# Proteomics Approach to Identify Cardiokine Signals in Human iPSC Models

> **NIH NIH K99** · STANFORD UNIVERSITY · 2020 · $129,536

## Abstract

PROJECT SUMMARY: The human heart is known to be a source of secreted signaling proteins, referred
to as cardiokines. Evidence suggests that crosstalk signaling mediated by cardiokines may play key roles in
fibrosis and other non-myocyte pathologies in patients with dilated cardiomyopathy (DCM), one of the most
common forms of inherited heart disease. Beyond a few well-known examples, currently little is known about
the identity of the proteins secreted by human heart cells and the signaling functions they carry. Research
into the “cardiac secretome” therefore has the potential to significantly advance our understanding of the
roles of cardiac crosstalk in disease mechanisms.
The Research Training Plan will leverage human induced pluripotent stem cell (iPSC), genome-editing, and
proteomics technologies to examine cardiokine signals in normal and DCM iPSC-derived cardiac cells (Aim1)
and their impact on crosstalk recipient cells (Aim 2). In Aim 1, the applicant Dr. Edward Lau will train with
mentor Dr. Joseph Wu in iPSC models and genome editing techniques in the K99 phase, investigate disease
mechanisms through functional and transcriptomic analyses, then determine secreted cardiokines from
normal vs. DCM iPSC-derived cardiomyocytes (iPSC-CM) using proteomics methods. The R00 phase will
leverage the genome-edited iPSC models to investigate the secretory dynamics of major cardiac cell types
and create a draft map of the human cardiac secretome in health and disease. In Aim 2, Dr. Lau will train in
iPSC-CM and iPSC-cardiac fibroblasts (iPSC-CF) co-culture models in the K99 phase, and complete a gene
expression and functional study on the effect of co-cultured CM and CM-conditioned medium on iPSC-CF
function. The R00 phase will further leverage this co-culture model to carefully examine the signaling impact
of individual cardiokines including fibroblast growth factor 7 (FGF7) and FGF18 in cardiac crosstalk.
Candidate Dr. Edward Lau has suitable prior training in cardiac proteomics and big data, with 32
publications including 10 as first-author since 2010. The Career Development Plan is tailored to enable Dr.
Lau to gain new experimental skills and concepts in human iPSC biology and genome editing, as well as
career skills through practice and coursework. Mentor Dr. Joseph Wu is a leading expert in stem cell biology
and cardiovascular medicine. Co-mentor Dr. Jennifer Van Eyk (clinical proteomics) and advisors Dr. Euan
Ashley (DCM) and Dr. Matt Porteus (genome-editing) offer complementary expertise. The Environment at
Stanford Cardiovascular Institute directed by Dr. Wu is outstanding for collaborative and innovative research.
Excellent infrastructure (iPSC biorepository, core facilities) is available. In summary, the strong mentoring
environment and training plan are anticipated to fully prepare Dr. Lau to launch his independent career. The
proposed studies promise to offer mechanistic insights into DCM pathogenesis, and may help identify
therapeutic ...

## Key facts

- **NIH application ID:** 9844496
- **Project number:** 5K99HL144829-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Edward Lau
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $129,536
- **Award type:** 5
- **Project period:** 2019-01-15 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844496

## Citation

> US National Institutes of Health, RePORTER application 9844496, Proteomics Approach to Identify Cardiokine Signals in Human iPSC Models (5K99HL144829-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9844496. Licensed CC0.

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