# Mitochondria, metabolic plasticity and cell fate in the developmental origin of fuel-mediated cardiomyopathy

> **NIH NIH P20** · SANFORD RESEARCH/USD · 2020 · $385,131

## Abstract

PROJECT SUMMARY
The Center for Pediatric Research aims to understand regulators of cellular pliancy in the developmental origin
of health and disease (DOHaD). Project 3 will determine the role of mitochondria and cellular metabolism in
cardiomyocyte fate as a key mediator of heart disease in offspring born following a diabetic pregnancy. Infants
who are born to mothers with diabetes or obesity are at higher risk of heart disease at birth and in adulthood,
purportedly through fuel-mediated influences on the developing heart. However, preventative and therapeutic
interventions are lacking because the underlying mechanism remains unknown.
The Baack Lab is well poised to solve this problem as it builds upon their recent discovery that maternal diabetes,
especially with a high-fat diet, incites mitochondrial dysfunction, altered cellular bioenergetics and
cardiomyopathy in the developing offspring's heart. Moreover, exposure to diabetic pregnancy was sufficient to
extend these cardiometabolic consequences into adulthood.
The proposed project builds upon this discovery using The Baack Lab's well-characterized and physiologically
relevant rat model, advanced systems biology tools, state-of-the-art live-cell metabolic assays, and
mesenchymal stem cell derived cardiac progenitors from human umbilical cords exposed to normal or diabetic
pregnancy. The proposed methods will uncover mechanisms of pathogenesis and translate findings to humans
while answering two unresolved questions:
 1) How does diabetic pregnancy cause mitochondrial dysfunction and altered cellular bioenergetics in
the developing offspring's heart?
 2) What are the downstream effects on cell pliancy, specifically cardiomyocyte proliferation, differentiation
and senescence as it relates to developmentally programmed heart disease?
Together with the Center for Pediatric Research, Project 3 will demonstrate the role of mitochondria and
metabolic plasticity in stem cell regulation and set a firm foundation needed to develop pre- and post-natal
interventions to prevent heart disease in this growing at-risk population.

## Key facts

- **NIH application ID:** 10004078
- **Project number:** 5P20GM103620-08
- **Recipient organization:** SANFORD RESEARCH/USD
- **Principal Investigator:** Michelle Leigh Baack
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,131
- **Award type:** 5
- **Project period:** 2013-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004078

## Citation

> US National Institutes of Health, RePORTER application 10004078, Mitochondria, metabolic plasticity and cell fate in the developmental origin of fuel-mediated cardiomyopathy (5P20GM103620-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004078. Licensed CC0.

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