# Nutrigenomics of Intestinal Vitamin D Action

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $517,831

## Abstract

Project Summary
 The most important function of vitamin D is the regulation of intestinal calcium absorption – a classical role of
vitamin D critical for bone health. Despite the importance of vitamin D in the intestine, the mechanisms of vitamin
D action in intestine are not clear. Although most Ca absorption research has focused on the proximal small
intestine, our novel preliminary data using distal intestine specific knockout (KO) or transgenic mice reveal an
essential role for VDR in the distal intestine. The proposed research employs a genomic approach coupled
to physiology studies in novel mouse models to test the hypothesis that the proximal and distal segments of
the intestine have unique regulatory pathways controlling VDR expression and vitamin D action, and that calcium
absorption and expression of VDR target genes in the distal intestine contribute significantly to bone and mineral
metabolism. To address this hypothesis we have developed two specific aims. Aim 1: Define the functional
genomics of VDR expression and signaling that mediate calcium absorption in the proximal and distal
intestine and its impact on whole body calcium and bone metabolism. Using a genome-wide approach we
will identify spatial (proximal vs distal intestine; villus vs crypt) and temporal (pre vs post weaning; young vs
adult) effects on chromatin architecture of the Vdr gene locus to identify critical upstream regulators of Vdr
expression in proximal and distal intestine. Next, VDR target genes in the proximal and distal intestine and in
progenitor vs differentiated cells will be identified on a genome-wide scale. The human relevance of VDR targets
as well as VDR regulatory mechanisms will be determined in studies using human-derived organoid cultures.
Finally, we will test the hypothesis that Ca absorption in the distal intestine contributes significantly to bone and
mineral metabolism using unique animal models including VDR KO mice with transgenic expression of VDR only
in the distal intestine. We will also determine for the first time the effect of VDR deletion throughout the intestine
or specifically in the distal intestine in adult mice on calcium and bone metabolism. Aim 2: Determine the
translational potential of targeting the distal intestine to improve calcium balance and protect bone. We
will test whether targeting the absorptive capacity of the distal intestine can be an effective way to maximize Ca
absorption and minimize adult bone loss. This will be done using transgene-enhanced expression of VDR in the
distal intestine and use of a natural, distal intestine-targeted vitamin D form (25 β glucuronide 1,25(OH)2D3) to
improve calcium balance and protect against bone loss. This proposed research is responsive to PA-16-332
“Nutrigenetics and Nutrigenomics Approaches for Nutrition Research.” It combines expertise in vitamin D
biology, nutrition, and genomics to determine how the molecular actions of vitamin D can be utilized to improve
Ca status in gr...

## Key facts

- **NIH application ID:** 9906893
- **Project number:** 5R01DK112365-04
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** SYLVIA S CHRISTAKOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,831
- **Award type:** 5
- **Project period:** 2017-07-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906893

## Citation

> US National Institutes of Health, RePORTER application 9906893, Nutrigenomics of Intestinal Vitamin D Action (5R01DK112365-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9906893. Licensed CC0.

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