# Engineering a power switch to study the contribution of stem cell-derived cardiomyocytes on heart regeneration

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2021 · $171,720

## Abstract

PROJECT SUMMARY
I am an instructor of Medicine at Johns Hopkins University and my goal is to become an independent
physician-scientist in the field of heart regeneration with a focus on deciphering the mechanisms of stem cell
regeneration therapy in damaged myocardium. Cardiac regeneration therapy holds great potential to repair
damaged hearts and improve their function. In the past 15 years, several trials have tested the efficacy of
various types of stem cell-based therapies in different cardiomyopathy models with varying results. A critical
question that remains unanswered is whether stem cells and/or progenitor cells can differentiate into
cardiomyocytes capable of establishing stable electromechanical integration with the host cardiac tissue to
generate meaningful force and thus significantly improve systolic function. Alternatively, it is also possible that
the beneficial effects are due to paracrine factor and exosome secretions that boost reparative pathways and
prevent cell death. In this study, I propose a novel approach to directly test this fundamental question by using
a conditional power switch to control the excitation and contraction, of stem cell-derived cardiomyocytes.
Excitation and contraction will be controlled by conditionally expressing a GTPase named Rem1, which inhibits
the voltage-activated calcium channel Cav1.2 (ICa,L), a channel essential for cardiomyocyte excitation. Rem1
under control of a doxycycline-inducible promoter was introduced into stem cells that differentiate into
cardiomyocytes and upon doxycycline induction can be turned on or off. This proposal will introduce these
myocytes into infarcted rat hearts and repetitively turn the power switch on and off to assess their systolic
contributions. The influence of Cav1.2 inhibition by Rem1 on paracrine factor and exosome secretions, as well
as transcription factor expression and mitochondria function of stem cell-derived cardiomyocytes will also be
studied. Overall, this proposal will provide important insights into the mechanisms of cardiac regeneration
therapy that will be critical for future refinement and widespread clinical application of this treatment. To
successfully carry out this proposal, I have assembled an outstanding team. This includes leaders in cardiac
physiology such as my mentor Dr. David Kass and my consultant Dr. Leslie Tung, my co-mentor Dr. Chulan
Kwon an expert in heart development, and my consultants Drs. Charles Murry a world leader in cardiac
regeneration and Dr. Patrick Cahan an expert in bioinformatics. They will all provide outstanding training in
every method I need and will oversee and support my scientific progress and career development as an
independent investigator. I already have my own lab space, lab technician and funds and I will have full access
to state-of-art equipment both at the Johns Hopkins University Core facilities and in the division of Cardiology.

## Key facts

- **NIH application ID:** 10213825
- **Project number:** 5K08HL145135-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Emmanouil Tampakakis
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $171,720
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213825

## Citation

> US National Institutes of Health, RePORTER application 10213825, Engineering a power switch to study the contribution of stem cell-derived cardiomyocytes on heart regeneration (5K08HL145135-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213825. Licensed CC0.

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