# Minerals in Nutrition and Development

> **NIH NIH UC2** · JOHNS HOPKINS UNIVERSITY · 2024 · $972,718

## Abstract

SUMMARY
The health and development of the infant is inherently linked to the health of the mother through the absorption
and secretion of nutrients. Dietary minerals, including metals (Cu, Zn, Ca, Mn, Fe) are essential nutrients
required for all aspects of physiological function. Yet the transport proteins critical for nutrient absorption and
secretion are poorly defined and there is a paucity of functional data in human tissues or in vitro models
derived from normal human cells to elucidate how and what adaptations in transporters occur to support
pregnancy and lactation. This fundamental gap must be bridged to improve health outcomes for children and
mothers. Our Transport Elucidation Center (TEC) on Minerals In Nutrition and Development (MINeD) will
capitalize on our rich scientific, clinical, and mentoring expertise to serve as a hub for discovery, bench-to-
bedside translation, and training in the area of human metal transport and nutrient uptake. The initial focus of
the MINeD center 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. However, given the ethical challenges of acquiring human samples and
establishing suitable in vitro models for transport flux studies, a functional understanding of metal transporters
and their broader role in nutrient transport during lactogenesis is lacking. In Aim 1, we will address this gap in
knowledge by defining the human ‘transportome’ in lactating mammary epithelium and how it relates to the
mammary metallome to elucidate how nutrients are transported into milk. We will use human in vitro organoid
models of mammary gland function to identify functional modules of transporters that are synchronously
induced and discretely localized to accomplish transepithelial metal transport. Using gene-editing technology,
we will systematically engineer deletions in the SLC family of solute carriers to de-orphanize understudied
transporters and reveal potential new roles in milk production and secretion. In Aim 2, complementary studies
using human adult and pediatric duodenal and jejunal enteroids will determine the role of metal transporters in
intestinal adaptation and nutrient absorption to support child development, maternal pregnancy and lactation.
We will ask how pregnancy- and lactogenic hormones change intestinal proliferation, transporter protein
abundance at the plasma membrane, fat absorption, and metal content and distribution. Aim 3 of MINeD is to
build the infrastructure and fundamental discovery pipeline to support future studies on human transporters.
MINeD is well positioned to serve as a nexus for collaborations between basic and clinical research, to foster
interactions in the scientific community by sharing kno...

## Key facts

- **NIH application ID:** 10900804
- **Project number:** 5UC2HD113036-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RAJINI RAO
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $972,718
- **Award type:** 5
- **Project period:** 2023-08-07 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900804

## Citation

> US National Institutes of Health, RePORTER application 10900804, Minerals in Nutrition and Development (5UC2HD113036-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10900804. Licensed CC0.

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