Goals and Objectives
Research Focus
The Sharma Lab advances cardiometabolic and transplant medicine through three integrated research areas:
- Advanced metabolic imaging using hyperpolarized carbon-13 MRI and stable-isotope carbon-13 tracer methods to visualize cardiac metabolism in living tissue and patients.
- Advanced multi-omics integrating transcriptomics and stable isotope-resolved metabolomics to map heart failure, ischemic heart disease, and donor organ biology while optimizing perfusion strategies for hearts and lungs.
- Artificial intelligence and machine learning to develop explainable AI tools that support clinical decision-making in cardiothoracic surgery and transplantation.
This study demonstrates that biomarkers of mitochondrial and cytosolic redox may be detected simultaneously in functioning tissues using co-polarized [1-13C]pyruvate and [1,3-13C2]AcAc and 13C MRS and that changes in mitochondrial redox may precede changes in cytosolic redox.
Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload.
In this study, we used hyperpolarized (HP) 13C-magnetic resonance spectroscopy to study the impact of a PDK2/PDK4 double knockout (DKO) on pyruvate metabolism in perfused livers from lean and diet-induced obese (DIO) mice and validated the HP observations with high-resolution 13C-nuclear magnetic resonance (NMR) spectroscopy of tissue extracts and steady-state isotopomer analyses.
In this study, we examined the conversion of hyperpolarized (HP) 13C-acetoacetate (AcAc) to 13C-β-hydroxybutyrate (β-HB) as a potential imaging biomarker for mitochondrial redox and dysfunction in perfused rat hearts.
