# Regulation of IGF-1R in acute and chronic thyroid eye disease

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $76,756

## Abstract

Project Summary/Abstract
Thyroid eye disease (TED) is a debilitating orbital and ocular condition that affects up to 50% of patients with
Grave’s hyperthyroidism. Tissue fibrosis and hyaluronan overproduction in active TED leads to proptosis, eye
movement restriction, eyelid retraction, dry eye, and optic nerve compression. After 2-3 years, patients enter a
chronic phase of TED where symptoms persist but do not acutely worsen. The molecular basis of acute and
chronic TED is a mystery. Prior studies have found insulin like growth factor 1 receptor (IGF-1R) to be an
important cell surface protein in effecting the fibrosis and hyaluronan production of active TED. IGF-1R is
important in a variety of body processes from metabolism to cancer to TED and was found to be overexpressed
in TED orbital tissue. Exactly how IGF-1R effects the phenotypic changes in TED, and how the IGF-1R gene is
regulated is unknown. The utility of IGF-1R or other related targets in chronic TED is also not known. This study
examines the cell type landscape of acute and chronic TED and how IGF-1R is expressed and regulated in the
two phases of TED. Aim 1 will determine the cell type trophism of IGF-1R in acute and chronic TED compared
to un-diseased orbit tissue using single nuclei multiome sequencing of orbit tissue isolated from patients
undergoing surgery. Spatial transcriptomics will be used to distinguish microenvironments of isolated cell types
and interacting cell surface receptors. Aim 2 will investigate the regulation of IGF-1R expression by cis-regulatory
elements from single-nuclear Assay for Transposase-Accessible Chromatin (ATAC)-sequencing. Promising
targets will be tested through an in-vitro CRISPR-screen on human orbital fibroblasts from acute and chronic
TED patients to determine the effect on fibroblast proliferation of knocking down key regulatory regions. These
studies will generate a greater understanding of the cell type landscape of TED and how IGF-1R and other key
cell surface proteins are regulated in acute and chronic TED. The results could yield new therapeutic targets or
better understanding of how to use existing treatments most effectively. The proposed research training plan
features mentorship from the basic sciences and clinical sciences and access to state-of-the-art techniques and
facilities. This plan also incorporates professional development and unites collaborative resources between the
department of cellular and molecular medicine and the department of ophthalmology to maximize my training
potential.

## Key facts

- **NIH application ID:** 10996866
- **Project number:** 1F32EY036715-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Sarah Cheng
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,756
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996866

## Citation

> US National Institutes of Health, RePORTER application 10996866, Regulation of IGF-1R in acute and chronic thyroid eye disease (1F32EY036715-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10996866. Licensed CC0.

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