# Exploring the link between mutant RNA expression and trinucleotide repeat disease

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $34,011

## Abstract

Project Summary/Abstract
 Fuchs’ endothelial corneal dystrophy (FECD) is the most common expanded
repeat disorder, affecting 4% of the US population. FECD causes progressive blindness
due to premature senescence and apoptosis in corneal endothelium. Currently, the only
curative treatment for FECD is a corneal transplant. This project aims to develop an
understanding of the disease at a molecular level to inform the development of
treatments. In 70% of late onset FECD, a CTG trinucleotide expansion in intron 2 of the
TCF4 gene produces a mutant CUG RNA which can be found in foci in the nucleus of
corneal endothelial cells. These mutant RNA foci are thought to cause cellular dysfunction
in FECD corneal endothelial cells. This project seeks to answer the question of how a
handful of molecules can have a dramatic impact on cell physiology. The first aim is to
identify proteins that bind mutant CUG-repeat RNA using mass spectrometry (MS). The
second aim is to identify post-translational modifications on Muscleblind-like protein
(MBNL) in a FECD patient-derived cells. MBNL has been implicated by previous
researchers for its propensity to CUG repeat RNA. MBNL is a splicing factor and its loss
of function may explain splicing defects seen in FECD. The third aim is to validate the
candidate proteins and post-translational modification results generated in aim one and
aim two.
 The environment in the Corey laboratory is collaborative and trainees benefit from
Dr. Corey’s mentorship and also the assistance of several senior researchers. This
project is in collaboration with Dr. Vinod Mootha in the UT Southwestern Ophthalmology
Department. There are four principal goals for this fellowship training period: 1) to be
knowledgeable of the literature in RNA biology and RNA related diseases, 2) to be a
proficient and successful grant and manuscript writer, 3) to be a proficient experimentalist,
and 4) to be an articulate and engaging speaker to all audiences. The skills obtained
through these goals will aid in the ultimate achievement of becoming a lead investigator
in a research laboratory.

## Key facts

- **NIH application ID:** 9944312
- **Project number:** 5F31EY030336-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Samantha Tori Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,011
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944312

## Citation

> US National Institutes of Health, RePORTER application 9944312, Exploring the link between mutant RNA expression and trinucleotide repeat disease (5F31EY030336-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944312. Licensed CC0.

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