# Transcriptional control of proteostasis in photoreceptors

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $102,134

## Abstract

ABSTRACT
 Degenerative diseases of the retina are caused by ~4,500 distinct mutations in more than 250 genes.
Such incredible genetic diversity suggests that the most useful therapeutic interventions would target
common pathobiological pathways. In our previous work, we have demonstrated that insufficient ubiquitin-
proteasome activity contributes to photoreceptor loss in several forms of retinal degenerations. More
recently, we have discovered that an increase in proteolytic capacity of photoreceptors improves their
survival during retinal degeneration. Therefore, our studies have established the ubiquitin-proteasome
system as a promising therapeutic target. The ubiquitin-proteasome system (UPS) is a complex fine-tuned
cellular network composed of several hundreds of different proteins working in concert with chaperone and
autophagy systems. One of the most efficient strategies to manipulate such complex cellular systems is to
target transcriptional factor(s) or pathways controlling the expression levels of its key components. In this
proposal we will identify pathways governing transcriptional control of proteasomal biogenesis in
photoreceptors in coordinated manner. Specifically, we will explore the role of two regulators of proteasome
biogenesis, mTOR and NFE2L1, in rod photoreceptors in mice. Our studies will employ genetic approaches
to stimulate NFE2L1 and mTOR pathways. We will use multiple methods to study how stimulation of these
pathways affects ubiquitin-proteasome system, autophagy and translation. We will investigate the impact of
these pathways on two independent models of retinitis pigmentosa. Understanding mechanisms of
proteostasis regulation in photoreceptors would provide insights into therapeutic potential to manipulate
these pathways in the future studies.

## Key facts

- **NIH application ID:** 10672216
- **Project number:** 5R01EY030043-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Ekaterina Lobanova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $102,134
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10672216

## Citation

> US National Institutes of Health, RePORTER application 10672216, Transcriptional control of proteostasis in photoreceptors (5R01EY030043-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10672216. Licensed CC0.

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