The biochemistry of metabolism undergoes significant remodeling during a) physiological stages associated with growth and development and b) onset and progressive stages of obesity, fatty liver and type II diabetes mellitus (T2DM). Our lab is interested in identifying the critical pathways involved in metabolic regulation during growth and development, and also identifying shared metabolic defects contributing to the onset of obesity, type II diabetes mellitus and fatty liver disease. Our specific interest is in understanding various mechanisms through which hepatic mitochondria integrates substrate flux, oxidative phosphorylation, ATP synthesis and inflammation, to maintain normal cell function. Strategies or agents targeting to alleviate mitochondrial dysfunction could be a promising strategy to a) enhance growth and development and b) for treatment of metabolic diseases.
We utilize various in vitro cell culture systems together with in vivo animal models to tease out mechanisms regulating mitochondrial function. These animal models include diet-induced/ transgenic mice models to probe mitochondrial dysfunction during fatty liver disease and developing chicken embryo/ neonatal chick to probe metabolic transition of mitochondrial networks during growth and development. Towards profiling of shared metabolic networks, we utilize stable isotope based techniques for metabolic flux analysis, together with targeted metabolomics of plasma and tissue metabolites. These mass spectrometry and/or nuclear magnetic resonance (NMR) based approaches in combination with standard measures in molecular biology provide us a functional index of tissue-specific metabolism.
Our research is currently funded by a grant from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, R01DK112865.