# Subproject Investigator: Celine A. Beamer

> **NIH NIH P20** · UNIVERSITY OF MONTANA · 2020 · $217,500

## Abstract

Inflammatory lung diseases such as asthma affect nearly 300 million people worldwide, including
approximately 11% of the U.S. population. Currently, chronic inflammatory lung diseases can be controlled, but
not cured; thus placing them among the most expensive diseases for long-term healthcare. A hallmark of
chronic airway inflammation is the increase in cytokines that provoke inflammation in the lung and airway
hyper-responsiveness. Current therapies revolve around the use of corticosteroids for suppression of
inflammation, which while effective, have significant side effects. A potentially powerful approach would be
small molecule manipulation of the cytokine response.
The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor belonging to the Per-ARNT-SIM
(PAS)-basic-helix-loop-helix (bHLH) protein family that modulates immune cell differentiation and function in
response to natural and synthetic ligands. The AhR interacts with structurally diverse ligands resulting in
differential effects on cytokine secretion by innate lymphoid cells (ILCs). Our preliminary results support the
premise that functional differences in AhR ligands may be exploited to manipulate the expression of regulatory
(e.g. IL-22) vs. inflammatory (e.g. IL-17) cytokines in airway inflammation, thus reducing it. If we can design
small molecules that selectively induce IL-22 production by group 3 ILCs, it should be possible to promote this
effect, and use this knowledge to develop novel therapies for inflammatory lung diseases.
Therefore, this project will focus on understanding the mechanisms by which YH439 and custom-designed
analogs activate the AhR and induce the expression of IL-22 in ILCs, leading to a non-toxic immune-
modulatory action. We will then create a novel photoaffinity probe for the purposes of: 1) interrogating AhR-
ligand interactions, 2) elucidating AhR structure, function, and conformation changes, and 3) identifying novel
or alternative binding sites in proteins. The results generated from the successful completion of this project are
expected to support the concept that modulation of AhR signaling pathways in the lungs impacts the
progression of inflammatory diseases by altering the functional capacity of ILCs.

## Key facts

- **NIH application ID:** 10004086
- **Project number:** 5P20GM103546-10
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** CELINE A BEAMER
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,500
- **Award type:** 5
- **Project period:** 2011-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004086

## Citation

> US National Institutes of Health, RePORTER application 10004086, Subproject Investigator: Celine A. Beamer (5P20GM103546-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004086. Licensed CC0.

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