Magee-Womens Research Institute & Foundation

Research in Brief

I am a practicing Maternal-Fetal Medicine physician, and my research is directed towards answering challenges encountered at the bedside. In particular, work in our lab focuses on the mechanistic and clinical determinants of fetal growth abnormalities, particularly fetal growth restriction. Fetal growth restriction confers risk for stillbirth, neonatal death and morbidity, as well as long-term health problems throughout an individual’s lifetime. Despite these broad public health implications, early delivery remains the only therapy to treat, prevent, or ameliorate fetal growth restriction. Moreover, there is limited consensus on the appropriate diagnostic criteria or management strategies for fetal growth restriction, leaving broad gaps in our understanding of the optimal ways to define and manage this common clinical problem.

We employ parallel strategies to approach this problem from different perspectives. Our first line of investigation is translational in nature, probing mechanisms of placental injury and dysfunction. Recent work has focused on the effect of hypoxia and oxidative stress, two common placental insults germane to fetal growth restriction, on placental function. Specifically, we are investigating the impact of cholesterol oxidation and cholesterol oxidation products (oxysterols) on the transcription factors LXRα, LXRβ, and SREBP2, and gene expression pathways that regulate trophoblast viability, differentiation, steroid hormone synthesis, and lipid trafficking.

Our second line of investigation focuses on the diagnostic criteria and prognostic implications of fetal growth restriction. Fetal growth restriction is currently defined as a fetal weight below the 10th percentile in a population distribution, irrespective of the risk of morbid outcomes associated with this weight threshold. Moreover, the appropriate methodology to determine the 10th percentile as well as the appropriate reference population remains undefined. We are actively engaged in uncovering the underlying relationship between perinatal mortality and fetal growth through the analysis of large data sets. This analysis will facilitate the determination of diagnostic criteria for fetal growth restriction that will reflect relevant clinical risk thresholds.