# Determination of maternal-fetal phosphate transport mechanisms and the role of sodium-dependent phosphate transporters in extraembryonic tissues

> **NIH NIH R00** · TUFTS MEDICAL CENTER · 2020 · $248,999

## Abstract

Project Summary: I aim to establish a biomedical research lab that investigates mechanisms of placental
development and pathophysiology. Dr. Alan Guttmacher recently identified the placenta as “the least
understood human organ” when discussing the Human Placenta Project, a new initiative of the National
Institute of Childhood Health and Human Development (Kaiser J. 2014. Science 344(6188):1073).
Placental dysfunction and resulting syndromes are poorly understood despite the clear significance to
human health. Impaired placental function can lead to fetal growth restriction and is linked to preeclampsia,
a pregnancy specific life-threatening hypertensive syndrome within unknown etiology. Preeclampsia is a
leading cause of maternal and neonatal death. It occurs in 3-8% of pregnancies, and ~4% of these cases
result in mortality. Other cases lead to premature birth, developmental disorders in offspring, increased risk
for cardiovascular and kidney diseases later in life for mothers, and substantial health care costs.
Unfortunately, the number of preeclampsia cases is increasing. Stephen Hodgins, Deputy-in-Chief of
Global Health: Science and Practice, recently published an editorial titled “Pre-eclampsia as an Underlying
Cause for Perinatal Deaths: Time for Action” (Hodgins S. 2015. GHSP; 3(4):525-527), highlighting this
important global public health issue. A better understanding of the placenta is greatly needed in order to
diagnose, treat, and prevent preeclampsia and other health issues resulting from placental dysfunction.
My work will address several key unknowns in placental development and pathophysiology. I will begin by
determining molecular mechanisms of maternal-fetal phosphate transport. Phosphorus is an essential
nutrient and it is required for several processes in growth and development, such as DNA and cell
membrane structure, bone deposition, oxidative phosphorylation, and others. Remarkably, the molecular
mechanisms and proteins that regulate maternal-fetal phosphate transport remain unknown. I have
identified a likely family of maternal-fetal phosphate transporters and developed loss of function mouse
models that revealed specific developmental requirements. PiT-1 loss results in embryonic lethality,
decreased endocytosis, and impaired angiogenesis (Wallingford et al. 2014. Mech. Dev. 133:189-202).
PiT-2 deficiency results in fetal growth restriction, decreased bone density, and abundant placental
calcification (Wallingford et al. Reprod. Biol. and Wallingford et al. Brain Pathology – both in process). The
PiT-2 null mouse is the first and only placental calcification model available. My data suggests that PiT-2
mediated anti-calcific mechanisms may play a key role in preventing placental dysfunction, and clinical
studies have indeed correlated altered expression levels of PiT-1 and PiT-2 with preeclampsia (Yang et al.
2014. Mol. Reprod. & Dev. 81:851-860). Further, calcification of the placenta is frequently observed in
humans, and...

## Key facts

- **NIH application ID:** 9895837
- **Project number:** 5R00HD090198-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Mary Catherine Wallingford
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2018-04-18 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895837

## Citation

> US National Institutes of Health, RePORTER application 9895837, Determination of maternal-fetal phosphate transport mechanisms and the role of sodium-dependent phosphate transporters in extraembryonic tissues (5R00HD090198-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895837. Licensed CC0.

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