# Alternative protein isoforms in ventricular remodeling

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $389,096

## Abstract

PROJECT SUMMARY
Many cardiac genes undergo alternative splicing to produce cardiac vs. skeletal, and adult vs. fetal isoforms.
Differential regulation of alternative splicing patterns is a central component of the altered genetic program
during cardiac remodeling after ischemic injuries. Alternative splicing has been shown to causally modulate
the severity of cardiac remodeling, and thus represents a potential therapeutic target to halt disease
progression. Nevertheless, although a large number of alternative isoform transcripts have now been
discovered in the cardiac genome, current knowledge on the protein coding potential and hence molecular
functions of these alternative isoform is poor. The majority of discovered isoforms were yet to be detected at
the protein level -- therefore the effects of alternative isoforms on protein abundance, motif features, and
protein-protein interactions are virtually unknown. This knowledge gap obstructs a fuller understanding on
the impact of alternative splicing on the myocardium in health and disease.
 Proteomics technologies have advanced in recent years and are now well positioned to transform
cardiovascular sciences, but the detection of isoform proteins remains a substantial challenge. We and
others have recently shown that transcriptomics (RNA-seq) and proteomics (mass spectrometry) data may
be combined to probe more deeply into the cardiac proteome. In this project, we will combine the
respective strengths of RNA-seq (modeling transcript isoforms) and proteomics (providing protein-level
evidence) to examine cardiac alternative splicing. Specifically, we will apply this RNA-seq-guided-
proteomics approach to: (i) define the landscape of alternative protein isoforms in fetal and adult hearts; (ii)
identify disease signature isoforms in remodeling hearts using mouse models of myocardial infarction and
isoproterenol stimulation; (iii) examine the functional consequence of protein isoforms by identifying isoform-
specific protein-protein interactions and modulators of isoform expression in disease; and (iv) elucidate the
impact of isoform-specific overexpression/knockdown on myocyte functional phenotypes. We anticipate the
completion of the proposed studies will open new avenues into understanding the role of alternative splicing
in heart diseases.

## Key facts

- **NIH application ID:** 10133722
- **Project number:** 5R01HL141278-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Maggie Lam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,096
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133722

## Citation

> US National Institutes of Health, RePORTER application 10133722, Alternative protein isoforms in ventricular remodeling (5R01HL141278-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133722. Licensed CC0.

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