing all biological signals (cardio-respiratory monitoring, lab measurements etc.) for infants in the NICU.  We are analyzing this extensive dataset to develop new strategies and algorithms to predict illness severity and adverse events in high-risk newborns.  

 

 

 

 

 

 

 

 

 

 

 

 

 

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