# Spatial and Temporal Resolution of EosinophilSpecialization in Allergic Microenvironments

> **NIH NIH DP2** · UNIVERSITY OF COLORADO DENVER · 2024 · $468,000

## Abstract

ABSTRACT
Eosinophilic inflammation is a key feature of many human pathologies, and therapeutic targeting of eosinophils
is of clinical interest, as illustrated by the new class of eosinophil-depleting drugs in development for allergic
and inflammatory diseases. The full potential and consequences of these drugs are active areas of medical
research, particularly as eosinophil depletion does not uniformly cause symptom reduction. Despite their post-
mitotic state and short circulating lifespan, eosinophils can persist for days to weeks in certain tissue
environments. Increasingly, there is evidence of a positive role of long-lived, “tissue-resident” eosinophils in
tissue structure development and maintenance that counters the historic view of eosinophils as only having
pro-inflammatory functions. Given the prevalence of eosinophilic inflammatory conditions and development of
eosinophil-depleting drugs, there is a significant need to understand 1) which factors enable eosinophil
differentiation, 2) how differentiated eosinophils interact with the surrounding tissue, and 3) what molecular
events prolong survival of an otherwise short-lived post-mitotic cell. This project will elucidate the regulation
and function of tissue-resident eosinophils at steady state and during allergic disease. We hypothesize that
eosinophils respond to pro-survival signals in the epithelial environment by engaging cell cycle machinery to
prevent apoptosis and support rapid gene expression during specialization. The three research areas will 1)
target cell cycle machinery to manipulate eosinophil specialization in mucosal tissue, 2) delineate pre- and
post-transcriptional events in eosinophil re-specialization, and 3) define and inhibit pathogenic functions of
specialized eosinophils. These studies are technically and conceptually innovative in that they use high-
sensitivity immunoassays, 3D organotypic tissue models, next-generation sequencing, and chromatin looping
technologies to expand on paradigm-shifting evidence of a dynamic, long-lasting role of eosinophils in tissue.
The technical approach is creative and designed to address eosinophil functions that are poorly understood but
central to understanding and treating eosinophilic diseases, type 2 allergic diseases, autoimmune pathologies,
and certain cancers. This research is ideally suited to the NIAID DP2 award due to its potentially transformative
effect on the understanding of granulocyte biology. The applicant is well suited to lead the proposed work given
her technical and analytical skill, research productivity, and success in creative problem-solving and
collaborative project development. The DP2 award will augment the resources accompanying her newly
independent position and allow Dr. Dunn to apply impactful new technologies to a clinically relevant but
understudied area of eosinophil biology that has broader implications for the converging fields of clinical
immunology, personalized medicine, and nuclear str...

## Key facts

- **NIH application ID:** 10949165
- **Project number:** 1DP2AI184728-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Julia Louise Malik Dunn
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $468,000
- **Award type:** 1
- **Project period:** 2024-08-12 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949165

## Citation

> US National Institutes of Health, RePORTER application 10949165, Spatial and Temporal Resolution of EosinophilSpecialization in Allergic Microenvironments (1DP2AI184728-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10949165. Licensed CC0.

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