# Optogenetic protein design for hypertrophic signaling pathways

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $388,750

## Abstract

Optogenetics has primarily employed light gated ion channels (derived from lower organisms) to trigger or inhibit
the neuronal action potential. Analogous studies in the cardiovascular field have used these photoresponsive
foreign proteins to regulate contractility and pacing. However, light gated ion channels are unable to interrogate
the intracellular mechanisms that control behavior and homeostasis. As a consequence, we have developed a
protein engineering strategy for creating light responsive analogs of endogenous proteins. The proposed
research program is focused on the design, construction, and validation of optogenetic signaling for proteins that
contribute to myocardial homeostasis, and the application of this technology to unravel the mechanisms that
drive cardiac hypertrophy and fibrosis. Aim 1: Optogenetic Engineering to Access the Biochemical
Pathways of Hypertrophy and Fibrosis. We will employ a novel optogenetic engineering strategy to create
light responsive signaling cascades localized at specific intracellular sites, with a focus on cAMP-mediated
signaling pathways. Aim 2: Light Guided Mapping of the Signaling Domains that Mediate Hypertrophy. The
optogenetic constructs outlined in Aim 1 will be used to explore the impact of signaling events at distinct
intracellular locations on cardiomyocyte behavior, with an emphasis on hypertrophic relevant responses. Aim 3:
Light Guided Mapping of the Intercellular Communication that Mediates Fibrosis. Optogenetic analogs of
endogenous proteins will be used to assess intercellular crosstalk between two distinct cardiac cell types. Light-
triggered activation of engineered signaling pathways offers the opportunity to tease apart a collaborative
signaling network that has been observed between these distinct cell populations.

## Key facts

- **NIH application ID:** 10518784
- **Project number:** 1R01HL159194-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lauren L Haar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518784

## Citation

> US National Institutes of Health, RePORTER application 10518784, Optogenetic protein design for hypertrophic signaling pathways (1R01HL159194-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10518784. Licensed CC0.

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