# Multi-Omics Approach to Identify Cardiokines in Human iPSC Models

> **NIH NIH R00** · UNIVERSITY OF COLORADO DENVER · 2022 · $239,892

## Abstract

The human heart actively releases protein messengers into the extracellular space. Recent work suggests
that these secreted proteins, termed cardiokines, can mediate cellular crosstalk that plays important roles
in the development of cardiomyopathies and heart failure. Although several classical cardiokines such as
the natriuretic peptides have been extensively characterized, there have been few efforts to systematically
catalog the proteins secreted by human cardiac cells. Using proteomics and human induced pluripotent
stem cell (hiPSC) models, we recently created a draft map of the human cardiac secretome through
identifying and contrasting secreted molecules from hiPSC-derived cardiomyocytes, cardiac fibroblasts,
and endothelial cells. The results revealed a surprisingly large number of candidate cardiokines released
from each cell type including many secreted proteins with uncharacterized function in the cardiovascular
system. Moreover, we found broad changes in the secretome patterns of cardiomyocytes carrying dilated
cardiomyopathy causal variants over normal cells. Building on these findings, our aims in the R00 phase
are now to (i): identify cardiomyocyte secreted proteins that function in fibroblast crosstalk and predict the
biological processes they regulate; and (ii) prioritize disease-relevant cardiokines and validate their effects
on recipient fibroblast gene expression. To achieve these aims, we will employ a combination of
computational, single-cell sequencing, and proteomics strategies building on hiPSC models as our
foundation. If successful, the proposed research has the potential to uncover a number of novel secreted
proteins and their function in human cardiac cells, and shed light on the role of cellular communications in
the development and progression of cardiomyopathies.

## Key facts

- **NIH application ID:** 10450844
- **Project number:** 5R00HL144829-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Edward Lau
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $239,892
- **Award type:** 5
- **Project period:** 2020-08-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450844

## Citation

> US National Institutes of Health, RePORTER application 10450844, Multi-Omics Approach to Identify Cardiokines in Human iPSC Models (5R00HL144829-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450844. Licensed CC0.

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