# Molecular pathways controlling cardiac gene expression

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $397,500

## Abstract

Summary
In response to pathophysiologic stress or disease the adult heart undergoes hypertrophic
enlargement such as concentric remodeling where individual adult cardiomyocytes primarily
thicken. The heart can also undergo substantial dilation with more eccentric remodeling in
response to different or progressive disease states in which myocytes more exclusively
lengthen. These disease states involve neuroendocrine regulatory circuits initiated at the
sarcolemma through G-protein coupled-receptors and receptor tyrosine kinases that in turn
activate intermediate signal transduction pathways such as mitogen-activated protein kinases
(MAPK). Previous literature indicates that each of the three major MAPK signaling branches
(extracellular signal-regulated kinases [ERKs], c-Jun N-terminal kinases [JNKs] and p38) act as
important regulators of cardiomyocyte growth dynamics. The myocyte itself is also thought to
sense tension and/or stretch which can also initiate signal transduction, such as through the
MAPK pathways to regulate growth. Past funding of this award focused on how MAPK
signaling through GATA4/5/6 transcription factors regulated cardiac growth or dilation. We also
previously showed that MEK1-ERK1/2 signaling specifically controls the decision of an adult
cardiomyocyte to grow in width versus length. Here we propose an innovative renewal of this
19 year running award to mechanistically examine how myocytes respond to their environment
and decide to grow in width versus length, and how this then impacts the remodeling of the
entire 3-dimensional heart as either concentric or dilatory growth, such as in the familial
hypertrophic (HCM) and dilated cardiomyopathies (DCM). Our 3 specific aims are 1) to define
the cellular and molecular dynamics of MEK1-ERK1/2 in the heart and identify potential novel
effectors of myocyte directional growth; 2) to perform a mechanistic interrogation of ERK1/2
targets as effectors of directional myocyte growth, and 3) to define the role of MEK1-ERK1/2
signaling in regulating myocyte directional growth in genetic models of HCM and DCM.

## Key facts

- **NIH application ID:** 9963034
- **Project number:** 5R01HL060562-23
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jeffery D Molkentin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,500
- **Award type:** 5
- **Project period:** 1998-07-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963034

## Citation

> US National Institutes of Health, RePORTER application 9963034, Molecular pathways controlling cardiac gene expression (5R01HL060562-23). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963034. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*