# CIS-REGULATORY MECHANISMS UNDERLYING RETINOPATHY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $343,125

## Abstract

Project Summary 
 
Different human mutations in the photoreceptor-specific gene Crx are linked with
multiple retinopathies that vary in their severity and age of onset. How different
mutations in this single gene lead to different pathologies is not well understood.
Because CRX is a transcription factor, these disease mutations must act by altering the
ability of CRX to regulate gene expression. Our goal is to understand how different
classes of CRX mutations modify its regulatory function. To achieve this, we will apply a
recently developed massively parallel reporter gene technology to systematically and
comprehensively measure CRX regulatory function in live retina from multiple mouse
knock-in models that carry human CRX disease mutations. We will use the data to train
and test a mechanistic, quantitative model that describes how CRX mutations alter
protein-DNA and protein-protein interactions to modify gene regulation. In a
complementary approach, we will use the knock-in mouse models to determine the
effects of CRX disease mutations on its in vivo genome-wide binding, and on the
binding of the cooperatively interacting transcription factors OTX2, NRL, and NR2E3.
Using these two approaches, we aim to understand how different classes of CRX
disease mutations modify gene regulation in photoreceptors, and discover new
mechanisms of disease pathogenesis. Our results will provide a strong basis for
classifying new CRX mutations, and for designing targeted therapies to treat different
genetic forms of retinopathy.

## Key facts

- **NIH application ID:** 9893881
- **Project number:** 5R01EY027784-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** SHIMING CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893881

## Citation

> US National Institutes of Health, RePORTER application 9893881, CIS-REGULATORY MECHANISMS UNDERLYING RETINOPATHY (5R01EY027784-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9893881. Licensed CC0.

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