# GGT Targeting Suppresses Mast Cell Activation by IgE and IL-33

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $371,875

## Abstract

Mast cell activation by IgE or IL-33 elicits powerful inflammatory responses contributing to
allergic disease, a significant health burden in need of novel therapies. Cholesterol-lowering
statin drugs targeting HMG Co-A reductase (HMGCR) suppress allergic inflammation in some
clinical trials, but effects are inconsistent. Our data suggest that this variability is due to statin
resistance that can be circumvented by targeting geranylgeranyl transferase (GGT) downstream
of HMGCR. Therefore, this application will test the hypothesis that GGT inhibition suppresses
mast cell functions induced by IgE and IL-33. Our preliminary data show statins and GGT
inhibitors can block mast cell function in vitro and in vivo. The proposed studies include
mechanistic investigations of how GGT blockade alters specific Ras family proteins, as well as
the effect of GGT inhibition on IL-33-mediated glycolysis. We further include studies of human
mast cells and in vivo models that will reveal fundamental insights into mast cell biology and
offer translational potential. We have two Specific Aims:
Aim 1: We will determine the effects of GGT blockade on IgE signaling, in vitro and in vivo.
Aim 2: We will determine the effects of GGT inhibition on IL-33-mediated mast cell function, in
vitro and in vivo.

## Key facts

- **NIH application ID:** 10459343
- **Project number:** 5R01AI138495-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** John J Ryan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,875
- **Award type:** 5
- **Project period:** 2018-08-08 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459343

## Citation

> US National Institutes of Health, RePORTER application 10459343, GGT Targeting Suppresses Mast Cell Activation by IgE and IL-33 (5R01AI138495-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10459343. Licensed CC0.

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