Molecular and cellular approaches to placental development and function

Description of projects available to graduate students:
Our lab utilizes molecular and cellular approaches to decipher mechanisms underlying placental development and differentiation. The trophoblast at the feto-maternal interface fulfills critical functions for embryonic development, including gas exchange, supply of nutrients, removal of waste products, endocrine regulation, and immunological defense. Using cultured primary human placental cells, genetically-altered mice, and placental samples from abnormal human pregnancies, we examine trophoblast response to diverse stressors that adversely influence the homeostatic balance between cell injury and regeneration. These stressors contribute to placental dysfunction and fetal growth restriction, which predispose to childhood neurodevelopmental dysfunction and metabolic derangements in the adult.

Specific research areas include: (1) Placental uptake and processing of metabolic fuels: the lab studies the uptake, storage, and trafficking of fatty acids that are critical for feto-placental development. The transcription factor PPARg and its targets play a critical role in this process. We use lentiviruses to knockdown or overexpress these targets, and analyze the effect of these perturbations on placental function and lipotoxicity. (2) The role of microRNA in placental function: having shown that microRNA biogenesis pathways are functional in placental trophoblasts, we used microRNA microarrays, northern analysis and qPCR to define a set of trophoblastic miRNA species that exhibit altered expression in response to hypoxic stress. By combining computationally identified set of miRNA targets with transcriptomic analysis, we defined placental microRNA targets that are essential for trophoblast function. We use overexpression and silencing approaches to interrogate the function of unique, placenta-specific imprinted miRNA clusters. (3) Placental injury and adaptation: building upon a defined a hypoxic trophoblast signature transcript that either governs trophoblast adaptation to injury, we examine the in vivo function and mechanism of action of NDRG1, which protects trophoblasts against hypoxic injury.

Techniques graduate student will learn:
Cultures of primary human trophoblasts as well as cell lines
Analysis of mRNA and protein
Use of lentiviruses for modification (shRNA-based) of gene expression in primary cells
Isolation, analysis and manipulations of microRNAs
Performance of mRNA- and microRNA arrays, and their bioinformatics-based analysis
Examination of mouse feto-placental phenotype