Reproductive success and pregnancy health are critically dependent on intact development of the early embryo and the placenta. These processes are regulated by genetic and epigenetic mechanisms that control gene expression. Our perinatal biology group studies these pathways, and how they shape feto-placental development, cellular differentiation, and growth.
Throughout pregnancy and until birth, the placenta is obligatory for embryonic organogenesis, fetal growth, immunological support, and maintenance of healthy maternal-fetal communication, while preserving maternal health. Centrally positioned to support fetal development, the placenta is a target for diverse intrauterine injuries spanning epigenetic, genetic, molecular, and acquired perturbations that impact common, severe diseases of pregnancy, including fetal growth restriction. Placental dysfunction leaves its mark on the developing embryo, rendering it vulnerable to a host of childhood and adult diseases.
Our laboratories have joined forces to define placental dysfunction and its molecular and metabolic consequences to the fetus, which are pertinent to our understanding of the biology of pregnancy.
We center on the process of genomic imprinting, defined as a mechanism of transcriptional regulation that restricts expression to one parental allele. This multi-step process begins in the gametes, where epigenetic modifications differentially mark the parental alleles. These marks must then be stably maintained in the developing embryo, where they are translated into parental-specific expression and play a key role in remodeling chromatin during the pre-implantation and post-implantation developmental periods.
We also study placental processing of metabolic fuels, their availability to the fetus, and the impact of dysregulated molecular, epigenetic and cellular influences on trophoblast storage of caloric nutrients, such as glycogen and lipids. Metabolic dysfunction may lead to lipotoxicity, trophoblast damage, and inadequate supply of nutrients to the fetus.
Lastly, we investigate the function of trophoblast-specific microRNAs that govern placental resistance to viruses, and extracellular vesicle-based communication between the fetal, placental, and maternal compartments.
- Yaacov Barak, PhD
- J. Richard Chaillet, MD, PhD
- Jacob Larkin, MD
- Mellissa Mann, PhD
- Yoel Sadovsky, MD
- Transcriptional and Developmental Regulation of Placental Fuel Storage and Metabolism (NIH P01HD069316, Project w PI: Barak)
- The Role of Genomic Imprinting in Placental Metabolic Function (NIH P01HD069316, Project 1 PI: Chaillet)
- The Role of Oxysterols in Placental Biology (NIH R21HD084914, PI: Larkin)
- Magee-Womens Auxiliary Research Scholar Award (PI: Mann)
- Placental Storage and Metabolism of Neutral Lipids (NIH P01HD069316, PD and Project 3 PI: Sadovsky)
- Primary Human Trophoblasts and the Transfer of Viral Resistance (NIH R01HD075665, PI: Sadovsky)
- Extracellular Vesicles and Their ncRNA Cargo as Markers of Trophoblast Injury (NIH R01HD086325, PI: Sadovsky)
- Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) in Pittsburgh (NIH K12HD043441, PI: Sadovsky)
- University of Pittsburgh Clinical and Translational Science Institute Special Populations Core (NIH UL1TR001857, Core PI: Sadovsky)
- March of Dimes Center for Prematurity Research at the University of Pennsylvania Theme 3: Placental dysfunction (Project PI: Sadovsky)
- The Impact of Maternal-Placental-Fetal Communication on Pregnancy Health (25 Club of Magee-Womens Hospital, PI: Sadovsky)
- Society for Reproductive Investigation
- Placenta (Scientific Journal)
- University of Santa Cruz (UCSC) Genome Browser
- Deciphering the Mechanisms of Developmental Disorders (DMDD) database