# Identification, Quantification, and Functional Characterization of Transporters in Human Placenta, Developing Gut and Fetal Brain

> **NIH NIH UC2** · UNIVERSITY OF WASHINGTON · 2024 · $912,344

## Abstract

SUMMARY
The placenta, often referred to as the “intestine” of the fetus, is an essential organ that controls the exchange of
nutrients (including vitamins) and xenobiotics (i.e., dietary supplements and FDA approved drugs) between the
mother and her fetus. The fetus can also ingest nutrients and xenobiotics via the digestive tract, so do neonates
and infants through breastfeeding after birth. The fetal, neonate, and infant blood-brain barrier (BBB) serves a
critical role in protecting the developing brain from xenobiotics and supplying nutrients to the brain. Thus, the
placenta, the developing BBB and gut are key organs responsible for nutrient and xenobiotic distribution and
absorption impacting early human development and xenobiotic toxicity. Transporters can play an essential
role in the absorption, systemic exposure, and tissue distribution of nutrients and xenobiotics in the
fetus, neonates, and infants across the placental, intestinal, and blood-brain barriers. Identification and
quantification of transporters in these tissue barriers is important for understanding and predicting fetal or
neonate/infant uptake of, and exposure to, nutrients and xenobiotics, and hence impacting early development as
well as the safe and efficacious use of medications/supplements in these vulnerable populations. While the
expression and function of a few ABC transporters in human term placenta, such as P-glycoprotein (P-gp) and
Breast Cancer Resistance Protein (BCRP), have been well-delineated, such data are sorely missing for
transporters in early gestation placenta, and in the developing gut and BBB during pregnancy and after birth. In
this application, we propose to establish a Transporter Elucidation Center (TEC) at the University of Washington
that addresses the goals articulated in RFA-HD-23-003. Using quantitative global and targeted proteomics,
we will systematically identify and quantify the ontogeny of transporters in the human placenta (from early
gestation to term), the developing gut as well as the developing BBB (from early and mid-gestation and after
birth). Then, through in vitro (transporter-transfected cells, immunohistochemistry, immunolocalization) and ex
vivo (e.g., placental perfusion, intestinal organoids, and iPSC-derived human fetal BBB models) transport
studies, we will determine novel substrates, cellular localization, and transport activity of highly abundant
transporters in these tissues. Combined, these studies will address a critical knowledge gap in our
understanding of transporters that control essential physiological functions and xenobiotic disposition in the
developing fetus and neonate/infant. Consequently, the proposed studies will enhance our ability to predict the
toxicity or efficacy of xenobiotics and physiological efficacy of nutrients (or lack thereof) in these vulnerable
populations.

## Key facts

- **NIH application ID:** 10906208
- **Project number:** 5UC2HD113041-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JASHVANT D Unadkat
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $912,344
- **Award type:** 5
- **Project period:** 2023-08-11 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906208

## Citation

> US National Institutes of Health, RePORTER application 10906208, Identification, Quantification, and Functional Characterization of Transporters in Human Placenta, Developing Gut and Fetal Brain (5UC2HD113041-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10906208. Licensed CC0.

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