Research

Investigating how metabolism, mitochondrial function, and NAD⁺ biology contribute to heart disease.

Metabolism and Heart Disease

Our laboratory studies how metabolism affects the pathogenesis of heart disease induced by major cardiac risk factors, including diabetes, obesity, hypertension, and aging. We are particularly interested in understanding how mitochondrial metabolism and NAD⁺ metabolism influence cardiac function.

NAD⁺ regulates substrate catabolism as a redox cofactor through the recycling of NAD⁺ and NADH. Our previous studies showed that a reduced NAD⁺/NADH ratio is induced by pressure overload or diabetes and contributes to cardiac dysfunction.

Key publications: Lee et al., Circulation 2016, PMID: 27489254; Chiao et al., Circulation: Heart Failure 2021, PMID: 34374300.

NAD⁺ Metabolism

Cellular NAD⁺ levels are governed by the balance between NAD⁺ consumption and three major synthesis pathways. Emerging data show that enzymes and metabolites in these pathways regulate cellular function, mitochondrial biology, and cell death.

Our projects explore how NAD⁺ metabolism affects nuclear, cellular, mitochondrial, and cardiac functions in health and disease.

NAD⁺ metabolic pathways regulating cardiac and mitochondrial function.

Current Research Directions

NAD⁺ Redox State, Consumption, and Synthesis

We investigate how NAD⁺ redox imbalance affects NAD⁺ consumption and synthesis pathways, promoting cardiac dysfunction under stress conditions.

This work uses genetic models that manipulate NAD⁺ redox state and synthesis, combined with targeted multi-omics analyses.

Diet-Induced Obesity, Aging, and NAD⁺ Metabolism

We study how diet-induced obesity and aging alter cardiac NAD⁺ metabolism and contribute to diastolic dysfunction.

This direction aims to identify both unique and shared metabolic changes caused by obesity and aging, two major risk factors for diastolic heart failure.

Mitochondrial Function and Arrhythmogenesis

We investigate how mitochondrial function interacts with NAD⁺ metabolism and CaMKII signaling in arrhythmogenesis.

This project examines how mitochondrial and metabolic dysfunction contribute to abnormal cardiac rhythm.