# From stomach tissue to cellular mechanisms: unraveling the role of mononuclear phagocytes in the pathophysiology of gastroparesis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $1

## Abstract

ABSTRACT
Gastroparesis is a chronic gastrointestinal motility disorder characterized by delayed gastric emptying, chronic
abdominal pain, nausea and vomiting. Its incidence has increased 3-fold in the last decade, which has increased
healthcare costs by 10-fold. It is suggested that immune dysregulation plays a role in the pathophysiology of the
disease; however, the immune cellular mechanisms remain largely unknown, especially in humans. This is
largely in part because of limited knowledge on the types and functions of immune cells present in the human
stomach. This gap in knowledge presents a significant barrier to understanding the cellular mechanisms of
disease, and for the rational design of novel therapeutic strategies. Our preliminary data using mass cytometry
(CyTOF) shows that the human stomach harbors mononuclear phagocyte populations that are more diverse
than previously appreciated. Our studies also point, for the first time, to a disease that affects not only the
stomach muscularis as previously suggested, but also the stomach mucosa. Importantly, mononuclear
phagocytes in the mucosa of gastroparesis patients are dysregulated in numbers and function, which correlates
with delayed stomach emptying. Based on these data, our central hypothesis is that gastroparesis patients
harbor dysregulated mucosa and muscularis mononuclear phagocytes that contribute to the pathophysiology of
the disease. In three specific aims, we propose to resolve the identity and dysregulation of stomach mucosa and
muscularis mononuclear phagocytes in gastroparesis patients at a resolution that has not been done until now.
We will also explore the role of a neuronal peptide in modulating stomach mononuclear phagocyte function
during gastroparesis. To achieve these aims, we will take advantage of approaches that allow for the
identification of mononuclear phagocytes in an unbiased fashion. These approaches will be combined with ex
vivo functional assays and a mouse model of stomach emptying with the goal of unraveling cellular mechanisms
of disease. Our rationale is that by investigating the identity, i.e., phenotype and function, of human stomach
mononuclear phagocytes, we can elucidate the cellular mechanisms underpinning delayed stomach emptying
in gastroparesis. This proposal has the potential to impact the rational design of therapeutic strategies for
gastroparesis.

## Key facts

- **NIH application ID:** 10690620
- **Project number:** 5R01DK131500-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Juliana Idoyaga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2021-09-30 → 2023-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690620

## Citation

> US National Institutes of Health, RePORTER application 10690620, From stomach tissue to cellular mechanisms: unraveling the role of mononuclear phagocytes in the pathophysiology of gastroparesis (5R01DK131500-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690620. Licensed CC0.

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