# Skin Neuroimmune Mechanisms of Urticarial Itch

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2024 · $146,181

## Abstract

PROJECT SUMMARY
This proposal defines a 5-year plan to prepare Aaron Ver Heul, MD, PhD, to reach his long-term goal of
independence as a physician-scientist studying the neuroimmunology of allergic diseases. He is currently an
Instructor in the Division of Allergy and Immunology at Washington University doing post-doctoral studies in the
laboratory of Dr. Brian Kim. There, Dr. Ver Heul has studied basic mechanisms of itch to complement his clinical
interest in chronic spontaneous urticaria (CSU), an itchy skin condition characterized by exaggerated mast cell
(MC) responses. He has demonstrated that the cytokine interleukin (IL)-33 enhances itch in a MC-dependent
manner and proposes to extend these studies to CSU. Thus, the primary scientific goal of this proposal is to
understand the role of IL-33 in CSU and itch.
Washington University is an ideal place to perform the proposed training and research, with outstanding
resources and expertise readily available. Dr. Brian Kim, the primary mentor, is an expert in neuroimmunology,
atopic dermatitis, and itch. Dr. Steve Brody, the co-mentor, is an expert in translational models of epithelial
biology. Both have strong records of continuous funding and training successful scientists. Dr. Ver Heul has also
assembled an advisory committee with expertise in immunology, neuroscience, functional genomics, and in vivo
microscopy, who will provide crucial scientific training and career guidance. He will take didactics in genomics,
microscopy, and scientific writing. He will have multiple opportunities to present his work locally and to the larger
scientific community. Dr. Ver Heul’s immediate objectives during the award period are to acquire requisite skills
to complete the proposed research, publish the results, and successfully obtain independent funding.
IL-33 is increased in a variety of allergic diseases including CSU, which affects 1% of the population. MCs are
highly responsive to IL-33, and exaggerated MC activation is a major contributor to CSU pathogenesis. Recently,
two distinct pathways by which MCs can be activated to cause itch were identified. One responds to allergens,
while the other responds to a variety of small molecules including neuropeptides and many common drugs
(known as basic secretagogues). Taken together with the demonstration that IL-33 enhances histaminergic itch,
Dr. Ver Heul now proposes to test the hypothesis that IL-33 broadly amplifies different forms of MC-mediated
itch responses. By completing the proposed aims, Dr. Ver Heul will define 1) how IL-33 enhances allergen-
mediated itch and 2) how IL-33 enhances basic secretagogue-mediated itch. The proposed studies determine
mechanisms of IL-33-enhanced MC activation in vitro and in mouse models of itch and extend these findings to
analyses of CSU patient samples. Fulfilling the aims will provide new insight into mechanisms of CSU and itch
and establish Dr. Ver Heul as an independent investigator in allergy and immunology.

## Key facts

- **NIH application ID:** 10909941
- **Project number:** 5K08AR080219-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** AARON VER HEUL
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $146,181
- **Award type:** 5
- **Project period:** 2022-08-15 → 2025-05-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909941

## Citation

> US National Institutes of Health, RePORTER application 10909941, Skin Neuroimmune Mechanisms of Urticarial Itch (5K08AR080219-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909941. Licensed CC0.

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