Define the Placental Transporter Proteome in Healthy and Diseased Pregnancies

The developing baby needs nutrition from its mother in order to grow and properly develop.  One means to obtain this nutrition is through a placenta – an organ that comes from the baby and connects to the mother. Nutrients cross the placenta – but so do medications, supplements, and toxicants. Our research seeks to reveal how these chemicals move back and forth between mother and baby.

We are integrating data obtained from human pregnancies to define the transporter proteome healthy pregnancies as well as those complicated by diseases such as preeclampsia and gestational diabetes.

Predict and Test Novel Functional and Regulatory Interactions of Chemicals with Transporters

Drugs and chemicals are often too large to enter and exit cells unassisted. Transporter proteins can be used as gates that regulate which chemicals enter and leave cells. In fact, the Solute Carriers (SLC) are proteins that can regulate the uptake or removal of chemicals from cells or organelles. In addition, the ATP-binding cassette transporters (ABC) function as efflux pumps that remove chemicals from the cell.

We are applying cheminformatic and machine learning approaches to reveal new substrates and inhibitors of placental SLC and ABC transporters.

Evaluate Drug and Chemical Transfer in a Human Placenta-on-a-Chip Model

Pregnancies in animals such as mice and rats are quite different from humans!  We are using bioengineering and microfabrication approaches to create simple and complex physiological systems that resemble the maternal-fetal barrier.

For these studies, placenta-on-a-chip systems are fabricated, seeded with human placental cells, and placed under dynamic flow that allow for selective infusion and sampling of nutrients, drugs, supplements, and toxicants.

UWTEC

PIs: Dr. Joanne Wang and Jashvant Unadkat

The broad goals of this Transporter Elucidation Center (TEC) at the University of Washington are:

1.  to identify and quantify transporters in the human placenta from early gestation to term, and in the developing gut (fetal and neonate/infant);
2.  to functionally characterize and determine the cellular localization of the highly abundant transporters identified in these human organs.

Read more here.

UCSF TEC

PIs: Dr. Kathy Giacomini and Robert Stroud

The overall goal of the TECUCSF is to elucidate the ligand specificity, protein structure and cellular localization of SLC and ABC transporters in the human blood-brain barrier. Based on preliminary studies from our global proteomic analyses, we will prioritize a list of 30 highly expressed and understudied/orphan SLC and ABC transporters in the human blood-brain barrier. Read more here.

MINeD

PI: Dr. Rajini Rao

The initial focus of the Minerals In Nutrition and Development (MINeD) center at Johns Hopkins University will be in the developing gut and adapting maternal intestine and breast. During pregnancy and lactation, drastic remodeling of the mammary gland enables the synthesis and secretion of milk to sustain and nourish the infant. Importantly, transcriptional data from human milk-derived epithelial cells point to a key role for metal homeostasis. A functional understanding of metal transporters and their broader role in nutrient transport during lactogenesis is critically needed. Read more here.