# Cardiac Mitohormesis Protects Against Diabetic Cardiomyopathy Through Mitophagy

> **NIH NIH R00** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $248,999

## Abstract

PROJECT SUMMARY
This proposal describes a five-year career development program to prepare the candidate, Dr. Sang-Ging
Ong, for a career as an independent investigator. This program will expand Dr. Ong's scientific background in
cardiovascular research by providing additional technical training and expertise in mitochondria biology and
stem cell biology, areas in which Dr. Ong has already made significant achievements. The mentor is Dr.
Joseph Wu, a Professor of Medicine/Cardiology and Director of the Stanford Cardiovascular Institute at
Stanford University. The proposed mentor is a physician scientist with significant expertise in stem cell
biology and is an expert in cardiovascular disease modeling. The K99 phase will consist of structured
mentorship by the primary mentor, complementary meetings with the advisory committee, formal coursework,
a provocative research project, and a program of career transition.
 Diabetes is at epidemic proportions with 300 million people expected to suffer from diabetes by 2025.
Cardiovascular disease is the major cause of death among these patients of which the major contributing
factor is coronary artery disease (CAD). However, diabetic patients also suffer from diabetic cardiomyopathy
(DCM) independent of the vascular effects of hypertension or CAD. The mechanisms underlying DCM are
unclear, and there are currently no specific effective treatments for it. In all cells, including those of heart
muscle, the autophagy/lysosome system provides proteolytic mechanisms to regulate protein turnover and
degradation. Mitophagy is an autophagic process that specifically removes damaged mitochondria and may
be crucial for the proper maintenance of cardiac function when in excess nutrient. The role of mitophagy in
the diabetic heart is currently unknown, and in this proposal, Dr. Ong intends to understand the importance of
mitophagy in DCM, and explore the underlying mechanisms that regulate mitophagy which may help in
translational science.
 Combining Dr. Ong's expertise in mitochondrial biology with his skills in stem cell biology and
genomics/proteomics biology that he is developing while working with Dr. Wu puts him in a unique position to
be able to study the importance of mitophagy in human cardiac cells and the molecular mechanisms
pertaining to it in ways that have not been done before. Dr. Ong has generated preliminary data
demonstrating that mitophagy is impaired in human induced pluripotent-stem cells-derived cardiomyocytes
(iPSC-CMs) subjected to hyperglycemia although there is a heterogeneous response. Dr. Ong will seek to
conclusively prove that impaired mitophagy increases the susceptibility of iPSC-CMs to hyperglycemic
damage, and to potentially identify a molecular signature of mitophagy which may be useful in the future for
predicting response to excess glucose (Aim 1). Dr. Ong's preliminary results have also revealed an
interesting phenomenon in that cells resistant to hyperglycemic stress are associated...

## Key facts

- **NIH application ID:** 9941118
- **Project number:** 5R00HL130416-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Sang Ging Ong
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2016-08-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941118

## Citation

> US National Institutes of Health, RePORTER application 9941118, Cardiac Mitohormesis Protects Against Diabetic Cardiomyopathy Through Mitophagy (5R00HL130416-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9941118. Licensed CC0.

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