# Novel ARNT-mediated Regulatory Paradigm of AHR Signaling

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $71,463

## Abstract

SUMMARY/ABSTRACT
 AHR is a cytoplasmic receptor that has affinity for numerous xenobiotic ligands, which include
halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), one of the most potent
AHR activators, and AHR signaling mediates the detrimental effects of environmental contaminants on body
tissues and organs. Ligand binding induces nuclear translocation of AHR and interaction with the AHR binding
partner, aryl hydrocarbon receptor nuclear translocator (ARNT), allowing recognition of specific DNA enhancer
sequences. More recently endogenous and natural AHR ligands, such as tryptophan metabolites and dietary
compounds, have been identified. These ligands induce AHR-mediated immunomodulatory effects such as
controlling normal T cell differentiation and immune tolerance. ARNT is expressed as two isoforms, isoform 1
and 3, which differ in only 15 amino acids present in isoform 1. Despite their sequence similarity, we have found
that the ARNT isoforms appear to have opposing functions in AHR signaling. As such, through work funded by
my parent R01 (ES025809), we find that ARNT activity is a function of both unique phosphorylation of isoform 1
and the given isoform ratio within a particular cell type, which in turn is important for regulating the
magnitude/outcome of the AHR response. Moreover, these data suggest that by modulating the ARNT isoform
ratio will allow for fine-tuning of an immune response to control inflammation and resolution. Thus, it is critical
that my laboratory maintain consistency in the face of the ongoing pandemic in order to continue these cutting-
edge investigative avenues that have potential for clinical translation to treat a wide range of environmentally
linked immune disorders. Accordingly, this supplement application is to request a portion of salary lost during
the past year of COVID shutdowns and quarantine protocols to help support my senior research scientist until
new long-term funding is secured.

## Key facts

- **NIH application ID:** 10378798
- **Project number:** 3R01ES025809-05S2
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Casey W Wright
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $71,463
- **Award type:** 3
- **Project period:** 2021-08-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378798

## Citation

> US National Institutes of Health, RePORTER application 10378798, Novel ARNT-mediated Regulatory Paradigm of AHR Signaling (3R01ES025809-05S2). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10378798. Licensed CC0.

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