# Spatial and temporal resolution to dissect cellular circuits controlling intestinal physiology, immunity, and inflammatory pathologies

> **NIH NIH RC2** · BROAD INSTITUTE, INC. · 2024 · $1,892,806

## Abstract

PROJECT SUMMARY
As a critical barrier tissue, the intestinal mucosa must balance complex environmental stimuli — including dietary
components, microbes, metabolites, and xenobiotics — to fine-tune immune development and tolerance. In
health, homeostasis is maintained via a constellation of specialized cell types that connect host physiology to
these external signals. Disruption of intestinal physiology results in numerous diseases, including inflammatory
conditions such as Crohn’s disease and ulcerative colitis. Here, we propose a framework to dissect the cellular
mechanisms underlying the homeostatic and inflamed states in the small intestine and colon at unprecedented
spatial and temporal resolution. In Aim 1, we will spatially profile gene and protein expression across human gut
samples in health and disease, developing the necessary computational tools to identify critical disruptions in
cell-cell communication networks that result from inflammation. Computational tools developed in this context
will have broad application in studying tissue biology. Additionally, we will make cross-disease comparisons (e.g.,
Crohn’s disease, celiac disease, and eosinophilic gastroenteritis) to identify common inflammatory mechanisms
independent of tissue type. In Aim 2, we will leverage experimental mouse models to spatially profile the
dynamics of inflammation (from homeostasis through induction and resolution of inflammation) and dietary stress
in the mouse gut — generating temporally resolved maps of these processes. In Aim 3, we will use organoid and
cell-cell coculture models to determine how chemosensory pathways are translated into the coordinated cellular
responses that maintain homeostasis.

## Key facts

- **NIH application ID:** 10894610
- **Project number:** 5RC2DK135492-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Caroline Uhler
- **Activity code:** RC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,892,806
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894610

## Citation

> US National Institutes of Health, RePORTER application 10894610, Spatial and temporal resolution to dissect cellular circuits controlling intestinal physiology, immunity, and inflammatory pathologies (5RC2DK135492-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894610. Licensed CC0.

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