# Genetic Regulation of IgE Glycosylation

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $153,518

## Abstract

Project Summary
 Allergic diseases including asthma, eczema, and food allergy have increased substantially over the last
few decades. These diseases affect almost 5% of the population and having an annual economic burden of over
80 billion dollars. Allergic reactions can be life-threatening. While we have learned much about how an allergic
reaction occurs, much remains unknown about how allergies develop. Genetic predisposition is important in
developing allergies, but few defined mutations in specific genes are known to cause allergic disease.
 Recently, we conducted an allergy screen in mutagenized mice to discover genes that regulate
production of allergen-specific IgE, which mediates allergic reactions. Among several phenotypes of interest,
benadryl is marked by 90% reduced IgE levels and resistance to anaphylaxis with otherwise normal immunity.
benadryl was ascribed to a mutation a gene that produces mannose used for glycosylation (adding sugars to
proteins), metabolism and targeting proteases to the lysosome. IgE glycosylation is important for its structure
and function.
 Therefore (1), we will determine how the benadryl mutation affects IgE by identifying the cell type
responsible for low IgE through a combination of in vitro cell assays and conditional knock-out mouse models.
To determine the effect of altered mannose (2), we will examine alterations to IgE glycosylation, stability, and
function along with measuring changes to metabolism and lysosomal trafficking. To assess the importance of
benadryl in allergic disease (3), we will determine whether benadryl mice are resistant to IgE mediated
anaphylaxis and food allergy.
 Upon successful completion, the findings of this study will reveal a new pathway important for IgE
production that would be an appealing therapeutic target. I plan to use these results to launch my career using
this mouse strain to understand how altered IgE glycosylation regulates IgE stability, clearance and function.
Few other investigators are exploring this topic, which will allow me to study this into the future independently
without overlap with my current mentor’s line of scientific investigation.
 My career goal is to be an independent physician scientist determining the genes that regulate IgE
production, which can be clinically translated to genetic tests and potential therapeutic targets. This career
development award will help me gain skills in molecular biology, animal models of allergy, cellular immunology,
and proteomics. Biannual meetings with my mentoring committee will guide early career milestones including
submission of multiple papers. Institutional grant writing resources will be used to successfully compete for an
R01 to gain independence.

## Key facts

- **NIH application ID:** 10452683
- **Project number:** 5K08AI155832-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jeffrey SoRelle
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $153,518
- **Award type:** 5
- **Project period:** 2021-07-16 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452683

## Citation

> US National Institutes of Health, RePORTER application 10452683, Genetic Regulation of IgE Glycosylation (5K08AI155832-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10452683. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*