# Oxysterol Regulation of Mast Cell Biology

> **NIH NIH K22** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $160,835

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal details a two-year plan to allow the candidate, Daniel Dwyer, PhD, to transition to a stable
independent research career. The focus of this study is on characterizing a novel regulatory axis capable of
mediating the recruitment and activation of mast cells (MCs) during type 2 inflammation (T2I). MCs are potent
effector cells that play key pathogenic roles in type 2 inflammatory diseases through the generation and
release of a broad range of inflammatory mediators, including histamine, proteases, lipid mediators, and
cytokines. The specific mechanisms underlying the expansion of MC during type 2 inflammation or the
persistent activation of these cells associated with these diseases are unclear. This proposal identifies novel
expression of a G protein-coupled receptor (GPCR) in both human and mouse MCs. Ligation of this receptor
elicits mediating MC migration in vitro and additionally induces MC activation both in vivo and in vitro. Further,
this proposal further identifies upregulation of a necessary enzyme for synthesis of the ligand across a
spectrum of human T2I disease and finds that murine MC progenitor recruitment during allergic pulmonary
inflammation is virtually absent in mice lacking the enzyme. Aim 1 of this proposal will utilize two murine
models of allergic lung inflammation to assess which cells express and upregulate the enzyme in the context of
T2I, followed by in vitro approaches to determine the mechanism driving this upregulation. Aim 2 of this
proposal details the generation of a novel mouse strain in which the GPCR is specifically deleted in MC. After
an initial confirmation of specific deletion and characterization of the MC compartment across tissues, the
specific role of this GPCR in regulating constitutive MC activation and MC progenitor recruitment will be
assessed in two inflammatory models.

## Key facts

- **NIH application ID:** 9806198
- **Project number:** 1K22AI146281-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Daniel F Dwyer
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,835
- **Award type:** 1
- **Project period:** 2020-08-13 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9806198

## Citation

> US National Institutes of Health, RePORTER application 9806198, Oxysterol Regulation of Mast Cell Biology (1K22AI146281-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9806198. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*